Massive Haematochezia due to Splenic Artery Bleeding into the Colon: Unusual Manifestation of Advanced Pancreatic Cancer.

We describe a case of an uncommon early pancreatic cancer presentation in a patient in his 60s who had haemorrhagic shock from extensive haematochezia and required blood transfusions as well as surveillance in an intensive care unit. A splenic artery pseudoaneurysm that had been effectively embolized by angiography was seen to be actively bleeding into the colon lumen on a computerized tomography (CT) scan along with a necrotic mass of the pancreatic tail. A pancreatic mucinous adenocarcinoma was diagnosed by a transgastric biopsy. A pancreatico-colic fistula was discovered by CT scan after a colic contrast enema. A transabdominal drainage of the necrotic collection and targeted antibiotic treatment had been performed with a satisfying patient outcome. In order to assess a potential secondary surgical resection, systemic chemotherapy was planned. In conclusion, haematochezia with hemodynamic instability originated from a splenic artery pseudoaneurysm fistulising into the colon (arterio-colic fistula) and sepsis originating from a tumoral pancreatic abscess fistulising into the colon (tumoral pancreatico-colic fistula).

Therapeutic implications of NK cell regulation of allogeneic CD8 T cell-mediated immune responses stimulated through the direct pathway of antigen presentation in transplantation.

Natural killer (NK) cells are a population of innate type I lymphoid cells essential for early anti-viral responses and are known to modulate the course of humoral and cellular-mediated T cell responses. We assessed the role of NK cells in allogeneic CD8 T cell-mediated responses in an immunocompetent mouse model across an MHC class I histocompatibility barrier to determine its impact in therapeutic clinical interventions with polyclonal or monoclonal antibodies (mAbs) targeting lymphoid cells in transplantation. The administration of an NK cell depleting antibody to either CD8 T cell replete or CD8 T cell-depleted naïve C57BL/6 immunocompetent mice accelerated graft rejection. This accelerated rejection response was associated with an in vivo increased cytotoxic activity of CD8 T cells against bm1 allogeneic hematopoietic cells and bm1 skin allografts. These findings show that NK cells were implicated in the control host anti-donor cytotoxic responses, likely by competing for common cell growth factors in both CD8 T cell replete and CD8 T cell-depleted mice, the latter reconstituting in response to lymphopenia. Our data calls for precaution in solid organ transplantation under tolerogenic protocols involving extensive depletion of lymphocytes. These pharmacological biologics with depleting properties over NK cells may accelerate graft rejection and promote aggressive CD8 T cell cytotoxic alloresponses refractory to current immunosuppression.

Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries.

Incisional hernia after robotic single-site cholecystectomy: a pilot study.

PURPOSE: Robotic LaparoEndoscopic Single-Site Surgery Cholecystectomy has been performed for 5 years using a dedicated platform (da Vinci® Single-Site®) with the da Vinci® Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). While short-term feasibility has been described, long-term assessment of this method is currently outstanding. The aim of this study was to assess long-term parietal complications of this technique. METHODS: In this retrospective study, patients operated between 2011 and 2013 were evaluated. Parietal incision was assessed with ultrasonography and patients screened for residual pain from scar tissue. Demographic and perioperative data were also collected. RESULTS: We evaluated 48 patients [38 female, 79.2%; median age 49 years (range: 24-81 years)]; mean BMI 25.9 kg/m2 [±SD 4.1 kg/m2]. After a median follow-up of 39 months (range: 25-46 months), six incisional hernias (two patients had a positive echography but a negative clinical examination) were found (12.5%, 95% CI 7.5-30.2), and two patients had a surgical repair. The overall rate of incisional hernia was 16.7% (95% CI 7.5-30.2). Residual pain was observed in 5 of 48 patients. CONCLUSION: This preliminary study suggests that a clinically significant rate of incisional hernias can occur after R-LESS-C. Larger studies comparing R-LESS-C to alternative methods with long-term follow-up are necessary.

Persistence of Indirect but Not Direct T Cell Xenoresponses in Baboon Recipients of Pig Cell and Organ Transplants.

