recent journal articles: surgery




Recent Articles in Annals of Surgery

Mukherjee S
Mental training in surgical education.
Ann Surg. 2007 Dec;246(6):1118. [Abstract]

Immenroth M, Bürger T, Brenner J, Nagelschmidt M, Troidl H, Eberspächer H
Mental Training in Surgical Education.
Ann Surg. 2007 Dec;246(6):1118-1119. [Abstract]

Oelschlager B, Pellegrini C, Nelson J, Mitsumori L, Hunter J, Sheppard B, Jobe B, Soper N, Brunt M, Pollisar N, Swanstrom L
Does a Biologic Prosthesis Really Reduce Recurrence After Laparoscopic Paraesophageal Hernia Repair?
Ann Surg. 2007 Dec;246(6):1117-1118. [Abstract]

Lange JF, Wijsmuller A, van Geldere D
Prophylactic Ilioinguinal Neurectomy in Open Inguinal Hernia Repair: A Double-blind Randomized Controlled Trial.
Ann Surg. 2007 Dec;246(6):1116. [Abstract]

Rice TW, Blackstone EH
Does a biologic prosthesis really reduce recurrence after laparoscopic paraesophageal hernia repair?
Ann Surg. 2007 Dec;246(6):1116-7. [Abstract]

Shah A, Pietrobon R, Cook C, Sheth NP, Nguyen L, Guo L, Jacobs DO, Kuo PC
Little Science, Big Science: Strategies for Research Portfolio Selection in Academic Surgery Departments.
Ann Surg. 2007 Dec;246(6):1110-1115.
OBJECTIVE:: To evaluate National Institutes of Health (NIH) funding for academic surgery departments and to determine whether optimal portfolio strategies exist to maximize this funding. SUMMARY BACKGROUND DATA:: The NIH budget is expected to be relatively stable in the foreseeable future, with a modest 0.7% increase from 2005 to 2006. Funding for basic and clinical science research in surgery is also not expected to increase. METHODS:: NIH funding award data for US surgery departments from 2002 to 2004 was collected using publicly available data abstracted from the NIH Information for Management, Planning, Analysis, and Coordination (IMPAC) II database. Additional information was collected from the Computer Retrieval of Information on Scientific Projects (CRISP) database regarding research area (basic vs. clinical, animal vs. human, classification of clinical and basic sciences). The primary outcome measures were total NIH award amount, number of awards, and type of grant. Statistical analysis was based on binomial proportional tests and multiple linear regression models. RESULTS:: The smallest total NIH funding award in 2004 to an individual surgery department was a single $26,970 grant, whereas the largest was more than $35 million comprising 68 grants. From 2002 to 2004, one department experienced a 336% increase (greatest increase) in funding, whereas another experienced a 73% decrease (greatest decrease). No statistically significant differences were found between departments with decreasing or increasing funding and the subspecialty of basic science or clinical research funded. Departments (n = 5) experiencing the most drastic decrease (total dollars) in funding had a significantly higher proportion of type K (P = 0.03) grants compared with departments (n = 5) with the largest increases in total funding; the latter group had a significantly increased proportion of type U grants (P = 0.01). A linear association between amount of decrease/increase was found with the average amount of funding per grant and per investigator (P < 0.01), suggesting that departments that increased their total funding relied on investigators with large amounts of funding per grant. CONCLUSIONS:: Although incentives to junior investigators and clinicians with secondary participation in research are important, our findings suggest that the best strategy for increasing NIH funding for surgery departments is to invest in individuals with focused research commitments and established track records of garnering large and multiple research grants. [Abstract]

Walter CJ, Dumville JC, Hewitt CE, Moore KC, Torgerson DJ, Drew PJ, Monson JR
The Quality of Trials in Operative Surgery.
Ann Surg. 2007 Dec;246(6):1104-1109.
OBJECTIVE:: This study aimed to assess the reported quality of trials in operative surgery. SUMMARY BACKGROUND DATA:: Randomized controlled trials (RCTs) in operative surgery have previously been criticized for using weak methodology despite no evidence to suggest their quality is any different from nonsurgical trials. STUDY DESIGN:: All surgical RCTs published in the British Medical Journal, the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine between 1998 and 2004 were identified. The adequacy of the reported methodology used to perform the randomization, power calculation, and recruitment was assessed for each trial using predefined criteria. The results from the surgical trials were compared with a randomly selected control group of nonsurgical RCTs, which were matched for journal and year of publication. RESULTS:: Sixty-six surgical RCTs were identified. Adequate reporting of randomization sequence generation was seen in 42% (n = 28) of surgical trials and 30% (n = 20) of nonsurgical trials, and adequate allocation concealment was recorded in 46% (n = 30) and 47% (n = 31), respectively. When combining these 2 interrelated steps of randomization, only 26% (n = 17) of surgical trials and 23% (n = 15) of nonsurgical trials reported both adequately. Adequate recruitment was recorded in 52% (n = 33 of 63) surgical and 55% (n = 33 of 60) nonsurgical trials, with approximately a quarter (n = 17 and n = 16, respectively) of the trials in both the surgical and nonsurgical categories reporting an adequate power calculation. CONCLUSIONS:: There was no evidence that the reported quality of surgical trials was different to nonsurgical trials. However, approximately half or less of all the trials reviewed reported adequate methodology. [Abstract]

Englesbe MJ, Dimick JB, Sonnenday CJ, Share DA, Campbell DA
The Michigan Surgical Quality Collaborative: Will a Statewide Quality Improvement Initiative Pay for Itself?
Ann Surg. 2007 Dec;246(6):1100-1103.
OBJECTIVE:: In this article, we detail a unique collaboration between hospitals in Michigan and a major third party payer, using a "pay for participation model." The payer has made a significant investment in this regional surgical quality improvement (QI) program and funds each center's participation. RESULTS:: Based on the documented costs and incidence of surgical complications at our center, we estimate that a 1.8% annual reduction in complication rates is required for the payer to recoup its investment in this regional QI program. If we achieve our goal of a 3% reduction in complications per year over the 3-year program, the payer will save $2.5 million in payments. Our findings suggest that only a very modest improvement in surgical results, of a magnitude that seems realistically achievable based on similar QI initiatives, is necessary to financially justify payer involvement in a statewide quality improvement initiative. CONCLUSION:: The framework of this program should be used by surgeons to attract private payers into QI collaboratives, facilitating improved patient outcomes and decreased health care expenditures. [Abstract]

Lopushinsky SR, Fowler RA, Kulkarni GS, Fecteau AH, Grant DR, Wales PW
The Optimal Timing of Intestinal Transplantation for Children With Intestinal Failure: A Markov Analysis.
Ann Surg. 2007 Dec;246(6):1092-1099.
OBJECTIVE:: Identify an optimal approach to the timing of intestinal transplantation for children dependent on total parenteral nutrition (PN). SUMMARY BACKGROUND DATA:: Children with short bowel syndrome are frequently dependent on PN for growth and development. Intestinal transplantation is often considered after PN-related complications occur, but optimal timing of transplantation is controversial. METHODS:: A Markov analytic model was used to determine life expectancy (LY) and quality-adjusted life years on a theoretical cohort of 4-year-old subjects for two treatment strategies: (1) standard care consisting of PN and referral to transplantation according to accepted guidelines and (2) early listing for isolated small intestine transplantation. RESULTS:: Early listing for intestinal transplantation was associated with 0.27 additional life years (13.16 vs. 12.89) and 0.76 additional quality-adjusted life years (10.51 vs. 9.75) as compared with current standard care. The unadjusted analysis was sensitive to the development of PN-associated liver disease, at a threshold of approximately 11% per year, and its related probability of dying at a threshold of 80% 2-year mortality. Early listing for transplantation was the dominant strategy until the probability of late bowel rejection reached 35% per year. CONCLUSIONS:: Children with short bowel syndrome dependent on PN should be considered for intestinal transplantation earlier than what is current practice. [Abstract]

Sosa JA, Mehta PJ, Wang TS, Yeo HL, Roman SA
Racial disparities in clinical and economic outcomes from thyroidectomy.
Ann Surg. 2007 Dec;246(6):1083-91.
CONTEXT:: Thyroid disease is common, and thyroidectomy is a mainstay of treatment for many benign and malignant thyroid conditions. Overall, thyroidectomy is associated with favorable outcomes, particularly if experienced surgeons perform it. OBJECTIVE:: To examine racial differences in clinical and economic outcomes of patients undergoing thyroidectomy in the United States. DESIGN, SETTING, PATIENTS:: The nationwide inpatient sample was used to identify thyroidectomy admissions from 1999 to 2004, using ICD-9 procedure codes. Race and other clinical and demographic characteristics of patients were collected along with surgeon volume and hospital characteristics to predict outcomes. MAIN OUTCOME MEASURES:: Inpatient mortality, complication rates, length of stay (LOS), discharge status, and mean total costs by racial group. RESULTS:: In 2003-2004, 16,878 patients underwent thyroid procedures; 71% were white, 14% black, 9% Hispanic, and 6% other. Mean LOS was longer for blacks (2.5 days) than for whites (1.8 days, P < 0.001); Hispanics had an intermediate LOS (2.2 days). Although rare, in-hospital mortality was higher for blacks (0.4%) compared with that for other races (0.1%, P < 0.001). Blacks trended toward higher overall complication rates (4.9%) compared with whites (3.8%) and Hispanics (3.6%, P = 0.056). Mean total costs were significantly lower for whites ($5447/patient) compared with those for blacks ($6587) and Hispanics ($6294). The majority of Hispanics (55%) and blacks (52%) had surgery by the lowest-volume surgeons (1-9 cases per year), compared with only 44% of whites. Highest-volume surgeons (>100 cases per year) performed 5% of thyroidectomies, but 90% of their patients were white (P < 0.001). Racial disparities in outcomes persist after adjustment for surgeon volume group. CONCLUSIONS:: These findings suggest that, although thyroidectomy is considered safe, significant racial disparities exist in clinical and economic outcomes. In part, inequalities result from racial differences in access to experienced surgeons; more data are needed with regard to racial differences in thyroid biology and surveillance to explain the balance of observed disparities. [Abstract]

Tonelli F, Marcucci T, Fratini G, Tommasi MS, Falchetti A, Brandi ML
Is Total Parathyroidectomy the Treatment of Choice for Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1?
Ann Surg. 2007 Dec;246(6):1075-1082.
OBJECTIVE:: The aim of the present report is to describe the results obtained with total parathyroidectomy (TPTX) guided by rapid intraoperative parathyroid hormone (PTH) evaluation, followed by immediate parathyroid autograft with fresh tissue. SUMMARY BACKGROUND DATA:: Surgery for hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 (MEN1) is performed with various surgical approaches. METHODS:: We report our 16-year experience of surgical treatment of 51 MEN1-HPT patients using TPTX and thymectomy. Forty-five patients underwent TPTX as the first surgical procedure, whereas for 6 patients, a parathyroid operation was the second surgical procedure. PTH intraoperative values less than 10 pg/mL, at the end of the surgery, were indicative for reimplantation of a few fragments ( approximately 7) of fresh parathyroid tissue in the brachioradial muscle of the forearm. Parathyroid autograft was performed in all patients, except 3 in whom the fourth parathyroid gland was not found. RESULTS:: Persistent hypoparathyroidism occurred in 13 patients (25%), with higher incidence in patients undergoing a second surgical revision for cervical recurrence than in patients submitted to the first surgery. At follow-up, 5 recurrences ( approximately 10%) in the forearm were observed after a mean time of 7 +/- 5 (M +/- SD) years. No cervical recurrence was documented. The forearm recurrence was treated with removal of 1 or 2 enlarged fragments obtaining the resolution of HPT in all but 1 case. CONCLUSIONS:: Based on the occurrence of complications in our experience, TPTX followed by autograft and guided by intraoperative PTH monitoring represents a better surgical option in MEN1-HPT compared with other surgical approaches. [Abstract]

Halazun KJ, Al-Mukhtar A, Aldouri A, Malik HZ, Attia MS, Prasad KR, Toogood GJ, Lodge JP
Right Hepatic Trisectionectomy for Hepatobiliary Diseases: Results and an Appraisal of Its Current Role.
Ann Surg. 2007 Dec;246(6):1065-1074.
OBJECTIVE:: To assess the results of 275 patients undergoing right hepatic trisectionectomy and to clarify its current role. SUMMARY BACKGROUND DATA:: Right hepatic trisectionectomy is considered one of the most extensive liver resections, and few reports have described the long-term results of the procedure. METHODS:: Short- and long-term outcomes of 275 consecutive patients who underwent right hepatic trisectionectomy from January 1993 to January 2006 were analyzed. RESULTS:: Of the 275 patients, 160 had colorectal metastases, 49 had biliary tract cancers, 20 had hepatocellular carcinomas, 20 had other metastatic tumors, and 12 had benign diseases. Fourteen of the 275 patients underwent right hepatic trisectionectomy as part of auxiliary liver transplantation for acute liver failure and were excluded. Concomitant procedures were carried out in 192 patients: caudate lobectomy in 45 patients, resection of tumors from the liver remnant in 57 patients, resection of the extrahepatic biliary tree in 45 patients, and lymphadenectomy in 45 patients. One-, 3-, 5-, and 10-year survivals were 74%, 54%, 43%, and 36%, respectively. Overall hospital morbidity and 30-day and in-hospital mortalities were 41%, 7%, and 8%, respectively. Survivals for individual tumor types were acceptable, with 5-year survivals for colorectal metastasis and cholangiocarcinoma being 38% and 32%, respectively. Multivariate analysis disclosed the amount of intraoperative blood transfusion to be the sole independent predictor for the development of hospital morbidity. Age over 70 years, preoperative bilirubin levels, and the development of postoperative renal failure were found to be independent predictors of long-term survival. CONCLUSION:: Right hepatic trisectionectomy remains a challenging procedure. The outcome is not influenced by additional concomitant resection of tumors from the planned liver remnant. Caution must be taken when considering patients older than 70 years for such resections. [Abstract]

Mathur A, Pitt HA, Marine M, Saxena R, Schmidt CM, Howard TJ, Nakeeb A, Zyromski NJ, Lillemoe KD
Fatty pancreas: a factor in postoperative pancreatic fistula.
Ann Surg. 2007 Dec;246(6):1058-64.
OBJECTIVE:: To determine whether patients who develop a pancreatic fistula after pancreatoduodenectomy are more likely to have pancreatic fat than matched controls. BACKGROUND:: Pancreatic fistula continues to be a major cause of postoperative morbidity and increased length of stay after pancreatoduodenectomy. Factors associated with postoperative pancreatic fistula include a soft pancreas, a small pancreatic duct, the underlying pancreatic pathology, the regional blood supply, and surgeon's experience. Fatty pancreas previously has not been considered as a contributing factor in the development of postoperative pancreatic fistula. METHODS:: Forty patients with and without a pancreatic fistula were identified from an Indiana University database of over 1000 patients undergoing pancreatoduodenectomy and matched for multiple parameters including age, gender, pancreatic pathology, surgeon, and type of operation. Surgical pathology specimens from the pancreatic neck were reviewed blindly for fat, fibrosis, vessel density, and inflammation. These parameters were scored (0-4+). RESULTS:: The pancreatic fistula patients were less likely (P < 0.05) to have diabetes but had significantly more intralobular (P < 0.001), interlobular (P < 0.05), and total pancreatic fat (P < 0.001). Fistula patients were more likely to have high pancreatic fat scores (50% vs. 13%, P < 0.001). Pancreatic fibrosis, vessel density, and duct size were lower (P < 0.001) in the fistula patients and negative correlations (P < 0.001) existed between fat and fibrosis (R = -0.40) and blood vessel density (R = -0.15). CONCLUSIONS:: These data suggest that patients with postoperative pancreatic fistula have (1) increased pancreatic fat and (2) decreased pancreatic fibrosis, blood vessel density, and duct size. Therefore, we conclude that fatty pancreas is a risk factor for postoperative pancreatic fistula. [Abstract]

Ikeyama T, Nagino M, Oda K, Ebata T, Nishio H, Nimura Y
Surgical Approach to Bismuth Type I and II Hilar Cholangiocarcinomas: Audit of 54 Consecutive Cases.
Ann Surg. 2007 Dec;246(6):1052-7.
OBJECTIVE:: To clarify the optimal surgical strategy for Bismuth type I and II hilar cholangiocarcinomas. SUMMARY BACKGROUND DATA:: Local or hilar resections is often performed for Bismuth type I and II tumors; however, reported outcomes have been unsatisfactory with a high recurrence and low survival rate. To improve survival, some authors have recommended right hepatectomy. However, the clinical value of this approach has not been validated. METHODS:: Records of 54 consecutive patients who underwent resection of a Bismuth type I or II hilar cholangiocarcinoma were analyzed retrospectively. Through 1996, bile duct resection or the smallest necessary hepatic segmentectomy was performed. Beginning in 1997, choice of resection was based on the cholangiographic tumor type. For nodular or infiltrating tumor, right hepatectomy was indicated; for papillary tumor, bile duct resection with or without limited hepatectomy was chosen. RESULTS:: Right hepatectomy was performed in 5 (20.8%) of 24 patients through 1996 and was done in 22 (73.3%) of 30 patients from 1997 (P = 0.0003). In patients without pM1 disease, R0 resection was achieved more frequently in the later period than in the earlier period (23 of 24 = 95.8% vs. 13 of 21 = 61.9%, P = 0.0073), which lead to better survival (5-year survival, 44.3% vs. 25.0%, P = 0.0495). In the 31 patients with nodular or infiltrating tumor, who tolerated surgery and did not have pM1 disease, survival was better in the 18 patients who underwent right hepatectomy than in those who did not (5-year survival, 62.9% vs. 23.1%, P = 0.0030). In cases of papillary tumor, bile duct resection with or without limited hepatectomy was sufficient to improve long-term survival. CONCLUSIONS:: The surgical approach to Bismuth type I and II hilar cholangiocarcinomas should be determined according to cholangiographic tumor type. For nodular and infiltrating tumors, right hepatectomy is essential; for papillary tumor, bile duct resection with or without limited hepatectomy is adequate. [Abstract]

Ishizuka M, Nagata H, Takagi K, Horie T, Kubota K
Inflammation-based prognostic score is a novel predictor of postoperative outcome in patients with colorectal cancer.
Ann Surg. 2007 Dec;246(6):1047-51.
OBJECTIVE:: To investigate the significance of preoperative Glasgow prognostic score (GPS) for postoperative prognostication of patients with colorectal cancer. BACKGROUND:: Recent studies have revealed that the GPS, an inflammation-based prognostic score that includes only C-reactive protein (CRP) and albumin, is a useful tool for predicting postoperative outcome in cancer patients. However, few studies have investigated the GPS in the field of colorectal surgery. METHODS:: The GPS was calculated on the basis of admission data as follows: patients with an elevated level of both CRP (>10 mg/L) and hypoalbuminemia (Alb <35 g/L) were allocated a score of 2, and patients showing 1 or none of these blood chemistry abnormalities were allocated a score of 1 or 0, respectively. Prognostic significance was analyzed by univariate and multivariate analyses. RESULTS:: A total of 315 patients were evaluated. Kaplan-Meier analysis and log-rank test revealed that a higher GPS predicted a higher risk of postoperative mortality (P < 0.01). Univariate analyses revealed that postoperative TNM was the most sensitive predictor of postoperative mortality (odds ratio, 0.148; 95% confidence interval, 0.072-0.304; P < 0.0001). Multivariate analyses using factors such as age, sex, tumor site, serum carcinoembryonic antigen, CA19-9, CA72-4, CRP, albumin, and GPS revealed that GPS (odds ratio, 0.165; 95% confidence interval, 0.037-0.732; P = 0.0177) was associated with postoperative mortality. CONCLUSIONS:: Preoperative GPS is considered to be a useful predictor of postoperative mortality in patients with colorectal cancer. [Abstract]

Uen YH, Lin SR, Wu DC, Su YC, Wu JY, Cheng TL, Chi CW, Wang JY
Prognostic Significance of Multiple Molecular Markers for Patients With Stage II Colorectal Cancer Undergoing Curative Resection.
Ann Surg. 2007 Dec;246(6):1040-1046.
OBJECTIVE:: The aim of this study was to determine whether our constructed high-sensitivity colorimetric membrane-array method could detect circulating tumor cells (CTCs) in the peripheral blood of stage II colorectal cancer (CRC) patients and so identify a subgroup of patients who are at high risk for relapse. SUMMARY BACKGROUND DATA:: Adjuvant chemotherapy is not routinely recommended in patients diagnosed with UICC stage II CRC. However, up to 30% of patients with stage II disease relapse within 5 years of surgery from recurrent or metastatic disease. The identification of reliable prognostic factors for high-risk stage II CRC patients is imperative. METHODS:: Membrane-arrays consisting of a panel of mRNA markers that included human telomerase reverse transcription (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20), and carcinoembryonic antigen (CEA) mRNA were used to detect CTCs in the peripheral blood of 194 stage II CRC patients who underwent potentially curative (R0) resection between January 2002 and December 2005. Digoxigenin (DIG)-labeled cDNA were amplified by RT-PCR from the peripheral blood samples, which were then hybridized to the membrane-array. All patients were followed up regularly, and their outcomes were investigated completely. RESULTS:: Overall, 53 of 194 (27.3%) stage II patients were detected with the expression of all 4 mRNA markers using the membrane-array method. After a median follow up of 40 months, 56 of 194 (28.9%) developed recurrence/metastases postoperatively. Univariately, postoperative relapse was significantly correlated with the depth of invasion (P < 0.001), the presence of vascular invasion (P < 0.001), the presence of perineural invasion (P = 0.048), the expression of all 4 mRNA markers (P < 0.001), and the number of examined lymph nodes (P = 0.031). Meanwhile, using a multivariate logistic regression analysis, T4 depth of tumor invasion (P = 0.013), the presence of vascular invasion (P = 0.032), and the expression of all 4 mRNA markers (P < 0.001) were demonstrated to be independent predictors for postoperative relapse. Combination of the depth of tumor invasion, vascular invasion, and all 4 mRNA markers as predictors of postoperative relapse showed that patients with any 1 positive predictor had a hazard ratio of about 27-fold to develop postoperative relapse (P < 0.001; 95% CI = 11.42-64.40). The interval between the detection of all 4 positive molecular markers and subsequently developed postoperative relapse ranged from 4 to 10 months (median: 7 months). Furthermore, the expression of all 4 mRNA markers in all stage II CRC patients, or either stage II colon or rectal cancer patients were strongly correlated with poorer relapse-free survival rates by survival analyses (all P < 0.001). CONCLUSIONS:: The pilot study suggests that the constructed membrane-array method for the detection of CTCs is a potential auxiliary tool to conventional clinicopathological variables for the prediction of postoperative relapse in stage II CRC patients who have undergone curative resection. [Abstract]

Chevallier JM, Paita M, Rodde-Dunet MH, Marty M, Nogues F, Slim K, Basdevant A
Predictive Factors of Outcome After Gastric Banding: A Nationwide Survey on the Role of Center Activity and Patients' Behavior.
Ann Surg. 2007 Dec;246(6):1034-1039.
BACKGROUND:: Systematic studies of postoperative outcome of bariatric surgery provide information on the predictors of success. Surgeon's and institution experience and patient's behavior after surgery are key determinant of success or failure. Data on clinical trials generally reflect the experience of skilled obesity surgery centers. Little is known about the current practice at a nationwide level. The present study was realized in the frame of a national survey on medical and surgical practices conducted by the public health insurance system. The objective was to analyze systematically and prospectively the outcome of all bariatric surgery procedures consecutively performed in a given period, as registered by the French National Medical Insurance Service. This study at a nationwide level focused on predictive factors of success and analyzed how the experience of the centers relates to the patients' outcomes at 1 and 2 years after surgery. METHODS:: This study examined prospectively the 2-year predictors of success of all consecutive 1236 bariatric operations performed at a nationwide level. Most (87.3%) were laparoscopic adjustable gastric banding (LAGB), so that the non-LAGB were eliminated from the study. Data were collected independently by consultants of the French National Medical Insurance Service: characteristics of the patients, evolution of body mass index (BMI), physical activity and comorbidities, changes in behavior, complications, reoperations. Information was available on the activity of the surgical teams. Excess weight loss (EWL) >50% was considered a "success," and EWL <50% "not a success." A backstep logistic regression (likelihood ratio test) was used to determine predictive factors. RESULTS:: Statistical analysis showed significant differences in EWL with the following data: age <40 years (P < 0.01), initial BMI <50 kg/m (P < 0.001), experience of the surgeon(s) >2 procedures per week (P < 0.01), recovery of physical activity (P < 0.001), and change in eating habits (P < 0.001). Compared with 15- to 39-year-old patients, 40- to 49-year-old patients have a 1.5 higher risk not to have a success after surgery and over 50-year-old patients a 1.8 higher risk. Morbidly obese patients (40 < BMI < 49) had a 2.6 times higher risk not to have a success than patients with severe obesity (35 < BMI < 39). Superobese patients (BMI >50) had a 5.4 times higher risk not to succeed than patients with severe obesity. Being operated by a team with a surgical activity over 15 bariatric procedures/2 months doubles the chance of a successful operation when compared with patients operated by surgical teams having only performed 1 or 2 bariatric procedures. Patients who had not recovered or increased their physical activity after operation had a 2.3 times higher risk not to have a success than those who did. Patients who had not changed their eating habits had a 2.2 times higher risk not to have a success than those who did. CONCLUSIONS:: This nationwide survey shows that the best profile for a success after gastric banding is a patient <40 years, with an initial BMI <50 kg/m, willing to change his eating habits and to recover or increase his physical activity after surgery and who has been operated by a team usually performing >2 bariatric procedures per week. This study emphasizes that obesity surgery requires a significant experience of the surgical team and a multidisciplinary approach to improve behavioral changes. [Abstract]

Peeters A, O?brien PE, Laurie C, Anderson M, Wolfe R, Flum D, Macinnis RJ, English DR, Dixon J
Substantial Intentional Weight Loss and Mortality in the Severely Obese.
Ann Surg. 2007 Dec;246(6):1028-1033.
OBJECTIVE:: To compare all-cause mortality in a surgical weight loss cohort with a similarly aged, obese population-based cohort. SUMMARY BACKGROUND DATA:: Significant weight loss following bariatric surgery improves the comorbidities associated with obesity. Improved survival as a result of surgical weight loss has yet to be clearly demonstrated using clinical data. METHODS:: The surgical weight loss cohort was a series of consecutive patients treated with a laparoscopic adjustable gastric band in Melbourne between June 1994 and April 2005. The Melbourne Collaborative Cohort Study (MCCS) provided a community control cohort, recruited between 1992 and 1994 and followed to June 2005 to determine vital status. Height and weight were recorded at baseline in both studies. Subjects between 37 and 70 years and with a body mass index (BMI) of >/=35 were included. Vital status was determined by follow-up and searching of death registries. Survival time was compared using Kaplan-Meier estimates, and hazard of death was determined using Cox regression, adjusting for sex, age at baseline, and BMI at baseline. RESULTS:: Of 966 weight loss patients (mean age 47 years, mean BMI 45 kg/m), the median follow-up time was 4 years. Mean weight loss after 2 years was 22.8% +/- 9% (58% of excess weight). The MCCS cohort included 2119 severely obese members (mean age, 55 years; mean BMI, 38 kg/m; median follow-up time, 12 years). There were 4 deaths in the weight loss cohort and 225 deaths in the MCCS cohort. Weight loss patients had 72% lower hazard of death than the community control cohort (hazard ratio, 0.28; 95% confidence interval, 0.10-0.85). CONCLUSIONS:: Substantial surgical weight loss in a morbidly obese population was associated with a significant survival advantage. [Abstract]

Nguyen NT, Hinojosa MW, Fayad C, Varela E, Konyalian V, Stamos MJ, Wilson SE
Laparoscopic surgery is associated with a lower incidence of venous thromboembolism compared with open surgery.
Ann Surg. 2007 Dec;246(6):1021-7.
BACKGROUND:: Although laparoscopy now plays a major role in most general surgical procedures, little is known about the relative risk of venous thromboembolism (VTE) after laparoscopic compared with open procedures. OBJECTIVE:: To compare the incidence of VTE after laparoscopic and open surgery over a 5-year period. PATIENTS AND INTERVENTIONS:: Clinical data of patients who underwent open or laparoscopic appendectomy, cholecystectomy, antireflux surgery, and gastric bypass between 2002 and 2006 were obtained from the University HealthSystem Consortium Clinical Database. The principal outcome measure was the incidence of venous thrombosis or pulmonary embolism occurring during the initial hospitalization after laparoscopic and open surgery. RESULTS:: During the 60-month period, a total of 138,595 patients underwent 1 of the 4 selected procedures. Overall, the incidence of VTE was significantly higher in open cases (271 of 46,105, 0.59%) compared with laparoscopic cases (259 of 92,490, 0.28%, P < 0.01). Our finding persists even when the groups were stratified according to level of severity of illness. The odds ratio (OR) for VTE in open procedures compared with laparoscopic procedures was 1.8 [95% confidence interval (CI) 1.3-2.5]. On subset analysis of individual procedures, patients with minor/moderate severity of illness level who underwent open cholecystectomy, antireflux surgery, and gastric bypass had a greater risk for developing perioperative VTE than patients who underwent laparoscopic cholecystectomy (OR: 2.0; 95% CI: 1.2-3.3; P < 0.01), antireflux surgery (OR: 24.7; 95% CI: 2.6-580.9; P < 0.01), and gastric bypass (OR: 3.4; 95% CI: 1.8-6.5; P < 0.01). CONCLUSIONS:: Within the context of this large administrative clinical data set, the frequency of perioperative VTE is lower after laparoscopic compared with open surgery. The findings of this study can provide a basis to help surgeons estimate the risk of VTE and implement appropriate prophylaxis for patients undergoing laparoscopic surgical procedures. [Abstract]

Bright T, Watson DI, Tam W, Game PA, Astill D, Ackroyd R, Wijnhoven BP, Devitt PG, Schoeman MN
Randomized Trial of Argon Plasma Coagulation Versus Endoscopic Surveillance for Barrett Esophagus After Antireflux Surgery: Late Results.
Ann Surg. 2007 Dec;246(6):1016-1020.
OBJECTIVE:: To determine the efficacy of endoscopic argon plasma coagulation (APC) for ablation of Barrett esophagus. SUMMARY BACKGROUND DATA:: APC has been used to ablate Barrett esophagus. However, the long-term outcome of this treatment is unknown. This study reports 5-year results from a randomized trial of APC versus surveillance for Barrett esophagus in patients who had undergone a fundoplication for the treatment of gastroesophageal reflux. METHODS:: Fifty-eight patients with Barrett esophagus were randomized to undergo either ablation using APC or ongoing surveillance. At a mean 68 months after treatment, 40 patients underwent endoscopy follow-up. The efficacy of treatment, durability of the neosquamous re-epithelialization, and safety of the procedure were determined. RESULTS:: Initially, at least 95% ablation of the metaplastic mucosa was achieved in all treated patients. At the 5-year follow-up, 14 of 20 APC patients continued to have at least 95% of their previous Barrett esophagus replaced by neosquamous mucosa, and 8 of these had complete microscopic regression of the Barrett esophagus. Five of the 20 surveillance patients had more than 95% regression of their Barrett esophagus, and 4 of these had complete microscopic regression (1 after subsequent APC treatment). The length of Barrett esophagus shortened significantly in both study groups, although the extent of regression was greater after APC treatment (mean 5.9-0.8 cm vs. 4.6-2.2 cm). Two patients who had undergone APC treatment developed a late esophageal stricture, which required endoscopic dilation, and 2 patients in the surveillance group developed high-grade dysplasia during follow-up. CONCLUSIONS:: Regression of Barrett esophagus after fundoplication is more likely, and greater in extent, in patients who undergo ablation with APC. In most patients treated with APC the neosquamous mucosa remains stable at up to 5-year follow-up. The development of high-grade dysplasia only occurred in patients who were not treated with APC. [Abstract]

Braga M, Frasson M, Vignali A, Zuliani W, Di Carlo V
Open right colectomy is still effective compared to laparoscopy: results of a randomized trial.
Ann Surg. 2007 Dec;246(6):1010-5.
OBJECTIVE:: The primary goal of this study was to clarify whether a laparoscopic (LPS) approach could be considered the dominant strategy in patients undergoing right colectomy. SUMMARY BACKGROUND DATA:: Because few nonrandomized or small sized studies have been carried out so far, definitive conclusions about the role of LPS right colectomy cannot be drawn. METHODS:: Two hundred twenty-six patients, candidates for right colectomy, were randomly assigned to LPS (n = 113) or open (n = 113) resection. The postoperative care protocol was the same for both groups. Trained members of the surgical staff who were not involved in the study registered postoperative morbidity. Follow-up was carried out for 30 days after hospital discharge. The following costs were calculated: surgical instruments, operative room occupation, routine care, postoperative morbidity, and hospitalization. RESULTS:: Conversion rate in the LPS group was 2.6% (3 of 113). Operative time (in minutes) was longer in the LPS group (131 vs. 112, P = 0.01). Postoperative morbidity rate was 18.6% in the open group and 13.3% in the LPS group (P = 0.31). Postoperative stay was one day longer in the open group (P = 0.002). No difference was found in postoperative quality of life. The additional operative charge in the LPS group was euro980 per patient randomized (euro821 for surgical instruments and euro159 for longer operative time). The savings in the LPS group was euro390 per patient randomized (euro144 for shorter length of hospital stay and euro246 for the lower cost of postoperative morbidity). The net balance resulted in a euro590 extra charge per patient randomly allocated to the LPS group. CONCLUSION:: LPS slightly improved postoperative recovery. This translated into a savings that covered only 40% of the extra operative charge. Therefore, open right colectomy could be still considered an effective procedure. [Abstract]

Morino M, Toppino M, Forestieri P, Angrisani L, Allaix ME, Scopinaro N
Mortality After Bariatric Surgery: Analysis of 13,871 Morbidly Obese Patients From a National Registry.
Ann Surg. 2007 Dec;246(6):1002-1009.
OBJECTIVE:: To define mortality rates and risk factors of different bariatric procedures and to identify strategies to reduce the surgical risk in patients undergoing bariatric surgery. SUMMARY BACKGROUND DATA:: Postoperative mortality is a rare event after bariatric surgery. Therefore, comprehensive data on mortality are lacking in the literature. METHODS:: A retrospective analysis of a large prospective database was carried out. The Italian Society of Obesity Surgery runs a National Registry on bariatric surgery where all procedures performed by members of the Society should be included prospectively. This Registry represents at present the largest database on bariatric surgery worldwide. RESULTS:: Between January 1996 and January 2006, 13,871 bariatric surgical procedures were included: 6122 adjustable silicone gastric bandings (ASGB), 4215 vertical banded gastroplasties (VBG), 1106 gastric bypasses, 1988 biliopancreatic diversions (BPD), 303 biliointestinal bypasses, and 137 various procedures. Sixty day mortality was 0.25%. The type of surgical procedure significantly influenced (P < 0.001) mortality risk: 0.1% ASGB, 0.15% VBG, 0.54% gastric bypasses, 0.8% BPD. Pulmonary embolism represented the most common cause of death (38.2%) and was significantly higher in the BPD group (0.4% vs. 0.07% VBG and 0.03% ASGB). Other causes of mortality were the following: cardiac failure 17.6%, intestinal leak 17.6%, respiratory failure 11.8%, and 1 case each of acute pancreatitis, cerebral ischemia, bleeding gastric ulcer, intestinal ischemia, and internal hernia. Therefore, 29.4% of patients died as a result of a direct technical complication of the procedure. Additional significant risk factors included open surgery (P < 0.001), prolonged operative time (P < 0.05), preoperative hypertension (P < 0.01) or diabetes (P < 0.05), and case load per Center (P < 0.01). CONCLUSIONS:: Mortality after bariatric surgery is a rare event. It is influenced by different risk factors including type of surgery, open surgery, prolonged operative time, comorbidities, and volume of activity. In defining the best bariatric procedure for each patient the different mortality risks should be taken into account. Choice of the procedure, prevention, early diagnosis, and therapy for cardiovascular complications may reduce postoperative mortality. [Abstract]

Omloo JM, Lagarde SM, Hulscher JB, Reitsma JB, Fockens P, van Dekken H, Ten Kate FJ, Obertop H, Tilanus HW, van Lanschot JJ
Extended Transthoracic Resection Compared With Limited Transhiatal Resection for Adenocarcinoma of the Mid/Distal Esophagus: Five-Year Survival of a Randomized Clinical Trial.
Ann Surg. 2007 Dec;246(6):992-1001.
OBJECTIVE:: To determine whether extended transthoracic esophagectomy for adenocarcinoma of the mid/distal esophagus improves long-term survival. BACKGROUND:: A randomized trial was performed to compare surgical techniques. Complete 5-year survival data are now available. METHODS:: A total of 220 patients with adenocarcinoma of the distal esophagus (type I) or gastric cardia involving the distal esophagus (type II) were randomly assigned to limited transhiatal esophagectomy or to extended transthoracic esophagectomy with en bloc lymphadenectomy. Patients with peroperatively irresectable/incurable cancer were excluded from this analysis (n = 15). A total of 95 patients underwent transhiatal esophagectomy and 110 patients underwent transthoracic esophagectomy. RESULTS:: After transhiatal and transthoracic resection, 5-year survival was 34% and 36%, respectively (P = 0.71, per protocol analysis). In a subgroup analysis, based on the location of the primary tumor according to the resection specimen, no overall survival benefit for either surgical approach was seen in 115 patients with a type II tumor (P = 0.81). In 90 patients with a type I tumor, a survival benefit of 14% was seen with the transthoracic approach (51% vs. 37%, P = 0.33). There was evidence that the treatment effect differed depending on the number of positive lymph nodes in the resection specimen (test for interaction P = 0.06). In patients (n = 55) without positive nodes locoregional disease-free survival after transhiatal esophagectomy was comparable to that after transthoracic esophagectomy (86% and 89%, respectively). The same was true for patients (n = 46) with more than 8 positive nodes (0% in both groups). Patients (n = 104) with 1 to 8 positive lymph nodes in the resection specimen showed a 5-year locoregional disease-free survival advantage if operated via the transthoracic route (23% vs. 64%, P = 0.02). CONCLUSION:: There is no significant overall survival benefit for either approach. However, compared with limited transhiatal resection extended transthoracic esophagectomy for type I esophageal adenocarcinoma shows an ongoing trend towards better 5-year survival. Moreover, patients with a limited number of positive lymph nodes in the resection specimen seem to benefit from an extended transthoracic esophagectomy. [Abstract]

Maathuis MH, Manekeller S, van der Plaats A, Leuvenink HG, 't Hart NA, Lier AB, Rakhorst G, Ploeg RJ, Minor T
Improved Kidney Graft Function After Preservation Using a Novel Hypothermic Machine Perfusion Device.
Ann Surg. 2007 Dec;246(6):982-991.
OBJECTIVE:: To study graft function and ischemia/reperfusion injury of porcine kidneys after preservation with the new Groningen Machine Perfusion (GMP) system versus static cold storage (CS). INTRODUCTION:: The increasing proportion of marginal and nonheart beating donors necessitates better preservation methods to maintain adequate graft viability. Hypothermic machine preservation (HMP) is a promising alternative to static CS. We have therefore developed and tested an HMP device, which is portable and actively oxygenates the perfusate via an oxygenator. The aim of the present study was to examine the efficacy of the GMP system in a transplantation experiment. MATERIALS AND METHODS:: In a porcine autotransplantation model, kidneys were retrieved and either cold stored in University of Wisconsin CS for 20 hours at 4 degrees C or subjected to HMP using University of Wisconsin machine perfusion at 4 degrees C with 2 different pressure settings: 30/20 mm Hg or 60/40 mm Hg. RESULTS:: HMP at 30/20 mm Hg was found to better preserve the viability of kidneys reflected by improved cortical microcirculation, less damage to the proximal tubule, less damage mediated by reactive oxygen species, less proinflammatory cytokine expression, and better functional recovery after transplantation. However, high perfusion pressures (60/40 mm Hg) resulted in higher expression of von Willebrand factor and monocyte chemotactic peptide-1 in postpreservation biopsies and subsequent graft thrombosis in 2 kidneys. CONCLUSIONS:: It is concluded that the GMP system improves kidney graft viability and perfusion pressures are critically important for outcome. [Abstract]

Westerdahl J, Bergenfelz A
Unilateral Versus Bilateral Neck Exploration for Primary Hyperparathyroidism: Five-Year Follow-up of a Randomized Controlled Trial.
Ann Surg. 2007 Dec;246(6):976-81.
OBJECTIVE:: To compare long-term patient outcome in a prospective randomized controlled trial between unilateral and bilateral neck exploration for primary hyperparathyroidism (pHPT). SUMMARY BACKGROUND DATA:: Minimal invasive and/or focused parathyroidectomy has challenged the traditional bilateral neck exploration for pHPT. Between 1997 and 2001, we conducted the first unselected randomized controlled trial of unilateral versus bilateral neck exploration for pHPT. The results showed that unilateral exploration is a surgical strategy with distinct advantages in the early postoperative period. However, concerns have been raised that limited parathyroid exploration could increase the risk for recurrent pHPT during long-term follow-up. METHODS:: Ninety-one patients with the diagnosis of pHPT were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. Follow-up was performed after 6 weeks, 1 year, and 5 years postoperatively. RESULTS:: Seventy-one patients were available for 5-year follow-up. There were no differences in serum ionized calcium and parathyroid hormone, respectively, between patients in the unilateral and bilateral group. Overall 6 patients have been found to have persistent (n = 3) or recurrent (n = 3) pHPT; 4 patients in the unilateral group (3 of these 4 patients were bilaterally explored) and 2 patients in the bilateral group. Three of 6 failures were unexpectedly found to have multiple endocrine neoplasia mutations. One patient with solitary adenoma in the bilateral group still required vitamin D substitution 5 years after surgery. CONCLUSION:: Unilateral neck exploration with intraoperative parathyroid hormone assessment provides the same long-term results as bilateral neck exploration, and is thus a valid strategy for the surgical treatment of pHPT. [Abstract]

Müller MW, Friess H, Kleeff J, Dahmen R, Wagner M, Hinz U, Breisch-Girbig D, Ceyhan GO, Büchler MW
Is There Still a Role for Total Pancreatectomy?
Ann Surg. 2007 Dec;246(6):966-975.
OBJECTIVE:: To evaluate the perioperative and long-term results of total pancreatectomy (TP), and to assess whether it provides morbidity, mortality, and quality of life (QoL) comparable to those of the pylorus-preserving (pp)-Whipple procedure in patients with benign and malignant pancreatic disease. SUMMARY BACKGROUND DATA:: TP was abandoned for decades because of high peri- and postoperative morbidity and mortality. Because selected pancreatic diseases are best treated by TP, and pancreatic surgery and postoperative management of exocrine and endocrine insufficiency have significantly improved, the hesitance to perform a TP is disappearing. PATIENTS AND METHODS:: In a prospective study conducted from October 2001 to November 2006, all patients undergoing a TP (n = 147; 100 primary elective TP [group A], 24 elective TP after previous pancreatic resection [group B], and 23 completion pancreatectomies for complications) were included, and perioperative and late follow-up data, including the QoL (EORTC QLQ-C30 questionnaire), were evaluated. A matched-pairs analysis with patients receiving a pp-Whipple operation was performed. RESULTS:: Indications for an elective TP (group A + B) were pancreatic and periampullary adenocarcinoma (n = 71), other neoplastic pancreatic tumors (intraductal papillary mucinous neoplasms, neuroendocrine tumors, cystic tumors; n = 34), metastatic lesions (n = 8), and chronic pancreatitis (n = 11). There were 73 men and 51 women with a mean age of 60.9 +/- 11.3 years. Median intraoperative blood loss was 1000 mL and median operation time was 380 minutes. Postoperative surgical morbidity was 24%, medical morbidity was 15%, and mortality was 4.8%. The relaparotomy rate was 12%. Median postoperative hospital stay was 11 days. After a median follow-up of 23 months, global health status of TP patients was comparable to that of pp-Whipple patients, although a few single QoL items were reduced. All patients required insulin and exocrine pancreatic enzyme replacements. The mean HbA1c value was 7.3% +/- 0.9%. CONCLUSION:: In this cohort study, mortality and morbidity rates after elective TP are not significantly different from the pp-Whipple. Because of improvements in postoperative management, QoL is acceptable, and is almost comparable to that of pp-Whipple patients. Therefore, TP should no longer be generally avoided, because it is a viable option in selected patients. [Abstract]

Gertsch P, Vandoni RE, Pelloni A, Krpo A, Alerci M
Localized Hepatic Ischemia After Liver Resection: A Prospective Evaluation.
Ann Surg. 2007 Dec;246(6):958-965.
OBJECTIVE:: To prospectively assess the frequency, severity, and extension of localized ischemia in the remaining liver parenchyma after hepatectomy. BACKGROUND:: Major blood loss and postoperative ischemia of the remnant liver are known factors contributing to morbidity after liver surgery. The segmental anatomy of the liver and the techniques of selective hilar or suprahilar clamping of the Glissonian sheaths permit identification of ischemia on the surface of the corresponding segments for precise section of the parenchyma. Incomplete resection of a segment, or compromised blood supply to the remaining liver, may result in ischemia of various extension and severity. METHODS:: Patients undergoing hepatectomy received enhanced computerized tomodensitometry with study of the arterial and venous phases within 48 hours after resection. We defined hepatic ischemia as reduced or absent contrast enhancement during the venous phase. We classified the severity of ischemia as hypoperfusion, nonperfusion, or necrosis. The extension of ischemia was identified as marginal, partial, or segmental. Factors that may influence postoperative ischemia were analyzed by univariate and multivariate analyses. RESULTS:: One hundred fifty consecutive patients (70 F, 80 M, mean age 62 +/- 12 years) underwent 64 major and 81 minor hepatectomies and 5 wedge resections. We observed radiologic signs of ischemia in 38 patients (25.3%): 33 hypoperfusions (17 marginal, 12 partial, and 4 segmental), 3 nonperfusions (1 marginal, 1 partial, and 1 segmental), and 2 necroses (1 partial, 1 segmental). One patient with a segmental necrosis underwent an early reoperation. In all other cases, the evolution was spontaneously favorable. Postoperative peak levels of serum aspartate aminotransferase and alanine aminotransferase were significantly higher in patients with ischemia. Patients with ischemia had a significantly higher risk of developing a biliary leak (18.4% vs. 2.6%, P < 0.001). There was no correlation between liver ischemia and mortality (2%). None of the following factors were associated with ischemia after univariate and multivariate analysis: age, preoperative bilirubin level, liver fibrosis, malignant tumor, type of hepatectomy, surface of transection, weight of resected liver, Pringle maneuver, blood loss, and number of transfusions. CONCLUSIONS:: Some form of localized ischemia after hepatectomy was detected in 1 of 4 of our patients. Its clinical expression was discreet in the large majority of cases, even if it might have been one of the underlying causes of postoperative biliary fistulas. Clinical observation is sufficient to detect the rare patient with suspected postoperative liver ischemia that will require active treatment. [Abstract]

Lerut JP, Orlando G, Adam R, Schiavo M, Klempnauer J, Mirza D, Boleslawski E, Burroughs A, Sellés CF, Jaeck D, Pfitzmann R, Salizzoni M, Söderdahl G, Steininger R, Wettergren A, Mazzaferro V, Le Treut YP, Karam V
The Place of Liver Transplantation in the Treatment of Hepatic Epitheloid Hemangioendothelioma: Report of the European Liver Transplant Registry.
Ann Surg. 2007 Dec;246(6):949-957.
BACKGROUND:: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up. MATERIAL AND METHODS:: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT. RESULTS:: HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early (<3 months) and late (>3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6-98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion. CONCLUSIONS:: The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder. [Abstract]

