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E Andereggen

Publications and source records attributed to E Andereggen.

At least 19 recordsLinked to original sources
PubMed2001

[Thyroid cancers: the Geneva experience].

AIM OF THE STUDY: To study the survival of patients with thyroid cancer operated in the same centre from 1978 to 1999. PATIENTS AND METHOD: This retrospective study included 218 patients operated on for thyroid carcinoma from january 1978 to december 1999. Modified neck dissection was performed only in the presence of one or more suspected lymph nodes. The stage of the cancer was defined according to the last TNM classification (1997). Survival data were taken from the Geneva Tumour Registry (168 patients = 77% of the series, 109 papillary carcinomas, 37 follicular, 14 undifferentiated and 8 medullary carcinomas). RESULTS: The overall 5, 10 and 15-year survival rates were respectively 88%, 84% and 80%. Papillary carcinoma was associated with the best survival at 5, 10 and 15 years (99%, 97% and 93%), despite a recurrence rate of 20% treated mainly by surgery often associated with radioiodine therapy. Follicular carcinoma had a survival rate of 83% at 5 years and 75% at 10 years. Undifferentiated carcinoma had a median survival rate of 56 days. None of the 8 patients with medullary carcinoma had died from that cancer in this series. CONCLUSION: Thyroid carcinoma carries such a good prognosis (except for undifferentiated carcinoma) that invasive surgery at first operation, like radical neck dissection, is not justified, despite a high rate of recurrence.

Adenocarcinoma, Follicular↗
PubMed2000

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

BACKGROUND: A 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. METHODS: Islet 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. RESULTS: Eleven 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. CONCLUSIONS: In 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.

Autoimmunity↗
PubMed1999

Improvement of the effect of hepatocyte isograft in the Gunn rat by cotransplantation of islets of Langerhans.

PURPOSE: Hepatocyte transplantation (HcTX) has been investigated for many years as an alternative therapy to orthotopic liver transplantation to treat hepatic congenital enzymatic deficiency disease. The animal model most used is the Gunn rat, which presents a hyperbilirubinemia caused by the lack of uridine-diphosphate-glucuronyl-transferase. Some investigators have clearly described a hepatotrophic effect mediated by islets of Langerhans (IL) when transplanted with hepatocytes (Hc). In this study, the functional effect of cotransplanted IL on hepatocytes (co-HcTX) in Gunn rats in an isograft model is assessed. METHODS: Two groups are compared: group 1 (n = 6), HcTX to group 2 (n = 6), co-HcTX. Cells isolated by enzymatic digestion are transplanted directly into the splenic parenchyma. Blood samples are taken regularly until day 100 to measure the unconjugated bilirubin (UB). Histological examination of the spleen is performed at the end of the experiment. RESULTS: Both groups show a significant decrease of the UB: group 1, 47%; group 2, 65%. The decrease is statistically more pronounced with co-HcTX. The histological analysis shows a trophic effect of the IL on the grafted hepatocytes in the co-HcTX group. CONCLUSIONS: The HcTX and the co-HcTX correct partially the hyperbilirubinemia of the Gunn rat. A functional assessment has been performed to evaluate the effect of cotransplanted IL on HcTX.

Analysis of Variance↗
PubMed1999

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.

Animals↗
PubMed1998

[Long-term follow-up of 9 islets of Langerhans autografts after resection of the pancreas].

INTRODUCTION: Preservation of physiological endocrine pancreatic function represents a major problem in pancreatectomised patients. In 40 to 100%, pancreatic resection can result in diabetes, which is often difficult to manage. Islet autotransplantation has been proposed to prevent this severe metabolic consequence. PATIENTS AND METHODS: Between March 1992 and January 1997 we performed 9 human islet autotransplantations in Geneva. The patients comprised 6 males and 3 females aged 40 to 81 years (median: 51 years). The pancreatectomy was total in 3 cases, subtotal (95%) in 2 cases and partial (40-80%) in the others. Indications for resection were alcohol-induced chronic pancreatitis (6 cases) and focal benign pancreatic pathologies (3 cases). After collagenase digestion, unpurified islets were injected intraportally and embolised into the liver. Patient metabolic status was regularly tested by 24-hour serum glucose profile, measurement of glycosylated haemoglobin, oral and intravenous glucose tolerance tests and glucagon stimulation test. RESULTS: Immediately after autotransplantation, one patient had persistent insulin-dependent diabetes. Among the 8 patients who were insulin-independent soon after the graft, 4 presented a progressive deterioration of endocrine pancreatic function and required insulin therapy 5, 8, 24 and 36 months after the graft. Currently, 4 patients are insulin-independent: three of them have normal glucose tolerance tests (24, and 48 months after the graft) and the last presented with glucose intolerance 22 months after the graft but still does not require exogenous insulin. CONCLUSION: Islet autotransplantation can be considered a useful therapeutic option serving to prevent or delay the occurrence of surgically-induced diabetes. In our opinion, islet autotransplantation should be offered to any non diabetic patient needing to undergo major pancreatic resection.

