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Background: The hernia defects that develop in liver transplant recipients tend to be complex. Unfortunately, there is a paucity of data to guide post-transplant hernia management. Our goal was to evaluate the outcomes following laparoscopic ventral hernia repair (LVHR) in liver transplant recipients., Methods: A retrospective review of a prospectively kept database of liver transplant patients at a single tertiary healthcare facility was completed. All patients between 2007 and 2020 who underwent LVHR for a hernia at their transplant incision site were included. The primary outcome studied was hernia recurrence. Secondary outcomes included time-to-hernia repair, complications, and length of stay (LOS)., Results: There were 89 patients who met inclusion criteria. 82% were male, mean age was 60 years, and mean body mass index was 30.2 kg/m 2 . 94.4% were on tacrolimus and 36% on mycophenolate mofetil. Median time-to-hernia repair was 16 months with a mean mesh size of 743 cm 2 and length of stay of 3.7 days. None required conversion to an open operation. Postoperative complications included ileus (20.2%), acute kidney injury (11.2%), pneumonia (6.7%), and bleeding requiring re-operation (1.1%). Hernia-related complications included chronic suture site pain (1.1%), seroma requiring intervention (3.3%), surgical site infection (3.3%), nonoperative mesh infection (1.1%), and mesh infection requiring explantation (1.1%). Median follow-up was 23 months. Hernia recurrence occurred in 4.5% and no predictive variables for recurrence were identified., Conclusions: Although the hernia defects that develop in liver transplant recipients are complex and their comorbidities significant, LVHR can safely and effectively repair these defects with low rates of recurrence and complications., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Centers for Medicare and Medicaid Services is a major payer for abdominal transplant services. Reimbursement reductions could have a major impact on the transplant surgical workforce and hospitals. Yet government reimbursement trends in abdominal transplantation have not been fully characterized., Methods: We performed an economic analysis to characterize changes in inflation-adjusted trends in Medicare surgical reimbursement for abdominal transplant procedures. Using the Medicare Fee Schedule Look-Up Tool, we performed a procedure code-based surgical reimbursement rate analysis. Reimbursement rates were adjusted for inflation to calculate overall changes in reimbursement, overall year-over-year, 5-year year-over-year, and compound annual growth rate from 2000 to 2021., Results: We observed declines in adjusted reimbursement of common abdominal transplant procedures, including liver (-32.4%), kidney with and without nephrectomy (-24.2% and -24.1%, respectively), and pancreas transplant (-15.2%) (all, P < .05). Overall, the yearly average change for liver, kidney with and without nephrectomy, and pancreas transplant were -1.54%, -1.15%, -1.15%, and -0.72%. Five-year annual change averaged -2.69%, -2.35%, -2.64%, and -2.43%, respectively. The overall average compound annual growth rate was -1.27%., Conclusion: This analysis depicts a worrisome reimbursement pattern for abdominal transplant procedures. Transplant surgeons, centers, and professional organizations should note these trends to advocate sustainable reimbursement policy and to preserve continued access to transplant services., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Lobar torsion is a rare occurrence in which a portion of the lung is twisted on its bronchovascular pedicle. The vast majority are observed in the acute postoperative period often following right upper lobectomy. Spontaneous middle lobe torsion independent of pulmonary resection is exceptionally rarer; fewer than 15 cases have been recorded. We present an institutional case series of 2 patients postorthotopic liver transplantation who developed spontaneous middle lobe torsion due to large pleural effusions., Methods: We provide the medical course as well as intraoperative techniques for our 2 patients along with a review of the literature., Results: Both patients in this case series underwent orthotopic liver transplant complicated postoperatively by a large pulmonary effusion. Patient one developed an abdominal hematoma requiring evacuation and repair, after which he developed progressive shortness of breath. Bronchoscopy revealed a right middle lobe obstruction; upon thoracotomy, 180-degree torsion with widespread necrosis was evident and the middle lobe was removed. He is doing well to date. Patient 2 experienced postoperative pleural effusion and mucus plugging; computed tomography revealed abrupt middle lobe arterial occlusion prompting urgent operative intervention. Again, the middle lobe was grossly ischemic and dissection revealed a 360-degree torsion around the pedicle. It was resected. He is doing well to date., Conclusions: As the result of its rarity, radiographic and clinical diagnosis of spontaneous pulmonary lobar torsion is challenging; a high index of suspicion for spontaneous middle lobe torsion must be maintained to avoid delays in diagnosis. Prompt surgical intervention is essential to improve patient outcomes., (© 2023 The Author(s).)

Background: The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission., Methods: Abdominal solid organs from SARS-CoV-2-infected donors were transplanted into uninfected recipients., Results: Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2-infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA., Conclusions: Transplanting nonlung organs from SARS-CoV-2-infected donors into uninfected recipients demonstrated no evidence of virus transmission., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Introduction and Objectives: Acute on chronic liver failure (ACLF), leads to high mortality. These patients are at risk of being delisted for liver transplantation (LT). Emerging data shows 1y post-transplant survival of 80-92%. The Share 35 (S35) policy was implemented to prioritize patients with MELD ≥35 on the LT waitlist. Our aim was to compare the LT outcomes of ACLF patients as a result of S35., Materials and Methods: Data from the UNOS scientific registry were used to classify ACLF patients using the NACSELD criteria. For the analyses, data were divided into two eras; 2 years before S35 (Era 1) and 2 years after S35 (Era 2). Waitlist status was classified into categories: Transplanted, Death or Too Sick to Transplant and Still Waiting/Other. LT cumulative incidence between the populations in the eras was calculated using Fine and Gray's method. A proportional hazards model was used to investigate the era effect on cumulative incidence of LT., Results: 46,861 patients were reviewed, of which 817 had ACLF. 366 patients (mean MELD: 37.1) were identified in Era 1 and 451 patients (mean MELD: 37.3) in Era 2. We found that ACLF patients were more likely to receive a liver transplant in Era 2 (p=0.0074). In both eras, transplanted patients had a significantly higher survival than those who were not transplanted (p<0.0001)., Conclusions: Our study shows that S35 improved LT rate for ACLF suggesting that there should be broader recognition of ACLF and early transplantation should be pursued., (Copyright © 2020 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To evaluate the outcomes and perioperative complication rates following robot- assisted transplant nephrectomy ((RATN)., Methods: All patients who underwent RATN at our institution were included. No exclusion criteria were applied. Clinical records were retrospectively reviewed and reported. This included preoperative, intraoperative, and postoperative outcomes. Complications were reported utilizing the Clavien-Dindo classification system. Descriptive statistics were reported using frequencies and percentages for categorical variables, means and standard deviation for continuous variables., Results: Between July 2014 and April 2018, 15 patients underwent RATN. Most patients had the transplant in the right iliac fossa (13/15). Ten patients underwent a concomitant procedure. The total operative time for the entire cohort was 336 (±102) minutes (including cases who had concomitant procedures) and 259 (±46 minutes) when cases with concomitant procedures were excluded. Mean estimated blood loss was 383 (±444) mL. Postoperatively, 3 patients required blood transfusion. Average hospital stay was 4 (±2.7) days. Most patients had finding consistent with graft rejection on final pathology. There were 5 complications; 3 of which were minor (grade 2 = 2 and grade 3 = 1); one patient had a wound infection requiring dressing (3A) and one patient died due to pulmonary embolism following discharge. Limitations include small series and retrospective nature of the study., Conclusion: This case series demonstrate that RATN is technically feasible. With continued experience and larger case series, the robotic approach may provide a minimally invasive alternative to open allograft nephrectomy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) is a leading cause of post-liver transplant death, and variable care patterns may affect outcomes. We aimed to describe epidemiology and outcomes of inpatient CVD care across US hospitals. Using a merged data set from the 2002-2011 Nationwide Inpatient Sample and the American Hospital Association Annual Survey, we evaluated liver transplant patients admitted primarily with myocardial infarction (MI), stroke (cerebrovascular accident [CVA]), congestive heart failure (CHF), dysrhythmias, cardiac arrest (CA), or malignant hypertension. Patient-level data include demographics, Charlson comorbidity index, and CVD diagnoses. Facility-level variables included ownership status, payer-mix, hospital resources, teaching status, and physician/nursing-to-bed ratios. We used generalized estimating equations to evaluate patient- and hospital-level factors associated with mortality. There were 4763 hospitalizations that occurred in 153 facilities (transplant hospitals, n = 80). CVD hospitalizations increased overall by 115% over the decade (P < 0.01). CVA and MI declined over time (both P < 0.05), but CHF and dysrhythmia grew significantly (both P < 0.03); a total of 19% of hospitalizations were for multiple CVD diagnoses. Transplant hospitals had lower comorbidity patients (P < 0.001) and greater resource intensity including presence of cardiac intensive care unit, interventional radiology, operating rooms, teaching status, and nursing density (all P < 0.01). Transplant and nontransplant hospitals had similar unadjusted mortality (overall, 3.9%, P = 0.55; by diagnosis, all P > 0.07). Transplant hospitals had significantly longer overall length of stay, higher total costs, and more high-cost hospitalizations (all P < 0.05). After risk adjustment, transplant hospitals were associated with higher mortality and high-cost hospitalizations. In conclusion, CVD after liver transplant is evolving and responsible for growing rates of inpatient care. Transplant hospitals are associated with poor outcomes, even after risk adjustment for patient and hospital characteristics, which may be attributable to selective referral of certain patient phenotypes but could also be related to differences in quality of care. Further study is warranted., (© 2018 by the American Association for the Study of Liver Diseases.)