McCormack L, Petrowsky H, Jochum W, Mullhaupt B, Weber M, Clavien PA
Use of Severely Steatotic Grafts in Liver Transplantation: A Matched Case-Control Study.
Ann Surg. 2007 Dec;246(6):940-948.
BACKGROUND:: Although there is a worldwide need to expand the pool of available liver grafts, cadaveric livers with severe steatosis (>60%) are discarded for orthotopic liver transplantation (OLT) by most centers. METHODS:: We analyzed patients receiving liver grafts with severe steatosis between January 2002 and September 2006. These patients were matched 1:2 with control patients without severe steatosis according to status the waiting list, recipient age, recipient body mass index (BMI), and model for end-stage liver disease (MELD) score. Primary end points were the incidence of primary graft nonfunction (PNF), and graft and patient survival. Secondary end points included primary graft dysfunction (PDF), the incidence of postoperative complications, and histologic assessment of steatosis in follow-up biopsies. We also conducted a survey on the use of grafts with severe steatosis among leading European liver transplant centers. RESULTS:: During the study period, 62 patients dropped out of the waiting list and 45 of them died due to progression of disease. Of 118 patients who received transplants 20 (17%) received a graft with severe steatosis during this period. The median degree of total liver steatosis was 90% (R = 65%-100%) for the steatotic group. The steatotic (n = 20) and matched control group (n = 40) were comparable in terms of recipient age, BMI, MELD score, and cold ischemia time. The steatotic group had a significantly higher rate of PDF and/or renal failure. Although the median intensive care unit (ICU) and hospital stay were not significantly different between both groups, the proportion of patients with long-term ICU (>/=21 days) and hospital (>/=40 days) stay was significantly higher for patients with a severely steatotic graft. Sixty-day mortality (5% vs. 5%) and 3-year patient survival rate (83% vs. 84%) were comparable between the control and severe steatosis group. Postoperative histologic assessment demonstrated that the median total amount of liver steatosis decreased significantly (median: 90% to 15%, P < 0.001). Our survey showed that all but one of the European centers currently reject liver grafts with severe steatosis for any recipient. CONCLUSION:: Due to the urgent need of liver grafts, severely steatotic grafts should be no longer discarded for OLT. Maximal effort must be spent when dealing with these high-risk organs but the use of severely steatotic grafts may save the lives of many patients who would die on the waiting list. [Abstract]

Sperti C, Bissoli S, Pasquali C, Frison L, Liessi G, Chierichetti F, Pedrazzoli S
18-Fluorodeoxyglucose Positron Emission Tomography Enhances Computed Tomography Diagnosis of Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas.
Ann Surg. 2007 Dec;246(6):932-939.
OBJECTIVE:: To assess the reliability of 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) in distinguishing benign from malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and its contribution to surgical decision making. SUMMARY BACKGROUND DATA:: Pancreatic IPMNs are increasingly recognized, often as incidental findings, especially in people over age 70 and 80. Computed tomography (CT) and magnetic resonance (MR) are unreliable in discriminating a benign from a malignant neoplasm. 18-FDG PET as imaging procedure based on the increased glucose uptake by tumor cells has been suggested for diagnosis and staging of pancreatic cancer. METHODS:: From January 1998 to December 2005, 64 patients with suspected IPMNs were prospectively investigated with 18-FDG PET in addition to conventional imaging techniques [helical-CT in all and MR and magnetic resonance cholangiopancreatography (MRCP) in 60]. 18-FDG PET was analyzed visually and semiquantitatively using the standard uptake value (SUV). The validation of the diagnosis was made by a surgical procedure (n = 44), a percutaneous biopsy (n = 2), main duct cytology (n = 1), or follow-up (n = 17). Mean and median follow-up times were 25 and 27.5 months, respectively (range, 12-90 months). RESULTS:: Twenty-seven patients (42%) were asymptomatic. Forty-two patients underwent pancreatic resection, 2 palliative surgery, and 20 did not undergo surgery. An adenoma was diagnosed in 13 patients, a borderline tumor in 8, a carcinoma in situ in 5, and an invasive cancer in 21; in 17 patients a tumor sampling was not performed and therefore the histology remained undetermined. Positive criteria of increased uptake on 18-FDG PET was absent in 13 of 13 adenomas and 7 of 8 borderline IPMNs, but was present in 4 of 5 carcinoma in situ (80%) and in 20 of 21 invasive cancers (95%). Conventional imaging technique was strongly suggestive of malignancy in 2 of 5 carcinomas in situ and in 13 of 21 invasive carcinomas (62%). Furthermore, conventional imaging had findings that would be considered falsely positive in 1 of 13 adenomas (8%) and in 3 of 8 borderline neoplasms (37.5%). Therefore, positive 18-FDG PET influenced surgical decision making in 10 patients with malignant IPMN. Furthermore, negative findings on 18-FDG PET prompted us to use a more limited resection in 15 patients, and offered a follow-up strategy in 18 patients (3 positive at CT scan) for the future development of a malignancy. CONCLUSIONS:: 18-FDG PET is more accurate than conventional imaging techniques (CT and MR) in distinguishing benign from malignant (invasive and noninvasive) IPMNs. 18-FDG PET seems to be much better than conventional imaging techniques in selecting IPMNs patients, especially when old and asymptomatic, for surgical treatment or follow-up. [Abstract]

Recent Articles in American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons

Mueller TF, Reeve J, Jhangri GS, Mengel M, Jacaj Z, Cairo L, Obeidat M, Todd G, Moore R, Famulski KS, Cruz J, Wishart D, Meng C, Sis B, Solez K, Kaplan B, Halloran PF
The Transcriptome of the Implant Biopsy Identifies Donor Kidneys at Increased Risk of Delayed Graft Function.
Am J Transplant. 2007 Nov 16;
Improved assessment of donor organ quality at time of transplantation would help in management of potentially usable organs. The transcriptome might correlate with risk of delayed graft function (DGF) better than conventional risk factors. Microarray results of 87 consecutive implantation biopsies taken postreperfusion in 42 deceased (DD) and 45 living (LD) donor kidneys were compared to clinical and histopathology-based scores. Unsupervised analysis separated the 87 kidneys into three groups: LD, DD1 and DD2. Kidneys in DD2 had a greater incidence of DGF (38.1 vs. 9.5%, p < 0.05) than those in DD1. Clinical and histopathological risk scores did not discriminate DD1 from DD2. A total of 1051 transcripts were differentially expressed between DD1 and DD2, but no transcripts separated DGF from immediate graft function (adjusted p < 0.01). Principal components analysis revealed a continuum from LD to DD1 to DD2, i.e. from best to poorest functioning kidneys. Within DD kidneys, the odds ratio for DGF was significantly increased with a transcriptome-based score and recipient age (p < 0.03) but not with clinical or histopathologic scores. The transcriptome reflects kidney quality and susceptibility to DGF better than available clinical and histopathological scoring systems. [Abstract]

Harbell JW, Dunn TB, Fauda M, John DG, Goldenberg AS, Teperman LW
Transmission of Anaplastic Large Cell Lymphoma via Organ Donation After Cardiac Death.
Am J Transplant. 2007 Nov 16;
Recently, donation after cardiac death (DCD) has been encouraged in order to expand the donor pool. We present a case of anaplastic T-cell lymphoma transmitted to four recipients of solid organ transplants from a DCD donor suspected of having bacterial meningitis. On brain biopsy, the donor was found to have anaplastic central nervous system T-cell lymphoma, and the recipient of the donor's pancreas, liver and kidneys were found to have involvement of T-cell lymphoma. The transplanted kidneys and pancreas were excised from the respective recipients, and the kidney and pancreas recipients responded well to chemotherapy. The liver recipient underwent three cycles of chemotherapy, but later died due to complications of severe tumor burden. We recommend transplanting organs from donors with suspected bacterial meningitis only after identification of the infectious organism. In cases of lymphoma transmission, excision of the graft may be the only chance at long-term survival. [Abstract]

Schaub S, Scornik JC
High-Tech Detection of HLA Antibodies and Complement: Prospects and Limitations.
Am J Transplant. 2007 Nov 16; [Abstract]

Ulrich C, Heine GH, Gerhart MK, Köhler H, Girndt M
Proinflammatory CD14+CD16+ Monocytes Are Associated With Subclinical Atherosclerosis in Renal Transplant Patients.
Am J Transplant. 2007 Nov 16;
Atherosclerotic cardiovascular disease is a major cause of death in renal transplant (TX) recipients. Atherosclerotic lesions are characterized by monocytic infiltration. Circulating monocytes can be divided into functionally distinct subpopulations, among which CD14++CD16+ and CD14+CD16+ monocytes (summarized as CD16+ monocytes) are proinflammatory cells. We hypothesized that the frequency of circulating CD16+ monocytes is associated with subclinical atherosclerosis in TX patients. Monocyte subpopulations were quantified in 95 TX and 31 hemodialysis patients (HD). In TX patients, subclinical atherosclerosis was determined by carotid intima media thickness (IMT) measurement. TX patients had lower frequencies of CD16+ monocytes than HD patients. When stratifying by immunosuppressive treatment, patients on methylprednisolone (MP) therapy had fewer CD14+CD16+ monocytes than patients not receiving MP. CD14+CD16+ monocytes decrease very shortly after transplantation. CD14+CD16+ monocyte frequency correlated with IMT in TX recipients (r = 0.34, p < 0.001). This correlation was most pronounced among patients without MP treatment (r = 0.55, p = 0.02). In a multivariate regression analysis, the association of CD14+CD16+ monocytes with IMT was independent from traditional cardiovascular risk factors. The frequency of proinflammatory CD14+CD16+ monocytes is independently associated with subclinical atherosclerosis in transplant recipients. Further studies on the association between circulating leukocytes and atherosclerosis should take monocyte heterogeneity into account. [Abstract]

Setoguchi K, Ishida H, Shimmura H, Shimizu T, Shirakawa H, Omoto K, Toki D, Iida S, Setoguchi S, Tokumoto T, Horita S, Nakayama H, Yamaguchi Y, Tanabe K
Analysis of Renal Transplant Protocol Biopsies in ABO-Incompatible Kidney Transplantation.
Am J Transplant. 2007 Nov 16;
Numerous studies have shown that protocol biopsies have predictive power. We retrospectively examined the histologic findings and C4d staining in 89 protocol biopsies from 48 ABO-incompatible (ABO-I) transplant recipients, and compared the results with those of 250 controls from 133 ABO-compatible (ABO-C) transplant recipients given equivalent maintenance immunosuppression. Others have shown that subclinical rejection (borderline and grade I) in ABO-C grafts decreased gradually after transplantation. In our study, however, subclinical rejection in the ABO-I grafts was detected in 10%, 14% and 28% at 1, 3 and 6-12 months, respectively. At 6-12 months, mild tubular atrophy was more common in the ABO-C grafts whereas the incidence of transplant glomerulopathy did not differ between the two groups (ABO-C: 7%; ABO-I: 15%; p = 0.57). In the ABO-I transplants, risk factors for transplant glomerulopathy in univariate analysis were positive panel reactivity (relative risk, 45.0; p < 0.01) and a prior history of antibody-mediated rejection (relative risk, 17.9; p = 0.01). Furthermore, C4d deposition in the peritubular capillaries was detected in 94%, with diffuse staining in 66%. This deposition, however, was not linked to antibody-mediated rejection. We conclude that, in the ABO-I kidney transplantation setting, detection of C4d alone in protocol biopsies might not have any diagnostic or therapeutic relevance. [Abstract]

Konishi N, Ishizaki Y, Sugo H, Yoshimoto J, Miwa K, Kawasaki S
Impact of a Left-Lobe Graft Without Modulation of Portal Flow in Adult-to-Adult Living Donor Liver Transplantation.
Am J Transplant. 2007 Nov 16;
In adult-to-adult living donor liver transplantation (LDLT), left-lobe grafts can sometimes be small-for-size. Although attempts have been made to prevent graft overperfusion through modulation of portal inflow, the optimal portal venous circulation for a liver graft is still unclear. Hepatic hemodynamics were analyzed with reference to graft function and outcome in 19 consecutive adult-to-adult LDLTs using left-lobe grafts without modulation of graft portal inflow. Overall mean graft volume (GV) was 398 g, which was equivalent to 37.8% of the recipient standard liver volume (SV). The GV/SV ratio was less than 40% in 13 of the 19 recipients. Overall mean recipient portal vein flow (PVF) was much higher than the left PVF in the donors. The mean portal contribution to the graft was markedly increased to 89%. Average daily volume of ascites revealed a significant correlation with portal vein pressure, and not with PVF. When PVP exceeds 25 mmHg after transplantation, modulation of portal inflow might be required in order to improve the early postoperative outcome. Although the study population was small and contained several patients suffering from tumors or metabolic disease, all 19 patients made good progress and the 1-year graft and patient survival rate were 100%. A GV/SV ratio of less than 40% or PVF of more than 260 mL/min/100 g graft weight does not contraindicate transplantation, nor is it necessarily associated with a poor outcome. Left-lobe graft LDLT is still an important treatment option for adult patients. [Abstract]

Molinero LL, Zhou P, Wang Y, Harlin H, Kee B, Abraham C, Alegre ML
Epidermal Langerhans Cells Promote Skin Allograft Rejection in Mice With NF-kappaB-impaired T Cells.
Am J Transplant. 2007 Nov 16;
T cells play a major role in the acute rejection of transplanted organs. Using mice transgenic for a T-cell-restricted NF-kappaB super-repressor (IkappaBalphaDeltaN-Tg mice), we have previously shown that T-cell-NF-kappaB is essential for the acute rejection of cardiac but not skin allografts. In this study, we investigated the mechanism by which skin grafts activate IkappaBalphaDeltaN-Tg T cells. Rejection was not due to residual T-cell-NF-kappaB activity as mice with p50/p52(-/-) T cells successfully rejected skin grafts. Rather, skin but not cardiac allografts effectively induced proliferation of graft-specific IkappaBalphaDeltaN-Tg T cells. Rejection of skin grafts by IkappaBalphaDeltaN-Tg mice was in part dependent on the presence of donor Langerhans cells (LC), a type of epidermal dendritic cells (DC), as lack of LC in donor skin grafts resulted in prolongation of skin allograft survival and injection of LC at the time of cardiac transplantation was sufficient to promote cardiac allograft rejection by IkappaBalphaDeltaN-Tg mice. Our results suggest that LC allow NF-kappaB-impaired T cells to reach an activation threshold sufficient for transplant rejection. The combined blockade of T-cell-NF-kappaB with that of alternative pathways allowing activation of NF-kappaB-impaired T cells may be an effective strategy for tolerance induction to highly immunogenic organs. [Abstract]

Roche SL, Burch M, O'Sullivan J, Wallis J, Parry G, Kirk R, Elliot M, Shaw N, Flett J, Hamilton JR, Hasan A
Multicenter Experience of ABO-Incompatible Pediatric Cardiac Transplantation.
Am J Transplant. 2007 Nov 16;
Although ABO blood group incompatible cardiac transplantation in neonates and infants reduces waiting list mortality without compromising outcome, the technique has not been adopted by all centers, and to date Toronto remains the only center to have published results from a large case series. We present a review of ABO-incompatible heart transplantation in the United Kingdom (UK) where current recipient selection criteria differ somewhat from those used in the United States (US) and Canada. Between February 2000 and November 2006, 21 ABO-incompatible cardiac transplants were performed in children aged 2-40 months (median 10.0). Immunosuppression followed standard regimens. Pretransplant donor-specific isohemagglutinins of >1:4, (the UNOS cutoff), were present in five patients and reduced by plasma exchange. After transplantation, 19/21 recipients demonstrated persisting deficiency of donor-specific isohemagglutinins. Significant donor-specific isohemagglutinins levels were detected repeatedly in 2/21 recipients who have shown no clinical or biopsy evidence of rejection. All recipients survive without retransplantation and there have been no episodes of humoral rejection. We conclude it is possible for other centers to replicate the excellent results achieved in Toronto and that ABO-incompatible transplantation may be performed successfully in some patients beyond infancy with established isohemagglutinin production providing preoperative antibody removing strategies are used. [Abstract]

Sweet IR, Gilbert M, Scott S, Todorov I, Jensen R, Nair I, Al-Abdullah I, Rawson J, Kandeel F, Ferreri K
Glucose-Stimulated Increment in Oxygen Consumption Rate as a Standardized Test of Human Islet Quality.
Am J Transplant. 2007 Nov 16;
Standardized assessment of islet quality is imperative for clinical islet transplantation. We have previously shown that the increment in oxygen consumption rate stimulated by glucose (DeltaOCR(glc)) can predict in vivo efficacy of islet transplantation in mice. To further evaluate the approach, we studied three factors: islet specificity, islet composition and agreement between results obtained by different groups. Equivalent perifusion systems were set up at the City of Hope and the University of Washington and the values of DeltaOCR(glc) obtained at both institutions were compared. Islet specificity was determined by comparing DeltaOCR(glc) in islet and nonislet tissue. The DeltaOCR(glc) ranged from 0.01 to 0.19 nmol/min/100 islets (n = 14), a wide range in islet quality, but the values obtained by the two centers were similar. The contribution from nonislet impurities was negligible (DeltaOCR(glc) was 0.12 nmol/min/100 islets vs. 0.007 nmol/min/100 nonislet clusters). The DeltaOCR(glc) was statistically independent of percent beta cells, demonstrating that DeltaOCR(glc) is governed more by islet quality than by islet composition. The DeltaOCR(glc), but not the absolute level of OCR, was predictive of reversal of hyperglycemia in diabetic mice. These demonstrations lay the foundation for testing DeltaOCR(glc) as a measurement of islet quality for human islet transplantation. [Abstract]

Yao F, Seed C, Farrugia A, Morgan D, Cordner S, Wood D, Zheng MH
The risk of HIV, HBV, HCV and HTLV infection among musculoskeletal tissue donors in Australia.
Am J Transplant. 2007 Dec;7(12):2723-6.
In Australia, there are no current national estimates of the risks of transmission of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human T-lymphotrophic virus (HTLV) by musculoskeletal tissue transplantation. We determined the prevalence rates of antibodies against HIV (anti-HIV), HCV (anti-HCV) and HTLV (anti-HTLV) and Hepatitis B surface antigen (HBsAg) for 12,415 musculoskeletal tissue donors from three major bone tissue banks across Australia for the period 1993-2004. The prevalence (per 100,000 persons) was 64.44 for anti-HIV, 407.13 for HBsAg, 534.63 for anti-HCV and 121.88 for anti-HTLV. The estimated probability of viremia at the time of donation was 1 in 128,000, 1 in 189,000, 1 in 55,000 and 1 in 118,000, respectively. With the addition of nucleic acid amplification testing (NAT), the probability of donor viremia would be reduced to 1 in 315,000 for HIV, 1 in 385,000 for HBV and 1 in 500,000 for HCV. The prevalence of HIV, HBV, HCV and HTLV although low, are higher among musculoskeletal tissue donors than among first-time blood donors. The risks associated with musculoskeletal donation will be reduced with NAT, though further cost analysis is required prior to its implementation. [Abstract]

Truong W, Plester JC, Hancock WW, Merani S, Murphy TL, Murphy KM, Kaye J, Anderson CC, Shapiro AM
Combined coinhibitory and costimulatory modulation with anti-BTLA and CTLA4Ig facilitates tolerance in murine islet allografts.
Am J Transplant. 2007 Dec;7(12):2663-74.
Complex interactions between positive and negative cosignaling receptors ultimately determine the fate of the immune response. The recently identified coinhibitory receptor, B and T lymphocyte attenuator (BTLA), contributes to regulation of autoimmune and potentially alloimmune responses. We investigated the role of BTLA in a fully major histocompatibility complex-mismatched mouse islet transplant model. We report that anti-BTLA mAb (6F7) alone does not accelerate graft rejection. Rather, while CTLA4Ig alone improved allograft survival, the addition of anti-BTLA mAb to CTLA4Ig led to indefinite (>100 days) allograft survival. Immediately after treatment with anti-BTLA mAb and CTLA4Ig, islet allografts showed intact islets and insulin production despite a host cellular response, with local accumulation of Foxp3+ cells. We clearly demonstrate that combined therapy with anti-BTLA mAb and CTLA4Ig mice induced donor-specific tolerance, since mice accepted a second donor-specific islet graft without further treatment and rejected third party grafts. CTLA4Ig and anti-BTLA mAb limited the initial in vivo proliferation of CFSE-labeled allogeneic lymphocytes, and anti-BTLA mAb enhanced the proportion of PD-1 expressing T cells while depleting pathogenic BTLA+ lymphocytes. We conclude that targeting the BTLA pathway in conjunction with CTLA4Ig costimulatory blockade may be a useful strategy for promoting immunological tolerance in murine islet allografts. [Abstract]

Fishman JA, Greenwald MA, Kuehnert MJ
Enhancing transplant safety: a new era in the microbiologic evaluation of organ donors?
Am J Transplant. 2007 Dec;7(12):2652-4. [Abstract]

Colvin RB
Getting out of flatland: into the third dimension of microarrays.
Am J Transplant. 2007 Dec;7(12):2650-1. [Abstract]

Schold JD, Srinivas TR, Kayler LK, Meier-Kriesche HU
The Overlapping Risk Profile Between Dialysis Patients Listed and Not Listed for Renal Transplantation.
Am J Transplant. 2007 Nov 2;
The survival advantage of kidney transplantation extends to many high-risk ESRD patients; however, numerous factors ultimately determine which patients are evaluated and listed for the procedure. Broad goals of patient evaluation comprise identifying patients who will benefit from transplantation and excluding patients who might be placed at risk. There is limited data detailing whether current access limitations and screening strategies have achieved the goal of listing the most appropriate patients. The study estimated the life expectancy of adult patients in the United States prior to transplantation with ESRD onset from 1995 to 2003. Factors associated with transplant listing were examined based on patient prognosis after ESRD. Approximately one-third of patients listed for transplantation within 1 year of ESRD had </=5-year life expectancy on dialysis. In contrast, one-third of patients not listed had >5-year life expectancy. The number of patients not listed with 'good' prognosis was significantly higher than those listed with 'poor' prognosis (134 382 vs. 16 807, respectively). Age, race, gender, insurance coverage and body mass index (BMI) were associated with likelihood for listing with 'poor' prognosis and not listing with 'good' prognosis. Over the past decade, many ESRD patients viable for transplantation have not listed for transplantation while higher-risk patients have listed rapidly. [Abstract]

Yabu JM, Ho B, Scandling JD, Vincenti F
Rituximab Failed to Improve Nephrotic Syndrome in Renal Transplant Patients With Recurrent Focal Segmental Glomerulosclerosis.
Am J Transplant. 2007 Nov 2;
Focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients with FSGS receiving a first renal transplant and in over 80% of patients receiving a second transplant after a recurrence. Recurrence often leads to graft failure. The pathogenesis remains unknown and may involve a circulating permeability factor that initiates injury to the glomerular capillary. There are anecdotal reports of pediatric patients with posttransplant lymphoproliferative disorder (PTLD) and recurrent FSGS who have had remission of proteinuria after treatment with rituximab. These observations have prompted speculation that B cells may play a role in the pathogenesis of recurrent FSGS. We report four consecutive adult patients with early recurrent FSGS refractory or dependent on plasmapheresis who received rituximab (total dose 2000-4200 mg). None of the patients treated with rituximab achieved remission in proteinuria, and one patient experienced early graft loss. In these four adult renal transplant patients with recurrent FSGS, rituximab failed to diminish proteinuria. [Abstract]

Frei U, Noeldeke J, Machold-Fabrizii V, Arbogast H, Margreiter R, Fricke L, Voiculescu A, Kliem V, Ebel H, Albert U, Lopau K, Schnuelle P, Nonnast-Daniel B, Pietruck F, Offermann R, Persijn G, Bernasconi C
Prospective Age-Matching in Elderly Kidney Transplant Recipients-A 5-Year Analysis of the Eurotransplant Senior Program.
Am J Transplant. 2007 Oct 31;
Renal transplantation faces challenges: the organ shortage resulting in extended waiting times and an aging population resulting in death with a functioning graft. The Eurotransplant Senior Program (ESP) allocates kidneys within a narrow geographic area from donors aged >/=65 years to recipients >/=65 years regardless of HLA. This analysis investigates the impact of the ESP on waiting time, graft and patient survival. The ESP group (n = 1406, old to old) was compared to two groups allocated via the Eurotransplant Kidney Allocation System (ETKAS) with either similar donor age (old to any [O/A], donor age >/=65, n = 446) or recipient age (any to old, [A/O], recipient age 60-64, n = 1687). All patients were transplanted between 1999 and 2004. Since initiation of the ESP (1999), availability of elderly donors doubled and waiting time for ESP patients decreased. Local allocation led to shorter cold ischemia time (11.9 vs. >17.0 h, p < 0.001) and less delayed graft function (DGF, ESP 29.7% vs. O/A 36.2%, p = 0.047) but 5-10% higher rejection rates. Graft and patient survival were not negatively affected by the ESP allocation when compared to the standard allocation. The ESP age matching of elderly donors and recipients is an effective allocation system for organs from elderly donors. [Abstract]

Valta H, Jalanko H, Holmberg C, Helenius I, Mäkitie O
Impaired Bone Health in Adolescents After Liver Transplantation.
Am J Transplant. 2007 Oct 31;
Long-term complications related to immunosuppressive medication are an important problem after liver transplantation (OLT). This study was carried out to evaluate the bone health and risk factors for osteoporosis and fractures in 40 pediatric liver transplant recipients. The results of 208 longitudinal bone mineral density (BMD) measurements were analyzed retrospectively. In addition, a dual-energy X-ray absorptiometry was performed to assess the bone mineral content more precisely and to detect subclinical vertebral fractures (VF). The median age of the patients was 14 years and mean postoperative follow-up 7.0 years. The results showed that over half (58%) had lumbar spine (LS) Z-score </=-1.0 and one-fifth (18%) had asymptomatic VF. LS Z-score tended to increase from the first year after OLT, but during puberty the bone mass gain was suboptimal and Z-scores decreased in some subjects. Patients with VF were older at the time of OLT (p = 0.002) and their LS Z-score was lower (p = 0.001). Children transplanted before 10 years of age had less VF (p = 0.004) and higher LS Z-score (p = 0.005) than older patients. In conclusion, adolescent liver recipients are prone to osteoporosis and prevention should be targeted especially to this age group. [Abstract]

Ding JW, Zhou T, Ma L, Yin D, Shen J, Ding CP, Tang IY, Byrne GW, Chong AS
Expression of Complement Regulatory Proteins in Accommodated Xenografts Induced by Anti-alpha-Gal IgG(1) in a Rat-to-Mouse Model.
Am J Transplant. 2007 Oct 31;
Anti-graft antibodies are often associated with graft rejection. Under special conditions, grafts continue to function normally even in the presence of anti-graft antibodies and complement. This condition is termed accommodation. We developed a xenograft accommodation model in which baby Lewis rat hearts are transplanted into Rag/GT-deficient mice, and accommodation is induced by repeated i.v. injections of low-dose anti-alpha-Gal IgG(1). The accommodated grafts survived a bolus dose of anti-alpha-Gal IgG(1), while freshly transplanted second grafts were rejected. To study the mechanism of anti-alpha-Gal IgG(1)-mediated accommodation, both real-time PCR and immunohistochemical staining revealed elevated expression of DAF, Crry and CD59 in the accommodated grafts. In vitro exposure of rat endothelial cells to anti-alpha-Gal IgG(1) also induced the up-regulation of DAF, Crry and CD59, as revealed by Western blot analyses, and was associated with an acquired resistance to antibody and complement-mediated lysis in vitro. Collectively, these studies suggest that the up-regulation of complement regulatory proteins may abrogate complement-mediated rejection and permit the development of xenograft accommodation. [Abstract]

Vo AA, Wechsler EA, Wang J, Peng A, Toyoda M, Lukovsky M, Reinsmoen N, Jordan SC
Analysis of Subcutaneous (SQ) Alemtuzumab Induction Therapy in Highly Sensitized Patients Desensitized With IVIG and Rituximab.
Am J Transplant. 2007 Oct 31;
Here we report on our experience with subcutaneous (SQ) Alemtuzumab in an uncontrolled study in highly HLA-sensitized patients (HS). From 3/05-4/07, 54 HS patients received Alemtuzumab 30 mg SQ as induction. Patient and graft survival, AR episodes, serum creatinines, absolute lymphocyte counts, monthly PCR monitoring for viruses, AE/SAEs and infectious complications were monitored. No patient to date has developed acute injection-related reactions after SQ Alemtuzumab; however, bone marrow suppression was occasionally seen requiring reduction or elimination of mycophenolate mofetil approximately 1-2 months posttransplant. Patient and graft survival at 12 M was 98%/96%, respectively. AR episodes occurred in 35% with 20% being C4d+ AMR. Mean SCrs at 12 M were 1.4 +/- 0.3 mg/dL. The nadir ALC was 0.17 +/- 0.19 within 24 h and sustained up to 365 days posttransplant. Infections occurred in eight patients (five with polyoma BK viremia [PBK], one CMV/PBK and two CMV viremia). SQ Alemtuzumab was well tolerated and resulted in prolonged lymphocyte depletion. Compared to our previous experience with daclizumab and rabbit ATG induction in HS patients, single-dose SQ Alemtuzumab was more cost effective, showed similar infection rates and did not reduce the AMR rates posttransplant. Although uncontrolled, these observations suggest that induction therapy with Alemtuzumab appears feasible and indeed promising, but awaits more definitive study. [Abstract]

Dean PG, Kudva YC, Larson TS, Kremers WK, Stegall MD
Posttransplant Diabetes Mellitus After Pancreas Transplantation.
Am J Transplant. 2007 Oct 31;
Some patients do not achieve normoglycemia after an otherwise successful pancreas transplant. The aim of this study was to define the incidence and risk factors for the development of persistent diabetes mellitus after pancreas transplantation. We studied the outcomes of 144 pancreas transplants performed at our institution between January 2001 and December 2005. Diabetes mellitus was defined as the persistent need for pharmacologic treatment of diabetes mellitus despite evidence of allograft function. Data are expressed as median (25-75% inter-quartile range). Median follow-up was 39 months (IQR 26-55 months). During the follow-up period, 28 patients (19%) developed diabetes mellitus with a functioning allograft. Factors predicting hyperglycemia included: pretransplant insulin dose, BMI and acute rejection episodes (p < 0.0001, p = 0.0002 and p < 0.02, respectively). The median pretransplant hemoglobin A1c for patients developing diabetes was 8.3% (IQR 7.0-9.4%) compared to 6.2% (IQR 5.8-7.4%) at 2 years after transplant (p = 0.0069). In conclusion, persistent diabetes mellitus can occur despite the presence of a functioning pancreas allograft and is due to increased pretransplant BMI, high pretransplant insulin requirements and episodes of acute rejection. [Abstract]

D'Alessandro AM, Peltier JW, Phelps JE
An Empirical Examination of the Antecedents of the Acceptance of Donation After Cardiac Death by Health Care Professionals.
Am J Transplant. 2007 Oct 31;
Findings are reported from a US Department of Health and Human Services (DHHS) funded study to identify barriers to increasing support for donations after cardiac death by health professionals. A donations after cardiac death (DCD) acceptance model is conceptualized and tested via 806 survey responses from certified requestors, all of whom had their identities protected through Institutional Review Board (IRB) protocol. The overall model was significant and explained 35% of the variation in DCD support. Greater knowledge about DCD, greater trust in the organ procurement organization (OPO) and a belief that futility has been reached were all positively associated with DCD acceptance. Negative perceptions of DCD versus brain death, transitioning from caregiving to donation advocate, concerns about the DCD process and the idea that DCD leads to active participation in the death reduced its support. The three greatest impediments to support of DCD exist when health professionals feel they are playing an active role in killing the patient, that a state of death has not yet been reached, and that DCD has more psychological barriers than does the brain death donation process. Opportunities and strategic initiatives are discussed to overcome these barriers, including the value of communication and education initiatives and the need for well-trained requestors. The implementation of these strategic guidelines helped to increase the number of DCD donors by 225%. [Abstract]

Lee J, Clayton F, Shihab F, Goldfarb-Rumyantzev A
Successful Treatment of Recurrent Henoch-Schönlein Purpura in a Renal Allograft with Plasmapheresis.
Am J Transplant. 2007 Oct 31;
Acute and severe cases of Henoch-Schönlein purpura (HSP) nephritis have been treated with plasmapheresis (PA) in both adults and children. It has been used either alone or with steroids, antiplatelets or cytoxic drugs. Generally, renal function has been shown to improve when PA is utilized. The role of PA in recurrent HSP after renal transplantation is unclear and has not been well described in the literature. We report a 29-year-old female with HSP who developed end-stage renal disease and subsequently underwent a renal transplantation with eventual loss of the allograft 5 years later due to recurrent HSP nephritis. Retransplantion was performed and the patient developed active HSP nephritis in her second allograft within a week after transplantation. In an effort to preserve her allograft, four cycles of PA were performed. Her proteinuria resolved and renal biopsies afterwards demonstrated marked reduction in mesangial IgA deposition. We conclude that PA may be useful in recurrent HSP nephritis, especially when used early. The risk of additional immunosuppression caused by PA needs to be considered. More studies need to be done to evaluate the efficacy of PA in this setting as well as to define the optimal treatment regimen. [Abstract]

Starzl TE, Shapiro R
In Memoriam-James S. Wolf.
Am J Transplant. 2007 Oct 31; [Abstract]

Levitsky J, Singh N, Wagener MM, Stosor V, Abecassis M, Ison MG
A Survey of CMV Prevention Strategies After Liver Transplantation.
Am J Transplant. 2007 Oct 31;
The degree of variability in the use of CMV prevention strategies and choice of antiviral regimens among LT centers has not been previously investigated. An electronic survey on current CMV prevention strategies was sent to all US and Canadian LT centers. A total of 58 (53%) centers completed the survey. Most use CMV PCR for screening or diagnosis. Prophylaxis was the most common prevention strategy for all donor/recipient subtypes except D-/R- who often receive no prophylaxis. Prophylaxis was usually given for 3 months after LT with valganciclovir the most frequently used agent. In the small percentage of centers utilizing the preemptive approach, monitoring for CMV was typically performed with PCR for 3 months and valganciclovir was most frequently used for treatment of detectable CMV viremia. In conclusion, the majority of LT centers utilize CMV prophylaxis over other strategies. Valganciclovir is the most commonly used agent for both antiviral prophylaxis and treatment of CMV viremia in the preemptive approach. [Abstract]

Bograd AJ, Mital S, Schwarzenberger JC, Mosca RS, Quaegebeur JM, Addonizio LJ, Hsu DT, Lamour JM, Chen JM
Twenty-Year Experience With Heart Transplantation for Infants and Children With Restrictive Cardiomyopathy: 1986-2006.
Am J Transplant. 2007 Oct 31;
Idiopathic restrictive cardiomyopathy (RCM) is a rare cardiomyopathy in children notable for severe diastolic dysfunction and progressive elevation of pulmonary vascular resistance (PVR). Traditionally, those with pulmonary vascular resistance indices (PVRI) >6 W.U. x m(2) have been precluded from heart transplantation (HTX). The clinical course of all patients transplanted for RCM between 1986 and 2006 were reviewed. Preoperative, intraoperative and postoperative variables were evaluated. A total of 23 patients underwent HTX for RCM, with a mean age of 8.8 +/- 5.6 years and a mean time from listing to HTX of 43 +/- 60 days. Preoperative and postoperative (114 +/- 40 days) PVRI were 5.9 +/- 4.4 and 2.9 +/- 1.5 W.U. x m(2), respectively. At time of most recent follow-up (mean = 5.7 +/- 4.6 years), the mean PVRI was 2.0 +/- 1.0 W.U. x m(2). Increasing preoperative mean pulmonary artery pressure (PA) pressure (p = 0.04) and PVRI > 6 W.U. x m(2) (chi(2)= 7.4, p < 0.01) were associated with the requirement of ECMO postoperatively. Neither PVRI nor mean PA pressure was associated with posttransplant mortality; 30-day and 1-year actuarial survivals were 96% and 86%, respectively. Five of the seven patients with preoperative PVRI > 6 W.U. x m(2) survived the first postoperative year. We report excellent survival for patients undergoing HTX for RCM despite the high proportion of high-risk patients. [Abstract]

Nash KL, Collier JD, French J, McKeon D, Gimson AE, Jamieson NV, Wallwork J, Bilton D, Alexander GJ
Cystic Fibrosis Liver Disease: To Transplant or Not to Transplant?
Am J Transplant. 2007 Oct 31;
Biliary cirrhosis complicates some adults with cystic fibrosis (CF) and may require transplantation. Cardio-respiratory disease severity varies such that patients may require liver transplantation, heart/lung/liver (triple) grafts or may be too ill for any procedure. A 15-year experience of adults with CF-related liver disease referred for liver transplantation is presented with patient survival as outcome. Twelve patients were listed for triple grafting. Four died of respiratory disease after prolonged waits (4-171 weeks). Eight underwent transplantation (median wait 62 weeks); 5-year actuarial survival was 37.5%. Four died perioperatively; only one is alive at 8-years. Eighteen patients underwent liver transplant alone (median wait 7 weeks); 1- and 5-year actuarial survival rates were 100% and 69%. Three long-term survivors required further organ replacement (two heart/lung and one renal). Two others were turned down for heart/lung transplantation and four have significant renal impairment. Results for triple grafting were poor with unacceptable waiting times. Results for liver transplant alone were satisfactory, with acceptable waiting times and survival. However, further grafts were required and renal impairment was frequent. The policy of early liver transplantation for adults with CF with a view to subsequent heart/lung or renal transplantation needs assessment in the context of long-term outcome. [Abstract]

Jalanko H, Peltonen S, Koskinen A, Puntila J, Isoniemi H, Holmberg C, Pinomäki A, Armstrong E, Koivusalo A, Tukiainen E, Mäkisalo H, Saland J, Remuzzi G, de Cordoba S, Lassila R, Meri S, Jokiranta TS
Successful Liver-Kidney Transplantation in Two Children With aHUS Caused by a Mutation in Complement Factor H.
Am J Transplant. 2007 Oct 31;
A 12-month-old boy and his 16-year-old aunt became acutely ill 6 months apart and were diagnosed to have atypical hemolytic uremic syndrome (aHUS). Genetic analysis revealed heterozygous R1215Q mutation in complement factor H (CFH) in both patients. The same mutation was found in five healthy adult relatives indicating incomplete penetrance of the disease. The patients developed terminal renal failure and experienced reversible neurological symptoms in spite of plasma exchange (PE) therapy. In both cases, liver-kidney transplantation was successfully performed 6 months after the onset of the disease. To minimize complement activation and prevent thrombotic microangiopathy or overt thrombotic events due to the malfunctioning CFH, extensive PE with fresh frozen plasma was performed pre- and perioperatively and anticoagulation was started a few hours after the operation. No circulatory complications appeared and all four grafts started to function immediately. Also, no recurrence or other major clinical setbacks have appeared during the postoperative follow-up (15 and 9 months) and the grafts show excellent function. While more experience is needed, it seems that liver-kidney transplantation combined with pre- and perioperative PE is a rational option in the management of patients with aHUS caused by CFH mutation. [Abstract]

Connor A, Lunt PW, Dolling C, Patel Y, Meredith AL, Gardner A, Hamilton NK, Dudley CR
Mosaicism in Autosomal Dominant Polycystic Kidney Disease Revealed by Genetic Testing to Enable Living Related Renal Transplantation.
Am J Transplant. 2007 Oct 31;
Patients with end-stage renal disease (ESRD) secondary to autosomal dominant polycystic kidney disease (ADPKD) receive fewer living-related kidney (LRK) transplants than other groups with ESRD. This relates to the difficulties in excluding the disease in potential donors. We report a case which highlights these difficulties and, by discovery of mosaicism for a new mutation, illustrates the role of clinical and molecular genetic resources in assessing young related kidney donors for patients with ADPKD. [Abstract]

Reischig T, Jindra P, Hes O, Svecová M, Klaboch J, T?e?ka V
Valacyclovir Prophylaxis Versus Preemptive Valganciclovir Therapy to Prevent Cytomegalovirus Disease After Renal Transplantation.
Am J Transplant. 2007 Oct 31;
Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (>/=2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 +/- 22 vs. 187 +/- 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation. [Abstract]

Charpentier B
TRIBUTE: Professor R. Küss, 1913-2006.
Am J Transplant. 2007 Dec;7(12):2655-6. [Abstract]

Recent Articles in The American Journal of Surgical Pathology

Zembowicz A, Knoepp SM, Bei T, Stergiopoulos S, Eng C, Mihm MC, Stratakis CA
Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions.
Am J Surg Pathol. 2007 Nov;31(11):1764-75.
Pigmented epithelioid melanocytoma (PEM) is a recently described entity comprising most cases previously described as "animal-type melanoma" and epithelioid blue nevus (EBN) occurring in patients with the multiple neoplasia syndrome Carney complex (CNC). Mutations of the protein kinase A regulatory subunit type 1alpha (R1alpha) (coded by the PRKAR1A gene) are found in more than half of CNC patients. In this study, we investigated whether PEM and EBN are related at the molecular level, and whether changes in the PRKAR1A gene status and the expression of the R1alpha protein may be involved in the pathogenesis of PEM and other melanocytic lesions. Histologic analysis of hematoxylin and eosin-stained sections and immunohistochemistry (IHC) with R1alpha antibody were performed on 34 sporadic PEMs, 8 CNC-associated PEMs from patients with known PRKAR1A mutations, 297 benign and malignant melanocytic tumors (127 conventional sections of 10 compound nevi, 10 Spitz nevi, 5 deep-penetrating nevi, 5 blue nevi, 6 cellular blue nevi, 2 malignant blue nevi, 3 lentigo maligna, and 86 melanomas of various types); in addition, 170 tissue microarray sections consisting of 35 benign nevi, 60 primary melanomas, and 75 metastatic melanomas, and 5 equine dermal melanomas, were examined. Histologic diagnoses were based on preexisting pathologic reports and were confirmed for this study. DNA studies [loss of heterozygosity (LOH) for the 17q22-24 locus and the PRKAR1A gene sequencing] were performed on 60 melanomas and 7 PEMs. IHC showed that R1alpha was expressed in all but one core from tissue microarrays (169/170), and in all 127 melanocytic lesions evaluated in conventional sections. By contrast, R1alpha was not expressed in the 8 EBN from patients with CNC and PRKAR1A mutations. Expression of R1alpha was lost in 28 of 34 PEMs (82%). R1alpha was expressed in the 5 equine melanomas studied. DNA studies correlated with IHC findings: there were no PRKAR1A mutations in any of the melanomas studied and the rate of LOH for 17q22-24 was less than 7%; 5 of the 7 PEMs showed extensive 17q22-24 LOH but no PRKAR1A mutations. The results support the concept that PEM is a distinct melanocytic tumor occurring in a sporadic setting and in the context of CNC. They also suggest that PEM differs from melanomas in equine melanotic disease, further arguing that the term animal-type melanoma may be a misnomer for this group of lesions. Loss of expression of R1alpha offers a useful diagnostic test that helps to distinguish PEM from lesions that mimic it histologically. [Abstract]

Siami K, McCluggage WG, Ordonez NG, Euscher ED, Malpica A, Sneige N, Silva EG, Deavers MT
Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas.
Am J Surg Pathol. 2007 Nov;31(11):1759-63.
Thyroid transcription factor-1 (TTF-1) is widely used in the diagnosis of lung and thyroid carcinomas. Although there have been reports of TTF-1 immunoreactivity in tumors other than those originating in the lung or thyroid, endocervical and endometrial adenocarcinomas have not been studied in large numbers. Our study provides data regarding the incidence and distribution of TTF-1 expression in these tumors. Twenty-eight endocervical (9 well, 12 moderately, and 7 poorly differentiated), 32 endometrioid endometrial adenocarcinomas (11 grade I, 8 grade II, and 13 grade III), and 13 uterine serous carcinomas were retrieved and stained with TTF-1. None of the tumors had a neuroendocrine component. The hematoxylin and eosin and anti-TTF-1 antibody stained sections were reviewed, and the presence and distribution of TTF-1 nuclear positivity was recorded. A semiquantitative grading system used to evaluate the distribution of TTF-1 staining (0 = negative, 1+ = <5%, 2+ = 5% to 25%, 3+ = 26% to 50%, 4+ = 51% to 75%, and 5+ = >75%). TTF-1 expression was seen in 1 of 28 (4%) of the endocervical adenocarcinomas and this was 4+ in distribution. The positive endocervical carcinoma was poorly differentiated. TTF-1 expression was present in 6 of 32 (19%) of the endometrioid adenocarcinomas (1 grade I, 2 grade II, and 3 grade III) and varied from 1+ to 4+ in distribution. Only 2 of 32 (6%) of the endometrioid adenocarcinomas stained diffusely (4+). There was no apparent correlation between the degree of differentiation and TTF-1 positivity in the adenocarcinomas. Three of 13 (23%) serous carcinomas were also positive (1 case 5+ and 2 cases 1+). Although TTF-1 is generally considered to be a relatively specific marker for lung and thyroid neoplasms, the occasional expression of endometrial and endocervical carcinomas should be kept in mind when evaluating neoplasms of uncertain origin. It should also be taken into consideration in the evaluation of adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy. [Abstract]

Johnson K, Kotiesh A, Boitnott JK, Torbenson M
Histology of symptomatic acute hepatitis C infection in immunocompetent adults.
Am J Surg Pathol. 2007 Nov;31(11):1754-8.
Acute hepatitis C in immunocompetent individuals is rarely symptomatic and rarely biopsied. Thus, the histologic descriptions of acute hepatitis C remain limited. The histology of 5 cases of acute hepatitis C in adults were studied by selecting cases from the consult and surgical pathology files of a single institution. The 5 individuals, 3 males and 2 females, had an average age at biopsy of 50+/-17 years. They presented with jaundice and other nonspecific abdominal symptoms. The time interval from clinical presentation to biopsy ranged from 2 to 18 weeks. The average alanine aminotransferase/aspartate aminotransferase/alkaline phosphatase at the time of biopsy was 308/73/85 U/L. The average total bilirubin was 5.2 mg/dL. Each individual had a single liver biopsy. The histologic findings of the 2 cases biopsied in close temporal proximity to the initial clinical presentation showed similar histologic findings of mixed portal infiltrates with lymphocytes and neutrophils along with bile ductular proliferation that raised the possibility of down stream biliary tract disease. The lobules showed canalicular cholestasis and mild to moderate inflammation. In the third and fourth case, obtained 8 weeks after presentation, the biopsies showed mild to moderate portal and lobular lymphocytic inflammation, findings that were also present in the last case, obtained 18 weeks after presentation. In conclusion, early after acute hepatitis C viral infection, biopsies can have a cholestatic pattern whereas later biopsies tend to show mild nonspecific portal and lobular lymphocytic inflammation. Proper histologic diagnosis can be aided by an awareness of the various histologic findings, which vary depending on the time interval from clinical symptoms to biopsy. [Abstract]

