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M Gundlach

Publications and source records attributed to M Gundlach.

At least 37 records · Page 2Linked to original sources

Living donor for liver transplantation.

Since living related liver transplantation was first performed in 1989, more than 150 cases have been performed worldwide, mostly in the United States and Japan. This paper reports the first series of living related liver transplantation in Europe. Twenty living related liver transplantation surgeries were performed over a 13-mo period, with an overall patient survival of 85%. For patients who underwent elective transplantation (n = 13), the survival rate was 100%. Technical complications included one arterial thrombosis necessitating retransplantation and five bile leaks requiring surgical revision. The technical improvements that permit avoidance of these complications are discussed. A detailed description of the living related liver procurement is given. All procurements yielded grafts of excellent quality. No intraoperative complications occurred, and no reoperations were necessary. No heterologous blood transfusion was needed. In two patients, incisional hernias developed after wound infection. Living related liver transplantation does not absolve the transplant community of efforts to promote cadaveric organ procurement. Nevertheless, living related liver transplantation does have the advantage of a readily available graft of excellent quality, permitting transplantation with optimal timing under elective conditions. Several centers are now preparing living related segmental liver transplants, following the model of our protocol, for three reasons: (a) to obtain superior results compared with cadaveric liver transplantation; (b) to overcome cadaveric organ shortage and further reduce pretransplantation mortality and (c) to provide viable organs in countries where cadaveric organ procurement is not established. When performed by a team experienced in pediatric liver transplantation and in adult liver resection, living related liver transplantation is an excellent modality for the treatment of end-stage liver disease in children.

Adult↗

[The status of liver transplantation in therapy of hepatocellular carcinoma].

The state of the art in liver transplantation for hepatocellular carcinoma is presented through a review of our own data and the pertinent literature. Preoperative evaluation should stage the tumor precisely to allow therapeutic consequences to be drawn. The major obstacle is correct preoperative lymph node staging which is currently possible in less than 50% of the patients. If candidates are selected for transplantation, early vascular exclusion should be performed during the operation to prevent tumor cell dissemination. The results of recent reports on liver transplantation for hepatocellular carcinoma following strict selection criteria are encouraging. Patients with cirrhosis and hepatocellular carcinoma (diameter < 10 cm) fared significantly better after liver transplantation than after resection. Patients with uninodular or binodular disease and tumors smaller than 3 cm even showed a recurrence-free 3 year survival of 83% [3]. We conclude that for some patients liver transplantation offers the only chance for cure. Only prospective, controlled trials will define the patients that profit most from liver transplantation. The rising need for donor organs will currently restrict this modality to a highly selected group of patients. Once effective adjuvant therapies become available more patients might, however, become eligible.

Carcinoma, Hepatocellular↗

Intestinal allograft survival in the rat following pretreatment with donor-specific UV-B-irradiated leukocytes and peritransplant immunosuppression with cyclosporine.

Previous studies from our laboratory showed that pretreatment with ultraviolet-B-irradiated donor leukocytes (UV-B DL) combined with brief peritransplant cyclosporine (CyA) resulted in indefinite survival of Wistar/Furth rat cardiac allografts in Lewis recipients. This study was designed to examine the effect of pretransplant UV-B DL with or without peritransplant CyA on orthotopic intestinal allografts in the same rat strain combination. The results showed that while low-dose CyA treatment alone (10 mg/kg i.m. on days 0, +1, and +2) had no effect on intestinal allograft rejection, 20 mg/kg (on days 0, +1, and +2) CyA significantly (P less than or equal to 0.001) prolonged graft survival, with 33% of the hosts surviving indefinitely. The highest dose of CyA (30 mg on days 0, +1, and +2) abrogated rejection, but most transplant recipients succumbed to infection and functional ileus due to a toxic side effect of CyA. Pretreatment with UV-B DL on days -14 and -7 alone did not prolong intestinal allograft survival. Combination of a subtherapeutic CyA dose (20 or 10 mg/kg) given on days 0, +1, and +2 with pretransplant UV-B DL on days -14 and -7 did not alter the survival of intestinal allografts compared to treatment with CyA alone. This suggests that pretreatment with UV-B DL with or without peritransplant administration of CyA has no effect on intestinal allograft survival, in contrast to the effect of such combined treatment on cardiac allograft survival, where indefinite graft survival is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential effects of pretreatment with ultraviolet-B modified or unmodified donor-specific leukocyte transfusions on intestinal and cardiac allograft survival in the rat.