Background: Significant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO 2peak ), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing., Methods and Results: We outlined a pre-renal transplant screening algorithm to incorporate VO 2peak testing among a population of asymptomatic high-risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO 2peak <17 mL/kg per minute (equivalent to <5 metabolic equivalents) underwent further noninvasive cardiac screening tests. We conducted a retrospective study of the a priori dichotomization of the VO 2peak <17 versus ≥17 mL/kg per minute to determine negative and positive predictive value of future cardiac events and all-cause mortality. We report a high (>90%) negative predictive value, indicating that VO 2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all-cause mortality. However, lower VO 2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant., Conclusions: We conclude that incorporating an objective measure of cardiorespiratory fitness with VO 2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher-risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Aim: To determine whether hospital characteristics predict cirrhosis mortality and how much variation in mortality is attributable to hospital differences., Methods: We used data from the 2005-2011 Nationwide Inpatient Sample and the American Hospital Association Annual survey to identify hospitalizations for decompensated cirrhosis and corresponding facility characteristics. We created hospital-specific risk and reliability-adjusted odds ratios for cirrhosis mortality, and evaluated patient and facility differences based on hospital performance quintiles. We used hierarchical regression models to determine the effect of these factors on mortality., Results: Seventy-two thousand seven hundred and thirty-three cirrhosis admissions were evaluated in 805 hospitals. Hospital mean cirrhosis annual case volume was 90.4 (range 25-828). Overall hospital cirrhosis mortality rate was 8.00%. Hospital-adjusted odds ratios (aOR) for mortality ranged from 0.48 to 1.89. Patient characteristics varied significantly by hospital aOR for mortality. Length of stay averaged 6.0 ± 1.6 days, and varied significantly by hospital performance ( P < 0.001). Facility level predictors of risk-adjusted mortality were higher Medicaid case-mix (OR = 1.00, P = 0.029) and LPN staffing (OR = 1.02, P = 0.015). Higher cirrhosis volume (OR = 0.99, P = 0.025) and liver transplant program status (OR = 0.83, P = 0.026) were significantly associated with survival. After adjusting for patient differences, era, and clustering effects, 15.3% of variation between hospitals was attributable to differences in facility characteristics., Conclusion: Hospital characteristics account for a significant proportion of variation in cirrhosis mortality. These findings have several implications for patients, providers, and health care delivery in liver disease care and inpatient health care design., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose.

Nontuberculous mycobacteria are ubiquitous environmental organisms that are infrequently implicated as pathogens. Peritoneal infection with nontuberculous mycobacteria is rare and published reports are most commonly associated with peritoneal dialysis. This study describes a case of a 41-year-old woman with cirrhosis who had Mycobacterium abscessus peritonitis and an abdominal abscess resulting from infection of a remotely placed gastric band (Lap-Band; Apollo Endosurgery, Inc).

