portal hypertension secondary to graft infusion, and 3) difficulty in applying the successful technique in a nor- mal dog pancreas to an extensively scarred human ...
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LETTERS TO THE EDITOR
Ann. Surg. November 1981 *
2. Gordon AB, Bates T, Fiddian RV. A controlled clinical trial of drainage after cholecystectomy. Br J Surg 1976; 63:278-282. 3. Edlund G, Gedda S, van der Linden W. Intraperitoneal drains and nasogastric tubes in elective cholecystectomy. A controlled clinical trial. Am J Surg 1979; 137:775-779.
Dear Editor: In their remarkable article "Human Pancreatic Cell Autotransplantation Following Total Pancreatectomy" (Ann. Surg. 1981; 193:191-95), Dr. L. W. Traverso and collaborators analyze three factors that might negatively influence the success of the graft: 1) the preoperative endocrine status, 2) systemic hypotension and portal hypertension secondary to graft infusion, and 3) difficulty in applying the successful technique in a normal dog pancreas to an extensively scarred human pancreas". The authors claim that in their patients, the preoperative endocrine insufficiency was not promptly relieved after the operation because of the small amounts of transplanted tissue; to maintain normoglycaemia they "helped" patients with immediate postoperative administrations of insulin. This could be the wrong approach, because in our experiments in dogs, we found that regardless of its origin, early postoperative hyperglycemia-functional demand-was a mandatory condition for the nidulation and ulterior function of the autotransplant. There was no take or trace of insulin release after animals had been maintained normoglycaemic during the first three postoperative weeks.' Moreover, after a critical amount of tissue, about a third of the gland, had been transplanted, the total volume of the graft was no longer important for the maintenance of normoglycemia following simultaneous total pancreatectomy. The authors were rightly impressed by the dramatic and frightening picture of acute portal hypertension during the intraportal injection of tissue and they were compelled to limit the volume of the transplant. This phenomenon regularly appears in dogs, with all its catastrophic consequences of profuse bleeding, systemic hypotension, shock and early postoperative death. However, in dogs, this obstacle could be greatly diminished, if not completely abolished, by more appropriate incubation conditions, thorough removal of collagenase and its digestion products, a smaller final volume of the implant, and slow, gentle injections.2 The authors are right when they suspect that an efficient technique of tissue preparation which had been developed in dogs may not be directly applicable to the human gland. It is our conviction that the excellent and very reproducible results obtained in dogs are nothing more than an indication that a successful transplant of pancreatic cells is feasible in a larger animal than ro-
dents.3 In order to investigate in greater detail the possibility of a direct transfer of the technique developed in dogs to the human pancreas, we have used nude mice as recipients that could demonstrate whether the tissue preparation procedure was correct.4 When canine pancreas was prepared using the most reproducible technique' and impanted subcutaneously or intraperitoneally into the nude mice, all animals recovered without trouble and normal-looking endocrine tissue was repeatedly indentified under the microscope three weeks after operation. On the other hand, whenever human pancreas was processed with the same incubation procedure, the mice succumbed during the first hours after implantation with extensive liquefaction-necrosis around the sites of implantation in the subcutaneous tissue, muscles and abdominal organs. The worst results were recorded with the gland removed from a patient with chronic pancreatitis. With these convincing, negative results we wholeheartedly agree with Dr. L. W. Traverso and his collaborators that at present the lack of an adequate, efficient and highly reproducible technique of tissue preparation is the principal obstacle to the successful transplantation of pancreatic cells in humans. V. MIRKOVITCH, M.D. F. MOSIMANN, M.D. B. WINISTORFER, M.D. Lausanne, Switzerland References 1. Mirkovitch V., Winistorfer B, Campiche M, et al. Total and immediate pancreatectomy as the mandatory requirement for the ulterior function of autotransplanted islets in dogs. Transplant
Proc. 1979; 9:1502-1505. 2. Mosimann R, Rausis C, Mirkovitch V. Prevention du diabEte chez le chien pancreatectomise par autotransplantation de tissu pancreatique dans le foie. Helv. Chir Acta 1976; 43:241-252. 3. Mirkovitch V, Campiche M. Intrasplenic autotransplantation of canine pancreatic tissue. Eur Surg Res 1977; 9:173-190. 4. Mirkovitch V, Mosimann F, Winist6rfer B. Transplantation of pancreatic cells into nude mice. Unpublished data.
Dear Editor: Dr. Mirkovitch' is recognized as the first to describe a successful intrasplenic, mixed cell pancreatic autotransplantation technique in the dog. At the time of his report,2 we were involved in much more complicated islet isolation techniques but were quickly able to reproduce his simpler method in the dog. With this method, if we did not temporarily occlude the splenic vessels during the intrasplenic injection of the mixed cell pancreatic autograft, transient portal hypertension would occur. This vascular reaction was similar to the more severe portal hypertension that occurred when the cells were injected directly into the portal vein. We called the agent in the transplant which causes these