Adult↗
PubMed1998

[Isolation of the pig islets of Langerhans: evaluation of in vitro and in vivo function].

Pig islets are considered the best alternative to human islets in the treatment of insulin-dependent diabetes. Pigs could represent a potential islet donor for xenotransplantation in humans because of the close similarity between human and porcine insulin and the theoretically unlimited availability of porcine pancreas. From November 1991 to January 1997 we performed 221 pig islet isolations from 3 pig sources: group 1: minipigs (age 9-18 months) and white pigs (3-8 months), group 2: large white pigs (5-8 months), group 3: large white pigs (12-24 months). Islets were isolated according to a semi-automated method using enzymatic digestion and purification through discontinuous Euro-Ficoll gradients. The pancreases were surgically removed in our laboratory for group 1, while pancreases from groups 2 and 3 were removed at the slaughterhouse with an average warm ischemia time of 15 minutes. In vitro islet function was assessed by static incubations and perifusions, and in vivo islet function by transplantation under the kidney capsule of nude diabetic mice. The results were as follows: [table: see text] Insulin secretion increased twofold after in vitro glucose stimulation. We obtained restoration of euglycemia in diabetic mice which survived > 3 months after the graft and returned to diabetes after nephrectomy. This study shows that our isolated pig islets are viable and functional in vitro and in vivo after transplantation.

Animals↗
PubMed1997

Islet autotransplantation in a cirrhotic liver.

Chronic pancreatitis resulting from alcohol abuse might in some rare cases require a total surgical resection of the pancreas to treat severe local complications. We have learned from the new techniques developed for islet isolation that it is now possible to obtain a sufficient number of good quality islets from one single pancreas to be transplanted into one recipient. We present a case of total surgical pancreatectomy for chronic pancreatitis in a previously non-diabetic patient with immediate islet isolation and autotransplantation. At operation, a cirrhotic liver was found, but no portal hypertension. We still decided to embolize a non purified preparation of endocrine tissue into the liver without alteration of liver function or durable modification of the portal pressure. One year after this procedure, the patient remains insulin-independent with a close to normal glycemic regulation as demonstrated by stimulation tests. Islet autotransplantation does not appear to be generally contra-indicated in the presence of a cirrhotic liver; provided the portal pressure is within normal limits. Under these circumstances, satisfactory glycemic control is achieved.

Blood Glucose↗
PubMed1997

[Islands of Langerhans autotransplantation after pancreatic resection for benign pathology].

One way to prevent the occurrence of insulin-dependent diabetes after major pancreatic resection is to perform islet of Langerhans autotransplantation. Thus far, we have performed nine autotransplantations. The last three autotransplantations were performed in patients with benign tumoral pathology (one corporeal mucinous cyst, one isthmic insulinoma and one corporeal cystadenoma). In these three cases, we performed a distal 40%, 75% and 80% pancreatectomy respectively, since enucleation was not indicated or not feasible. After resection and removal of the tumoral lesion, pancreatic segments were injected intraductally with collagenase and digested according to a modified semi-automated Ricordi's technique. We obtained 105,000, 415,000 and 144,300 non-purified islets which were then embolized into the liver by intraportal injection during the same operative procedure. After surgery, all patients were insulin-independent. There was no morbidity or mortality. In a patient who presented acute pancreatitis of the residual pancreas five months after transplantation, insulin therapy was introduced. More than one year after the graft, the two other patients remain insulin-independent. In conclusion, we propose islet autotransplantation after pancreatic resection for benign focal pathology, to prevent or delay the occurrence of insulin-dependent diabetes.

Adult↗
PubMed1996

Improved insulin secretion of cryopreserved human islets by antioxidant treatment.

The viability of islets of Langerhans prior to grafting is believed to influence the clinical outcome of islet transplantation. To determine whether oxidative stress occurs during the isolation-purification procedure as well as during tissue culture and cryopreservation, we have measured the glutathione redox state (GSH/GSSG) of islets. Human islets were purified by standard techniques from organ donors, cultured, and cryopreserved. Glucose-induced insulin release was monitored in parallel during static incubations to assess the function of the islets. Cultured human islets responded by a 2.2-fold increase in insulin release to a glucose challenge. After cryopreservation the hormonal response was lower. Immediately after islet isolation the GSH/GSSG ratio was 25.2 +/- 5.2, and it increased slightly to 32.0 +/- 6.1 after 1-3 days in tissue culture. The GSH/GSSG decreased significantly after cryopreservation to 12.2 +/- 3.4, suggesting that the freezing and thawing procedures imposed oxidative stress on the islets. To explore this hypothesis further, cryopreserved islets were treated with the antioxidant butylated hydroxyanisole (BHA). Islets exposed to BHA showed an improved glucose-induced insulin release and had an increased insulin content. BHA also protected the islets when they were exposed to alloxan, a free radical generating agent. However, after cryopreservation, BHA treatment did not modify the glutathione redox state. Although the BHA effect could not be explained merely by a change in the glutathione redox state, it is not precluded that redox changes of other cell components ameliorate the glucose sensitivity of the beta cells. Further studies will be needed to determine possible ways of improving islet cryopreservation with antioxidant treatments and particularly, to validate the present observations by in vivo experiments in the context of clinical islet transplantation.

