Search

Liver metastases occur in 75% to 80% of patients with neuroendocrine tumors (NETs), and are considered significant adverse prognostic indicators. Management of NETs liver metastases is challenging and requires aggressive therapy. Currently, there are many therapeutic options for metastatic NETs. However, there is considerable controversy regarding the optimal management. Although complete surgical resection remains the optimal therapy, a variety of other minimally invasive surgical and medical options are available, this includes thermal ablative techniques (e.g., radiofrequency ablation, microwave ablation, cryotherapy), embolization using transcatheter embolization, chemoembolization, or radioembolization, and medical therapy (e.g., chemotherapy, biotherapy with somatostatin analogues and interferon). Currently there is no evidence-based data directly comparing surgical versus alternative liver-directed treatment options. An aggressive surgical approach, coupled with additional liver-directed procedures is often recommended as it extends the overall survival. Optimal patient care should be directed by a multidisciplinary team to assure that all treatment options are explored for decision-making while treating this aggressive disease.

Background and Objective: Robotic-assisted surgery offers a solution to fundamental limitations of conventional laparoscopic surgery, and its use is gaining wide popularity. However, the application of this technology has yet to be established in hepatic surgery., Methods: A retrospective analysis of our prospectively collected liver surgery database was performed. Over a 6-month period, all consecutive patients who underwent robotic-assisted hepatic resection for a liver neoplasm were included. Demographics, operative time, and morbidity encountered were evaluated., Results: A total of 7 robotic-assisted liver resections were performed, including 2 robotic-assisted single-port access liver resections with the da Vinci-Si Surgical System (Intuitive Surgical Sunnyvalle, Calif.) USA. The mean age was 44.6 years (range, 21-68 years); there were 5 male and 2 female patients. The mean operative time (± SD) was 61.4 ± 26.7 minutes; the mean operative console time (± SD) was 38.2 ± 23 minutes. No conversions were required. The mean blood loss was 100.7 mL (range, 10-200 mL). The mean hospital stay (± SD) was 2 ± 0.4 days. No postoperative morbidity related to the procedure or death was encountered., Conclusion: Our initial experience with robotic liver resection confirms that this technique is both feasible and safe. Robotic-assisted technology appears to improve the precision and ergonomics of single-access surgery while preserving the known benefits of laparoscopic surgery, including cosmesis, minimal morbidity, and faster recovery.

Background: We sought to compare the outcomes in patients with hepatic carcinoid tumor metastases treated with open versus laparoscopic liver resection., Methods: A retrospective analysis of our liver surgery database was performed. All patients who underwent liver resection for hepatic carcinoid tumor metastases were included. Patients were divided into 2 groups depending on the surgical approach. Patients with concomitant primary and metastatic liver lesions underwent open resection., Results: Thirty-six patients underwent resection over a 10-year period (21 open and 15 laparoscopic). Both groups were similar in terms of gender, body mass index, tumor size, incidence of carcinoid syndrome, and extent of resection (P > .05). The laparoscopic group had less mean operative time (2.7 vs 5.4 hours), less mean blood loss (158.3 vs 538.9 mL), and a shorter hospital stay (3.2 vs 7.5 days; P < .05 for all). Complications were similar in both groups (20% vs 33%; P = .21). Two laparoscopic cases required conversion. The 3-year disease-free survival for the laparoscopic group was 73.3% compared to 47.6% for the open group (P = .2)., Conclusion: To our knowledge, this is the first reported study comparing laparoscopic versus open liver resection in the treatment of liver metastases from carcinoid tumors. Our series confirms that selective cases can safely be managed laparoscopically., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: The role of socioeconomic factors that affect survival, particularly for hepatocellular cancer (HCC), has yet to be fully analyzed. This study attempts to elucidate those racial and socioeconomic factors that affect differences in survival for patients with HCC., Methods: In a retrospective cohort study of 206 patients with HCC diagnosed in an inner-city urban center from 2003 to 2011, outcomes by race (African Americans versus white) were analyzed. Additional attention was paid to socioeconomic factors. Continuous variables were compared with the Student t-test, and categorical variables were compared with the χ(2) or Fisher exact test. Multivariate analysis was conducted using a logistic regression model. Patient death and survival data were analyzed with Kaplan-Meier and Cox proportional hazards., Results: Comparison of 138 white and 68 African-American patients revealed that African-American patients were more likely to present with larger tumor size at the time of diagnosis (4.7 vs 3.7 cm; P < .05). African-American patients were also more likely to be intravenous drug users (25.4% vs 11.6%; P < .05) and have cirrhosis from hepatitis C (81% vs 60%; P < .01). African-American patients were less likely to have private insurance compared with white patients (68% vs 92%; P < .01). Despite these findings in our inner-city practice, there was no difference in liver transplantation rates or survival rates between the 2 groups., Conclusion: Despite presentation with less-favorable tumor characteristics, African-American patients are able to achieve survival that is comparable with their white counterparts when treated in a program that is attuned to the challenges faced by their specific population., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Kidney transplantation (KTx) alone in patients with cirrhosis and renal failure (end-stage renal disease [ESRD]) infected with hepatitis C virus (HCV) is controversial. The aim of this study was to compare outcomes of HCV+ patients with ESRD and cirrhosis (C group) versus HCV+ patients with ESRD but with no cirrhosis (NC group) listed for KTx., Methods: Ninety HCV+ patients with ESRD were evaluated for KTx between 2003 and 2010. Listed patients underwent transjugular liver biopsy with hepatic portal venous gradient (HPVG) measurements. Only patients with HPVG less than 10 mm Hg were considered for KTx alone. We analyzed patient demographics, waitlist/liver disease characteristics, and posttransplant outcomes between groups., Results: Sixty-four patients listed for KTx alone were studied. Twelve patients (18.75%) showed biopsy-proven cirrhosis. Thirty-seven patients underwent KTx alone (9 from C and 28 from NC). No patients developed decompensation of their liver disease, although one patient for NC group developed metastatic hepatocellular carcinoma 16 months after transplantation. One- and three-year graft survival rates were 75% and 75% versus 92.1% and 75.1% for groups C and NC, respectively (P=0.72). One- and three-year patient survival rates were 88.9% and 88.9% versus 96.3% and 77.9% for groups C and NC, respectively (P=0.76). Only increasing recipient age and decreasing albumin levels were significantly associated with worse graft and patient survival., Conclusions: Our study suggests that KTx alone may be safe in patients with compensated HCV, cirrhosis, and ESRD with HPVG less than 10 mm Hg. A simultaneous liver-kidney transplantation may be an unnecessary use of a liver allograft in these patients.

Unlabelled: Induction immunosuppression has provided great advances in reducing the incidence of acute rejection (AR) following kidney transplantation. Despite this success, there has been recent concern over possible increased rates of viral complications when such powerful immunosuppressive therapy is used. This study was undertaken to determine the incidence of BK viral infection following kidney transplantation under alemtuzumab induction therapy., Methods: With institutional review board approval, a retrospective study was performed of all patients undergoing kidney transplantation under alemtuzumab induction at a single center. The incidence of BK viremia was determined, and univariate analysis was performed to determine factors associated with the development of BK viremia. Further analysis was undertaken, using standard statistical methods, to determine the rates of graft survival and hazard ratio (HR) for AR in patients with and without BK viremia., Results: There were 456 patients in the current study, with a mean age of 51 years. The majority of these (61.8%) were male, and 73.5% were Caucasian. The overall incidence of BK viremia identified on routine screening was 6.6%. Univariate analysis failed to identify any significant predictors of BK viremia. One-, 3-, and 5-year graft survival for patients who developed BK viremia was 96.6%, 91.7%, and 91.7%, respectively, compared with 94.1%, 87.8%, and 80.2% for patients without BK viremia (P = 0.860). BK viremia was associated with a significantly increased risk for AR (HR 3.48, 95% confidence interval 1.24-9.76; P = 0.018)., Conclusion: The incidence of BK viremia following alemtuzumab induction appears to be in concordance with the published literature, with satisfactory graft survival rates. BK viremia is, however, associated with an increased risk for AR., (© 2011 John Wiley & Sons A/S.)

