374 Letters to the Editor ] Am Coil Surg

Dr. Barie has described a small series of pa­ Pancreas Transplantation tients with AIDS who underwent percutaneous Robert]. Corry, MD, FACS, and Thomas E. Starzl, cholecystostomy for acute cholecystitis, with good results and little associated morbidity. Because of MD, phD, FACS, Professors of Surgery, Pittsburgh, PA this limited experience, he suggests that this is the The article entitled " ...Surgical Risk of Pancreas "standard of care" at his institution. Percutaneous Transplantation ..." by Gruessner, Sutherland, and cholecystostomy has a distinct role in the manage­ associates in the August issue emphasizes several im­ ment of patients for whom the risks of operative portant points about this complex procedure, which intervention and anesthesia are overwhelming. is still viewed as "experimental" by several health care But our institutional experience and an extensive funding agencies, including the Health Care Financ­ review of the literature suggest that surgery is con­ ing Administration. traindicated in only the smallest minority of pa­ The Minnesota group, which initiated the clini­ tients with AIDS-related biliary disease. We have cal procedure in 1966,1 has pioneered the evolution demonstrated that cholecystectomy is a safe inter­ of pancreas transplantation for the past 3 decades vention in this population of patients. Cholecys­ under the direction of David Sutherland. The ques­ tectomy resolves the pathology by removing the tion has always been raised whether the procedure, infected organ and provides more lasting benefit. which is associated with considerable morbidity, is The expected survival after a bout with cholecys­ worth the potential risk. The authors have presented titis is measured in years, not weeks or months. For an honest appraisal of the risk factors together with this reason, the likelihood of ultimately having to details, statistics, and results, including the effects of intervene surgically is high after a temporizing surgical complications on graft success rates and pa­ procedure such as cholecystostomy. tient survival. Of particular interest, the subgroup of There are other reasons to avoid cholecystostomy recipients that required relaparotomy (32%) had a in patients with AIDS. Longterm, indwelling drains 77% I-year patient survival rate in the pancreas/ in patients with infectious disease may pose a biohaz­ kidney group compared with an 87% survival rate in ard, both in the hospital and in the home setting. the remaining 68% who did not require reoperation. Definitive cholecystectomy may also help to resolve The effect of relaparotomy on I-year graft survival infection in the remaining portion of the biliary tree. was more devastating: 32% versus 82%. Our experience with a small number of patients who In our series of 123 consecutive patients who had biliary tree (including gallbladder) overgrowth received cadaveric pancreas transplantation in the with either cryptosporidium or cytomegalovirus sug­ last 3 years (all but 17 having simultaneous trans­ gests that once the gallbladder is removed, over­ plantation with a kidney), one died after multiple reoperations for septic complications. Two others growth of the biliary tree regresses. I am concerned having no relaparotomy died at 4 and 8 months of that such regression in disease may not follow drain­ posttransplant lymphoma and a midbrain stroke, re­ age alone. spectively. Our graft success rate (median followup As our understanding of HIV and AIDS has 1-5 years) was 56% in the 41 reoperated patients grown, we have been better able to discern the true versus 95% in the 82 patients who did not require role of surgery in the treatment of its complications. relaparotomy. If nine patients with low perfusion/ The most difficult distinction is in determining thrombosis requiring graft removal within the first what level of therapy is "too" aggressive and what week were excluded from the reoperated group, the is not aggressive enough. In our experience, cho­ graft success rate was 78%. lecystectomy represents the appropriate level of Although we continue to use bladder drainage in care for patients with HIV/AIDS who have some recipients of pancreas-only to monitor the uri­ cholecystitis. nary amylase level as an indicator of rejection, we have increasingly used enteric drainage for all pan­ creas grafts because of its lower complication rate. 2 References Dehydration and acidosis do nor occur, eliminating the conversion from bladder to enteric drainage, 1. Flum DR. Stcinberg SD. Sarkis AY. er al. The role of cholecvstcc­ tomv in acquired immunodeflciencv syndrome. J Am Coil Surg which has been necessary in nearly 20% of patients at 1997: 184:233-239. some centers.3 Vol. 3, No. March, 372-3761998 Letters to the Editor 375

