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Pascal Bucher

Publications and source records attributed to Pascal Bucher.

30 records · Page 2Linked to original sources

Does mechanical bowel preparation have a role in preventing postoperative complications in elective colorectal surgery?

BACKGROUND: mechanical bowel preparation (MBP) consists of orthograde fluid preparation to clean the bowel. MBP is considered to prevent postoperative complications. METHODS: meta-analysis of prospective randomised clinical trials (RCT) evaluating MBP versus no MBP. RESULTS: following a medline search we retrieved 15 prospective trials of which only 5 where RCT comparing MBP versus no MBP in elective colorectal surgery. For the randomised studies, there were respectively 186, 179, 149, 267 and 380 patients, including all type of resections. The total number of patients in these 5 studies was 1144 (565 with MBP and 579 with no preparation). All patients received perioperative antibiotic prophylaxis. Only one of these RCT show a significant decrease in anastomotic leak (AL), but among all the patients enrolled, AL is significantly more frequent in the group with MBP (Odds Ratio 1.8). Wound infection, re-operation and intra-abdominal abscess rates were more frequent in the MBP group but the difference did not reach statistical significance and the odds ratios for a 95% confidence interval were extremely large. CONCLUSION: there is limited evidence in the literature to support the use of MBP in patient undergoing elective colorectal surgery. Available data tend to suggest that MBP could be harmful with respect to the incidence of anastomotic leak. Moreover, MBP does not reduce the incidence of other infectious complications. Further RCTs are needed to establish an evidence-based rationale for the use of MBP in elective colorectal surgery.

Anastomosis, Surgical↗

Mechanical bowel preparation for elective colorectal surgery: a meta-analysis.

HYPOTHESIS: There is little scientific evidence to support the routine practice of mechanical bowel preparation (MBP) before elective colorectal surgery in order to minimize the risk of postoperative septic complications. DATA SOURCES: Trials were retrieved using a MEDLINE search followed by a manual search of the bibliographic information in select articles. Languages were restricted to English, French, Spanish, Italian, and German. There was no date restriction. STUDY SELECTION: Only prospective randomized clinical trials (RCTs) evaluating MBP vs no MBP before elective colorectal surgery were included. DATA EXTRACTION: Outcomes evaluated were anastomotic leakage, intra-abdominal infection, wound infection, reoperation, and general and extra-abdominal morbidity and mortality rates. Data were extracted by 2 independent observers. DATA SYNTHESIS: Seven RCTs were retrieved. The total number of patients in these RCTs was 1297 (642 who had received MBP and 655 who had not). Among all the RCTs reviewed, anastomotic leak was significantly more frequent in the MBP group, 5.6% (36/642), compared with the no-MBP group, 2.8% (18/655) (odds ratio, 1.84; P = .03). Intra-abdominal infection (3.7% for the MBP group vs 2.0% for the no-MBP group), wound infection (7.5% for the MBP group vs 5.5% for the no-MBP group), and reoperation (5.2% for the MBP group vs 2.2% for the no-MBP group) rates were nonstatistically significantly higher in the MBP group. General morbidity and mortality rates were slightly higher in the MBP group. CONCLUSIONS: There is no evidence to support the use of MBP in patients undergoing elective colorectal surgery. Available data tend to suggest that MBP could be harmful with respect to the incidence of anastomotic leak and does not reduce the incidence of septic complications.

Cathartics↗

Are there any prognostic factors for small intestinal stromal tumors?

BACKGROUND: Stromal tumors of the digestive tract, or gastrointestinal stromal tumors (GIST), originate from an intestinal mesenchymal precursor cell. Criteria that predict the outcome of small intestinal stromal tumors (SIST) after surgical resection are not clearly established. The aim of the study was to define prognostic criteria for SIST. METHODS: All c-kit positive SIST treated in our center over a 10-year period were reviewed. RESULTS: Eighteen patients with SIST treated by surgical resection were included. Overall actuarial 5-year survival was 74% (median follow-up of 69 months). We developed a panel of five criteria (tumor size, mitotic rate, proliferation index, presence of necrosis, and invasion of mucosa or adjacent structures) that permitted distinction between low and high malignant potential SIST. Presence of any four of these five criteria defined a high malignant potential SIST, and was associated with disease recurrence and poor prognosis after surgical resection (P <0.01). Patients with low malignant potential SIST had a 5-year survival of 92%, compared with 0% for high malignant potential SIST (P <0.01). CONCLUSIONS: This study demonstrates that a panel of morphologic factors can reliably distinguish between low and high malignant potential SIST. Although patients with low malignant potential SIST have an excellent prognosis after surgical resection, the role of adjuvant treatment for high malignant potential SIST remains to be defined.

Actuarial Analysis↗

Activation of human macrophages by allogeneic islets preparations: inhibition by AOP-RANTES and heparinoids.