We investigated the contributions of direct and indirect T cell antigen recognition pathways to the immune response to porcine antigens in naïve baboons and baboon recipients of pig xenografts. In naïve baboons, in vitro culture of peripheral blood T cells with intact pig cells (direct xenorecognition pathway) or pig cell sonicates and baboon antigen-presenting cells (indirect xenorecognition pathway) induced the activation and expansion of xenoreactive T cells producing proinflammatory cytokines, interleukin-2 and interferon-γ. Primary indirect xenoresponses were mediated by preexisting memory T cells, whose presence is not typically observed in primary alloresponses. Next, baboons were conditioned with a nonmyeloablative regimen before short-term immunosuppression and transplantation of xenogeneic peripheral blood progenitor cells and a kidney, heart, or pancreatic islets from a miniature swine. All transplants were rejected acutely within 30 days after their placement. Posttransplantation, we observed an inhibition of the direct xenoresponse but a significant expansion of indirectly activated proinflammatory T cells. These results suggest that additional treatment to suppress indirect T cell immunity in primates may be required to achieve tolerance of pig xenografts through hematopoietic chimerism.

[Cell transplantation: current treatments and future prospects]. / Transplantation cellulaire: traitements actuels et perspectives d'avenir.

Regenerative medicine aims to replace a body function or specific cell loss. It includes therapies at the forefront of modem medicine, issuing from translational biomedical research. Transplantation of organs and cells has revolutionized the management of patients for whom medical treatment is a failure. Unfortunately, organ shortage is limiting treatment possibility. As an example, among the 15,000 patients with type I diabetes in Switzerland, only approximately 30 can receive a pancreas or an islet transplant per year. Second example, 500 patients die each year in Switzerland from alcoholic cirrhosis because no treatment is available. Transplantation of islet cells, hepatocytes, mesenchymal stem cells or dopaminergic neurons represents hope fora therapy available for large populations of patients.

[Robotic-assisted organ transplantation]. / Transplantation d'organes avec assistance robotique.

Advanced surgical procedures have traditionally been a domain of open surgery. However, minimally invasive approaches are evolving with the development of robotic technology which appears capable to overcome technical limitations of conventional laparoscopy. While traditionally perceived as impossible indications for minimally invasive surgery, reports on robotic organ transplantations have surfaced with promising results.

HVEM/LIGHT/BTLA/CD160 cosignaling pathways as targets for immune regulation.

Immunosuppression is currently the treatment of choice to attenuate the chronic deterioration of tissue function as a result of the effector mechanisms of the immunological response in transplant rejection and autoimmune diseases. However, global immunosuppression greatly increases the risk of acquiring life-threatening infections and is associated with organ toxicity when used long-term. Thus, alternative approaches that inhibit only the unwanted immune responses and preserve general immunity are highly desirable. The receptor/ligand pairs involved in the cross-talk between DC and T cells have been the focus of intense and exciting research during the last decade. The HVEM/LIGHT/BTLA/CD160 costimulatory/coinhibitory pathway has emerged as a potential target for the development of immune therapeutic interventions. Herein, we will summarize and discuss how blockade of the costimulatory HVEM/LIGHT interaction or agonist signaling through the inhibitory BTLA and CD160 receptors could contribute to the control of deleterious immune responses.

Renal and cardiac endothelial heterogeneity impact acute vascular rejection in pig-to-baboon xenotransplantation.

Xenograft outcomes are dictated by xenoantigen expression, for example, Gal alpha1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons postcardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants.

[Surgical therapy of abdominal cystic lymphangioma in adults and children]. / Le traitement chirurgical du lymphangiome kystique abdominal chez l'adulte et chez l'enfant.

BACKGROUND: Cystic lymphangioma is a rare malformative benign tumor of the lymphatic vessels. In the abdomen it generally develops as a mesenteric and/or retroperitoneal cyst, but any organ can be involved. The present retrospective study aims to define the symptoms, complications and differences noted between adults and children suffering from abdominal cystic lymphangioma; it is based on patients who underwent surgery for this condition at the Geneva University Hospital. PATIENTS AND METHODS: Since 1995, 16 patients (9 adults and 7 children) were surgically treated for abdominal cystic lymphangioma. Their medical files were reviewed retrospectively. The follow-up was based either on the last physical examination or on a telephone interview with the patients. RESULTS: The mean follow-up was 45 months. The most common presenting symptom was abdominal pain (38%). Ultrasonography was the most efficacious diagnostic modality. The lesions were mostly micropolycystic (44%), and found in retroperitoneal locations (50%). The surgical excision was complete in 14 patients and partial in 2 patients. These last 2 were the only ones who developed complications after the surgery, including one recurrence. CONCLUSIONS: A total surgical excision, if feasible without a major sacrifice of adjacent organs, seems to be the best therapeutic option to minimize the risk of recurrence of symptomatic abdominal cystic lymphangiomas. In our clinical experience, the presentation and evolution of the abdominal cystic lymphangioma seemed to be similar in adults and children.

