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Pascal Bucher

Publications and source records attributed to Pascal Bucher.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of surgery for rectal cancer in octogenarians.

INTRODUCTION: The aim of this study was to assess the outcome of surgery for rectal cancer in patients 80 years of age or more. METHODS: A retrospective study of 29 patients older than 80 years, who presented in our institution between 1997 and 2001 with the diagnosis of rectal adenocarcinoma, was undertaken. RESULTS: Median follow-up was 54 (range 27-78) months, and the median age of patients was 85 (range 80-94) years. Twenty-four out of 29 patients (83%) underwent surgery, 23 being operated electively. Twenty out of 24 patients (83%) underwent resection with curative intent, while four patients (17%) had a palliative procedure. Median hospital stay was 13 (range 10-35) days. Postoperative morbidity and mortality were 46% and 12.5%, respectively. However, when considering only elective procedures with curative intent, operative mortality was 5%. At the time of last follow-up, 13 patients were alive, five of them with no evidence of recurrent disease at 5 years, for an overall 2- and 5-year survival rate of 80% and 67%, respectively. Four out of the 7 deaths, which occurred after surgery, were due to medical causes unrelated to cancer. CONCLUSION: In our institution, two thirds of patients older than 80 years who presented with rectal cancer underwent surgery with curative intent. In this selected population, good results in terms of short-term survival can be achieved, at the price of an elevated postoperative morbidity. Whenever possible, treatment with curative intent should be considered in patients with rectal cancer, irrespective of the age.

Aged, 80 and over↗
PubMed2006

Morphologic alterations associated with mechanical bowel preparation before elective colorectal surgery: a randomized trial.

PURPOSE: The feasibility and safety of left-sided colorectal procedures with avoidance of mechanical bowel preparation has recently been demonstrated. Moreover, mechanical preparation has been associated with an increased risk for abdominal septic complications, including anastomotic leakage. This study was designed to determine whether mechanical bowel preparation is associated with histologic alterations in the colon. METHODS: Fifty patients (mean age, 61 (range, 45-78) years) scheduled to undergo elective colorectal surgery were prospectively randomized to receive mechanical preparation (polyethylene glycol; Group 1) or no preparation (Group 2) preoperatively. A macroscopically healthy segment of the bowel was excised at the proximal margin of the colectomy piece. A pathologist, blinded to the patient's group allocation, assessed various morphologic parameters. RESULTS: Indications for colectomy (cancer and complicated diverticulosis) did not differ between groups. Bowel wall alterations were more frequent in patients who received a preparation. The most striking alterations associated with mechanical preparation were loss of superficial mucus (moderate-to-severe in 96 and 52 percent in Groups 1 and 2, respectively; P < 0.001) and epithelial cells (moderate-to-severe in 88 and 40 percent in Groups 1 and 2, respectively; P < 0.01). In addition, inflammatory changes, i.e., lymphocytes (severe in 48 and 12 percent in Groups 1 and 2, respectively; P < 0.02) and polymorphonuclear cells infiltration (severe in 52 and 8 percent in Groups 1 and 2, respectively; P < 0.02), were more prevalent after mechanical preparation. CONCLUSIONS: Mechanical bowel preparation is associated with structural alteration and inflammatory changes in the large bowel wall. Although bowel wall inflammation is a known risk factor for anastomotic leak, it remains to be elucidated whether these changes have a direct relation to the deleterious effect of mechanical bowel preparation in terms of abdominal morbidity.

Aged↗
PubMed2005

The duration of postoperative ileus after elective colectomy is correlated to surgical specialization.