Background: Currently, transplant patients have limited metrics available to understand transplant center quality. Graft and patient survival do not capture the patient experience, and patients may use more general consumer assessments of hospital care to help select transplant centers. We evaluated whether consumer assessments of hospital quality correlate with short- and long-term kidney transplant center performance., Materials and Methods: CMS uses the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) to publicly report patients' perspectives on hospital care. We merged 2012 SRTR kidney transplant (n = 200 centers), HCAHPS and American Hospital Association survey data. Center performance was determined by variation in observed-to-expected (O/E) ratios for 1-month and 1-year graft failure. We used multivariate regression to determine whether HCAHPS measures correlate with center performance, after risk-adjusting for structural characteristics and volume., Results: Center-specific graft failure varied significantly (30 day O/E range: 0-4.1). At 30 days, compared to average centers, cleanliness (OR = 1.26, P = .001), patient recommendation (OR = 1.18, P = .005), and high overall ratings (OR = 1.11, P = .036) predicted high performance. Poor nursing-patient communication (OR = 0.70, P = .030), lower cleanliness (OR = 0.67, P < .001), poor overall ratings (OR = 0.79, P = .038), and no recommendation (OR = 0.68, P = .019) correlated with average/low performance. There was no significant correlation between HCAHPS measures and 1-year outcomes., Conclusions: The association between hospital consumer assessments of hospital care and center performance after kidney transplantation is limited. More specific metrics oriented to capturing transplant patient perspectives may be valuable in further defining transplant quality., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The aim of this study was to determine the clinical and histologic outcomes related to transplanting kidneys from deceased donors with glomerular fibrin thrombi (GFT). We included all cases transplanted between October 2003 and October 2014 that had either a preimplantation biopsy or an immediate postreperfusion biopsy showing GFT. The study cohort included 61 recipients (9.9%) with GFT and 557 in the control group without GFT. Delayed graft function occurred in 49% of the GFT group and 39% in the control group (p = 0.14). Serum creatinine at 1, 4, and 12 months and estimated GFR at 12 months were similar in the two groups. Estimated 1-year graft survival was 93.2% in the GFT group and 95.1% in the control group (p = 0.22 by log-rank). Fifty-two of the 61 patients in the GFT group (85%) had a 1-month protocol biopsy, and only two biopsies (4%) showed residual focal glomerular thrombi. At the 1-year protocol biopsy, the prevalence of moderate to severe interstitial fibrosis and tubular atrophy was 24% in the GFT group and 30% in the control group (p = 0.42). We concluded that GFT resolves rapidly after transplantation and that transplanting selected kidneys from deceased donors with GFT is a safe practice., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: While simultaneous pancreas kidney transplant (SPKTx) is a therapeutic option for patients with type 1 diabetes (T1DM) and renal failure, few centers offer SPKTx to "select" non-T1DM patients. To address concerns that existing insulin resistance may limit the benefits of the pancreas allograft among non-T1DM, we compared several indices of glucose homeostasis, in "select" non-T1DM and T1DM patients who received SPKTx., Methods: Criteria for "select" non-T1DM included the following: positive C-peptide, BMI <30 kg/m(2) , treatment with oral agents before insulin initiation, and insulin at <1 unit/kg/d. We compared several indices of glucose homeostasis within 1 yr post-SPKTx among seven "select" patients with non-T1DM and nine patients with T1DM with similar age, BMI, and immunosuppression. Measurements of insulin resistance included the following: homeostatic model, insulin sensitivity index, and insulin-glucose ratio; insulin secretion measures included the following: corrected insulin response., Results: Non-T1DM had similar pre-transplant metabolic (fasting glucose, HbA1c, blood pressure, and lipid) parameters to the T1DM cohort. There were no significant differences in the various measures of insulin resistance and secretion between T1DM and "select" non-T1DM patients., Conclusion: Our results suggest SPKTx should be considered in the therapeutic armamentarium among carefully select non-T1DM with features of minimal insulin resistance; however, a larger cohort with longer follow-up is needed to confirm our results., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Robotic surgery offers three-dimensional visualization and precision of movement that could be of great value to hepatobiliary surgeons. Previous reports of robotic choledochocele resections in adults have detailed extracorporeal jejunojejunostomies. We describe a total robotic excision of a choledochal cyst with hepaticojejunostomy and intracorporeal Roux-en-Y anastomosis., Methods: A 58-year-old woman underwent a robotic excision of a small choledochocele with hepaticojejunostomy and intracorporeal Roux-en-Y., Result: Port placement was determined via collaborative surgical discussion and previously reported robotic right hepatectomies. Total operative time was 386 min and total robot working time was 330 min. The hepaticojejunostomy was performed using 5-0 PDS suture with parachute-style back wall and running front wall sutures. The jejunojejunostomy was a stapled anastomosis. Estimated blood loss was less than 100 mL. The patient was ambulating and tolerating oral intake on post-operative day 1, and was discharged home on post-operative day 2., Conclusions: Robotic resection of choledochal cyst with intracorporeal Roux-en-Y anastomosis is feasible, with advantages over open surgery such as superior visualization, precision, and post-operative patient recovery.

Solid organ transplantation is encumbered by an increasing number of waitlisted patients unrequited by the current organ supply. Preclinical models suggest that advances in deceased donor management and treatment can increase the quantity and quality of organs available for transplantation. However, the science of donor intervention and the execution of high quality, prospective, multi-center, randomized-controlled trials are restricted by a myriad of logistical challenges mired in regulatory and ethical ambiguity. By highlighting the obstacles to conducting research in deceased donors, this report endeavors to stimulate the creation of a multi-disciplinary framework to facilitate the design, implementation and supervision of innovative trials that increase the quantity and/or quality of deceased donor organs., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Improved outcomes have expanded the indications for liver transplantation, thus aggravating the already limited supply of donor organs. Domino liver transplantation (DLT) has been one strategy to augment the supply of donor organs in cases of inborn errors of metabolism. One such disease is maple syrup urine disease (MSUD), an inherited disorder of branched-chain amino acid (BCAA) metabolism., Methods: We report on the transplantation of a deceased donor liver into a patient with MSUD, and the sequential transplantation of the explanted liver into a patient with hemophilia A, HIV, hepatitis C, and a low priority on the transplant waiting list., Results: At 30 months, the MSUD recipient has had significant correction of BCAA metabolism on a protein-unrestricted diet and no progression of neuropsychiatric symptoms. The DLT recipient has been cured of hemophilia and has normal BCAA homeostasis. This case provides further evidence that elective orthotopic liver transplantation for MSUD attenuates the disease with restoration of BCAA metabolism, and that DLT in this setting can achieve excellent results in ESLD patients., Conclusion: It is possible that domino grafts from patients with MSUD could be used in more conventional recipients, but additional studies and longer-term outcomes are needed to determine the validity of DLT in MSUD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Tacrolimus pharmacokinetics vary due to single nucleotide polymorphisms (SNPs) in metabolizing enzymes and membrane transporters that alter drug elimination. Clinically we observed that Native Americans require lower dosages of tacrolimus to attain trough levels similar to Caucasians. We previously demonstrated that Native Americans have decreased oral clearance of tacrolimus, suggesting that Native Americans may have more variant SNPs and, therefore, altered tacrolimus pharmacokinetic parameters. We conducted 12-hour pharmacokinetic studies on 24 adult Native American kidney transplant recipients on stable doses of tacrolimus for at least 1 month posttransplantation. Twenty-four Caucasian kidney transplant recipients were compared as controls. SNPs encoding the genes for the enzymes (CYP3A4, CYP3A5) and transporters (ABCB1, BCRP, and MRP1) were typed using TaqMan. The mean daily tacrolimus dose in the Native Americans was 0.03 ± 0.02 compared with the Caucasians 0.5 ± 0.3 (mg/kg/d; P = .002), with no significant differences in trough levels, (6.7 ± 3.1 vs 7.4 ± 2.1 ng/dL; P = .4). Many Native Americans, but not Caucasians, demonstrated the 3/*3 - C3435T CC and the *3/*3 -G2677T GG genotype combination previously associated with low tacrolimus dosing. Native Americans required significantly lower tacrolimus doses than Caucasians to achieve similar tacrolimus trough levels, in part due to lower tacrolimus clearance from decreased drug metabolism and excretion., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To describe aspects of anesthesia for combined cardiac surgery and orthotopic liver transplant (OLT)., Design: Retrospective case series., Setting: Hospital with cardiac surgery and liver transplant programs., Participants: Nine patients between September 1998 and July 2006., Intervention: Combined cardiac surgery and OLT., Measurement and Main Results: Demographic and outcome data were recorded for each patient. Multiple intraoperative parameters were collected at baseline, after induction of anesthesia, after cardiac surgery, and after OLT. Five patients underwent combined OLT and coronary artery bypass graft (CABG) surgery. Four patients underwent combined OLT and aortic valve replacement (AVR) to relieve aortic stenosis. One of these 4 patients also had a saphenous vein graft to the left anterior descending artery. The CABG/OLT patients had hypertension, diabetes, or both, and multiple coronary arteries were affected although ejection fraction was preserved. The 1 death in this group was unrelated to a coronary event. The AVR/OLT patients had aortic stenosis that met American Heart Association guidelines for AVR. One death, within 24 hours of surgery, was associated with severe pulmonary artery hypertension. The median transfusion volumes were 12 units of packed red blood cells, 22 units of fresh frozen plasma, and 30 units of platelets. Three of the 9 patients required renal replacement therapy postoperatively. The median duration of intubation was 2 days, and length of stay in the intensive care unit was 5.5 days., Conclusion: Combined cardiac and OLT surgery is complex and serious morbidity occurs, but successful outcomes are attainable., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objective: To compare mortality, graft loss, and postoperative complications after liver transplant in older patients (> or =70 years) with those in younger patients (<60 years)., Patients and Methods: Outcomes for 42 patients aged 70 years or older who underwent liver transplant were compared with those of 42 matched controls younger than 60 years. All patients underwent transplants between March 19, 1998, and May 7, 2004. Information was collected on patient characteristics, comorbid conditions, laboratory results, donor and operative variables, medical and surgical complications, and mortality and graft loss., Results: Preoperative characteristics were similar across age groups, except for creatinine (P=.01) and serum albumin (P=.03) values, which were higher in older patients, and an earlier year of transplant in younger patients (P<.001). Intraoperatively, older patients required more erythrocyte transfusions (P=.04) and more intraoperative fluids (P=.001) than did younger patients. Postoperatively, bilirubin level (P=.007) and international normalized ratios (P=.01) were lower in older patients, whereas albumin level was higher (P<.001). The median follow-up was 5.1 years (range, 0.1-8.5 years). Compared with younger patients, older patients were not at an increased risk of death (relative risk, 1.00; 95% confidence interval, 0.43-2.31; P>.99) or graft loss (relative risk, 1.17; 95% confidence interval, 0.54-2.52; P=.70). The frequency of other complications did not differ significantly between age groups, although older patients had more cardiovascular complications., Conclusion: Five-year mortality and graft loss in older recipients were comparable with those in younger recipients, suggesting that age alone should not exclude older patients from liver transplant.