Our use of tacrolimus-based immunosuppres­ based (over cydosporine-based) immunosuppression sion without prophylactic antilymphoid induction has also been documented in a multicenter analysis.2 therapy and rapid tapering of steroids has reduced In our historic overview, patients receiving tacroli­ the incidence of both viral and bacterial infections, mus were not included. while allowing good control of rejection. In recipient Since August 1, 1994, we have used tacrolimus­ selection, it is important to avoid patients with ad­ based immunosuppression for 234 pancreas trans­ vanced, uncorrectable coronary artery disease. In our plant recipients. As in the Pittsburgh experience, our opinion, donor exclusion based on an arbitrary age I-year patient and graft survival rates (95% and ceiling is unnecessarily restrictive. A decision to use 78%, respectively) have been significantly higher an organ can be made wisely from its gross appear­ with tacrolimus than with cyclosporine. A total of 51 ance and texture, the adequacy of the venous efflux of (22%) patients receiving tacrolimus underwent re­ chilled flush solution after benchwork reconstruc­ laparotomy (compared with 32% in the cyclosporine tion, and the quality of the vessels. era, as stated in our article). Similarly, only 23 recip­ Surgical complications associated with pancreas ients (10%) of tacrolimus required treatment for in­ transplantation should not necessarily result in an traabdominal infection (compared with 20% in the increased mortality rate or a high incidence of graft cyclosporine era, as stated in our article). In the ta­ loss. crolimus era, not only has the surgical complication rate decreased, but the number of graft losses from References rejection has also decreased. These improvements in 1. Kelly WD, Lillehei Re, Merkel FK, et aI. Allotransplantation ofthe overall outcome are largely due to tacrolimus, but pancreas and duodenum along with the kidney in diabetic ne­ also reflect the introduction of another new immu­ phropathy. Surgery 1967;61:827-837. 2. Corry RJ, Egidi MF. Shapiro R, et aI. Pancreas transplantation with nosuppressive drug, mycophenolate mofetil; the use enteric drainage under tacrolimus induction therapy. Transplant of more efficient, yet less toxic, antimicrobial agents; Pmc 1997;29:642. 3. Sollinger HW, Messing EM, Eckhoff DE, et aI. Urological compli­ refinements of the transplant procedure itself; bener l cations in 210 consecutive simultaneous pancreas kidney trans­ diagnosis of rejection because of more liberal use of plants with bladder drainage. Ann Surg 1993;218:561-570. ! biopsies; and better selection of donors and recipients. I In Reply Drs. Corry and Starzl suggest that tacrolimus­ based immunosuppression allows avoidance of pro­ Rainer W. G. Gruessner, MD, PhD, Minneapolis, MN phylactic anti-T-cell induction therapy after pan­ We appreciate the interest and the insightful com­ creas transplantation. This possibility still needs to be ments of Drs. Corry and Starzl regarding our article studied prospectively. A multicenter study will begin "The Surgical Risk of Pancreas Transplantation in by the end of this year that will use tacrolimus-based the Cyclosporine Era: An Overview," published in immunosuppression and will compare outcomes the Journal ofthe American College ofSurgeons in Au­ with, versus without, anti-T-cell induction therapy. gust 1997. 1 Drs. Corry and Starzl of the University of 2} The optimal technique to handle pancreas Pittsburgh raised the following issues, all pivotal ro graft exocrine secretions has been the subject of on­ successful pancreas transplantation: 1) immunosup­ going discussion since the beginning of pancreas pressive therapy, 2) management of pancreas graft transplantation. Historically, the incidence of techni­ exocrine secretions, 3) donor and recipient selection cal failure has been greater with enteric (versus blad­ criteria, and 4) the impact of surgical complications der) drainage--one of the reasons that bladder drain­ on outcome. age has become the most common technique to drain 1) As stated in its tide, our article represents a the exocrine secretions. In addition, bladder drainage hisroric overview of the surgical risk of pancreas allows graft exocrine function to be monitored by transplantation in the cyclosporine era, covering the measuring pancreas enzymes secreted directly inro period from January 1, 1986 through July 31, 1994. the urine. The disadvantage of bladder drainage is Since mid-1994, tacrolimus has been used by many that it can cause metabolic, pancreatic, or urinary transplant centers (including ours) as the mainstay of complications that may ultimately require takedown immunosuppressive therapy after pancreas trans­ of the duodenocystostomy and conversion (0 enteric plantation. Drs. Corry and Stanl reported improved drainage. patient and graft outcomes in their series when ta­ Enteric drainage will replace bladder drainage I. crolimus was used. The superiority of tacrolimus- only if it can be shown that graft survival is equiva- 376 Letters to the Editor ] Am Coll Surg

