Nadey Hakim

The surgical risk of pancreas transplantation in the cyclosporine era: an overview

BACKGROUNDnPancreas transplants are still associated with the highest surgical complication rate of all routinely performed solid organ transplants. To date, the impact of serious surgical complications in the cyclosporine era on perioperative patient morbidity, graft and patient survival, and hospital costs has not been analyzed in detail.nnnSTUDY DESIGNnWe retrospectively studied surgical complications after 445 consecutive pancreas transplants (45% simultaneous pancreas-kidney [SPK], 24% pancreas after kidney [PAK], and 31% pancreas transplant alone [PTA]). Of these, 80% were primary transplants, 20% were retransplants. Cadaver donors were used in 92%, living related donors in 8%. To develop guidelines for their prevention and management, we studied the impact of significant surgical complications (intra-abdominal infections, vascular graft thrombosis, and anastomotic leak) requiring relaparotomy on graft and patient survival.nnnRESULTSnRelaparotomy was required after 32% of all pancreas transplants (SPK: 36%, PAK: 25%, PTA: 16% [p = 0.04]). Perioperative mortality was 9%. Graft and patient survival rates were significantly lower for recipients with (versus without) relaparotomy. The most common procedures were drainage of intra-abdominal abscess with graft necrosectomy (50% of all relaparotomies) and transplant pancreatectomy (34%). The most common causes of relaparotomy were intra-abdominal infection, vascular graft thrombosis, and anastomotic leak. Intra-abdominal infection occurred in 20% (SPK: 18%, PAK: 24%, PTA: 20% [p = NS]). The rate was significantly higher for living related donor (42%) versus cadaver donor (18%) recipients and for those with enteric-drained (39%) versus bladder-drained (18%) transplants. Graft and patient survival rates were significantly lower for recipients with (versus without) intra-abdominal infection. Outcome was better after bacterial (versus fungal) infections. For SPK recipients, those not on dialysis before the transplant had significantly higher graft survival than those on dialysis. Vascular graft thrombosis occurred in 12% of all recipients. The rate was significantly higher for PAK (21%) than for PTA (10%) and SPK (9%) recipients. It was significantly lower for recipients of grafts with donor iliac Y-graft reconstruction (versus all other types of arterial reconstruction) and with right-sided (versus left-sided) graft placement. Of note, patient survival was not different for recipients with versus without vascular graft thrombosis. The incidence of anastomotic or duodenal stump leaks was 10%; of these recipients, 70% required relaparotomy. Patient and graft survival rates were no different for recipients with versus without leaks.nnnCONCLUSIONSnSerious surgical complications occurred in 35% of pancreas recipients and had a significant impact on patient and graft survival. Based on multivariate risk factor analyses, we recommend the following: donors over 45 years and those dying of cerebrocardiovascular disease should not be used; recipients over 45 years and those with a history of cardiac disease should be considered for a kidney transplant alone (KTA); surgical technique for graft procurement, preparation, and implantation should be meticulous; right-sided implantation and arterial Y-graft reconstruction should be performed when possible, since they had the highest success rates; when complications require relaparotomy, the focus must switch from graft salvage to life preservation; and the threshold for pancreatectomy should be low. Diagnosis should be timely, and treatment and relaparotomy expeditious. These cornerstones of success should help decrease the risk of surgical complications and mortality after pancreas transplants.