Adult polycystic liver disease (PLD) can cause massive hepatomegaly leading to pain, caval obstruction, and hemorrhage. Many surgical techniques including aspiration, fenestration, and resection have been used to treat PLD. In addition to substantial morbidity and mortality, conservative surgery may have limited success, and palliation may be temporary. With improved results of liver transplantation, it has become the definitive treatment for PLD. We retrospectively reviewed our experience in patients with PLD between 1998 and 2007. Thirteen patients underwent liver only or liver-kidney transplantation. All surgical procedures were performed with preservation of the recipient inferior vena cava and without venovenous bypass (piggyback technique). Our patients experienced a high rate of perioperative morbidity. However, long-term patient and graft survival were excellent.

The use of donation after cardiac death (DCD) donors may provide a valuable source of organs for liver transplantation. Concerns regarding primary nonfunction (PNF) and intrahepatic biliary stricture (IHBSs) have limited the enthusiasm for their use. A retrospective analysis of 1436 consecutive deceased donor liver transplants performed between December 1998 and October 2006 was conducted. These included 108 DCD liver transplants, which were compared to 1328 transplants performed with organs from donors meeting the criteria for donation after brain death (DBD). The median follow-up was 48 months. The 1-, 3-, and 5-year patient survival and graft survival for DCD donors were 91.5%, 88.1%, and 88.1% and 79.3%, 74.5%, and 71.0%, respectively. The 1-, 3-, and 5-year patient survival and graft survival for DBD donors were 87.3%, 81.1%, and 77.2% and 81.6%, 74.7%, and 69.1%, respectively. Patient survival and graft survival were not significantly different between DCD donors less than 60 years old, DCD donors greater than 60 years old, and DBD donors. Causes of graft loss included IHBSs (n = 9), PNF (n = 4), recurrent hepatitis C virus (n = 4), hepatic artery thrombosis (n = 1), rejection (n = 2), and patient death (n = 13). Contrary to previously published data, excellent long-term patient survival and graft survival can be obtained with DCD allografts, and in our experience, they are equivalent to those obtained from DBD allografts., ((c) 2009 AASLD.)

Arterial vasodilation is common in end-stage liver disease, and systemic hypotension often may develop, despite an increase in cardiac output. During the preparation for and the performance of orthotopic liver transplantation, expected and transient hypotension may be caused by induction agents, anesthetic agents, liver mobilization, or venous clamping. A mild decrease of the already low systemic vascular resistance is often observed, and intermittent use of short-acting agents for vasopressor support is not uncommon. In this report, we describe a patient with unexpected and prolonged hypotension due to vasodilation during and after orthotopic liver transplantation. The preoperative end-stage liver disease evaluation, intraoperative events, and intensive care unit course were reviewed, and no cause for the vasodilation and prolonged hypotension was evident. The explant pathology report was later available and showed systemic mastocytosis. We hypothesize that the unexpected hypotension and vasodilation were caused by mast cell degranulation and its systemic effects on arterial tone.

Background: Risk factors for surgical site infection (SSI) after liver transplantation and outcomes associated with these infections have not been assessed using consensus surveillance and optimal analytic methods., Methods: A cohort study was performed of patients undergoing first liver transplantation at Mayo Clinic, Jacksonville, Florida, in 2003 and 2004. SSIs were identified by definitions and methods of the National Nosocomial Infections Surveillance System. Measures of known or suspected risk factors for SSI, graft loss, or death were collected on all patients. Associations of SSI with these factors and also with the primary composite endpoint of graft loss or death within 1 year of liver transplantation were examined using Cox proportional hazards models; relative risks (RRs) were estimated along with 95% confidence intervals (CIs)., Results: Of 370 patients, 66 (18%) had SSI and 57 (15%) died or sustained graft loss within 1 year after liver transplantation. Donor liver mass-to-recipient body mass ratio of less than 0.01 (RR 2.56; 95% CI 1.17-5.62; P=0.019) and increased operative time (RR 1.19 [1-hr increase]; 95% CI 1.03-1.37; P=0.018) were associated with increased SSI risk. SSI was associated with increased risk of death or graft loss within the first year after liver transplantation (RR 3.06; 95% CI 1.66-5.64; P<0.001)., Conclusion: SSI is associated with increased risk of death or graft loss during the first year after liver transplantation. Increased operative time and decreased donor liver-to-recipient body mass ratio showed evidence of association with SSI.

Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non-heart-beating or donation after cardiac death (DCD) are encouraging. However, long-term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow-up >4.5 years. During 1998-2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart-beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non-function and biliary complications as compared with SCD and ECD. The overall one-, two-, and five-yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long-term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Background: Timely transplantation of sensitized kidney recipients remains a challenge. Patients with a complement-dependent cytotoxicity negative and flow cytometry (FC) positive crossmatch carry increased risk of antibody-mediated rejection and thus graft loss. Solid phase assays are available to confirm donor specificity for antibody identified by FC crossmatch. Treatment using induction therapy with rabbit antithymocyte globulin (RATG) and intravenous immunoglobulin (IVIG) may allow successful transplant of these high-risk patients., Methods: A retrospective study of 264 consecutive patients after exclusions yielded 94 complement-dependent cytotoxicity anti-human globulin crossmatch-negative patients, including group 1: 58 primary transplants with panel-reactive antibody (PRA) less than 20%, group 2: 16 retransplants and PRA more than 20% who were FC crossmatch-negative, and group 3: 20 retransplants and PRA more than 20% who were FC crossmatch-positive. All were treated with RATG induction and maintenance therapy with tacrolimus, mycophenolate mofetil, and corticosteroids. Only group 3 received IVIG at 500 mg/kg daily in three doses., Results: Eighteen of 20 patients in group 3 had donor-specific antibody identified by solid phase assay. Cellular- and antibody-mediated rejections were statistically higher in group 3. Two-year serum creatinine and glomerular filtration rate along with 3-year patient and graft survival were comparable between the groups., Conclusions: Sensitized patients with positive FC crossmatch and donor-specific antibody identified by solid phase assays can be successfully transplanted using standard RATG induction, IVIG, and maintenance immunosuppression with equal renal function and graft survival to immunologically lower risk recipients. Given these results, this patient group should not be excluded from transplantation based on antibody specificities determined by virtual crossmatch techniques.

Alveolar soft-part sarcoma is a highly vascular soft-tissue tumor that is uniformly malignant. It comprises less than 1 per cent of all soft-tissue sarcomas. Patients with alveolar soft-part sarcoma most frequently are aged 15 to 35 years, and the soft tissues of the lower extremities typically are affected. In the pediatric population, it most frequently occurs in the head and neck and particularly affects the tongue and orbit. Alveolar soft-part sarcoma has been described as a primary lesion in the trunk, upper extremities, and retroperitoneum; more novel locations include the mediastinum, female genital tract, stomach, bone, and larynx. Numerous case reports describe alveolar soft-part sarcoma in diverse anatomic locations, but this report is, to our knowledge, the first documentation of primary alveolar soft-part sarcoma of the liver. We describe a 47-year-old woman with such a manifestation. Despite surgical resection and numerous chemotherapeutic regimens, this patient had widespread metastasis and died approximately 2 years after the diagnosis was established.

Peritonitis occurring after liver transplantation (PLT) has been poorly characterized to date. The aims of this study were to define the incidence, risk factors, microbiology profiles, and outcome of nonlocalized PLT. This was a retrospective study of 950 cadaveric liver transplantation (LT) procedures in 837 patients, followed for a mean of 1,086 days (range, 104-2,483 days) after LT. PLT was defined as the presence of at least one positive ascitic fluid culture after LT. There were 108 PLT episodes in 91 patients occurring at a median of 14 days (range, 1-102 days) after LT. Significant risk factors associated with the development of PLT by multivariate analysis included pre-LT model for end-stage liver disease score, duration of LT surgery, Roux-en-Y biliary anastomosis, and renal replacement therapy after LT. Biliary complications, intra-abdominal bleeding, and bowel leak/perforation were associated with 34.3%, 26.9%, and 18.5% of episodes, respectively. Multiple organisms, gram-positive cocci, fungus, and multidrug-resistant bacteria were isolated in 61.1%, 92.6%, 25.9%, and 76.9% of ascitic fluid cultures, respectively. The 28 fungal PLT episodes were associated with bowel leak/perforation and polymicrobial peritonitis. Patients who developed PLT after their first LT had a significantly greater risk of graft loss or mortality compared to unaffected patients. Parameters significantly associated with these adverse outcomes by multivariate analysis were recipient age at LT and bowel leak or perforation after LT. In conclusion, PLT is a serious infectious complication of LT, associated with significant intra-abdominal pathology and reduced recipient and graft survival., ((c) 2006 AASLD.)

Carcinosarcoma of the gallbladder is a rare malignancy characterized by both malignant epithelial and mesenchymal components. The clinical behavior of this tumor is extremely aggressive. Only 26 cases have been reported in the world literature to date. We report the case of a 64-year-old woman who had fever associated with a right upper quadrant mass. An exploratory laparotomy through a right upper quadrant incision was performed at another institution, and the patient was thought to have severe acute cholecystitis that would require additional antibiotic therapy before attempted resection. She was referred to our center, where abdominal CT showed a 6.4 x 8.2 cm pericholecystic mass involving the hepatic flexure of the colon. The patient underwent cholecystectomy and hepatic wedge resection, pancreaticoduodenectomy, and right hemicolectomy. Pathologic examination of the surgical specimen revealed two histologic components consisting of squamous cell carcinoma and spindle cell sarcoma of gallbladder origin, consistent with carcinosarcoma. All seven lymph nodes in the pancreaticoduodenectomy specimen were negative for tumor. We present this case and a review of the literature and current treatment recommendations.

Background: The use of liver allografts from an older donor (OD) (age>50 years) is a widespread strategy to manage the disparity between supply and demand of organs for liver transplantation. This study determines the effect of OD allografts on fibrosis progression and graft survival after liver transplantation in patients with and without infection caused by hepatitis C virus (HCV)., Methods: All patients undergoing liver transplantation at our center from March 1998 to December 2001 were analyzed. Protocol liver biopsies were performed at 1, 16, and 52 weeks after transplantation and yearly thereafter. One liver pathologist scored all biopsy specimens for modified hepatic activity index (0-18) and fibrosis (0-6)., Results: A total of 402 patients (167 with HCV and 235 without HCV) underwent liver transplantation during the study period. Among patients with HCV, baseline characteristics of OD recipients were similar to younger donor (YD) (age<50 years) recipients. In patients with HCV, graft survival was shorter in OD graft recipients than in YD recipients (P<0.001). In patients without HCV, graft survival was independent of donor age. In patients with HCV, a fibrosis score of 3 or greater was present in 17% of OD recipients at 4 months and in 26% at 12 months after transplantation, compared with 8% of YD recipients at 4 months and 13% at 12 months (P<0.001)., Conclusions: Liver transplantation with OD grafts is associated with rapid progression of fibrosis and decreased graft survival in patients with HCV, but not in patients without HCV. OD grafts should be considered preferentially for patients without HCV.

Intracranial hypertension leading to brain stem herniation is a major cause of death in fulminant hepatic failure (FHF). Mannitol, barbiturates, and hyperventilation have been used to treat brain swelling, but most patients are either refractory to medical management or cannot be treated because of concurrent medical problems or side effects. In this study, we examined whether allogeneic hepatocellular transplantation may prevent development of intracranial hypertension in pigs with experimentally induced liver failure. Of the two preparations tested--total hepatectomy (n = 47), and liver devascularization (n = 16)--only pigs with liver ischemia developed brain edema provided, however, that animals were maintained normothermic throughout the postoperative period. This model was then used in transplantation studies, in which six pigs received intrasplenic injection of allogeneic hepatocytes (2.5 x 10(9) cells/pig) and 3 days later acute liver failure was induced. In both models (anhepatic state, liver devascularization), pigs allowed to become hypothermic had significantly longer survival compared to those maintained normothermic. Normothermic pigs with liver ischemia had, at all time points studied, ICP greater than 20 mmHg. Pigs that received hepatocellular transplants had ICP below 15 mmHg until death; at the same time, cerebral perfusion pressure (CPP) in transplanted pigs was consistently higher than in controls (45 +/- 11 mmHg vs. 16 +/- 18 mmHg; p < 0.05). Spleens of transplanted pigs contained clusters of viable hepatocytes (hematoxylin-eosin, CAM 5.2). It was concluded that removal of the liver does not result in intracranial hypertension; hypothermia prolongs survival time in both anhepatic pigs and pigs with liver devascularization, and intrasplenic transplantation of allogeneic hepatocytes prevents development of intracranial hypertension in pigs with acute ischemic liver failure.