Although a number of factors contributing to the disparity in graft survival between African American (AA) and Caucasian kidney transplant recipients have been described, the role of donor quality is less well understood. This study was undertaken to determine the impact of donor quality differences on this disparity, based on review of UNOS (United Network for Organ Sharing) data on deceased donor renal transplantation from 2000 to 2010. Donor quality was determined by the kidney donor risk index (DRI), and was compared between AA and Caucasian recipients. There were 33,405 Caucasians and 22,577 African Americans in the study, with mean DRI of 1.17 versus 1.27 (p < 0.001), respectively. In analysis 2,446 recipients of each race matched by propensity scoring (based on medical, socioeconomic and immunologic covariates), mean DRI was 1.25 for Caucasians and 1.28 (p = 0.02) for AA. The hazard ratio (HR) for graft failure associated with AA race was 1.8 (p < 0.001) on unadjusted analysis, and decreased to 1.6 (p < 0.001) after matching for DRI. These results indicate a significant disparity in quality of kidneys received by African Americans, which propensity analysis indicates is partially explained by differences in medical, immunologic and socioeconomic factors. Furthermore, this difference in donor quality partially accounts for poorer graft survival in African Americans., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives:   In hilar cholangiocarcinoma, resection provides the only opportunity for longterm survival. A US experience of hilar cholangiocarcinoma was examined to determine the effect of clinical experience on negative margin (R0) resection rates., Methods:   We conducted a retrospective analysis of 110 consecutive hilar cholangiocarcinoma patients presenting over an 18-year period. Analyses were performed using chi-squared, Wilcoxon rank sum and Kaplan-Meier methods, and multivariable Cox and logistic regression modelling., Results:   Of the 110 patients in the cohort, 59.1% were male and 90.9% were White. The median patient age was 64 years. A total of 59 (53.6%) patients underwent resection; 37 of these demonstrated R0. The 30-day mortality rate was 5.1%; the complication rate was 39.0%. The rate of resectability increased over time (36.4% vs. 70.9%; P= 0.001), as did the percentage of R0 resections (10.9% vs. 56.5%; P < 0.001). Of the 59 patients who underwent resection, 23 (39.0%) experienced recurrence. Multivariable Cox regression analysis identified resection margins [hazard ratio (HR) = 4.124 for positive vs. negative; P= 0.002] and type of operation (HR = 5.075 for exploration vs. resection; P= 0.001) as significant to survival., Conclusions:   Although R0 resection can be achieved in only a minority of patients, these patients have a reasonable chance of longterm survival. The last decade has seen a significant rise in rates of resectability of Klatskin's tumour at specialty centres., (© 2011 International Hepato-Pancreato-Biliary Association.)

Background: Laparoscopic liver resection is a procedure in evolution. In the last decade it has evolved from a novel procedure to a standard part of the hepatic surgeon's armamentarium. Few data exist on the development of a laparoscopic resection program., Study Design: With IRB approval, a retrospective review of 300 consecutive laparoscopic liver resections was undertaken. To determine changing results and patterns of practice, the cohort was divided into 3 consecutive groups of 100 patients. Patient demographics, indications for operation, operative factors, and in-hospital outcomes were examined. Continuous variables were analyzed with the Kruskal-Wallis test; continuous variables were compared with Fisher's exact test. Univariate and multivariate analyses of major complications (≥grade 3) were performed using logistic regression., Results: Of the 300 patients, 173 (61.6%) were female, with a median age of 54 years. There were 133 (44.3%) major resections. The median number of segments resected increased (3 vs 2, p = 0.015), as did the percentage of repeat hepatectomies (13.0% vs 2.0%, p = 0.001). At the same time, median operative time decreased (2.25 vs 3.0 hours, p < 0.001).and estimated blood loss was similar (150 mL vs 150 mL, p = 0.635). Morbidity was similar (11% vs 14%, p = 0.300), as was mortality (1% vs 3%, p = 0.625)., Conclusions: Laparoscopic liver resection has evolved from a novel procedure to a vital technique in liver surgery. Our group has demonstrated the ability over time to perform more difficult resections with similar morbidity and decreased operative length., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To determine malignant melanoma cause-specific and overall survival among patients with melanoma diagnosed after organ transplantation compared with a national sample with malignant melanoma., Design: Retrospective review., Setting: Mayo Clinic sites., Patients: Immunosuppressed organ transplant recipients with malignant melanoma identified from surgical and medical databases at Mayo Clinic (1978-2007), the Organ Procurement and Transplantation Network/United Network for Organ Sharing database (1999-2006), and the Israel Penn International Transplant Tumor Registry (1967-2007)., Main Outcome Measures: Prognostic analyses by Breslow thickness and Clark level of overall and melanoma cause-specific survival. Expected survival rates were estimated by applying the age-, sex-, and calendar year-specific survival rates of patients with malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program to the study cohort., Results: Malignant melanoma was diagnosed in 638 patients (724 cases) after transplantation. Breslow thickness was available for 123 patients; Clark level, for 175. Three-year overall survival rates for patients stratified by Breslow thickness (≤ 0.75, 0.76-1.50, 1.51-3.00, and >3.00 mm) were 88.2%, 80.8%, 51.2%, and 55.3%, respectively, and 3-year cause-specific survival rates (95% confidence intervals) were 97.8% (93.7%-100%), 89.4% (76.5%-100%), 73.2% (53.2%-100%), and 73.9% (56.4%-96.6%), respectively. Three-year cause-specific survival rates (95% confidence intervals) for patients stratified by Clark level (I-IV) were 100%, 97.4% (92.4%-100%), 82.8% (65.3%-100%), and 65.8% (51.8%-83.7%), respectively. For patients with Breslow thickness of 1.51 to 3.00 mm and Clark level III or IV, the cause-specific survival rate in the study sample was significantly different from the expected estimates for patients with the same Breslow thickness or Clark level., Conclusions: Compared with the expected survival rates derived from malignant melanoma cases reported in the Surveillance, Epidemiology, and End Results Program, immunosuppressed organ transplant recipients with thicker melanomas (ie, with a Clark level of III or IV or a Breslow thickness of 1.51 to 3.00 mm) had a significantly poorer malignant melanoma cause-specific survival rate. The overall survival rate was worse among patients with a prior history of transplantation, regardless of Breslow thickness or Clark level.