During transplantation, pancreatic islets release chemokines which promote macrophage attraction, hampering engraftment of islets. The aim of this study was to modulate chemotaxis and the immune response of human macrophages induced by islets. Human monocyte-derived macrophages of healthy subjects were exposed to supernatants of human islets. Chemotaxis, tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) release were evaluated. To modulate migration, human macrophages were incubated in the presence of aminooxypentane-regulated on activation, normal, T-cell expressed, and secreted (AOP-RANTES), a potent antagonist of CCR5. Chemotactic activity of islets supernatant was modulated by the addition of heparin or heparinoids [pentosan and calix[8S]arene (C8S)]. AOP-RANTES significantly reduced, in a dose-dependent manner, macrophage chemotaxis and cytokine release induced by islets supernatant. The chemotactic index was reduced from 3.05 +/- 0.27 to 0.71 +/- 12, TNF-alpha from 1205 +/- 52 to 202 +/- 12 pg/ml, and IL-1beta from 234 +/- 12 to 10 +/- 6 pg/ml. The trapping of chemokines by heparinoids reduced the chemotactic activity of islets supernatant from 3.05 +/- 0.27 to 1.2 +/- 0.1 with heparin or pentosan and to 1.72 +/- 0.22 with C8S, and also decreased the TNF-alpha release by human macrophages from 1205 +/- 35 to 1000 +/- 26 (C8S), 250 +/- 21 (heparin) and 320 +/- 19 (pentosan) pg/ml, and IL-1beta from 234 +/- 13 to 151 +/- 5 (C8S), 50 +/- 3 (heparin) and 57 +/- 4 (pentosan) pg/ml. In conclusion, AOP-RANTES and heparinoids inhibit human macrophage activation and migration induced by islets supernatant.

Adult↗

Cost analysis of human islet transplantation for the treatment of type 1 diabetes in the Swiss-French Consortium GRAGIL.

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 transplanted in the Swiss-French Groupe Rhône-Alpes, Rhin et Geneve pour la transplantation d'Ilots Langerhans (GRAGIL) consortium between March 1999 and June 2000. The direct medical costs were estimated from Social Security's perspective from the inclusion of the patient to 1 year after transplantation. All cost components were computed separately and included evaluation, screening and candidacy, organ retrieval, islet processing, pancreas and islet transportation, hospitalization for transplantation, follow-up, medications (immunosuppressive, antidiabetic, and adjuvant drugs), and adverse events requiring hospitalization. RESULTS: During the study period, 56 pancreata were processed and 14 islet preparations were transplanted. The average cost of an islet transplantation (procedure and 1-year follow-up) was 77,745 euro (French rate, year 2000). The four main cost components were islet preparation (30% of the total cost), adverse events (24%), drugs (14%), and hospitalization (13%). CONCLUSIONS: Overall costs of islet transplantation are slightly higher than those of pancreas transplantation. The cell isolation process is a critical point; a reduction in overall cost will require more efficient ways of isolating high yields of viable islets. Costs generated by shipments within the GRAGIL network did not represent an economic burden. It can be expected that the costs will decrease with growing experience and improving technology.

Chemotherapy, Adjuvant↗

Intra-portal injection of 400- microm microcapsules in a large-animal model.

To date, encapsulated grafts have usually been implanted in the peritoneal cavity. This site is, however, not ideal, mainly because of its low blood supply. We have investigated the feasibility of intra-portal injection of (400 microm) microcapsules in the pig. Ten-thousand microcapsules per kilogram body weight were injected into six Large White pigs. Portal pressure, various biological tests, portographies and liver histology were recorded before and at various time points after injection. As a result, portal pressure increased after injection (15+/-2.3 vs 8.7+/-1.7 mmHg) but remained within an acceptable range (<20 mmHg) and returned to normal values at 3 months (8.5+/-3.7 mmHg). During the 3-month follow up, liver function and liver tests remained stable. Portographies showed a homogenous implantation of the capsule, with the portal flow always directed to the liver. At histological examination after 3 months the capsules demonstrated various degrees of fibrosis. We can thus conclude that these results demonstrate that intra-portal injection of microcapsules is feasible in a large-animal model. Hemodynamic, biological and radiological results are similar to those observed in clinical free-islet transplantation.

Animals↗

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. We present the cases and the metabolic follow up of two patients, 81 and 73 years old, with insulinoma localized close to the main duct in the pancreatic neck. Both patients underwent an 80% left pancreatectomy, avoiding a pancreatico-enteric anastomosis. In order to prevent postpancreatectomy diabetes, the islets from the tumor-free part of the resected pancreas were isolated and injected via a right colic vein into the portal system. After a follow up of 6 and 3 years respectively, both patients remained insulin-independent without any dietary restrictions. Fasting and glucagon-stimulated C-peptide-levels and glycosylated hemoglobin remained within normal range. There were no signs of recurrent insulinoma. Liver biopsy performed in one patient at 1 year after autotransplantation, showed intact, insulin-producing islets within the portal spaces. In conclusion, autologous islet transplantation can preserve the insulin secretory reserve after extended left pancreatectomy for the treatment of benign tumors in the pancreatic neck.

Aged↗

Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function.