Yantiss RK, Panczykowski A, Misdraji J, Odze RD, Rennert H, Chen YT
A comprehensive study of nondysplastic and dysplastic serrated polyps of the vermiform appendix.
Am J Surg Pathol. 2007 Nov;31(11):1742-53.
Serrated colorectal polyps often show DNA hypermethylation and/or BRAF mutations and have been implicated in the "serrated neoplastic pathway." Although similar lesions occur in the appendix, they have never been systematically investigated. We evaluated a study group of 56 serrated polyps, a control group of 17 mucinous cystadenomas, and 4 adenocarcinomas with adjacent serrated polyps of the appendix to better understand their pathogenesis. The study cases were classified as nondysplastic or dysplastic serrated polyps and evaluated for MLH-1, MSH-2, MGMT, beta-catenin, p53, and Ki-67 expression, BRAF and KRAS mutations, and microsatellite instability. Serrated polyps usually occurred in older adults with no sex predilection. Most (59%) lacked dysplasia, but all showed similar molecular features, regardless of the degree of dysplasia present. Decreased MLH-1 (50%, P<0.001) and/or MGMT (59%, P<0.001) expression and BRAF (29%, P=0.007) mutations were significantly more common in serrated polyps, but BRAF mutations were detected in a minority of the extracted DNA in 15/16 cases. Of the 28 cases with decreased MLH-1 expression, none showed high-frequency microsatellite instability. Loss of MLH-1 (25%) or MGMT (50%) expression and BRAF or KRAS mutations (50%) were inconsistently present in adenocarcinomas and were not identified in combination in any cases. We conclude that molecular features of the "serrated neoplastic pathway" are present with similar frequencies among dysplastic and nondysplastic serrated appendiceal polyps and are not highly prevalent in adjacent carcinomas. These features, including BRAF mutations, may be more closely related to a serrated morphology in appendiceal polyps rather than biologically important changes. [Abstract]

Srivastava A, Odze RD, Lauwers GY, Redston M, Antonioli DA, Glickman JN
Morphologic features are useful in distinguishing barrett esophagus from carditis with intestinal metaplasia.
Am J Surg Pathol. 2007 Nov;31(11):1733-41.
Barrett esophagus (BE) and carditis with intestinal metaplasia (CIM) differ in their risk of malignancy and implications for patient management, but are difficult to distinguish in mucosal biopsies from the gastroesophageal junction region. The present study was performed to evaluate the role of routine morphology in distinguishing BE from CIM in mucosal biopsies and to assess the degree of interobserver variability in recognizing morphologic parameters that are of significance in making this distinction. Several morphologic features, including presence of crypt disarray and atrophy, incomplete and diffuse intestinal metaplasia, multilayered epithelium, squamous epithelium overlying columnar crypts with intestinal metaplasia, hybrid glands, and esophageal glands/ducts, were significantly associated with a diagnosis of BE. The latter 3 features were observed exclusively in BE biopsies. Furthermore, multiple BE-associated morphologic features were often present together in BE but not CIM biopsies. There was substantial agreement (kappa=0.6) among expert gastrointestinal pathologists for distinguishing BE from CIM even in the absence of clinical/endoscopic information. The interobserver agreement in recognition of BE-associated morphologic features ranged from almost perfect for some features like esophageal glands/ducts (kappa=0.83) to slight for multilayered epithelium (kappa=0.17). In conclusion, our findings indicate that several morphologic features are helpful in distinguishing BE from CIM. The combined presence of multiple BE-associated morphologic features can be used in making this distinction with a high degree of accuracy. Larger prospective studies need to be performed to validate these findings and evaluate the reproducibility of this approach in routine clinical practice. [Abstract]

Mao TL, Kurman RJ, Huang CC, Lin MC, Shih IeM
Immunohistochemistry of choriocarcinoma: an aid in differential diagnosis and in elucidating pathogenesis.
Am J Surg Pathol. 2007 Nov;31(11):1726-32.
Choriocarcinoma is traditionally described as being composed of cytotrophoblast and syncytiotrophoblast. Microscopically, these 2 types of cells are intimately associated with each other, forming a characteristic biphasic plexiform pattern, however, the nature of these 2 types of trophoblastic cells is not well understood. In this study, we used immunohistochemistry for several trophoblastic markers to analyze the trophoblastic subpopulations in 36 gestational choriocarcinomas. Eighty-one specimens including placenta, complete mole, placental site nodule, epithelioid trophoblastic tumor, and placental site trophoblastic tumor were analyzed. The antibodies included Mel-CAM, HLA-G, MUC-4, and beta-catenin. A semiquantitative assessment of positive cells and the cellular localization of these markers were recorded. We found diffuse strong membranous and cytoplasmic staining for MUC-4 in mononucleate cells in all 36 cases (100%) and a similar pattern of localization in 28 cases (78%) for HLA-G. This distribution was similar to that in normal placentas, where MUC-4 and HLA-G are expressed in the trophoblastic cells of the trophoblastic columns and implantation site. In choriocarcinoma, mononucleate trophoblastic cells showed moderate immunoreactivity for Mel-CAM, a specific marker for implantation site intermediate trophoblast, in 78% of the cases. The MUC-4, HLA-G, and Mel-CAM-positive trophoblastic cells were larger than cytotrophoblastic cells, with more abundant cytoplasm, consistent with the morphology of intermediate trophoblast. In contrast, 31% of the choriocarcinomas contained a very small proportion (<5%) of mononucleate trophoblastic cells compatible with cytotrophoblast that was positive for nuclear beta-catenin, a cytotrophoblast-associated marker. These results suggest that choriocarcinoma is composed predominantly of a mixture of syncytiotrophoblast and intermediate trophoblast with only a small proportion of cytotrophoblast. The presence of nuclear beta-catenin staining in the cytotrophoblast of choriocarcinoma is consistent with the view that choriocarcinoma develops from transformed cytotrophoblastic cells which are presumably the cancer stem cells that differentiate into either intermediate trophoblast or syncytiotrophoblast. [Abstract]

Abraham SC, Krasinskas AM, Correa AM, Hofstetter WL, Ajani JA, Swisher SG, Wu TT
Duplication of the muscularis mucosae in barrett esophagus: an underrecognized feature and its implication for staging of adenocarcinoma.
Am J Surg Pathol. 2007 Nov;31(11):1719-25.
Depth of invasion is one of the most important prognostic indicators in esophageal adenocarcinoma. Unlike other regions of the gastrointestinal tract, the esophagus in Barrett metaplasia frequently develops duplication of the muscularis mucosae (MM), but this feature is underrecognized, and its effect on appropriate staging of superficially invasive adenocarcinoma is unclear. We first randomly selected 50 esophageal resections for high-grade dysplasia or T1 adenocarcinoma in Barrett esophagus (BE) to evaluate the sensitivity and specificity of MM duplication for BE and its histologic characteristics, including percentage of the Barrett segment involved by MM duplication, origin of the duplicated muscle layer, and appearance of the tissue between duplicated MM. Twenty esophageal resections for squamous cell carcinoma served as controls. Next, to study the clinical significance of MM duplication, we evaluated 30 resections for BE that had superficial adenocarcinoma confined to regions of duplicated MM. Each case was classified as: depth of invasion (inner MM, space between duplicated MM, or outer MM), angiolymphatic invasion, and rate of lymph node metastasis. We observed MM duplication in 46 of 50 (92%) BE resections, involving 5% to >90% of the Barrett segment, in contrast to none in 20 (0%) resected squamous cell carcinoma, P<0.0001. In 5 (10%) cases, the MM was focally triplicated. The outer MM was continuous with the single MM beneath squamous epithelium, suggesting that outer MM represents the "original" muscle layer. The space between duplicated MM predominantly consisted of loose fibrovascular tissue similar to submucosa; in 15 (30%) cases, there were also areas of fibrosis or thin muscle strands joining the 2 MM layers. Of 30 adenocarcinomas invading duplicated MM, 10 (33%) invaded only inner MM, 12 (40%) invaded the space between MM, and 8 (27%) invaded the outer MM. Angiolymphatic invasion was present in 5 (17%) cases, and nodal metastases in 3 (10%, 1 case each of invasion into inner MM, between MM, and outer MM). These data show that MM duplication is a characteristic finding in BE, but it can pose difficulty in proper staging of superficial adenocarcinomas. The 17% rate of angiolymphatic invasion and 10% rate of lymph node metastases in our patients with invasion into duplicated MM suggest that these tumors can behave aggressively despite their technically intramucosal location. [Abstract]

Preusser M, Hoischen A, Novak K, Czech T, Prayer D, Hainfellner JA, Baumgartner C, Woermann FG, Tuxhorn IE, Pannek HW, Bergmann M, Radlwimmer B, Villagrán R, Weber RG, Hans VH
Angiocentric glioma: report of clinico-pathologic and genetic findings in 8 cases.
Am J Surg Pathol. 2007 Nov;31(11):1709-18.
Angiocentric glioma has recently been described as a novel epilepsy associated tumor with distinct clinico-pathologic features. We report the clinical and pathologic findings in 8 additional cases of this rare tumor type and extend its characterization by genomic profiling. Almost all patients had a history of long-standing drug-resistant epilepsy. Cortico-subcortical tumors were located in the temporal and parietal lobes. Seizures began at 3 to 14 years of age and surgery was performed at 6 to 70 years. Histologically, the tumors were characterized by diffuse growth and prominent perivascular tumor cell arrangements with features of astrocytic/ependymal differentiation, but lacking neoplastic neuronal features. Necrosis and vascular proliferation were not observed and mitoses were sparse or absent. MIB-1 proliferation indices ranged from <1% to 5%. Immunohistochemically, all cases stained positively for glial fibrillary acidic protein, vimentin, protein S100B, variably for podoplanin, and showed epithelial membrane antigen-positive cytoplasmic dots. Electron microscopy showed ependymal characteristics in 2 of 3 cases investigated. An analysis of genomic imbalances by chromosomal comparative genomic hybridization revealed loss of chromosomal bands 6q24 to q25 as the only alteration in 1 of 8 cases. In 1 of 3 cases, a high-resolution screen by array-comparative genomic hybridization identified a copy number gain of 2 adjacent clones from chromosomal band 11p11.2 containing the protein-tyrosine phosphatase receptor type J (PTPRJ) gene. All patients are seizure free and without evidence of tumor recurrence at follow-up times ranging from 1/2 to 6.9 years. Our findings support 2 previous reports proposing that angiocentric glioma is a novel glial tumor entity of low-grade malignancy. [Abstract]

Henriksen KJ, Meehan SM, Chang A
Non-neoplastic renal diseases are often unrecognized in adult tumor nephrectomy specimens: a review of 246 cases.
Am J Surg Pathol. 2007 Nov;31(11):1703-8.
The pathologic evaluation of tumor nephrectomy specimens focuses on the diagnosis, grading, and staging of the neoplasm. The presence of coincidental non-neoplastic diseases in these specimens may have significant implications for patient outcomes. The purpose of this study is to determine the spectrum of non-neoplastic disease processes that may be overlooked in tumor nephrectomies, and to ascertain the extent to which surgical pathologists are trained to recognize these lesions. We reviewed the hematoxylin and eosin-stained slides of 246 adult tumor nephrectomy specimens with an emphasis on the non-neoplastic renal parenchyma. Further analysis of cases with pathologic alterations included special stains and direct immunofluorescence microscopy. The surgical pathology reports were reviewed to determine whether the non-neoplastic lesions were originally identified. We also surveyed United States pathology residency programs to determine how many require training in medical renal pathology. Forty-one cases (16.7%) had alterations, such as diffuse and/or nodular mesangial sclerosis, mesangial hypercellularity, or glomerular basement membrane thickening that warranted further study. After further work-up and clinical correlation, the pathologic changes in 24 cases were categorized as follows: diabetic nephropathy (19 cases) of which one demonstrated atheroembolic disease, thrombotic microangiopathy (3 cases), sickle cell nephropathy (1 case), and focal segmental glomerulosclerosis (1 case). Twenty-one (88%) of these diagnoses were not identified at initial pathologic evaluation. Only 35 of 98 pathology residency programs that responded to our survey require any formal training in medical renal pathology. Although accurate pathologic evaluation of renal neoplasms remains essential, surgical pathologists should be aware that coincidental non-neoplastic renal diseases are common, often not recognized, and may have important implications for patient care. Further consideration should be given to the training requirements of pathology residents and the guidelines for evaluation of nephrectomy specimens to avoid missing non-neoplastic renal lesions. [Abstract]

Murakami YI, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita Y, Morito N, Yoh K, Fujioka Y, Matsuno F, Hata H, Mitsuya H, Imagawa S, Suzuki A, Esumi H, Sakai M, Takahashi S, Mori N
c-Maf expression in angioimmunoblastic T-cell lymphoma.
Am J Surg Pathol. 2007 Nov;31(11):1695-702.
The oncogene c-Maf was recently found to be overexpressed in approximately 50% of multiple myeloma cases, and a role for c-Maf in promoting cyclin D2 expression has been postulated. We previously examined c-Maf expression in various T-cell lymphomas by reverse-transcription polymerase chain reaction and found extremely elevated c-Maf levels in angioimmunoblastic T-cell lymphoma (AILT). In this study, we examined T-cell lymphomas for c-Maf and cyclin expression immunohistochemically. Of 93 cases of T-cell lymphomas we investigated in the current study, c-Maf expression was seen in 23 out of 31 cases of AILT, 3 out of 11 of adult T-cell leukemia/lymphoma, 4 out of 19 of peripheral T-cell lymphoma, unspecified [PTCL(U)], and 0 out of 11 cases of mycosis fungoides, 0 out of 11 of anaplastic large cell lymphoma, and 1 out of 10 of extranodal NK/T-cell lymphoma, nasal type. Double immunostaining in AILT revealed that the majority of c-Maf-positive cells were also positive for CD43 (MT1), CD45RO (UCHL-1), and CD4 but were negative for CD20 (L26). Additionally, cyclins D1 and D2, which stimulate cell cycle progression, were overexpressed in a large number of the c-Maf-positive AILT samples. Quantitative reverse-transcription polymerase chain reaction analysis also showed that c-Maf was overexpressed in 8/31 cases of AILT, 0/19 cases of PTCL(U), 0/11 cases of anaplastic large cell lymphoma, 0/10 cases of extranodal NK/T-cell lymphoma, nasal type, and 2/8 cases of multiple myeloma, presenting significant difference between AILT and PTCL(U) (P=0.016, chi test).These findings strongly suggest that CD4-positive neoplastic T cells in AILT show c-Maf expression and provide new insight into the pathogenesis of AILT suggesting c-Maf to be a useful diagnostic marker for AILT. [Abstract]

Seethala RR, Hunt JL, Baloch ZW, Livolsi VA, Leon Barnes E
Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.
Am J Surg Pathol. 2007 Nov;31(11):1683-94.
High-grade transformation of adenoid cystic carcinoma (ACC) (previously referred to as dedifferentiation) is a rare phenomenon that does not fit into the traditional ACC grading schemes. The importance and minimal criteria for distinction from solid (grade III) ACC are not well established. We report 11 new cases and review the literature to further define the profile of this tumor. The median age was 61 years (range: 32 to 72 y) with a male predominance (male to female ratio of 1.75:1). The most commonly involved sites were sinonasal (4/11) and submandibular (4/11). Lymph nodes were pathologically positive in 4/7 (57.1%) cases. Distant metastases to the lung (n=2) and soft tissue of the shoulder (n=1) were observed. Five of 9 patients (55.6%) died, all within 5 years with a median overall survival of 12 months. Histologically, ACC with high-grade transformation was distinguished from conventional ACC by nuclear enlargement and irregularity, higher mitotic counts, and the loss of the biphasic ductal-myoepithelial differentiation. Useful supportive criteria were prominent comedonecrosis and fibrocellular desmoplasia. The most common morphologies for the high-grade component were poorly differentiated cribriform adenocarcinoma and solid undifferentiated carcinoma. Micropapillary and squamoid patterns were occasionally present. Ki-67 and p53 labeling indices were elevated in the high-grade components, though c-kit and cyclin-D1 were not. ACC-high-grade transformation is a highly aggressive salivary gland tumor with a variety of histologic patterns. The high propensity for lymph node metastases suggests a role for neck dissection in patients with this rare tumor. [Abstract]

Schmitt AM, Anlauf M, Rousson V, Schmid S, Kofler A, Riniker F, Bauersfeld J, Barghorn A, Probst-Hensch NM, Moch H, Heitz PU, Kloeppel G, Komminoth P, Perren A
WHO 2004 criteria and CK19 are reliable prognostic markers in pancreatic endocrine tumors.
Am J Surg Pathol. 2007 Nov;31(11):1677-82.
BACKGROUND: It is difficult to predict the biologic behavior of pancreatic endocrine tumors in absence of metastases or invasion into adjacent organs. The World Health Organization (WHO) has proposed in 2004 size, angioinvasion, mitotic activity, and MIB1 proliferation index as prognostic criteria. Our aim was to test retrospectively the predictive value of these 2004 WHO criteria and of CK19, CD99, COX2, and p27 immunohistochemistry in a large series of patients with long-term follow-up. DESIGN: The histology of 216 pancreatic endocrine tumor specimens was reviewed and the tumors were reclassified according to the 2004 WHO classification. The prognostic value of the WHO classification and the histopathologic criteria necrosis and nodular fibrosis was tested in 113 patients. A tissue microarray was constructed for immunohistochemical staining. The staining results were scored quantitatively for MIB1 and semiquantitatively for CK19, COX2, p27, and CD99. The prognostic value of these markers was tested in 93 patients. RESULTS: The stratification of the patients into 4 risk groups according to the 2004 WHO classification was reliable with regard to both time span to relapse and tumor-specific death. In a multivariate analysis, the CK19 status was shown to be independent of the WHO criteria. By contrast, the prognostic significance of COX2, p27, and CD99 could not be confirmed. CONCLUSIONS: The 2004 WHO classification with 4 risk groups is very reliable for predicting both disease-free survival and the time span until tumor-specific death. CK19 staining is a potential additional prognostic marker independent from the WHO criteria for pancreatic endocrine tumors. [Abstract]

Hahn HP, Hornick JL
Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis.
Am J Surg Pathol. 2007 Nov;31(11):1669-76.
Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis. [Abstract]

Baker AC, Rezeanu L, O'Laughlin S, Unni K, Klein MJ, Siegal GP
Juxtacortical chondromyxoid fibroma of bone: a unique variant: a case study of 20 patients.
Am J Surg Pathol. 2007 Nov;31(11):1662-8.
BACKGROUND: Chondromyxoid fibroma (CMF) is a rare neoplasm of the appendicular skeleton of young adults. We report 20 cases of a poorly recognized subtype which arises on the surface of long bones and erodes the cortical surface causing a periosteal reaction. This entity should be included in the differential diagnosis of bone surface lesions as it may be mistaken for a more aggressive neoplasm. DESIGN: A retrospective review at the Mayo Clinic identified 259 CMF cases, 13 of which were parosteal. Additionally, 2 cases were diagnosed at the University of Alabama at Birmingham and 5 cases were from one of our authors' files. We reviewed the clinical radiographic and pathologic findings of all 20 cases. RESULTS: Juxtacortical CMF occurred over a large age range (12 to 82 y) with a median age of 40.2 years. A slight male predilection (5:4) was seen. The most common presentation was bone pain. All 20 cases showed solitary, radiolucent surface lesions with sclerotic margins and extension into the overlying soft tissues. Most of the lesions were in the proximal tibial metaphysis. Histologically, the tumors had characteristic features of CMF. Several cases contained distinctive areas of calcification, which is not a feature of conventional CMF. Eleven of 12 cases were cured with simple excision. CONCLUSION: CMF should be included in the differential diagnosis of bone surface lesions. The clinical and radiologic findings must be known. The morphology of this lesion is similar to conventional CMF with the exception of focal exuberant calcification. Conservative therapy is the treatment of choice. [Abstract]

Ferguson SE, Tornos C, Hummer A, Barakat RR, Soslow RA
Prognostic features of surgical stage I uterine carcinosarcoma.
Am J Surg Pathol. 2007 Nov;31(11):1653-61.
Uterine carcinosarcomas (CSs) are aggressive neoplasms, with 5-year overall survival (OS) rates of less than 35%. They are customarily separated into types harboring either heterologous or homologous mesenchymal elements, but the prognostic significance of this finding is controversial. Our goal was to study clinicopathologic features of possible prognostic relevance in surgical stage I uterine CS. A retrospective clinical and histopathologic review was performed for all women diagnosed with surgical stage I uterine CS. These tumors were compared with stage I high-grade endometrial (HGEm) carcinomas for clinical outcomes. There were 42 cases of surgical stage I uterine CS identified between January 1990 and January 2004. The disease-free survival and OS rates for patients with stage I CS were significantly worse compared with stage I HGEm (P=0.001; P=0.01). The median disease-free survival for patients with heterologous CS was 15 months and had not been reached for women with homologous CS (P=0.001). The 3-year OS rates were 45% versus 93% in women with heterologous compared with homologous stage I CS (P<0.001). The 3-year OS rates for homologous CS and HGEm were both >90%. Homologous stage I CSs have survival outcomes that are similar to HGEm. This further supports the concept that homologous stage I CSs are carcinomas with sarcomatoid features, not sarcomas. More importantly, the presence of heterologous sarcomatous elements is a powerful negative prognostic factor in surgical stage I uterine CS. [Abstract]

Williams MD, Roberts D, Blumenschein GR, Temam S, Kies MS, Rosenthal DI, Weber RS, El-Naggar AK
Differential expression of hormonal and growth factor receptors in salivary duct carcinomas: biologic significance and potential role in therapeutic stratification of patients.
Am J Surg Pathol. 2007 Nov;31(11):1645-52.
Salivary duct carcinoma (SDC), a rare malignancy, manifests remarkable morphologic and biologic resemblance to high-grade mammary ductal carcinoma. We contend that, similar to mammary ductal carcinoma, hormones and growth factors may play a role in SDCs. Our aim was to determine the incidence and clinical significance of the expression of several hormone and growth factor receptors and evaluate their potential in therapeutic stratification of SDC patients in the largest cohort studied to date. Eighty-four archived tumor tissue blocks were analyzed immunohistochemically for expression of estrogen receptor-beta (ERbeta), androgen receptor (AR), and proline, glutamic acid, and leucine-rich protein-1 and growth factor receptors HER-2 and epidermal growth factor receptor. The results were correlated with available pathologic, demographic, and clinical data from 59 of 84 cases. Proline, glutamic acid, and leucine-rich protein-1, ERbeta, and AR were expressed individually in 94% (71/76), 73% (57/80), and 67% (56/84) of SDCs, respectively, and coexpressed in 45% (34/75). AR was expressed significantly more often in SDCs of men than in SDCs of women [79% (35/57) vs. 33% (9/27), P<0.001]. Epidermal growth factor receptor and HER-2 were overexpressed individually in 48% (40/83) and 25% (21/84), respectively, and co-overexpressed in 12% (10/83). Survival decreased significantly in patients with lymph node metastasis (P=0.002) and positive surgical margins (P=0.006). Lack of ERbeta expression correlated with increased local and regional recurrence (P=0.05 and P=0.002, respectively). Together, these results indicate that (a) ERbeta down-regulation is associated with adverse clinical features, (b) lymph node and surgical margin status are significant survival factors, and (c) the differential expression of these hormones and growth factor receptors may assist in triaging patients with SDC for novel therapies. [Abstract]

Mitsunaga S, Hasebe T, Kinoshita T, Konishi M, Takahashi S, Gotohda N, Nakagohri T, Ochiai A
Detail histologic analysis of nerve plexus invasion in invasive ductal carcinoma of the pancreas and its prognostic impact.
Am J Surg Pathol. 2007 Nov;31(11):1636-44.
Nerve plexus invasion is regarded as one of the most important prognostic factors in invasive ductal carcinoma (IDC) of the pancreas, though nerve plexus invasion has not been evaluated in terms of prognostic impact on the basis of detailed histologic investigation. The purpose of this study was to precisely examine morphologic characteristics of nerve plexus invasion and analyze its prognostic predictive power compared with the well-known prognostic parameters of pancreatic IDCs. The outcome and histologic features of 75 patients with pancreatic IDC in the pancreas head were investigated, and 422 lesions of nerve plexus invasion were evaluated. Tumor cells invading nerve plexus showed a duct-forming differentiated feature and predominantly existed in the perineurium and perineural space. Multivariate analyses revealed that the important prognostic factors, in addition to invasive tumor size and tumor necrosis, were at long distances from nerve plexus invasion to pancreatic capsule and perineural invasion in nerve plexus invasion. [Abstract]

Abraham SC, Krasinskas AM, Hofstetter WL, Swisher SG, Wu TT
"Seedling" mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction.
Am J Surg Pathol. 2007 Nov;31(11):1629-35.
Gastrointestinal stromal tumors (GISTs) are the most common nonepithelial neoplasm of the gastrointestinal tract and show a predilection for the stomach. Most are detected because of symptoms, but some are incidental findings at autopsy or surgery for other reasons. Incidental GISTs tend to be smaller at diagnosis, but even small (<1 cm) GISTs have been shown to harbor activating KIT mutations at rates similar to advanced GISTs. However, the prevalence and characteristics of small GISTs in surgical resections of the esophagogastric junction (EGJ) remains unclear. We studied 150 esophagogastric resections for esophageal or EGJ carcinomas (100 with preoperative chemoradiation and 50 untreated cases) that had been extensively embedded for histologic examination (mean 30 sections/case). Number, size, morphology, and location of all GISTs and leiomyomas were recorded. All potential GISTs were evaluated with CD117 and CD34 immunohistochemistry, and a subset (35) leiomyomas with smooth muscle actin, desmin, and CD117. We found 18 incidental GISTs in 15 of 150 (10%) patients; 3 patients harbored 2 separate lesions. Prevalence of GIST was identical in treated (10 of 100) and untreated (5 of 50) cases. All (100%) showed positivity for both CD117 and CD34 and all were of spindle cell morphology. Lesions ranged from 0.2 to 3.0 mm in size (mean 1.3 mm). Eight (44%) were based in the outer muscularis propria, 7 (39%) in inner muscularis, and 3 (17%) between the muscle layers. The lesions tended to cluster near the EGJ, with 8 (44%) on the gastric side, 9 (50%) on the esophageal side, and 1 (6%) undetermined owing to overlying ulceration. Leiomyomas were even more common than GIST, occurring in 47% of patients (44% of treated and 52% of untreated, P=0.39), with a mean of 3 leiomyomas per patient (range 1 to 13) and mean size of 1.7 mm (range 0.2 to 12 mm). Unlike colorectal leiomyomas, most (91%) EGJ leiomyomas were located in the inner muscularis propria and only rarely (1%) in muscularis mucosa. These results suggest that GIST and leiomyoma are common incidental "seedling" lesions of the EGJ, found in 10% and 47% of patients undergoing surgery for esophageal carcinoma. The common occurrence of microscopic GISTs compared with the rarity of clinically manifest and malignant esophagogastric GISTs suggests that additional genetic or epigenetic alterations must happen for neoplastic progression. [Abstract]

Bergmann F, Esposito I, Michalski CW, Herpel E, Friess H, Schirmacher P
Early Undifferentiated Pancreatic Carcinoma With Osteoclastlike Giant Cells: Direct Evidence for Ductal Evolution.
Am J Surg Pathol. 2007 Dec;31(12):1919-1925.
Undifferentiated (anaplastic) carcinomas of the pancreas are rare. To a variable degree, they may contain osteoclastlike giant cells and are then sometimes referred to as osteoclastlike giant cell tumors. The histogenesis of these tumors has been discussed with great controversy. Thus, as a result from numerous histomorphologic, immunohistochemical, ultrastructural, and molecular examinations, frequently performed as single case studies, it has been concluded that undifferentiated carcinomas and osteoclastlike giant cell tumors of the pancreas originate from epithelial cells, mesenchymal cells, undifferentiated precursor cells, or stem cells. However, to date, early stage tumors have not been described, most likely because of the fact that at the time of diagnosis the tumors have commonly reached advanced stages with large tumor size. In this report, we present the case of an undifferentiated pancreatic carcinoma with osteoclastlike giant cells, which was incidentally detected at a very early stage in a pancreatitis specimen. Our histomorphologic and immunohistochemical findings not only provide evidence for a ductal origin, but for the first time document initial steps in the evolution of these tumors. Therefore, we suggest that the tumor should be considered as an anaplastic variant of pancreatic ductal adenocarcinoma. [Abstract]

Djordjevic B, Euscher ED, Malpica A
Growing Teratoma Syndrome of the Ovary: Review of Literature and First Report of a Carcinoid Tumor Arising in a Growing Teratoma of the Ovary.
Am J Surg Pathol. 2007 Dec;31(12):1913-1918.
We report the first case of a secondary tumor arising from a peritoneal nodule of mature teratoma in a patient with growing teratoma syndrome (GTS) of the ovary. The patient originally presented 19 years ago with an immature teratoma of the ovary and positive retroperitoneal lymph nodes. After surgery and chemotherapy, mature teratomas recurred as abdominal and pelvic masses after 1, 6, and 19 years. Upon the last recurrence, a trabecular carcinoid tumor developed in a mature teratoma associated with the liver. This case illustrates the importance of long-term follow-up for patients with GTS of the ovary, where the recurrent masses can appear many years after the primary tumor, compress the abdominal and pelvic structures and give rise to secondary neoplasms. In addition, we present a literature review of GTS of the ovary and some novel observations about this entity. On the basis of our review of ovarian GTS cases in the literature, we have found that ovarian GTS nodules tend to appear for the first time within 2 years of the initial primary. They remain confined almost exclusively to the pelvis, abdomen, and the retroperitoneum and do not venture to distant systemic sites. This new information may help identify and screen women with germ cell tumors of the ovary at risk for GTS. [Abstract]

Tan KB, Moncrieff M, Thompson JF, McCarthy SW, Shaw HM, Quinn MJ, Li LX, Crotty KA, Stretch JR, Scolyer RA
Subungual Melanoma: A Study of 124 Cases Highlighting Features of Early Lesions, Potential Pitfalls in Diagnosis, and Guidelines for Histologic Reporting.
Am J Surg Pathol. 2007 Dec;31(12):1902-1912.
Subungual melanoma (SUM) is an uncommon variant of melanoma that is often difficult to diagnose, both clinically and pathologically. In an attempt to provide pathologic clues to diagnosis, especially in early lesions or small biopsies, and to provide practical advice to pathologists in reporting, the clinicopathologic features of 124 cases of SUM were reviewed, the largest series reported to date. The features of 28 cases of subungual melanoma in situ (MIS), comprising 4 cases of MIS and 24 cases where areas of MIS were present adjacent to dermal-invasive SUMs, were compared with those of a similar number of acral nevi to identify useful distinguishing features. The median age of the patients was 59 years and the most common site was the great toe (24%). Nine percent of cases were AJCC stage 0, 14% were stage I, 41% were stage II, 32% were stage III, and 4% were stage IV at initial diagnosis. The commonest histogenetic subtype was acral lentiginous (66%), followed by nodular (25%) and desmoplastic (7%). The majority of tumors were locally advanced at presentation with 79% being Clark level IV or V. The median Breslow thickness was 3.2 mm. The median mitotic rate was 3 per mm and 33% of cases demonstrated primary tumor ulceration. Seven of 29 patients (24%) who underwent a sentinel lymph node biopsy had nodal disease. Multivariate Cox-regression analysis showed higher disease stage to be the only significant predictor of shortened survival. In comparison to acral nevi, MIS more frequently showed lack of circumscription, a prominent lentiginous growth pattern, predominance of single cells over nests, moderate-to-severe cytologic atypia, a dense and haphazard pagetoid intraepidermal spread of melanocytes, and the presence of junctional/subjunctional lymphocytes ("tumor infiltrating lymphocytes"). Tumor infiltrating lymphocytes have not been highlighted previously as a feature of subungual MIS and represent a useful diagnostic clue. Guidelines for the reporting of SUMs are also presented. Knowledge and recognition of the pathologic features of SUMs and the important features that distinguish them from nevi should reduce the frequency of misdiagnosis. [Abstract]

Walsh SN, Hurt MA, Santa Cruz DJ
Am J Surg Pathol. 2007 Dec;31(12):1897-1901.
Cornoid lamellation is a specific disorder of epidermal maturation manifested by a vertical "column" of parakeratosis and is the hallmark of porokeratosis. The cornoid lamella is characterized by a ridgelike parakeratosis. We present 11 patients with solitary lesions of a distinct pattern of cornoid lamellation. The mean age at presentation clinically was 57 years; there were 9 men and 2 women. The duration of the lesions ranged from 3 months to 5 years (mean of 23 mo). All lesions were solitary, distributed mainly on the distal upper and lower limbs, and were clinically described as hyperkeratotic plaques or nodules; some were verrucous. Histologic examination showed a well-defined lesion characterized by acanthosis and verrucous hyperplasia with prominent multiple and confluent cornoid lamellae. No additional lesions were identified in any patient, with a mean follow-up duration of 34 months. No personal or family history of porokeratosis was elicited and no immunosuppressive conditions were noted. These lesions with multiple and confluent cornoid lamellae represent benign acanthomas with features of porokeratosis. As a solitary tumorlike lesion, it is akin to warty dyskeratoma and epidermolytic acanthoma, thus we have coined the term porokeratoma. [Abstract]

Ho V, Keating S, Kingdom J, Shannon P
Misoprostol Associated Refractile Material in Fetal and Placental Tissues After Medical Termination of Pregnancy.
Am J Surg Pathol. 2007 Dec;31(12):1893-1896.
Misoprostol is a synthetic prostaglandin analog administered vaginally to induce labor for intrauterine death or termination of pregnancy for congenital abnormalities. We encountered a case of misoprostol induction of labor at 14 weeks of gestation for fetal acrania associated with amniotic bands. Histology demonstrated abundant deposits of refractile material appearing to be of vegetable fiber origin on the maternal surface of the fetal membranes. Misoprostol tablet scrapings had a similar microscopic appearance. Ten additional placentas from cases of misoprostol induction of labor between 16 and 18 weeks of gestation were examined and half were found to contain such deposits. No deposits were seen in cases between 15 and 18 weeks of gestation where misoprostol was not used. We attribute the refractile material to a nonmedicinal ingredient, microcrystalline cellulose, in the misoprostol tablet preparation. This study demonstrates that vaginal administration of misoprostol tablets can be detected microscopically in at least half of cases and may have a florid appearance simulating a potential causative factor of fetal malformation. Despite the large amounts of microcrystalline cellulose and its apparent embedding in placental tissue, the misoprostol in our index case was unlikely to have caused the amniotic bands and the resulting cranial abnormality. [Abstract]

Petrella T, Maubec E, Cornillet-Lefebvre P, Willemze R, Pluot M, Durlach A, Marinho E, Benhamou JL, Jansen P, Robson A, Grange F
Indolent CD8-positive Lymphoid Proliferation of the Ear: A Distinct Primary Cutaneous T-cell Lymphoma?
Am J Surg Pathol. 2007 Dec;31(12):1887-1892.
The authors report 4 cases of cutaneous lymphoproliferation unusual by their histology and their clinical presentation. Each presented with a history of a slow growing nodule on the ear. Despite the indolent clinical evolution, the histology suggested a high-grade lymphoma. All lesions consisted of a dense, diffuse proliferation of monomorphous medium-sized T cells throughout the dermis and subcutis. There was no epidermotropism and a grenz zone was clearly present in each case. The tumor cells displayed irregular blastlike nuclei, with small nucleoli and clear chromatin and had a CD3, CD8, CD4, TIA1, granzyme Bimmunophenotype with a loss of other T-cell antigens. The 3 cases with available material for polymerase chain reaction studies displayed a monoclonal T-cell rearrangement of the T-cell receptor-gamma chain. These cases do not correspond to a recognized cutaneous T-cell lymphoma as described in the recent WHO/EORTC classification. The apparent striking propensity for the ear suggests that they might represent a specific entity. Further cases are needed to confirm this hypothesis. It is important for such indolent lesions to be known to avoid over treatment. [Abstract]

Lewin MR, Fenton H, Burkart AL, Sheridan T, Abu-Alfa AK, Montgomery EA
Poorly Differentiated Colorectal Carcinoma With Invasion Restricted to Lamina Propria (Intramucosal Carcinoma): A Follow-up Study of 15 Cases.
Am J Surg Pathol. 2007 Dec;31(12):1882-1886.
Invasive colorectal carcinomas (CRCs) with invasion confined to the lamina propria (LP) [intramucosal carcinoma (IMC)] lack access to lymphatics and therefore have no potential for metastases and local intervention (usually polypectomy) should be adequate treatment. For this reason, they are classified as "Tis" in the TNM system. It is believed that carcinomas invading the submucosa with unfavorable histology (tumors at/near the margin, and/or vascular invasion, and/or poor differentiation) require additional intervention after polypectomy, whereas those with favorable histology can be safely treated endoscopically. However, there are few data on poorly differentiated (PD) carcinomas showing invasion confined to the LP. Polypectomy is theoretically curative but in practice this has not been well demonstrated. Thus, the clinicopathologic features of 15 cases of PD CRCs with invasion limited to the LP on initial biopsies were studied to determine the best course of management for this rare subset of carcinomas. A computer search and histologic review of cases seen at Johns Hopkins Hospital was performed. Fifteen cases of PD CRC with invasion limited to the LP were identified. The clinicopathologic features of these tumors were reviewed. All 15 cases showed PD IMC with single cells infiltrating only the LP. Patients were 38 to 79 years (median, 62) of age with a male predominance (M:F=4:1). Three cases had signet ring cell differentiation, 1 had focal small cell features, and another had focal squamous differentiation. Fourteen of the cases were associated with background adenomas or adenomalike lesions including: 7 involving tubulovillous or villous adenomas, 6 involving tubular adenomas, 1 involving dysplasia associated with chronic inflammatory bowel disease. Nine of the lesions had surrounding high-grade dysplasia. One case showed no background dysplasia or adenoma. One patient was lost to follow-up and the remaining 14 were followed for 1 to 96 months (mean, 21.3 mo; median, 13 mo). Seven patients had no residual disease on follow-up colonoscopy, and no resection was performed. The remaining 7 patients were treated with partial colectomy (6) or low anterior resection (1), and of these, 5 had no infiltrating carcinoma and negative lymph nodes. One patient had a separate large colorectal (T3) carcinoma with 8/10 positive regional lymph nodes; the IMC seen on biopsy was presumably a metastasis as it was unassociated with an in situ component. Finally, the resected rectum from which an IMC had been previously detected had no residual invasive carcinoma, but the anal skin was involved by Paget disease. Thus, of the 15 cases of PD CRCs limited to the LP, 1 was a metastasis from a separate CRC and another had associated Paget disease of the anal skin. As such, even in the setting of PD carcinomas, no metastatic disease was seen arising from any of the cases that were confirmed as early primary lesions. These preliminary findings suggest that patients with isolated intramucosal PD CRCs may be managed endoscopically. [Abstract]

Di Cristofano C, Minervini A, Menicagli M, Salinitri G, Bertacca G, Pefanis G, Masieri L, Lessi F, Collecchi P, Minervini R, Carini M, Bevilacqua G, Cavazzana A
Nuclear Expression of Hypoxia-inducible Factor-1alpha in Clear Cell Renal Cell Carcinoma is Involved in Tumor Progression.
Am J Surg Pathol. 2007 Dec;31(12):1875-1881.
OBJECTIVES: The most frequent genomic abnormality in clear cell renal cell carcinoma (cc-RCC) is inactivation of Von Hippel-Lindau gene (VHL). pVHL19 is a ligase promoting proteosomal degradation of hypoxia-inducible factor-1alfa (HIF-1alpha); pVHL30 is associated with microtubules. VHL exert its oncogenetic action both directly and through HIF-1alpha activation. TNM classification is unable to define a correct prognostic evaluation of intracapsular cc-RCC. The nucleo-cytoplasmic trafficking in VHL/HIF-1alpha pathway could be relevant in understanding the molecular pathogenesis of renal carcinogenesis. This study analyzes VHL/HIF-1alpha proteins in a large series of intracapsular cc-RCCs, correlating their expression and cellular localization with prognosis. MATERIALS AND METHODS: Two anti-pVHL (clones Ig32 and Ig33) and 1 anti-HIF-1alpha were used on tissue microarrays from 136 intracapsular cc-RCCs (mean follow-up: 74 mo). Clone 32 recognizes both pVHLs, whereas clone 33 only pVHL30. Results were matched with clinicopathologic variables and tumor-specific survival (TSS). RESULTS: A strong cytoplasmic positivity was found for all antibodies in the largest part of cases, associated to a strong nuclear localization in the case of HIF-1alpha. All pVHL-negative cases were associated with high HIF-1alpha expression. pVHL negativity and HIF-1alpha nuclear positivity significantly correlated with shorter TSS. In multivariate analysis both pVHL negativity and HIF-1alpha nuclear expression were independent predictors of TSS. CONCLUSIONS: The localization of the proteins well matches with their role and with the supposed tumor molecular pathways. The correlation with prognosis of VHL/HIF-1alpha alterations confirms the relevance of their molecular pathway and of the cellular trafficking of their products in the pathogenesis of renal cancer. [Abstract]

Hahn HP, Fletcher CD
Primary Mediastinal Liposarcoma: Clinicopathologic Analysis of 24 Cases.
Am J Surg Pathol. 2007 Dec;31(12):1868-1874.
Liposarcomas are rare in the mediastinum. Here, we report the clinicopathologic features of 24 cases of mediastinal liposarcoma. Patients included 13 males and 11 females, with an age range of 3 to 72 years (median 58). Nine tumors were located in the anterior mediastinum, 7 in the posterior mediastinum, 1 in the superior mediastinum, and the precise location was not specified in 7 cases. Of the anterior mediastinal tumors, 3 appeared to arise from the thymus. Tumors were well-circumscribed, multinodular masses and ranged in size from 2.2 to 61 cm in greatest dimension (median 16 cm). Histologic examination revealed that most of the cases were well-differentiated liposarcomas (10), followed by dedifferentiated liposarcomas (8), pleomorphic liposarcomas (4), and myxoid liposarcomas (2). Of the pleomorphic liposarcomas, 2 had areas that resembled myxofibrosarcoma with atypical hyperchromatic spindle cells in a myxoid stroma, but the focal presence of lipoblasts confirmed the diagnoses. Clinical follow-up was obtained in 15 cases (range 1 to 59 mo; median 26). Complete surgical excision was attempted in 13 patients; however, local recurrence was common (5 cases), including 1 patient whose tumor recurred twice. Eleven patients were alive with no evidence of disease at last follow-up (5 well-differentiated, 5 dedifferentiated, and 1 myxoid liposarcoma). Two patients developed distant metastases (dedifferentiated and pleomorphic liposarcoma). One patient was alive with disease (pleomorphic liposarcoma), and 2 died of disease (pleomorphic and dedifferentiated liposarcoma). Overall, mediastinal liposarcomas appear to be similar, in clinicopathologic terms, to liposarcomas arising in the retroperitoneum. [Abstract]

Jones TD, Zhang S, Lopez-Beltran A, Eble JN, Sung MT, Maclennan GT, Montironi R, Tan PH, Zheng S, Baldridge LA, Cheng L
Urothelial Carcinoma With an Inverted Growth Pattern Can be Distinguished From Inverted Papilloma by Fluorescence In Situ Hybridization, Immunohistochemistry, and Morphologic Analysis.
Am J Surg Pathol. 2007 Dec;31(12):1861-1867.
Inverted papilloma of the urinary bladder and urothelial carcinoma with an inverted (endophytic) growth pattern may be difficult to distinguish histologically, especially in small biopsies. The distinction is important as these lesions have very different biologic behaviors and are treated differently. We examined histologic features and undertook immunohistochemical staining and UroVysion fluorescence in situ hybridization (FISH) to determine whether these methods could aid in making this distinction. We examined histologic sections from 15 inverted papillomas and 29 urothelial carcinomas with an inverted growth pattern. Each tumor was stained with antibodies to Ki-67, p53, and cytokeratin 20. In addition, each tumor was examined with UroVysion FISH for gains of chromosomes 3, 7, and 17 and for loss of chromosome 9p21 signals. None of the inverted papillomas stained positively for Ki-67 or for cytokeratin 20. Only 1 of 15 inverted papillomas stained positively for p53. By contrast, 66%, 59%, and 59% of urothelial carcinomas with an inverted growth pattern stained positively for Ki-67, p53, and cytokeratin 20, respectively. Only 3 of the urothelial carcinomas stained negatively for all 3 immunohistochemical markers. UroVysion FISH produced normal results for all cases of inverted papilloma. By contrast, 21 of 29 cases (72%) of urothelial carcinoma with an inverted growth pattern demonstrated chromosomal abnormalities typical of urothelial cancer and were considered positive by UroVysion FISH criteria. Morphologic features, as well as immunohistochemical stains (including stains for Ki-67, p53, and cytokeratin 20) and/or UroVysion FISH can help to distinguish inverted papilloma from urothelial carcinoma with an inverted growth pattern. [Abstract]

Cai B, Ronnett BM, Stoler M, Ferenczy A, Kurman RJ, Sadow D, Alvarez F, Pearson J, Sings HL, Barr E, Liaw KL
Longitudinal Evaluation of Interobserver and Intraobserver Agreement of Cervical Intraepithelial Neoplasia Diagnosis Among an Experienced Panel of Gynecologic Pathologists.
Am J Surg Pathol. 2007 Dec;31(12):1854-1860.
Histologic diagnoses of cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3) are the key end points in clinical trials that evaluate the efficacy of a prophylactic quadrivalent human papillomavirus vaccine against cervical cancer. Adjudication of end points uses a panel of 4 pathologists. Quality control slides (n=185) from a nonclinical trial study with preestablished gold standard CIN diagnoses were used to characterize the panel's agreement on CIN diagnoses and monitor performance longitudinally. At 3-month intervals over 2 years, 1 of 6 different batches of quality control slides (n=30-31) was included with clinical trial slides for independent review by each of the 4 panelists. Unweighted kappas (kappa) were estimated within each panelist pair by dichotomizing the diagnoses as CIN+ versus non-CIN+ (including normal, unsatisfactory, and atypical immature metaplasia) or CIN 2/3+ versus non-CIN 2/3+ (including normal, unsatisfactory, atypical immature metaplasia, and CIN 1). Quadratic weighted kappa was calculated within each panelist pair using 4 diagnostic categories: normal, CIN 1, CIN 2, and CIN 3 or worse. Substantial interobserver agreement was observed (weighted kappa=0.765 to 0.865). Agreement with weighted kappa=0.779 to 0.887 was observed between the individual panelists and the gold standard, which is almost perfect agreement by Landis-defined categories. Intraobserver agreement was very high (weighted kappa=0.756 to 0.883). Some fluctuation in intraobserver and interobserver agreement was observed over the study period but there was no decreasing time trend. These data indicate that the interpretation of histologic end points used in the quadrivalent vaccine clinical trial program is highly valid and reliable. [Abstract]

Rodriguez FJ, Aubry MC, Tazelaar HD, Slezak J, Aidan Carney J
Pulmonary Chondroma: A Tumor Associated With Carney Triad and Different From Pulmonary Hamartoma.
Am J Surg Pathol. 2007 Dec;31(12):1844-1853.
The Carney triad is the clinical association of gastric stromal sarcomas, pulmonary cartilaginous tumors, and extra-adrenal paragangliomas. The pulmonary tumors are its second commonest component and have been misinterpreted clinically and pathologically as metastases from the gastric tumors and pulmonary cartilaginous hamartomas, respectively. They have not been previously described in detail in the pathology literature or compared with pulmonary cartilaginous hamartomas. Forty-two patients with pulmonary cartilaginous tumors as a component of Carney triad were identified. Clinical, radiographic, and pathologic findings in the cases were tabulated. Hematoxylin and eosin-stained sections of the neoplasms were evaluated for a series of histologic features. A subgroup of 41 tumors from the latter was compared with those in a group of pulmonary cartilaginous hamartomas. Patients with Carney triad group were predominantly young women. Their pulmonary neoplasm(s) were usually asymptomatic, often multiple, well circumscribed, medium-sized (mean diameter=2.8 cm), and composed almost exclusively of cartilage and bone surrounded by a fibrous pseudocapsule. The cartilage was usually myxoid, less frequently hyaline, and commonly calcified, ossified, or both. They showed no fat, smooth muscle or entrapped respiratory epithelium, tissues that were common in pulmonary hamartoma (P<0.0001). None of the tumors metastasized or was fatal. The pulmonary neoplasms in the Carney triad are well-differentiated benign cartilaginous tumors that are best designated as chondromas. They differ pathologically from pulmonary cartilaginous hamartomas on the basis of the presence of a thin fibrous pseudocapsule, frequent bone metaplasia, and calcification, and also the absence of entrapped epithelium and fat. [Abstract]