We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobes necrosis. After this procedure, lack of regenerative response in the residual viable liver tissue (omental lobes) was associated with elevated plasma hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1) levels and delayed expression of HGF and c-met mRNA in the remnant liver. Here, we investigated whether syngeneic isolated hepatocytes transplanted in the spleen will prolong survival and facilitate liver regeneration in FHF rats. Inbred male Lewis rats were used. Group I rats (n = 46) received intrasplenic injection of 2 x 10(7) hepatocytes and 2 days later FHF was induced. Group II FHF rats (n = 46) received intrasplenic injection of saline. Rats undergoing partial hepatectomy of 68% (PH; n = 30) and a sham operation (SO; n = 30) served as controls. In 20 FHF rats (10 rats/group), survival time was determined. The remaining 72 FHF rats (36 rats/group) were used for physiologic studies (liver function and regeneration and plasma growth factor levels). In Group I rats survival was longer than that of Group II controls (73 +/- 22 hr vs. 33 +/- 9 hr; P < 0. 01). During the first 36 hr, Group I rats had lower blood ammonia, lactate, total bilirubin, PT, and PTT values, lower activity of liver enzymes, and higher monoethylglycinexylidide (MEGX) production than Group II rats. In Group I rats, livers increased in weight at a rate similar to that seen in PH controls and showed distinct mitotic and DNA synthetic activity (incorporation of bromodeoxyuridine and proliferation cell nuclear antigen expression). Plasma HGF and TGF-beta1 levels in these rats decreased and followed the pattern seen in PH rats; additionally, c-met expression in the remnant liver was accelerated. Hepatocyte transplantation prolonged survival in FHF rats and facilitated liver regeneration. Even though the remnant liver increased in weight four times reaching 30% of the original liver mass, the transplant-bearing rats expired due to inability of the regenerating liver to support the rat., (Copyright 1997 Academic Press.)

Objective: The purpose of this study was to develop a bioartificial liver (BAL) to treat patients with severe liver failure until they can be either transplanted or recover spontaneously., Summary Background Data: Severe acute liver failure is associated with high mortality. Liver transplantation has emerged as an effective therapy for patients who did not respond to standard management. However, because of the donor organ shortage and urgent need for transplantation, many patients die before they can be transplanted and others do not survive after transplantation, primarily because of intracranial hypertension., Methods: Three groups of patients with severe acute liver failure were treated with the BAL. In group 1 (n = 18) were patients with fulminant hepatic failure (FHF), in group 2 (n = 3) were patients with primary nonfunction (PNF) of a transplanted liver, and in group 3 (n = 10) were patients with acute exacerbation of chronic liver disease. Patients in groups 1 and 2 were candidates for transplantation at the time they entered the study, whereas patients in group 3 were not., Results: In group 1, 16 patients were "bridged" successfully to transplantation, 1 patient was bridged to recovery without a transplant, and 1 patient died because of concomitant severe pancreatitis. In group 2, all patients were bridged successfully to retransplantation. In group 3, two patients were supported to recovery and successful transplants at later dates; the other eight patients, although supported temporarily with the BAL, later died because they were not candidates for transplantation., Conclusions: The authors' clinical experience with the BAL has yielded encouraging results. A randomized, controlled, prospective trial (phase II-III) is being initiated to determine the efficacy of the system.

A reproducible experimental animal model of fulminant hepatic failure (FHF) resembling the clinical condition is needed. We have developed such a model in the rat by combining resection of the two anterior liver lobes (68% liver mass) with ligation of the right lobes pedicle (24% liver mass), resulting in liver necrosis; the remaining two omental lobes (8% liver mass) are left intact. Adult Sprague-Dawley rats (250-300 g) were used. Survival time was determined in 60 rats. Because maintenance of body temperature at 37 degrees C shortened survival time by half, FHF rats were not warmed during the postinduction period and were allowed to gradually enter a state of mild to moderate hypothermia (29-32 degrees C). Additionally, 42 FHF rats were killed in batches of six rats each 2, 6, 12, 18, 24, 30, and 36 hours postoperatively to evaluate changes in blood chemistry (glucose, lactate, liver function tests, prothrombin time) and to assess liver regenerative response in the residual omental liver lobes (weight, protein content, incorporation of bromodeoxyuridine [BrdU], expression of proliferation cell nuclear antigen [PCNA], mitotic activity), plasma levels of hepatocyte growth factor (HGF) and transforming growth factor beta (TGF-beta1), and tissue expression of the HGF and it's receptor c-met. Rats undergoing partial hepatectomy of 68% (PH; n = 42) and a sham operation (SO; n = 42) served as controls. All SO and PH controls survived. PH rats showed only transient decreases in body temperature, signs of modest early hepatic dysfunction (hyperlactemia, hyperammonemia, prolonged PT time), and normal restitution of liver mass. All FHF rats became comatose by 24 hours postoperatively. Most animals (90%) died within 24-48 hours postoperatively (mean, 39 +/- 11 hours). Changes in blood chemistry reflected rapid development of liver failure. Plasma HGF levels were markedly elevated and at all time points were higher than in PH controls (P < .05). At the same time, expression of HGF and c-met messenger RNA in the remnant liver was delayed. Plasma TGF-beta1 levels increased early (18 hours) and remained twofold to threefold higher than that of PH and SO controls (P < .05). There was only a 20% increase in the weight of the remnant liver lobes due to swelling. No hepatocytes stained positively for BrdU and PCNA, and none showed mitotic figures. In contrast, all PH controls showed vigorous liver regeneration. In conclusion, we have developed and characterized a novel model of FHF in rats that has a number of physiological and biochemical features seen clinically in FHF, including severely impaired ability of the residual liver tissue to regenerate.

