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OBJECTIVE--To evaluate the cost of islet transplantation in type 1 diabetic patients with a functional renal graft in a multicenter network. RESEARCH DESIGN AND METHODS--The study involved nine diabetic patients [...]

Normoglycemia is maintained in the face of insulin resistance until the pancreatic β-cells become unable to produce sufficient quantities of insulin, at which point type 2 diabetes begins. A major [...], Glucotoxicity and lipotoxicity contribute to the impaired β-cell function observed in type 2 diabetes. Here we examine the effect of saturated and monounsaturated fatty acids at different glucose concentrations on human β-cell turnover and secretory function. Exposure of cultured human islets to saturated fatty acid and/or to an elevated glucose concentration for 4 days increased β-cell DNA fragmentation and decreased β-cell proliferation. In contrast, the monounsaturated palmitoleic acid or oleic acid did not affect DNA fragmentation and induced β-cell proliferation. Moreover, each monounsaturated fatty acid prevented the deleterious effects of both palmitic acid and high glucose concentration. The cell-permeable ceramide analogue [C.sub.2]-ceramide mimicked both the palmitic acid-induced β-cell apoptosis and decrease in proliferation. Furthermore, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on β-cell turnover. In addition, palmitic acid decreased Bcl-2 expression and induced release of cytochrome c from the mitochondria into the cytosol, which was prevented by fumonisin B1 and by oleic acid. Finally, each monounsaturated fatty acid improved β-cell secretory function that was reduced by palmitic acid and by high glucose. Thus, in human islets, the saturated palmitic acid and elevated glucose concentration induce β-cell apoptosis, decrease β-cell proliferation, and impair β-cell function, which can be prevented by monounsaturated fatty acids. The deleterious effect of palmitic acid is mediated via formation of ceramide and activation of the apoptotic mitochondrial pathway, whereas Bcl-2 may contribute to the protective effect of monounsaturated fatty acids.

OBJECTIVE -- To compare the glycemic profiles of patients with type 1 diabetes treated with either an implantable insulin pump or pancreas or islet transplantation by the means of the [...]

Islet transplantation is a promising treatment for type 1 diabetes. However, islet grafts are submitted to multiple injuries, including immunosuppressive drug toxicity, hyperglycemia, hypoxia, unspecific inflammatory reactions, as well as [...]

Abstract: Background: Robot-assisted Roux-en-Y gastric bypass (RYGBP) is rapidly evolving as an important surgical approach in the bariatric field. However, the specific learning curve associated with this new approach remains poorly investigated. This study aimed to evaluate the learning curve for robot-assisted RYGBP. Methods: A series of 64 consecutive robot-assisted RYGBP procedures were performed between December 2008 and December 2010 by a single surgeon already experienced in advanced laparoscopic procedures but not in bariatric surgery. All data were collected prospectively in a database and reviewed retrospectively. The learning curve was evaluated using the cumulative sum (CUSUM) method. Results: Women comprised 76.6% and men 23.4% of this series. These patients had a mean age of 43 years and a mean body mass index (BMI) of 44.5 kg/m2. The mean operative time (OT) was 238.1 min (range, 150–400 min). A total of six complications occurred (9.4%). The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 14 cases; mean OT, 288.9 min) and phase 2 (the subsequent cases; mean OT, 223.6 min), which represented the mastery phase, with a decrease in OT (P = 0.0001). The two groups were similar in terms of gender, age, and BMI. The two phases did not differ in terms of complications or hospital stay. Conclusions: This series confirms previous study findings concerning the feasibility and the safety of robotic RYGBP even after a limited experience with laparoscopic RYGBP. The data reported in this article suggest that the learning phase for robot-assisted RYGBP can be achieved with 14 cases.

Abstract: Background: Recent population survey has shown a preference for transumbilical laparoendoscopic single-site surgery (U-LESS) compared with natural orifice transluminal endoscopic surgery (NOTES) for cholecystectomy, assuming similar surgical risk. This study was designed to evaluate the perception and preference of women regarding conventional laparoscopy, U-LESS, and transvaginal NOTES (TV-NOTES) with particular interest to access perception. Methods: An anonymous questionnaire on laparoscopic, U-LESS, and TV-NOTES cholecystectomy, without regards to risks or advantages, was given to female medical/paramedical staff (n = 100), patients (n = 100), and the general population (n = 100). Women participants (median age, 35 (range, 16–79) years) were queried about preference, perception of the different accesses, and personal informations. Of the respondents, 54% had children, 79% had stable relationships, and 96% were sexually active (vaginal intercourse). Results: With similar operative risk, 87% preferred U-LESS, 4% TV-NOTES and 8% laparoscopy. LESS/NOTES choice was influenced by a desire of improved cosmetics (82%) and lower pain (44%). 96% had worries regarding transvaginal access, among them: dyspareunia (68%), decreased sensibility during intercourse (43%), refuse of short-term sexual abstinence (40%), and infertility (23%). Transumbilical access evocated worries in 35%: umbilical pain (19%), postoperative umbilical sensibility (15%), and incisional hernia (11%). Postoperative intercourse abstinence after TV-NOTES evocated worries in 76% (defined as 3 weeks in survey): feel less attractive (40%), less feminine (32%), tension with their intimate (35%), lover non-acceptation (20%), possible abortion of new relationship (26%), and feel less comfortable socially (16%). Conclusions: The high acceptation rate for U-LESS approach compared with TV-NOTES may be related to fears regarding postoperative sexuality and fertility. The importance of temporary postoperative sexual abstinence (vaginal intercourse) is high and may be difficult to influence. Future research on TV-NOTES should focus on the access risk to be able to scientifically reassure our patients. For now, U-LESS seems to be favor compared with TV-NOTES for cholecystectomy in female patients.

Abstract: Background: Although still under development, single-port access (SPA) approach may be of interest in patients prone to port-side incisional hernia, ensuring absence of increased fascial incision. This forms the basis for evaluating SPA for prosthetic ventral hernia repair. We report a new SPA technique of ventral hernia repair using working-channel endoscope, standard laparoscopic instruments, and 10-mm port. Methods: Prospective experience with SPA prosthetic repair of primary and incisional ventral hernia in 52 patients for 55 ventral hernias is presented. Median (range) patient age was 46 years (26–85 years), and BMI was 28 kg/m2 (20–38 kg/m2). Mean fascial defect was 16.2 cm2 for primary hernia (n = 23) and 48.3 cm2 for incisional hernia (n = 32). Intraperitoneal composite mesh repair was achieved through single 10-mm flank port using working-channel endoscope. Meshes were fixed using absorbable tackers and transfascial stitches. Results: SPA repair of primary and incisional ventral hernia was completed in all cases without conversion to standard laparoscopy. Median (range) operative time was 54 min (39–95 min). Mesh size ranged from 118 to 500 cm2. No intra- or postoperative complications were recorded, except two seromas. Median (range) hospital stay was 1 day (1–5 days). One patient presented prolonged postoperative pain on mesh fixation that resolved after 3 months. No recurrence or port-site incisional hernias have been recorded at median (range) follow-up of 16 months (3–28 months). Conclusions: SPA prosthetic repair of primary and incisional ventral hernia is easily feasible according to natural exposition by pneumoperitoneum and gravity. In the present series, SPA ventral hernia repair appears to be safe for experienced SPA surgeons. It may decrease parietal trauma and scarring in patients prone to incisional hernia. SPA repair may be associated with a decrease in rate of port-site incisional hernia compared with multiport laparoscopy, but this has to be verified by randomized trial with standard laparoscopic approach on long-term follow-up.

Abstract: Background: Laparoendoscopic single-site surgery (LESS) and natural orifice translumenal endoscopic surgery (NOTES) are prospected as the future of minimally invasive surgery. While scarless surgery (NOTES and LESS) is gaining increasing popularity, perception of these approaches should be investigated. Methods: An anonymous questionnaire describing laparoscopy, LESS, and NOTES was given to medical staff (n = 120), paramedical staff (n = 100), surgical patients (n = 100), and the general population (n = 100). The survey participants (median age, 37 years; range, 18–81 years) were queried about their expectations for surgical treatment and their approach preference. Results: The first concern of the survey responders was the risk of surgical complications (92%). When asked about the respective importance of surgical safety, cure, and cosmetics, cure was placed first by 74%, safety by 33%, and cosmetics by 3%. These results were not influenced by sex, age, prior surgery or endoscopy, or education. When operative risk was similar, 90% of the participants preferred a scarless approach (75% preferred LESS and 15% preferred NOTES) to laparoscopy. The scarless approach preference was significantly higher among the younger participants (age <40 years; p = 0.026), whereas sex showed no influence. The LESS preference was significantly higher among patients and the general population (86%) than among medical (67%) and paramedical (70%) staffs (p < 0.001). A decreasing trend of preference for LESS and NOTES was observed with increased procedural risks. Conclusion: Although cure and safety remain the main concern, the population has a favorable perception of scarless surgery, even in the case of increased procedural risk, with LESS favored over NOTES. Such a popular adoption of scarless surgery should warrant the promotion of further research, technological innovations, and the establishment of surgeon training to improve its safety.

Transumbilical single-port access (SPA) surgery is a rapidly evolving field that combines in part the cosmetic advantage of natural orifice transluminal endoscopic surgery (NOTES) with the ability to perform the operation with standard laparoscopic instruments. We report our experience with the first transumbilical single-port access radical left colectomy conforming to surgical oncologic principle and minimally invasive colectomy technique.

Abstract: Background: Laparoscopic gastrojejunostomy allows effective palliation and rapid recovery for the patient with limited survival due to advanced pancreatic cancer presenting with gastric outlet obstruction. Transumbilical single-incision laparoscopic surgery (SILS) offers excellent cosmetic results and may be associated with decreased postoperative pain, reduced need for analgesia, and thus accelerated recovery. The authors report the first transumbilical single-incision laparoscopic intracorporeal anastomosis for gastrojejunostomy. Methods: Preliminary experience with transumbilical single-incision, intracorporeal anastomosis for gastrojejunostomy for a patient with gastric outlet obstruction caused by advanced pancreatic cancer is reported. Results: Transumbilical single-incision laparoscopic intracorporeal anastomosis for gastrojejunostomy was performed with a linear endoscopic stapler using an omega loop. The operative time was 117 min. No intra- or postoperative complications were recorded. Conclusion: Transumbilical single-incision laparoscopic intracorporeal anastomoses are feasible using the endoscopic linear stapler. Transumbilical single-incision gastrojejunostomy for gastric outlet obstruction may improve cosmetic results and allow accelerated recovery for patients with limited survival. This anastomosis technique of single-incision laparoscopic surgery for other digestive tract procedures needs further evaluation.

A number of surgical techniques for colorectal anastomosis have been described for laparoscopic left-sided colectomies. Due to the complexity of these procedures, open preparation of the proximal bowel for circular stapler anastomosis through a Pfannenstiel incision has become the gold standard. We report a new laparoscopic technique for totally intracorporeal colorectal circular anastomosis (TLCCA) using a circular stapler.Preliminary experience using TLCCA in three patients scheduled for laparoscopic left colectomies (two) and sigmoidectomy (one).Side-to-end colorectal anastomosis through TLCCA was feasible in all patients scheduled for preliminary experience. Median time from anvil insertion into abdominal cavity to anastomosis was 14 (11–17) minutes. No postoperative complications were recorded.Side-to-end anastomosis can be easily and safely performed using conventional circular stapler through TLCCA. TLCCA is performed using four laparoscopic ports without additional skin incision (except trocars incision) and allows the retrieval of surgical pieces through a specimen bag.