AIM: Postoperative ileus is an important factor of complications following gastrointestinal procedures. Its pathophysiology and the parameters, which may impact on its duration, remain unclear. The aim of this study was to measure the role of various clinical determinants on restoration of intestinal function after elective colorectal surgery. METHODS: From July 2002 to September 2003, all patients who underwent laparotomy for colectomy (laparoscopic resections excluded) with either an ileotransverse, colocolic, or high colorectal anastomosis were entered in this prospective study. The intervals in hours between the end of the surgical procedure and passing of flatus (PG) and passing of stool (PS) were recorded by an independent investigator. PG and PS were eventually correlated with the following parameters: type of colectomy, early removal of nasogastric tube (NGT), mechanical bowel preparation (MBP), type of underlying disease, systemic administration of opiates, and surgical training (colorectal fellowship or other). RESULTS: One hundred twenty-four patients were entered in this study. Four patients (3.2%) developed septic complications (3 anastomotic leaks and 1 intraabdominal abscess) and were excluded from the analysis. Median age in this population was 68 (range 30-95) years. Mean duration of postoperative ileus was 70+/-28 h (PG) and 99+/-34 h (PS). The type of colectomy, underlying disease, MBP, and early NGT removal failed, in univariate analysis, to correlate with the duration of postoperative ileus. By contrast, time intervals PG and PS were statistically shorter in the group of patients treated by a colorectal surgeon [56+/-23 vs 74+/-28 h (PG); 82+/-26 vs 103+/-35 h (PS), p=0.004], as well as in patients who received systemic opiates for less than 2 days [64+/-27 vs 75+/-28 h (PG), p=0.04; 88+/-32 vs 108+/-33 h (PS), p=001]. CONCLUSION: Restoration of normal intestinal function after elective open colectomy takes 3 (PG) to 4 (PS) days. In our series, specialized training in colorectal surgery has a positive impact on the duration of postoperative ileus. Surgical specialization should be considered an important parameter in future clinical trials aiming to minimize postoperative ileus.

Adult↗
PubMed2005

Transplantation of discordant xenogeneic islets using repeated therapy with anti-CD154.

BACKGROUND: 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. METHODS: Streptozotocin-induced diabetic C57/BL6 mice were transplanted with 1000 human islet equivalents. After 14 days, mice were nephrectomized (graftectomy) and retransplanted with human leukocyte antigen (HLA)-mismatched human islets under contralateral kidney capsule. Four groups were performed: I: all transplants (Tx) without MR1; II: first Tx without MR1, second Tx with MR1; III: first Tx with MR1, second Tx without MR1; and IV: all Tx with MR1. Recipient serums were analyzed by cross-match for serum-mediated cytotoxicity against human lymphocytes and islets. RESULTS: In group I, the second graft rejection was accelerated (graft survival, 5 +/- 3 days) compared with the first graft without MR1 (13 +/- 7 days). In groups II and III, second graft survivals were 16 +/-1 3 and 62 +/- 15 days, respectively. In group IV, second graft function was maintained for >100 days. Pretransplant cross-matches were all negative. Post-second Tx cross-matches were positive in groups I and II and negative in group IV. In group III, post-second Tx cross-matches were negative only for cells with HLA molecules present in the first donor. CONCLUSIONS: MR1 was unable to induce tolerance after sensitization. MR1 given at the first Tx only allowed prolonged survival of the second Tx, but rejection still occurred with development of antibodies against molecules not present on first donor cells, indicating that costimulatory blockade does not induce linked-suppression against species-specific antigens of xenografts but can induce donor-specific unresponsiveness. MR1 given for all sequential transplantation allowed long-term regraft survival and prevented occurrence of antidonor antibodies.

Animals↗
PubMed2005

Surgical management of abdominal and retroperitoneal Castleman's disease.

BACKGROUND: Abdominal and retroperitoneal Castleman's disease could present either as a localized disease or as a systemic disease. Castleman's disease is a lymphoid hyperplasia related to human Herpes virus type 8, which could have an aggressive behavior, similar to that of malignant lymphoid neoplasm mainly with the systemic type, or a benign one in its localized form. METHODS: The authors report two cases of localized Castleman's disease in the retroperitoneal space and review the current and recent progress in the knowledge of this atypical disease. CASES PRESENTATION: The two patients were young healthy women presenting with a hyper vascular peri-renal mass suggestive of malignant tumor. Both have been resected in-toto. One of them had an extensive resection with nephrectomy, while the second had a kidney preserving surgery. Pathological examination revealed localized Castleman's disease and surgical margins were free of disease. Postoperative course was uneventful, and after more than 5-years of follow-up no recurrences have been observed. CONCLUSION: Localized Castleman's disease should be considered when facing a solid hypervascular abdominal or retroperitoneal mass. A better knowledge of this disorder and its characteristic would help surgeon to avoid unnecessarily extensive resection for this benign disorder when dealing with abdominal or retroperitoneal tumors. Surgical resection is curative for the localized form, when complete, while splenectomy could be indicated for the systemic form.

