Jonathan T. Carter

Laparoscopic Procurement of Kidneys with Multiple Renal Arteries is Associated with Increased Ureteral Complications in the Recipient

This study investigates the effect of renal artery multiplicity on donor and recipient outcomes after laparoscopic donor nephrectomy. Three‐hundred and sixty‐one sequential procedures were performed over a 4‐year period. Forty‐nine involved accessory renal arteries; of these, 36 required revascularization and 13 were small polar vessels and ligated. The 312 remaining kidneys with single arteries served as controls. Study variables included operative times, blood loss, hospital stay, graft function and donor and recipient complications.

Tumors of the Ampulla of Vater: Histopathologic Classification and Predictors of Survival

BACKGROUND The histology and clinical behavior of ampullary tumors vary substantially. We speculated that this might reflect the presence of two kinds of ampullary adenocarcinoma: pancreaticobiliary and intestinal. STUDY DESIGN We analyzed patient demographics, presentation, survival (mean followup 44 months), and tumor histology for 157 consecutive ampullary tumors resected from 1989 to 2006. Histologic features were reviewed by a pathologist blinded to clinical outcomes. Survival was compared using Kaplan-Meier/Cox proportional hazards analysis. RESULTS There were 33 benign (32 adenomas and 1 paraganglioma) and 124 malignant (118 adenocarcinomas and 6 neuroendocrine) tumors. One hundred fifteen (73%) patients underwent a Whipple procedure, 32 (20%) a local resection, and 10 (7%) a palliative operation. For adenocarcinomas, survival in univariate models was affected by jaundice, histologic grade, lymphovascular, or perineural invasion, T stage, nodal metastasis, and pancreaticobiliary subtype (p < 0.05). Size of tumor did not predict survival, nor did cribriform/papillary features, dirty necrosis, apical mucin, or nuclear atypia. In multivariate models, lymphovascular invasion, perineural invasion, stage, and pancreaticobiliary subtype predicted survival (p < 0.05). Patients with pancreaticobiliary ampullary adenocarcinomas presented with jaundice more often than those with the intestinal kind (p = 0.01) and had worse survival. CONCLUSIONS In addition to other factors, tumor type (intestinal versus pancreaticobiliary) had a major effect on survival in patients with ampullary adenocarcinoma. The current concept of ampullary adenocarcinoma as a unique entity, distinct from duodenal and pancreatic adenocarcinoma, might be wrong. Intestinal ampullary adenocarcinomas behaved like their duodenal counterparts, but pancreaticobiliary ones were more aggressive and behaved like pancreatic adenocarcinomas.

Thymoglobulin‐Associated Cd4+ T‐Cell Depletion and Infection Risk in HIV‐Infected Renal Transplant Recipients

HIV‐infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulins effect on CD4+ T‐cell count, risk of infection and rejection reversal in 20 consecutive HIV‐infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T‐cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 ± 192 to 9 ± 10 cells/μL (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T‐cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV‐infected kidney recipients, but produces profound and long‐lasting suppression of the CD4+ T‐cell count associated with increased risk of infections requiring hospitalization.

Evaluation of the older cadaveric kidney donor: the impact of donor hypertension and creatinine clearance on graft performance and survival.

Background. The use of older donors for cadaveric renal transplantation (CRT) remains controversial because older donors are associated with decreased graft survival, yet offer the opportunity for donor pool expansion.We investigated the impact of two age-related donor factors, hypertension and calculated creatinine clearance (C Cr), as predictors of graft outcome in recipients of CRTs from donors ≥55 years of age. Methods. We reviewed 33,595 recipients of CRTs reported to UNOS since 4/1/94, of which 4,732 were from donors aged ≥55 years. Outcome measures were graft survival, serum creatinine, and incidence of delayed graft function with 3 years of follow-up. We first analyzed the effect of hypertension on outcome from donors ≥55 years: 2679 donors had no hypertension, 1058 had hypertension ≤10 years, and 557 had hypertension >10 years. Next, the effect of donor C Cr as a risk predictor was investigated. Based on this analysis, recipients of older donors were grouped into two cohorts for comparison: 2570 donors with C Cr <80 ml/min and 2162 donors with C Cr ≥80 ml/min. Results. Actuarial graft survival from donors aged <55 years was 88.0, 83.4, and 78.5% at 1, 2, and 3 years, vs. 80.6, 73.5, and 65.3% from donors ≥55 years (P <0.0001). When stratified by hypertension, older donors hypertensive >10 years had survivals of 77, 66, and 57% vs. 81, 73, and 65% from donors without hypertension (P <0.017) and 80, 74, and 66% from donors hypertensive <10 years (P <0.017). When stratified by C Cr, older donors with C Cr <80 ml/min had survivals of 77, 69, and 62% vs. 83, 76, and 66% from donors with C Cr ≥80 (P <0.0001). Finally, older donors with both hypertension >10 years and C Cr <80 ml/min had survivals of 77, 61, and 53%. Conclusions. Long-standing hypertension and low calculated creatinine clearance are risk factors for decreased graft survival of CRTs from older donors. When both factors are present, graft survival is significantly decreased.