This study compares the effects of pretreatment with donor-specific leukocytes (DL) or UV-B irradiated donor-specific (UV-B DL) transfusion on day -7 relative to organ transplantation, in the induction of specific immunologic unresponsiveness to intestinal and cardiac allografts in the Lewis-to-ACI rat strain combination. Recipients of orthotopic small intestinal allografts, who were pretreated with UV-B DL survived for 7.2 +/- 3.6 days compared with 7.5 +/- 0.5 days in the control group. Pretreatment with unmodified DL induced hyperacute rejection of intestinal allografts, suggesting a sensitizing effect of DL in this model. In contrast, pretreatment with DL and UV-B DL transfusions significantly prolonged cardiac allograft survival with 25% (DL) and 50% (UV-B DL) of the grafts surviving indefinitely (greater than 120 days). To define the underlying mechanisms of the differential effects of DL and UV-B DL pretreatment on intestinal and cardiac allograft survival, we evaluated the ability of DL and UV-B DL transfusions to induce alloantibodies and donor-directed cytotoxic T lymphocytes (CTL). The finding that recipients of DL developed donor-specific cytotoxic alloantibodies and CTL may partially explain the accelerated rejection of intestinal allografts in such recipients while the disparity of the findings in cardiac and intestinal transplantation may be due to a higher affinity of the induced cytotoxic alloantibodies to antigens on the intestine than on the heart. Since UV-B DL pretreatment prevents the induction of cytotoxic alloantibodies and CTL, there is a significant difference in recipients transfused with DL as compared with UV-B DL. The proliferative response to donor alloantigens (MLR) of lymphocytes obtained from DL and UV-B DL pretreated animals was down-regulated as compared with the MLR response of lymphocytes obtained from unmodified animals. Subsequent coculture experiments demonstrated the appearance of suppressor cells following pretreatment with DL and UV-B DL. While DL and UV-B DL transfusions significantly increased cardiac allograft survival, there was no prolongation of intestinal allografts in our model despite the abrogation of the sensitizing effect of DL transfusions by prior UV-B irradiation. These differential effects on graft survival emphasize the importance of specific organ immunogenicity.

Animals↗

[Distribution of immunocompetent cells small intestine transplantation in rats].

Heterotopic small bowel transplantation was performed in allogeneic rats with and without cyclosporine. Syngeneic animals served as controls. Small bowel allografts, lymphoid tissues and small bowel of the host were investigated by immunohistochemistry using antibodies against T-cells and macrophages. During rejection, increasing numbers of macrophages infiltrated preferentially the deep layers of the small bowel wall, whereas only a slight T-cell infiltration was observed. No histological changes were noted in the organs of the host. Cyclosporine prevented lymphoid as well as macrophage infiltration of the transplant. Rejection monitoring of small bowel transplants is possible by investigation of macrophage infiltration in deep biopsies including the submucosa.

Animals↗

[Small intestine transplantation--a causal therapy in short bowel syndrome].

The problems of surgical technique, graft physiology and immunological reactions in small-bowel transplantation have been investigated in extended animal experiments. In these experiments, the fundamentals of a successful clinical application of small-bowel transplantation could be laid. A successful human small-bowel transplantation could be carried out by the Kiel Group for the first time in 1988. A graft which had been removed from a related donor showed a complete adaptation after 22 months, so that the patient became completely independent from parenteral nutrition. After that, in several cases small-bowel and combined liver and small-bowel transplantation have been carried out. Thus, the clinical small-bowel transplantation represents the causal therapy of short-bowel syndrome and should be developed in further clinical trials.

Adult↗

Small bowel transplantation.

Small intestinal transplantation has had several clinical attempts based on extensive experimental work during the past two decades. Several models, such as auxiliary (heterotopic) or orthotopic models, have been developed in regard to problems with graft immunology and function. The question of mesenteric-portal or mesenteric-caval graft drainage was raised, and the answer seems to be open. Concerning lipid absorption, interest was directed to the reconstitution of lymphatic vessels, because orally administered cyclosporine A is absorbed by the lipid mechanism. Carbohydrate digestion and absorption are used for determination of graft function and for monitoring graft rejection. This article summarizes these problems and deals with the surgical procedure of small bowel transplantation in the rat.

Anastomosis, Surgical↗