Unlabelled: The only clinically proven effective treatment of fulminant hepatic failure (FHF) is orthotopic liver transplant (OLT). However, many patients die before an organ becomes available. Thus, there is a need for development of an extracorporeal liver support system to "bridge" these patients either to OLT or spontaneous recovery. We developed a bioartificial liver (BAL) based on plasma perfusion through a circuit of a hollow-fiber cartridge seeded with matrix-anchored porcine hepatocytes to treat patients with severe acute liver failure. Two groups of patients were studied. Group 1 (n = 12): patients with FHF. All patients were successfully "bridged" to OLT. "Bridge" time to OLT was 21-96 hr (mean: 39.3 hr). All patients were discharged neurologically intact. Reversal of decerebration was noted in all 11 deep stage 4 coma patients. There was reduction in intracranial pressure (ICP mmHg, 18.2 +/- 2.2 to 8.5 +/- 1.2; p < 0.004) and increase in cerebral perfusion pressure (CPP mmHg, 71.1 +/- 4.0 to 84.7 +/- 2.6; p < 0.006). Laboratory values pre- and post-BAL treatment: glucose (mg/dl) 122 +/- 11 to 183 +/- 21, p < 0.002; ammonia (mumol/l) 155.6 +/- 13.2 to 121.6 +/- 9.5, p < 0.02; total bilirubin (mg/dl) 21.6 +/- 2.8 to 18.2 +/- 2.2, p < 0.001; PT (sec) 23.2 +/- 1.7 to 21.9 +/- 1.0, p < 0.3. Group II (n = 8): patients with chronic liver failure experiencing acute exacerbation. Two patients survived and later underwent OLT. Six patients (not OLT candidates) died 1-14 days after last BAL treatment. Laboratory values pre- and post-treatment: ammonia (mumol/l) 201 +/- 47 to 143 +/- 25, p < 0.06; total bilirubin (mg/dl) 22.8 +/- 5.2 to 19.5 +/- 4.4, p < 0.01; PT (sec) 22.5 +/- 2.0 to 21.8 +/- 1.1, p < 0.6., Conclusion: our clinical experience with the BAL suggests that it may serve as "bridge" to OLT in patients with FHF primarily by reversing intracranial hypertension, but it is not a substitute for OLT in patients with end-stage liver disease who are non-transplant candidates.

Numerous studies have reported successful allotransplantation of hepatocytes. However, none have shown long-term correction of a liver-related metabolic defect. In this study, we used a method of regional hepatocyte transplantation and subsequent induction of transplanted cell proliferation by regeneration response in the transplant-bearing liver lobes. New Zealand White rabbits were used as cell donors and Watanabe heritable hyperlipidemic (WHHL) rabbits were used as cell recipients (2 x 10(8) cells/rabbit). All recipient rabbits were maintained on daily cyclosporine. Two weeks after baseline serum cholesterol determination, group I WHHL rabbits (n = 7) received an infusion of cells into the right lateral liver lobe, and a loose ligature was placed around the portal venous branch supplying the anterior lobe. After 1 week, to allow engraftment, the portal venous branch was ligated, which resulted in the atrophy of the affected liver parenchyma and induction of hyperplasia in the transplant-bearing liver tissue. Group II rabbits (n = 6) were transplanted with New Zealand White hepatocytes without portal branch ligation (PBL) and group III rabbits (n = 4) were subjected to sham transplantation (saline) and PBL. The experimental period extended to 150 days after transplantation. All WHHL rabbits transplanted with normal hepatocytes showed reduction in serum cholesterol and low-density lipoprotein (LDL) levels. Group I (PBL-stimulated) recipients demonstrated a more pronounced and sustained effect than group II animals (P < 0.05). Group III controls showed only a slight, typical for aging decrease in serum cholesterol. Group I recipient livers perfused with LDL labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (DiI) showed much higher numbers of DiI-LDL-positive hepatocytes than those of group II recipients. In conclusion, a liver regeneration stimulus enhanced the population of transplanted hepatocytes and their functional effect in a large animal model of inborn error of liver metabolism.

Purpose: There is a widespread belief that performing hemorrhoidectomy on a patient infected with human immunodeficiency virus (HIV) is an invitation for disaster. Aim of this study was to compare morbidity of hemorrhoidectomy in HIV-positive (HIV+) with HIV-negative (HIV-) patients., Methods: Charts of 27 HIV+ and 30 HIV- male patients less than age 50 years who underwent hemorrhoidectomy were reviewed., Results: Mean age of the 57 study group patients was 38 years. Open hemorrhoidectomy was performed in 26 patients (46 percent), and a closed technique was used in 31 patients (54 percent). HIV+ and HIV- patient groups were well matched to all preoperative and intraoperative variables. Mean T-cell helper count in the HIV+ patient group was 301 (range, 9-1,040) cells/microliter. There were no deaths, and complications were seen in 15 patients (26 percent). There was no difference in overall complication rates between HIV+ and HIV- patient groups. Urinary retention was seen in ten patients (18 percent), three of whom were HIV+ (11 percent) vs. seven of whom were HIV- (23 percent) (P = not significant). Although no patient required reoperation for bleeding, postoperative hemorrhage was seen in three patients (1 HIV+, 2 HIV-). None of the patients developed fecal incontinence. Mean time to complete wound healing was 6.8 (range, 4-12) weeks for HIV+ patients vs. 6.6 (range, 4-14) weeks for HIV- patients (P = not significant)., Conclusions: These data suggest that HIV status of a patient should not alter indications for surgical management of hemorrhoidal disease.

The author reports on a study of the liquid nitrogen treatment of warts at the Rutgers University Student Health Center. He demonstrates that liquid nitrogen therapy is a safe, effective treatment method, appropriate for use by nurses and other primary providers in a college health setting.

Acetaminophen (APAP)-induced nephrotoxicity is age-dependent in male Sprague-Dawley (SD) rats: middle-aged (9-12 months old) rats exhibit nephrotoxicity at lower dosages of APAP than do young adults (2-3 months old). The present study was designed to test the hypothesis that the intrinsic susceptibility of renal tissue to APAP toxicity is increased in middle-aged rats. APAP toxicity was evaluated in renal slices from naive 3- and 12-month-old male SD rats incubated with 0-50 mM APAP for 2-8 h. Renal slice glutathione (GSH) and APAP concentrations were determined; renal function was assessed by organic anion (para-aminohippurate, PAH) and cation (tetraethylammonium, TEA) accumulation; and cell viability was assessed by lactate dehydrogenase (LDH) leakage. At each concentration of APAP tested, accumulation of APAP by renal slices was similar in 3- and 12-month-olds. APAP toxicity in renal slices from both 3- and 12-month-old rats was characterized by concentration-dependent increases in LDH leakage. In contrast to APAP nephrotoxicity in vivo, APAP toxicity in renal slices was accompanied by decreased accumulation of PAH and TEA. Additionally, APAP produced marked reductions in renal slice GSH content in a concentration-dependent manner: however, in contrast to APAP nephrotoxicity in vivo, APAP-induced GSH depletion in vitro did not precede cytotoxicity. No consistent age-dependent differences in the time- and concentration-response curves for APAP nephrotoxicity were observed. These data suggest that APAP cytotoxicity in vitro is not increased in 12-month-old rats. However, since the pattern (and mechanisms) of APAP cytotoxicity in vitro appears to be different from that observed in vivo, extrapolation of in vitro cytotoxicity to in vivo nephrotoxicity is limited. Therefore, age differences in intrinsic susceptibility of the intact kidney cannot be excluded as a mechanism contributing to enhanced APAP nephrotoxicity in middle-aged rats.