Recent Articles in Annals of Surgical Oncology: The Official Journal of the Society of Surgical Oncology

Ko CY, Parikh J, Zingmond D
Secondary Analyses of Large Population-Based Data Sets: Issues of Quality, Standards, and Understanding.
Ann Surg Oncol. 2007 Dec 11; . [Abstract]

Ha TK, An JY, Youn HK, Noh JH, Sohn TS, Kim S
Indication for endoscopic mucosal resection in early signet ring cell gastric cancer.
Ann Surg Oncol. 2007 Dec 11;
BACKGROUND: The aim of this study was to compare the clinicopathological characteristics of an early signet ring cell carcinoma (SRC) with an early undifferentiated carcinoma (mucinous, poorly differentiated adenocarcinoma) and early differentiated carcinoma (well or moderately differentiated tubular adenocarcinoma, papillary adenocarcinoma) and find indications for endoscopic mucosal resection (EMR) in early SRC. METHODS: 1520 patients with early gastric cancer (EGC), who underwent a curative gastrectomy, were analyzed retrospectively. Among them, 388 patients with SRC were compared with 253 patients with undifferentiated carcinoma (UDC) and 879 with a differentiated carcinoma (DC). RESULTS: SRC was more common in young female patients than UDC. SRC had a tendency to be confined to the mucosa, with smaller size than UDC. The lymph node metastasis rate for SRC was lower than that for UDC, but similar to that of DC. Multivariate analysis revealed lymph node metastasis (LNM) to be associated with the depth of invasion, tumor size, histological type, and lymphatic involvement. SRC had no LNM in the case of a mucosal tumor, smaller than 2cm, and in the absence of lymphatic involvement. The prognosis of SRC was more favorable than UDC. CONCLUSIONS: Early SRC has different characteristics from early UDC. In view of the lower rate of lymph node metastasis and better prognosis, we suggest that EMR can be performed on patients with early SRC limited to the mucosa, less than 2cm in size, and with no lymphatic involvement. [Abstract]

Graesslin O, Chantot-Bastaraud S, Lorenzato M, Birembaut P, Quéreux C, Daraï E
Fluorescence in situ Hybridization and Immunohistochemical Analysis of p53 Expression in Endometrial Cancer: Prognostic Value and Relation to Ploidy.
Ann Surg Oncol. 2007 Dec 11;
BACKGROUND: Endometrial carcinoma is the most common gynecological malignancy. Several molecular biological characteristics have been studied for their potential value in patient management. OBJECTIVES: Our objectives were to compare p53 immunohistochemical expression with P53 gene status determined by fluorescence in situ hybridization (FISH) and to compare these characteristics with ploidy and with classical clinical and histological prognostic factors. MATERIALS AND METHODS: We reviewed stored specimens from 43 patients with endometrial cancer diagnosed in 1999-2004. P53 FISH and immunohistochemistry were performed, together with imaging cytometry to calculate DNA ploidy. RESULTS: Thirteen of the 43 endometrial carcinomas (30.2%) showed P53 loss of heterozygosity (LOH). P53 LOH correlated with the histological type (P = .03) and the histological grade (P = .004). Quantitative immunohistochemical expression of p53 protein correlated with the histological type (P = .0001). With a cutoff of 10% of p53-positive cells, p53 overexpression correlated with the histological type (P = .003) and grade (P = .0008). No relation was found between P53 LOH or immunohistochemical expression and the disease stage, the depth of myometrial invasion, lymph node status, lymphovascular space involvement, recurrence, or death from cancer. Nondiploid carcinomas showed deeper myometrial invasion than diploid carcinomas (P = .01). No relation was observed between ploidy and qualitative or semiquantitative p53 expression or P53 LOH. CONCLUSION: In endometrial cancer, FISH analysis of P53 status adds no significant prognostic information compared with immunohistochemical p53 analysis. [Abstract]

Shanafelt T
A Career in Surgical Oncology: Finding Meaning, Balance, and Personal Satisfaction.
Ann Surg Oncol. 2007 Dec 12;
The practice of surgical oncology provides opportunities for both personal distress as well as personal satisfaction. While many surgical oncologists experience career burnout, others derive great meaning and satisfaction from their work. In this article, we review the literature on surgeon burnout, discuss potential personal and professional consequences, and consider steps individual surgeons can take to promote personal and professional satisfaction. [Abstract]

Intra M, Garcia-Etienne CA, Renne G, Trifirò G, Rotmensz N, Gentilini OD, Galimberti V, Sagona A, Mattar D, Sangalli C, Gatti G, Luini A, Veronesi U
When Sentinel Lymph Node is Intramammary.
Ann Surg Oncol. 2007 Dec 6;
INTRODUCTION: Sentinel lymph node biopsy is an accepted standard of care for staging the axilla in patients with early-stage breast cancer. Little attention has been placed to the presence of intramammary sentinel lymph nodes (intraMSLNs) on preoperative lymphoscintigraphy. METHODS: Between December 2001 and September 2006, in 9632 breast cancer patients with clinically uninvolved axillary nodes, lymphoscintigraphy was performed at the European Institute of Oncology (EIO). An axillary SLN (axSLN) was identified in 99.4% of cases. An intraMSLN was identified in association with the axillary sentinel lymph node in 22 patients (0.2%). In 15 cases both the axSLN and the intraMSLN were excised. RESULTS: The intraMSLN was positive in six patients (micrometastatic in three cases). The axSLNs were negative in all 15 cases. Two patients with positive intraMSLNs and one patient with a negative intraMSLN underwent axillary dissection; all three cases had negative axillary nodes. At a median follow-up of 24 months, no locoregional or systemic recurrences were observed. CONCLUSIONS: Positive intraMSLNs can improve disease staging but do not necessarily portend axillary lymph node metastasis. When intraMSLNs and axSLNs are present, we advocate biopsy of both sites and that management of the axilla should rely on axSLN status. In cases with intraMSLNs as the only draining site on lymphoscintigraphy, decisions on axillary management should be made on individualized basis. [Abstract]

Hyuk Baik S, Kyu Kim N, Young Lee K, Kook Sohn S, Hwan Cho C, Jin Kim M, Kim H, Shinn RK
Factors Influencing Pathologic Results after Total Mesorectal Excision for Rectal Cancer: Analysis of Consecutive 100 Cases.
Ann Surg Oncol. 2007 Dec 5;
BACKGROUND: The aim of this study was to analyze clinical and anatomical factors affecting the pathologic quality of the resected specimen after total mesorectal excision (TME) for rectal cancer. METHODS: A total of 100 patients who underwent TME for mid or low rectal cancer were evaluated prospectively. MRI pelvimetry data (transverse diameter, obstetric conjugate, interspinous distance, sacrum length, and sacrum depth) were analyzed as anatomically affecting factors to postoperative specimen quality. Sex, body mass index (BMI), type of surgery, tumor size, and tumor distance from the anal verge were analyzed as clinically affecting factors. The gross judgment of resected specimen, circumferential resection margin and the number of harvested lymph nodes were used to access postoperative specimen quality. RESULTS: The univariate and multivariate analysis showed that narrow obstetric conjugate and shorter interspinous distance were related to the inadequate quality of the mesorectum in the specimen (P = 0.022, P = 0.030). Interspinous distance was a predicting factor of a positive circumferential resection margin (P = 0.007). There were no clinical factors affecting the inadequate quality of the mesorectum or positive circumferential resection margin. Moreover, there were no clinico-anatomical factors affecting the number of harvested lymph nodes after TME. CONCLUSION: Narrow obstetric conjugate and shorter interspinous distance were factors leading to poor postoperative specimen quality. Rectal cancer patients with narrow obstetric conjugate or shorter interspinous distance should be considered as high-risk patients with regard to specimen quality, which is in turn related to oncological outcome. [Abstract]

Bleicher RJ, Abrahamse P, Hawley ST, Katz SJ, Morrow M
The Influence of Age on the Breast Surgery Decision-Making Process.
Ann Surg Oncol. 2007 Dec 6;
BACKGROUND: Mastectomy rates have been assumed to be a function of physician recommendations, although they correlate with patient involvement in decision making. The influence of age on the decision-making process and treatment choice is poorly described. METHODS: All women with ductal carcinoma in situ (DCIS) and a random sample with invasive breast cancer were identified from two Surveillance Epidemiology and End Results (SEER) program registries and surveyed 6 months postoperatively. Women older than 79 years with noninvasive or localized invasive breast cancer diagnosed in 2002 were included. Women with breast-conserving therapy (BCT) contraindications were excluded. Women were questioned about involvement in surgical decision-making, inquiring if this decision was patient-based, surgeon-based, or shared. Knowledge and concerns were assessed. RESULTS: The response rate was 77.0%. There were 1,259 patients who met the study eligibility criteria and age data was available for 1,131. Median patient age was 59.9 years. The frequency of patient-based decisions did not vary with age (p = 0.20), but older women had less knowledge for decision making. The mastectomy rate overall was 19.7%, with no differences in mastectomy choice by age (p = 0.18). In logistic regression for the likelihood of undergoing mastectomy, patient involvement (p < 0.0001), larger tumor size (p < 0.0001), lower education (p = 0.0002), number of surgeons consulted (p = 0.0005), and nonwhite race origin (p = 0.011) were significant predictors, while age, invasion, and comorbidities were not significant. CONCLUSION: Older women participate equally in breast cancer surgical decision making and are equally likely to select mastectomy, but use less knowledge to make the decision. The impact of education and ethnic origin on mastectomy use indicates the need for improved educational strategies for these groups. [Abstract]

Hanisch E, Ziogas D, Roukos D, Hottenrott C
Advances in Laparoscopic Gastrectomy Expand Clinical Use.
Ann Surg Oncol. 2007 Dec 6; [Abstract]

Date RS, Mughal MM
Locally Advanced GISTs Need Aggressive Therapy Pending the Results of Trials.
Ann Surg Oncol. 2007 Dec 6; [Abstract]

Shaha AR
Editorial: Complications of Neck Dissection for Thyroid Cancer.
Ann Surg Oncol. 2007 Dec 6; [Abstract]

Wong SK, Chiu PW, Leung SF, Cheung KY, Chan AC, Au-Yeung AC, Griffith JF, Chung SS, Ng EK
Concurrent Chemoradiotherapy or Endoscopic Stenting for Advanced Squamous Cell Carcinoma of Esophagus: A Case-Control Study.
Ann Surg Oncol. 2007 Dec 5;
BACKGROUND: We evaluated the role of chemoradiotherapy (CRT) for patients with inoperable squamous esophageal cancer. METHODS: Patients with locally advanced or metastatic squamous esophageal carcinoma who received CRT were recruited. The CRT consists of continuous infusion of 5-fluorouracil at 200 mg/m(2)/day, and cisplatin at 60 mg/m(2) on days 1 and 22, with concurrent radiotherapy for a total of 50 to 60 Gy in 25 to 30 fractions over 6 weeks. Efficacy was assessed by endoscopy and computed tomographic scan before and 8 weeks after completion of the treatment program. Median survival and the need for palliative esophageal stenting were compared with another group of patients who received endoscopic stenting. RESULTS: From 1996 to 2003, a total of 36 consecutive patients (33 male, mean +/- SD age 63.2 +/- 9.5 years) with T4 disease (81%) with or without cervical nodal metastasis (50%) received CRT, while 36 patients treated with endoscopic stenting alone were recruited as controls. Both groups were comparable in demographics, pretreatment dysphagia score, comorbidities, and tumor characteristics. CRT was completed in 32 patients (89%). There was no treatment-related mortality. Tumor volume was greatly reduced after CRT in 19 patients. Four patients (11%) received salvage esophagectomy 9 to 42 months after CRT. Compared with the stenting group, CRT statistically significantly improved 5-year survival (15% vs. 0%, P = .01), median survival (10.8 months vs. 4.0 months, P < .005), and need for stenting (22% vs. 100%, P = .005). CONCLUSIONS: Palliative CRT can effectively improve the symptoms of dysphagia in patients with inoperable squamous esophageal carcinoma. It results in better survival compared with endoscopic stenting in these patients. [Abstract]

Lykoudis E, Xeropotamos N, Ziogas D, Fatouros M
Breast Conservation Therapy: Multiple Reexcisions or Subcutaneous and Nipple-Sparing Mastectomy?
Ann Surg Oncol. 2007 Dec 5; [Abstract]

Sano T, Shimada K, Sakamoto Y, Ojima H, Esaki M, Kosuge T
Prognosis of Perihilar Cholangiocarcinoma: Hilar Bile Duct Cancer versus Intrahepatic Cholangiocarcinoma Involving the Hepatic Hilus.
Ann Surg Oncol. 2007 Dec 5;
BACKGROUND: Clinically hepatobiliary resection is indicated for both hilar bile duct cancer (BDC) and intrahepatic cholangiocarcinoma involving the hepatic hilus (CCC). The aim of this study was to compare the long-term outcome of BDC and CCC. METHODS: Between 1990 and 2004, we surgically treated 158 consecutive patients with perihilar cholangiocarcinoma. The clinicopathological data on all of the patients were analyzed retrospectively. RESULTS: The overall 3-year survival rate, 5-year survival rate, and median survival time for BDC patients were 48.4%, 38.4 %, and 33.7 months, respectively, and 35.8%, 24.5 %, and 22.7 months, respectively, in CCC patients (P = .033). On multivariate analysis, three independent factors were related to longer survival in BDC patients: achieved in curative resection with cancer free margin (R0) (P = .024, odds ratio 1.862), well differentiated or papillary adenocarcinoma (P = .011, odds ratio 2.135), and absence of lymph node metastasis (P < .001, odds ratio 3.314). Five factors were related to longer survival in CCC patients: absence of intrahepatic daughter nodules (P < .001, odds ratio 2.318), CEA level </=2.9 ng/mL (P = .005, odds ratio 2.606), no red blood cell transfusion requirement (P = .016, odds ratio 2.614), absence or slight degree of lymphatic system invasion (P < .001, odds ratio 4.577), and negative margin of the proximal bile duct (P = .003, odds ratio 7.398). CONCLUSIONS: BDC and CCC appear to have different prognoses after hepatobiliary resection. Therefore, differentiating between these two categories must impact the prediction of postoperative survival in patients with perihilar cholangiocarcinoma. [Abstract]

Theodore L
Reexcisions in Breast-Conserving Surgery for Breast Cancer: Can They Be Avoided?
Ann Surg Oncol. 2007 Dec 5; [Abstract]

Kim TH, Jeong SY, Choi DH, Kim DY, Jung KH, Moon SH, Chang HJ, Lim SB, Choi HS, Park JG
Lateral Lymph Node Metastasis Is a Major Cause of Locoregional Recurrence in Rectal Cancer Treated with Preoperative Chemoradiotherapy and Curative Resection.
Ann Surg Oncol. 2007 Dec 5;
BACKGROUND: In rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection, we evaluated the effect of clinical parameters on lateral pelvic recurrence and made an attempt to identify a risk factor for lateral pelvic recurrence. METHODS: The study involved 366 patients who underwent preoperative CRT and curative resection between October 2001 and December 2005. Clinical parameters such as gender, age, tumor size, histologic type, cT and cN classification, ypT and ypN classification, circumferential resection margin, tumor regression grade, chemotherapeutic regimen, and lateral lymph node size were analyzed to identify risk factors associated with lateral pelvic recurrence. RESULTS: Of the 366 patients, 29 patients (7.9%) had locoregional recurrence: 6 (20.7%) with central pelvic recurrence and 24 (82.7%) had lateral pelvic recurrence, of which 1 had simultaneous central and lateral pelvic recurrence. Multivariate analysis showed that ypN classification and lateral lymph node size were significantly associated with lateral pelvic recurrence (P < .001). Of 250 ypN0 patients, lateral pelvic recurrence developed in 1.4%, 2.9%, and 50% of patients with lateral lymph node sizes of <5, 5-9.9, and >/=10 mm, respectively (P < .001). Of 116 ypN+ patients, lateral pelvic recurrence developed in 4.3%, 35.7%, and 87.5% of patients with lateral lymph node sizes of <5, 5-9.9, and >/=10 mm, respectively (P < .001). CONCLUSIONS: In our study, lateral pelvic recurrence was a major cause of locoregional recurrence, and ypN+ and lateral lymph node size were risk factors for lateral pelvic recurrence. [Abstract]

van Leeuwen BL, Graf W, Pahlman L, Mahteme H
Swedish Experience with Peritonectomy and HIPEC. HIPEC in Peritoneal Carcinomatosis.
Ann Surg Oncol. 2007 Dec 5;
BACKGROUND: Peritonectomy with heated intraperitoneal chemotherapy (HIPEC) has shown a survival benefit in selected patients with peritoneal carcinomatosis. This prospective non-randomized study was designed to identify factors associated with postoperative morbidity and survival after peritonectomy HIPEC in patients with this condition. METHOD: Data were prospectively collected from all patients with peritoneal carcinomatosis treated by means of peritonectomy and HIPEC at Uppsala University Hospital between October 2003 and September 2006. Depending on the primary tumor, mitomycin C or a platinum compound was used as a chemotherapeutic agent for perfusion. RESULTS: A total of 103 patients were treated. Primary tumors were pseudomyxoma peritonei (47 patients), colorectal cancer (38 patients), gastric cancer (6 patients), ovarian cancer (6 patients) and mesothelioma (5 patients). Postoperative morbidity was 56.3% and was significantly lower in patients treated with mitomycin C for pseudomyxoma peritonei (42%) than in those with another diagnosis treated with platinum compound (71%, P < 0.05). Postoperative mortality was less than 1%. At 2 years, overall survival was estimated to be 72.3%, and disease-free survival was 33.5%. Factors influencing overall and disease-free survival were tumor type and optimal cytoreduction. CONCLUSION: Postoperative morbidity is dependent mainly on a tumor type; however, the chemotherapeutic agent used might also influence morbidity. Survival is determined by optimal cytoreduction and tumor type. Irrespective of age, patients with good performance status benefit from this treatment. [Abstract]

Ogawa E, Takenaka K, Katakura H, Adachi M, Otake Y, Toda Y, Kotani H, Manabe T, Wada H, Tanaka F
Perimembrane Aurora-A Expression is a Significant Prognostic Factor in Correlation with Proliferative Activity in Non-Small-Cell Lung Cancer (NSCLC).
Ann Surg Oncol. 2007 Nov 28;
PURPOSE: Aurora-A, also known as STK15/BTAK, is a member of the protein serine/threonine kinase family, and experimental studies have revealed that Aurora-A plays critical roles in cell mitosis and in carcinogenesis. However, no clinical studies on Aurora-A expression in non-small-cell lung cancer (NSCLC) have been reported. Thus, the present study was conducted to assess the clinical significance of Aurora-A status. EXPERIMENTAL DESIGN: A total of 189 consecutive patients with resected pathologic (p-)stage I-IIIA, NSCLC were retrospectively reviewed, and immunohistochemical staining was used to detect Aurora-A expression. RESULTS: Aurora-A expression was negative in 31 patients (16.4%); among Aurora-A positive patients, 124 patients showed pure diffuse cytoplasmic Aurora-A expression and the other 34 patients showed perimembrane Aurora-A expression. Perimembrane Aurora-A tumors showed the highest proliferative index (PI) (mean PIs for negative, diffuse cytoplasmic, and perimembrane tumors: 49.2, 41.7, and 63.5, respectively; P < .001). Five-year survival rates of Aurora-A negative, diffuse cytoplasmic, and perimembrane patients were 67.8%, 66.7%, and 47.6%, respectively, showing the poorest postoperative survival in perimembrane patients (P = .033). Subset analyses revealed that perimembrane Aurora-A expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. A multivariate analysis confirmed that perimembrane Aurora-A expression was an independent and significant factor to predict a poor prognosis. CONCLUSIONS: Perimembrane Aurora-A status was a significant factor to predict a poor prognosis in correlation with enhanced proliferative activity in NSCLC. [Abstract]

Dawood S, Broglio K, Gonzalez-Angulo AM, Kau SW, Yang W, Albarracin C, Meric F, Hortobagyi G, Theriault R
Development of New Cancers in Patients with DCIS: The M.D. Anderson Experience.
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: The purpose of this study was to describe clinical characteristics and outcome of mammographically and clinically detected new cancers in patients with previously diagnosed ductal carcinoma in situ (DCIS). METHOD: Our database was searched to identify patients with a primary diagnosis of DCIS. Those with prior evidence of invasive carcinoma were excluded from the analysis. Cumulative incidence of new cancers was estimated according to the method of Gray. Survival times were estimated using the Kaplan Meier product limit method. RESULTS: A total of 799 patients diagnosed and treated for DCIS were included in the analysis. Median age at diagnosis was 54 years (range 22-88 years) and median tumor size was 1.4 cm (range 0.2-15 cm). After a median follow-up of 2.9 years, 45 patients (5.6%) had a second event: 14 (31%) with in-situ and 31 (69%) with invasive disease. Median disease-free interval was 3.5 years (range 0.5-20.8 years). The majority of second events (63%) occurred in the opposite breast (P = 0.048) and the cumulative incidence at 5 years was 6.6%. Overall survival at 5 years was 97.4%; that for the second event was 76.1%. For mammography and self-palpation, respectively, the 5-year survival by method of detection of the second event was 63.2% and 100% (P = 0.08 with a 33% power to detect a difference). CONCLUSION: Second events following DCIS occurs primarily in the opposite breast and have a negative impact on survival. [Abstract]

Lagios MD, Silverstein MJ
Ductal Carcinoma in Situ: Through a Glass, Darkly.
Ann Surg Oncol. 2007 Nov 28; [Abstract]

Baratti D, Kusamura S, Nonaka D, Langer M, Andreola S, Favaro M, Gavazzi C, Laterza B, Deraco M
Pseudomyxoma Peritonei: Clinical Pathological and Biological Prognostic Factors in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: Surgical cytoreduction combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been recently advocated as the standard of care for pseudomyxoma peritonei (PMP). We reviewed our 10-year monoinstitutional case series to identify selection factors predicting postoperative outcome. METHODS: One hundred and four patients with PMP were operated on with the aim of performing adequate cytoreduction (residual tumor nodules </=2.5 mm) and closed-abdomen HIPEC with mytomicin-C and cisplatin. Previously, 26 patients had systemic chemotherapy. PMP was histologically classified into disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and intermediate/discordant group (ID). Immunohistochemical stains were performed for cytokeratin (CK)-7, CK-20, CDX-2, MUC-2, MUC-5AC, CD-44s. The significance of 22 potential clinical, pathological, and biological prognostic variables was assessed by multivariate analysis. RESULTS: Adequate cytoreduction was performed in 89 patients, suboptimal cytoreduction in six, palliative surgery in nine. Operative mortality was 1%. Seventy-eight patients were diagnosed with DPAM, 26 with PMCA, and none with ID. Median follow-up was 37 months (range, 1-110) for the overall series. Five-year overall survival (OS) and progression-free survival (PFS) were 78.3% and 31.1%, respectively. At multivariate analysis, adequate cytoreduction, no previous systemic chemotherapy, and DPAM correlated to better OS and PFS, elevated serum CA19.9 correlated only to better PFS. In most cases, CK20, CDX-2, and MUC-2 were diffusely positive, while CK-7, MUC-5AC, and CD44s were variably expressed. CK20 expression correlated to prognosis at univariate analysis. CONCLUSIONS: Favorable outcome after comprehensive treatment can be expected in patients with DPAM, not treated with preoperative systemic chemotherapy and amenable to adequate cytoreduction. MUC-2, CK-20, and CD44s expression may be related to PMP unique biologic behavior. [Abstract]

Fink AM, Lass H, Hartleb H, Jurecka W, Salzer H, Steiner A
S-Classification of Sentinel Lymph Node Predicts Axillary Nonsentinel Lymph Node Status in Patients with Breast Cancer.
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: One-half of breast cancer patients with positive sentinel lymph node (SN) have no further metastases in the axillary lymph node basin. The aim of the present study was to identify patients with positive SN who are unlikely to have further metastases in the axillary lymph node basin, using a new classification of SN, namely the S-classification. METHODS: Specimens of positive SN were subjected to a pathological review according to the previously published S-classification. S-stages of positive SN were correlated with the status of further metastases in the axillary lymph node basin after axillary lymph node dissection (ALND). RESULTS: Of 117 patients who underwent sentinel lymph node biopsy, 36 (30.8%) had a positive SN and were subjected to level I and II ALND. The occurrence of positive nonsentinel nodes was significantly related to the S-stage of SN. No patient with stage SI had additional metastases in the nonsentinel lymph nodes, while 14.3% of patients with SII stage disease and 60.9 % of patients with SIII disease had other non-SN that were metastatic. CONCLUSION: S-stages of positive SN are highly predictive for axillary nonsentinel node status. Especially patients with SI sentinel node metastases appear to be at low risk for further nonsentinel node metastases. [Abstract]

Origin of Cancer Stem Cells: The Role of Self-Renewal and Differentiation.
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: Self-renewal and differentiation potential is the feature of stem cells. Differentiation is usually considered to be a one-way process of specialization as cells develop the functions of their ultimate fate and lose their immature characteristics, such as self-renewal. Progenitor cells, the products of stem cells losing the activity of self-renewal, could differentiate to mature cells, which have the feature of differentiation and lose the activity of self-renewal.The roles for cancer stem cells have been demonstrated for some cancers. However, the origin of the cancer stem cells remains elusive. METHODS: This review focuses on current scientific controversies related to the establishment of the cancer stem cells - in particular, how self-renewal and differentiation block might contribute to the evolution of cancer. RESULTS: Cancer stem cells may be caused by transforming mutations occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells, mature cells and cancer cells. Progenitor cells obtain the self-renewal activity by activating the self-renewal-associated genes rather than dedifferentiate to tissue special stem cells. The transform multi-potential stem cells gain the differentiation feature of special tissue by differentiating to cancer cells. Mature cells and cancer cells may dedifferentiate or reprogram to cancer stem cells by genetic and / or epigenetic events to gain the self-renewal activity and lose some features of differentiation. The cancer-derived stem cells are not the "cause", but the "consequence" of carcinogenesis. The genetic program controlling self-renewal and differentiation is a key unresolved issue. CONCLUSION: Cancer stem cells may be caused by disturbance of self-renewal and differentiation occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells, mature cells and cancer cells. [Abstract]

Logan-Collins JM, Lowy AM, Robinson-Smith TM, Kumar S, Sussman JJ, James LE, Ahmad SA
VEGF Expression Predicts Survival in Patients with Peritoneal Surface Metastases from Mucinous Adenocarcinoma of the Appendix and Colon.
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: High levels of vascular endothelial growth factor (VEGF) in ovarian cancer metastases are associated with a worse prognosis in patients treated with chemotherapy. VEGF-directed therapy improves survival for those with metastatic colorectal cancer. Patients with mucinous adenocarcinomas metastatic to the peritoneal surfaces can be treated with cytoreductive surgery, and both tumor grade and cytoreduction status are prognostic. We hypothesized that angiogenic indices may be prognostic in patients undergoing cytoreductive surgery for mucinous adenocarcinoma of the appendix and colon. METHODS: Cytoreductive cases from a 5-year period from the University of Cincinnati peritoneal malignancy database were reviewed. CD 34 counts (blood vessels) and VEGF expression was evaluated by means of immunohistochemistry on specimens from patients undergoing cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP) for mucinous adenocarcinoma. RESULTS: A total of 26 males and 9 females, with a mean age of 50 years, underwent cytoreductive surgery and IPHP for mucinous adenocarcinoma of appendiceal (n = 32) or colonic (n = 3) origin. With a mean follow-up of 18 months (range 1-63 months), 23 had disease recurrence and 12 were alive without recurrence. The mean survival was 19 months (range 1-63 months). CD34 counts did not correlate with recurrence or survival; however, average VEGF counts correlated with survival (P = 0.017), and, for patients with recurrence, this correlation was stronger (P = 0.002). CONCLUSIONS: These results suggest that markers of tumor angiogenesis may predict survival in patients with peritoneal surface metastases from mucinous adenocarcinoma. These findings provoke the hypothesis that antiangiogenic therapies may be effective in patients with this devastating disease. [Abstract]

Namazi H
A Novel Use of Botulinum Toxin to Ameliorate Bone Cancer Pain.
Ann Surg Oncol. 2007 Nov 28; [Abstract]

Li C, Kim S, Lai JF, Oh SJ, Hyung WJ, Choi WH, Choi SH, Zhu ZG, Noh SH
Risk Factors for Lymph Node Metastasis in Undifferentiated Early Gastric Cancer.
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: Endoscopic surgery has not been accepted as a curative treatment for intramucosal undifferentiated early gastric cancer (EGC). The purpose of this study was to evaluate the predictive factors of lymph node metastasis and explore the possibility of using endoscopic surgery for undifferentiated EGC. METHODS: We retrospectively analyzed 646 patients with undifferentiated EGC who had undergone gastrectomy with D2 lymphadenectomy from January 2000 to March 2005. We used univariate and multivariate analysis to identify clinicopathological features that were predictive factors for lymph node metastasis. RESULTS: The incidence of lymph node metastasis was 4.2% in intramucosal and 15.9% in submucosal undifferentiated EGC. Multivariate analysis revealed that submucosal invasion, larger tumor size (greater than 2 cm), and presence of lymphovascular invasion (LVI), were significantly associated with lymph node metastasis in patients with undifferentiated EGC. Tumor size and LVI were independent risk factors for lymph node metastasis in cases of intramucosal EGC. Lymph node metastasis was found in only one patient (0.5%) who had neither of the two risk factors for intramucosal EGC. CONCLUSION: Complete endoscopic resection may be acceptable as a curative treatment for intramucosal undifferentiated EGC when the tumor size is less than or equal to 2 cm, and when LVI is absent in the postoperative histological examination. Radical gastrectomy should be recommended if LVI or unexpected submucosal invasion is present. [Abstract]

Suami H, Pan WR, Mann GB, Taylor GI
The Lymphatic Anatomy of the Breast and its Implications for Sentinel Lymph Node Biopsy: A Human Cadaver Study.
Ann Surg Oncol. 2007 Nov 28;
BACKGROUND: Current understanding of the lymphatic system of the breast is derived mainly from the work of the anatomist Sappey in the 1850s, with many observations made during the development and introduction of breast lymphatic mapping and sentinel node biopsy contributing to our knowledge. METHODS: Twenty four breasts in 14 fresh human cadavers (5 male, 9 female) were studied. Lymph vessels were identified with hydrogen peroxide and injected with a lead oxide mixture and radiographed. The specimens were cross sectioned and radiographed to provide three dimensional images. Lymph (collecting) vessels were traced from the periphery to the first-tier lymph node. RESULTS: Lymph collecting vessels were found evenly spaced at the periphery of the anterior upper torso draining radially into the axillary lymph nodes. As they reached the breast some passed over and some through the breast parenchyma, as revealed in the cross-section studies. The pathways showed no significant difference between male and female specimens. We found also perforating lymph vessels that coursed beside the branches of the internal mammary vessels, draining into the ipsilateral internal mammary lymphatics. In some studies one sentinel node in the axilla drained almost the entire breast. In most more than one sentinel node was represented. CONCLUSION: These anatomical findings are discordant with our current knowledge based on previous studies and demand closer examination by clinicians. These anatomical studies may help explain the percentage of false-negative sentinel node biopsy studies and suggest the peritumoral injection site for accurate sentinel lymph node detection. [Abstract]

McQuellon RP, Russell GB, Shen P, Stewart JH, Saunders W, Levine EA
Survival and Health Outcomes After Cytoreductive Surgery With Intraperitoneal Hyperthermic Chemotherapy for Disseminated Peritoneal Cancer of Appendiceal Origin.
Ann Surg Oncol. 2007 Nov 20;
BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis of appendiceal origin can alleviate symptoms and prolong survival. This aggressive therapy may impair patient quality of life (QOL). The purpose of this study was to monitor health outcomes before and after treatment. METHODS: Patients underwent cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal cancer. Patients completed questionnaires consisting of demographic information and the Functional Assessment of Cancer Therapy, the SF-36 Medical Outcomes Study survey, the Center for Epidemiologic Studies-Depression Scale, and the ECOG Performance Status Rating before (T1) and after surgery at 3 (T2), 6 (T3), 12 (T4), and 24 (T5) months. Time trends were assessed with the mixed model (SAS PROC MIXED) to allow use of all the observed data as well as to account for missing data. RESULTS: Fifty-eight patients (50% female) with a mean age 52.4 years (SD 12.6; range, 28-80) were assessed before surgery. Overall survival at 1 year was 78.7%. Emotional well-being improved over the study period, while physical well-being and physical functioning declined at T2 and then improved to near baseline levels at T3 and T4. Percentage of patients with depressive symptoms was as follows: T1 = 24%, T2 = 30%, T3 = 24%, and T4 = 33%. QOL scores improved over time. CONCLUSIONS: Although complications can affect short-term recovery, survival in appendix cancer patients with peritoneal cancer is good and for some can be achieved without major decrements in QOL at 1 year. Depressive symptoms and some physical limitations remain in surviving patients. [Abstract]

Liakakos T
Laparoscopic Gastrectomy: Feasibility, Safety and Efficacy.
Ann Surg Oncol. 2007 Nov 20; [Abstract]

Yu J, Park A, Morris E, Liberman L, Borgen PI, King TA
MRI Screening in a Clinic Population with a Family History of Breast Cancer.
Ann Surg Oncol. 2007 Nov 17;
BACKGROUND: Breast MRI is increasingly being used in patients at increased risk for breast cancer; however, guidelines for MRI screening are inadequately defined. We describe our experience with MRI screening in a large population of women with a family history of breast cancer. METHODS: We retrospectively reviewed the Memorial Sloan-Kettering breast cancer surveillance program prospective database from April 1999 to July 2006. Patients with a family history of breast cancer and at least 1 year follow-up were identified. All patients were offered biannual clinical breast examination (CBE) and annual mammography (MMG). MRI screening was performed at the discretion of the physician and patient. RESULTS: Family history profiles revealed 1,019 eligible patients; median follow-up was 5.0 years. MRI screening was performed in 374 (37%) patients resulting in a total of 976 MRIs during the study period. Cancer was detected in 9/374 patients (2%) undergoing MRI screening. Seven cancers were detected by MRI only, for a cancer detection rate of 0.7% (7/976) for screening MRI. When stratified by family risk profile, the positive predictive value (PPV) of MRI was higher (13%) in those patients with the strongest family histories and lower (6%) in patients with less significant family histories. CONCLUSIONS: MRI screening can be a useful adjunct to CBE and MMG in patients with high-risk family histories of breast cancer, yet it has low yield in patients with lower-risk family histories. These data suggest that MRI screening should be reserved for those at highest risk. [Abstract]

Coburn NG, Govindarajan A, Law CH, Guller U, Kiss A, Ringash J, Swallow CJ, Baxter NN
Stage-Specific Effect of Adjuvant Therapy Following Gastric Cancer Resection: a Population-based Analysis of 4,041 Patients.
Ann Surg Oncol. 2007 Nov 17;
BACKGROUND: Adjuvant chemoradiotherapy improved survival in patients with resected gastric adenocarcinoma in the Southwest Oncology Group/Intergroup 0116 trial. Our objective was to examine the impact of adjuvant treatment on overall survival (OS) in the general population. METHODS: Patients 18-85 years old who had undergone resection of non-metastatic gastric adenocarcinoma between May 2000 and December 2003, were identified from the Surveillance Epidemiology and End Results (SEER) database. Patients who had received pre-operative irradiation, had unknown stage or radiation status, or had a survival of 3 months or less from the date of diagnosis were excluded. Survival of those who received post-operative irradiation was compared with those who did not; Kaplan-Meier methods and Cox proportional hazards models were used. RESULTS: Of 4,041 patients, there was improved survival for those receiving adjuvant irradiation for stages III and IVM0, with a median OS of 31 versus 24 months (P = 0.005) and 20 versus 15 months (P < 0.001), respectively, and a trend for improved survival in univariate analysis of stage II (P = 0.0535). In final adjusted analysis, adjuvant irradiation significantly improved OS in stages III (HR: 0.71, P = 0.0007) and IVM0 (HR: 0.66, P < 0.0001). Adjusted analysis using a propensity score suggested that the benefit of adjuvant irradiation was similar in stage-II and -III patients. However, there was no statistical improvement in survival for stage-Ib and -II patients who had received adjuvant irradiation. CONCLUSIONS: In this population-based analysis, adjuvant radiotherapy for stage-III and IVM0 gastric cancer significantly improved OS. Analysis of stage-Ib and -II patients is limited by small numbers, but there may not be the same benefit. [Abstract]

Recent Articles in Liver Transplantation: Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society

Perkins JD
Evolving treatment of biliary strictures following liver transplantation.
Liver Transpl. 2007 Nov;13(11):1605-7.
BACKGROUND: The optimal endoscopic treatment for anastomotic biliary strictures after deceased donor liver transplantation is undefined. Endoscopic therapy with conventional methods of biliary dilation and stent placement has been successful but often requires prolonged therapy. OBJECTIVE: To determine the outcomes of an aggressive endoscopic approach that uses endoscopic dilation followed by maximal stent placement. SETTING: Tertiary-care academic medical center. PATIENTS: Of 176 patients who underwent deceased donor liver transplantation between June 1999 and July 2004, 25 were diagnosed with anastomotic biliary strictures. INTERVENTIONS: Patients were treated endoscopically with a combined technique of balloon dilation and maximal stent placement. MAIN OUTCOME MEASUREMENTS: Treatment outcomes, including bileduct patency, a need for surgical intervention, morbidity, and mortality, were evaluated retrospectively. RESULTS: Endoscopic dilation followed by maximal stent placement was performed until resolution of strictures in 22 or 25 patients (88% immediate success on intent-to-treat analysis). Persistent resolution of strictures was achieved in 18 of these 22 patients. Re-treatment was successful in 2 of 4 patients with recurrent strictures. Overall, 20 or 22 patients who completed endoscopic therapy (91%) avoided surgical intervention. Medical duration of endoscopic treatment was 4.6 months. Patients with early onset strictures required a significantly shorter duration of endoscopic therapy (3 vs 9 months; P < .01). Multiple stent placement was not technically difficult, and no major complications were encountered. CONCLUSIONS: Aggressive endoscopic therapy with combined biliary dilation and maximal stent placement allows resolution of anastomotic biliary strictures after deceased donor liver transplantation in a relatively short period, with sustained success and minimal complications. [Abstract]

Perkins JD
Early Development of nanoprobes for diagnostic imaging.
Liver Transpl. 2007 Nov;13(11):1604.
Fluorescence is increasingly used for in vivo imaging and has provided remarkable results. Yet this technique presents several limitations, especially due to tissue autofluorescence under external illumination and weak tissue penetration of low wavelength excitation light. We have developed an alternative optical imaging technique by using persistent luminescent nanoparticles suitable for small animal imaging. These nanoparticles can be excited before injection, and their in vivo distribution can be followed in realtime for more than 1 h without the need for any external illumination source. Chemical modification of the nanoparticles' surface led to lung or liver targeting or to long-lasting blood circulation. Tumor mass could also be identified on a mouse model. [Abstract]

Hao C, Erzheng C, Anwei M, Zhicheng Y, Baiyong S, Xiaxing D, Weixia Z, Chenghong P, Hongwei L
Validation of limited sampling strategy for the estimation of mycophenolic acid exposure in Chinese adult liver transplant recipients.
Liver Transpl. 2007 Dec;13(12):1684-93.
Mycophenolate mofetil (MMF) is indicated as immunosuppressive therapy in liver transplantation. The abbreviated models for the estimation of mycophenolic acid (MPA) area under the concentration-time curve (AUC) have been established by limited sampling strategies (LSSs) in adult liver transplant recipients. In the current study, the performance of the abbreviated models to predict MPA exposure was validated in an independent group of patients. A total of 30 MPA pharmacokinetic profiles from 30 liver transplant recipients receiving MMF in combination with tacrolimus were used to compare 8 models' performance with a full 10 time-point MPA-AUC. Linear regression analysis and Bland-Altman analysis were used to compare the estimated MPA-AUC(0-12h) from each model against the measured MPA-AUC(0-12h). A wide range of agreement was shown when estimated MPA-AUC(0-12h) was compared with measured MPA-AUC(0-12h), and the range of coefficient of determination (r(2)) was from 0.479 to 0.936. The model based on MPA pharmacokinetic parameters C(1h), C(2h), C(6h), and C(8h) had the best ability to predict measured MPA-AUC(0-12h), with the best coefficient of determination (r(2) = 0.936), the excellent prediction bias (2.18%), the best prediction precision (5.11%), and the best prediction variation (2SD = +/-7.88 mg . h/L). However, the model based on MPA pharmacokinetic sampling time points C(1h), C(2h), and C(4h) was more suitable when concerned with clinical convenience, which had shorter sampling interval, an excellent coefficient of determination (r(2) = 0.795), an excellent prediction bias (3.48%), an acceptable prediction precision (14.37%), and a good prediction variation (2SD = +/-13.23 mg . h/L). Measured MPA-AUC(0-12h) could be best predicted by using MPA pharmacokinetic parameters C(1h), C(2h), C(6h), and C(8h). The model based on MPA pharmacokinetic parameters C(1h), C(2h), and C(4h) was more feasible in clinical application. Liver Transpl 13:1684-1693, 2007. (c) 2007 AASLD. [Abstract]

Pelletier SJ, Schaubel DE, Wei G, Englesbe MJ, Punch JD, Wolfe RA, Port FK, Merion RM
Effect of body mass index on the survival benefit of liver transplantation.
Liver Transpl. 2007 Dec;13(12):1678-83.
Obese patients are at higher risk for morbidity and mortality after liver transplantation (LT) than nonobese recipients. However, there are no reports assessing the survival benefit of LT according to recipient body mass index (BMI). A retrospective cohort of liver transplant candidates who were initially wait-listed between September 2001 and December 2004 was identified in the Scientific Registry of Transplant Recipients database. Adjusted Cox regression models were fitted to assess the association between BMI and liver transplant survival benefit (posttransplantation vs. waiting list mortality). During the study period, 25,647 patients were placed on the waiting list. Of these, 4,488 (17%) underwent LT by December 31, 2004. At wait-listing and transplantation, similar proportions were morbidly obese (BMI >/= 40; 3.8% vs. 3.4%, respectively) and underweight (BMI < 20; 4.5% vs. 4.0%, respectively). Underweight patients experienced a significantly higher covariate-adjusted risk of death on the waiting list (hazard ratio [HR] = 1.61; P < 0.0001) compared to normal weight candidates (BMI 20 to <25), but underweight recipients had a similar risk of posttransplantation death (HR = 1.28; P = 0.15) compared to recipients of normal weight. In conclusion, compared to patients on the waiting list with a similar BMI, all subgroups of liver transplant recipients demonstrated a significant (P < 0.0001) survival benefit, including morbidly obese and underweight recipients. Our results suggest that high or low recipient BMI should not be a contraindication for LT. Liver Transpl, 2007. (c) 2007 AASLD. [Abstract]

Man K, Ng KT, Lo CM, Ho JW, Sun BS, Sun CK, Lee TK, Poon RT, Fan ST
Ischemia-reperfusion of small liver remnant promotes liver tumor growth and metastases-Activation of cell invasion and migration pathways.
Liver Transpl. 2007 Dec;13(12):1669-77.
Elucidating the mechanism of liver tumor growth and metastasis after hepatic ischemia-reperfusion (I/R) injury of a small liver remnant will lay the foundation for the development of therapeutic strategies to target small liver remnant injury, and will reduce the likelihood of tumor recurrence after major hepatectomy or liver transplantation for liver cancer patients. In the current study, we aimed to investigate the effect of hepatic I/R injury of a small liver remnant on liver tumor development and metastases, and to explore the precise molecular mechanisms. A rat liver tumor model that underwent partial hepatic I/R injury with or without major hepatectomy was investigated. Liver tumor growth and metastases were compared among the groups with different surgical stress. An orthotopic liver tumor nude mice model was used to further confirm the invasiveness of the tumor cells from the above rat liver tumor model. Significant tumor growth and intrahepatic metastasis (5 of 6 vs. 0 of 6, P = 0.015), and lung metastasis (5 of 6 vs. 0 of 6, P = 0.015) were found in rats undergoing I/R and major hepatectomy compared with the control group, and was accompanied by upregulation of mRNA levels for Cdc42, ROCK (Rho kinase), and vascular endothelial growth factor, as well as activation of hepatic stellate cells. Most of the nude mice implanted with liver tumor from rats under I/R injury and major hepatectomy developed intrahepatic and lung metastases. In conclusion, hepatic I/R injury of a small liver remnant exacerbated liver tumor growth and metastasis by marked activation of cell adhesion, invasion, and angiogenesis pathways. Liver Transpl 13:1669-1677, 2007. (c) 2007 AASLD. [Abstract]

Levy MF
Reply: Geographic disparities and deceased donor liver transplantation within a single UNOS region.
Liver Transpl. 2007 Dec;13(12):1761. [Abstract]

Emre S, Arnon R, Cohen E, Morotti RA, Vaysman D, Shneider BL
Resolution of hepatopulmonary syndrome after auxiliary partial orthotopic liver transplantation in abernethy malformation. A case report.
Liver Transpl. 2007 Dec;13(12):1662-8.
Congenital absence of portal vein and extrahepatic portocaval shunt, also referred to as an Abernethy type 1, is a rare malformation of the mesenteric vasculature. A 9-year-old girl presented with dyspnea on exertion and orthodeoxia. A diagnosis of an Abernethy malformation type 1b and hepatopulmonary syndrome (HPS) was made, and she underwent auxiliary partial orthotopic liver transplantation (APOLT). Symptoms and signs of HPS resolved 2 months after the operation. HPS in Abernethy syndrome is a manifestation of normal portal blood flow bypassing the liver and can be ameliorated by redirecting blood flow to a segment of liver with normal portal anatomy. APOLT is a feasible and successful surgical procedure for patients with Abernethy malformation and HPS. Liver Transpl 13:1662-1668, 2007. (c) 2007 AASLD. [Abstract]

Boyd SD, Stenard F, Lee DK, Goodnough LT, Esquivel CO, Fontaine MJ
Alloimmunization to red blood cell antigens affects clinical outcomes in liver transplant patients.
Liver Transpl. 2007 Dec;13(12):1654-61.
Transfusion therapy of liver transplant patients remains a challenge. High volumes of intraoperative blood transfusion have been shown to increase the risk of poor graft or patient survival. We conducted a retrospective study of 209 consecutive liver transplant cases at our institution. Only patients receiving their first liver transplant, with no other simultaneous organ transplants, were included. Cox proportional hazard modeling was used to identify clinical variables correlated with postoperative patient mortality. Statistically significant variables for poor patient survival were the number of red blood cell and plasma units transfused, a history of red blood cell alloantibodies, and the immunosuppressive regimen used. History of pregnancy also approached statistical significance but was less robust than the other 3 variables. Our findings suggest that blood transfusion and immune modulation greatly affect the survival of patients after liver transplantation. Liver Transpl 13:1654-1661, 2007. (c) 2007 AASLD. [Abstract]

Gow PJ, Warrilow S, Lontos S, Lubel J, Wongseelashote S, Macquillan GC, Jones RM, Bellomo R, Angus PW
Time to review the selection criteria for transplantation in paracetamol-induced fulminant hepatic failure?
Liver Transpl. 2007 Dec;13(12):1762-3. [Abstract]

Goss JA, Barshes NR, Washburn WK
Reply: Geographic disparities and deceased donor liver transplantation within a single UNOS region.
Liver Transpl. 2007 Dec;13(12):1760. [Abstract]