Vascular invasion in pancreatic cancer: evaluation of endoscopic ultrasonography, computed tomography, ultrasonography, and angiography.

PRINCIPLES: Current methods for detecting vascular invasion in pancreatic cancer can be inaccurate, invasive, and expensive. The aim of this study is to assess the value of current imaging modalities in determining vascular invasion by pancreatic cancer. METHODS: The results of Endoscopic Ultrasonography (EUS), Computed Tomography (CT), Ultrasonography (US), and Angiography performed in 170 patients, suffering from pancreatic cancer, were retrospectively studied and correlated with intra-operative findings and surgical anatomopathological diagnosis after resection. We assessed sensitivity, specificity, positive and negative predictive values, and accuracy for detecting vascular invasion. RESULTS: EUS turned out to be the most reliable imaging technique for detecting vascular invasion in pancreatic cancer, with a sensitivity of 55%, specificity of 90%, positive predictive value of 61.1%, negative predictive value of 87.5%, and accuracy of 82.2%. CT results were 39.4%, 90%, 52%, 84.4%, and 79.1% for the respective categories, with however, better results with multislice CT. The US results were 3.7% for the sensitivity, 96.3% for the specificity, 25% for the positive predictive value, 75.2% for the negative predictive value, and 73.4% for the accuracy. For angiography, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy were 52.6%, 72.3%, 43.5%, 79.1%, and 66.7% respectively. CONCLUSION: In this study, EUS was the most valuable imaging modality in assessing vascular invasion (especially for venous invasion) for pancreatic cancer, with an accuracy of more than 80%. A further prospective study should be carried out to evaluate the combination of imaging modalities for the detection of vascular involvement, especially with multi-slice CT which almost reached the performances obtained by EUS.

An audit of surgical management of gastrointestinal stromal tumours (GIST).

AIM: To analyze GIST outcome after primary resection and to determine if a new grading system could adequately predict there prognosis. METHODS: A retrospective review (1993-2002) identified 80 patients who underwent primary surgical resection for, c-KIT positive, GIST. Follow-up was complete for all patients (median follow-up 42, range 1-132, months). GIST were classified as low or high grade according to the following parameters: size, mitotic rate, mitotic index (MiB1), presence of necrosis, invasion of adjacent structure and presence of metastasis. RESULTS: GIST originated from the stomach (46), small bowel (30), colon and rectum two and mesentery two. At surgery, 94% of cases presented with localized disease and 6% blood born metastasis with or without lymph node invasion. Resections were complete (R0) in 72 cases. R0 resection correlated with prognosis (p<0.01). Sixty GIST were classified as low grade (median follow-up 60 months) and 20 as high grade (median follow-up 27 months). Five-year actuarial survival of patients with low or high grade GIST were of 95 and 21%, respectively, (p<0.001). CONCLUSION: Prognosis of GIST after surgical treatment is influenced by completeness of primary resection and tumour malignant potential. Low grade GIST have an excellent prognosis after surgery alone, while high grade GIST have a high rate of recurrence after primary resection. Adjuvant treatment should be advocated for patient with either high grade GIST or after incomplete primary resection. The presented grading system can reliably predict GIST outcome after primary surgical treatment. Complete surgical resection offers good chance of cure for low grade GIST, while for high grade GIST surgery alone is not sufficient. The presented grading system could be used to identify patients who may benefit of adjuvant treatment with imatinib mesylate after GIST resection.

Treatment of gastrointestinal hemorrhage.

BACKGROUND: We assessed the value of selective arteriography in the diagnosis and management of acute gastrointestinal hemorrhage. METHODS: We reviewed the records of 107 consecutive patients who had gastrointestinal hemorrhage and underwent selective arteriography between January 1992 and October 2003: 10 had upper gastrointestinal bleeding, 79 had lower gastrointestinal bleeding, and 18 had varicose bleeding with portal hypertension. Selective embolization was attempted in 15 patients to obtain hemostasis. Angiographic findings were reviewed and prospective reports were compared with the final diagnosis and outcome. RESULTS: Of 129 angiographic studies, 36 correctly revealed the bleeding site and 93 were negative. Extravasation was seen in 24 cases at the level of stomach (n = 2), duodenum (n = 1), small bowel (n = 5), or colon (n = 16). Indirect signs of bleeding sources were identified in 12 patients (stomach in one, small bowel in four, large bowel in four, liver in three). Transcatheter embolization induced definitive hemostasis in 11 of 15 patients (73%), namely in the stomach (n = 2), small bowel (n = 3), colon (n = 7), and liver (n = 3). Three patients required surgery after embolization. CONCLUSION: Abdominal arteriography may localize gastrointestinal bleeding sources in approximately one-third of cases. Selective embolization may provide definitive hemostasis in most instances.