Laparoscopic sleeve gastrectomy is safe and efficacious for pretransplant candidates

BACKGROUND Morbid obesity is a relative contraindication for organ transplant because it is associated with higher postoperative morbidity and mortality. The safety and efficacy of laparoscopic sleeve gastrectomy (LSG) as a weight loss method for patients awaiting transplant has not been examined. METHODS A retrospective review was performed on morbidly obese patients awaiting liver or kidney transplant who underwent LSG from 2006 to 2012. Data included patient demographic characteristics, operative details, 30-day complications, percentage of excess weight loss, postoperative laboratory data, and status of transplant candidacy. RESULTS Twenty-six pretransplant patients underwent LSG. The mean age was 57 years, and 17 (65%) were women. Six patients had end-stage renal disease, and 20 patients had end-stage liver disease. The preoperative mean body mass index was 48.3 kg/m(2) (range 38-60.4 kg/m(2)). There were no deaths, and there were 6 postoperative complications: 2 superficial wound infections, 1 staple line leak, 1 postoperative bleed requiring blood transfusion, 1 transient encephalopathy, and 1 temporary renal insufficiency. The mean percentage of excess weight loss at 1, 3, and 12 months was 17% (n = 24/26), 26% (n = 23/26), and 50% (n = 18/20), respectively. All patients met our institutions body mass index cutoffs for transplantation by 12 months after the procedure. One patients renal function stabilized, and he was taken off the transplant list. Eight patients eventually underwent solid organ transplant. Six received liver transplants, 1 patient received a combined liver and kidney transplant, and 1 received a kidney transplant. The mean time between LSG and transplant was 16.6 months. CONCLUSIONS This is the largest case series involving LSG in patients awaiting solid organ transplantation. LSG is well tolerated, is technically feasible, and improves candidacy for transplantation.

Outcome of patients with hepatitis B virus and human immunodeficiency virus infections referred for liver transplantation

The outcome of patients with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) referred for liver transplantation (LT) is unknown. A high frequency of lamivudine‐resistant (LAM‐R) HBV infection may increase the risk of liver‐related death pre‐transplantation and prophylaxis failure post‐transplantation. We evaluated the association of LAM‐R HBV on pre‐transplant survival and post‐transplant outcomes in 35 consecutive HIV‐HBV coinfected patients referred for LT between July 2000 and September 2002. At the time of referral, the median CD4 count was 273/mm, MELD was 14, and LAM‐R HBV infection was present in 67%. Among these referred patients, 26% were listed, 29% not listed due to relative/absolute contraindications; 26% not listed as too early for LT; 9% not listed as too sick for LT; and 11% died during transplant evaluation. Of the 9 listed patients, 4 remained listed, 1 died 18 months post‐referral, and 4 were transplanted (11% of total) 3 to 40 months after listing. Of 17 evaluated but not listed patients, 5 died (p=0.38 compared to listed group) and all deaths were liver‐related. All the HBV‐HIV coinfected patients, who were transplanted, are HBsAg negative and have undetectable HBV DNA levels on prophylactic therapy using hepatitis B immune globulin (HBIG) plus lamivudine, with and without tenofovir or adefovir, with median 33.1 months follow‐up. Late referral and the presence of LAM‐R HBV pre‐transplantation are common in referred HIV‐HBV patients. In HIV‐HBV coinfected patients undergoing LT, HBV recurrence is successfully prevented with combination prophylaxis using HBIG and antivirals. Liver Transpl 12:801–807, 2006.

Expanded Criteria Donor Kidney Allocation: Marked Decrease in Cold Ischemia and Delayed Graft Function at a Single Center

Expanded criteria donor (ECD) kidney allocation aims to increase utilization and facilitate placement. We implemented an ECD program for pre‐consented candidates and studied whether ECD allocation decreased cold ischemia time and delayed graft function (DGF). We compared donor, recipient and transplant data for ECD transplants performed during the first year of our program to those performed in the preceding 5½ years. Logistic regression identified risk factors for DGF. Of 356 candidates, 107 (30%) consented, 32 (9%) completed evaluation and 20 (6%) underwent ECD transplantation during the programs first year. The recent and historical ECD cohorts had similar donor and recipient characteristics, except that recent ECD recipients were older. The rate of donor kidney biopsy dropped from 85% to 24% (p < 0.001). Cold ischemia time decreased from 16.4 to 7.4 h (p < 0.001), as did the incidence of DGF from 43% to 15% (p = 0.031). Three independent risk factors for DGF emerged: recipient height (OR 1.21/10 cm; p = 0.008), >4 HLA mismatches (OR 20.46; p = 0.0033) and cold ischemia time (OR 1.24/h; p = 0.0036). We conclude the ECD designation provides a description of kidney quality that may obviate biopsy. ECD allocation decreased cold ischemia time and DGF, which may improve graft survival.