Journal Article↗
PubMed2005

Macrophage depletion prolongs discordant but not concordant islet xenograft survival.

BACKGROUND: 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. MATERIALS AND METHODS: In vitro, we performed mouse anti-rat and anti-human mixed lymphocyte reactions (MLR) after depletion of responder or stimulator antigen-presenting cells by magnetic sorting. In vivo, streptozotocin-induced diabetic C57BL/6 mice were treated by gadolinium chloride (GdCl) to deplete macrophages, and rat or human islets were transplanted under the kidney capsule. Islet function was followed by glycemia, and xenografts were analyzed at regular intervals for histology and immunohistochemistry. RESULTS: Mouse anti-rat MLR showed a predominant direct antigen presentation pathway, whereas in mouse anti-human MLR, direct and indirect pathways were similarly involved. Survival of rat islets was not modified by GdCl therapy. In contrast, survival of human islets was significantly prolonged in GdCl-treated mice. Macrophage infiltration was decreased in concordant and discordant GdCl-treated xenografts at day 4 compared with controls. At day 15, macrophage, CD4+, and CD8+ cell infiltration was similar in all groups. CONCLUSIONS: Our results indicate that direct antigen presentation is dominant in the rejection mechanism of concordant islet xenografts and cannot be influenced by host macrophage depletion. Both direct and indirect antigen presentation are involved in rejection of discordant xenogeneic islets. Macrophage depletion should only be considered as therapeutic tool for discordant islet xenotransplantation.

Animals↗
PubMed2005

Assessment of a novel two-component enzyme preparation for human islet isolation and transplantation.

BACKGROUND: 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. METHODS: We compared the results of human-islet isolations performed either with Collagenase NB1 supplemented with Neutral Protease NB (group I, n=9) or with Liberase (group II, n=9). RESULTS: Endotoxin contents of the enzyme preparations were lower in group I. Total islet yields were similar in both groups, but islet equivalents per gram of pancreas was higher in group I (4,020+/-1,240 vs. 2,360+/-1,350; P<0.05). Islet morphology was improved in group I with significantly higher proportion of free and intact islets (71+/-9% vs. 52+/-14%; P<0.01). In vitro function was improved and apoptosis rate was lower in group I. CONCLUSIONS: This new enzyme blend was as efficient as Liberase in terms of islet yields and showed improvements in islet morphology, viability, and in vitro function. The possibility to control lot-to-lot variability and the low endotoxin contents make Collagenase NB1 a promising product for human-islet isolation.

Adult↗
PubMed2005

Surgical treatment of appendiceal adenocarcinoid (goblet cell carcinoid).

Adenocarcinoid of the appendix is an infrequent tumor with histologic features of both adenocarcinoma and carcinoid tumor. Although its malignant potential remains unclear, adenocarcinoids seem to be biologically more aggressive than conventional carcinoids. The aim of this study was to analyze long-term results of surgical treatment for appendiceal adenocarcinoid. A retrospective review (1991-2003) identified seven patients (median age 72, range 27-81 years) treated for appendiceal adenocarcinoid. The clinical data of these patients were reviewed. Follow-up was complete for all patients (median 60 months, range 24-108 months). Most cases presented with associated acute appendicitis (71%). First intention surgery consisted of appendectomy (m = 6) and right hemicolectomy (m = 1). In three patients, additional surgical procedures were performed (right colectomy). Indications for colectomy were tumor size (three cases) associated with appendectomy margin invasion in one case. One patient with lymph node and peritoneal involvement experienced recurrence 9 months after hemicolectomy and died of the disease at 2 years. One patient subsequently died of colon carcinoma 6 years after adenocarcinoid treatment. Five patients were alive without disease at the time of the last follow-up. Synchronous or metachronous colon carcinomas developed in three patients (43%). Our results suggest that appendectomy alone could be used for appendiceal adenocarcinoid provided that the tumor (1) is less than 1 cm; (2) does not extend beyond the appendix adventitia; (3) has less than 2 mitoses/10 high power fields; and (4) has surgical margins that are tumor free. Otherwise, carcinologic right colectomy seems to be indicated. The risk for developing colorectal adenocarcinoma seems to be extremely high in patients treated for appendiceal adenocarcinoid and warrants close follow-up with colonoscopic screening.

