PANCREAS TRANSPLANTATION

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					 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
                                                                       MD, phD, FACS, Professors of Surgery, Pittsburgh, PA
results and little associated morbidity. Because of
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-
            phropathy. Surgery 1967;61:827-837.
                                                                                  also reflect the introduction of another new immu-
         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-
            plants with bladder drainage. Ann Surg 1993;218:561-570.
                                                                                  diagnosis of rejection because of more liberal use of
     !
                                                                                  biopsies; and better selection of donors and

     I   In Reply
         Rainer W. G. Gruessner,         MD, PhD,    Minneapolis, MN
                                                                                  recipients.
                                                                                       Drs. Corry and Starzl suggest that tacrolimus-
                                                                                  based immunosuppression allows avoidance of pro-
                                                                                  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
                                                                                  only if it can be shown that graft survival is equiva-
I.       crolimus was used. The superiority of tacrolimus-
 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-
of death with a functioning graft. 4 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.

				
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