A prospective, randomized controlled trial of single-incision laparoscopic vs conventional 3-port laparoscopic appendectomy for treatment of acute appendicitis.

BACKGROUND Proponents of single-incision laparoscopic surgery (SILS) claim patients have less pain, faster recovery, and better long-term cosmetic results than patients who undergo multiport laparoscopy. However, randomized comparisons are lacking. This study presents the results of a prospective randomized trial of SILS or 3-port laparoscopic appendectomy. STUDY DESIGN Adults with uncomplicated acute appendicitis were randomized 1:1 to either SILS or 3-port laparoscopic appendectomy. The primary end point was early postoperative pain (measured by opiate usage and pain score in the first 12 hours). Secondary end points were operative time, complication rate (including conversions), and recovery time (days of oral opiate usage and return to work). After 6 months, body image and cosmetic appearance were assessed using a validated survey. RESULTS The trial was planned for 150 patients, but was halted after 75 patients when planned interim analysis showed that SILS patients had more postoperative pain (pain score: 4.4 ± 1.6 vs 3.5 ± 1.5; p = 0.01) and higher inpatient opiate usage (hydromorphone use: 3.9 ± 1.9 mg vs 2.8 ± 1.7 mg; p = 0.01) than 3-port laparoscopy. Operative time for SILS averaged 40% longer (54 ± 17 minutes vs 38 ± 11 minutes; p < 0.01). Only 1 SILS case was converted to 3-port. There were no significant differences in length of stay, complications, oral pain medication usage after discharge, or return to work. After 6 months, body image and cosmetic appearance were excellent for both groups and indistinguishable by most measures. However, 3-port patients reported better physical attractiveness (4.0 ± 0.4 vs 3.8 ± 0.4; p = 0.04) and SILS patients reported better scars (score 18.4 ± 2.7 vs 16.4 ± 3.0; p < 0.01). Results are reported as mean ± SD. CONCLUSIONS Single-incision laparoscopic surgery appendectomy resulted in more pain and longer operative times without improving short-term recovery or complications. Long-term body image and cosmetic appearance were excellent in both groups.

Intestinal Calcium Absorption Decreases Dramatically After Gastric Bypass Surgery Despite Optimization of Vitamin D Status

Roux‐en‐Y gastric bypass (RYGB) surgery has negative effects on bone, mediated in part by effects on nutrient absorption. Not only can RYGB result in vitamin D malabsorption, but the bypassed duodenum and proximal jejunum are also the predominant sites of active, transcellular, 1,25(OH)2D‐mediated calcium (Ca) uptake. However, Ca absorption occurs throughout the intestine, and those who undergo RYGB might maintain sufficient Ca absorption, particularly if vitamin D status and Ca intake are robust. We determined the effects of RYGB on intestinal fractional Ca absorption (FCA) while maintaining ample 25OHD levels (goal ≥30 ng/mL) and Ca intake (1200 mg daily) in a prospective cohort of 33 obese adults (BMI 44.7 ± 7.4 kg/m2). FCA was measured preoperatively and 6 months postoperatively with a dual stable isotope method. Other measures included calciotropic hormones, bone turnover markers, and BMD by DXA and QCT. Mean 6‐month weight loss was 32.5 ± 8.4 kg (25.8% ± 5.2% of preoperative weight). FCA decreased from 32.7% ± 14.0% preoperatively to 6.9% ± 3.8% postoperatively (p < 0.0001), despite median (interquartile range) 25OHD levels of 41.0 (33.1 to 48.5) and 36.5 (28.8 to 40.4) ng/mL, respectively. Consistent with the FCA decline, 24‐hour urinary Ca decreased, PTH increased, and 1,25(OH)2D increased (p ≤ 0.02). Bone turnover markers increased markedly, areal BMD decreased at the proximal femur, and volumetric BMD decreased at the spine (p < 0.001). Those with lower postoperative FCA had greater increases in serum CTx (ρ = −0.43, p = 0.01). Declines in FCA and BMD were not correlated over the 6 months. In conclusion, FCA decreased dramatically after RYGB, even with most 25OHD levels ≥30 ng/mL and with recommended Ca intake. RYGB patients may need high Ca intake to prevent perturbations in Ca homeostasis, although the approach to Ca supplementation needs further study. Decline in FCA could contribute to the decline in BMD after RYGB, and strategies to avoid long‐term skeletal consequences should be investigated.

Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study☆ , ☆☆ ,★

Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2% ± 3.5% and 4.1% ± 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% ± 2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots.