Frédéric Triponez

Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations.

BACKGROUNDnA series of 13 islet autotransplantations and 13 islet allotransplantations performed between 1992 and 1999 at the University Hospital of Geneva are presented. Factors affecting the outcome are analyzed.nnnMETHODSnIslet autotransplantation has been performed in seven patients with chronic pancreatitis and in six patients with benign tumors undergoing extensive pancreatectomy. Islet allografts were performed in C-peptide-negative patients simultaneously or after a kidney or lung transplantation. Each recipient received islets from one to four donors. Panel-reactive antibodies were monitored by microlymphocytotoxicity test.nnnRESULTSnEleven of 13 patients who underwent autotransplantation maintained insulin independence for 6 months to 5 years. Two years after autologous islet transplantation, five of nine patients were insulin independent with an glycosylated hemoglobin of 5.9%. Three late islet failures occurred in patients with chronic pancreatitis. Islet yield was significantly lower in patients with chronic pancreatitis than in patients with benign tumors (2044 equivalent islet number/gram resected pancreas versus 5184 equivalent islet number/gram; P=0.037). In islet allotransplantation, no early graft loss was found. All 13 patients who underwent allotransplantation had basal C-peptide levels above 0.3 nmol/L for 3 months to 5 years. Mean glycosylated hemoglobin decreased from 9.1% before transplantation to 5.5% at month 3. Insulin independence was achieved in two type I diabetic patients. In four of six patients with graft failure, the graft had induced panel-reactive antibodies.nnnCONCLUSIONSnIn islet autotransplantation, the reduced number of islets that can be isolated from fibrotic pancreata may be the major limiting factor. In islet allotransplantation, early graft function can now be consistently achieved. Islet allografts seem to be highly immunogenic, and chronic islet failure cannot be prevented consistently by conventional immunosuppression.

Isolation of adult porcine islets of Langerhans

While human islet allotransplantation is limited due to the shortage of donors, pig islet xenotransplantation appears to be a possible alternative. Enzymatic digestion is the method most commonly used for adult pig islet isolation, but since the description of the semiautomated isolation technique in the late 1980s, yields of pig islet isolations have not increased significantly. This review article is intended to collate published information on adult pig islet isolation to provide the reader with a clear overview of the relevant issues in this field, and to detail the current state of the art.

Surgical management of adrenal metastases

PurposeThis paper aims to review controversies in the management of adrenal gland metastasis and to reach an evidence-based consensus.Materials and methodsA review of English-language studies addressing the management of adrenal metastasis, including indications for surgery, diagnostic imaging, fine-needle aspiration, surgical approach, and outcome was carried out. Results were discussed at the 2011 Workshop of the European Society of Endocrine Surgeons devoted to adrenal malignancies and a consensus statement agreed.ResultsPatients should be managed by a multidisciplinary team. Positron emission tomography coupled with computed tomography (PET/CT) scanning is the technique of choice for suspected adrenal metastasis. When PET/CT is not available or results are inconclusive, the CT scan or magnetic resonance imaging can be used. Patients should undergo complete hormonal evaluation. Adrenal biopsy should be reserved for cases in which the results of non-invasive techniques are equivocal. If malignancy has been reliably ruled out, patients with adrenal incidentalomas should be managed like noncancer patients.ConclusionsA patient with suspected adrenal metastasis should be considered a candidate for adrenalectomy when: (a) control of extra-adrenal disease can be accomplished, (b) metastasis is isolated to the adrenal gland(s), (c) adrenal imaging is highly suggestive of metastasis or the patient has a biopsy-proven adrenal malignancy, (d) metastasis is confined to the adrenal gland as assessed by a recent imaging study, and (e) the patient’s performance status warrants an aggressive approach. In properly selected patients, laparoscopic (or retroperitoneoscopic) adrenalectomy is a feasible and safe option.

A lung segmentectomy performed with 3D reconstruction images available on the operating table with an iPad.

Anatomic lung segmentectomy is the procedure of choice in a growing number of patients, either because the lesion is small and/or because of poor lung function. The procedure requires a good knowledge of intrapulmonary anatomy. However, the experience for the different types of segmentectomy is not easy to obtain during thoracic surgical training due to the relatively small number of patients. Any help to better visualize and apprehend the anatomy pre- and intraoperatively is useful for training, teaching and for performing safer surgical procedures. This paper describes an anatomic segmentectomy procedure (upper segment of the left lower lobe) performed with the assistance of an iPad tablet used during the intervention to display and manipulate 3D images reconstructed prior to the surgery with the Open Source OsiriX software.

Influence of preservation solution on human islet isolation outcome.

Background. The influence of the preservation solution used for in situ perfusion of the donor and pancreas storage on islet isolation has received little attention. Methods. In this prospective controlled trial, we compared the outcome of human islet isolation from pancreata perfused with University of Wisconsin (UW) solution or Celsior, an alternative colloid-free extracellular solution. Results. At the 1-year interim analysis, the viability and insulin secretion of islets isolated from donors perfused with UW (n=19) or Celsior (n=5) were identical. However, total islet recovery (IEQ) and isolation yield (IEQ/g) were 1.8-fold and 2.1-fold inferior in the Celsior group (P<0.05 vs. UW). Overall, 13 (68%) of islet preparations were effectively transplanted from the UW group vs. none from the Celsior group (P=0.01). The clinical study was discontinued and the causes of these differences were further explored in the pig (n=14). In contrast to UW, Celsior induced cell swelling and pancreas edema after only four hours of cold storage. These abnormalities were delayed when the donor was perfused with Solution de Conservation dOrganes et de Tissus (SCOT), an extracellular solution containing polyethylene glycol. Conclusions. Our results suggest that colloid-free preservation solutions might be suboptimal for pancreas perfusion and cold storage prior to islet isolation and transplantation. Because pancreata are now frequently recovered for islet transplantation, preliminary experimental and clinical data about islet isolation should be obtained prior to the routine implementation of new preservation solutions for abdominal perfusion during multiorgan recovery.

Islet Autotransplantation After Left Pancreatectomy for Non‐Enucleable Insulinoma

Insulinoma is a rare, almost always benign endocrine tumor of the pancreas, clinically characterized by hyperinsulinemic, hypoglycemic episodes. Surgical excision is the therapy of choice, which may lead to postpancreatectomy diabetes mellitus in the case of extensive pancreatic resection.

Clinical Islet Transplantation: A Review

ABSTRACT: For decades, the inability of insulin therapy to physiologically control glycemia in type I diabetic patients has motivated the search for insulin‐delivering grafts. Islet autotransplantation is such a therapeutic approach to prevent diabetes mellitus following a major pancreatectomy, whereas allo‐transplantation is generally prescribed for type I diabetic patients with a functional solid organ graft, or for patients awaiting one. As of today, over 150 patients have been autotransplanted world‐wide, following total or subtotal pancreatectomy, permitting an insulin‐independence in nearly 40% of patients. Furthermore, more than 350 islet allotransplantations have been performed. Recent results show improved metabolic control in over 50% of cases and insulin‐independence in approximately 20%. This chapter presents a literature review including preliminary human islet transplantation data from the University of Geneva.

Riedel's thyroiditis with increased IgG4 plasma cells: evidence for an underlying IgG4-related sclerosing disease?

BACKGROUNDnRiedels thyroiditis (RT) is a very rare chronic fibrosing disorder of unknown etiology that is often associated with multifocal fibrosclerosis (MFS). Immunoglobulin (Ig) G4-related sclerosing disease (IgG4-RSD), a new clinico-pathological entity also associated with MFS, is characterized by IgG4+ plasma cell infiltration and fibrosis in one or more organs. Although the association of RT and IgG4-RSD has been suggested, it has seldom been studied or reported. We report a classical case of RT with serological (IgG4 levels) and immunohistochemical (IgG and IgG4) assessment, in search of an underlying IgG4-RSD.nnnPATIENTnThe patient was a 57-year-old woman who underwent a subtotal thyroidectomy for a long-standing goiter with a rapidly enlarging isthmic nodule.nnnRESULTSnHistopathological examination of the surgical specimen revealed all of the morphological features of RT and IgG4-RSD, including partial fibrosis of the thyroid gland with destruction of the thyroid follicular architecture; obliterative phlebitis; and a mixed infiltrate composed of lymphocytes, eosinophils, and plasma cells. The fibro-inflammatory process extended beyond the thyroid capsule into the surrounding tissues. Immunohistochemical examination revealed approximately 70 IgG4+ plasma cells per high power field (HPF) with an IgG4/IgG ratio of 35%. Although serum levels of IgG4 were normal (20u2009mg/dL), total IgG levels were slightly elevated (1370u2009mg/dL). There was no evidence of involvement of other organs at the time of RT diagnosis.nnnCONCLUSIONSnThe morphological similarities between RT and IgG4-RSD suggest that these entities are closely related. Therefore, RT with increased IgG4+ plasma cells, with or without elevated IgG4 serum levels, may represent the first clinical manifestation of an underlying IgG4-RSD. However, due to the rarity of both conditions and the limited specificity and sensitivity of both IgG4 serum levels and IgG/IgG4 immunohistochemistry in the diagnosis of IgG4-RSD, further studies are needed to verify this hypothesis.