Renal transplantation for patients 60 years of age or older: A single- institution experience

ObjectiveThe authors reviewed renal transplant outcomes in recipients 60 years of age or older. BackgroundBefore cyclosporine, patients older than 45 years of age were considered to be at high risk for transplantation. With cyclosporine, the age limits for transplantation have expanded. MethodsThe authors compared patient and graft survival, hospital stay, the incidence of rejection and rehospitalization, and the cause of graft loss for primary kidney recipients 60 years of age or older versus those 18 to 59 years of age. For those patients ≥ 60 years transplanted since 1985, the authors analyzed pretransplant extrarenal disease and its impact on post-transplant outcome. In addition, all surviving recipients ≥ 60 years completed a medical outcome survey (SF-36). ResultsPatient and graft survival for those ≥ 60 years of age versus those 18 to 59 years of age were similar 3 years after transplant. Subsequently, mortality increased for the older recipients. Death-censored graft survival was identical in the two groups. There were no differences in the cause of graft loss. Those 60 years of age or older had a longer initial hospitalization, but had fewer rejection episodes and fewer rehospitalizations. Quality of life for recipients 60 years of age or older was similar to the age-matched U.S. population. ConclusionRenal transplantation is successful for recipients 60 years of age or older. Most of them had extrarenal disease at the time of transplantation; however, extrarenal disease was not an important predictor of outcome and should not be used as an exclusion criterion. Post-transplant quality of life is excellent.

Correlation between cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants.

BACKGROUNDnUrinary amylase (UA) remains the most common biochemical parameter to detect rejection in bladder-drained pancreas allografts. With the development of the cystoscopic transduodenal pancreas transplant biopsy technique, tissue samples of the pancreas graft are now frequently obtained. A definitive correlative analysis between UA activity and biopsy results has not been done in the three different pancreas transplant categories (simultaneous pancreas-kidney, pancreas transplant alone, and pancreas after kidney).nnnMETHODSnWe studied 66 pancreaticoduodenal biopsy specimens obtained for hypoamylasuria. Rejection was defined as a greater than 25% decrease from stable posttransplantation baseline on two consecutive measurements at least 12 hours apart. To perform biopsies we used our newly developed 14- and 16-gauge core-cut needles (50 cm long). Biopsy specimens were considered positive if either pancreatic or duodenal rejection was found. To assess the quality of UA activity we studied 13 biopsy specimens from patients with stable UA levels; these 13 specimens were negative for rejection.nnnRESULTSnAcute rejection was diagnosed in 36 biopsy specimens (55%). The mean decrease in UA levels was 67% +/- 8% (range, 28% to 99%) for the positive biopsy results, and 57% +/- 16% (range, 22% to 92%) for the negative biopsy results (p = 0.147). Within 1 month, UA levels returned to baseline in 19% of our patients with positive biopsy results versus 97% with negative results; postbiopsy 1-year graft survival was 64% versus 97% (p < or = 0.05). In assessing the test quality of our biopsy specimens (including 13 obtained for reasons other than hypoamylasuria), we found a sensitivity of 100% (stable UA levels mean no rejection) and a specificity of 30%. The predictive value of a positive test was 53%; of a negative test it was 100%. By performing biopsies we avoided antirejection treatment in 47% of the patients studied. We found no biopsy-related complications.nnnCONCLUSIONSnStable UA levels reliably rule out rejection; a decrease is a marker for acute rejection but is unspecific. Performing biopsy is currently the only way to reliably diagnose rejection in solitary pancreas recipients (pancreas transplant alone and pancreas after kidney) and in simultaneous pancreas-kidney recipients with isolated hypoamylasuria. The procedure is safe and should always be attempted to avoid unnecessary rejection treatment.

Duodenal complications in bladder-drained pancreas transplantation

BACKGROUNDnThe most common type of pancreas transplantation is whole pancreaticoduodenal (with bladder drainage) from a cadaver donor. Complications can arise not only from the pancreas itself but also from the simultaneously transplanted duodenum. The purpose of this study was to analyze the incidence, diagnosis, and treatment of duodenal complications and their impact on patient and pancreas graft survival rates.nnnMETHODSnOur retrospective study is based on 425 pancreaticoduodenal transplantations performed between July 1, 1986, and June 30, 1994. Complications pertaining to the duodenal segment were labeled early if they occurred within the first postoperative month and late otherwise. Mean follow-up was 55 months (range, 13 to 108 months).nnnRESULTSnWe noted 85 (20%) duodenal complications: duodenal leaks (n = 42), hematuria (n = 26), recurrent urinary tract infections (n = 9), duodenal ulceration or necrosis (n = 6), and bladder stones (n = 2). Of these complications, 40 (48%) required surgical intervention. In all, duodenal complications resulted in 14 (16%) enteric conversions and eight (9%) pancreas graft losses (six because of duodenal leak and 2 because of hematuria). The mortality rate from duodenal complications was 0%.nnnCONCLUSIONSnDuodenal complications were common, but they were not associated with a high rate of pancreas graft loss (only 9%). With early diagnosis and treatment, morbidity can be reduced and death avoided in pancreas transplant recipients.