Ravaioli M, Cescon M, Mikus E, Grazi GL, Ercolani G, Kimura T, Tuci F, Mikus PM, Bernardi M, Pinna AD
Liver and partial atrium transplantation for chronic Budd-Chiari syndrome.
Liver Transpl. 2007 Dec;13(12):1758-9. [Abstract]

Cescon M, Grazi GL, Ravaioli M, Cucchetti A, Ercolani G, Pinna AD
Modified outflow reconstruction with a venous patch in domino liver transplantation.
Liver Transpl. 2007 Dec;13(12):1756-7. [Abstract]

Maheshwari A, Maley W, Li Z, Thuluvath PJ
Biliary complications and outcomes of liver transplantation from donors after cardiac death.
Liver Transpl. 2007 Dec;13(12):1645-53.
Biliary complications after liver transplantation (LT) using organs retrieved from donors after cardiac death are not well characterized. The aim of this study was to evaluate the severity of biliary complications and outcomes after donation after cardiac death liver transplantation (DCD-LT). A retrospective evaluation of 20 DCD-LTs from 1997-2006 was performed. The recipient age was 53 +/- 8.7, and the donor age was 35 +/- 11 years. The warm ischemia time, cold ischemia time, peak alanine aminotransferase level, and peak aspartate aminotransferase level were 33 +/- 12 minutes, 8.7 +/- 2.7 hours, 1757 +/- 1477 U/L, and 4020 +/- 3693 U/L, respectively. The bilirubin and alkaline phosphatase levels at hospital discharge after LT were 3.2 +/- 5.4 mg/dL and 248 +/- 200 U/L, respectively. During a median follow-up of 7.5 months (range: 1-73), 5 patients (25%; 1 death after re-LT) died (3 from sepsis, 1 from recurrent hepatocellular carcinoma at 4 months, and 1 from a cardiac event at 46 months), and additionally, 4 patients (20%) required re-LT (1 because of hepatic artery thrombosis, 1 because of primary graft nonfunction, and 2 because of biliary strictures). Twelve (60%) developed biliary complications, and of these, 11 (55%) had serious biliary complications. The biliary complications were as follows: a major bile leak for 2 patients (10%; both eventually underwent retransplantation), anastomotic strictures for 5 patients (25%), hilar strictures for 7 patients (35%), extrahepatic donor duct strictures for 9 patients (45%), intrahepatic strictures for 10 patients (50%), stones for 1 patients (5%), casts for 7 patients (35%), and debris for 2 patients (10%). More than 1 biliary complication was seen in most patients, and these were unpredictable and required multiple diagnostic or therapeutic procedures. Serious biliary complications are common after DCD-LT, and research should focus on identifying donor and recipient factors that predict and prevent serious biliary complications. Liver Transpl 13:1645-1653, 2007. (c) 2007 AASLD. [Abstract]

Perkins JD
Venous outflow obstruction in liver transplantation is associated with the anastomotic technique.
Liver Transpl. 2007 Dec;13(12):1751-5.
The outflow venovenous anastomosis represent a crucial aspect during orthotopic liver transplantation (OLT) with inferior vena cava (IVC) preservation. The modified Belghiti liver hanging maneuver applied to the last phase of hepatectomy, lifting the liver, provides a better exposure of the suprahepatic region and allows easier orthogonal clamping of the three suprahepatic veins with a minimal portion of IVC occlusion. The outflow anastomosis constructed with a common cloacae of the three native suprahepatic veins is associated with a lower incidence of graft related venous outflow complications. The procedure planned in 120 consecutive OLT was achieved in 118 (99%). The outflow anastomosis was constructed on the common cloaca of the three hepatic veins in 111/120 cases (92.5%). No major complications were observed (bleeding during tunnel creation, graft outflow dysfunction, etc) except in one patient with acute Budd-Chiari, who successfully underwent retransplantation. [Abstract]

Reed A, Herndon JB, Ersoz N, Fujikawa T, Schain D, Lipori P, Hemming A, Li Q, Shenkman E, Vogel B
Effect of prophylaxis on fungal infection and costs for high-risk liver transplant recipients.
Liver Transpl. 2007 Dec;13(12):1743-50.
We sought to determine whether the prophylactic use of amphotericin B products (conventional amphotericin B and liposomal amphotericin B) reduces the incidence of fungal infections in high-risk liver transplant recipients, and if so, whether this lowers the cost of care. The study sample comprised 232 adult orthotopic liver transplants performed from 1994 to 2005 at a single center for patients classified as being at high risk for fungal infections. High-risk patients who received transplants with a prophylaxis regimen of amphotericin B (n = 58 transplants) were compared with high-risk patients who received no prophylaxis (n = 174 transplants). Fungal infections occurred in 3 transplants (5.17%) of those who received amphotericin B and 28 transplants (16.09%) in those without prophylaxis (P = 0.0432). Regression models were used to analyze fungal infection and costs for the 232 high-risk transplants. Failure to offer prophylaxis conferred a 4-fold greater risk of fungal infection (P = 0.046) compared with those who received amphotericin B. A fungal infection in a high-risk recipient increased mean costs by 46.48%. The indirect effect of prophylaxis (operating through infection reduction) is estimated to reduce overall costs in high-risk patients by 8.73%. Liver Transpl 13: 1743-1750, 2007. (c) 2007 AASLD. [Abstract]

Ito T, Takada Y, Ueda M, Haga H, Maetani Y, Oike F, Ogawa K, Sakamoto S, Ogura Y, Egawa H, Tanaka K, Uemoto S
Expansion of selection criteria for patients with hepatocellular carcinoma in living donor liver transplantation.
Liver Transpl. 2007 Dec;13(12):1637-44.
In the present study, the results of living donor liver transplantation (LDLT) for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine optimal criteria exceeding the Milan criteria (MC) but still with predictably good outcomes. On the basis of pretransplant imaging studies, 70 patients met the MC, and 55 patients did not. Patients who exceeded the MC but presented with </=10 tumors all </=5 cm in diameter (n = 30) displayed 5-year recurrence rates (7.3%) similar to those of patients within the MC (9.7%, P = 0.8787). According to the results of multivariate analysis of risk factors for recurrence among preoperative tumor variables, we have defined the new criteria, namely </=10 tumors all </=5 cm in diameter and protein induced by vitamin K absence or antagonist-II (PIVKA-II) </=400 mAU/mL. The 78 patients who met the new criteria showed significantly lower 5-year recurrence rates (4.9%) than the 40 patients who exceeded them (60.5%, P < 0.0001). Similarly, 5-year survival rates significantly differed between these groups (86.7% versus 34.4%, respectively; P < 0.0001). In conclusion, selection criteria for patients with HCC undergoing LDLT may be safely extended to </=10 tumors all </=5 cm in diameter and PIVKA-II </=400 mAU/mL with acceptable outcomes. Liver Transpl 13: 1637-1644, 2007. (c) 2007 AASLD. [Abstract]

Fung JJ, Eghtesad B, Patel-Tom K
Using livers from donation after cardiac death donors-A proposal to protect the true Achilles heel.
Liver Transpl. 2007 Dec;13(12):1633-6. [Abstract]

Lee HW, Suh KS, Shin WY, Cho EH, Yi NJ, Lee JM, Han JK, Lee KU
Classification and prognosis of intrahepatic biliary stricture after liver transplantation.
Liver Transpl. 2007 Dec;13(12):1736-42.
Intrahepatic biliary stricture (IHBS) after liver transplantation (LT) may develop in patients with hepatic artery thrombosis, chronic rejection, or ABO incompatibility, as well as in patients with prolonged warm ischemia in non-heart-beating donor (NHBD) LT. However, the clinical course and methods of management have not been well defined for IHBSs to date. Thus, the purpose of this study was to provide a classification of post-LT IHBS and to investigate patient prognosis. Forty-four patients who developed IHBS after NHBD LT were enrolled. On the basis of the cholangiographic appearance, patients were classified into 4 groups: unilateral focal (UF, n = 8), confluence (CO, n = 10), bilateral multifocal (BM, n = 21), and diffuse necrosis (DN, n = 5). The UF type was defined as cases with stricture only in the segmental branch of the unilateral hemiliver; the CO type in cases with several strictures at confluence level; and the BM type in cases with multiple strictures bilaterally. Cases with diffuse obliteration of peripheral ducts or destruction of the central architectural integrity, over a long segment, were classified as the DN type. Five patients with the CO type required several interventions requiring biliary dilatation, yet all patients with the UF or CO type had a good prognosis. Among the patients with the BM type, 3 patients (14.3%) died or underwent retransplantation due to biliary complications, and 7 (33.3%) required repeated interventions for >1 year without improvement. Moreover, among 5 patients classified as the DN type, 1 (20%) died of biliary sepsis, 2 (40%) underwent retransplantation, and the remaining 2 (40%) did not recover from persistent jaundice and life-threatening cholangitis despite multiple interventions. In conclusion, all patients classified as UF or CO had a good outcome with or without additional interventions. However, all patients with the DN type and about half the patients with the BM type did not recover from life-threatening complications, despite repeated aggressive interventions; early retransplantation was therefore the only treatment option for these patients. Liver Transpl 13:1736-1742, 2007. (c) 2007 AASLD. [Abstract]

Wells JT, Said A, Agni R, Tome S, Hughes S, Dureja P, Lucey MR
The impact of acute alcoholic hepatitis in the explanted recipient liver on outcome after liver transplantation.
Liver Transpl. 2007 Dec;13(12):1728-35.
Patients with clinical acute alcoholic hepatitis (AAH) are not considered suitable candidates for orthotopic liver transplantation (OLT). The histological correlates of AAH are often seen in the explanted liver at the time of transplantation. The importance of these findings remains inconclusive regarding their role as a prognostic marker for patient or allograft health. Our aim was to examine the explanted liver of patients with purely alcoholic liver disease (ALD) for findings of histologic AAH and to correlate these to patient and graft outcomes. We compared patients with and without histological AAH with patients transplanted for non-ALD. Of 1,097 liver transplant recipients, 148 had ALD and 125 were non-ALD control patients with similar demographics. Thirty-two of 148 ALD patients had histologic AAH, and 116 had bland alcoholic cirrhosis (BAC). Twenty-eight percent of the ALD patients reported <6 months abstinence, and 54% reported <12 months abstinence. There was a statistically significant relationship between the presence of histologic AAH and abstinence durations <12 months (P = 0.009), but not <6 months. Overall, posttransplantation patient and graft survival between the ALD and non-ALD groups was not significantly different (P = 0.53). Furthermore, patient and graft survival between ALD patients with histologic AAH and BAC were similar (P = 0.13 and P = 0.11, respectively). The rate of posttransplantation relapse among ALD patients was 16%; however, there was no increase in graft loss, nor was there decreased survival compared with controls. The patients with histologic AAH and those with BAC had no differences in posttransplantation relapse (P = 0.13). In multivariate analysis, patient and graft survival was not influenced by pretransplantation abstinence or posttransplantation relapse. In conclusion, histological alcoholic hepatitis in the explant did not predict worse outcome regarding relapse, and allograft or patient survival for liver transplant recipients. Caution should be exercised when liver histology is used to discriminate among suitable candidates for OLT concerning alcoholic patients. Liver Transpl 13: 1728-1735, 2007. (c) 2007 AASLD. [Abstract]

Lopez-Plaza I
Transfusion guidelines and liver transplantation: Time for consensus.
Liver Transpl. 2007 Dec;13(12):1630-2. [Abstract]

Thuluvath PJ
Morbid obesity with one or more other serious comorbidities should be a contraindication for liver transplantation.
Liver Transpl. 2007 Dec;13(12):1627-9. [Abstract]

Ozaki M, Todo S
Surgical stress and tumor behavior: Impact of ischemia-reperfusion and hepatic resection on tumor progression.
Liver Transpl. 2007 Dec;13(12):1623-6. [Abstract]

Ghabril M, Dickson RC, Machicao VI, Aranda-Michel J, Keaveny A, Rosser B, Bonatti H, Krishna M, Yataco M, Satyanarayana R, Harnois D, Hewitt W, Willingham DD, Grewal H, Hughes CB, Nguyen J
Liver retransplantation of patients with hepatitis C infection is associated with acceptable patient and graft survival.
Liver Transpl. 2007 Dec;13(12):1717-27.
Infection with hepatitis C virus (HCV) is the leading cause of liver transplantation (LT), while liver retransplantation (RT) for HCV is controversial as a result of concerns over poor outcomes. We sought to compare patient and graft survival after RT in patients with and without HCV. We performed a retrospective chart review of all patients undergoing RT at our center between February 1998 and April 2004. Indications for RT, HCV status, patient, and donor characteristics, laboratory values, and hospitalization status at RT were collected. A total of 108 patients (48 HCV and 60 non-HCV) underwent RT during the study period, with mean post-RT follow-up of 1,096 days (range, 0-2,888 days). Grafts from donors aged >60 years were used less frequently in HCV patients at RT (6%) compared with LT (47%), P < 0.001. There was no difference between HCV vs. non-HCV patients in 1- and 3-year patient survival (respectively, 79% vs. 63%, and 71% vs. 63%) and graft survival (respectively, 67% vs. 66%, and 59% vs. 56%). Post-RT mortality and graft failure in HCV patients occurred within the first year in 89% of patients, and 83% were unrelated to HCV recurrence. We conclude that patients should not be excluded from consideration for retransplantation solely on the basis of a diagnosis of HCV. Liver Transpl 13:1717-1727, 2007. (c) 2007 AASLD. [Abstract]

Ghabril M, Nguyen J, Kramer D, Genco T, Mai M, Rosser BG
Presentation of an acquired urea cycle disorder post liver transplantation.
Liver Transpl. 2007 Dec;13(12):1714-6.
The liver's role as the largest organ of metabolism and the unique and often critical function of liver-specific enzyme pathways imply a greater risk to the recipient of acquiring a donor metabolic disease with liver transplants versus other solid organ transplants. With clinical consequences rarely reported, the frequency of solid organ transplant transfer of metabolic disease is not known. Ornithine transcarbamylase deficiency (OTCD), although rare, is the most common of the urea cycle disorders (UCDs). Because of phenotypic heterogeneity, OTCD may go undiagnosed into adulthood. With over 5000 liver transplant procedures annually in the United States, the likelihood of unknowingly transmitting OTCD through liver transplantation is very low. We describe the clinical course of a liver transplant recipient presenting with acute hyperammonemia and encephalopathy after receiving a liver graft form a donor with unrecognized OTCD. Liver Transpl 13: 1714-1716, 2007. (c) 2007 AASLD. [Abstract]

Kwo PY, Saxena R, Cummings OW, Tector AJ
Intravenous interferon during the anhepatic phase of liver retransplantation and prevention of recurrence of cholestatic hepatitis C virus.
Liver Transpl. 2007 Dec;13(12):1710-3.
Cholestatic hepatitis C virus (HCV) infection post orthotopic liver transplantation is associated with a poor prognosis. We describe 2 patients who received interferon and ribavirin for cholestatic HCV infection with clearance of HCV RNA from the serum. Both developed signs of graft failure necessitating repeat orthotopic liver transplantation, and at surgery, interferon was administered during the anhepatic phase to prevent graft reinfection. Both patients are doing well with no evidence of recurrent viremia at 36 and 24 months of follow-up after repeat transplantation, respectively. Our results suggest that in those with cholestatic HCV infection, repeat transplantation after viral clearance is feasible and can occur without reinfection of the graft, challenging the current practice of denying retransplantation for patients with cholestatic HCV. The role of anhepatic administration of interferon deserves further examination, and this combination may provide a solution in a subset of patients with an otherwise poor prognosis. Liver Transpl 13:1710-1713, 2007. (c) 2007 AASLD. [Abstract]

Watson CJ, Gimson AE, Alexander GJ, Allison ME, Gibbs P, Smith JC, Palmer CR, Bradley JA
A randomized controlled trial of late conversion from calcineurin inhibitor (CNI)-based to sirolimus-based immunosuppression in liver transplant recipients with impaired renal function.
Liver Transpl. 2007 Dec;13(12):1694-702.
Renal impairment is common in patients after liver transplantation and is attributable in large part to the use of calcineurin inhibitor (CNI)-based immunosuppression. We sought to determine whether conversion to sirolimus-based immunosuppression was associated with improved renal function. In a single-center, randomized, controlled trial, 30 patients at least 6 months post liver transplantation were randomized to remain on CNI-based immunosuppression or to switch to sirolimus-based immunosuppression. The primary outcome measure was change in measured glomerular filtration rate (GFR) between baseline and 12 months. Of 30 patients randomized, 3 were withdrawn at randomization, leaving 14 patients on CNI and 13 on sirolimus. There was a significant improvement in delta GFR following conversion to sirolimus at 3 months (7.7 mL/minute/1.73 m(2); 95% confidence interval, 3.5-11.9) and 1 yr (6.1 mL/minute/1.73 m(2); 95% confidence interval, 0.9-11.4). The difference in absolute GFR between the 2 study groups was significant at 3 months (P = 0.02), but not at 12 months (P = 0.07). The principal adverse events following conversion were the development of skin rash (9 of 13 patients, 69%) and mouth ulcers (5 of 13 patients, 38%). Two patients developed acute rejection at 2 and 3 months following conversion, 1 in association with low sirolimus levels and 1 having stopped the drug inadvertently. In conclusion, overall, this study suggests that conversion to sirolimus immunosuppression is associated with a modest improvement in renal function. Side effects were common, but tolerable in most patients and controlled with dose reduction. Liver Transpl 13:1694-1702, 2007. (c) 2007 AASLD. [Abstract]

Arthurs SK, Eid AJ, Pedersen RA, Dierkhising RA, Kremers WK, Patel R, Razonable RR
Delayed-onset primary cytomegalovirus disease after liver transplantation.
Liver Transpl. 2007 Dec;13(12):1703-9.
Clinical practice guidelines recommend antiviral prophylaxis to cytomegalovirus (CMV) donor-positive/recipient-negative (D+/R-) liver transplant recipients. We assessed the outcome of this strategy by determining the incidence, clinical features, and risk factors of CMV disease among CMV D+/R- liver transplant recipients who received antiviral prophylaxis. Sixty-seven CMV D+/R- liver transplant recipients (mean age +/- standard deviation: 49.5 +/- 11.4 years; 75% male) received oral ganciclovir [n = 9 (13%)] or valganciclovir [n = 58 (87%)] prophylaxis for a median duration of 92 days (interquartile range: 91-100). No breakthrough CMV disease was observed during antiviral prophylaxis. However, primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylaxis was stopped. The incidence of delayed-onset primary CMV disease was similar between those who received oral ganciclovir and valganciclovir. Nine (47%) patients had CMV syndrome, 8 (42%) had gastrointestinal CMV disease, and 2 (11%) had CMV hepatitis. Female patients (P = 0.01) and younger age at transplant (P = 0.03) were associated with an increased risk, whereas diabetes mellitus (P < 0.001) was significantly associated with a lower risk of delayed-onset primary CMV disease. Allograft loss or mortality occurred in 8 (12%) patients during the median follow-up period of 3.31 (range: 0.8-5.9) years. No significant association was observed between CMV disease and patient and allograft survival. In conclusion, CMV disease remains a common complication in CMV D+/R- liver transplant patients during the contemporary era of antiviral prophylaxis. Female patients and younger patients are at increased risk of delayed-onset primary CMV disease. Liver Transpl 13: 1703-1709, 2007. (c) 2007 AASLD. [Abstract]

Perkins JD
Liver Transpl. 2007 Oct;13(10):1466-7. [Abstract]

Perkins JD
Transplanted patients with combined hepatocellular-cholangiocarcinoma: now what?
Liver Transpl. 2007 Oct;13(10):1465-6. [Abstract]

Ahmad J, Downey KK, Akoad M, Cacciarelli TV
Impact of the MELD score on waiting time and disease severity in liver transplantation in United States veterans.
Liver Transpl. 2007 Nov;13(11):1564-9.
Organ allocation for liver transplantation (LT) in the United States is based on the Model for End-Stage Liver Disease (MELD) score. The MELD score prioritizes organ distribution to sicker patients. There is limited data on the effect of this policy on transplantation in the Veterans Affairs (VA) healthcare system. The aim of this study was to determine the impact of the MELD score on U.S. veteran patients undergoing LT. Comparison of MELD scores and waiting time of LT recipients before and after the introduction of the MELD system was done. A total of 192 LT recipients were analyzed. Blood type, diagnosis, listing MELD score, and Child-Turcotte-Pugh (CTP) score at transplant did not differ although MELD era recipients were older (mean 54.3 vs. 51.3 yr, P = 0.009). Mean waiting time decreased from 461 days (pre-MELD) to 252 days (MELD era) (P = 0.004). Mean MELD score at LT increased from 23.4 (MELD era) compared to 20.3 (pre-MELD) (P = 0.01). In conclusion, waiting time for LT in U.S. veterans has decreased significantly in the MELD era. The MELD score of patients transplanted in the MELD era is significantly higher and patients are still being listed at a high MELD score. The MELD system has lead to sicker veterans being transplanted with shorter waiting times. [Abstract]

Recent Articles in Journal of Vascular Surgery: Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter

Yunus TE, Tariq N, Callahan RE, Niemeyer DJ, Brown OW, Zelenock GB, Shanley CJ
Changes in inferior vena cava filter placement over the past decade at a large community-based academic health center.
J Vasc Surg. 2007 Nov 28;
OBJECTIVE: A significant increase in the frequency of inferior vena cava (IVC) filter placement at our large community-based academic health center led us to evaluate changes in indications, devices, and providers over the past decade. METHODS: A single-center retrospective review of all filter placements was performed comparing 76 patients in 1995 with 470 patients in 2005. Demographic data, provider data, filter type, and indications for placement were tabulated. Complications, follow-up evaluation, filter removal, and patient outcomes were examined. RESULTS: There was a greater than sixfold increase in the number of filters placed in 2005 vs 1995. There were no significant differences in patient demographics or the extent of venous thromboembolic (VTE) disease during this period except for an increase in median age. Filter placement by interventional radiologists remained approximately 50% of the total whereas placement by vascular/trauma surgeons increased to 24% and placement by cardiologists decreased to 29% (P < .001). In 2005, a smaller percentage of filters were placed for absolute indications, while filter placements for relative and prophylactic indications increased over the same time period, especially among cardiologists (P = .02). Potentially retrievable filters are increasingly being used for prophylaxis; however, only 2.4% were retrieved. An increasing number of filters were placed in patients with only infrapopliteal deep venous thrombosis (P = .07). A shift was seen to lower profile and removable filter types. Long-term patient follow-up showed little change in disease progression or in morbidity and mortality of filter insertion. CONCLUSIONS: Technological and practice pattern changes have led to an increase in filters inserted by vascular and trauma surgeons in the operating room and intensive care units. Increased diagnosis of VTE disease and newer low profile delivery systems in patients may also have contributed to the significant increase in filter placement. A shift in indications for placement from absolute toward relative indications and prophylaxis is evident over time and across providers, indicating the need for consensus development of appropriate criteria. [Abstract]

Ballotta E, Da Giau G, Bridda A, Gruppo M, Pauletto A, Martella B
Open abdominal aortic aneurysm repair in octogenarians before and after the adoption of endovascular grafting procedures.
J Vasc Surg. 2007 Nov 28;
OBJECTIVE: This study evaluated (1) elective open abdominal aortic aneurysm repair (OAR) in patients aged >/=80 years before and after stent graft devices for endovascular aneurysm repair (EVAR) became commercially available and (2) the effect on perioperative (30-day) outcome of the anatomic constraints that led to EVAR being excluded for many of them. METHODS: A review was conducted on the records of 111 patients aged >/=80 years who underwent elective OAR during a 14-year period at the University of Padua School of Medicine. Patients were separated into two groups: group 1 (n = 65) had OAR before and group 2 (n = 46) after an EVAR program was adopted at the medical school in mid-2000. Perioperative death and morbidity, location of proximal aortic clamp, management of the left renal vein, associated iliac aneurysmal or occlusive diseases, the type of surgical reconstruction, operating time, and lengths of stay in the intensive care unit and the hospital were recorded. All the data were compared between the two groups. RESULTS: Retroperitoneal approach, suprarenal clamping, left renal vein division, and longer operating room time were statistically more common in group 2 (36.9% vs 12.3%, P = .002; 15.2% vs 3.1%, P = .032; 23.9% vs 7.7%, P = .026; and 117 +/- 8 min vs 95 +/-7 min, P < .001, respectively). Although group 2 had significantly more iliac aneurysms (52.1% vs 32.3%; P = .036), the number of bifurcated reconstructions was comparable. The overall perioperative mortality rate was 1.8% (2 of 111), and the figures for groups 1 and 2 were comparable (3.1% vs 0%; P = .510). No deaths were cardiac related. Group 2 had a significantly higher incidence of kidney failure (8.7% vs 0%; P = .027). Kaplan-Meier analysis showed an overall 3-, 5-, and 10-year survival rate of 80.6%, 67.2%, and 59.4%, respectively, with a 3- and 5-year survival rate comparable between groups 1 and 2 (77.8% and 66.7% vs 87.8% and 45.8%, respectively; log-rank test, P = .921). CONCLUSIONS: Octogenarians can tolerate OAR with acceptable rates of perioperative mortality and morbidity. Although the complexity of OAR has increased significantly in the era of EVAR, the perioperative outcome has not changed. [Abstract]

Heng MS, Fagan MJ, Collier JW, Desai G, McCollum PT, Chetter IC
Peak wall stress measurement in elective and acute abdominal aortic aneurysms.
J Vasc Surg. 2007 Nov 28;
BACKGROUND: Abdominal aortic aneurysm (AAA) rupture occurs when wall stress exceeds wall strength. Engineering principles suggest that aneurysm diameter is only one aspect of its geometry that influences wall stress. Finite element analysis considers the complete geometry and determines wall stresses throughout the structure. This article investigates the interoperator and intraoperator reliability of finite element analysis in the calculation of peak wall stress (PWS) in AAA and examines the variation in PWS in elective and acute AAAs. METHOD: Full ethics and institutional approval was obtained. The study recruited 70 patients (30 acute, 40 elective) with an infrarenal AAA. Computed tomography (CT) images were obtained of the AAA from the renal vessels to the aortic bifurcation. Manual edge extraction, three-dimensional reconstruction, and blinded finite element analysis were performed to ascertain location and value of PWS. Ten CT data sets were analyzed by four different operators to ascertain interoperator reliability and by one operator twice to ascertain intraoperator reliability. An intraclass correlation coefficient was obtained. The Mann-Whitney U test and independent samples t test compared groups for statistical significance. RESULTS: The intraclass correlation coefficient was 0.71 for interoperator reliability and 0.84 for intraoperator reliability. There was no statistically significant difference in the mean (SD) maximal AAA diameter between elective (6.47 [1.30] cm) and acute (7.08 [1.39] cm) patients (P = .073). The difference in PWS between elective (0.67 [0.30] MPa) and acute (1.11 [ 0.51] MPa) patients (P = .008) was statistically significant, however. CONCLUSION: Interoperator and intraoperator reliability in the derivation of PWS is acceptable. PWS, but not maximal diameter, was significantly higher in acute AAAs than in elective AAAs. [Abstract]

Calligaro KD, Toursarkissian B, Clagett GP, Towne J, Hodgson K, Moneta G, Sidawy AN, Cronenwett JL
Guidelines for hospital privileges in vascular and endovascular surgery: Recommendations of the Society for Vascular Surgery.
J Vasc Surg. 2007 Nov 28;
The Clinical Practice Council of the Society for Vascular Surgery (SVS) was charged with providing an updated consensus on guidelines for hospital privileges in vascular and endovascular surgery. One compelling reason to update these recommendations is that vascular surgery as a specialty has continued to evolve with a significant shift towards endovascular therapies. The Society for Vascular Surgery is making the following four recommendations concerning guidelines for hospital privileges for vascular and endovascular surgery. First, anyone applying for new hospital privileges to perform vascular surgery should have completed an Accreditation Council for Graduate Medical-accredited vascular surgery residency and should obtain American Board of Surgery certification in vascular surgery within 3 years of completion of their training. Second, we reaffirm and provide updated recommendations concerning previous established guidelines for peripheral endovascular procedures, thoracic and abdominal aortic endograft replacements, and carotid artery balloon angioplasty and stenting for trainees and already credentialed physicians who are adding these new procedures to their hospital credentials. Third, we endorse the Residency Review Committee for Surgery recommendations regarding open and endovascular cases during vascular residency training. Fourth, we endorse the Inter-societal Commission for Accreditation of Vascular Laboratories (ICAVL) recommendations for noninvasive vascular laboratory interpretations and examinations to become a registered physician in vascular interpretation (RPVI) or a registered vascular technologist (RVT). [Abstract]

J Vasc Surg. 2007 Nov 28; [Abstract]

Alvarez B, Ribo M, Maeso J, Quintana M, Alvarez-Sabin J, Matas M
Transcervical carotid stenting with flow reversal is safe in octogenarians: A preliminary safety study.
J Vasc Surg. 2007 Nov 28;
BACKGROUND: The use of carotid stenting in octogenarian patients is controversial; some authors consider this population at high risk for the procedure. Anatomic vascular complexity may be an important reason for the high reported rates of periprocedural thromboembolic complications. Transcervical carotid angioplasty and stenting (TCS) with flow reversal avoids aortic arch instrumentation. In this study, we analyzed our experience with TCS in octogenarian patients and compared the results with those of carotid endarterectomy (CEA) in the same age group in terms of safety. METHODS: The study included 81 patients, >/=80 years, a retrospective cohort of 45 consecutive patients treated with CEA (January 2002 to January 2005), and a prospective cohort of 36 consecutive patients treated with TCS with protective flow reversal (January 2005 to January 2007). Patients were considered symptomatic according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Stenting indication was established on the SAPPHIRE criteria. General anesthesia was used in patients undergoing CEA, and local anesthesia in those receiving TCS. Primary endpoints were: stroke, death, or acute myocardial infarction within 30 days. Secondary endpoints were peripheral nerve paralysis and cervical hematoma. Statistical significance for between-group differences was assessed by Pearson chi(2) or Fisher exact test, and Student t test. A P value of <.05 was considered statistically significant. Follow-up was limited to 30 days. RESULTS: Baseline epidemiological characteristics and revascularization indications were similar between both groups. Mean age was significantly higher in the TCS group (83.5 +/- 3.35) than the CEA group (81.7 +/- 1.55) (P = .004). Percentage of symptomatic lesions was similar: 30.6% in TCS vs 44.4% in CEA (P = .2). Comorbid conditions (respiratory or cardiac) were more frequent in TCS group (61.6% vs 26.6%; P = .002). There were no significant differences between groups for the primary endpoints: 4.4% (one stroke, one acute myocardial infarction) for CEA vs 0% for TCS (P = .5). Among CEA patients, there were two peripheral nerve palsies (4.4%) and one cervical hematoma (2.2%); there were no such complications with TCS (P = .5 and P = 1, respectively). In one asymptomatic TCS patient, Doppler study at 24 hours following the procedure showed a common carotid artery dissection, which was treated by a common carotid to internal carotid bypass. CONCLUSIONS: In this preliminary experience, transcervical carotid angioplasty and stenting with flow reversal for cerebral protection was as safe at short term as carotid endarterectomy in octogenarian patients, who additionally had considerable comorbidity; thus, it may be possible to extend the indications for carotid revascularization in this population. Studies in larger patient series are required to confirm the trends observed in this study. [Abstract]

Beck AW, Murphy EH, Hocking JA, Timaran CH, Arko FR, Clagett GP
Aortic reconstruction with femoral-popliteal vein: Graft stenosis incidence, risk and reintervention.
J Vasc Surg. 2007 Nov 28;
BACKGROUND: Management using femoral-popliteal vein (FPV) of aortic graft infections, failing aortofemoral bypass, and aortoiliac occlusive disease in young patients with a small aorta is now an accepted therapeutic method and is performed frequently at our institution. A high reintervention rate for FPV graft stenosis has recently been reported. The purpose of this study was to determine the incidence of FPV graft failure due to stenosis after neoaortoiliac system (NAIS) reconstruction, and to identify risk factors for this complication. METHODS: A review was performed of 240 patients who underwent NAIS reconstruction at our institution between January 1991 and December 2005. All patients were entered into a prospective database and were evaluated for the incidence of vein graft stenosis requiring reintervention, risk factors for stenosis, and the rate and type of reintervention required to assist patency. Patients with occlusion are evaluated and reported, but excluded from detailed analysis. Risk factors assessed included gender, operative features, FPV size (diameter), smoking history, and medical comorbidities. RESULTS: Of the 240 NAIS procedures performed during this time period, 11 (4.6%) patients have required 12 graft revisions (one patient required a second intervention) for stenosis using open and endovascular techniques. Over the same time period, graft occlusion occurred in nine patients (3.8%). This provided a primary patency at 2 and 5 years of 87% and 82%, and an assisted primary patency rate of 96% and 94%. Mean time to revision was 23.5 months (range 5.5 to 83.5 months). Median FPV graft size in the nonrevised patients was 7.8 mm (range 4.0 to 11.4 mm), and 6.4 mm (range 4.7 to 8.7 mm) in the revised group (P = .006). Survival analysis revealed small vein graft size (<7.2 mm), coronary artery disease (CAD), and extensive smoking history as independent predictors of time to stenosis (P = .002, .02, .01, respectively), with multivariable analysis confirming these results (P = .002, .06, .012). Patients with CAD combined with small graft size were found to be at especially high risk for stenosis, with 8/36 (22.2%) requiring revision vs 3/184 (1.6%) of patients without both factors (P < .0001). CONCLUSIONS: FPV graft stenosis requiring revision after NAIS reconstruction is uncommon. Risk factors for stenosis include small graft size, history of CAD, and smoking. All patients merit aggressive counseling for smoking cessation, and patients exhibiting multiple risk factors should undergo close postoperative surveillance for graft stenosis. [Abstract]

J Vasc Surg. 2007 Nov 6; [Abstract]

Ricco JB, Probst H
Long-term results of a multicenter randomized study on direct versus crossover bypass for unilateral iliac artery occlusive disease.
J Vasc Surg. 2007 Nov 6;
OBJECTIVE: To compare late patency after direct and crossover bypass in good-risk patients with unilateral iliac occlusive disease not amenable to angioplasty. METHODS: Between May 1986 and March 1991, 143 patients with unilateral iliac artery occlusive disease and disabling claudication were randomized into two surgical treatment groups, ie, crossover bypass (n = 74) or direct bypass (n = 69). The size of the patient population was calculated to allow detection of a possible 20% difference in patency in favor of direct bypass with a one-sided alpha risk of 0.05 and a beta risk of 0.10. Patients underwent yearly follow-up examinations using color flow duplex scanning with ankle-brachial systolic pressure index measurement. Digital angiography was performed if hemodynamic abnormalities were noted. Median follow-up was 7.4 years. Primary endpoints were primary patency and assisted primary patency estimated by the Kaplan-Meier method with 95% confidence interval. Secondary endpoints were secondary patency and postoperative mortality and morbidity. RESULTS: Cardiovascular risk factors, preoperative symptoms, iliac lesions TASC class (C in 87 [61%] patients and D in 56 [39%] patients), and superficial femoral artery (SFA) run-off were comparable in the two treatment groups. One patient in the direct bypass group died postoperatively. Primary patency at 5 years was higher in the direct bypass group than in the crossover bypass group (92.7 +/- 6.1% vs 73.2 +/- 10%, P = .001). Assisted primary patency and secondary patency at 5 years were also higher after direct bypass than crossover bypass (92.7 +/- 6.1% vs 84.3 +/- 8.5%, P = .04 and 97.0 +/- 3.0% vs 89.8 +/- 7.1%, P = .03, respectively). Patency at 5 years after crossover bypass was significantly higher in patients presenting no or low-grade SFA stenosis than in patients presenting high-grade (>/=50%) stenosis or occlusion of the SFA (74.0 +/- 12% vs 62.5 +/- 19%, P = .04). In both treatment groups, patency was comparable using polytetrafluoroethylene (PTFE) and polyester grafts. Overall survival was 59.5 +/- 12% at 10 years. CONCLUSION: This study showed that late patency was higher after direct bypass than crossover bypass in good-risk patients with unilateral iliac occlusive disease not amenable to angioplasty. Crossover bypass should be reserved for high-risk patients with unilateral iliac occlusion not amenable to percutaneous recanalization. [Abstract]

Tang GL, Tehrani HY, Usman A, Katariya K, Otero C, Perez E, Eskandari MK
Reduced mortality, paraplegia, and stroke with stent graft repair of blunt aortic transections: A modern meta-analysis.
J Vasc Surg. 2007 Oct 31;
OBJECTIVE: Stent grafting has become the first-line approach to traumatic thoracic aortic transections (TTAT) in some trauma centers due to a perceived decrease in morbidity and mortality compared with standard open repair. We reviewed contemporary outcomes of patients undergoing endovascular repair of TTAT (endoTTAT) and those undergoing open repair (openTTAT) to determine if current reported results support first-line use of endoTTAT. METHOD: Retrospective, nonrandomized studies published in English (>5 cases/report) involving TTAT listed in PubMed between 2001 and 2006 were systematically reviewed. Periprocedural outcomes between endoTTAT and openTTAT were analyzed. Mean follow-up was 22.9 months for endoTTAT (reported for 22 of 28 studies) and 48.6 months for openTTAT (reported for 5 of 12 studies). For statistical analysis, t tests were used. RESULTS: We analyzed 33 articles reporting 699 procedures in which 370 patients treated with endoTTAT and 329 patients managed with openTTAT. No statistical differences were found between patient groups in mean age (41.3 vs 38.8 years, P < .10), injury severity score (39.8 vs 36.0, P < .10), or technical success rates of the procedure (96.5% vs 98.5%, P = .58). In contrast, mortality was significantly lower in the endoTTAT group (7.6% vs 15.2%, P = .0076) as were rates of paraplegia (0% vs 5.6%, P < .0001) and stroke (0.85% vs 5.3%, P = .0028). The most common procedure-related complications for each technique were iliac artery injury during endoTTAT and recurrent laryngeal nerve injury after openTTAT. CONCLUSIONS: To our knowledge, no large multicenter prospective randomized trial comparing endoTTAT and openTTAT has been published in the literature. This meta-analysis of pooled data serves as a surrogate, demonstrating a significant reduction in mortality, paraplegia, and stroke rates in patients who undergo endoTTAT; however, the long-term durability of endoTTAT remains in question. [Abstract]

Chuter TA, Rapp JH, Hiramoto JS, Schneider DB, Howell B, Reilly LM
Endovascular treatment of thoracoabdominal aortic aneurysms.
J Vasc Surg. 2007 Oct 31;
OBJECTIVE: This study assessed the role of multibranched stent grafts for thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: Self-expanding covered stents were used to connect the caudally directed cuffs of an aortic stent graft with the visceral branches of a TAAA in 22 patients (16 men, 6 women) with a mean age of 76 +/- 7 years. All patients were unfit for open repair, and nine had undergone prior aortic surgery. Customized aortic stent grafts were inserted through surgically exposed femoral (n = 16) or iliac (n = 6) arteries. Covered stents were inserted through surgically exposed brachial arteries. Spinal catheters were used for cerebrospinal fluid pressure drainage in 22 patients and for and spinal anesthesia in 11. RESULTS: All 22 stent grafts and all 81 branches were deployed successfully. Aortic coverage as a percentage of subclavian-to-bifurcation distance was 69% +/- 20%. Mean contrast volume was 203 mL, mean blood loss was 714 mL, and mean hospital stay was 10.9 days. Two patients (9.1%) died perioperatively: one from guidewire injury to a renal arterial branch and the other from a medication error. Serious or potentially serious complications occurred in 9 of 22 patients (41%). There was no paraplegia, renal failure, stroke, or myocardial infarction among the 20 surviving patients. Two patients (9.1%) underwent successful reintervention: one for localized intimal disruption and the other for aortic dissection, type I endoleak, and stenosis of the superior mesenteric artery. One patient has a type II endoleak. Follow-up is >1 month in 19 patients, >6 months in 12, and >12 months in 8. One branch (renal artery) occluded for a 98.75% branch patency rate at 1 month. The other 80 branches remain patent. There are no signs of stent graft migration, component separation, or fracture. CONCLUSIONS: Multibranched stent graft implantation eliminates aneurysm flow, preserves visceral perfusion, and avoids many of the physiologic stresses associated with other forms of repair. The results support an expanded role for this technique in the treatment of TAAA. [Abstract]

Matsumura JS, Peterson BG, Brewster DC, Makaroun MS
J Vasc Surg. 2007 Nov;46(5):1089-90. [Abstract]

McMurtry MS, Beckman JA
Regarding "EXCLUDER trial events are excluded from EXCLUDER trial report".
J Vasc Surg. 2007 Nov;46(5):1088-9; author reply 1089-90. [Abstract]

Ballotta E, Baracchini C
J Vasc Surg. 2007 Nov;46(5):1088. [Abstract]

Park SJ, Yim SB, Cha DW, Kim SC
Regarding "Endovenous laser treatment of the short saphenous vein: efficacy and complications".
J Vasc Surg. 2007 Nov;46(5):1087. [Abstract]

Golledge J
Regarding "Duplex surveillance following carotid surgery: effect of management policy".
J Vasc Surg. 2007 Nov;46(5):1087-8; author reply 1088. [Abstract]

Gibson K
J Vasc Surg. 2007 Nov;46(5):1086-7. [Abstract]

Mehta TA, Clarke JM
Regarding "Glomerular filtration rate after left renal vein division and reconstruction during infrarenal aortic aneurysm repair".
J Vasc Surg. 2007 Nov;46(5):1085; author reply 1085. [Abstract]

O'Donnell TF
Regarding "Endovenous laser treatment of the short saphenous vein: EFficacy and complications".
J Vasc Surg. 2007 Nov;46(5):1085-6; author reply 1086-7. [Abstract]

Marrocco-Trischitta MM, Melissano G, Chiesa R
J Vasc Surg. 2007 Nov;46(5):1085. [Abstract]

Jones JW, McCullough LB
What to do when a patient's international medical care goes south.
J Vasc Surg. 2007 Nov;46(5):1077-9. [Abstract]

Comerota AJ, Gravett MH
Iliofemoral venous thrombosis.
J Vasc Surg. 2007 Nov;46(5):1065-76.
Iliofemoral deep vein thrombosis (DVT) is associated with serious short- and long-term physical, social, and economic sequelae for patients. Most physicians treat patients with acute iliofemoral DVT in the same manner as they treat all acute DVT patients: with anticoagulation alone. Yet a growing body of evidence suggests that, in this subset of DVT patients, a treatment strategy that includes thrombus removal plus optimal anticoagulation significantly improves outcomes. This article reviews the evidence supporting this strategy and discusses current and promising techniques of thrombus removal, including contemporary venous thrombectomy, intrathrombus catheter-directed thrombolysis, and pharmacomechanical thrombolysis. [Abstract]

Neequaye SK, Aggarwal R, Van Herzeele I, Darzi A, Cheshire NJ
Endovascular skills training and assessment.
J Vasc Surg. 2007 Nov;46(5):1055-64.
OBJECTIVE: Evolving endovascular therapies have transformed the management of vascular disease. At the same time, the increasing use of non-invasive vascular imaging techniques has reduced the opportunities to gain the required basic wire and catheter handling skills by performing diagnostic catheterizations. This article reviews the evidence for alternative tools currently available for endovascular skills training and assessment. METHODS: A Literature search was performed on pubmed using combinations of the following keywords; endovascular, skills, training, simulation, assessment and learning curve. Additional articles were retrieved from the reference lists of identified papers as well as discussion with experts in the arena of medical education. RESULTS: Available alternatives to training on patients inclue synthetic models, anesthetized animals, human cadavers and virtual reality (VR) simulation. VR simulation is a useful tool enabling objective demonstration of improved skills performance both in simulated performance and in subsequent in-vivo performance. Assessment modalities reviewed include time action analysis, error analysis, global rating scales, procedure specific checklists and VR simulators. Assessment in training has been widely validated using VR simulation. Rating scales and checklists are presently the only assessment modalities that have demonstrated utility outside the training lab. CONCLUSION: The tools required for a structured proficiency based endovascular training curriculum are already available. Organization of training programs needs to evolve to make full use of modern simulation capability for technical and non-technical skills training. [Abstract]

Lawrence PF, Vardanian AJ
Light-assisted stab phlebectomy: report of a technique for removal of lower extremity varicose veins.
J Vasc Surg. 2007 Nov;46(5):1052-4.
We report a new technique to remove varicose veins and reduce recurrence from missed veins. A rigid cannula with a light source injects tumescent solution and transilluminates under veins. Varicose veins are removed with stab phlebectomy using a modified crochet hook and mosquito clamp. Additional tumescent solution flushes hematomas and compresses empty vein channels, resulting in less pain, bleeding, and pigmentation. More than 200 patients have undergone light-assisted stab phlebectomy at the Gonda Vascular Center, with high patient and surgeon satisfaction. This sutureless technique allows complete and rapid varicose branch vein removal with few missed varicose veins, little bruising, and an excellent cosmetic result. [Abstract]

Rosenthal RL, Shutze WP
Aortic coarctation diagnosed by 64-slice computed tomography angiography.
J Vasc Surg. 2007 Nov;46(5):1051. [Abstract]

López Garcia D, Arranz MA, Tagarro S, Camarero SR, Gonzalez ME, Gimeno MG
Bilateral popliteal aneurysm as a result of vascular type IV entrapment in a young patient: a report of an exceptional case.
J Vasc Surg. 2007 Nov;46(5):1047-50.
Popliteal artery entrapment syndrome is recognized as a cause of claudication and arterial occlusion in young patients. Aneurysmal degeneration is a reported but rare complication. We present the case of a young male patient with large bilateral popliteal aneurysms due to symptomatic anatomic entrapment. The left aneurysm was acutely thrombosed, and urgent bypass surgery was required. The contralateral aneurysm was resected by a posterior approach and replaced with an autologous vein graft. Type IV popliteal entrapment by a fibrous band independent of the gastrocnemius muscle was diagnosed during surgery and divided. Early detection of popliteal entrapment is highly important to prevent the development of this serious complication. [Abstract]

Zhou W, Huynh TT, Kougias P, El Sayed HF, Lin PH
Traumatic carotid artery dissection caused by bungee jumping.
J Vasc Surg. 2007 Nov;46(5):1044-6.
Bungee jumping is a popular recreational activity in which participant experiences transient freefall while connected to a bungee cord. The rapid freefall and the resultant rebound force created by the bungee cord can result in a variety of bodily injuries. We report herein a case of traumatic carotid artery dissection caused by bungee jumping. The symptoms related to carotid artery dissection were successfully treated with anticoagulation. The etiology of carotid dissection related to bungee jumping is discussed. Physicians should be cognizant of this potential injury due to the force created by the freefall and rebound motion associated in this recreational sport. [Abstract]

Gonzales AJ, Hughes JD, Leon LR
Probable zoonotic aortitis due to group C streptococcal infection.
J Vasc Surg. 2007 Nov;46(5):1039-43.
Human infections due to group C streptococcus (SGC) are unusual. Among them, vascular compromise, especially aortic involvement, is extremely rare. A case of microbial aortitis with aneurysm formation, likely secondary to a SGC soft tissue infection, in a 61-year-old patient who was caring for a purulent leg wound of his horse, is presented. He was successfully treated with antibiotics and in situ aortic replacement with a prosthetic graft and an omental wrap. He remains well almost 2 years after surgical intervention. Aortic infection caused by SGC is a rare condition that can be successfully treated with in situ prosthetic graft replacement. [Abstract]