lent, both shortterm and longterm. According to the 2: 45 years old can be transplanted successfully, but latest update by the International Pancreas Trans­ results are more consistently good with donors < 45 plant Registry,3 the I-year graft survival rate with years of age. bladder drainage is 83%; with enteric drainage with 4) In our experience, surgical complications con­ Roux-en-Y, 80%; and with enteric drainage without tinue to have a negative impact on graft outcomes Roux-en-Y, 77% (overall p < 0.1). The difference in and hospital costs,5 despite the use of tacrolimus. In graft survival is not significant for bladder drainage the Pittsburgh series, graft survival was 39% lower versus enteric drainage with Roux-en-Y or for enteric for recipients who underwent a relaparotomy after drainage with versus without Roux-en-Y. But the dif­ transplantation versus those who did not. In our se­ ference is significant for bladder drainage versus en­ ries, I-year graft survival in recipients of tacrolimus teric drainage without Roux-en-Y. 3 These results was 83% without versus 55% with a relaparotomy have been reported only for recipients of simulta­ after transplantation (p < 0.0001). Pancreas trans­ neous pancreas-kidney transplants, in whom the kid­ plantation remains a procedure that requires metic­ ney graft is considered a surrogate marker of rejec­ ulous attention to technical detail. Any minor tech­ tion. Because renal markers for rejection cannot be nical error can have catastrophic consequences. used after solitary pancreas transplantation, we cur­ In conclusion, we agree with Drs. Corry and rently recommend against enteric drainage for soli­ Starzl that tacrolimus has further improved the re­ tary pancreas grafts. sults of pancreas transplantation. More than 1,000 3) Outcomes after pancreas transplantation are pancreas transplant procedures are now performed largely influenced by prudent selection of donors and annually in the United States. This procedure has recipients. In a multivariate analysis, we showed pre­ become a well-established treatment option for pa­ viously that the presence of pretransplant cardiac dis­ tients with insulin-dependent type I diabetes melli­ ease (myocardial infarction, bypass, angioplasty) tus. We hope that, in the near future, Medicare and placed pancreas transplant recipients at a higher risk Medicaid will join the increasing number of insur­ 4 of death with a functioning graft. This finding is in ance providers that cover pancreas transplants. line with Drs. Corry and Starzl's recommendation not to perform transplantation in candidates with advanced, uncorrectable coronary artery disease. References We have recommended against the use of donors 1. Gruessner RWG. Sutherland DER. Troppmann C. et al. The sur­ > 45 years old. We agree that this arbitrary age ceil­ gical risk of pancreas transplantation in the cyclosporine era: an overview. JAm ColI Surg 1997;185:128-144. ing is restrictive, but it provides a guideline for 2. Gruessner RWG. Tacrolimus in pancreas transplantation: a multi­ smaller transplant centers. Repeated analyses by the center analysis. Clin Transplant 1997; 11 :299-312. 3. Gruessner AC. Sutherland DER. and Gruessner RWG. RepOrt of International Pancreas Transplant Registry have the International Pancreas Transplant Registry (IPTR). Transplant shown significantly less favorable outcomes with do­ Proc (in press). nors 2: 45 years 01d.3 Surgeons with experience in 4. Gruessner RWG. Dunn DL. Gruessner AC. et al. Recipient risk factors have an impact on technical failure and patient and graft pancreas transplantation can and should weigh other survival rates in bladder-drained pancreas transplants. Transplanta­ factors (besides donor age) in deciding on a particular tion 1994;57:1598-1606. 5. Gruessner AC. Troppmann C, Sutherland DER. and Gruessner donor organ, such as its gross appearance and texture. RWG. Donor and recipient risk factors significantly affect COSt of In our own experience, pancreas grafts from donors pancreas transplants. Transplant Proc 1997;29:656-657.