Combined transplantation of small and large bowel : FK506 versus cyclosporine A in a porcine model

Clinically, FK506 is superior to CsA after solitary small bowel transplantation (SBTx). Development of diarrhea after SBTx has been the rationale for adding the colon to small bowel grafts. However, the additional lymphoid and bacterial content transferred with total small plus large bowel transplants (TBTx) might aggravate the alloimmune response-rejection and graft-versus-host disease (GVHD)-and increase the risk of infection. We studied the incidence of rejection, GVHD, and infection after TBTx and the impact of CsA versus FK506. We performed orthotopic TBTx with portal drainage after total enterectomy in outbred Yorkshire Landrace pigs, divided into 3 groups: control pigs (n=6) received no immunosuppression; CsA pigs (n= 14) received CsA (5 mg/kg), antilymphocyte globulin (10 mg/kg for 10 days), prednisone (2 mg/kg), and AZA (2.5 mgtkg); and FK506 pigs (n=9) received FK506 (0.2 mg/kg) and prednisone (2 mg/kg). Trough CsA whole blood levels were >400 ng/ml for the first 7 days and >200 ng/ml thereafter. FK506 levels were > 15 ng/ml. We excluded from further analysis 5 early deaths (<3 days) due to anesthesiologic (n=2) or technical reasons (n=3). Median survival of control pigs was 9.5 days (range, 4-13). Cyclosporine did not extend survival: median, 9 days (range, 5-31) (P=0.6). FK506 prolonged survival: median, 37 days (range, 21-49) (P<0.001 vs. control and CsA pigs). Of FK506 pigs, 60% gained weight (+75 g/day), whereas 100% of controls and 75% of CsA pigs lost weight (-550 g/day and -300 g/day, respectively). All control pigs died of rejection within 2 weeks versus none of the FK506 pigs. However, 36% of CsA pigs died of rejection. Groupwise comparison showed less rejection in FK506 versus control pigs (P<0.001) and in FK506 versus CsA pigs (P<0.03), but no difference between CsA and control pigs. None of the control pigs died of GVHD versus 18% of CsA pigs (by day 31) and 37% of FK506 pigs (by day 49). Groupwise comparison showed increased GVHD in FK506 versus control pigs (P<0.001) and a tendency toward increased GVHD in FK506 versus CsA pigs (P=0.08). None of the control pigs died of infection alone versus 22% of CsA pigs (by day 31) and 67% of FK506 pigs (by day 49). Groupwise comparison showed increased infection in FK506 versus control pigs (P<0.001). We detected significant endotoxemia early and late postoperatively. But we saw no specific correlation between endotoxemia, rejection, GVHD, or infection. Based on this study, we have drawn several conclusions: (1) In untreated pigs, TBTx provokes a severe rejection response, but no lethal GVHD. (2) Cyclosporine and particularly FK506 pigs have a high incidence of infection and lethal GVHD, a complication that we had not seen after solitary SBTx. (3) FK506 is superior to CsA in controlling rejection and in prolonging graft and recipient survival; FK506, however, does not reduce GVHD, but rather tends to augment it. (4) TBTx causes endotoxemia. As with solitary SBTx, FK506 is superior to CsA after TBTx. However, longterm survival is difficult to achieve on FK506 recipients because of the development of GVHD and infection.