Naidu SG, Chong BW, Huettl EA, Stone WM
Percutaneous embolization of a lumbar pseudoaneurysm in a patient with type IV Ehlers-Danlos syndrome.
J Vasc Surg. 2007 Nov;46(5):1036-8.
Ehlers-Danlos syndrome (EDS) is a rare hereditary connective tissue disorder. Patients with type IV EDS are prone to develop visceral pseudoaneurysms and aortic aneurysms. Surgical and endovascular interventions are fraught with complications and high morbidity. We present a case of a patient with type IV EDS who presented with a new psoas pseudoaneurysm arising from a hypertrophied lumbar artery which was treated with percutaneous embolization by using n-butyl cyanoacrylate glue and coils. [Abstract]

Lee WA, Martin TD, Hess PJ, Beaver TM, Huber TS
Maldeployment of the TAG thoracic endograft.
J Vasc Surg. 2007 Nov;46(5):1032-5.
The TAG thoracic endograft is a commercially available device used for endovascular repair of thoracic aneurysms. It has a single-action deployment mechanism, similar to its abdominal counterpart, consisting of an expanded polytetrafluoroethylene string, which is used to constrain the self-expanding stent graft within an integral external expanded polytetrafluoroethylene corset. This report describes two cases of deployment failure of the TAG device and the bailout techniques used to correct the problem and complete the procedure. In one case, this complication resulted in a devastating intraoperative stroke that led to the death of the patient. Although this is an extremely rare occurrence, the rapid recognition of the problem and ability to correct it by using catheter-based techniques are important during endovascular treatment of thoracic aortic diseases using the TAG device. [Abstract]

Recent Articles in The British Journal of Surgery

Chen JR, Chiang JM, Changchien CR, Chen JS, Tang RP, Wang JY
Mismatch repair protein expression in Amsterdam II criteria-positive patients in Taiwan.
Br J Surg. 2007 Dec 6;
BACKGROUND:: Hereditary non-polyposis colorectal cancer (HNPCC) is characterized genetically by germline mutations in DNA mismatch repair (MMR) genes. Immunohistochemistry (IHC) has high sensitivity and specificity for identifying MMR-deficient tumours. This study investigated the clinical presentations and frequency of HNPCC in Taiwan by combined Amsterdam II criteria (AC-II) and IHC. METHODS:: In 1995-2003, 7108 patients with primary colorectal cancer registered in Chang Gung Memorial Hospital's Colorectal Cancer Registry were screened using AC-II. Tumour specimens were analysed for MMR protein expression by IHC, and relevant clinicopathological details were documented. RESULTS:: Some 83 patients fulfilled the AC-II. Clinicopathologically, 43 patients (52 per cent) had proximal tumours, ten (12 per cent) had poorly differentiated cancers, 17 (20 per cent) had mucinous adenocarcinoma and 51 (61 per cent) had stage I-II tumours. Seventeen patients developed second primary colonic and extracolonic cancers over a mean 7.2-year follow-up. Immunohistochemically, 58 patients were MMR protein deficient. They had a significantly earlier age of onset (P < 0.001), more proximal tumour location (P = 0.002), less advanced tumour stage (P = 0.008) and more second primary cancers (P = 0.017) compared with MMR-competent patients. CONCLUSION:: These data show significant differences in clinical features between MMR protein-deficient and MMR competent subgroups. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Guo Q, Li QF, Liu HJ, Li R, Wu CT, Wang LS
Sphingosine kinase 1 gene transfer reduces postoperative peritoneal adhesion in an experimental model.
Br J Surg. 2007 Dec 6;
BACKGROUND:: Recovery of the surgically damaged mesothelial cell layer is a major process in reducing postoperative peritoneal adhesions. Sphingosine kinase (SPK) 1 is a signalling molecule involved in the regulation of proliferation and migration of various cell types. This study determined the effect of SPK-1 gene transfer on the recovery of damaged mesothelial cells and on peritoneal adhesion formation after surgery. METHODS:: Rat mesothelial cells were isolated and characterized by their expression of cytokeratin and vimentin. Their migration was determined by scratch wound motility assay. Cellular SPK-1 activity was measured by [gamma-(32)P]adenosine 5'-triphosphate incorporation. Wistar rats underwent laparotomy with subsequent caecum or uterine horn abrasion. Rats were randomized to either SPK-1 gene (Ad-SPK-1) transfer or control groups. The animals were killed 14 days after operation and peritoneal adhesions were graded. RESULTS:: Adenovirus-mediated SPK-1 gene transfer increased the cellular SPK-1 activity of mesothelial cells, leading to enhanced migration. Median adhesion scores were significantly lower in the Ad-SPK-1 group than in controls in both rat caecum (0.98 versus 2.60; P < 0.001) and rat uterine horn (0.28 versus 1.83; P < 0.001) models. CONCLUSION:: Adenovirus-mediated SPK-1 gene transfer promotes recovery of the surgically damaged mesothelial cell layer and prevents postoperative peritoneal adhesion formation. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Keshtgar MR, Khalili A, Coen PG, Carder C, Macrae B, Jeanes A, Folan P, Baker D, Wren M, Wilson AP
Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards.
Br J Surg. 2007 Nov 27;
BACKGROUND:: This study aimed to establish the feasibility and cost-effectiveness of rapid molecular screening for hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA) in surgical patients within a teaching hospital. METHODS:: In 2006, nasal swabs were obtained before surgery from all patients undergoing elective and emergency procedures, and screened for MRSA using a rapid molecular technique. MRSA-positive patients were started on suppression therapy of mupirocin nasal ointment (2 per cent) and undiluted chlorhexidine gluconate bodywash. RESULTS:: A total of 18 810 samples were processed, of which 850 (4.5 per cent) were MRSA positive. In comparison to the annual mean for the preceding 6 years, MRSA bacteraemia fell by 38.5 per cent (P < 0.001), and MRSA wound isolates fell by 12.7 per cent (P = 0.031). The reduction in MRSA bacteraemia and wound infection was equivalent to a saving of 3.78 beds per year ( pound276 220), compared with the annual mean for the preceding 6 years. The cost of screening was pound302 500, making a net loss of pound26 280. Compared with 2005, however, there was a net saving of pound545 486. CONCLUSION:: Rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteraemia during the screening period, although a causal link cannot be established. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Falconi M, Mantovani W, Crippa S, Mascetta G, Salvia R, Pederzoli P
Pancreatic insufficiency after different resections for benign tumours.
Br J Surg. 2007 Nov 26;
BACKGROUND:: Pancreatic resections for benign diseases may lead to long-term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long-term results after different pancreatic resections for benign disease. METHODS:: Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal chymotrypsin and oral glucose tolerance test. RESULTS:: The incidence of pancreatic fistula was significantly higher after AR than after LP (11 of 36 versus seven of 64; P = 0.028). The long-term incidence of endocrine pancreatic insufficiency was significantly lower after AR than after PD (P < 0.001). Exocrine insufficiency was more common after PD (P < 0.001) and LP (P = 0.009) than after AR. The probability of developing both endocrine and exocrine insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent respectively at 1 year; 58, 29 and 3 per cent at 5 years; P < 0.001). CONCLUSION:: Different pancreatic resections are associated with different risks of developing long-term pancreatic insufficiency. AR represents the best option in terms of long-term endocrine and exocrine function, although it is associated with more postoperative complications. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Becher G, Kinsella J
Mid-term survival after abdominal aortic aneurysm surgery predicted by cardiopulmonary exercise testing (Br J Surg 2007; 94: 966-969).
Br J Surg. 2007 Dec;94(12):1575; author reply 1575-6. [Abstract]

Aldrighetti L, Pulitano C
Authors' reply: A risk score for predicting perioperative blood transfusion in liver surgery (Br J Surg 2007; 94: 860-865).
Br J Surg. 2007 Dec;94(12):1574-1575. [Abstract]

Combeer EL, Quiney NF, Karanjia ND, Fawcett WJ
A risk score for predicting perioperative blood transfusion in liver surgery (Br J Surg 2007; 94: 860-865).
Br J Surg. 2007 Dec;94(12):1574; author reply 1574-5. [Abstract]

Estourgie SH
Authors' reply: Excision biopsy of breast lesions changes the pattern of lymphatic drainage (Br J Surg 2007; 94: 1088-1091).
Br J Surg. 2007 Dec;94(12):1573-1574. [Abstract]

Heuts E
Excision biopsy of breast lesions changes the pattern of lymphatic drainage (Br J Surg 2007; 94: 1088-1091).
Br J Surg. 2007 Dec;94(12):1573; discussion 1573-4. [Abstract]

Dwerryhouse S
Authors' reply: Salvage oesophagectomy after local failure of definitive chemoradiotherapy (Br J Surg 2007; 94: 1059-1066).
Br J Surg. 2007 Dec;94(12):1573. [Abstract]

O'Neill S, Danbury C, Kitching A
Salvage oesophagectomy after local failure of definitive chemoradiotherapy (Br J Surg 2007; 94: 1059-1066).
Br J Surg. 2007 Dec;94(12):1572; author reply 1573. [Abstract]

Turner S, Derham C, Orsi NM, Bosomworth M, Bellamy MC, Howell SJ
Randomized clinical trial of the effects of methylprednisolone on renal function after major vascular surgery.
Br J Surg. 2007 Nov 16;
BACKGROUND:: Perioperative renal dysfunction following abdominal aortic aneurysm (AAA) repair is multifactorial and may involve hypotension, hypoxia and ischaemia-reperfusion injury. Studies of cardiac and hepatic transplant surgery have demonstrated beneficial effects on renal function of high-dose methylprednisolone administered before surgery. METHODS:: Twenty patients undergoing elective open AAA repair were randomized to receive either methylprednisolone 10 mg/kg or dextrose (control) before induction of anaesthesia. Blood was analysed for a panel of cytokines representative of T helper cell type 1 and 2 subsets. Urine was analysed for subclinical markers of renal dysfunction (albumin, alpha(1)-microglobulin and N-acetyl-beta-D-glucosaminidase). RESULTS:: Data from 18 patients were analysed. Both groups demonstrated glomerular and proximal convoluted tubular dysfunction that was unaffected by steroid treatment. Steroid administration increased serum levels of urea and creatinine (both P < 0.001). The steroid group had increased interleukin 10 levels (P = 0.005 compared to controls). There were no differences between groups in overall surgical complications, length of intensive care unit (P = 0.821) and hospital (P = 0.719) stay, or 30-day mortality. CONCLUSION:: Methylprednisolone administration altered the cytokine profile favourably but adversely affected postoperative renal function. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Thomas JM
Authors' reply: Retroperitoneal sarcoma (Br J Surg 2007; 94: 1057-1058).
Br J Surg. 2007 Dec;94(12):1572. [Abstract]

Shukla PJ, Barreto SG, Shrikhande SV
Retroperitoneal sarcoma (Br J Surg 2007; 94: 1057-1058).
Br J Surg. 2007 Dec;94(12):1572; author reply 1572. [Abstract]

Meta-analysis of oral water-soluble contrast agent in the management of adhesive small bowel obstruction S. M. Abbas, I. P. Bissett, B. R. Parry. British Journal of Surgery, 2007; 94: 404-411.
Br J Surg. 2007 Dec;94(12):1578.
The original article to which this Erratum refers was published in British Journal of Surgery 94, 2007, 404-411. [Abstract]

Scientific surgery.
Br J Surg. 2007 Dec;94(12):1577. [Abstract]

Bissett IP
Ileocolic anastomosis.
Br J Surg. 2007 Dec;94(12):1447-8. [Abstract]

Kiessling R, Choudhury A
Cancer vaccines.
Br J Surg. 2007 Dec;94(12):1449-50. [Abstract]

Carlisle J, Swart M
Authors' reply: Mid-term survival after abdominal aortic aneurysm surgery predicted by cardiopulmonary exercise testing (Br J Surg 2007; 94: 966-969).
Br J Surg. 2007 Dec;94(12):1575-1576. [Abstract]

Bollen TL, van Santvoort HC, Besselink MG, van Leeuwen MS, Horvath KD, Freeny PC, Gooszen HG
The Atlanta Classification of acute pancreatitis revisited.
Br J Surg. 2007 Nov 5;
BACKGROUND:: In a complex disease such as acute pancreatitis, correct terminology and clear definitions are important. The clinically based Atlanta Classification was formulated in 1992, but in recent years it has been increasingly criticized. No formal evaluation of the use of the Atlanta definitions in the literature has ever been performed. METHODS:: A Medline literature search sought studies published after 1993. Guidelines, review articles and their cross-references were reviewed to assess whether the Atlanta or alternative definitions were used. RESULTS:: A total of 447 articles was assessed, including 12 guidelines and 82 reviews. Alternative definitions of predicted severity of acute pancreatitis, actual severity and organ failure were used in more than half of the studies. There was a large variation in the interpretation of the Atlanta definitions of local complications, especially relating to the content of peripancreatic collections. CONCLUSION:: The Atlanta definitions for acute pancreatitis are often used inappropriately, and alternative definitions are frequently applied. Such lack of consensus illustrates the need for a revision of the Atlanta Classification. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Anegg U, Lindenmann J, Maier A, Smolle J, Smolle-Jüttner FM
Influence of route of gastric transposition on oxygen supply at cervical oesophagogastric anastomoses.
Br J Surg. 2007 Nov 1;
BACKGROUND:: The microcirculation and oxygen supply at the oesophagogastric anastomosis are crucial factors that influence anastomotic healing after oesophagectomy. METHODS:: Twenty-nine patients (mean age 61.7 years) underwent gastric transposition via an orthotopic (14) or retrosternal (15) route. Interstitial partial pressure of oxygen (PO(2)) of the stomach in the anastomotic region was measured during oesophagectomy and in the intensive care unit. Interstitial PO(2) values were determined after ligation of the short gastric vessels, after ligation of the left gastric artery, after forming the conduit and after gastric transposition. Postoperative measurements were recorded during endotracheal intubation, while breathing oxygen by mask or through the nose, and while breathing air. RESULTS:: Interstitial PO(2) levels were significantly higher before ligation of the left gastric artery than after ligation (mean 76.1 (95 per cent confidence interval 54.9 to 103.1) versus 44.9 (24.6 to 77.1) mmHg; P = 0.001). Levels were also higher following orthotopic transposition compared with the retrosternal route (68.2 (44.0 to 118.8) versus 24.6 (10.7 to 39.4) mmHg; P = 0.001) and during each postoperative measurement period. No differences were found between the various oxygen supply systems. CONCLUSION:: Oxygen supply at the anastomosis of the gastric conduit reaches higher levels after orthotopic than retrosternal gastric transposition. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Gemmill EH, McCulloch P
Systematic review of minimally invasive resection for gastro-oesophageal cancer.
Br J Surg. 2007 Dec;94(12):1461-7.
BACKGROUND: This article reviews the evidence on the safety and efficacy of minimally invasive surgery for gastric and oesophageal cancer. METHODS: An electronic search of the literature between 1997 and 2007 was undertaken to identify primary studies and systematic reviews; studies were retrieved and analysed using predetermined criteria. Information on the safety and efficacy of minimally invasive surgery for gastric and oesophageal cancer was recorded and analysed. RESULTS: From 188 abstracts reviewed, 46 eligible studies were identified, 23 on oesophagectomy and 23 on gastrectomy. There were 35 case series, eight case-matched studies and three randomized controlled trials. Compared with the contemporary results of open surgery, reports on minimally invasive surgery indicate potentially favourable outcomes in terms of operative blood loss, recovery of gastrointestinal function and hospital stay. However, the quality of the data was generally poor, with many potential sources of bias. CONCLUSION: Minimally invasive surgery is feasible but evidence of benefit is currently weak. [Abstract]

David GG, Al-Sarira AA, Willmott S, Deakin M, Corless DJ, Slavin JP
Management of acute gallbladder disease in England.
Br J Surg. 2007 Oct 29;
BACKGROUND:: Recent literature suggests that early laparoscopic cholecystectomy for acute gallbladder disease is safe and efficacious, but few data are available on the management of acute gallbladder disease in England. METHODS:: Hospital Episode Statistics data for the years 2003-2005 were obtained from the Department of Health. All patients admitted as an emergency with acute gallbladder disease during the period from April 2003 to March 2004 were included as a cohort. Repeat emergency admissions for acute gallbladder disease, and cholecystectomies performed during the first admission, an emergency readmission or an elective admission were followed up until March 2005. RESULTS:: Some 25 743 patients were admitted as an emergency with acute gallbladder disease, of whom 3791 had an emergency cholecystectomy during the first admission (open cholecystectomy (OC) 29.8 per cent, laparoscopic conversion rate (LCR) 10.7 per cent) and 9806 patients had an elective cholecystectomy (OC 11.3 per cent, LCR 8.3 per cent) during the study period. CONCLUSION:: Early cholecystectomy for acute gallbladder disease is not widely practised by surgeons in England. Open cholecystectomy is more commonly used in the emergency than in the elective setting. Early laparoscopic cholecystectomy following an emergency admission carries a higher conversion rate than elective cholecystectomy. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Breitenstein S, Rickenbacher A, Berdajs D, Puhan M, Clavien PA, Demartines N
Systematic evaluation of surgical strategies for acute malignant left-sided colonic obstruction.
Br J Surg. 2007 Dec;94(12):1451-60.
BACKGROUND: Surgical strategy for acute colorectal obstruction due to colorectal cancer remains controversial. One-, two- and three-stage surgical procedures, and preoperative stenting of the stenosis as a bridge to surgery, are available. METHODS: A systematic review was conducted, searching MEDLINE, EMBASE and CENTRAL, as well as bibliographies of included studies, to identify randomized and non-randomized controlled trials that compared two or more surgical procedures in acute colonic obstruction. RESULTS: After screening 1748 titles and abstracts, 209 were selected for full text assessment; 29 studies with 2286 patients were finally included. In general, the quality of the studies was limited, with only three randomized trials. Eight non-randomized studies comparing one-stage with two- or three-stage surgery consistently favoured a one-stage procedure in terms of mortality (relative risk difference from - 2 to - 27 per cent), but reported morbidity rates were not different. Trials of different one-stage procedures (segmental and total/subtotal colectomy) showed none to be clearly superior. Stenting procedures were superior to non-stenting treatments. CONCLUSION: One-stage surgery appears to be superior to two- or three-stage procedures. Stenting is a promising option, allowing the resection to be carried out in an elective setting. [Abstract]

Bolliger D, Seeberger MD, Lurati Buse GA, Christen P, Gürke L, Filipovic M
Randomized clinical trial of moxonidine in patients undergoing major vascular surgery.
Br J Surg. 2007 Dec;94(12):1477-84.
BACKGROUND: Myocardial ischaemia is the leading cause of perioperative morbidity and mortality after surgery in patients with coronary artery disease. The aim of this study was to evaluate the effects of moxonidine, a centrally acting sympatholytic agent, on perioperative myocardial ischaemia and 1-year mortality in patients undergoing major vascular surgery. METHODS: In this double-blind, placebo-controlled two-centre trial, 141 patients were randomly assigned to receive moxonidine or placebo on the morning before surgery and on the following 4 days. Levels of cardiac troponin I (cTnI) were analysed before surgery and on days 1, 2, 3 and 7 thereafter. Holter electrocardiograms were recorded for 48 h starting before the administration of the study drug. Patients were followed daily during admission and by telephone interview 12 months after surgery. RESULTS: The incidence of raised perioperative cTnI levels or alteration in the ST segment in the Holter electrocardiogram or both was 40 per cent in the moxonidine group and 37 per cent in the placebo group (P = 0.694). All-cause mortality rates within 12 months were 10 per cent in the moxonidine group and 11 per cent in the placebo group (P = 0.870). CONCLUSION: Small oral doses of moxonidine did not reduce the incidence of perioperative myocardial ischaemia and had no effect on mortality in patients undergoing vascular surgery. Registration number: NCT00244504 ( [Abstract]

Abisi S, Burnand KG, Humphries J, Waltham M, Taylor P, Smith A
Effect of statins on proteolytic activity in the wall of abdominal aortic aneurysms.
Br J Surg. 2007 Oct 29;
BACKGROUND:: The aim of this study was to examine the effect of statin treatment on the activity of proteases in the wall of abdominal aortic aneurysms (AAAs). METHODS:: The activities of matrix metalloproteinases (MMPs) 9 and 3, cathepsins B, H, K, L and S, and the cystatin C level were measured in extracts of AAA wall taken from 82 patients undergoing AAA repair; 21 patients were receiving statin treatment before surgery. All values were standardized against soluble protein (SP) concentration in the extract, and reported as median (interquartile range) or mean(s.e.m.). RESULTS:: The two groups had similar demographics. Reduced activity of MMP-9 (43 (34-56) versus 80 (62-110) pg per mg SP; P < 0.001), cathepsin H (183 (117-366) versus 321 (172-644) nmol 4-methylcoumarin-7-amide released per mg SP; P = 0.016) and cathepsin L (102 (51-372) versus 287 (112-816) micromol 7-amino-4-trifluoromethylcoumarin released per mg SP; P = 0.020) was found in the statin-treated aortas compared with AAAs from patients not taking a statin. The statin-treated group had lower MMP-3 activity, but this did not reach statistical significance (P = 0.053). Cystatin C levels were higher in statin-treated aortas than in controls (41.3(3.1) versus 28.9(2.1) ng per mg SP; P = 0.003). CONCLUSION:: Statins decreased the activity of proteases that have been implicated in aneurysm disease. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Kuijt GP, Roumen RM
Second thoughts on sentinel lymph node biopsy in node-negative breast cancer.
Br J Surg. 2007 Oct 19; [Abstract]

Hurlstone DP, Atkinson R, Sanders DS, Thomson M, Cross SS, Brown S
Achieving R0 resection in the colorectum using endoscopic submucosal dissection.
Br J Surg. 2007 Dec;94(12):1536-42.
BACKGROUND: Endoscopic mucosal resection is established for the removal of non-invasive colorectal tumours smaller than 20 mm but is unsatisfactory for larger lesions. Endoscopic submucosal dissection (ESD) enables en bloc resection of lesions larger than 20 mm. A UK-based prospective feasibility study of ESD for colorectal tumours was undertaken; primary endpoints were R0 resection, safety and recurrence. METHODS: Patients with Paris 0-II adenomas or laterally spreading tumours (LSTs) greater than 20 mm in diameter were enrolled between November 2004 and August 2006. Lesions were assessed by chromoscopy and high-frequency ultrasonography. Dysplasia, resection status, 30-day complication rates and recurrence after ESD were recorded. RESULTS: ESD was performed in 42 of 56 identified patients; en bloc resection was possible in 33. Fourteen Paris 0-II lesions and 28 LSTs were identified; 40 were dysplastic adenomas and two adenocarcinomas. R0 resection was achieved in 31 patients (74 per cent). The 30-day mortality rate was 0 per cent. Perforation occurred in one patient and uncomplicated bleeding in five. The 6-month cure rate was 81 per cent (34 of 42 patients). CONCLUSION: High cure rates are achievable using ESD for Paris 0-II adenomas and LSTs greater than 20 mm in diameter, with R0 resection possible in most patients. ESD is feasible throughout the colorectum with no increase in complication rates. It should be considered for selected Tim/T1 N0 colorectal lesions. [Abstract]

Sujendran V, Wheeler J, Baron R, Warren BF, Maynard N
Effect of neoadjuvant chemotherapy on circumferential margin positivity and its impact on prognosis in patients with resectable oesophageal cancer.
Br J Surg. 2007 Oct 18;
BACKGROUND:: The significance of circumferential resection margin (CRM) involvement in oesophageal cancer surgery is controversial. This study investigated the relationship between CRM involvement, locoregional recurrence and survival, after surgery alone or with neoadjuvant chemotherapy. METHODS:: Patients operated on by one surgeon at a tertiary referral centre between October 1997 and May 2004 were identified from a prospective database. RESULTS:: Some 242 patients underwent oesophagectomy; 91 had surgery alone, 142 had neoadjuvant chemotherapy and nine neoadjuvant chemoradiotherapy. Among patients with histologically confirmed T3 tumours, 26 (55 per cent) of 47 who underwent surgery alone had CRM involvement, compared with 27 (31 per cent) of 88 patients who completed two cycles of neoadjuvant chemotherapy (P = 0.005). Thirty-seven (42 per cent) of 89 patients with a negative CRM developed locoregional recurrence, compared with 33 (59 per cent) of 56 with a positive margin (P = 0.032); median survival was 28 and 12 months respectively (P < 0.001). Cox multivariable regression analysis identified CRM involvement as an independent prognostic factor (P = 0.006). CONCLUSION:: A positive CRM is an independent predictor of overall survival after oesophageal cancer resection. There has been a significant decrease in CRM involvement with the introduction of neoadjuvant chemotherapy. Copyright (c) 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [Abstract]

Nakajima T, Kinoshita T, Nashimoto A, Sairenji M, Yamaguchi T, Sakamoto J, Fujiya T, Inada T, Sasako M, Ohashi Y
Randomized controlled trial of adjuvant uracil-tegafur versus surgery alone for serosa-negative, locally advanced gastric cancer.
Br J Surg. 2007 Dec;94(12):1468-76.
BACKGROUND: This prospective randomized study compared the survival of patients with tumour node metastasis (TNM) stage T2 N1-2 gastric cancer treated by gastrectomy alone or gastrectomy followed by uracil-tegafur. METHODS: Patients were randomly assigned to surgery alone or to surgery and postoperative uracil-tegafur 360 mg per m(2) per day orally for 16 months. The primary endpoint was overall survival. Relapse-free survival and site of recurrence were secondary endpoints. RESULTS: Of 190 registered patients, 95 were randomized to each group; two patients with early cancer were subsequently excluded from the chemotherapy group. The trial was terminated before the target number of patients was reached because accrual was slower than expected. Drug-related adverse effects were mild, with no treatment-related deaths. At a median follow-up of 6.2 years, overall and relapse-free survival rates were significantly higher in the chemotherapy group (hazard ratio for overall survival 0.48, P = 0.017; hazard ratio for relapse-free survival 0.44, P = 0.005), confirming the survival benefit shown in an interim analysis performed 2 years earlier. CONCLUSION: Interim and final analyses revealed a significant survival benefit for postoperative adjuvant chemotherapy with uracil-tegafur in patients with serosa-negative, node-positive gastric cancer. Registration number: NCT00152243 ( [Abstract]

Recent Articles in Transplantation

Hoerbelt R, Benjamin LC, Shoji T, Johnston DR, Muniappan A, Guenther DA, Allan JS, Houser SL, Madsen JC
The Effects of Tolerance Induction on the Actions of Interferon-gamma on Cardiac Allografts.
Transplantation. 2006 Jul 15;82(1 Suppl 2):754-5.
It is well known that Interferon-gamma (IFN-gamma) not only plays a critical role in antigen-dependent but in antigen-independent tissue injury, but it is not clear how tolerance induction affects the actions of IFN-gamma in the transplant setting. To address this question, we compared the effects of IFN-gamma on porcine recipients of syngeneic, rejecting and tolerant heart transplants. IFN-gamma was perfused continuously into the left anterior descending artery of hearts transplanted into three groups of MHC inbred miniature swine, each treated with a 12-day course of CyA. Group 1 recipients received a class I disparate heart, Group 2 recipients received a near syngeneic heart and Group 3 recipients were cotransplanted with a class I disparate heart and kidney, which uniformly induces tolerance to both grafts. An additional, group of animals were not transplanted but received intracoronary IFN-gamma infusion into their native hearts. IFN- perfusion not only accelerated the acute rejection of class I disparate hearts (mean survival time = 19+/-7.21 vs. 38+/-8.19, p=0.025) but caused near syngeneic, heart transplants, which otherwise survive indefinitely, to reject within 35 days (n=3). In contrast, IFN-gamma perfusion had no demonstrable effects on either interstitial rejection, the development of vascular lesions or graft survival in tolerant heart plus kidney allograft recipients (n=4) or in autologous hearts (n=2). These results suggest that tolerance induction mitigates the damaging effects of IFN-gamma itself and that the beneficial effects of tolerance induction on acute and chronic rejection may extend to antigen-independent factors like ischemia/reperfusion injury. [Abstract]

Mukherjee S, Ariyarantha K
Successful Hepatitis C Eradication With Preservation of Renal Function in a Liver/kidney Transplant Recipient Using Pegylated Interferon and Ribavirin.
Transplantation. 2007 Nov 27;84(10):1374-5. [Abstract]

Losanoff JE, Millis JM
Giant necrotizing abscess of a liver transplant after gunshot injury.
Transplantation. 2007 Nov 27;84(10):1373-4. [Abstract]

Truong W, Plester JC, Hancock WW, Kaye J, Merani S, Murphy KM, Murphy TL, Anderson CC, Shapiro AM
Negative and positive co-signaling with anti-BTLA (PJ196) and CTLA4Ig prolongs islet allograft survival.
Transplantation. 2007 Nov 27;84(10):1368-72.
The novel coinhibitory receptor B and T lymphocyte attenuator (BTLA) has been implicated in the regulation of autoimmune and may potentially play a role in alloimmune responses. An anti-BTLA monoclonal antibody has been reported to prolong fully major histocompatibility complex-mismatched cardiac allograft survival, and we test the hypothesis that anti-BTLA monoclonal antibody PJ196 may synergize with cytotoxic T lymphocyte antigen-4 immunoglobulin (CTLA4Ig) costimulatory blockade in islet transplantation. We investigated the potential of PJ196, and show that it did not deplete BTLA expressing cells, but it caused down-regulation of BTLA on the surface of lymphocytes and accumulation of cells with regulatory phenotype at the graft site, promoting islet allograft acceptance together with CTLA4Ig. The combination of BTLA coinhibitory modulation and CTLA4Ig costimulatory blockade may be an effective adjunctive strategy for inducing long-term allograft survival. [Abstract]

Haramati J, Soppe C, Zúñiga MC
A rapid method for skin grafting in mice that greatly enhances graft and recipient survival.
Transplantation. 2007 Nov 27;84(10):1364-7.
A streamlined method of skin grafting in mice is described. This procedure eliminates bandages, sutures, and dressings. The elimination of bandages renders the overall procedure fast and easy to learn. More importantly, the elimination of bandaging results in an increased survival of engrafted mice and a drastic reduction in graft displacement. Finally the lack of bandages also makes it possible to monitor the graft even in the earliest stages after engraftment. [Abstract]

Englert C, Grabhorn E, Richter A, Rogiers X, Burdelski M, Ganschow R
Liver transplantation in children with progressive familial intrahepatic cholestasis.
Transplantation. 2007 Nov 27;84(10):1361-3.
Progressive familial intrahepatic cholestasis (PFIC) is caused by mutations of the bile salt export pump or the multidrug resistance P-glycoprotein, resulting in chronic hepatic failure. Partial external diversion of bile or ileal bypass is effective in some cases and, in others, liver transplantation (OLT) is necessary. Forty-two children were included in this study. Twenty-six children suffered from PFIC type 2 and 16 from PFIC type 3. Symptoms included pruritus, cholestasis, liver cirrhosis, and growth retardation. Seventeen patients received external biliary diversion. Ten had to undergo OLT in the following course. As of this report, three of the remaining patients were on the wait list for OLT. Twenty-three children received a liver graft primarily with excellent outcome. Our data show that OLT is the option of choice in symptomatic PFIC and whenever liver cirrhosis is present. We suggest a very restrictive recommendation of external biliary diversion. However, gene therapy may be a future option for children with PFIC. [Abstract]

Rickels MR, Naji A, Teff KL
Acute insulin responses to glucose and arginine as predictors of beta-cell secretory capacity in human islet transplantation.
Transplantation. 2007 Nov 27;84(10):1357-60.
Islet transplantation for type 1 diabetes can enable the achievement of near-normal glycemic control without severe hypoglycemic episodes. How much an islet (beta-cell) graft may be contributing to glycemic control can be quantified by stimulatory tests of insulin (or C-peptide) secretion. Glucose-potentiation of arginine-induced insulin secretion provides a measure of functional beta-cell mass, the beta-cell secretory capacity, as either AIR(pot) or AIR(max), but requires conduct of a hyperglycemic clamp. We sought to determine whether acute insulin responses to intravenous glucose (AIR(glu)) or arginine (AIR(arg)) could predict beta-cell secretory capacity in islet recipients. AIR(arg) was a better predictor of both AIR(pot) and AIR(max) (n=10, r2=0.98, P<0.0001 and n=7, r2=0.97, P<0.0001) than was AIR(glu) (n=9, r2=0.78, P=0.002 and n=6, r2=0.76, P=0.02). Also, the measures of beta-cell secretory capacity were highly correlated (n=7, r2=0.98, P<0.0001). These results support the use of AIR(arg) as a surrogate indicator of beta-cell secretory capacity in islet transplantation. [Abstract]

Diswall M, Angström J, Schuurman HJ, Dor FJ, Rydberg L, Breimer ME
Studies on glycolipid antigens in small intestine and pancreas from alpha1,3-galactosyltransferase knockout miniature swine.
Transplantation. 2007 Nov 27;84(10):1348-56.
BACKGROUND: To avoid hyperacute rejection of xeno-organs, alpha1,3-galactosyltransferase knockout (GalT-KO) pigs have been produced. Galalpha1,3Gal determinant elimination may expose cryptic carbohydrate antigens and/or generate new antigens. This is the first biochemical study of carbohydrate antigens in GalT-KO pig organs. METHODS: Neutral and acidic glycolipids were isolated from small intestine and pancreas of two GalT-KO and one wild-type (WT) pig. Glycolipid immune reactivity was tested on thin-layer chromatograms. Small intestine neutral glycolipids were separated by high-performance liquid chromatography and selected fractions were analyzed by proton nuclear magnetic resonance spectroscopy. Total gangliosides were quantified on thin-layer chromatograms and in microtiter wells. RESULTS: Using Galalpha1,3nLc4 glycolipid reference, total Galalpha1,3Gal glycolipid antigens in the WT animal was estimated at about 30 microg (small intestine) and 3 microg (pancreas) per gram of dry tissue. Galalpha1,3Gal determinants were not detected in GalT-KO tissues at a detection limit of less than 0.25% (small intestine) and 0.5% (pancreas) of the WT tissues. Isoglobotriaosylceramide (iGb3) was absent but trace amounts of Fuc-iGb3 was found in both GalT-KO and WT pig small intestine. Blood group H type 2 core saccharide compounds were increased in GalT-KO pancreas. Total amount of gangliosides was decreased in GalT-KO tissues. The alpha1,3-galactosyltransferase acceptor, N-acetyllactosamine determinant, was not increased in GalT-KO tissues. Human serum antibodies reacted with WT organ Galalpha1,3Gal antigens and gangliosides, of which the ganglioside reactivity remained in GalT-KO tissues. CONCLUSIONS: Knockout of porcine alpha1,3-galactosyltransferase gene results in elimination of Galalpha1,3Gal-terminated glycolipid compounds. GalT-KO genetic modification did not produce new compensatory glycolipid compounds reactive with human serum antibodies. [Abstract]

Zandberg M, van Son WJ, Harmsen MC, Bakker WW
Infection of human endothelium in vitro by cytomegalovirus causes enhanced expression of purinergic receptors: a potential virus escape mechanism?
Transplantation. 2007 Nov 27;84(10):1343-7.
BACKGROUND: Human cytomegalovirus (CMV) uses different strategies to escape from human host defense reactions. Previously we have observed that infection of endothelial cells with CMV in vitro leads to enhanced activity of endothelial ectonucleotidases. These ectoenzymes are responsible for hydrolysis of extracellular adenine nucleotides, resulting in the formation of adenosine. Infection with CMV in vivo therefore may result in local increase of adenosine production, providing an anti-inflammatory and antiaggregatory microenvironment, which may facilitate entry of the virus into the target cell. METHODS: The present study focuses on the expression of P2 type purinergic receptors on endothelial cells after infection with CMV. Human endothelial cells were infected with CMV and compared with either uninfected cells or endothelial cells infected with other herpesviruses (herpes simplex virus [HSV] 1 or 2) for the expression of P2 receptors such as P2Y1, P2Y2, or P2X7. For comparison, cells stimulated with nonspecific agents were also studied. RESULTS: A strong upregulation of the P2 receptors tested was shown, exclusively in CMV-infected cells. Stimulation with either HSV-1 or HSV2, nonspecific stimulants, or various cytokines did not affect the expression of these P2 receptors significantly. CONCLUSION: Infection of endothelium with CMV causes significant upregulation of the P2 receptors studied. As these receptors may potentially be able to concentrate nucleotides along the ectonucleotidases of the endothelial cell membrane, rapid local hydrolysis of adenosine triphosphate and adenosine diphosphate may be facilitated by enhanced P2 receptor expression. Such a CMV induced mechanism might enable the virus to escape from an important host defense response, such as local microthrombus formation. [Abstract]

Jonigk D, Lehmann U, Stuht S, Wilhelmi M, Haverich A, Kreipe H, Mengel M
Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions of cardiac allografts.
Transplantation. 2007 Nov 27;84(10):1335-42.
BACKGROUND: The contribution of extracardiac cells to tissue turnover in heart allografts has recently been demonstrated. Complex subendocardial infiltrates, known as Quilty lesions, are frequently observed in cardiac allografts. The origin of the different cellular components of Quilty lesions is not known. METHODS: Different constituents of these lymphonodular infiltrates were analyzed with regard to donor or recipient derivation. Laser-assisted microdissection with subsequent short tandem repeat polymerase chain reaction (PCR)-based "genetic fingerprinting" was employed. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for confirmation in cases of gender-mismatched transplantation. Expression of angiogenic factors (FGF-2, PDGF-alpha, PDGF-alpha-receptor, and VEGF-alpha) was analyzed by quantitative real-time reverse-transcription PCR and immunohistochemistry. RESULTS: The inflammatory, nonvascular component of Quilty lesions was completely recipient-derived. Blood vessels were of mixed origin. Different compartments of blood vessels displayed different rates of recipient derivation (endothelium up to 50%, smooth muscle cells up to 15%). Lymphatic vessels were mainly recipient-derived. Of the angiogenic molecules, VEGF-alpha expression was significantly increased in the adjacent myocardium, compared to controls and the Quilty lesions themselves. CONCLUSIONS: The inflammatory compartment of Quilty lesions is of recipient origin and shows chimeric neoangiogenesis of blood and lymphatic vessels. VEGF-alpha produced in the adjacent myocardium appears to stimulate the chimeric neoangiogenesis. [Abstract]

Lee CY, Lotfi-Emran S, Erdinc M, Murata K, Velidedeoglu E, Fox-Talbot K, Liu J, Garyu J, Baldwin WM, Wasowska BA
The involvement of FcR mechanisms in antibody-mediated rejection.
Transplantation. 2007 Nov 27;84(10):1324-34.
BACKGROUND: Antibody-mediated rejection is characterized by macrophage margination against vascular endothelium. The potential interactions triggered by antibodies between endothelial cells (EC) and macrophages have not been examined thoroughly in transplants. We used in vivo and in vitro models of antibody-mediated rejection. METHODS: Passive transfer of monoclonal alloantibodies (Allo-mAbs) to donor major histocompatibility complex-class I antigens was used to restore acute rejection of B10.A (H-2a) hearts to C57BL/6 (H-2b) immunoglobulin knockout (IgKO) recipients. Intragraft cytokine mRNA expression was measured by real-time polymerase chain reaction. In vitro, mouse EC were cultured in the presence of Allo-mAbs to donor major histocompatibility complex class I antigens and mononuclear cells. Levels of cytokines in culture supernatants were determined in enzyme-linked immunosorbent assay. RESULTS: Expression of MCP-1, IL-6 and IL-1alpha mRNA was higher in rejecting transplants from recipients treated with Allo-mAbs compared to non-rejecting transplants. EC sensitized with Allo-mAbs produced high levels of MCP-1 and KC. The addition of macrophages to sensitized EC stimulated high levels of IL-6 in addition to MCP-1, KC, Rantes, and TIMP-1. The levels of MCP-1 and IL-6 were significantly lower in co-cultures of EC sensitized with IgG1 Allo-mAbs in the presence of mononuclear cells from Fcgamma-Receptor III KO (FcgammaRIII-KO) graft recipients compared to co-cultures with wild-type cells. The levels of both cytokines were also lower in co-cultures of EC stimulated with F(ab')2 fragments of antibody. CONCLUSIONS: Our findings indicate that IgG1 Allo-mAbs to major histocompatibility complex class I antigens can augment graft injury by stimulating EC to produce MCP-1 and by activating mononuclear cells through their Fc receptors. [Abstract]

Bharat A, Saini D, Benshoff N, Goodman J, Desai NM, Chapman WC, Mohanakumar T
Role of intra-islet endothelial cells in islet allo-immunity.
Transplantation. 2007 Nov 27;84(10):1316-23.
BACKGROUND: Intra-islet endothelial cells (IECs) express high levels of major histocompatibility complex (MHC) and are pivotal for posttransplant islet revascularization. We postulated that donor-specific sensitization would result in hyperacute rejection of IECs and prevent islet engraftment. Furthermore, ligation of endothelial cells with subsaturating concentrations of anti-MHC class I antibody (Ab) results in "accommodation" conferring protection against Ab/complement-mediated lysis. Therefore, we investigated whether accommodation of IECs would prevent hyperacute rejection of islets in sensitized recipients. METHODS: Islets were transplanted beneath the kidney capsule and allograft survival monitored using daily blood glucose (diabetes >300 mg/dL, normoglycemia <150 mg/dL). Recipients were presensitized with donor islets, splenocytes, or skin. Accommodation was induced by incubating human or murine islets with varying concentrations of anti-MHC class I Ab ex vivo. RESULTS: Isografts remained functional for >100 days, whereas allografts were rejected by day 14. Islet allo-transplantation induced donor-specific but not third-party anti-MHC Abs. Donor-specific, but not third-party, sensitization induced hyperacute rejection of subsequent islet allografts (median survival 1 day) associated with complement deposition. Preincubation of islets with subsaturating concentrations of anti-MHC-I Abs (1-100 ng/mL) up-regulated Bcl-2, Bcl-xl, and HO-1 within CD31+ IEC. These accommodated islets were resistant against hyperacute rejection when transplanted into donor-(splenocyte) sensitized recipients without any immunosuppression (median survival 6 days). CONCLUSIONS: Pretransplant sensitization against donor antigens results in hyperacute rejection of murine islets. IECs may play a crucial role in development of donor-specific immunity after islet transplantation. Significantly, accommodation of IEC may confer resistance to hyperacute rejection in sensitized recipients. [Abstract]

Skuk D, Paradis M, Goulet M, Tremblay JP
Ischemic central necrosis in pockets of transplanted myoblasts in nonhuman primates: implications for cell-transplantation strategies.
Transplantation. 2007 Nov 27;84(10):1307-15.
BACKGROUND: Several cell-transplantation strategies implicate the injection of cells into tissues. Avascular accumulations of implanted cells are then formed. Because the diffusion of oxygen and nutrients from the surrounding tissue throughout the implanted cell accumulations may be limited, central ischemic necrosis could develop. We analyzed this possibility after myoblast transplantation in nonhuman primates. METHODS: Macaca monkeys were injected intramuscularly with different amounts of myoblasts per single site. These sites were sampled 1 hr later and at posttransplantation days 1, 3, 5, and 7 and analyzed by histological techniques. RESULTS: One day posttransplantation, the largest pockets of implanted cells showed cores of massive necrosis. The width of the peripheral layer of living cells was approximately 100-200 microm. We thus analyzed the relationship between the amount of myoblasts injected per site and the volume of ischemic necrosis. Delivering 0.1 x 10(6) and 0.3 x 10(6) myoblasts did not produce ischemic necrosis; pockets of 1 x 10(6), 3 x 10(6), 10 x 10(6), and 20 x 10(6) myoblasts exhibited, respectively, a mean of 2%, 9%, 41%, and 59% of central necrosis. Intense macrophage infiltration took place in the muscle, invading the accumulations of necrotic cells and eliminating them by posttransplantation days 5 to 7. CONCLUSIONS: The desire to create more neoformed tissue by delivering more cells per injection site is confronted with the fact that the acute survival of the implanted cells is restricted to the peripheral layer that can profit of the diffusion of oxygen and nutriments from the surrounding recipient's tissue. [Abstract]

Weng X, Zhong M, Liang Z, Lu S, Hao J, Chen X, Li J, Gong F, Wu X
Peptide-dependent inhibition of alloreactive T-cell response by soluble divalent HLA-A2/IgG molecule in vitro.
Transplantation. 2007 Nov 27;84(10):1298-306.
BACKGROUND: Induction of peripheral tolerance in an antigen-specific manner is a critical goal of transplant biology. The specificity and avidity of multimerized peptide/major histocompatibilty complexes suggest their potential ability to modulate antigen-specific T-cell sensitization and effector functions. METHODS: A soluble divalent HLA-A2/IgG molecule (HLA-A2 dimer) was constructed and loaded with a self-protein origin peptide (Tyr(368-376)) to form a divalent Tyr/HLA-A2 molecule (Tyr/HLA-A2 dimer), which allowed for specific targeting to the epitope-specific cytotoxic T lymphocytes in bulk alloreactive T cells. Alloreactive T-cell response was induced by coculture of Tyr(368-376) -pulsed T2 cells (T2/Tyr) with peripheral blood lymphocytes of HLA-A2-negative (HLA-A2-ve) sample; five samples of HLA-A2-ve individuals were included in this study. After the coculture in the presence of Tyr/HLA-A2 dimer, the suppression of the dimer on alloresponse was characterized by analyzing allogeneic T-cell proliferation, specific cytolytic activity against the T2/Tyr, and specific Tyr/HLA-A2 tetramer staining. RESULTS: The Tyr/HLA-A2 dimer suppresses alloreactive T-cell response by inhibiting its proliferation and cytotoxicity against specific target T2/Tyr in vitro, and it is interesting that the suppression is peptide-specific. The Tyr/HLA-A2 tetramer staining suggests the reduced function of CD8+ T cell is caused by inhibiting the generation of the epitope-specific alloreactive T cells by the Tyr/HLA-A2 dimer in three samples. Moreover, the existence of epitope-specific but function-negative T cells in the other two samples suggests that another mechanism might exist that is involved in silencing alloreactive responses by the dimer. CONCLUSION: Peptide-loaded dimers offer a novel approach to induce peptide-specific immunosuppression and may be useful in promoting graft survival. [Abstract]

Inoue F, Zhang Q, Akiyoshi T, Aramaki O, Iwami D, Matsumoto K, Kitagawa Y, Shirasugi N, Niimi M
Prolongation of survival of fully allogeneic cardiac grafts and generation of regulatory cells by a histamine receptor 2 antagonist.
Transplantation. 2007 Nov 27;84(10):1288-97.
BACKGROUND: The effects of histamine on immunologic responses via the histamine receptor 2 (HR2) have been studied, but few investigations explored the immunomodulatory role of histamine in vivo. We examined whether the HR2 antagonist ranitidine affects the alloimmune response in a murine model of cardiac transplantation. METHODS: CBA (H-2k) recipients were given no treatment or one intravenous injection of ranitidine on the day of transplantation of a heart from C57BL/10 (H-2b) donors. Survival of the allografts was recorded. The effect of the ranitidine treatment on cell proliferation and cytokine production was assessed by mixed leukocyte culture and enzyme-linked immunosorbent assays. An adoptive transfer study was conducted to determine whether regulatory cells were generated. The effect on graft survival of adding FK506 to the ranitidine treatment was also examined. RESULTS: CBA recipients given ranitidine (60 mg/kg) had prolonged graft survival (median survival time [MST], 87 days). Ranitidine treatment also suppressed the proliferation of splenocytes and production of interleukin (IL)-2 and up-regulated IL-10 production. Adoptive transfer of splenocytes and CD4 cells from ranitidine-treated allograft recipients induced significant prolongation of allograft survival in naive secondary recipients (MST, 71 and >100 days, respectively). CBA recipients given both ranitidine and FK506 (0.1 mg/kg/day for 14 days) had indefinite survival of cardiac allografts (MST, >100 days). CBA recipients treated with FK506 alone rejected the allografts (MST, 27 days). CONCLUSION: In our model, ranitidine treatment induced significantly prolonged survival of fully allogeneic cardiac grafts, generated CD4 regulatory cells, and indefinite survival when combined with FK506 (0.1 mg/kg/day). [Abstract]

Kaczorowski DJ, Nakao A, Mollen KP, Vallabhaneni R, Sugimoto R, Kohmoto J, Tobita K, Zuckerbraun BS, McCurry KR, Murase N, Billiar TR
Toll-like receptor 4 mediates the early inflammatory response after cold ischemia/reperfusion.
Transplantation. 2007 Nov 27;84(10):1279-87.
BACKGROUND: Ischemia/reperfusion (I/R) injury leads to graft dysfunction and may contribute to alloimmune responses posttransplantation. The molecular mechanisms of cold I/R injury are only partially characterized but may involve toll-like receptor (TLR)-4 activation by endogenous ligands. We tested the hypothesis that TLR4 mediates the early inflammatory response in the setting of cold I/R in a murine cardiac transplant model. METHODS: Syngeneic heart transplants were performed in mutant mice deficient in TLR4 signaling (C3H/HeJ) and wild-type mice (C3H/HeOuJ). Transplants were also performed between the strains (mutant hearts into wild-type recipients and the converse). Donor hearts were subjected to 2 hr of cold ischemia. The grafts were retrieved at 3 and 24 hr after reperfusion. Serum samples were collected for cytokine analysis. Reverse-transcription polymerase chain reaction and histologic analysis were used to assess intra-graft inflammation. RESULTS: After transplant, serum tumor necrosis factor (TNF), interleukin (IL)-6, JE/monocyte chemotractant protein (MCP)-1, IL-1beta, and troponin I levels, as well as intragraft TNF, IL-1beta, IL-6, early growth response (EGR)-1, intercellular adhesion molecule (ICAM)-1, and inducible nitric oxide synthase (iNOS) mRNA levels, were significantly lower in the mutant-->mutant group compared to the wild-type-->wild-type group (P< or =0.05). Intermediate levels of serum IL-6, JE/MCP-1, as well as intragraft TNF, IL-1beta, IL-6, and ICAM-1 mRNA were observed after transplants in the mutant-->wild-type and wild-type-->mutant groups. Immunohistochemistry revealed less myocardial nuclear factor-kappaB nuclear translocation at and less neutrophil infiltration in the mutant-->mutant group compared to the wild-type-->wild-type group. CONCLUSIONS: These findings demonstrate that TLR4 signaling is central to both the systemic and intragraft inflammatory responses that occur after cold I/R in the setting of organ transplantation and that TLR4 signaling on both donor and recipient cells contributes to this response. [Abstract]

Zaman MB, Leonard MO, Ryan EJ, Nolan NP, Hoti E, Maguire D, Mulcahy H, Traynor O, Taylor CT, Hegarty JE, Geoghegan JG, O'Farrelly C
Lower expression of Nrf2 mRNA in older donor livers: a possible contributor to increased ischemia-reperfusion injury?
Transplantation. 2007 Nov 27;84(10):1272-8.
BACKGROUND: The cellular mechanisms involved in mediating cytoprotection against ischemia-reperfusion (IR) injury are not well understood. In animal models, NF-E2-related factor-2 (Nrf2) protects against IR injury by transcriptional activation of phase II antioxidants. Here, we investigate how the expression of Nrf2 mRNA in human donor livers in the setting of liver transplantation (LT) correlates with the histological damage associated with IR injury and whether or not this influences the outcome of LT. METHODS: Pairs of biopsies were acquired from 14 donor livers; the first biopsy of each pair was taken at the start of the retrieval operation, prior to the IR phase of LT and the second at the end of transplantation. RNA was extracted from snap frozen tissue and cDNA was prepared. Nrf2 mRNA expression was determined using real-time polymerase chain reaction (PCR). The modified Suzuki scoring system was used for histological grading of IR injury and relevant donor, recipient, and after LT clinical data were compiled. RESULTS: Nrf2 expression was observed in all biopsies, both before and after IR. Some donor organs had greater expression of Nrf2 mRNA before IR injury, and these organs had lower Suzuki scores and better liver functions (ALT) after LT. Donors of livers with greater Nrf2 levels were significantly younger (40.5 yrs, range 28-53 yrs) than those with low Nrf2 levels (55.5 yrs, range 48-61 yrs), P<0.05. CONCLUSION: Livers from older donors have lower levels of Nrf2 perhaps exposing these organs to more IR-related damage. [Abstract]

Mas VR, Maluf DG, Archer KJ, Yanek KC, Fisher RA
Angiogenesis soluble factors as hepatocellular carcinoma noninvasive markers for monitoring hepatitis C virus cirrhotic patients awaiting liver transplantation.
Transplantation. 2007 Nov 27;84(10):1262-71.
BACKGROUND: Physiological angiogenesis occurs during liver regeneration, leading to the formation of new functional sinusoids. Pathological angiogenesis occurs in hepatocellular carcinoma (HCC). We aimed to evaluate the expression of angiogenic factors in hepatitis C virus (HCV)-HCC tissues and the utility of angiogenesis soluble factors as noninvasive markers of HCC and tumor growth. METHODS: Thirty-eight HCV-HCC tumors with 10 corresponding nontumor cirrhotic tissues, as well as 42 independent HCV cirrhotic and 6 normal liver tissues were studied using high-density oligonucleotide arrays. Human angiogenesis microarray was used for the protein detection of EGF, TIMP-1, TIMP-2, HGF, angiopn-1, angiopn-2, VEGF-A, IP-10, PDGF, KGF, angiogenin, VEGF-D, ICAM-1, and FGF in plasma samples from 40 patients (30 HCCs and 10 HCV cirrhosis). RESULTS: From the gene expression analysis of the HCV-HCC tumors compared to normal livers, we found an important number of genes related to angiogenesis differentially expressed (alpha=0.01), including VEGF, PDGF, AGPTL2, ANG, EGFL6, EGFR, angiopn-1, angiopn-2, ICAM2, TIMP-2, among others. Moreover, angiogenic genes were also differentially expressed when HCV-HCC samples were compared to HCV cirrhotic tissues (alpha=0.01; VEGF, EGFL3, EGFR, VEGFB, among others). Ten out of 14 angiogenic proteins analyzed were statistically differentially expressed between HCV cirrhosis and HCV-HCC groups (TIMP-1, TIMP-2, HGF, angiopn-1, angiopn-2, VEGF-A, IP-10, PDGF, KGF, and FGF; P<0.05). In addition, we observed that angiopn-2 was the most significant predictor (area under the curve: 0.83). CONCLUSION: Differentially expressed angiogenesis genes were observed between HCV patients with and without HCC. Soluble angiogenic factors might be useful for monitoring high-risk HCV patients. [Abstract]

Hayashi A, Noma S, Uehara M, Kuwabara H, Tanaka S, Furuno Y, Hayashi T
Relevant factors to psychological status of donors before living-related liver transplantation.
Transplantation. 2007 Nov 27;84(10):1255-61.
BACKGROUND: While previous surveys have demonstrated the psychological impact on living-related liver transplantation (LRLT) donors, such as anxiety, depression, ambivalence and anger, the details regarding the relevant factors that affect donors' psychological status have not been well described. METHODS: To evaluate environmental factors, 66 donors were interviewed to obtain information regarding donors' decision-making motivation, process, conflicts, and internal pressure about donation just before surgery. To determine the donors' psychological status, they completed the State-Trait Anxiety Inventory, Beck Depression Inventory, and World Health Organization Quality of Life 26 standardized psychological tests for anxiety, depression, and quality of life (QOL). Respective recipients completed the same tests separately, in order to determine psychological synchronization with the donors. With regard to motivation, donors were divided into two groups, and further divided into three groups based on processes. Donors were also sorted in groups of those "with conflict" and "with pressure." Their psychological test results were compared within groups, as well as with those from recipients. RESULTS: Donors from the nonvolunteer or postponement groups were significantly more anxious and depressed than other donors. Donors from the "with conflict" or "with pressure" groups were significantly more anxious, more depressed, and had worse QOL. There was a significant positive correlation between donors' and recipients' test results for anxiety and QOL, especially when donors belonged to the volunteer group. CONCLUSIONS: Our results suggest that donors' decision-making process and recipients' psychological status, especially donors' state anxiety should be considered when assessing donors' psychological status before LRLT. [Abstract]

Genís BB, Granada ML, Alonso N, Lauzurica R, Jiménez JA, Barluenga E, Homs M, Pastor MC, Salinas I, Quintero JC, Sanmartí A, Romero R
Ghrelin, glucose homeostasis, and carotid intima media thickness in kidney transplantation.
Transplantation. 2007 Nov 27;84(10):1248-54.
BACKGROUND: Abnormalities in glucose homeostasis (AGH) frequently occur in kidney transplantation and favor vascular lesions. The purpose of this study was to analyze whether C-reactive protein (CRP), adiponectin, and ghrelin are markers of AGH and indicators of carotid atherosclerosis in kidney transplant patients with fasting plasma glucose below 126 mg/dL. METHODS: This was a cross-sectional study of 85 kidney transplant patients (59 men; mean age: 52.4 +/- 11.6 years; median posttransplant follow-up 31 (range 3-61) months). All patients underwent an oral glucose tolerance test. Abnormalities in glucose homeostasis were diagnosed following American Diabetes Association criteria. CRP, adiponectin, and ghrelin levels were determined. Doppler ultrasound of the carotid artery was performed to determine intima media thickness (IMT) and atheromatous plaque. RESULTS: A total of 50.5% of patients had AGH (12.9% were diagnosed with new-onset diabetes mellitus after transplantation and 37.7% had impaired glucose tolerance or impaired fasting glucose), whereas 49.4% were normoglycemic. Patients with AGH were older (P=0.002), had greater carotid IMT (P=0.022), and lower ghrelin concentrations (P=0.017) than normoglycemic patients. Logistic regression analyses showed ghrelin to be an independent marker for AGH (P=0.012) and AGH to be related to greater IMT (P=0.041). No differences in adiponectin or CRP were found in relation to AGH or atherosclerosis; however, there was a positive correlation between adiponectin levels and prednisone dose (r=0.240; P=0.044). CONCLUSIONS: A total of 50.5% of the study patients had abnormalities in glucose homeostasis. Patients with AGH had a higher percentage of preclinical atherosclerosis (greater carotid IMT). Ghrelin is an independent marker for abnormalities in glucose homeostasis. [Abstract]

Israni AK, Li N, Sidhwani S, Rosas S, Kong X, Joffe M, Rebbeck T, Feldman HI
Association of hypertension genotypes and decline in renal function after kidney transplantation.
Transplantation. 2007 Nov 27;84(10):1240-7.
BACKGROUND: Polymorphisms of genes such as angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin receptor type I (AGTR1) have been associated with hypertension. Hypertension, in turn, has been associated with decreased renal allograft survival. Therefore, this study investigated whether single nucleotide polymorphisms (SNPs) in these genes are associated with decline in renal function posttransplantation. METHODS: We enrolled patients from a prospective cohort of renal transplant recipients of deceased donor kidneys being conducted at 9 centers in the Delaware Valley Region. Medical records were assessed every 6 months and estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease equation. Genotypes of 10, 2, and 5 SNPs in the AGTR1, AGT, and ACE gene were analyzed, respectively. RESULTS: The G and the T alleles of the respective AGTR1 SNPs rs275704 and rs5182 were both associated with 50% decline in eGFR (HR for rs275704: CG=1.22, 95% confidence interval [CI] 0.67-2.25 and GG=2.55, 95% CI 1.22-5.32, overall P=0.03; HR for rs5182: CT=1.26, 95% CI 0.72-2.19 and TT=3.09, 95% CI 1.50-6.37, overall P=0.007) in the adjusted analysis. Similarly, haplotype analysis showed that AGTR1 SNPs were associated with 50% decline in eGFR (global P=0.010). The GG genotype of SNP rs275704 occurred more frequently in African Americans than in non-African Americans (44% vs. 7%, chi2=36.03, P<0.0001). In contrast, the TT genotype of SNP rs5182 occurred more frequently in non-African Americans than in African-Americans (24% vs. 2%, chi2=21.40, P<0.0001). Polymorphisms in the ACE and AGT genes were not associated with renal allograft outcomes. CONCLUSIONS: SNPs in AGTR1 gene are associated with decline in renal function posttransplantation. [Abstract]

Machimoto T, Yasuchika K, Komori J, Ishii T, Kamo N, Shimoda M, Konishi S, Saito M, Kohno K, Uemoto S, Ikai I
Improvement of the survival rate by fetal liver cell transplantation in a mice lethal liver failure model.
Transplantation. 2007 Nov 27;84(10):1233-9.
BACKGROUND: The use of cell transplantation as an alternative therapy for orthotopic liver transplantation has been widely anticipated due to a chronic donor shortage. We previously reported the method used to enrich hepatic progenitor cells (HPCs) forming cell aggregations. In this study, we transplanted HPCs into the liver injury model mice to determine whether HPC transplantation may improve the liver dysfunction. METHODS: We obtained donor cells from E13.5 fetal livers of green fluorescent protein (GFP) transgenic mice. We transplanted GFP-positive fetal liver cells into the transgenic mice which express diphtheria toxin (DT) receptors under the control of an albumin enhancer/promoter. Subsequently, we induced selective liver injury to recipient mice by DT administration. We then evaluated the engraftment of the transplanted cells and their effect on survivorship. RESULTS: The low dose of DT induced sublethal liver injury and the high dose of DT was lethal to the liver injury model mice. The transplanted GFP-positive cells were engrafted into the recipient livers and expressed albumin, resembling mature hepatocytes. They continued to proliferate, forming clusters. The survival rate at 25 days after transplantation of the cell-transplanted group (8 of 20; 40.0%) was improved significantly (P=0.0047) in comparison to that of the sham-operated group (0 of 20; 0%). CONCLUSIONS: The transplanted cells were engrafted and repopulated the liver of recipient mice, resulting in the improvement of the survival rate of the liver injury model mice. We therefore propose that HPCs are a desirable cell source for cell transplantation. [Abstract]

Lai JY, Chen KH, Hsiue GH
Tissue-engineered human corneal endothelial cell sheet transplantation in a rabbit model using functional biomaterials.
Transplantation. 2007 Nov 27;84(10):1222-32.
BACKGROUND: This study was performed to investigate whether transplantation of bioengineered human corneal endothelial cell (HCEC) sheet grafts into corneas denuded of endothelium could restore corneal function and clarity in a rabbit model. METHODS: After being labeled with PKH26 fluorescent dye, the adult HCECs derived from eye bank corneas were cultivated on the thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm)-grafted surfaces for 3 weeks at 37 degrees C, and were harvested as transplantable cell sheets after incubation for 45 min at 20 degrees C. Attached by gelatin hydrogel discs, the bioengineered cell monolayers were transplanted to rabbit corneas denuded of endothelium (HCEC sheet group). Traumatized rabbit corneas were served as controls. Postsurgical corneas underwent clinical observations and histological examinations for 6 months. RESULTS: By transmission electron microscopy and Western blot analysis of zonula occludens-1 and Na+,K+ -adenosine triphosphatase proteins, the structure and function of HCEC sheets resembled those of native corneal endothelium. After endothelial cells were removed, corneas of each group turned severe edematous and opaque. In the HCEC sheet groups, corneal clarity was gradually restored and corneal thickness was significantly less than that in the control groups (P<0.05). The attached PKH26-positive HCECs spread on rabbit Descemet's membrane after receiving cell sheet grafts. Intraocular delivery of HCEC sheets by means of a minimally invasive technique (i.e., small-incision surgery using biodegradable hydrogels) demonstrated long-term graft integration with damaged corneas. CONCLUSIONS: These results indicate that using cultured HCECs and functional biomaterials, PNIPAAm and gelatin, an effective cell sheet-based therapy can be developed for the treatment of corneal endothelium deficiency. [Abstract]

Hjelmesaeth J, Jenssen T, Hartmann A
Ghrelin, atherosclerosis, and glucose: GAG or causal relationships?
Transplantation. 2007 Nov 27;84(10):1220-1. [Abstract]

Ashton-Chess J, Giral M, Brouard S, Soulillou JP
Spontaneous operational tolerance after immunosuppressive drug withdrawal in clinical renal allotransplantation.
Transplantation. 2007 Nov 27;84(10):1215-9.
Tolerance is the so-called "Holy Grail" of transplantation, but achieving this state is proving a major challenge, particularly in the clinical setting. Even in rodents, the definition of true transplant tolerance is not applicable to many models, with late graft damage often occurring despite long-term graft survival. Hence the term "operational tolerance," based more on graft function and absence of exogenous immunosuppression, is being adopted. Although the most sought-after goal in this field is to intentionally induce this state in a controlled manner, translating protocols across species from rodents to the clinic, the current literature demonstrates that this is proving a formidable task. A complementary approach is to address transplant tolerance from a different angle, by studying tolerance-like phenomena that occur "unintentionally" in transplant patients after immunosuppressive drug weaning. Such spontaneous operational tolerance, which can take place after years of immunosuppression, is rare in kidney transplant recipients. However, determining exactly how this state arises and how it can be detected may make it possible to induce it in a greater number of patients and then to return to the drawing board to rationally design protocols that have a greater chance of clinical success. Moreover, the study of such patients should help in the identification of biomarkers of low immunological risk that could be used to select patients for potential weaning. Collaborative efforts through international networks, together with the application of newer and more powerful technologies to diagnostic, prognostic, and mechanistic research, may help transplanters to achieve this goal. [Abstract]

Cooper DK
Response to Commentaries on "alpha1,3-Galactosyltransferase Gene-Knockout Pigs for Xenotransplantation: Where Do We Go From Here?".
Transplantation. 2007 Nov 15;84(9):1212-3. [Abstract]

Fishbein TM, Matsumoto CS
Authors' reply.
Transplantation. 2007 Nov 15;84(9):1209. [Abstract]

Chaib E, Massad E
Comparing the dynamics of kidney and liver transplantation waiting list in the state of sao paulo, Brazil.
Transplantation. 2007 Nov 15;84(9):1209-11. [Abstract]

Abu-Elmagd KM
Preservation of the native spleen, duodenum, and pancreas in patients with multivisceral transplantation: nomenclature, dispute of origin, and proof of premise.
Transplantation. 2007 Nov 15;84(9):1208-9. [Abstract]

Bueno V, Binet I, Steger U, Bundick R, Ferguson D, Murray C, Donald D, Wood K
The Specific Monocarboxylate Transporter (MCT1) Inhibitor, AR-C117977, a Novel Immunosuppressant, Prolongs Allograft Survival in the Mouse.
Transplantation. 2007 Nov 15;84(9):1204-1207.
Novel small molecular weight compounds that act by inhibiting the monocarboxylate transporter (MCT1) receptor have been found to cause profound inhibition of T-cell responses to alloantigen in vitro. Here, we have investigated the ability of one compound in this series, AR-C117977, a potent MCT1 inhibitor, to prevent the acute and chronic rejection of vascularized and nonvascularized allografts in the mouse. Treatment with AR-C117977 or cyclosporin A (CsA) administered at a dose of 30 mg/kg subcutaneously for 15 days to adult CBA. Ca (H2) mice, commencing either 3 days or 1 day before transplantation, was found to prolong the survival of an allogeneic (C57BL/10 H2; NZW H2; or BALB/c H2) heart, aorta, or skin allograft significantly compared with treatment with vehicle alone (median survival time [MST] AR-C117977 treated 15; 19 and 18 days [skin] and 73; 66 and 67 days ([heart] vs. vehicle treated 8, 8 and 9 days [skin] and 9, 8, 10 days [heart] for B10, NZW and BALB grafts, respectively). AR-C117977 also inhibited the development of transplant arteriosclerosis in aortic allografts partially, but was unable to inhibit alloantibody production after transplantation. The specific MCT1 inhibitor AR-C117977 has potent immunosuppressive properties in vivo effectively preventing acute but not chronic allograft rejection in the mouse. [Abstract]

Recent Articles in Journal of Neurology, Neurosurgery, and Psychiatry

Bleuse S, Cassim F, Blatt JL, Labyt E, Bourriez JL, Derambure P, Destée A, Defebvre L
Anticipatory postural adjustments associated with arm movement in Parkinson's disease: a biomechanical analysis.
J Neurol Neurosurg Psychiatry. 2007 Nov 26; .
OBJECTIVE: to study anticipatory postural adjustments (APAs) in Parkinson's disease (PD) via a biomechanical analysis, including vertical torque (Tz). METHODS: Ten parkinsonian patients (in the "off-drug" condition) and 10 age-matched controls were included. While standing on a force platform, the subject performed a right shoulder flexion in order to grasp a handle in front of him/her, in 3 conditions (all at maximal velocity): movement triggered by a sound signal and loaded/non-loaded, self-paced movement. The anteroposterior coordinates of the center of pressure (COP) and the vertical torque were calculated. RESULTS: A group effect was observed for Tz and COP in PD patients (compared with controls): the maximal velocity peak appeared later and the amplitude of the COP backward displacement and the area of the positive phase of Tz were lower, whereas the duration of the positive phase of Tz was greater. Interaction analysis showed that the area of Tz was especially affected in the triggered condition and the loaded, self-paced condition. The onset of the COP backward displacement was delayed in the triggered condition. CONCLUSION: Our biomechanical analysis revealed that PD patients do indeed perform APAs prior to unilateral arm movement, although there were some abnormalities. The reduced APA magnitude appears to correspond to a strategy for not endangering postural balance. [Abstract]

Vetrugno R, Arnulf I, Montagna P
Disappearance of "Phantom Limb" and amputated arm usage during dreaming in REM sleep behaviour disorder.
J Neurol Neurosurg Psychiatry. 2007 Nov 26;
Limb amputation is followed, in approximately 90% of the patients, by "phantom limb" sensations during wakefulness. When amputated patients dream, however, the phantom limb may be present all the time, part of the time, intermittently or not at all.[1] The absence of the phantom limb when dreaming has been taken as evidence for a pre-existing kinesthetic body scheme, unaffected by the amputation, that is accessible to the patient when asleep.[2] Such dreaming experiences in amputees usually have been obtained only retrospectively in the morning, and moreover, dreaming is normally associated with muscular atonia, so the motor counterpart of the phantom limb experience cannot be observed directly. REM sleep behaviour disorder (RBD), in which muscle atonia is absent during REM sleep and patients act out their dreams,[3] allows a more direct analysis of the "phantom limb" phenomena, and their modifications during sleep. [Abstract]

Fish J, Manly T, Emslie H, Evans JJ, Wilson B
Compensatory strategies for acquired disorders of memory and planning: Differential effects of a paging system for patients with brain injury of traumatic versus cerebrovascular aetiology.
J Neurol Neurosurg Psychiatry. 2007 Nov 26;
BACKGROUND: Previous studies have demonstrated the effectiveness of paging systems in compensating for everyday memory and planning problems after brain injury. Recently, Wilson et al[1] reported the response of participants with traumatic brain injury (TBI) to such a system. METHODS: Here, in addition to further analyses of the TBI data from the randomised control crossover trial[1], results are reported from a sub-group of 36 participants with brain injury of cerebrovascular aetiology (CVA). RESULTS: Results indicate that, as with the TBI group, the pager was effective. However, the pattern of results upon cessation of treatment differed. At a group level, TBI participants demonstrated maintenance of pager-related benefit, whereas CVA participants' performance returned to baseline levels. Comparisons of demographic and neuropsychological characteristics of the groups showed that the CVA group was older, had a shorter interval post-injury, and had poorer executive function than the TBI group. Further, within the TBI group, maintenance was associated with executive functioning, such that executive dysfunction impeded maintenance. This correlation remained after controlling for demographic differences between groups. CONCLUSIONS: Together, these findings suggest that executive dysfunction may affect treatment, for example whether or not temporary use of the pager is sufficient to establish a subsequently self-sustaining routine. [Abstract]

Plaha P, Khan S, Gill SS
Bilateral stimulation of the caudal zona incerta nucleus for tremor control.
J Neurol Neurosurg Psychiatry. 2007 Nov 23;
INTRODUCTION: The ventralis lateral (VL) nucleus of the thalamus is the commonly chosen target for deep brain stimulation (DBS) to alleviate tremor. However, it has a poor efficacy in alleviating proximal tremor and patients may develop tolerance to the action component of tremor. We performed bilateral stimulation of the caudal or motor part of the zona incerta nucleus (cZI) to determine its safety and efficacy in alleviating tremor. METHODS: 5 patients with parkinsonian tremor and 13 with a range of tremors (Holmes(HT), Cerebellar(CT), Essential(ET), Multiple sclerosis(MS) and Dystonic tremor(DT) affecting both the proximal and distal body parts underwent MRI guided, bilateral cZI DBS. Tremor was assessed by the Fahn-Tolosa-Marin (FTM) tremor scale at baseline and at a mean follow up of 12-months. RESULTS: Resting PD tremor improved by 94.8% and postural by 88.2%. The total tremor score improved by 75.9% in 6 patients with ET. HT improved by 70.2%, proximal CT by 60.4% and proximal MS tremor by 57.2% in the total tremor rating score. In the single patient with DT there was improvement in both the dystonia and the tremor. Patients required low voltages of high frequency stimulation and did not develop tolerance to it. Stimulation related side effects were transient. CONCLUSION: This prospective study shows that the cZI may be an alternative target for the treatment of tremor with DBS. In contrast to bilateral DBS of the VL nucleus it improves all components of tremor affecting both the distal and proximal limbs as well as the axial musculature. [Abstract]

Plaha P, Filipovic S, Gill SS
Induction of parkinsonian resting tremor by stimulation of the caudal zona incerta nucleus: A clinical study.
J Neurol Neurosurg Psychiatry. 2007 Nov 23;
INTRODUCTION: We hypothesise that Parkinsonian tremor arises when the caudal zona incerta (cZI) and subthalamic nucleus (STN) are deprived of dopamine and become increasingly responsive to motor cortical alpha and beta frequency oscillations. These oscillations are synchronised and amplified through the basal ganglia thalamocortical loop and entrained into the cerebello-thalamocortical loop via the cZI. Upon receiving potent GABAergic alpha and beta frequency oscillations in cZI afferents, ventrolateral(VL) thalamocortical neurons become hyperpolarised and rebound burst fire, generating 4-6Hz tremor oscillations. We test this hypothesis by stimulating the cZI at alpha and beta frequencies using deep brain stimulation (DBS) in non tremulous parkinsonian patients to see whether a 4-6Hz tremor can be induced. METHOD: This study included 11 patients with non tremulous PD, who had DBS leads implanted in a range of targets including the cZI, STN, VL nucleus, globus pallidus internus (GPi), centromedian and parafascicular nucleus (CM/Pf), and the pedunculopontine nucleus (PPN). All patients underwent stimulation of active contacts within their respective targets at a standard pulse width, with frequencies ranging from 5-80Hz up to a maximum tolerated voltage. The frequency of the tremor induced in the hands was recorded by accelerometry. RESULT: Resting tremor in the 4-6Hz range could be readily induced following stimulation of the cZI and the VL nucleus between 5 and 40Hz. Tremor was also seen following STN stimulation, however, only at high stimulation voltages (>5volts). No tremor could be induced following CM/Pf, PPN or GPi stimulation. CONCLUSION: We discuss the implications of these findings and argue that resting tremor in PD is generated in the cortico-ZI-VL-thalamocortical loop rather than the cortico-basal ganglia--thalamocortical loop. [Abstract]

Selvarajah JR, Smith CJ, Hulme S, Georgiou RF, Vail A, Tyrrell PJ
Prognosis in patients with transient ischaemic attack (TIA) and minor stroke attending TIA services in the North West of England: The NORTHSTAR Study.
J Neurol Neurosurg Psychiatry. 2007 Nov 22;
BACKGROUND: The ABCD2 score predicts stroke risk within a few days of transient ischaemic attack (TIA). It is not clear whether the predictive value of the ABCD2 score can be generalised to UK TIA services, where delayed presentation of TIA and minor stroke are common. We investigated prognosis, and the use of the ABCD2 score, in patients attending TIA services in the North West of England with a diagnosis of TIA or minor stroke. METHODS: 711 patients with TIA or minor stroke were prospectively recruited from five centres (median duration from index event to recruitment 15 days). The primary outcome was the composite of incident TIA, stroke, acute coronary syndrome or cardiovascular death at the 3 month follow-up. Prognostic factors were analysed using Cox proportional hazards regression. RESULTS: The primary outcome occurred in 126 (18%) patients. Overall, there were 30 incident strokes. At least one incident TIA occurred in 100 patients (14%), but only four had a subsequent stroke. In multifactorial analyses, the ABCD2 score was unrelated to the risk of the primary outcome, but predicted the risk of incident stroke: score 4-5: hazard ratio (HR) 3.4 (95% CI 1.0 to 12); score 6-7:HR 4.8 (1.3 to 18). Of the components of the ABCD2 score, unilateral motor weakness predicted both the primary outcome (HR 1.8 (1.2 to 2.8)) and stroke risk (HR 4.2 (1.3 to 14)). CONCLUSIONS: In patients attending typical NHS TIA services, the risk of incident stroke was relatively low, probably reflecting delays to assessment. Current provision of TIA services, where delayed presentation to ''rapid access'' TIA clinics is common, does not appear to provide an appropriate setting for urgent evaluation, risk stratification or timely secondary prevention for those who may be at highest risk. [Abstract]

Sarker SJ, Heuschmann PU, Burger I, Wolfe CD, Rudd AG, Smeeton NC, Toschke AM
Predictors of survival after haemorrhagic stroke in a multi-ethnic population: The South London Stroke Register (SLSR).
J Neurol Neurosurg Psychiatry. 2007 Nov 23;
OBJECTIVES: To identify the predictors of long-term survival after haemorrhagic stroke. METHODS: Data were collected within the population-based South London Stroke Register covering a multiethnic source population of 271,817 inhabitants (2001) in South London. Death data were collected at post stroke follow-up. The impact of patients' demographic and clinical characteristics, ethnic origin, pre-stroke risk factors, and acute treatment on long-term survival were investigated. Survival methods included Kaplan-Meier curves and Cox's proportional hazards model. RESULTS: Between January 1995 and December 2004 a total of 566 patients with first ever-haemorrhagic stroke (395 primary intracerebral haemorrhage; 171 subarachnoid haemorrhage) were registered. Mean age was 62.3 years; 365 (64.5%) were white, 132 (23.3%) of black and 69 (12.2%) of other or unknown ethnic origin; there were 1340 person-years of follow up. After multivariable adjustment, age (p<0.001) and having diabetes (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.06-2.70) were associated with increased risk of death. Patients with severe stroke (Glasgow Coma Scale (GCS) < 9) had an increased risk of death (HR, 6.5; 95% CI, 4.68-8.90) compared to those with mild stroke (GCS>12). Treatment on a stroke unit reduced long-term risk of death (HR, 0.70; 95% CI, 0.50-0.98). Black patients had a reduced risk of death (HR, 0.62; 95% CI, 0.42-0.92) compared to white patients. CONCLUSIONS: Age, diabetes, stroke severity and stroke unit care influenced long-term risk of death after haemorrhagic stroke. An independent survival advantage was observed in black patients. These factors can be utilised for clinical predictions but the cause of the observations in black patients remain unclear. [Abstract]

Thompson SA, Calvin J, Hogg S, Ferdinandusse S, Wanders RJ, Barker RA
Relapsing encephalopathy in a patient with {alpha}-methylacyl-CoA racemase deficiency.
J Neurol Neurosurg Psychiatry. 2007 Nov 21;
alpha-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder of fatty acid metabolism which has recently been described in three adult cases. We have identified a further patient with clinical features of a relapsing encephalopathy, seizures and cognitive decline over a 40 year period. Biochemical studies revealed grossly elevated plasma pristanic acid levels, and a deficiency of AMACR in skin fibroblasts. Sequence analysis of AMACR cDNA identified a homozygous point mutation (c.154T>C). This case adds to the phenotypic variation seen in this peroxisomal disorder and highlights the importance of screening for plasma pristanic acid levels in patients with unexplained relapsing encephalopathies. [Abstract]

Dupont S, Samson S, Baulac M
Is anterior temporal lobectomy a precipitating factor for transient global amnesia?
J Neurol Neurosurg Psychiatry. 2007 Nov 21;
Little is known about the pathophysiology of transient global amnesia (TGA) and how it is related to epilepsy. We report here five typical episodes of TGA, each occurring several years after surgery for epilepsy. In all cases patients were seizure free after a surgery consisting of anterior temporal lobectomy for refractory medial temporal lobe epilepsy associated with hippocampal sclerosis (n=4) or linked with a dysembryoplastic neuroepithelial tumour (n=1). Investigations, including MRI or CT-scan, angio-MRI or echocardiogram or vascular echo Doppler, excluded a vascular origin . Using accepted criteria to distinguish between TGA and epileptic amnesic attacks, the typical clinical presentation, the long duration of the episode, the absence of other symptoms associated with seizures and the absence of recurrence, all argue that these patients suffered a TGA . These studies suggest that hippocampal resection carried out therapeutically in some epileptic patients may be a precipitating factor for TGA. [Abstract]

Punt TD, Kitadono K, Hulleman J, Humphreys GW, Riddoch MJ
From both sides now: crossover effects influence navigation in patients with unilateral neglect.
J Neurol Neurosurg Psychiatry. 2007 Nov 21;
Unilateral neglect is a challenging disorder that pervades a range of behaviours following stroke and hampers recovery. While a preponderance of clinical studies measure performance on a range of bedside assessments including line bisection and cancellation tasks, there have been calls for studies to embrace more relevant functional measures. Here, for the fist time, we present data from two separate tasks that characterise the performance of seven patients with unilateral neglect when navigating a power chair. The tasks involved negotiating an obstacle course and steering a central path between gaps of different sizes. Results from the obstacle course confirmed the clinical observation and predicted bias of contralesional errors. However, the second task revealed a robust 'crossover' effect. Patients deviated to the ipsilesional side for large gaps but deviated increasingly contralesionally when steering through small gaps in behaviour analogous to that previously shown on line bisection tasks. Contrary to being seen as an unintuitive finding, further analysis of these errors suggest patients are giving disproportionate weight to the location of the ipsilesional object when plotting a midline course between two objects. Our results provide a platform for further studies to investigate the modulation and rehabilitation of this important skill. [Abstract]

Seki M, Suzuki S, Iizuka T, Shimizu T, Nihei Y, Suzuki N, Dalmau J
Neurological response to early removal of ovarian teratoma in anti-NMDAR encephalitis.
J Neurol Neurosurg Psychiatry. 2007 Nov 21;
We report an 18-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, who developed psychiatric symptoms, progressive unresponsiveness, dyskinesias, hypoventilation, hypersalivation and seizures. Early removal of an ovarian teratoma followed by plasma exchange and corticosteroids resulted in a prompt neurological response and eventual full recovery. Serial analysis of antibodies to NR1/NR2B heteromers of the NMDAR showed an early decrease of serum titers, although the CSF titers correlated better with clinical outcome. Patientï¿(1/2)fs antibodies reacted with areas of the tumor that contained NMDAR-expressing tissue. Search for and removal of a teratoma should be promptly considered after the diagnosis of anti-NMDAR encephalitis. [Abstract]

Anheim M, Hannequin D, Boulay C, Martin C, Campion D, Tranchant C
Ataxic variant of Alzheimer's disease caused by Pro117Ala PSEN1 mutation.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Krasnianski M, Tacik P, Müller T, Zierz S
Attenuation of Kernig's sign by concomitant hemiparesis: forgotten aspects of a well known clinical test.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Junna MR, Rabinstein AA
Tacrolimus induced leukoencephalopathy presenting with status epilepticus and prolonged coma.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Krim E, Guehl D, Burbaud P, Lagueny A
Retrobulbar optic neuritis: a complication of Lyme disease?
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Werner P, Furtner M, Löscher WN, Gotwald T, Piza-Katzer H
A case of posterior interosseous nerve palsy: good recovery despite diagnostic delay.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Ahn JY, Cho JH, Lee JW
Distal lenticulostriate artery aneurysm in deep intracerebral haemorrhage.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):
Aneurysms of the distal lenticulostriate artery (LSA) are rare. Only 16 cases have been reported in the literature. Early detection and treatment of these aneurysms is also difficult because of their deep location, small size and angioarchitecture. We report two additional patients with aneurysms, arising from the distal LSA, who presented with deep intracerebral haemorrhage. The conclusions drawn from our experience and a comprehensive review of the literature include the following. (1) A distal LSA aneurysm should be considered in young (mean 38.5 years) and non-hypertensive (80%) patients with deep intracerebral haemorrhage. (2) These aneurysms are frequently very small (<5 mm). Therefore, they cannot be detected on initial angiograms in some cases. (3) These aneurysms have higher rates of associated vascular lesions. Deep intracerebral haemorrhage, even in those over the age of 50 years, can still be due to underlying, treatable structural abnormalities, and should not be dismissed as being a result of hypertension. In addition, a more comprehensive diagnostic approach seems to be warranted in younger patients and those without known hypertension. [Abstract]

Reid JM, Gubitz GJ, Dai D, Reidy Y, Christian C, Counsell C, Dennis M, Phillips SJ
External validation of a six simple variable model of stroke outcome and verification in hyper-acute stroke.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):
We aimed to validate a previously described six simple variable (SSV) model that was developed from acute and sub-acute stroke patients in our population that included hyper-acute stroke patients. A Stroke Outcome Study enrolled patients from 2001 to 2002. Functional status was assessed at 6 months using the modified Rankin Scale (mRS). SSV model performance was tested in our cohort. 538 acute ischaemic (87%) and haemorrhagic stroke patients were enrolled, 51% of whom presented to hospital within 6 h of symptom recognition. At 6 months post-stroke, 42% of patients had a good outcome (mRS < or = 2). Stroke patients presenting within 6 h of symptom recognition were significantly older with higher stroke severity. In our Stroke Outcome Study dataset, the SSV model had an area under the curve of 0.792 for 6 month outcomes and performed well for hyper-acute or post-acute stroke, age < or > or = 75 years, haemorrhagic or ischaemic stroke, men or women, moderate and severe stroke, but poorly for mild stroke. This study confirms the external validity of the SSV model in our hospital stroke population. This model can therefore be utilised for stratification in acute and hyper-acute stroke trials. [Abstract]

Giaccone G, Di Fede G, Mangieri M, Limido L, Capobianco R, Suardi S, Grisoli M, Binelli S, Fociani P, Bugiani O, Tagliavini F
A novel phenotype of sporadic Creutzfeldt-Jakob disease.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):
An atypical case of sporadic Creutzfeldt-Jakob disease (CJD) is described in a 78-year-old woman homozygous for methionine at codon 129 of the prion protein (PrP) gene. The neuropathological signature was the presence of PrP immunoreactive plaque-like deposits in the cerebral cortex, striatum and thalamus. Western blot analysis showed a profile of the pathological form of PrP (PrP(Sc)) previously unrecognised in sporadic CJD, marked by the absence of diglycosylated protease resistant species. These features define a novel neuropathological and molecular CJD phenotype. [Abstract]

Bogousslavsky J
Memory after Charcot: Paul Sollier's visionary work.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Yoon SS, Park KC
Neurological picture. Glossoplegia in a small cortical infarction.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Tahir M, Das CJ, Ahmad FU, Ahmad H
Neurological picture. Dorsal intramedullary tuberculoma.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Stores G
Clinical diagnosis and misdiagnosis of sleep disorders.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):
Sleep disorders are common in all sections of the population and are either the main clinical complaint or a frequent complication of many conditions for which patients are seen in primary care or specialist services. However, the subject is poorly covered in medical education. A major consequence is that the manifestations of the many sleep disorders now identified are likely to be misinterpreted as other clinical conditions of a physical or psychological nature, especially neurological or psychiatric disorders. To illustrate this problem, examples are provided of the various possible causes of sleep loss, poor quality sleep, excessive daytime sleepiness and episodes of disturbed behaviour at night (parasomnias). All of these sleep disorders can adversely affect mental state and behaviour, daytime performance or physical health, the true cause of which needs to be recognised by clinicians to ensure that appropriate treatment is provided. As conventional history taking in neurology and psychiatry pays little attention to sleep and its possible disorders, suggestions are made concerning the enquiries that could be included in history taking schedules to increase the likelihood that sleep disorders will be correctly identified. [Abstract]

Ricci S
Identification of "high risk" asymptomatic carotid stenosis: we need to get a better yield from invasive treatments.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Tang TY, Howarth SP, Miller SR, Graves MJ, U-King-Im JM, Trivedi RA, Li ZY, Walsh SR, Brown AP, Kirkpatrick PJ, Gaunt ME, Gillard JH
Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques contralateral to symptomatic carotid stenosis: an ultra small superparamagnetic iron oxide enhanced magnetic resonance study.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):
BACKGROUND: Inflammation is a recognised risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of magnetic resonance (MR) defined inflammation using ultra small superparamagnetic iron oxide (USPIO) particles within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis contralateral to the symptomatic side. METHODS: 20 symptomatic patients with contralateral disease and 20 completely asymptomatic patients underwent multi-sequence MR imaging before and 36 h after USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant was calculated following USPIO administration. Mean signal change was compared across all quadrants in the two groups. RESULTS: The mean percentage of quadrants showing signal loss was 53% in the contralateral group compared with 31% in completely asymptomatic individuals (p = 0.025). The mean percentages showing enhancement were 44% and 65%, respectively (p = 0.024). The mean signal difference between the two groups was 8.6% (95% CI 1.6% to 15.6%; p = 0.017). CONCLUSIONS: Truly asymptomatic plaques seem to demonstrate inflammation but not to the extent of the contralateral asymptomatic stenosis to the symptomatic side. Inflammatory activity may be a significant risk factor in asymptomatic disease. [Abstract]

Connor M
Stroke in patients with human immunodeficiency virus infection.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12): [Abstract]

Tipping B, de Villiers L, Wainwright H, Candy S, Bryer A
Stroke in patients with human immunodeficiency virus infection.
J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):
OBJECTIVE: To report the nature of stroke in patients infected with human immunodeficiency virus (HIV) in a region with high HIV seroprevalence and describe HIV associated vasculopathy. METHODS: Patients with first ever stroke, infected with HIV and prospectively included in the stroke register of the Groote Schuur Hospital/University of Cape Town stroke unit were identified and reviewed. RESULTS: Between 2000 and 2006, 67 of the 1087 (6.1%) stroke patients were HIV infected. Of these, 91% (n = 61) were younger than 46 years. Cerebral infarction occurred in 96% (n = 64) of the HIV positive patients and intracerebral haemorrhage in 4% (n = 3). HIV infected young stroke patients did not demonstrate hypertension, diabetes, hyperlipidaemia or smoking as significant risk factors for ischaemic stroke. Infection as a risk factor for stroke was significantly more common in HIV positive patients (p = 0.018, OR 6.4, CI 3.1 to 13.2). In 52 (81%) patients with ischaemic stroke, an aetiology was determined. Primary aetiologies comprised infectious meningitides/vasculitides in 18 (28%) patients, coagulopathy in 12 (19%) patients and cardioembolism in nine (14%) patients. Multiple aetiologies were present in seven (11%) patients with ischaemic stroke. HIV associated vasculopathy was identified in 13 (20%) patients. The HIV associated vasculopathy manifested either extracranially (seven patients) as total or significant carotid occlusion or intracranially (six patients) as medium vessel occlusion, with or without fusiform aneurysmal dilation, stenosis and vessel calibre variation. CONCLUSION: Investigation of HIV infected patients presenting with stroke will determine an aetiology in the majority of patients. In our cohort, 20% of patients demonstrated evidence of an HIV associated vasculopathy. [Abstract]

Powell HW, Parker GJ, Alexander DC, Symms MR, Boulby PA, Barker GJ, Thompson PJ, Koepp MJ, Duncan JS
Imaging language pathways predicts postoperative naming deficits.
J Neurol Neurosurg Psychiatry. 2007 Nov 15;
Naming difficulties are a well recognised, but difficult to predict, complication of anterior temporal lobe resection (ATLR) for refractory epilepsy. We used magnetic resonance (MR) tractography pre-operatively to demonstrate the structural connectivity of language areas in patients undergoing dominant hemisphere ATLR. Greater lateralisation of tracts to the dominant hemisphere was associated with greater decline in naming function. We suggest that this method has the potential to predict language deficits in patients undergoing ATLR. [Abstract]

Wu T, Hallett M
Neural correlates of dual task performance in patients with Parkinson's disease.
J Neurol Neurosurg Psychiatry. 2007 Nov 15;
BACKGROUND: Patients with Parkinson inverted exclamation marks disease (PD) have great difficulty in performing two tasks simultaneously, but the neural contribution to the problem has not been identified. In the current study, we investigated the pathophysiology of dual task performance in PD. METHODS: We studied 15 PD patients and 14 healthy controls. Functional MRIs were applied before and after practicing dual tasks with different complexity. RESULTS: After practice, 12 normal subjects performed all dual tasks correctly. 12 patients performed the simpler dual tasks correctly. However, only 3 patients could perform the more complex dual task correctly. Dual tasks activated similar brain regions in both groups. The bilateral precuneus was additionally activated during performance of dual tasks compared to the component tasks in both groups. Patients had greater activity in the cerebellum, premotor area, parietal cortex, precuneus, and prefrontal cortex compared to normal subjects. CONCLUSIONS: Difficulty in performing two tasks simultaneously in PD patients is likely due to limited attentional resources, defective central executive function, and less automaticity in performing the tasks. Practice can diminish dual task interference and improve performance in PD patients. [Abstract]

Tomkins O, Shelef I, Kaizerman I, Misk A, Afawi Z, Eliushin A, Gidon M, Cohen A, Zumsteg D, Friedman A
Blood-Brain Barrier Disruption in Post-Traumatic Epilepsy.
J Neurol Neurosurg Psychiatry. 2007 Nov 15;
BACKGROUND: Traumatic brain injury (TBI) is an important cause of focal epilepsy. Animal experiments indicate that disruption of the blood-brain barrier (BBB) plays a critical role in the pathogenesis of post-traumatic epilepsy (PTE). OBJECTIVE: To investigate the frequency, extent and functional correlates of increased BBB permeability following in PTE patients. METHODS: 32 head trauma patients were included in the study, with 17 suffering from PTE. Patients underwent brain magnetic resonance imaging (bMRI) and were evaluated for BBB disruption, using a novel semi-quantitative technique. Cortical dysfunction was measured using electroencephalography (EEG), and localized using standardized low resolution brain electromagnetic tomography (sLORETA). RESULTS: Spectral EEG analyses revealed significant slowing in TBI patients with no significant differences between epileptic and non-epileptic patients. While bMRI revealed that PTE patients were more likely to present with intracortical lesions (p=0.02), no differences in the size of the lesion were found between the groups (p=0.19). Increased BBB permeability was found in 76.9% of PTE compared to 33.3% of non-epileptic patients (p=0.047), and could be observed years following the trauma. Cerebral cortex volume with BBB disruption was larger in PTE patients (p=0.001). In 70% of patients, slow (delta band) activity was co-localized, by sLORETA, with regions showing BBB disruption. CONCLUSIONS: Lasting BBB pathology is common in mild TBI patients, with increased frequency and extent in PTE patients. A correlation between disrupted BBB and abnormal neuronal activity is suggested. [Abstract]