Antioxidants↗
PubMed1996

Expression, localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells.

We examined the presence of small molecular mass GTP-binding proteins of the Rab3 family in different insulin-secreting cells. Rab3B and Rab3C were identified by western blotting in rat and in human pancreatic islets, in two rat insulin-secreting cell lines, RINm5F and INS-1, as well as in the hamster cell line HIT-T15. In contrast, Rab3A was detected in rat pancreatic islets as well as in the two insulin-secreting rat cell lines but not in human pancreatic islets and was only barely discernible in HIT-T15 cells. These findings were confirmed by two-dimensional gel electrophoresis followed by GTP-overlay of homogenates of pancreatic islets and of the purified protein. Northern blotting analysis revealed that Rab3D is expressed in the same insulin-secreting cells as Rab3A. Separation of the cells of the rat islets by fluorescence-activated cell sorting demonstrated that Rab3A was exclusively expressed in beta-cells. Rab3A was found to be associated with insulin-containing secretory granules both by immunofluorescence, immunoelectron microscopy and after sucrose density gradient. Overexpression in HIT-T15 cells of a Rab3A mutant deficient in GTP hydrolysis inhibited insulin secretion stimulated by a mixture of nutrients and bombesin. Insulin release triggered by these secretagogues was also slightly decreased by the overexpression of wild-type Rab3A but not by the overexpression of wild-type Rab5A and of a Rab5A mutant deficient in GTP hydrolysis. Finally, we studied the expression in insulin-secreting cells of rabphilin-3A, a putative effector protein that associates with the GTP-bound form of Rab3A. This Rab3A effector was not detectable in any of the cells investigated in the present study. Taken together these results indicate an involvement of Rab3A in the control of insulin release in rat and hamster. In human beta-cells, a different Rab3 isoform but with homologous function may replace Rab3A.

Animals↗
PubMed1996

[Isolation and cryopreservation of human islets of Langerhans].

Islet transplantation represents an alternative to whole pancreas transplantation for the treatment of patients suffering from diabetes type I. The transplantation of a sufficient number of islets is an essential condition for successful allograft. Islet cryopreservation allows the storage of islet preparations for subsequent pooling, at the time of transplantation, of cryopreserved islets with a fresh preparation in order to increase the mass of transplanted pancreatic endocrine tissue. From May 1994 to April 1995, islets were isolated from 22 human pancreases using a modified automated method, and 19 preparations were cryopreserved. The function of cryopreserved islets was tested in vitro (static incubation and perifusion). The results of static incubation experiments confirmed that the insulin secretion of cryopreserved human islets in response to glucose stimulation was comparable to the response of islets that have not been frozen. In static incubation experiments, the mean (+/- SEM) insulin secretion of islets, prior to cryopreservation, was 239.3 (+/- 58.9) and 479.5 (+/- 59.5) pg/islet/15 min at 2.8 mM glucose and 16.7 mM glucose respectively. The mean (+/- SEM) insulin secretion of cryopreserved islets was 274 (+/- 103.2) and 468.5 (+/- 191.9) pg/islet/15 min at 2.8 mM and 16.7 mM glucose respectively. The perifusion experiments also demonstrated a significant increase of insulin secretion from cryopreserved islets perifused with a stimulating glucose concentration. Our experiments allow us to envisage the use of cryopreserved islet preparations for allotransplantation in diabetic patients.

Adult↗
PubMed1996

Combined islet-lung transplantation in a cystic fibrosis patient.

The prevalence of insulin-dependent diabetes mellitus (IDDM) in cystic fibrosis patients ranges from 2 to 8% and glucose intolerance up to 15%. In recent years, lung transplantation has helped to prolong life expectancy of cystic fibrosis patients and represents 10 to 30% of all indications for lung transplantation. The postoperative need for immunosuppressive therapy using diabetogenic agents has decompensatory effects on glucose regulation and will probably increase the number of insulin-dependent cystic fibrosis patients. We report the case of an insulin-dependent cystic fibrosis patient transplanted with a combined islet-lung allograft. The pre-transplantation C-peptide level was below 0.04 nmol/l and preoperative insulin requirement was some 100 U per day. A sequential bipulmonary lung transplantation was performed and, using the pancreas of the same donor, we isolated and purified the islets of Langerhans by a modified automated method. We obtained 232,200 islets equivalent, which were injected into the liver by portal embolization. The postoperative course was uncomplicated, the insulin requirement decreased to 50% of the preoperative need and the C-peptide value increased to normal values and remained with the normal range during a follow-up period of 15 months. In conclusion, we believe that, besides type I diabetic patients, insulin-dependent cystic fibrosis patients with a negative C-peptide value could also be good candidates for combined islet-lung allotransplantation.

Adult↗