Previous studies have suggested that ketonic solvents potentiate the hepatotoxic action of CHCl3 in rats. In addition, the relative potentiating capacity of the ketones appeared to be related to the length of their carbon skeleton. To test this hypothesis CHCl3-induced liver injury was evaluated in male Sprague-Dawley rats pretreated (15 mmol/kg, p.o.) with acetone (Ac), 2-butanone (Bu), 2-pentanone (Pn), 2-hexanone (Hx) or 2-heptanone (Hp). After 18 h, a challenging dose of CHCl3, (0.50 or 0.75 ml/kg, i.p.) was given. Liver damage was evaluated 24 h after CHCl3 administration by determining elevations in plasma GPT and OCT activity. Neither Ac, Bu, Pn, Hx, Hp or the CHCl3 challenging dosages produced marked liver injury when given alone. However, each of the ketones potentiated CHCl3-induced liver damage. The severity of the potentiated hepatotoxic response was significantly (positively) correlated with the ketone carbon chain length. These observations suggest that carbon skeleton length may play a role in determining the relative potentiating capacity of ketonic solvents.

Acute oral pretreatment of rats with isopropanol or acetone results in a dose-related potentiation of CCl4 hepatotoxicity. Minimally effective doses (MED) and noneffective doses (NED) of both agents were estimated to be 0.25 and 0.10 ml/kg, respectively. Six MED given twice a day over 3 d caused a greater potentiation than a single MED, but not as much as that produced by the total dose given singly. Six NED given over 3 d did not potentiate CCl4, whereas the total dose did when given singly. A threshold for isopropanol and acetone appears to exist in the rat. A total dose of 1.5 ml/kg acetone was administered by four different treatment regimens (bolus, divided doses, infusion) over 3 d. Potentiation of CCl4 hepatotoxicity was then correlated with blood pharmacokinetic parameters: area under the concentration-time curve and peak blood concentration. An excellent correlation was found between the degree of potentiation observed and the peak blood concentration attained, but no correlation was found with area under the curve. Results of iv acetone infusions (over 3 d) with higher doses support the hypothesis that a threshold concentration of acetone is critical in the potentiation of CCl4 hepatotoxicity in the rat.

The renal organic anion transport system has been linked to the selective extraction of nonesterified fatty acids (NEFA) from arterial blood. Consequently, p-aminohippurate (PAH) and palmitate may compete for a common intracellular binding site or may be handled by a common enzymatic pathway. The purpose of this study was to identify sites of interaction by correlating alterations in PAH accumulation and palmitate metabolism after selective stimulation of the PAH transport system. Penicillin treatment of immature rabbits increased PAH accumulation by suspensions of proximal tubules prepared nonenzymatically) and altered distribation of incorporated palmitate[14C] within tubule lipid classes. Penicillin increased palmitate[14C] esterified to triglycerides and decreased 14C recovered as NEFA. Administration of iodipamide had no effect on PAH accumulation and did not alter palmitate utilization. Penicillin treatment of mature rabbits did not alter either tubule PAH accumulation or palmitate esterification. These results suggested that palmitate and PAH share a common intracellular binding site and that penicillin enhanced PAH accumulation by removing endogenous inhibitors (NEFA).

Rats were treated with [14C]chloroform (14CHCl3) in corn oil (CO) or corn oil alone 18 hr following pretreatment with 2-hexanone (2-HX) in corn oil or corn oil alone. Livers were removed, homogenized 1,2, and 6 hr post-14CHCl3 administration, and glutathione (GSH) content, irreversible binding of 14CHCl3-derived radiolabel, and phospholipid composition were determined. The combination of 2-HX + CHCl3 reduced GSH content to 21% of control (CO + CO) 1 hr after CHCl3 administration. No significant rebound of GSH was observed 24 hr post-CHCl3 administration. In contrast, GSH was not altered by administration of CHCl3 to CO-pretreated rats. Although 14CHCl3-derived radiolabel was irreversibly bound to hepatic macromolecules of both CO- and 2-HX-pretreated rats, total irreversibly bound 14C was significantly enhanced in 2-HX-pretreated rats at all time points. The latter observation was consistent with the decrease in GSH of 2-HX-pretreated rats. Total 14C binding in 2-HX-pretreated rats reached a plateau 2 hr post-14CHCl3 administration and was distributed 52% in protein, 41% in lipid, and 7% in acid soluble fractions 6 hr post-14CHCl3 administration. 2-HX enhanced 14C binding to protein and lipid at each time point. Radiolabel was not detected in neutral lipids of control or 2-hexanone-treated animals, but was enhanced 33-fold in phospholipids of 2-hexanone-treated animals. Phospholipid fatty acid methyl ester derivatives did not contain 14C indicating the radiolabel was most likely associated with phospholipid polar head groups. Two dimensional thin layer chromatographic analysis of phospholipid from treated animals demonstrated that 87% of the total radiolabel was associated with a specific phospholipid (14C-PL) which had a 1:1 molar ratio of phosphate to 14C. The latter indicates that the 14C-PL was a monophospholipid derivative of 14CHCl3 reactive intermediate, generally thought to be phosgene. Concurrent decrease in phosphatidylethanolamine content from 23% of total phospholipid to 7%, accumulation of 14C-PL to 2.6% of total phospholipid, and increase in lysophosphatidylethanolamine from 1 to 7% of total phospholipid during 2-hexanone + 14CHCl3 treatment indicated that the amine moiety of phosphatidylethanolamine polar head groups was the probable target of phosgene-lipid interaction, and that a degradative pathway existed which removed the abnormal phospholipid from hepatic membranes. No phospholipid other than phosphatidylethanolamine was depleted. During models studies, 2% phosgene in toluene was reacted with liver phosphatidylethanolamine for 6 hr at 37 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS)

These experiments were designed to elucidate the initiating biochemical events mediating cephaloridine (CPH) nephrotoxicity. Renal cortical slices from naive male Fischer-344 rats were incubated at 37 degrees C in a phosphate- or bicarbonate-buffered medium containing 0, 1, 5, or 10 mM CPH. Slices were incubated for 15, 30, 45, 60, 90, 120, and 180 min and evaluated for accumulation of organic ions [p-aminohippurate (PAH) and tetraethylammonium (TEA)], pyruvate-stimulated gluconeogenesis, malondialdehyde (MDA) production, and reduced glutathione (GSH) content. Renal cortical slice accumulation of PAH and TEA was decreased by 5 and 10 mM CPH as early as 120 and 90 min of incubation, respectively. CPH-induced MDA production by renal cortical slices preceded the effects of CPH on organic ion accumulation. Coincubation of CPH with the antioxidants promethazine and N,N'-diphenyl-p-phenylenediamine inhibited CPH-induced lipid peroxidation and changes in organic ion accumulation. In contrast, 5 or 10 mM CPH inhibited gluconeogenic capacity at all time points examined, an effect which was not influenced by antioxidant treatment. Depletion of renal cortical GSH by 5 or 10 mM CPH was evident following 30 min of incubation and was also unaffected by antioxidant treatment. These results support the hypothesis that lipid peroxidation mediates the effects of CPH on renal organic ion transport. The early and profound inhibition of gluconeogenesis by CPH suggests that the biochemical pathways of gluconeogenesis are either proximal to or represent a primary target for CPH nephrotoxicity.