Infected necrotizing pancreatitis represents a serious and therapeutically challenging complication. Percutaneous drainage of infected pancreatic necrosis is often unsuccessful. Alternatively, open necrosectomies are associated with high morbidity. Recently, minimally invasive necrosectomy techniques have been tried with satisfying results; however, they frequently necessitate multiple sessions for definitive necrosectomy. To evaluate results of single large-port laparoscopic necrosectomy for proven infected necrotizing pancreatitis.

Costimulatory blockade has been shown to allow long-term survival of xenogeneic islets. The aim of the present study was to analyze the possibility of xenogeneic islet retransplantation using costimulatory blockade.

The aim of the study was to evaluate the role of recipient CD40 and CD154 in the rejection process of concordant and discordant islets xenotransplantation (Tx). Diabetic C57BL/6 mice, CD40- or CD154-knockout (KO) and complement C3-deficient (C3-/-) mice were transplanted with either rat or human islets. Group 1, C57BL/6 Tx without therapy; Group 2, C57BL/6 Tx with anti-CD154 monoclonal antibody (mAb) (MR1) therapy; Group 3, CD40-K0; and Group 4, CD154-KO Tx without therapy; Group 5, C3-/- Tx without therapy and Group 6, C3-/-Tx with MR1 therapy. Mixed lymphocyte reactions (MLR) were performed. Compared to Group 1, MR1 induced long-term survival of xenografts in Group 2, but not in Group 6, survival of islets was not prolonged significantly in Groups 3 and 4. MLR responses in Group 2 were reduced approximately 50% compared to Group 1. In Groups 3, 4 and 6, MLR responses were not modified by the absence of CD40 or CD154 molecules, or MR1 and were similar to Group 1. Improved graft survival and reduced MLR responses in Group 2, but not in Group 6, could be explained by specific targeting of activated T cells with inactivation by complement- or cellular-mediated mechanisms. Rejection of xenografts and strong MLR responses in Groups 3 and 4 are possible through efficient activation of alternate pathways of costimulation.

T cells and macrophages play a major role in the rejection of xenografted islets. Depending on the phylogenetic disparity, direct or indirect antigen presentation is predominant. The aim of this study was to analyze in vitro the predominance of direct or indirect presentation by depleting antigen-presenting cells in concordant and discordant xenogeneic combinations. In vivo, we analyzed the effect of macrophage depletion on concordant and discordant islet xenograft survival to assess in which combination this strategy can be used as therapeutic tool.

Biologic characteristics of enzyme products used for islet isolation are critical for the success of islet transplantation. In particular, lot-to-lot variability significantly affects the yields of the isolation procedure. In this study, we have evaluated a new enzyme preparation in which highly purified collagenase can be blended with separately supplied neutral protease in a predetermined ratio.

The influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients was evaluated within the GRAGIL network.

Currently, the number of patients with type I diabetes is continuously increasing, and shortage of available deceased organ donors is a major limitation for organ and cell transplantation. Research to develop alternative sources of insulin-producing tissues is ongoing, and xenogeneic islets represent an attractive solution. This review focuses on current questions regarding future clinical trials of islet xenotransplantation.

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.

The replacement of insulin-producing ? cells by islet transplantation can efficiently reverse diabetes. The recent improvements in clinical results were made possible by transplanting higher islet masses and through the introduction of new immunosuppressive protocols that avoid diabetogenicity. The need for alternatives to continuous immunosuppression, and an unlimited source of glucose-sensitive, insulin-secreting tissue, is emerging. In this review we discuss the various key steps in islet transplantation and offer perspectives for future developments in the replacement of insulin-producing ? cells for the treatment of type I diabetes.

We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.