Sander Florman

One Hundred Nine Living Donor Liver Transplants in Adults and Children: A Single-Center Experience

ObjectiveTo summarize the evolution of a living donor liver transplant program and the authors’ experience with 109 cases. Summary Background DataThe authors’ institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. MethodsDonors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. ResultsAfter ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. ConclusionLiving donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years.

Report of a national conference on liver allocation in patients with hepatocellular carcinoma in the United States.

A national conference was held to better characterize the long‐term outcomes of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) and to assess whether it is justified to continue the policy of assigning increased priority for candidates with early‐stage HCC on the transplant waiting list in the United States. The objectives of the conference were to address specific HCC issues as they relate to liver allocation, develop a standardized pathology report form for the assessment of the explanted liver, develop more specific imaging criteria for HCC designed to qualify LT candidates for automatic Model for End‐Stage Liver Disease (MELD) exception points without the need for biopsy, and develop a standardized pretransplant imaging report form for the assessment of patients with liver lesions. At the completion of the meeting, there was agreement that the allocation policy should result in similar risks of removal from the waiting list and similar transplant rates for HCC and non‐HCC candidates. In addition, the allocation policy should select HCC candidates so that there are similar posttransplant outcomes for HCC and non‐HCC recipients. There was a general consensus for the development of a calculated continuous HCC priority score for ranking HCC candidates on the list that would incorporate the calculated MELD score, alpha‐fetoprotein, tumor size, and rate of tumor growth. Only candidates with at least stage T2 tumors would receive additional HCC priority points. Liver Transpl 16:262–278, 2010.

Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys.

Recipients of extended‐criteria donor (ECD) kidneys have poorer long‐term outcomes compared to standard‐criteria donor kidney recipients. We report 3‐year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty‐three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept‐treated versus cyclosporine‐treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine‐treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept‐treated patients (27–30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept‐treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.

Belatacept-based regimens versus a cyclosporine A-based regimen in kidney transplant recipients: 2-year results from the BENEFIT and BENEFIT-EXT studies.

Background. At 1 year, belatacept was associated with similar patient/graft survival, better renal function, and an improved cardiovascular/metabolic risk profile versus cyclosporine A (CsA) in the Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT) studies. Acute rejection was more frequent with belatacept in BENEFIT. Posttransplant lymphoproliferative disorder (PTLD)—specifically central nervous system PTLD—was observed more frequently in belatacept-treated patients. This analysis assesses outcomes from BENEFIT and BENEFIT-EXT after 2 years of treatment. Methods. Patients received a more intensive (MI) or a less intensive (LI) regimen of belatacept or a CsA-based regimen. Results. Four hundred ninety-three of 666 patients (74%) in BENEFIT and 347 of 543 (64%) in BENEFIT-EXT completed 2 years of treatment. The proportion of patients who survived with a functioning graft was similar across groups (BENEFIT: 94% MI, 95% LI, and 91% CsA; BENEFIT-EXT: 83% MI, 84% LI, and 83% CsA). Belatacepts renal benefits were sustained, as evidenced by a 16 to 17 mL/min (BENEFIT) and an 8 to 10 mL/min (BENEFIT-EXT) higher calculated glomerular filtration rate in the belatacept groups versus CsA. There were few new acute rejection episodes in either study between years 1 and 2. Because PTLD risk was highest in Epstein-Barr virus (EBV) (−) patients, an efficacy analysis of EBV (+) patients was performed and was consistent with the overall population results. There were two previously reported cases of PTLD in each study between years 1 and 2 in the belatacept groups. The overall balance of safety and efficacy favored the LI over the MI regimen. Conclusions. At 2 years, belatacept-based regimens sustained better renal function, similar patient/graft survival, and an improved cardiovascular/metabolic risk profile versus CsA; outcomes that were maintained in EBV (+) patients. No new safety signals emerged.

Fulminant and fatal gas gangrene of the stomach in a healthy live liver donor

A 57‐year‐old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram‐positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patients death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin‐mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable. (Liver Transpl 2004;10:1315–1319.)

Post‐liver transplant acute renal failure: factors predicting development of end‐stage renal disease*

Abstract:  Background:  Acute renal failure (ARF) occurs in 5–50% ofpatients undergoing orthotopic liver transplantation (OLT). The aim of this study was to determine factors that might predict the development of end stage renal disease (ESRD) in patients who had ARF after OLT.

Liver transplantation for neuroendocrine tumors

Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2 ± 6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34 ± 40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option.

Isolated intestinal transplantation: proof of clinical efficacy.