Role of CD40-CD154 pathway in the rejection of concordant and discordant xenogeneic islets.

BACKGROUND: Costimulatory blockade has been shown to allow long-term survival of xenogeneic islets. The aim of the present study was to evaluate the role of recipient CD40 and CD154 in the rejection process of concordant and discordant islet xenotransplantation (Tx). METHODS: Diabetic C57BL/6 mice, CD40- or CD154 knockout (KO) mice were transplanted with either concordant rat or discordant human islets. EXPERIMENTAL DESIGN: group 1, control (ie, C57BL/6 mice received islet Tx without therapy); group 2, C57BL/6 mice received islet Tx with anti-CD154 monoclonal Ab (mAb) therapy; group 3, CD40 KO mice; and group 4, CD154 KO mice were used as recipients without therapy. Mouse anti-rat mixed lymphocyte reactions (MLR) were performed using mouse splenocytes obtained from animals transplanted with rat islets in groups 1 to 4. RESULTS: In group 2, short-term anti-CD154 mAb therapy significantly prolonged rat-to-mouse and human-to-mouse xenograft survival, compared to controls. In CD40-KO and CD154-KO recipients, survival of concordant or discordant islets was not prolonged significantly compared to control groups. Mouse anti-donor rat cellular responses were reduced approximately 50% in group 2 but remained unmodified in groups 3 and 4, when compared to group 1. CONCLUSIONS: Improved graft survival and reduced MLR responses against donor cells in vitro among the anti-CD154 mAb-treated mice could be explained by specific targeting of activated T cells with subsequent inactivation by anergy and/or elimination by apoptosis, or complement- or cellular-mediated mechanisms. Rejection of xenografts and strong MLR responses against donor cells in vitro in CD40 or CD154 KO animals is possible through efficient activation of alternate pathways of costimulation.

[Nephrology]. / Néphrologie.

Alternative to nephrotoxic calcineurin inhibitors regimens are feasible in renal transplantation. Sirolimus is an effective immunosuppressive drug with less drug-induced nephrotoxicity. Enteric-coated mycophenolate sodium provides a safety and efficacy alternative to mycophenolate mofetil. In peritoneal effluent, cancer antigen 125 (Ca 125) is a mesothelial cell marker and of in vivo biocompatibility of the new dialysis solutions. Longterm PD and peritoneal sclerosis are associated with a low number of mesothelial cells and a low concentration of dialysate Ca 125. Exposure to glucose and degradation products (GDPs) is important in the genesis of mesothelial damage. Short results of the more biocompatible solutions are promising (increasing of Ca 125). In the future, exposure to glucose can be reduced by using combinations of various osmotic agents, each in a low concentration (glycerol and amino acid solution).

[Long-term followup of patients with alveolar echinococcosis]. / Devenir à long terme des malades opérés et traités pour échinococcose alvéolaire.

INTRODUCTION: Alveolar Echinicoccosis is a severe parasitic disease: its natural evolution is comparable to a slowly progressive malignant liver tumour. There is no definitive medical therapy. Surgery remains the only option to assure a cure. This report is our surgical experience for the care of this affection. PATIENTS AND METHOD: Between 1980 and 2002, 12 patients were operated for an hepatic alveolar echinococcosis. For 11 of them, the affection was primary. Lesions were located in the right liver lobe (n = 9), in the left lobe (n = 1), in both lobes (n = 1) and close to the hilar region (n = 1). Twice there was a diaphragmatic infiltration and once a pleural infiltration. Resections consisted in: segmentectomies in the right lobe (n = 4), right hepatectomy (n = 5, associated once with a partial I and IV segmentectomy), left hepatectomy (n = 1), one liver transplantation (n = 1), one drainage of a parasitic cavity (n = 1). One pleurectomy and a partial diaphragmatic resection were made. All patients were treated postoperatively with benzimidazole chemotherapy. RESULTS: Three patients presented some complications: segmental necrosis with biloma (n = 1), biliary fistula tract (n = 1), subdiaphragmatic hematoma (n = 1), cholangitis (n = 1). 10 patients are alive (median follow-up of 10 years). Two patients still present some parasitic lesions; the situation remains doubtful for one of them. Two patients died (one of them in the context of a disease progression). CONCLUSION: Surgical treatment, associated with medical therapy, assured a control of the parasitic lesions or a definitive cure in most cases. When the disease is limited to the liver with no possibility for partial hepatectomy, a transplantation is an option.