Short-Term Preoperative High-Intensity Interval Training in Patients Awaiting Lung Cancer Surgery: A Randomized Controlled Trial

Introduction: Impairment in aerobic fitness is a potential modifiable risk factor for postoperative complications. In this randomized controlled trial, we hypothesized that a high‐intensity interval training (HIIT) program enhances cardiorespiratory fitness before lung cancer surgery and therefore reduces the risk of postoperative complications. Methods: Patients with operable lung cancer were randomly assigned to usual care (UC) (n = 77) or preoperative rehabilitation based on HIIT (Rehab) (n = 74). Maximal cardiopulmonary exercise testing and the 6‐minute walk test were performed twice before surgery. The primary outcome measure was a composite of death and in‐hospital postoperative complications. Results: The groups were well balanced in terms of patient characteristics. During the preoperative waiting period (median 25 days), the peak oxygen consumption and the 6‐minute walking distance increased (median +15%, interquartile range, 25th to 75 percentile [IQR25%–75%, %] = +9% to +22%, p = 0.003 and +15%, IQR25%–75% = +8% to +28%, p < 0.001, respectively) in the Rehab group, whereas peak oxygen consumption declined in the UC group (median –8%, IQR25%–75% = –16% to 0%], p = 0.005). The primary end point did not differ significantly between the two groups: at least one postoperative complication developed in 27 of the 74 patients (35.5%) in the Rehab group and 39 of 77 patients (50.6%) in the UC group (p = 0.080). Notably, the incidence of pulmonary complications was lower in the Rehab compared with in the UC group (23% versus 44%, p = 0.018), owing to a significant reduction in atelectasis (12.2% versus 36.4%, p < 0.001), and this decrease was accompanied by a shorter length of stay in the postanesthesia care unit (median –7 hours, IQR25%–75% = –4 to –10). Conclusions: In this randomized controlled trial, preoperative HIIT resulted in significant improvement in aerobic performances but failed to reduce early complications after lung cancer resection.

Decomplementation with cobra venom factor prolongs survival of xenografted islets in a rat to mouse model.

Although the involvement of complement in hyperacute rejection of xenotransplants is well recognized, its role in rejection of devascularized xenografts, such as pancreatic islets, is not completely understood. In this study, we investigated whether complement participates in the immunopathology of xeno‐islet transplantation in a concordant rat to mouse model. Rat pancreatic islets were implanted under the kidney capsule of normal and cobra venom factor (CVF)‐decomplementized diabetic C57BL/6 mice. Graft survival was monitored by blood glucose levels. Deposition of IgM and C3 on grafted islets in vivo or on isolated islets in vitro (after incubation with normal and decomplementized mouse serum), as well as CD4‐ and CD8‐positive leucocyte infiltration of grafts, was checked by immunohistochemistry. In addition, complement‐mediated cytotoxicity on rat islet cells was evaluated by a 3‐(4,5‐dimethythiazolyl)‐2.5‐diphenyl‐2H‐tetrazolium‐bromide (MTT) assay. A significant C3 deposition was found on grafted islets from the first day after transplantation in vivo, as well as on isolated islets after incubation with mouse serum in vitro. By MTT assay, complement‐mediated cytotoxicity for islet cells was found. Decomplementation by CVF decreased C3 deposition on either isolated or grafted islets, delayed CD4‐ and CD8‐positive leucocyte infiltration, led to significant inhibition of complement‐mediated cytotoxicity for islet cells, and prolonged graft survival (mean survival time 21·3 versus 8·5 days; P<0·01). Our results indicate that decomplementation can prolong the survival time of devascularized xenografts across concordant species. The deposition of complement on transplanted islets may contribute to xenograft rejection by direct cytotoxicity and by promoting leucocyte infiltration.