Glucotoxicity and lipotoxicity contribute to the impaired beta-cell function observed in type 2 diabetes. Here we examine the effect of saturated and monounsaturated fatty acids at different glucose concentrations on human beta-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 beta-cell DNA fragmentation and decreased beta-cell proliferation. In contrast, the monounsaturated palmitoleic acid or oleic acid did not affect DNA fragmentation and induced beta-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(2)-ceramide mimicked both the palmitic acid-induced beta-cell apoptosis and decrease in proliferation. Furthermore, the ceramide synthetase inhibitor fumonisin B1 blocked the deleterious effects of palmitic acid on beta-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 beta-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 beta-cell apoptosis, decrease beta-cell proliferation, and impair beta-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.

Adult↗

Molecular detection of circulating beta-cells after islet transplantation.

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 allo- and autoimmune destruction. Therapeutic approaches to these damage mechanisms require early detection of islet injury, which is currently not feasible because of the lack of efficient markers. Based on the hypothesis of islet dissociation and release of islet cells into the circulation during islet injury, we designed a highly sensitive and specific molecular assay, able to detect two beta-cells per milliliter of venous blood by RT-PCR of insulin mRNA. We report that circulating beta-cells can be demonstrated up to 10 weeks after intraportal islet transplantation, as assessed after six islet grafts in four type 1 diabetic patients. Furthermore, our results suggest that the time during which circulating islet cells can be detected may depend on the graft environment and the immunosuppressive regimen. This test may allow better estimation of islet cell loss and identification of factors involved in islet graft injury.

Adult↗

Reduction of blood glucose variability in type 1 diabetic patients treated by pancreatic islet transplantation: interest of continuous glucose monitoring.

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 continuous glucose monitoring system (CGMS; Minimed, Sylmar, CA). RESEARCH DESIGN AND METHODS: The CGMS enabled recording of subcutaneous glucose concentrations (range 2.2-22 mmol/l) over 72 h (288 measurements per day). Over 3 days, 26 patients with type 1 diabetes were connected to a CGMS: 10 patients were treated with intraperitoneal insulin infusion through an implantable pump (IPII), 9 patients were treated with simultaneous pancreas-kidney transplantation (SPK), and 7 patients were treated with pancreatic islet transplantation after kidney grafting (IAK). All SPK patients and four IAK patients were insulin independent, whereas three IAK patients had partial graft function and reduced exogenous insulin needs. Glucose control was evaluated by the mean glucose concentration, glucose variability, and the number and duration of hypoglycemic events (<3.3 mmol/l) over 3 days. RESULTS: The mean glucose concentration and the glucose variability in SPK and IAK patients were significantly lower than those observed in patients treated with IPII: 5.38 +/- 1.12 and 5.83 +/- 0.81 vs. 7.81 +/- 1.55 mmol/l (P < 0.001) and 1.40 +/- 0.42 and 1.32 +/- 0.53 vs. 3.47 +/- 1.66 mmol/l (P < 0.001), respectively. Furthermore, the mean glucose concentration and the glucose variability were comparable between SPK and IAK patients. Over 3 days, no hypoglycemic events were observed in SPK patients and insulin-independent IAK patients. A total of 4.12 +/- 1.66 hypoglycemic events were detected in the IPII patient group, whereas only 0.66 +/- 0.57 events were observed in IAK patients with partial graft function (P < 0.001). The duration of the hypoglycemic events was significantly longer in IPII patients as compared with IAK patients: 64 +/- 33 vs. 30 +/- 15 min for the day period and 130 +/- 62 vs. 30 +/- 27 min for the night period (P < 0.001). CONCLUSIONS: Use of subcutaneous CGMS confirms that islet transplantation can be as efficient as pancreas transplantation in restoring good metabolic control and reducing blood glucose variability. Metabolic improvement due to use of an implantable insulin pump requires insulin delivery by a closed loop.

Adult↗

Long-term results of radical resection for locally advanced duodenal adenocarcinoma.

BACKGROUND/AIMS: Duodenal adenocarcinomas are uncommon tumors characterized by non-specific symptoms and late diagnosis. The objective of this study was to assess long-term results of locally advanced duodenal adenocarcinoma treated by surgical resection. METHODOLOGY: A retrospective study, over a 10-year period, identified 9 patients (mean age 65 years) treated for duodenal carcinoma. RESULTS: Out of nine patients who were treated for duodenal adenocarcinoma, 8 underwent R0 resection (5 pancreaticoduodenectomies, 1 total pancreaticoduodenectomy and 2 segmental duodenal resections). All of them had tumor of stage II or III according to TNM classification. Median follow-up was 104 months (range 25 to 185). Five patients had lymph node metastases (stage III) at the time of surgery. Two- and five-year survival rates were 100% and 75%, respectively for the whole group. No correlation between lymph node status and survival was found. CONCLUSIONS: Radical surgical resection for locally advanced duodenal adenocarcinomas provides good long-term results in terms of patient survival, even for N1 tumors (stage III).

Adenocarcinoma↗