Recent Articles in Neurosurgery

Mut M, Dinç G, Naderi S
On the report of the first successful surgical treatment of brain abscess in the Ottoman Empire by Dr. Cemil Topuzlu in 1891.
Neurosurgery. 2007 Oct;61(4):869-72; discussion 872.
IN 1891, Dr. Cemil Topuzlu operated on a brain abscess that originated as a complication of a depression fracture of the cranial inner table. The patient presented with Jacksonian seizures on his left side after a sharp trauma resulting in a 15 cm-long scalp laceration and underlying linear cranial fracture in the right parietal bone. Dr. Topuzlu attributed Jacksonian epilepsy to the fracture irritating the motor area in the right hemisphere and attempted a craniotomy based on his measurements to localize the Rolandic fissure. The operation was complicated by a brain abscess, and Dr. Topuzlu reoperated to drain the abscess. He successfully treated the brain abscess and Jacksonian seizures and then presented this case in the Royal Society of Medicine of the Ottoman Empire and in the International Surgery Congress in Lyon in 1894. The case report was published in his surgery book in 1905. The case was not only the first case of brain abscess to be treated successfully with surgical intervention in the Ottoman Empire, it was also one of the first cases of neurological surgery performed using contemporary anesthesiological and surgical techniques, which reveals the importance of neurological examination and cerebral localization techniques in the era before x-rays. Dr. Topuzlu was the founder of modern surgery in the Ottoman Empire and deserves to be credited for his novel applications in the 19th century. [Abstract]

Lindholm J
A century of pituitary surgery: Schloffer's legacy.
Neurosurgery. 2007 Oct;61(4):865-7; discussion 867-8.
Although pituitary tumors were well recognized by the end of the 20th century, very few surgeons had attempted to remove such tumors. In 1906, Hermann Schloffer at the Innsbruck University Clinic of Surgery reviewed the subject of pituitary surgery. Very little was known about the function of the pituitary, and no reports had yet been published on attempts to surgically remove pituitary neoplasms. Schloffer pointed out that ophthalmological symptoms evidently reflected mass effect of the tumor and, hence, resection of the tumor would be beneficial. He also proposed a transsphenoidal approach to the sella, although he was well aware of the risk of meningitis associated with this procedure. On March 16, 1907, Schloffer performed the first transsphenoidal operation for a pituitary adenoma. Unfortunately, the patient died 2 months later from a large residual tumor. Within a few years, several patients had undergone operation with procedures similar to the one described by Schloffer, several of whom experienced acromegaly, thus introducing neurosurgery as routine therapy for acromegaly and settling the long debate on the etiology of acromegaly. [Abstract]

Schirmer CM, Malek AM
Wall shear stress gradient analysis within an idealized stenosis using non-Newtonian flow.
Neurosurgery. 2007 Oct;61(4):853-63; discussion 863-4.
OBJECTIVE: The endothelium is functionally regulated by the magnitude and spatiotemporal gradients of wall shear stress (WSS). Although flow separation and reversal occur beyond high-grade stenoses, little is known of the WSS pattern within clinically relevant mild to moderate stenoses. METHODS: An axisymmetric geometry with 25, 50, and 75% stenosis criteria (quantified in accordance with the North American Symptomatic Carotid Endarterectomy Trial) was used to generate a high-resolution, hybrid, tetrahedral-hexahedral computational mesh with boundary-layer enrichment to improve near-wall shear stress gradient (WSSG) computation. Time-dependent computational fluid dynamic analysis was performed using a non-Newtonian Carreau-Yasuda model of blood to yield the shear-dependent viscosity. RESULTS: Transition to secondary flow patterns was demonstrated in stenoses of 25, 50, and 75%. A focal region with near-wall flow reversal and retrograde WSS was identified within the stenosis itself and was found to migrate cyclically during the cardiac pulse. A zone of zero WSS and divergent WSSG that shifts in toward the throat with increasing stenotic severity was identified. Focal zones of high WSSG with converging and/or diverging direction were uncovered within the stenosis itself, as were expected changes in the distal poststenotic region. These zones of divergent WSSG shift over a substantial length of the stenosis during the course of the cardiac cycle. CONCLUSION: Luminal WSS demonstrates dynamic direction reversal and high spatial gradients within the distal stenosis throat of even clinically moderate lesions. These findings shed light on the complex vessel wall hemodynamics within clinical stenoses and reveal a mechanical microenvironment that is conducive to perpetual endothelial functional dysregulation and stenosis progression. [Abstract]

Schirmer CM, Malek AM
Prediction of complex flow patterns in intracranial atherosclerotic disease using computational fluid dynamics.
Neurosurgery. 2007 Oct;61(4):842-51; discussion 852.
OBJECTIVE: Although carotid and vertebral intracranial atherosclerotic disease (ICAD) can lead to both hemodynamic insufficiency and thromboembolism, its fluid dynamic properties remain undefined because of its intricate features and complex three-dimensional geometry. We used computational fluid dynamic (CFD) analysis to model the hemodynamics of symptomatic ICAD lesions. METHODS: Nine ICAD lesions (six carotid, two vertebral, one middle cerebral) underwent high-resolution catheter-based digital rotational angiography. The reconstructed three-dimensional volumes of the target lesions were segmented and used to generate hybrid computational meshes. Dynamic pulsatile CFD analysis was performed using a non-Newtonian shear-dependent model of blood's viscosity. RESULTS: CFD results revealed complex flow patterns within ICAD lesions with midstenotic shear rates of greater than 19,000/s, sufficiently high to induce high-shear platelet activation. Vorticity and helicity within the stenoses were followed by sudden deceleration with formation of vortex cores. Pressure gradients were significant mostly at greater than 75% stenosis with a mean time-averaged drop of 27.2 +/-17.8 mmHg. Unlike the smoothly-varying helicity imparted by the three-dimensional anatomy of the intracranial circulation, poststenotic regions of ICAD lesions showed significant and rapidly fluctuating helicity and vorticity patterns, which may contribute to the propagation of platelets activated by the high shear region within the stenosis throat. Stent angioplasty restored the hemodynamic profile of ICAD lesions to within contralateral controls. CONCLUSION: Patient-based symptomatic ICAD lesions studied using CFD analysis appear to harbor a hemodynamically pathological environment that favors the activation, aggregation and distal embolization of platelets and is reversed by endovascular stent angioplasty. [Abstract]

Bendok BR, Parkinson RJ, Hage ZA, Adel JG, Gounis MJ
The effect of vascular reconstruction device-assisted coiling on packing density, effective neck coverage, and angiographic outcome: an in vitro study.
Neurosurgery. 2007 Oct;61(4):835-40; discussion 840-1.
OBJECTIVE: The objective of this study was to assess the variations in packing density, effective neck coverage, and angiographic outcome between aneurysm coiling alone and with the support of the Enterprise Vascular Reconstruction Device (VRD; Cordis Neurovascular, Inc., Miami Lakes, FL). Although the use of VRD-assisted coiling is growing due to the availability of better devices, little is known about the impact of the VRDs on the aforesaid variables. METHODS: Ten groups of two silicone aneurysm models each were embolized with detachable coils, one with VRD support and one without. Coil embolization ceased once the microcatheter backed out of the aneurysm or there was a risk that further packing would lead to coil herniation. Angiograms were assessed using the Raymond classification scale. Gross macroscopic images of the aneurysm neck were taken to quantify the coil neck coverage, defined as the surface area fraction of coils at the neck divided by the total neck area. Packing density was calculated. RESULTS: Packing density significantly increased with VRD assistance (absolute increase, 10.5%; relative increase, 31%; P < 0.0001, paired t test). Effective neck coverage significantly increased by 9% with VRD deployment (P < 0.05, t test). Angiographically, aneurysms coiled without VRD support were more likely to have a dome remnant (P < 0.05, Fisher's exact test) and coil prolapse into the parent vessel. CONCLUSION: VRD deployment improves coil neck coverage and increases packing density. These results support the hypothesis that VRD deployment to reinforce coil embolization of cerebral aneurysms may lead to more durable aneurysm obliteration. [Abstract]

Beck J, Stummer W, Lehmberg J, Baethmann A, Uhl E
Arteriovenous transit time as a measure for microvascular perfusion in cerebral ischemia and reperfusion.
Neurosurgery. 2007 Oct;61(4):826-33; discussion 833-4.
OBJECTIVE: The aim of this study was to measure microvascular perfusion (MVP) on the brain surface in global ischemia and reperfusion by means of intravital fluorescence microscopy. METHODS: Global ischemia was induced in gerbils for 15 minutes with 3 hours of reperfusion. The passage of a rhodamine bolus (25 mul intravenously) from an arteriole to a venule was analyzed by intravital fluorescence microscopy through a cranial window. After the changes of fluorescence intensities in an arteriole and venule, the arteriovenous transit time and the MVP were calculated using the integral difference method. Additionally, regional cerebral blood flow was assessed by laser Doppler flowmetry and vessel diameters and blood pressure were recorded. RESULTS: The baseline mean MVP was 2.21 +/- 0.89 sec(-1) in the control group, remaining stable throughout observation in sham operated animals. In ischemic animals, the MVP was 2.11 +/- 0.47 sec(-1) at baseline, showing a significant decrease during ischemia to 0.07 +/- 0.16 sec(-1) (3%; P < 0.01). There was postischemic maximum hyperperfusion of 2.72 +/- 0.40 sec(-1) (134 +/- 11%; P < 0.05) at 15.4 +/- 6.9 minutes and hypoperfusion of 1.63 +/- 0.57 sec(-1) (77 +/- 13%; P = 0.19) at 36.6 +/- 16.4 minutes. There was a strong, significant correlation between MVP and regional cerebral blood flow (R = 0.82; P < 0.0001). CONCLUSION: MVP on the brain surface can be calculated from the transit time of a dye bolus from an arteriole to a venule. MVP shows a high correlation to regional cerebral blood flow. The assessment of MVP allows one to easily and repeatedly quantify perfusion changes of the microvascular network on the brain surface. [Abstract]

Deogaonkar M, Walter BL, Boulis N, Starr P
Clinical problem solving: finding the target.
Neurosurgery. 2007 Oct;61(4):815-24; discussion 824-5. [Abstract]

Proubasta IR, Lluch A, Lamas CG, Oller BT, Itarte JP
"Fat pad" and "little finger pulp" signs are good indicators of proper release of carpal tunnel.
Neurosurgery. 2007 Oct;61(4):810-3; discussion 813-4.
OBJECTIVE: The release of the transverse carpal ligament (TCL) for relief of carpal tunnel syndrome has been a standard operative procedure since the early 1950s. Although complications are not common after the open surgical technique, a small but significant group of patients will have similar symptoms after surgery or will experience new symptoms in the postoperative period. Incomplete section of the TCL is the major cause of these complications. The authors have described two signs that confirm a complete release of the TCL, called the "fat pad" and "little finger pulp" signs. METHODS: Between 2000 and 2003, we treated 643 hands in 611 patients (45 men and 566 women; age range, 32-76 yr; mean age, 58.2 yr). All patients were examined 6 months after the procedure, with special attention given to the persistence or recurrence of symptoms. The presence of palmar scar pain, residual numbness, patient satisfaction, and time to return to work were also evaluated. A longitudinal incision (2 cm) at the base of the palm was used to release the TCL. A good indicator that the distal TCL has been released is the visualization of a fatty tissue ("fat pad" sign). This fatty tissue is always present underneath the most distal fibers of the TCL, covering the sensory digital branches of the median nerve. To confirm the complete release of the proximal fibers of the TCL, we should be able to introduce the little finger pulp in a proximal direction underneath the distal flexion crease of the wrist ("little finger pulp" sign). When both signs are confirmed, we can be certain that the TCL is completely released. RESULTS: Night pain disappeared immediately after surgery in all patients except three. There were seven complications (1%) not related to the palmar scar and 10 complications (1.5%) related to it. However, all of these complications disappeared an average of 3 months postoperatively. Patient satisfaction was 100%, and the mean time to return to work and full activity was 22 days (range, 14-36 d). CONCLUSION: Two surgical observations that are reliable to confirm a complete release of the TCL were described. The first, called the "fat pad" sign, is useful to determine whether or not the distal end of the TCL has been adequately released, whereas the "little finger pulp" sign indicates whether or not the proximal end of the TCL has been fully divided. [Abstract]

Scheufler KM
Technique and clinical results of minimally invasive reconstruction and stabilization of the thoracic and thoracolumbar spine with expandable cages and ventrolateral plate fixation.
Neurosurgery. 2007 Oct;61(4):798-808; discussion 808-9.
OBJECTIVE: To evaluate the techniques of minimally invasive single- and multilevel corpectomy and reconstruction of the thoracic and thoracolumbar spine using expandable vertebral body replacement (VBR) cages and ventrolateral plate fixation (VPF) via anterolateral retropleural (ALRA) and combined thoracoabdominal approaches. METHODS: 38 patients with spondylitis, traumatic or metastatic lesions of thoracic or thoracolumbar vertebrae T4 to L2 underwent spinal decompression and ventral column reconstruction with correction of spinal deformity by VBR and VPF via ALRA or a combined lateral extrapleural/extraperitoneal (extracoelomic) thoracolumbar approach (CLETA). Overall clinical and neurological outcome, operative time, blood loss, reduction of deformity, and postoperative pain were assessed during a mean follow-up period of 22.8 months. RESULTS: VBR and VPF were carried out successfully without conversion to conventional approaches in all patients. Mean operative time (ALRA, 163 +/- 33 min; CLETA, 175 +/- 39 min), mean blood loss (ALRA, 280 +/- 160 ml; CLETA, 420 +/- 250 ml), average correction (19.3 degrees), loss of correction of sagittal deformity (0.9 degrees), and clinical outcome compare favorably to the results reported for open and endoscopic techniques. Postoperative pain levels (mean visual analog scale score at 24 h, 2.7 +/- 0.9) and the incidence of postoperative pulmonary dysfunction (three out of 38 patients) were low. The average length of stay was 7.4 days. ALRA and CLETA obviate routine chest tube insertion, thus allowing for early postoperative ambulation (average, 1.1 d). CONCLUSION: Minimally invasive VBR and VPF conducted via minimally invasive approaches (ALRA or CLETA) yields favorable clinical results at least equal to conventional open surgery, with significant reductions in perioperative morbidity and pain, expedited ambulation, and early discharge from the hospital. [Abstract]

Abouzari M, Rashidi A, Rezaii J, Esfandiari K, Asadollahi M, Aleali H, Abdollahzadeh M
The role of postoperative patient posture in the recurrence of traumatic chronic subdural hematoma after burr-hole surgery.
Neurosurgery. 2007 Oct;61(4):794-7; discussion 797.
OBJECTIVE: Chronic subdural hematoma (CSDH) is one of the most common types of intracranial hemorrhage, especially in the elderly, with a significant recurrence rate ranging from 9.2 to 26.5%. The role of postoperative patient posture in the recurrence of CSDH has not been studied sufficiently. METHODS: A total of 84 consecutive patients with unilateral traumatic CSDH without known risk factors of CSDH recurrence were prospectively enrolled in this study. All patients underwent burr-hole surgery with closed system drainage and were then allocated randomly to either of two groups: Group A (n = 42) patients were kept in a supine position for 3 days after the operation, whereas Group B (n = 42) patients assumed a sitting position in bed, with the head of the bed elevated to 30 to 40 degrees, for the same duration as Group A. After 3 days, there was no restriction in patients' activities in both groups. All patients were followed-up for at least 3 months after surgery. RESULTS: The groups were not significantly different in age, sex, presence of brain atrophy or hydrocephalus, preoperative hematoma width, and postsurgery subdural space width. The recurrence rate in Groups A and B were 2.3 and 19.0% (necessitating repeat surgery in one patient), respectively (P = 0.02). Other complications in Groups A and B, respectively, were atelectasis (10 versus seven; P = 0.41), pneumonia (five versus four; P = 0.72), decubitus ulcer (three versus two; P = 0.64), and deep vein thrombosis (zero versus one; P = 0.31). CONCLUSION: Assuming an upright posture soon after burr-hole surgery was associated with a significantly increased incidence of CSDH recurrence but not with a significant change in other position-related postsurgical complications. According to this result, it is not recommended that elderly patients assume an upright posture soon after burr-hole surgery to prevent postoperative atelectasis and dementia, as these might significantly increase the risk of CSDH recurrence. [Abstract]

Weigel R, Hohenstein A, Schlickum L, Weiss C, Schilling L
Angiotensin converting enzyme inhibition for arterial hypertension reduces the risk of recurrence in patients with chronic subdural hematoma possibly by an antiangiogenic mechanism.
Neurosurgery. 2007 Oct;61(4):788-92; discussion 792-3.
OBJECTIVE: Chronic subdural hematoma (CSH) is characterized by pathological vascularization of the parietal membrane. Plasma leakage from immature vessels may be involved in hematoma enlargement and recurrence. We tested the hypothesis that the antiangiogenic side-effect of angiotensin converting enzyme (ACE)-inhibitor treatment for the control of arterial hypertension reduces the risk of recurrence in CSH. METHODS: We analyzed the data of 438 patients with CSH treated by a standard surgical procedure for hematoma evacuation in our department between 1995 and 2003. Patients with coagulopathies, malignancies, and independent neurological disorders were excluded from this study. Patient records were screened for age, sex, pre- and postoperative Markwalder score, arterial hypertension, medication with ACE-inhibitors, and recurrence of CSH. The rate of ACE-inhibitor treatment in our CSH patients was compared with an age-matched control group treated for herniated lumbar disc at the same time. The concentration of vascular endothelial growth factor was analyzed in hematoma samples and corresponding venous blood in 40 consecutive patients. RESULTS: A total of 310 patients were included in this study. The demographic data of Group A (with ACE-inhibition) and Group B (without ACE-inhibition) were comparable. In Group A, 5% (four out of 81) of the patients experienced recurrence as opposed to 18% (42 out of 229) in Group B (P = 0.00345). A negative correlation was found between the yearly rates of medication with ACE-inhibitors and recurrence (r = -0.8488; P = 0.0044). The rate of ACE-inhibitor treatment was lower in the CSH patients (25%) than in the control group (40%). The VEGF content was significantly lower in the hematoma in patients with ACE-inhibition (mean, 8891 pg/ml; range, 4300-18,300 pg/ml) than in patients without (mean, 22,565 pg/ml; range, 4200-89,650 pg/ml; P = 0.0116). CONCLUSION: Our data suggest that ACE-inhibitor treatment for the control of arterial hypertension lowers the risk of recurrence in patients undergoing operation for CSH and possibly even the development of CSH. This effect might be the result of an antiangiogenic mechanism of ACE-inhibitors. [Abstract]

Jain R, Scarpace L, Ellika S, Schultz LR, Rock JP, Rosenblum ML, Patel SC, Lee TY, Mikkelsen T
First-pass perfusion computed tomography: initial experience in differentiating recurrent brain tumors from radiation effects and radiation necrosis.
Neurosurgery. 2007 Oct;61(4):778-86; discussion 786-7.
OBJECTIVE: To differentiate recurrent tumors from radiation effects and necrosis in patients with irradiated brain tumors using perfusion computed tomographic (PCT) imaging. METHODS: Twenty-two patients with previously treated brain tumors who showed recurrent or progressive enhancing lesions on follow-up magnetic resonance imaging scans and had a histopathological diagnosis underwent first-pass PCT imaging (26 PCT imaging examinations). Another eight patients with treatment-naïve, high-grade tumors (control group) also underwent PCT assessment. Perfusion maps of cerebral blood volume, cerebral blood flow, and mean transit time were generated at an Advantage Windows workstation using the CT perfusion 3.0 software (General Electric Medical Systems, Milwaukee, WI). Normalized ratios (normalized to normal white matter) of these perfusion parameters (normalized cerebral blood volume [nCBV], normalized cerebral blood flow [nCBF], and normalized mean transit time [nMTT]) were used for final analysis. RESULTS: Fourteen patients were diagnosed with recurrent tumor, and eight patients had radiation necrosis. There was a statistically significant difference between the two groups, with the recurrent tumor group showing higher mean nCBV (2.65 versus 1.10) and nCBF (2.73 versus 1.08) and shorter nMTT (0.71 versus 1.58) compared with the radiation necrosis group. For nCBV, a cutoff point of 1.65 was found to have a sensitivity of 83.3% and a specificity of 100% to diagnose recurrent tumor and radiation necrosis. Similar sensitivity and specificity were 94.4 and 87.5%, respectively, for nCBF with a cutoff point of 1.28 and 94.4 and 75%, respectively, for nMTT with a cutoff point of 1.44 to diagnose recurrent tumor and radiation necrosis. CONCLUSION: PCT may aid in differentiating recurrent tumors from radiation necrosis on the basis of various perfusion parameters. Recurrent tumors show higher nCBV and nCBF and lower nMTT compared with radiation necrosis. [Abstract]

Roche PH, Paris J, Régis J, Moulin G, Zanaret M, Thomassin JM, Pellet W
Management of invasive juvenile nasopharyngeal angiofibromas: the role of a multimodality approach.
Neurosurgery. 2007 Oct;61(4):768-77; discussion 777.
OBJECTIVE: Juvenile nasopharyngeal angiofibromas involving the cranial base and intracranial compartment are challenging tumors. We reviewed our experience of these tumors and analyzed the efficacy of a multimodality management. METHODS: Between 1981 and 2000, 15 extensive juvenile nasopharyngeal angiofibromas (Fisch Grade III or IV) were treated at our institution. The mean age of the patients was 14.5 years, and the mean interval between the first symptom and diagnosis was 12.9 months. Initial management included preoperative embolization of the external carotid artery feeders, followed by tumor removal. A maxillofacial procedure was performed in eight cases, a combination of maxillofacial and neurosurgical approach was performed in four cases, and a neurosurgical cranial base approach was performed in three cases. RESULTS: Total removal after the initial procedure was obtained in eight patients. Subtotal removal justified additional surgery in one case, gamma knife radiosurgery in two cases, and fractionated irradiation in four cases. True recurrences were observed in four cases at a mean interval of 37 months (range, 24-46 mo) and required tailored multimodality management. No cases of perioperative death were observed. One patient underwent hemiparesis after embolization in the early period of our experience. Permanent facial numbness was reported in four cases, moderate cosmetic problems were reported in three cases, and hyposmia was reported in three cases. Except for one patient who was lost to follow-up at 18 months, 12 patients were free of disease and two patients were free of tumor progression. All patients had normal or near-normal daily life at the last check-up, with a median follow-up period of 108 months (mean, 117 mo; range, 91-252 mo). CONCLUSION: Extensive juvenile nasopharyngeal angiofibromas are efficiently managed with a multimodal protocol in which preoperative embolization is followed by optimal surgical removal using various transcranial or transfacial approaches. Adjunctive gamma knife radiosurgery is a valuable option for intracavernous residual tumor. Our protocol offers long-term cure with acceptable morbidity. [Abstract]

Ullrich NJ, Raja AI, Irons MB, Kieran MW, Goumnerova L
Brainstem lesions in neurofibromatosis type 1.
Neurosurgery. 2007 Oct;61(4):762-6; discussion 766-7.
OBJECTIVE: The presence of multiple, nonenhancing areas of hyperintensity without mass effect are well recognized on magnetic resonance imaging scans in children with neurofibromatosis type 1 (NF1). Focal regions of brainstem enlargement with or without contrast enhancement are considerably less frequent; the neuroimaging characteristics and natural history of these lesions in patients with NF1 are poorly understood. The objective of this study was to define the clinical and radiographic course of brainstem lesions in children with NF1. METHODS: We retrospectively reviewed the neuroimaging studies of all patients with NF1 between 2000 and 2006 to determine the prevalence of brainstem lesions. Clinical features, previous treatments, and neuroimaging studies of the brainstem lesions were evaluated. RESULTS: A total of 125 patients underwent neuroimaging studies; of these, 23 patients (18.4%) showed evidence of brainstem mass lesions and had follow-up magnetic resonance imaging scans available for review. Eight patients in this cohort received additional treatment with surgery, radiation, or chemotherapy. Of these, two patients underwent surgery for lesions distant from the brainstem, and six patients underwent treatment that included the brainstem and were thought to potentially affect the natural history or progression of the brainstem abnormality. With a median follow-up period of 67 months for untreated patients (17 out of 23) and 102 months for patients who received therapy (six out of 23), only one previously untreated patient experienced radiographic and clinical progression. All patients but one remain alive. CONCLUSION: We conclude that brainstem lesions in NF1 are prevalent and behave in a biologically indolent nature; most do not require therapeutic intervention. [Abstract]

Aghi MK, Eskandar EN, Carter BS, Curry WT, Barker FG
Increased prevalence of obesity and obesity-related postoperative complications in male patients with meningiomas.
Neurosurgery. 2007 Oct;61(4):754-60; discussion 760-1.
OBJECTIVE: The female preponderance of meningiomas may reflect hormonal influences on meningioma growth. We hypothesized that because obesity affects male steroid hormone synthesis, male patients with meningiomas might exhibit a high obesity rate, which, in turn, might increase their frequency of postoperative complications. METHODS: We retrospectively reviewed male patients who underwent craniotomy for benign meningiomas at our institution between 2001 and 2005 (n = 32) and used male patients undergoing craniotomy for aneurysms (n = 32) or glioblastomas (n = 32) from 2001 to 2005 as control subjects. Body mass index (BMI) greater than 30 kg/m was considered obese. RESULTS: Male patients with meningiomas had a higher average BMI (30.2 kg/m) than male patients with aneurysms (BMI = 27.5 kg/m) or gliomas (BMI = 25.9 kg/m) (P = 0.04). The obesity rate in men with meningiomas (47%) exceeded that in men with aneurysms (19%) or gliomas (3%) (P = 0.2). The median age-normalized BMI percentile was greater in men with meningiomas (67 th percentile) than in men with aneurysms (49th percentile) or gliomas (52 nd percentile) (P = 0.02). Deep vein thrombosis/pulmonary embolus was more common in men with meningiomas (19%) than in men with aneurysms (0%) or gliomas (3%) (P = 0.002). Wound infections were more common in men with meningiomas (6%) than in men with aneurysms (3%) or gliomas (0%) (P = 0.2). The 53% of obese patients with meningiomas who were readmitted with postoperative complications exceeded the 18% of nonobese patients with meningiomas who were readmitted (P = 0.03); complications included deep vein thrombosis and pulmonary embolus (27 and 12%, respectively, in obese and nonobese patients with meningiomas) and postoperative fever (53 and 35%, respectively, in obese and nonobese patients with meningiomas). CONCLUSION: We found that many men with meningiomas are obese, suggesting a hormonal influence on meningiomas in men as well as women. Our results also underscore the high risk of postoperative complications in obese male patients with meningiomas. [Abstract]

Benzagmout M, Gatignol P, Duffau H
Resection of World Health Organization Grade II gliomas involving Broca's area: methodological and functional considerations.
Neurosurgery. 2007 Oct;61(4):741-52; discussion 752-3.
OBJECTIVE: Advances in functional mapping have enabled us to extend the indications of surgery for low-grade gliomas (LGGs) within eloquent regions. However, to our knowledge, no study has been specifically dedicated to the resection of LGGs within Broca's area. We report the first surgical series of LGGs involving this area by focusing on methodological and functional considerations. METHODS: Seven patients harboring an LGG in Broca's area (revealed by partial seizures) had a language functional magnetic resonance imaging scan and then underwent operation while awake using intrasurgical electrical mapping. RESULTS: The neurological examination was normal in all patients despite mild language disturbances shown using the Boston Diagnosis Aphasia Examination. Both pre- and intraoperative cortical mapping found language reorganization with recruitment of the ventral and dorsal premotor cortices, orbitofrontal cortex, and insula, whereas no or few language sites were detected within Broca's area. Subcortically, electrostimulation allowed the identification and preservation of four structures still functional, including the arcuate fasciculus, fronto-occipital fasciculus, fibers from the ventral premotor cortex, and head of the caudate. Postoperatively, after transient language worsening, all patients recovered and returned to a normal socioprofessional life. The resection was total in three cases, subtotal in three, and partial in one patient (operated twice). CONCLUSION: Our results indicate that, in patients with no aphasia despite LGGs within Broca's area, thanks to brain plasticity, the tumor can be removed while involving this "unresectable" structure without inducing sequelae and even improving the quality of life when intractable epilepsy is relieved on the condition that subcortical language connectivity is preserved. [Abstract]

Achrol AS, Kim H, Pawlikowska L, Trudy Poon KY, McCulloch CE, Ko NU, Johnston SC, McDermott MW, Zaroff JG, Lawton MT, Kwok PY, Young WL
Association of tumor necrosis factor-alpha-238G>A and Apolipoprotein E2 polymorphisms with intracranial hemorrhage after brain arteriovenous malformation treatment.
Neurosurgery. 2007 Oct;61(4):731-9; discussion 740.
OBJECTIVE: We previously reported specific genotypes of polymorphisms in two genes, tumor necrosis factor-alpha (TNF-alpha-238G > A) and Apolipoprotein E (ApoE e2), as independent predictors of new intracranial hemorrhage (ICH) in the natural course of untreated brain arteriovenous malformations. We hypothesized that the risk of posttreatment ICH would also be greater in patients with brain arteriovenous malformations with these genotypes. METHODS: Two hundred fifteen patients undergoing brain arteriovenous malformation treatment (embolization, arteriovenous malformation resection, radiosurgery, or any combination of these) were genotyped and followed longitudinally. Association of genotype with new symptomatic ICH after initiation of treatment was assessed using Cox proportional hazards adjusted for treatment type, demographics, and established ICH risk factors censored at the time of the last follow-up evaluation or death. RESULTS: The cohort was 48% male and 55% Caucasian, and 52% had an ICH before the initiation of treatment; the mean age +/- standard deviation was 36.6 +/- 17.2 years. Posttreatment ICH occurred in 34 (16%) patients with a median follow-up period of 1.9 years (interquartile range, 1.6 yr). After adjustment, the risk of posttreatment ICH was greater for TNF-alpha-238 AG genotype (hazard ratio [HR], 3.5; 95% confidence interval [CI], 1.3-9.8; P = 0.016) and ApoE e2 (HR, 3.2; 95% CI, 1.0-9.7; P = 0.042). Similar trends for the TNF-alpha-238 AG genotype were seen in surgery (HR, 4.2; 95% CI, 0.6-28.8; P = 0.14) and radiosurgery subsets (HR, 3.8; 95% CI, 0.7-19.4; P = 0.11). An effect of ApoE e2 was seen in radiosurgery subsets (HR, 10.9; 95% CI, 1.3-93.7; P = 0.030), but not in surgery subsets (HR, 1.4; 95% CI, 0.3-7.4; P = 0.67). CONCLUSION: Despite a variety of different mechanisms for posttreatment hemorrhage, these data suggest that the TNF-alpha and ApoE genotypes may contribute common phenotypes of enhanced vascular instability that increase the risk of hemorrhagic outcome. [Abstract]

Lopez KA, Waziri AE, Granville R, Kim GH, Meyers PM, Connolly ES, Solomon RA, Lavine SD
Clinical usefulness and safety of routine intraoperative angiography for patients and personnel.
Neurosurgery. 2007 Oct;61(4):724-9; discussion 729-30.
OBJECTIVE: The routine use of intraoperative angiography (IA) is still surrounded by controversy. We prospectively performed IAs in consecutive patients undergoing surgery for aneurysms, arteriovenous malformations, and dural arteriovenous fistulae. We calculated the percentage of identified residual pathologies, the cases requiring further surgical intervention, and the complication rates associated with the procedure. We also recorded radiation dose received by personnel during IA for comparison with elective procedures. If our review supported the routine use of IA, recommendations should be tempered by radiation dose to personnel regarding whether or not annual exposure would go beyond recommended limits and whether or not radiation doses indicate a need for specialized operating rooms. METHODS: Two hundred and four consecutive IAs were performed on 191 patients over a 2-year period. Angiographic findings were reviewed retrospectively and noted for additional interventions. Complications related to IA were recorded. Radiation doses received by personnel and fluoroscopy times were compiled from 18 IAs. Mean dose/minutes in intraoperative procedures was compared with mean dose/minutes of a separate cohort of 15 elective angiograms (Student's t test). RESULTS: Twenty-three percent of IAs revealed relevant findings. Clip repositioning or additional clip placement was performed in 8% of the patients. Resection of residual arteriovenous malformations or additional surgery for residual arteriovenous shunting in dural arteriovenous fistulae was performed in 2% of the patients. Fewer than 1% of the patients received intra-arterial verapamil or topical papaverine. The complication rate was less than 1%. The mean dose per procedure for physicians was 1.018 microsieverts (uSv) versus 0.988 uSv for technicians (P = 0.94). The mean effective dose/minutes in the angiogram suite was 0.9209 uSv/minute versus 1.213 uSv/minute in the operating room (P = 0.33). CONCLUSION: IA identifies a significant number of pertinent findings during open neurovascular surgery, half of which require additional intervention. It is associated with a low complication rate. Radiation dose received by personnel per procedure is negligible. IA radiation dose is not different from dose in the angiogram suite; thus, specialized operating rooms may not be necessary. These data support routine intraoperative angiography in open surgeries for neurovascular disorders. [Abstract]

Hoh BL, Sistrom CL, Firment CS, Fautheree GL, Velat GJ, Whiting JH, Reavey-Cantwell JF, Lewis SB
Bottleneck factor and height-width ratio: association with ruptured aneurysms in patients with multiple cerebral aneurysms.
Neurosurgery. 2007 Oct;61(4):716-22; discussion 722-3.
OBJECTIVE: Determining factors predictive of the natural risk of rupture of cerebral aneurysms is difficult because of the need to control for confounding variables. We studied factors associated with rupture in a study model of patients with multiple cerebral aneurysms, one aneurysm that had ruptured and one or more that had not, in which each patient served as their own internal control. METHODS: We collected aneurysm location, one-dimensional measurements, and two-dimensional indices from the computed tomographic angiograms of patients in the proposed study model and compared ruptured versus unruptured aneurysms. Bivariate statistics were supplemented with multivariable logistic regression analysis to model ruptured status. A total of 40 candidate models were evaluated for predictive power and fit with Wald scoring, Cox and Snell R2, Hosmer and Lemeshow tests, case classification counting, and residual analysis to determine which of the computed tomographic angiographic measurements or indices were jointly associated with and predictive of aneurysm rupture. RESULTS: Thirty patients with 67 aneurysms (30 ruptured, 37 unruptured) were studied. Maximum diameter, height, maximum width, bulge height, parent artery diameter, aspect ratio, bottleneck factor, and aneurysm/parent artery ratio were significantly (P < 0.05) associated with ruptured aneurysms on bivariate analysis. When best subsets and stepwise multivariable logistic regression was performed, bottleneck factor (odds ratio = 1.25, confidence interval = 1.11-1.41 for every 0.1 increase) and height-width ratio (odds ratio = 1.23, confidence interval = 1.03-1.47 for every 0.1 increase) were the only measures that were significantly predictive of rupture. CONCLUSION: In a case-control study of patients with multiple cerebral aneurysms, increased bottleneck factor and height-width ratio were consistently associated with rupture. [Abstract]

Ryttlefors M, Howells T, Nilsson P, Ronne-Engström E, Enblad P
Secondary insults in subarachnoid hemorrhage: occurrence and impact on outcome and clinical deterioration.
Neurosurgery. 2007 Oct;61(4):704-14; discussion 714-5.
OBJECTIVE: To study the occurrence of secondary insults during neurointensive care of patients with subarachnoid hemorrhage using a computerized multimodality monitoring system and to study the impact of secondary insults on clinical deterioration and functional outcome. METHODS: Patients with subarachnoid hemorrhage who were admitted to the neurointensive care unit between January 1999 and December 2002 with at least 120 hours of multimodality monitoring data within the first 240 hours of neurointensive care were included. Data were continuously recorded for intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial blood pressure, systolic blood pressure, oxygen saturation, and temperature. Secondary insult levels were defined as ICP of 20 or greater or 25 or greater; CPP of 60 or lower, 55 or lower, greater than 100, or greater than 110; mean arterial blood pressure of 80 or lower, 70 or lower, 120 or greater, or 130 or greater; systolic blood pressure of 110 or lower, 100 or lower, 180 or greater, or 200 or greater; temperature of 38 degrees C or higher or 39 degrees C or higher; and oxygen saturation of less than 95 or less than 90. Secondary insults were quantified as the proportion of good monitoring time at the insult level. Uni- and multivariate logistic regression analyses were performed with admission and secondary insult variables as explanatory variables and clinical deterioration and independent outcome as the dependent variable, respectively. RESULTS: Ninety-nine patients (67 women; mean age, 57.8 yr) met the inclusion criteria. In the univariate analysis, ICP of 20 or greater, ICP of 25 or greater, CPP of 60 or less, and CPP of 55 or less increased the risk of clinical deterioration, whereas CPP greater than 100 and systolic blood pressure greater than 180 decreased the risk of clinical deterioration. In the multivariate logistic regression, ICP of 25 or greater and CPP of greater than 100 had an independent effect on clinical deterioration. The occurrence of secondary insults had no significant effect on functional outcome. CONCLUSION: Elevated ICP not responding to treatment is predictive of clinical deterioration, whereas high CPP decreases the risk of clinical deterioration. It may be beneficial to not lower spontaneous high CPP in patients with subarachnoid hemorrhage. [Abstract]

Shenkar R, Shi C, Check IJ, Lipton HL, Awad IA
Concepts and hypotheses: inflammatory hypothesis in the pathogenesis of cerebral cavernous malformations.
Neurosurgery. 2007 Oct;61(4):693-702; discussion 702-3.
OBJECTIVE: Cerebral cavernous malformations (CCMs) affect more than one million Americans, predisposing them to a lifetime risk of hemorrhagic stroke and epilepsy. A potential role of the immune response in this disease has not been postulated previously but is compelling given the unique antigenic milieu of CCM lesions with sequestered thrombi and a leaky blood-brain barrier and the numerous examples of immune modulation of angiogenesis in other disease states. The objective of this article is to reveal novel observations about apparent immune responses in CCM lesions excised from human patients and to outline the potential pathobiological significance of these observations, specific hypotheses for future research, and potential clinical implications. METHODS: We reviewed data from differential gene expression revealing several immunoglobulin and other related genes markedly upregulated within human CCM lesions. Other observations are presented revealing infiltration of antibody-producing B lymphocytes and plasma cells in CCM lesions. We also present recent data demonstrating fivefold enrichment of gamma globulin to albumin ratio in a human lesion compared with serum from the same patient and oligoclonality of IgG in four of five CCM lesions, but not in paired sera from the same patients or in control specimens. RESULTS: We describe ongoing research aiming to characterize cellular and humoral components of the immune response in CCMs and initiating investigation into its clonality by isoelectric focusing on the predominant immunoglobulin isotypes isolated from the lesion, in comparison to the patient's serum, and by the distribution of lengths of complementary-determining region 3 of the immunoglobulin heavy chain genes in messenger ribonucleic acid isolated from lesions and from pooled plasma cells and B cells laser captured from CCMs in comparison to peripheral lymphocytes from the blood of the same patients. CONCLUSION: Immune response could play a role in or represent a potential marker of CCM lesion proliferation and hemorrhage or could otherwise contribute to lesion phenotype. The ongoing studies will generate preliminary data for future research aimed at comparing the immune response in quiescent versus clinically aggressive CCM lesions. An oligoclonal immune response shown in this research would stimulate future experiments to identify autoimmune or extrinsic antigenic triggers involved in CCM disease. [Abstract]

Chang WC, Hawkes EA, Kliot M, Sretavan DW
In vivo use of a nanoknife for axon microsurgery.
Neurosurgery. 2007 Oct;61(4):683-91; discussion 691-2.
OBJECTIVE: Microfabricated devices with nanoscale features have been proposed as new microinstrumentation for cellular and subcellular surgical procedures, but their effectiveness in vivo has yet to be demonstrated. In this study, we examined the in vivo use of 10 to 100 microm-long nanoknives with cutting edges of 20 nm in radius of curvature during peripheral nerve surgery. METHODS: Peripheral nerves from anesthetized mice were isolated on a rudimentary microplatform with stimulation microelectrodes, and the nanoknives were positioned by a standard micromanipulator. The surgical field was viewed through a research microscope system with brightfield and fluorescence capabilities. RESULTS: Using this assembly, the nanoknife effectively made small, 50 to 100 microm-long incisions in nerve tissue in vivo. This microfabricated device was also robust enough to make repeated incisions to progressively pare down the nerve as documented visually and by the accompanying incremental diminution of evoked motor responses recorded from target muscle. Furthermore, this nanoknife also enabled the surgeon to perform procedures at an unprecedented small scale such as the cutting and isolation of a small segment from a single constituent axon in a peripheral nerve in vivo. Lastly, the nanoknife material (silicon nitride) did not elicit any acute neurotoxicity as evidenced by the robust growth of axons and neurons on this material in vitro. CONCLUSION: Together, these demonstrations support the concept that microdevices deployed in a neurosurgical environment in vivo can enable novel procedures at an unprecedented small scale. These devices are potentially the vanguard of a new family of microscale instrumentation that can extend surgical procedures down to the cellular scale and beyond. [Abstract]

Neurosurgery. 2007 Oct;61(4):N5. [Abstract]

Neurosurgery. 2007 Oct;61(4):N4. [Abstract]

Tanner PG, Holtmannspötter M, Tonn JC, Goldbrunner R
Effects of drug efflux on convection-enhanced paclitaxel delivery to malignant gliomas: technical note.
Neurosurgery. 2007 Oct;61(4):E880-2; discussion E882.
OBJECTIVE: Convection-enhanced delivery (CED) is an approach in local brain tumor treatment. The spread of infusate in CED can be thought of as involving three phases: backflow, convection, and diffusion. Uncontrolled backflow may lead to efflux of the infusate outside the cranium. METHODS: Based on an interim analysis of a clinical trial, the effects of drug efflux on convection were assessed. In a Phase I/II trial, eight patients with recurrent glioblastomas were treated with CED of paclitaxel. The first group of patients was treated with paclitaxel at a concentration of 0.5 mg/ml according to previously approved protocols. RESULTS: These Group 1 patients developed severe skin necrosis due to an efflux of paclitaxel out of the cranium. The average volume of distribution (Vd) in these patients was 12.8 cm. To prevent paclitaxel efflux, the burr hole was sealed with bone wax during and after CED in Groups 2 and 3. Surprisingly, patients in Group 2 showed a larger Vd (22.9 cm per catheter), exceeding the boundaries of the previous tumor, which led to subsequent neurological deficits. To allow a large Vd without severe side effects, the infusion volume was maintained, but the concentration of paclitaxel was reduced (paclitaxel concentration in Group 3, 0.25 mg/ml). CONCLUSION: Vd remained high and no adverse effects were seen in Group 3. Sealing the burr hole during CED prevented efflux. The simple measure of sealing seems to increase Vd. These data demonstrate that uncontrolled backflow may have an important impact on CED and must be avoided. [Abstract]

Guerrero CA, Krayenbühl N, Husain M, Krisht AF
Ectopic suprasellar growth hormone-secreting pituitary adenoma: case report.
Neurosurgery. 2007 Oct;61(4):E879; discussion E879.
OBJECTIVE: Ectopic pituitary adenomas are rare. We present an unusual case of an ectopic growth hormone-secreting pituitary adenoma in the suprasellar space. CLINICAL PRESENTATION: A 31-year-old man presented with a history of chronic headache and typical clinical signs of acromegaly. Magnetic resonance imaging scans revealed a suprasellar mass not arising from the normal looking pituitary gland. INTERVENTION: The patient underwent gross total removal of the tumor through a pterional approach. At the time of follow-up, he met the criteria of endocrinological cure. Histological examination showed a growth hormone-secreting pituitary adenoma CONCLUSION: Although uncommon, growth hormone-secreting pituitary adenomas are encountered in the suprasellar region. They should be added to the differential diagnosis of tumors in this location. [Abstract]

Plans G, Torres A, Ferran E, Aparicio A, Acebes JJ
Contralateral hearing loss after vestibular schwannoma surgery: case report.
Neurosurgery. 2007 Oct;61(4):E878; discussion E878.
OBJECTIVE: To describe a case of contralateral hearing loss (CHL) in vestibular schwannoma (VS) surgery and to discuss the factors potentially related with this complication. CLINICAL PRESENTATION: A 48-year-old man awakened with complete bilateral hearing loss after an uneventful retrosigmoid excision of a 20 mm left-sided VS. The patient had no complaints of vertigo or facial palsy on the contralateral side. The hearing loss proved to be endocochlear in origin and no improvement was observed after a 24-month follow-up period. DISCUSSION: CHL in VS surgery is not commonly reported but can occur frequently as a subclinical phenomenon if it is specially addressed. The cause is a compensatory endolymphatic hydrops generated by the loss of cerebrospinal fluid. In this circumstance, the hearing loss is usually reversible within 3 months, but irreversible cases have been described. Vascular damage to the cochlea can be another explanation in irreversible cases. The significance of other potential factors described in the literature as a cause of CHL in VS surgery is less clear. CONCLUSION: A case of CHL after VS surgery is presented. The hearing loss proved to be endochlear in origin and irreversible in nature. Irreversible damage to the cochlea resulting from loss of cerebrospinal fluid or vascular injury is probably related in this case reported. [Abstract]

Toth G, Rubeiz H, Macdonald RL
Polytetrafluoroethylene-induced granuloma and brainstem cyst after microvascular decompression for trigeminal neuralgia: case report.
Neurosurgery. 2007 Oct;61(4):E875-7; discussion E877.
OBJECTIVE: Microvascular decompression is commonly performed for medically refractory trigeminal neuralgia. A piece of polytetrafluoroethylene (PTFE) is usually placed between the trigeminal nerve and the blood vessel causing the compression. The procedure is effective and relatively safe, and PTFE is presumed to be inert. Reactions to PTFE are rare. CLINICAL PRESENTATION: We report a patient who developed progressive neurological symptoms 5 years after microvascular decompression surgery. Imaging showed an enhancing cerebellopontine mass resembling a posterior fossa tumor with a large cyst compressing the brainstem. INTERVENTION: Craniotomy was performed to decompress the cyst. Biopsy of the enhancing mass showed granulomatous inflammation. The patient underwent a second brainstem decompression surgery with placement of a catheter in the cyst connected to an Ommaya reservoir; she has moderate to severe residual neurological deficits. CONCLUSION: This may be the first case of a severely disabling, space-occupying cyst resulting from a reaction to intracranial PTFE. Should this exceptionally rare complication be disclosed to patients or is it an idiosyncratic reaction unlikely to occur again? [Abstract]

Pickett GE, Laitt RD, Herwadkar A, Hughes DG
Visual pathway compromise after hydrocoil treatment of large ophthalmic aneurysms.
Neurosurgery. 2007 Oct;61(4):E873-4; discussion E874.
OBJECTIVE: Hydrogel-coated coils (MicroVention, Inc., Aliso Viejo, CA) for endovascular aneurysm treatment offer the theoretical advantages of increased volumetric occlusion, thrombus stabilization, and improved neointimal healing. Reports of local inflammation and hydrocephalus after coiling of unruptured aneurysms have raised questions about the safety profile or appropriate usage of these new devices. CLINICAL PRESENTATION: Two patients with large ophthalmic aneurysms underwent elective endovascular coiling with HydroCoils. Three to 4 weeks later, they developed profound, progressive bilateral visual loss. Magnetic resonance imaging scans demonstrated extensive enhancement of the coil ball, surrounding brain parenchyma, and optic chiasm, with perianeurysmal edema. INTERVENTION: Dexamethasone produced impressive but temporary improvement in vision in one patient; the other experienced only minor improvement. One patient also developed hydrocephalus; ventriculoperitoneal shunting reduced ventricular size but had no effect on vision. Follow-up imaging demonstrated persistent enhancement of the coil ball, as well as recurrence and extension of the abnormal signal in the parenchyma and along the optic tract. CONCLUSION: Both patients have been left with no functional vision in the eye ipsilateral to the aneurysm and have experienced marked visual field loss and reduced acuity in the contralateral eye. Ongoing international studies will provide more information on the rate of inflammatory complications. The biological mechanisms underlying the phenomenon also require investigation. Meanwhile, we caution against using HydroCoils in situations in which worsened mass effect or local inflammation would have highly deleterious consequences, such as in large aneurysms adjacent to the visual pathways or the brainstem. [Abstract]

Neurosurgery. 2007 Oct;61(4):A60. [Abstract]