Background and Aims. Isolated intestinal transplantation has been limited by poor patient and graft survival. If high survival could be achieved and if parenteral nutrition-associated liver disease were reversible, this procedure could be more widely applied, with early liver dysfunction indicating the need for transplant evaluation. Methods. Twenty-six patients who had failed parenteral nutrition received 28 isolated intestinal transplants. We analyzed patient and graft survival, the effect of sirolimus on the severity and frequency of rejection, and the reversibility of liver dysfunction after transplant. Results. Three-year actuarial patient and primary graft survival were 88% and 71%, respectively. Two patients underwent successful retransplants. Twenty-two patients are alive at a mean of 21±15 (median 18; range 3–51) months. Actuarial survival with freedom from parenteral support is 81% at 3 years (21 of 26 patients). Actuarial freedom from parenteral support among survivors is 95.5% at 3 years (21 of 22 patients). Early rejection was less frequent with sirolimus (34% vs. 70% without sirolimus) (P =0.007). Moderate and severe rejection was less frequent with sirolimus (1/11 episodes vs. 9/17 episodes without sirolimus) (P =0.05). No grafts were lost after introduction of sirolimus. In all four patients with advanced liver dysfunction, fibrosis and cholestasis regressed within 1 year. Conclusions. High patient survival and parenteral nutrition-free survival can be achieved after isolated intestinal transplantation. Sirolimus treatment has eliminated graft loss. Parenteral nutrition-associated liver disease is reversible with intestinal transplantation. Refractory liver dysfunction in patients receiving parenteral nutrition should prompt consideration for isolated intestinal transplantation.

Quality of life after lobectomy for adult liver transplantation.

INTRODUCTION Adult-to-adult living donor liver transplants are being increasingly performed. Although considerable data are available on the quality of life after kidney donation, there is little comparable information on liver donors. METHODS Between August 1998 and July 2000, 48 adults received liver grafts from living donors. At least 2 months after donation, donors were mailed a structured questionnaire and the standardized Medical Outcomes Study Short-Form Health Survey (SF-36), a generic measure assessing health-related quality of life outcomes using eight scales: mental health, emotional limits, vitality, social function, physical function, physical limits, pain, general health. RESULTS Thirty donors (62.5%) responded at a mean of 280+/-157 days after donation. Fifteen (50%) of their recipients had major complications (two deaths, four retransplants, nine biliary complications). Regarding overall satisfaction, all said they would donate again. Compared to published U.S. norms (n=2474), our group of donors scored higher than the general population in seven of eight domains on the SF-36. Donors whose recipients had no complications scored significantly higher in mental health (P<0.007) and general health (P<0.008) compared with U.S. norms. Donors whose recipients had major complications scored significantly lower on the mental health scale than those with recipients without major complications. CONCLUSIONS Donors did not regret their decision to donate; several felt the experience had changed their lives for the better. Donors scored as well as or better than U.S. norms in general health. Quality of life after donation must remain a primary outcome measure when we consider the utility of living-donor liver transplants.

Intestinal transplantation before and after the introduction of sirolimus

Introduction. Small bowel transplantation has been limited by high rates of rejection and graft loss. In June 2000, we began using sirolimus, an immunosuppression agent with proven efficacy in kidney transplantation. We reviewed results among intestinal transplant recipients before and after the introduction of sirolimus. Methods. Thirty-one intestinal transplants were performed in 29 patients at our center between July 1998 and April 2001. All patients were followed for at least 30 days posttransplant. In the first 19 transplants (group 1), patients received tacrolimus, steroids, and antibody induction therapy (either daclizumab or OKT3). In the next 12 consecutive transplants (group 2), patients received tacrolimus, steroids, basiliximab, and sirolimus. Results. Eighteen children (7 males and 11 females, mean age 2.1±2.2 years) and 11 adults (9 males and 2 females, mean age 38.1±12.4 years) underwent transplantation. All patients survived transplantation. The overall reoperation rate was 1.7 procedures per patient in group 1 and 1.1 procedures per patient in group 2. The most common indications were abscess (n=7), planned second look (n=7), leaks/fistulas (n=6), dehiscence (n=6), obstruction (n=4), ischemic bowel (n=3), perforations (n=3), stomal complications (n=3), and graft removal (n=3). The incidence of biopsy-proven rejection in the first 30 days was 73.7% in group 1 and 16.7% in group 2 (P <0.002). Sirolimus was temporarily held or discontinued in 66.7% of patients. Actuarial 1-year graft survival was 91.7% with sirolimus and 57.9% without sirolimus (P <0.04). Actuarial 1-year patient survival was 91.7% with sirolimus and 79% without sirolimus (P =0.12). Conclusions. An immunosuppressive regimen that includes sirolimus has improved graft survival. Furthermore, this regimen has significantly decreased the incidence of early rejection and has eliminated early graft loss caused by fulminant rejection.