This study was undertaken to examine short-term outcomes of laparoscopic donor nephrectomy performed by transplant surgeons at a medium volume institution, with the specific goal of determining the presence of a learning curve effect. With institutional review board approval, a retrospective chart review was performed examining patient demographics, operative factors, and in-hospital outcomes over a 12-year period. Specific attention was paid to differences in outcomes between patients undergoing operation in the first versus the most recent 6-year period. Continuous and categorical variables were examined using the Wilcoxon rank sum test and χ(2) analysis, respectively. The study group consisted of 129 patients. Median operative time was 234 minutes with a median estimated blood loss of 100. The median preoperative creatinine was 0.9, with a postoperative median creatinine of 1.3. The overall complication rate was 12.4 per cent, with ileus being the most common. There were two cases of post op acute renal failure, both of which were self limited and did not require dialysis. No patients died. Patients in the most recent 6 years (n = 77) enjoyed a shorter length of stay (2 vs 3 days, P < 0.001) than patients in the first 6-year period (n = 52). Additionally, there was a trend towards decreased complications in the second era that did not reach significance (9.1% vs 17.3%, P = 0.17). Laparoscopic donor nephrectomy is an attractive means of donation, and can be performed with low risk to the donor and minimal learning curve effect.

Donor liver allografts with positive serology for hepatitis B core antibody [HBc (+)] have been increasingly used for liver transplantation. However, the optimal prophylactic regimen to prevent development of de novo hepatitis B has not been determined. To evaluate this, we screened United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) registry data for adult recipients of HBc (+) organs who were HBsAg (-), and evaluated the effects of using prophylactic anti-viral therapies (HBIG and lamivudine) on patient and graft survival. Out of a total cohort of 958 patients transplanted since 2004, 61 received HBIG alone, 116 received lamivudine alone, 66 both, 509 neither and 206 were missing this information. Based on several multivariable Cox regression models, patients receiving HBIG therapy-only were observed to have a statistically significant (approximately 70%) reduction in risk of mortality compared with patients receiving lamivudine-only therapy [HR=0.29, 95% CI (0.10, 0.86), P=0.026], and a nonstatistically significant reduction in risk of graft failure. However, no graft failures were attributed to de novo hepatitis B, suggesting that any improved graft/patient survival possibly associated with HBIG therapy occurs independently of de novo hepatitis B virus (HBV) reduction. While this study cannot prove that HBIG therapy is protective for graft and patient survival after liver transplantation, these findings do highlight the need to further examine and study prophylactic use in recipients of HBc (+) donors., (© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.)

Background: Renal transplant recipients may have comorbidities requiring anticoagulation or antiplatelet therapy. While the effects of warfarin may be neutralized with plasma infusion, those of aspirin and clopidogrel are not easily reversible and may be associated with an increased risk of bleeding. We conducted this study to evaluate the risk of bleeding complications in patients receiving perioperative anticoagulation or antiplatelet therapy., Methods: Medical records of patients who underwent renal transplantation from July 1, 2005 to April 30, 2009 were retrospectively reviewed. Patients receiving perioperative anticoagulation or antiplatelet therapy were identified. The incidence of reoperation, transfusion utilization and decrease in serum hemoglobin from pre-operative value (ΔHgb) were compared to those on no therapy., Results: Of the 327 patients identified, 105 received pre-operative anticoagulation or antiplatelet therapy, 28 received therapy post-operatively, while 213 patients received no therapy. The incidence of reoperation, transfusion utilization and ΔHgb were not significantly increased with pre-operative anticoagulation or antiplatelet therapy. With post-operative heparin infusion, the incidence of reoperation and transfusion utilization were significantly increased (p values < 0.001). Patients with activated partial thromboplastin times (aPTT) >80 s experienced significant bleeding complications., Conclusion: A supratherapeutic aPTT with post-operative heparin infusion was associated with the greatest risk of bleeding complication., (© 2010 John Wiley & Sons A/S.)

Background: A laparoscopic approach has not been advocated for repeat hepatectomy on a large scale. This report analyzes the experience of 3 institutions pioneering laparoscopic repeat liver resection (LRLR). The aim of this study was to evaluate the feasibility, safety, oncologic integrity, and outcomes of LRLR., Study Design: All patients undergoing LRLR were identified. Since 1997, 76 LRLRs have been attempted. Operative indications were metastasis (n = 63), hepatocellular carcinoma (n = 3), and benign tumors (n = 10). All patients had 1 or more earlier liver resections (28 open, 44 laparoscopic), including 16 major resections (en bloc removal of 3 or more Couinaud segments)., Results: Eight conversions (11%) to open resections (n = 7) or radiofrequency ablation (n = 1) were required due to technical difficulties or hemorrhage. LRLRs included 49 wedge or segmental resections and 19 major hepatectomies. Median blood loss and operative time were 300 mL and 180 minutes. Patients with previous open liver resection (group B) experienced more intraoperative blood loss and transfusion requirements than those with earlier laparoscopic resections (group A) (p = 0.02; p = 0.01, respectively). R0 resection was achieved in 58 of 64 (91%) patients with malignant tumor. The incidence of postoperative complications and duration of hospital stay were not statistically different between the 2 groups. Bile leakages developed in 5 (6.6%) patients, including 1 requiring reoperation. There was no perioperative death. Median tumor size was 25 mm (range 5 to 125 mm) and the median number of tumors was 2 (range 1 to 7). Median follow-up was 23.5 months (range 0 to 86 months). There was no port-site metastasis. The 3- and 5-year actuarial survivals for patients with colorectal metastases were 83% and 55%, respectively., Conclusions: Laparoscopic repeat hepatic resections can be performed safely and with good results, particularly in patients with earlier laparoscopic resections., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose. The study was undertaken to evaluate a novel classification system developed to estimate financial cost of bile duct injury (BDI) and to aid in decision making for referral. Study Design. A retrospective review of patients referred for BDI was performed. Grade I injuries involve the duct of Luschka or accessory right hepatic ducts, grade II includes all other biliary injuries, and grade III includes all vasculobiliary injuries. Groups were compared using standard statistical methods. Results. There were 14 grade I, 74 grade II, and 20 grade III injuries. There was a significant difference in the cost and mortality of grade I ($12,457, 0%), grade II ($46,481, 1.4%), and grade III ($69,368, 15%, P = 0.002 and P = 0.030, resp.) injuries. Grade II and III injuries were significantly more likely to require surgical repair (OR 27.7, P < 0.001). Conclusion. We have presented a simple classification system that is able to accurately predict cost and need for surgical repair.

Purpose of Review: To review current opinions about the epidemiology, risk factors, and approaches to prevent malignancies in pediatric transplant recipients., Recent Findings: Recent studies looking at the risk of newer induction agents and viral etiologies are reviewed. The recent introduction of viral immunizations as prophylaxis is also discussed., Summary: Children remain one of the most vulnerable populations for developing cancer posttransplant. This is because of multiple variables, but especially because of immune naivete and longer periods of immunosuppression. As transplantation gets more complex, with discovery of newer immunosuppressive agents and viral agents, all of these affect the incidence of malignancy in the posttransplant period. A review of the latest literature in this aspect with data from the largest current transplant databases is herein presented.

This article reviews the risks of transplanting hepatitis B core antibody (anti-HBc)-positive (+) kidneys and strategies to minimize the risks to the recipient. In the United States, there is a shortage of kidneys available for transplantation. Presently, 4% of kidneys transplanted are anti-HBc (+). In published retrospective studies, the serologic conversion rate for recipients of anti-HBc (+) kidneys varied between 0% and 27%; and the development of elevated hepatic transaminases varied between 0% and 26%. Only one published article had a trend toward increased risk of graft loss. Other published studies had no significant difference in graft or patient survival. Factors that influence the risk of transmission include hepatitis B viral load, vaccination, and antiviral therapy. If the donor is anti-HBc (+) and hepatitis B DNA negative, the risk of transmission is negligible; unfortunately, this information may not be available at the time of transplant. Vaccinated recipients with a protective hepatitis B surface antibody of at least 10 mIU/mL had a 4% conversion rate compared with 10% in recipients with antibody levels not exceeding 10 mIU/mL. Both hepatitis B immunoglobulin and lamivudine have been used in recipients of anti-HBc (+) kidneys to decrease seroconversion with success. The data do support the use of anti-HBc (+) kidneys if precautions are taken. The recipients should be informed of the risk, should be vaccinated with an adequate response, and should have surveillance serologies performed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Advances in imaging techniques will dramatically decrease the number of undiagnosed tumors. New molecular techniques should allow the identification of pathologic factors that are predictive of complicated forms. Surgery should be limited to symptomatic benign tumors or those who have a risk for complication (hemorrhage, rupture, or degeneration). When surgery is indicated, patients with benign disease are the best candidates for laparoscopy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Percutaneous renal biopsy is a convenient method to obtain allograft tissue for histologic evaluation. Vascular complications, such as arteriovenous (AV) fistula and pseudoaneurysm, following renal biopsy are well known, and they usually resolve without further intervention. When symptomatic, they should be treated. We present a patient on chronic anticoagulation who developed a pseudoaneurysm after percutaneous renal biopsy. Applying techniques learned in the management of femoral artery pseudoaneurysm, we treated our patient with ultrasound-guided thrombin injection.

Objective: To analyze the results of 6 international surgical centers performing laparoscopic major liver resections., Summary Background Data: The safety and feasibility of laparoscopy for minor liver resections has been previously demonstrated. Major anatomic liver resections, initially considered to be unsuitable for laparoscopy, are increasingly reported by several centers worldwide., Methods: Prospective databases of 3 European, 2 U.S., and 1 Australian centers were combined. Between 1997 and 2008, 210 major liver resections were performed: 136 right and 74 left hepatectomies. Results and differences in surgical techniques between the 6 centers are outlined., Results: Surgical duration was 250 minutes (range: 90-655 minutes). Operative blood loss was 300 mL (range: 20-2500 mL). Thirty patients (14.3%) received blood transfusion. Conversion to open surgery was required in 26 patients (12.4%). Portal triad clamping was performed in 24 patients (11.4%). Median tumor size was 5.4 cm (range: 1-25 cm) and surgical margin was 10.5 mm (range: 0-70 mm). Two patients died during the postoperative period from pulmonary embolism and urosepsis. Liver-specific and general complications occurred in 17 (8.1%) and 29 patients (13.8%), respectively. Hospital length of stay was 6 days (range: 1-34 days). A further analysis of early (n = 90) and late (n = 120) experience showed improved surgical and postoperative results in the latter group., Conclusions: This multicenter study demonstrates that laparoscopic major liver resections are feasible in selected patients and results improve with experience. However, proficiency in both open liver surgery and advanced laparoscopy is compulsory and surgeons must begin with minor laparoscopic resections.

Objective: To evaluate a multicenter, international series on minimally invasive liver resection for colorectal carcinoma (CRC) metastasis., Summary Background Data: Multiple single series have been reported on laparoscopic liver resection for CRC metastasis. We report the first collaborative multicenter, international series to evaluate the safety, feasibility, and oncologic integrity of laparoscopic liver resection for CRC metastasis., Methods: We retrospectively reviewed all patients who underwent minimally invasive liver resection for CRC metastasis from February 2000 to September 2008 from multiple medical centers from the United States and Europe. The multicenter series of patients were accumulated into a single database. Patient demographics, preoperative, operative, and postoperative characteristics were analyzed. Actuarial overall survival was calculated with Kaplan-Meier analysis., Results: A total of 109 patients underwent minimally invasive liver resection for CRC metastasis. The median age was 63 years (range, 32-88 years) with 51% females. The most common sites of primary colon cancer were sigmoid/rectum (51%), right colon (25%), and left colon (13%). Synchronous liver lesions were present in 11% of patients. For those with metachronous lesions liver lesions, the median time interval from primary colon cancer surgery to liver metastasectomy was 12 months. Preoperative chemotherapy was administered in 68% of cases prior to liver resection. The majority of patients underwent prior abdominal operations (95%). Minimally invasive approaches included totally laparoscopic (56%) and hand-assisted laparoscopic (41%), the latter of which was employed more frequently in the US medical centers (85%) compared with European centers (13%) (P = 0.001). There were 4 conversions to open surgery (3.7%), all due to bleeding. Extents of resection include wedge/segmentectomy (34%), left lateral sectionectomy (27%), right hepatectomy (28%), left hepatectomy (9%), extended right hepatectomy (0.9%), and caudate lobectomy (0.9%). Major liver resections (> or =3 segments) were performed in 45% of patients. Median OR time was 234 minutes (range, 60-555 minutes) and blood loss was 200 mL (range, 20-2500 mL) with 10% receiving a blood transfusion. There were no reported perioperative deaths and a 12% complication rate. Median length of hospital stay for the entire series was 4 days (range, 1-22 days) with a shorter stay in medical centers in the United States (3 days) versus that seen in Europe (6 days) (P = 0.001). Negative margins were achieved in 94.4% of patients. Actuarial overall survivals at 1-, 3-, and 5-year for the entire series were 88%, 69%, and 50%, respectively. Disease-free survivals at 1-, 3-, and 5-year were 65%, 43%, and 43%, respectively., Conclusions: Minimally invasive liver resection for colorectal metastasis is safe, feasible, and oncologically comparable to open liver resection for both minor and major liver resections, even with prior intra-abdominal operations, in selected patients and when performed by experienced surgeons.

Objective: To summarize the current world position on laparoscopic liver surgery., Summary Background Data: Multiple series have reported on the safety and efficacy of laparoscopic liver surgery. Small and medium sized procedures have become commonplace in many centers, while major laparoscopic liver resections have been performed with efficacy and safety equaling open surgery in highly specialized centers. Although the field has begun to expand rapidly, no consensus meeting has been convened to discuss the evolving field of laparoscopic liver surgery., Methods: On November 7 to 8, 2008, 45 experts in hepatobiliary surgery were invited to participate in a consensus conference convened in Louisville, KY, US. In addition, over 300 attendees were present from 5 continents. The conference was divided into sessions, with 2 moderators assigned to each, so as to stimulate discussion and highlight controversies. The format of the meeting varied from formal presentation of experiential data to expert opinion debates. Written and video records of the presentations were produced. Specific areas of discussion included indications for surgery, patient selection, surgical techniques, complications, patient safety, and surgeon training., Results: The consensus conference used the terms pure laparoscopy, hand-assisted laparoscopy, and the hybrid technique to define laparoscopic liver procedures. Currently acceptable indications for laparoscopic liver resection are patients with solitary lesions, 5 cm or less, located in liver segments 2 to 6. The laparoscopic approach to left lateral sectionectomy should be considered standard practice. Although all types of liver resection can be performed laparoscopically, major liver resections (eg, right or left hepatectomies) should be reserved for experienced surgeons facile with more advanced laparoscopic hepatic resections. Conversion should be performed for difficult resections requiring extended operating times, and for patient safety, and should be considered prudent surgical practice rather than failure. In emergent situations, efforts should be made to control bleeding before converting to a formal open approach. Utilization of a hand assist or hybrid technique may be faster, safer, and more efficacious. Indications for surgery for benign hepatic lesions should not be widened simply because the surgery can be done laparoscopically. Although data presented on colorectal metastases did not reveal an adverse effect of the laparoscopic approach on oncological outcomes in terms of margins or survival, adequacy of margins and ability to detect occult lesions are concerns. The pure laparoscopic technique of left lateral sectionectomy was used for adult to child donation while the hybrid approach has been the only one reported to date in the case of adult to adult right lobe donation. Laparoscopic liver surgery has not been tested by controlled trials for efficacy or safety. A prospective randomized trial appears to be logistically prohibitive; however, an international registry should be initiated to document the role and safety of laparoscopic liver resection., Conclusions: Laparoscopic liver surgery is a safe and effective approach to the management of surgical liver disease in the hands of trained surgeons with experience in hepatobiliary and laparoscopic surgery. National and international societies, as well as governing boards, should become involved in the goal of establishing training standards and credentialing, to ensure consistent standards and clinical outcomes.

The complex vascular and biliary anatomy of the liver poses great challenges even to experienced surgeons. However, with the experience accrued over the past two decades, surgery of the liver has become standardized. In the past few years innovative surgical techniques have permitted liver surgery to be performed using the minimally invasive approach. Large clinical series have been reported which demonstrate the safety and oncological integrity of the approach. This review highlights the current state of laparoscopic liver surgery with emphasis on problems unique to the procedure.

Background: Liver transplantation is the best treatment option for endstage liver disease. The human T-cell lymphotrophic virus (HTLV) has been associated with leukemia/lymphoma and progressive neurologic disease. There has, however, been an increased utilization of HTLV (+) grafts with little data available to support or discourage their use., Methods: We performed univariate and multivariate analyses related to graft and patient survival for recipients of HTLV (+) donors and compared them with recipients of HTLV (-) donors using the United Network for Organ Sharing database. Complete analysis of recipient and donor clinical and demographic factors was performed., Results: There were 81 adult recipients of HTLV (+) donors and 29,747 HTLV (-) donor recipients. HTLV (+) donors were more likely to be older, women, and black, with a higher average donor risk index and creatinine, and were more likely to be shared nationally. Recipients of HTLV (+) organs were at slightly elevated risk of graft failure (HR=1.39, 95% CI 0.91-2.11) and death (HR=1.20, CI 0.71-2.02) relative to HTLV (-) donor recipients (P=0.12 and 0.5, respectively). The risk decreased after multivariate analysis - graft survival (HR=1.20, CI 0.79-1.83) and patient survival (HR=1.06, CI 0.63-1.79)., Conclusion: Our analysis reveals no statistically significant difference in graft or patient survival between recipients of HTLV (+) and (-) donors. Serious limitations of these data are that serologic testing for HTLV has a high false positive rate and that there was a short follow-up period. Until these issues are addressed, extreme caution should be exercised when using these organs.

Restoration of amputations and disfigurement are represented in ancient mythology, but the modern history of composite tissue allotransplantation begins with World War II injuries that generated seminal immunologic experiments by Medawar and co-workers. These studies led to the first successful human allografts in the 1950s by Peacock with composite tissue and Murray and co-workers with solid organs. Pharmacologic immunosuppression brought rapid growth of solid organ transplantation over the next 50 years, but composite tissue transplantation virtually disappeared. This evolution was judged to be a consequence of the greater antigenicity of skin, which that was insurmountable by the available immunosuppression. In the mid-1990s, progress in immunosupression allowed skin-bearing grafts, led by successful hand transplants, which produced a renaissance in composite tissue allotransplantation. Since then, graft types have expanded to over 10, and graft numbers to over 150, with success rates that equal or exceed solid organs. The field has emerged as one of the most exciting in contemporary medicine, although accompanied by substantial challenges and controversy. This paper reviews the origins and progress of this field, assessing its potential for future evolution.

Great advances have occurred in the field of laparoscopic hepatic surgery. It is now clear that in experienced hands, the laparoscopic method of liver resection is as safe as an open procedure. The key phrase in this last sentence is "in experienced hands". The new devices that are available might make an inexperienced hepatic surgeon, well-trained in laparoscopic surgery, embark on hepatic resection without thorough knowledge of hepatic anatomy. The converse may also be true. As no criteria for credentialing of laparoscopic hepatic surgeons exist, the decision as to who is sufficiently trained to perform these procedures is left to individual hospital credentialing boards. While a certification procedure defined by leaders in this field and supported by surgical societies would be welcomed, the ability to achieve and enforce these guidelines appear to be more of a challenge. In addition, while most comparison studies in this area conclude by suggesting that a randomized, clinical trial would be needed to definitively arrive at an answer regarding the benefits of minimally invasive liver surgery compared with open surgery, it would likely be extremely difficult to accrue patients, given the data presented in articles regarding the success of laparoscopic hepatic resections. The authors conclude that an internationalregistry of all laparoscopic cases should b e established to insure patient safety and a mechanism for self-monitoring.

Objective: The purpose of this study was to test ultrasound echo decorrelation imaging for mapping and characterization of tissue effects caused by radio frequency ablation (RFA)., Methods: Radio frequency ablation procedures (6-minute duration, 20-W power) were performed on fresh ex vivo bovine liver tissue (n = 9) with continuous acquisition of beam-formed ultrasound echo data from a 7-MHz linear array. Echo data were processed to form B-scan images, echo decorrelation images (related to rapid random changes in echo waveforms), and integrated backscatter images (related to local changes in received echo energy). Echo decorrelation and integrated backscatter values at the location of a low-noise thermocouple were assessed as functions of temperature. Echo decorrelation and integrated backscatter images were directly compared with ablated tissue cross sections and quantitatively evaluated as predictors of tissue ablation and overtreatment., Results: Echo decorrelation maps corresponded with local tissue temperature and ablation effects. Consistent echo decorrelation increases were observed for temperatures above 75 degrees C, whereas integrated backscatter maps showed a nonmonotonic temperature dependence complicated by acoustic shadowing, with high variance at large temperature elevations. In receiver operating characteristic curve analysis of echo decorrelation and integrated backscatter maps as predictors of local tissue ablation, echo decorrelation performed well (area under the receiver operating characteristic curve [AUROC] = 0.855 for ablation and 0.913 for overtreatment), whereas integrated backscatter performed poorly (AUROC < 0.6)., Conclusions: Echo decorrelation imaging can map tissue changes due to RFA in vitro, with local echo decorrelation corresponding strongly to local tissue temperature elevations and ablation effects. With further development and in vivo validation, echo decorrelation imaging is potentially useful for improved image guidance of clinical RFA procedures.

Background: Composite tissue allotransplantation (CTA) is a newly emerging field of transplantation that involves the simultaneous transfer of multiple tissues with differing antigenicity. Hand transplantation, the most widely recognized form of CTA, aims to improve function and the quality of life of upper limb amputees., Methods: In 1999, an institutional review board-approved hand transplantation protocol was implemented at the Jewish Hospital, University of Louisville. Suitable patients were evaluated and underwent hand transplantation. The surgical technique was akin to that used in limb reimplantation, and the immunosuppression protocol used was similar to renal transplantation., Results: Between 1999 and 2006, 3 patients underwent hand transplantation at our center. Although episodes of acute rejection were seen in all patients during the early postoperative period, only 1 immunologic event occurred after the first year. Graft function improved with time period. Carroll test scores were superior to those recorded with a prosthesis at the end of 1 year. Additionally, recovery of protective sensation was seen in all 3 patients and limited discriminatory sensation in 2. Complications related to immunosuppression have included cytomegalovirus infection in 2 patients, diabetes in 1, hyperlipidemia in 2, and osteonecrosis in 1. At a follow-up of 8, 6, and 1 year(s), all the recipients are healthy and have returned to a productive life., Conclusions: The long-term success reported here should encourage wider application of the CTA in general and hand transplantation in particular. Methods of minimizing long-term immunosuppression need to be pursued.

Objective: To evaluate our experience with more than 500 minimally invasive hepatic procedures., Summary Background Data: Recent data have confirmed the safety and efficacy of minimally invasive liver surgery. Despite these reports, no programmatic approach to minimally invasive liver surgery has been proposed., Methods: We retrospectively reviewed all patients who underwent a minimally invasive procedure for the management of hepatic tumors between January 2001 and April 2008. Patients were divided into 3 groups: laparoscopy with intraoperative ultrasound and biopsy only, laparoscopic radiofrequency ablation (RFA), and minimally invasive resection. To compare the various forms of surgery, we analyzed the incidence of complications, tumor recurrence, mortality, and cost. Statistical analysis was performed using chi(2) analysis, Student t test, Kaplan-Meier survival analysis with the log-rank test, and multivariable Cox models., Results: A total of 590 minimally invasive hepatic procedures were performed during 489 operative interventions. The representative tumor histologies were: hepatocellular carcinoma (HCC; N = 210), colorectal carcinoma (N = 40), miscellaneous liver metastases (N = 42), biliary cancer (N = 20), and benign tumors (N = 176). Thirty-five patients underwent laparoscopic ultrasound and confirmatory biopsy alone; 201 patients underwent 240 laparoscopic RFAs, and 253 patients underwent 306 minimally invasive resections. Conversion rates to open surgery for the RFA and resection group were 2% overall. One hundred ninety-nine (40.6%) patients were cirrhotic; 31 resections were performed in cirrhotic patients. Complication and mortality rates for RFA and resection were comparable (11% vs. 16%, and 1.5% vs. 1.6%). However, complication rates (14% vs. 29%; P = 0.02) and mortality (0.3% vs. 9.7%; P = 0.006) rates were higher in the cirrhotic versus noncirrhotic resection group. Overall recurrence rates for RFA and resection groups were 24% and 23%, respectively. Local recurrence rates were higher in the RFA group (6.3% versus 1.5%; P < 0.06). Overall patient survival differed between HCC patients receiving RFA alone and those receiving RFA and OLT (P < 0.0001). Overall survival for cancer patients receiving RFA versus resection differed significantly when unadjusted for other covariates (P = 0.01), and remained marginally significant in a multivariable model (P = 0.056)., Conclusions: Minimally invasive hepatic surgery has become a viable alternative to open hepatic surgery. Our present data are equivalent or superior to those encountered in any large open series. Our experience with RFA confirms a low local recurrence rate and an excellent technique for bridging patients to transplantation. Morbidity and mortality rates for minimally invasive hepatic resections in cirrhotics, is similar to other reported open resection series. This series confirmed excellent interim survival rates after laparoscopic HR and superiority over RFA in the treatment of cancer, with significantly lower local tumor recurrence rate.

Primary fascial closure is often difficult after adult orthotopic liver transplantation (OLT), complicated by donor-to-recipient graft size mismatch, post-reperfusion hepatic edema, coagulopathy, or intestinal edema. Attempts at closing the abdomen under these circumstances can cause increase in intra-abdominal pressures, resulting in significant complications, including graft loss. Temporary closure with silastic mesh has been used as a viable option in children receiving transplants, but there is no experience recorded with its use in adults. A retrospective review was conducted on 200 consecutive liver transplantations performed over 42 months (October 2002 to February 2006). Records were evaluated for patient and donor demographics, perioperative factors including Model for End-Stage Liver Disease and Child-Turcotte-Pugh scores, indications for OLT, ischemic times, blood product administration, and use of temporary silastic mesh closure. Patients requiring silastic mesh were further evaluated for indication, time to primary fascial closure, duration of intubation, length of stay, graft function, and complications (infectious, vascular, biliary, and hernia development). Comparisons were made with a cohort of patients undergoing OLT over the same time period but who were closed primarily, without the use of temporary silastic mesh. Fifty-one liver transplantations (25.5%) of the 200 total transplant cohort used silastic mesh closure. Comparison of the cohorts (primary closure vs. temporary mesh) revealed that no differences existed, except the requirement of all blood products was significantly greater in the silastic mesh group (P < 0.001). Bowel edema (47.1%) and coagulopathy (37.3%) were the most common indications for mesh closure, with less frequent reasons including donor to recipient size mismatch (11.8%), hemodynamic instability, and a large preexisting fascial defect (2.0% each). The average time from transplant to final fascial closure was 3.4 days (range 2-9 days). In the silastic cohort, 41 transplants where closed primarily, 3 required the addition of synthetic mesh, and 6 had component separation and flap closure. After fascial closure, the mean time to extubation was 1 day. The median length of follow-up was 1.3 years for the silastic closure group. Long-term wound complications in the silastic closure group included 1 instance of colonic fistula, 2 incisional hernias, and 2 wound infections. The 30-day and 1-year patient survival for this group were 93.6 and 82.4%, respectively, and the graft survival for those same periods were 90.2 and 77.7%, respectively. Wound complications, rates of hepatic artery thrombosis or stricture, portal vein thrombosis or stricture, biliary complications, and allograft and patient survival were no different than those in patients undergoing initial primary closure. In adult liver transplantation with a difficult (or potentially difficult) abdomen, temporary closure with silastic mesh was found to allow for uncomplicated fascial closure in a short period of time, with rapid extubation times, excellent graft function, and minimal instances of infectious or wound complications. In circumstances where large amounts of blood products are required, where a size mismatch exists, or where bowel edema is present during adult liver transplantation, temporary closure with silastic mesh is an ideal strategy., ((c) 2007 AASLD.)

Malignancy is a well defined complication of chronic immunosuppression. Post transplant malignancies appear to be related to cumulative doses of immunosuppression, and in pediatric patients, acute infection of previously naive patients. The most commonly encountered malignancy in this age population is Post Transplant Lymphoproliferative Disorder (PTLD). PTLD is not a single entity but rather represents a continuum of disease. Treatment of PTLD should be initiated with immunosuppression reduction. Standard dose chemotherapy leads to significant morbidity. With the introduction of anti-CD20 antibody treatment with rituximab, chemotherapy has become second line therapy. The occurrence of solid malignancy appears to be associated with chronic immunosuppression. These cancers include those of skin, gynecologic organs, and the rectum, all of which appear to have the strongest association with viral mediators. Several strategies have been postulated to minimize the occurrence of malignancy. These include ganciclovir prophylaxis for the prevention of PTLD and the use of mychophenolic acid and TOR inhibitor maintenance to diminish the incidence of PTLD and solid malignancies. This leaves transplant physicians with several new and novel immunosuppressive agents with uncertain oncologic potentials that will need to be examined over the next decade.