Adult↗
PubMed2005

Proximal location of colon cancer is a risk factor for development of metachronous colorectal cancer: a population-based study.

PURPOSE: This study was undertaken to assess the incidence of 1) metachronous colorectal cancer and 2) subsequent extracolonic cancers, in relation to the location (proximal or distal to the splenic flexure) of the first primary colorectal tumor. METHODS: In this population-based study, a cancer registry database was used to identify patients diagnosed with colorectal adenocarcinoma between 1970 and 1999. Patients with familial adenomatous polyposis and those with hereditary nonpolyposis colorectal cancer syndrome were excluded from the study, as were patients with nonepithelial tumors. Location of the first tumor was established according to International Classification of Diseases-Oncology-02 classification. The registry covers a population of 500,000 residents. RESULTS: A total of 5,006 patients had sporadic adenocarcinoma of the colon or rectum during this period of time, with 1,703 first primary tumors (34 percent) being located proximal to the splenic flexure. One hundred twenty occurrences of second primary colorectal cancer were observed in this population (2.39 percent). The risk for developing a second incidence of primary colorectal cancer was higher in patients whose initial tumor was located in the proximal colon (3.4 percent vs. 1.8 percent; odds ratio, 1.92; 95 percent confidence interval, 1.33-2.77; P < 0.001). The risk for each segment of the large bowel was as follows: cecum, 3.4 percent; right colon, 3 percent; transverse colon, 3.8 percent; left colon, 2.8 percent; sigmoid colon, 1.7 percent; and rectum, 1.8 percent. By contrast, the risk for developing a second, extracolonic tumor did not differ between patients with proximal and distal tumors (13.7 percent vs. 13.4 percent, P = 0.73). CONCLUSION: Patients with a first tumor located within the proximal colon are at twice the risk for developing metachronous colorectal cancer. From an epidemiologic standpoint, these data are in accordance with 1) the increasing incidence and 2) the better prognosis of proximal colon cancer in various populations. Our results confirm that proximal colon cancer is a distinct entity, which justifies the reporting of cases of colon cancer according to their location proximal or distal to the splenic flexure.

Adenocarcinoma↗
PubMed2005

Microbial surveillance during human pancreatic islet isolation.

The aim of the study was to investigate microbiological contamination rate during human pancreatic islet isolation. Between 1996 and 2002, pancreas preservation media and post-purification islet preparations were screened for microbiological contamination. After arrival in the laboratory, pancreata were washed prior to enzyme perfusion with either Hank's balanced salt solution (Group I, n = 170, 1996 to 2001) or decontaminated with polyvidonum-iodine, cefazoline, and amphotericine B (Group II, n = 45, 2001 to 2002). Microbiological contamination of preservation media was observed in 56% and 84% for Groups I and II, respectively. Analysis of contaminants revealed 74% Gram-positive, 21% Gram-negative bacteria and 5% fungi. Duration of transport had an influence on the rate of contamination (P < 0.05). After islet isolation, Group I presented microbial contamination of 16 islet preparations (9.4%) [i.e. Gram-positive bacteria (n = 10), Gram-negative bacteria (n = 4), and fungi (n = 2)]. In Group II, only 2 islet preparations (4.4%) presented microbial contamination. Microbial contamination during pancreas procurement occurs frequently. Most microorganisms are eliminated during islet isolation, and de novo contaminations during islet isolation are rare. Pancreas decontamination reduces the risk of infection of the final islet preparation.

Diabetes Mellitus, Type 1↗
PubMed2005

Xenotransplantation: an update on recent progress and future perspectives.

Currently, the number of patients awaiting transplantation is continuously increasing, and shortage of available deceased organ donors is the major limitation for organ and cell allotransplantation. Research to develop alternative sources of tissues is ongoing and xenogeneic organs or cells represent an attractive solution. This review focuses on recent progress achieved in this field, including the development of newly genetically modified animal donors and new immunosuppressive approaches. As xenotransplantation is moving closer to clinical application, future perspectives must establish guidelines to ensure that future clinical trials are carried out ethically and safely.

Animals↗
PubMed2005

Impairment of renal function after islet transplant alone or islet-after-kidney transplantation using a sirolimus/tacrolimus-based immunosuppressive regimen.