Treatment of hepatocellular carcinoma at the dawn of the third millennium: liver transplantation and its alternatives.

Hepatocellular carcinoma is one of the most frequent tumors worldwide, and its frequency is increasing. The management of hepatocellular carcinoma has changed in recent years, this because screening allows to discover tumors at an earlier stage, and because of effective treatments are available, such as liver transplantation, liver resection, percutaneous ablation and transarterial chemoembolization. Each one of these treatments has its own advantages and drawbacks, and range of application according to the stage of the tumor and of the underlying liver disease. This review summarizes the recent progress in the management of HCC and the practice in our unit.

Islet autotransplantation for the prevention of surgical diabetes after extended pancreatectomy for the resection of benign tumors of the pancreas.

OBJECTIVE: The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas. MATERIALS AND METHODS: Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period. RESULTS: Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels. CONCLUSIONS: Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Microbial surveillance during human pancreatic islet isolation.

OBJECTIVES: The study aim was to investigate the microbiological safety of islet isolation and transplantation. MATERIALS AND METHODS: Between 1996 and 2002, prospective microbiological screening was performed on all pancreata procured for islet transplantation. Pancreas transport media and postpurification preparations were screened for microbiological contamination. Prior to isolation, pancreata were washed with either Hanks solution (group I, n = 170) or decontaminated with antiseptic and antimicrobial drugs (group II, n = 45). RESULTS: Microbiological contamination of the pancreas preservation media was shown in 62%. Analysis of the contaminants showed 74% gram-positive, 21% gram-negative organisms, and 5% fungi. The donor condition or procurement center did not influence the contamination rate. Longer pancreas transport duration was significantly associated with bacterial contamination (P <.05). In group I, 16 (9.4%) of 170 islet preparations presented microbial contamination at the end of the isolation procedures. Gram-positive organisms were present in 10 (6%), gram-negative organisms in 4 (2.4%), and fungi in 2 (1.2%) preparations. Four islet preparations (2.4%) from pancreata with noninfected transport medium were positive on postpurification cultures, all with gram-positive organisms. In group II, only 2 of 45 islet preparations (4.4%) presented microbial contamination at the end of the isolation process. CONCLUSIONS: The rate of microbial contamination during pancreas procurement and transport is high. Significant contaminants present when beginning islet isolation become undetectable by the conclusion of isolation. Diminishing the bio-burden by pancreas decontamination reduces the risk of contamination of the final islet preparation.

Retransplantation of discordant xenogeneic islets with costimulatory blockade.

BACKGROUND: The aim of the study was to analyze the possibility of xenogeneic islet retransplantation using costimulatory blockade. METHODS: Streptozotocin-induced diabetic mice were transplanted under the kidney capsule with human islets. Mice were nephrectomized and retransplanted with 1000 human islets under the contralateral kidney capsule 14 days later. Four groups were performed group I, first and second Tx without MR1; group II, first Tx without MR1, second Tx with MR1; group III, first Tx with MR1, second Tx without MR1; group IV, first and second Tx with MR1. A control group was transplanted only once without MR1 with human islets. After second Tx, cross-matches between recipient, serum and human lymphocyte were done for detection of antidonor antibodies. RESULTS: In the control group, mean graft survival was 13 (+/-7) days. In group I, mean graft survival was 5 +/- 3 days. In group II, mean graft survival was 16 +/- 13 days. In group III, mean graft survival was 81 +/- 22 days. In group IV, no rejection were recorded and all graft survived more than 120 days. Pretransplant cross-matches were negative. In groups I and II all cross-matches were positive, while none were positive in group IV. CONCLUSION: Retransplantation of xenogeneic islets was associated with accelerated rejection. After presensitization, MR1 was unable to induce tolerance to a second Tx. MR1 given at the first Tx only allowed prolonged survival of the second Tx, but rejection still occurred. MR1 given at first and second Tx allowed long-term survival of retransplanted xenoislets and prevented occurrence of antidonor antibodies.