Steroids and calcineurin inhibitors (CNI) have been mainstays of immunosuppression but both have numerous side effects that are associated with substantial morbidity and mortality. This study was carried out to determine if steroids can be eliminated with early discontinuation of cyclosporine A (CsA) and later discontinuation of mycophenolate mofetil (MMF). Ninety-six patients with kidney transplants were entered into four subgroups of two pilot studies. All patients received Thymoglobulin induction, rapamycin (RAPA), and the immunonutrients arginine and an oil containing omega-3 fatty acids. Mycophenolate mofetil was started in standard doses and discontinued by 2 years. CsA was given in reduced doses for either 4, 6, or 12 months. Follow-up was 12-36 months. Thirteen first rejection episodes occurred during the first year (14%). Combining all patients, 86% were rejection-free at 1 year, 80% at 2 years and 79% at 3 years. No kidney has been lost to acute rejection. Ninety percent of the 84 patients at risk at the end of the study were steroid-free and 87% were off CNI. Fifty-seven percent of 54 patients with a functioning kidney at 3 years were receiving monotherapy with RAPA. We conclude that this therapeutic strategy is worthy of a prospective multi-center clinical trial.

Objective: We examined the occurrence of neoplasms among 1008 renal transplant recipients treated with a sirolimus-cyclosporine (CsA) +/- prednisone (Pred) regimen., Methods: A comprehensive database of demographic, laboratory, clinical, and histopathologic features of these patients all followed in our transplant center was analyzed using Student t test and Mann-Whitney U test for continuous and chi-square test for categorical variables. Comparisons were performed with information in the Israel Penn International Transplant Tumor Registry (IPITTR)., Results: During the mean patient follow-up of 62.3 +/- 26.1 months (range 27.1 to 131), 36 tumors occurred in 35 patients (3.6%) at 32.5 +/- 29.8 months. The most common neoplasms were skin tumors (2.4%), a value that was significantly lower than the 6% rate observed with CsA-azathioprine-Pred treatment. Also, the 0.4% incidence of posttransplant lymphoproliferative disorders and 0.2% incidence of renal cell carcinomas were less than half of those previously reported with a combination of tacrolimus and mycophenolate mofetil. The distribution of tumor types was similar to that reported to the IPITTR. The mean trough drug concentrations in affected recipients at the time of diagnosis were within the putative target ranges., Conclusion: Renal transplant recipients treated with the sirolimus-CsA +/- Pred combination showed a low incidence of tumors of similar types as those encountered with other regimens.

Sarcoma is generally a rare disease in the US, with poor survival in patients with both primary angiosarcoma and metastatic disease from sarcoma and GIST. In order to determine if liver transplantation for sarcoma is a realistic option, we examined records of all patients in the US component of the Israel Penn International Transplant Tumor Registry were reviewed. Those patients with liver failure from primary or metastatic liver sarcoma were evaluated. Patient outcome analysis was then performed. Patient and tumor demographics were reviewed as well as patient survival after transplantation. 19 patients are identified having received liver transplantation after treatment for sarcoma of the liver, 6 patients with primary hepatic sarcoma and 13 patients with metastatic sarcoma of the liver. Recurrence was almost universal in 18 of 19 patients (95%) after a median interval of 6 months. Survival for the group as a whole was 47% for 1-year, 15% for 3-years and 5% for 5-years. Given the early recurrence of tumor and meager 1-year survival outcome, liver transplantation is a poor therapeutic choice for patients with either primary or metastatic liver sarcoma, including high-grade leiomyosarcoma (GIST) regardless of primary site or primary therapy.

Background: Liver transplant recipients are at high risk for multi-drug resistant infections because of broad-spectrum antibiotic and immunosuppression. This study evaluates the clinical and financial impact of vancomycin resistant Enterococcus (VRE) in liver transplant recipients., Methods: Liver transplant recipients with VRE from 1995 to 2002 were identified and matched (age, gender, UNOS status, liver disease and transplant date) to controls. Demographics, clinical factors, co-infections, antibiotic use, length of stay, abdominal surgeries, biliary complications, survival and resource utilization were compared with matched controls., Results: Nineteen patients were found to have 28 VRE infections via evaluation of microbiologic culture results of all liver transplant patients in the transplant registry. Thirty-eight non-VRE patients served as matched controls. The four most common sites VRE was cultured from included blood (35%), peritoneal fluid (35%), bile (20%), and urine (12%). Median time from transplant to infection was 48 d (range of 4-348). No significant differences in demographics were observed. The VRE group had a higher incidence of prior antibiotic use than the non-VRE group (95% vs. 34%; p < 0.05). The VRE group also experienced more abdominal surgery (20/19 vs. 3/38; p = 0.029), biliary complications (9/19 vs. 9/38; p = 0.018) and a longer length of stay (42.5 vs. 21.7 d; p = .005). Survival in the VRE group was lower (52% vs. 82%; p = 0.048). Six of the 19 VRE patients were treated with linezolid for eight infection episodes, and four of six patients survived. Eight patients were treated with quinupristin/dalfopristin for nine infections, and two of eight survived. Increased cost of care was observed in the VRE group. Laboratory costs were higher in the VRE group (6500 dollars vs. 1750; p = 0.02) as well., Conclusion: VRE was associated with prior antibiotic use, multiple abdominal surgeries, biliary complications and resulted in decreased survival compared to non-VRE control patients. VRE patients also utilized more hospital resources. Linezolid showed a trend toward improved survival.

The purpose of this study was to define risk factors for acute rejection with early corticosteroid withdrawal (CSWD; within 7 days posttransplant) in renal transplantation. Data from prospective, IRB-approved early CSWD trials were analyzed. Overall acute rejection rate in 308 patients was 17.1%. Acute rejection rates and observed risks (OR) in patients with individual risk factors were: repeat transplants 38.6%; current PRA >25%; 29.4%; African Americans 23.5%; delayed graft function (DGF) 26.1%; HLA DR mismatches >0 17.9%; female gender 19.7%; Thymoglobulin induction 15.3%; type 1 diabetes 30.8%; type 2 diabetes 11.1%; deceased donor recipients 21%; and living donor recipients 14%. Logistic regression analysis provided the following risks (OR) for acute rejection: repeat transplant 2.51; current PRA > 25% 1.53; African Americans 1.47; DGF 1.58; HLA DR mismatches > 0 1.61; female gender 1.43; Thymoglobulin induction 0.61; type 1 diabetes 2.23, type 2 diabetes 0.5, deceased donor recipients 1.11, and living donor recipients 0.9. Risk factors for acute rejection under early corticosteroid withdrawal are similar to those previously defined under chronic corticosteroid therapy. These observations provide implications for future CSWD trials including: use of T cell depleting antibody induction therapy (thymoglobulin) to reduce acute rejection risk, 2) enrollment stratification for high risk groups, and 3) modified immunosuppression for high risk groups.

As newer immunosuppressive regimens have steadily reduced the incidence of acute rejection and have extended the life expectancy of allograft recipients, posttransplant malignancy has become an important cause of mortality. In fact, it is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next 2 decades. An understanding of the underlying pathobiology and how to minimize cancer risks in transplant recipients are essential. The etiology of posttransplant malignancy is believed to be multifactorial and likely involves impaired immunosurveillance of neoplastic cells as well as depressed antiviral immune activity with a number of common posttransplant malignancies being viral-related. Although calcineurin inhibitors and azathioprine have been linked with posttransplant malignancies, newer agents such as mycophenolate mofetil and sirolimus have not and indeed may have antitumor properties. Long-term data are needed to determine if the use of these agents will ultimately lower the mortality due to malignancy for transplant recipients.

