Pancreatic islet transplantation after upper abdominal exeriteration and liver replacement

Tzakis, Andreas G.; Zeng, Yijun; Fung, John J.; Todo, Satoru; Demetris, Anthony J.; Starzl, Thomas E.; Mintz, Daniel H.; Alejandro, Rodolfo; Ricordi, Camillo

doi:10.1016/0140-6736(90)91946-8

Cited by 264 publications

(110 citation statements)

References 27 publications

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“…In the clinical trials conducted to date, fresh isolates of islets with a similar range of purity were used for transplantation [2]. Whether the acinar tissue is capable of eliciting a potentially noxious non-specific inflammatory response because of enzyme release in humans is uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Human islets obtained from six different multi-organ donors were separated and purified as previously described [2,10,11]. A portion of the suspension was fixed in buffered formaldehyde and cell pellets obtained by centrifugation at 800 g for 3 min.…”

Section: Preparation Of Samplesmentioning

confidence: 99%

“…Recent advances in isolation procedures and immunosuppression have led to human islet allotransplantation in patients receiving cluster organ transplants with good survival of functional islets for more than 6 months [2]. Rejection of the transplanted islet cells, however, remains a confounding problem, and precludes the use of islet cell allografts in not otherwise immunosuppressed hosts.…”

Section: Introductionmentioning

confidence: 99%

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Composition of human islet cell preparations for transplantation

et al. 1992

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To study the cellular composition of human islet cell isolates for transplantation, formalin-fixed and paraffin-embedded cell pellets were stained by the immunoperoxidase method with a panel of antibodies characterising endocrine, epithelial, soft tissue and haematolymphoid components. Immediately after separation, the isolates contained 30-80% islet cells, differing mainly in the content of islet and acinar cells, whereas the soft tissue, ductal/ductular and haematolymphoid elements comprised a relatively constant 10-20%. After 1 week in culture the islet cell content of less highly purified isolates (30-40% islets) dropped dramatically to 5%. The highly purified isolates (70-80% islets) showed only a minimal change in cellular composition; however, approximately two-thirds of islet cells were degranulated and did not stain for insulin. Haematolymphoid components were still present in all cultured isolates. We conclude that primarily mechanical purification methods and short-term culture are not sufficient to eliminate highly immunogenic cells. In addition, short-term culture is deleterious to the isolate if a significant number of acinar cells is still present after enrichment.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Composition of human islet cell preparations for transplantation

et al. 1992

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“…Islets were isolated from the donor pancreas, purified by a COBE 2991 cell separator (COBE Laboratories, Lakewood, CO), resuspended in Hank's solution with 10% albumin, and infused through the portal vein into the newly engrafted liver. 4 …”

Section: Transplantationmentioning

confidence: 99%

Resection, including transplantation, for hepatoblastoma and hepatocellular carcinoma: Impact on survival

Tagge

Reyes

et al. 1992

Journal of Pediatric Surgery

118

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Long-term survival in children with primary hepatic malignancies can not be expected without complete tumor resection. In the last ten years we have treated 21 children with hepatocellular carcinoma (HCC) and 21 children with hepatoblastoma (HEP), with tumor extirpation our surgical goal. Operative treatment included partial hepatectomy ([PH] 20), either primary (10) or delayed (following chemotherapy) (10), total hepatectomy and orthotopic liver transplantation ([OLT] 13), or upper abdominal exenteration and multiple organ transplantation (2). Two patients had both PH and subsequent total hepatectomy and OLT. Overall survival was 48% (20/42), with 9 patients dying of progressive disease prior to removal of their tumor. HEP patient survival was 67% (14/21), including 2 of 6 who underwent primary PH, 7 of 8 who had delayed PH, and 5 of 6 who underwent OLT. Survival for the children with HCC was 29% (6/21), including 1 of 4 after primary PH, 1 of 2 following delayed PH, 3 of 7 following OLT, and 1 of 2 after exenteration and multiple organ transplantation. Preoperative chemotherapy facilitated removal of 10 initially unresectable tumors (8 HEP, 2 HCC) at a second-look procedure. Total hepatectomy and OLT markedly improved survival in patients with disease unresectable by standard methods. Partial hepatectomy, either primary or delayed, should be attempted in all children with hepatic malignancies. Total hepatectomy and OLT appears to be a viable adjunct in the treatment of childhood malignancies, and should be used for otherwise unresectable tumors as part of a carefully planned protocol. INDEX WORDSHepatoblastoma; hepatocellular carcinoma; liver transplantation Childhood liver tumors continue to have a poor prognosis despite increasingly sophisticated diagnostic methods, aggressive surgical techniques to achieve complete resection, and more effective systemic chemotherapy. Total surgical removal remains the mainstay of treatment, although there are rare reports of long-term survivors achieved with chemotherapy alone. Preoperative chemotherapy has increased the number of patients undergoing potentially curable resections. 1 However, a large proportion of children, especially with hepatocellular carcinoma (HCC), are not resectable by standard methods. Total hepatectomy and orthotopic liver transplantation (OLT), the only alternative for unresectable tumors, is still controversial due to the high incidence of tumor recurrence. 2Address reprint requests to Edward P. Tagge, MD,

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“…The technique has subsequently been modified to remove the need for the pancreatic and jejunal grafts. Pancreatic islet grafts have been successfully seeded within the hepatic graft, either from the original or a third party donor (Tzakis et al, 1990). …”

Section: Carcinoma Of the Biliary Tractmentioning

confidence: 99%