Background: Weight gain is a known complication of corticosteroid maintenance therapy. The purpose of the present study was to compare patterns of weight gain under chronic corticosteroid therapy (CCST) with that observed under early (i.e., within 7 days posttransplant) corticosteroid withdrawal (CSWD) in renal-transplant recipients., Methods: Renal-transplant recipients who underwent early CSWD under four prospective, institutional review board-approved clinical trials were compared with a historic control group of patients receiving maintenance CCST., Results: One hundred sixty-nine patients with early CSWD were compared with 132 patients who received CCST. Mean population weight gain was significantly higher in CCST patients at 3, 6, and 12 months posttransplant. Race influenced weight gain because white CSWD patients demonstrated greater reductions in weight gain compared with African-American patients. Sex also influenced weight gain: women demonstrated a greater benefit from CSWD than did men. Corticosteroid rejection therapy in CSWD patients completely restored weight gain because these patients showed weight gains similar to the CCST group. Finally, pretransplant body mass index (BMI) also influenced weight gain because patients who were overweight (BMI 25-30) or obese (BMI>30) demonstrated a greater reduction in weight gain with CSWD than did patients of normal weight (BMI<25)., Conclusions: Early CSWD minimizes weight gain in renal-transplant recipients. Women, whites, and patients with high pretransplant BMI had greater reductions in weight gain with early CSWD.

Significant mortality is associated with post-transplant lymphoproliferative disorder (PTLD) in kidney transplant recipients (KTX). Univariate/multivariate risk factor survival analysis of US PTLD KTX reported to Israel Penn International Transplant Tumor Registry from November 1968 to January 2000 was performed. PTLD presented 18 (median) (range 1-310) months in 402 KTX. Death rates were greater for those diagnosed within 6 months (64%) versus beyond 6 months (54%, p = 0.04). No differences in death risk for gender, race, immunosuppression, EBV, B or T cell positivity were identified. Death risk increased for multiple versus single sites (73% vs. 53%, hazards ratio (HR) 1.4). A 1-year increase in age increased HR for death by 2%. Surgery was associated with increased survival (55% vs. 0% without surgery) (p < 0.0001). Patients with allograft involvement, treated with transplant nephrectomy alone (n = 20), had 80% survival versus 53% without allograft removal (n = 15) (p < 0.001). Overall survival was 69% for allograft involvement alone versus 36% for other organ involvement plus allograft (n = 19 alive) (p < 0.0001). Death risk was greater for multiple site PTLD and increasing age, and risks were additive. Univariate analysis identified increased death risk for those not receiving surgery, particularly allograft involvement alone.

Unlabelled: Early corticosteroid withdrawal has been shown to be effective in low-risk patient populations in a number of US and European multicenter trials. However, patient populations traditionally considered to be at high risk for acute rejection (eg, African Americans, repeat transplant recipients, sensitized patients) are usually excluded from these trials. Since our initial experience with early withdrawal almost 10 years ago, we have included high-immunologic-risk patients. We have accumulated enough high-risk patients with early withdrawal to allow the first multivariate analysis of risk factors for acute rejection in early withdrawal under modern immunosuppression., Methods: Early withdrawal was performed under prospective IRB-approved protocols. Statistical analysis included chi square test and logistic regression. All rejection episodes were biopsy proven and graded by Banff 1997 criteria., Results: A total of 164 patients underwent early withdrawal: 82% had at least one mismatched DR antigen, 17% had delayed graft function, 33% were African American, and 18% were repeat transplant recipients. Multivariate analysis of risk factors for acute rejection indicated that two factors induced a statistically significant alteration in acute rejection risk: repeat transplant recipients (4.3-fold increased risk) and thymoglobulin induction (0.30 risk (ie, 70% reduction in risk compared to patients not receiving thymoglobulin induction). Sensitized recipients and African Americans were also at increased risk but did not quite reach statistical significance. These data strongly support the use of T-cell depleting antibody induction therapy in high-risk patients undergoing early withdrawal under modern immunosuppression.

Introduction: Very little published data exist regarding the results of chemotherapy treatment of posttransplant lymphoproliferative disorder (PTLD). The purpose of the study was to review the Israel Penn International Transplant Tumor Registry experience with PTLD treated with chemotherapy., Methods: Patients with PTLD who received chemotherapy were identified and data collected regarding demographics, tumor characteristics, recurrence rates, and survival., Results: One hundred ninety three solid organ transplant recipients with PTLD who received chemotherapy were identified. Most patients were male (142:51) and Caucasian (148; 16 AA, 29 unspecified). Most PTLD were B-cell predominant (81%), monoclonal (71), and CD 20+ (60% of patients tested). Organ transplanted included: kidney, 92 (48%); heart, 54 (28%); liver, 30 (16%); pancreas, 8 (4%); and lung, 9 (5%). Median time to presentation posttransplant was 24.5 months (range 0.8 to 226.5 months). Ninety patients received CHOP, 12 ProMACE, 65 other multidrug regimens, and 23 patients received single-agent chemotherapy. Five-year survival for these four regimens were: 24%, 25%, 32%, and 5%. PTLD-specific death rates were 34%, 34%, 40%, and 48%., Conclusions: Single-agent chemotherapy appears to be inferior to other chemotherapy regimens for PTLD as it is associated with lower survival.

Background: Few data exist regarding central nervous system (CNS) involvement in patients with posttransplant lymphoproliferative disorder (PTLD). The purpose of this study was to review the Israel Penn International Transplant Tumor Registry (IPITTR) experience with CNS involvement by PTLD., Methods: Nine hundred ten PTLD cases from the United States were reported to the IPITTR and reviewed for CNS involvement., Results: One hundred thirty-six transplant recipients with PTLD (15%) had CNS involvement. The highest incidence of CNS involvement occurred in pancreas (3 of 11; 27%) and kidney transplant recipients (76 of 429; 18%). Fifteen cases occurred in children and 121 cases in adults. For both children and adults, isolated CNS disease was associated with better survival when compared with multiple-site involvement (children: 29% vs 0%; adults: 12% vs 6%; P < .05). Three-year survival in PTLD patients with CNS involvement was 9.4% and without CNS involvement was 49.4% (P < .01). Radiation therapy alone appeared to provide the best survival rates (25%)., Conclusions: CNS involvement in transplant recipients with PTLD carries an ominous prognosis; however, isolated CNS involvement has a better prognosis than CNS plus extracranial involvement. Radiation therapy alone provides the best results, but this may be a reflection of isolated CNS disease.

Background: The first prospective trial of steroid withdrawal dedicated to high-immunologic-risk patients is reported herein., Methods: Twenty-five patients were enrolled prospectively in an IRB-approved HIPAA-compliant protocol. Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12 ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The protocol for the next 15 patients was modified because of high acute rejection rates to include received T-cell-depleting antibody induction therapy with thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes were diagnosed by biopsy and graded using Banff '97 criteria., Results: Twenty-five patients were enrolled and median follow-up was 402 days. Forty percent of recipients were black, 68% of patients were repeat transplant recipients, 68% received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute rejection, graft survival, and patient survival rates of 40%, 88%, and 96%, respectively, were observed for the duration of the study. Acute rejection occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute rejection rates fell to 27% when thymoglobulin was introduced (P = .1)., Conclusions: This study supports our previous observations in a multivariate analysis of early CSWD patients, wherein polyclonal antibody induction therapy reduced acute rejection. High-immunologic-risk patients may be able to undergo early CSWD with acceptable rates of acute rejection.