The immunosuppressive (IS) regimen based on sirolimus/low-dose tacrolimus is considered a major determinant of success of the Edmonton protocol. This regimen is generally considered safe or even protective for the kidney. Herein, we analyzed the impact of the sirolimus/low-dose tacrolimus combination on kidney function. The medical charts of islet transplant recipients with at least 6 months follow up were reviewed. There were five islet-after-kidney and five islet transplantation alone patients. Serum creatinin, albuminuria, metabolic control markers and graft function were analyzed. Impairment of kidney function was observed in six of 10 patients. Neither metabolic markers nor IS drugs levels were significantly associated with the decrease of kidney function. Although a specific etiology was not identified, some subsets of patients presented a higher risk for decline of kidney function. Low creatinin clearance, albuminuria and long-established kidney graft were associated with poorer outcome.

Adult↗
PubMed2005

Anti-CD154 mAb treatment but not recipient CD154 deficiency leads to long-term survival of xenogeneic islet grafts.

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-KO; 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.

Animals↗
PubMed2004

Two colons-two cancers: paradigm shift and clinical implications.

Embryological and physiological data suggest that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct anatomical and functional entities. Since 1990, molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in the pathogenesis of colon cancer (CC). Thus, a new paradigm has emerged with the discovery that CC is a heterogeneous disease; furthermore recent data have demonstrated that these two distinct pathways in colorectal carcinogenesis are characterized by a different clinical outcome. The implications for the clinicians are twofold; (1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and (2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in ongoing trials of adjuvant chemotherapy for CC. In the future, clinical decision-making regarding adjuvant chemotherapy might be stratified according to the MSI status of cancers located proximally to the splenic flexure.

Chemotherapy, Adjuvant↗
PubMed2004

[New results in allotransplantation of pancreatic islet cells].

An up-to-date synthesis of pancreatic islet allotransplantation is included in this summary, with emphasis on new developments and clinical results of the field. Rationale for islet transplantation in type 1 diabetes mellitus, current patient selection criteria, clinical data, technical aspects of organ procurement, islet isolation and transplantation are highlighted. The current challenges are also presented and analysed. Significant advances in clinical islet transplantation have been achieved recently. New immunosuppressive strategies were introduced, there were considerable changes in the patient selection criteria. International collaborations were established in order to standardize islet isolation and transplantation procedures. The spectacular results, recently reported by the Edmonton-group, represent a major breakthrough of the field and the outcomes are comparable with the results of whole pancreas transplantation. Islet transplantation became one of the most promising fields of tolerance induction research. Although still considered experimental, within the frameworks of expanding international collaborations, pancreatic islet allotransplantation gains more and more recognition in the clinical practice. These elements give hope that diabetes might be in the near future treated by islet cell transplantation.

Animals↗
PubMed2004

Influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients within the Swiss-French GRAGIL network.

BACKGROUND: The influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients was evaluated within the GRAGIL network. PATIENTS AND METHODS: From December 2001 to April 2003, 16 human pancreatic islet transplants were performed in 9 type 1 diabetic patients with an established kidney graft (functioning for at least 6 months) in four centers of the GRAGIL network. Islet isolation was performed in a core laboratory in Geneva, and the islet preparations were shipped by ambulance to each center for transplantation. One month after transplantation, the efficiency of the graft was assessed according to islet transportation time (ITT): ITT less than 2 hours (group 1, n=5), and ITT greater than 4.5 hours (group 2, n=4, mediant 5 hours). RESULTS: Primary graft dysfunction was observed in one patient in group 1 after one month. Two patients became insulin independent in groups 1 and 2. All other patients in both groups had a plasma C-peptide level greater than 0.5 ng/ml. The HbA1c level and the exogenous insulin needs decreased in both groups. CONCLUSIONS: ITT does not seem to influence the efficiency of pancreatic islet allotransplantation in type 1 diabetic patients. These results emphasize the scope for multicenter networks such as the GRAGIL group.

Adult↗
PubMed2004

Management of gastrointestinal stromal tumors: from diagnosis to treatment.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas or leiomyosarcomas, are today classified as GIST on the basis of molecular and immunohistological features. They originate from gastrointestinal pacemaker cells and are characterised by over-expression of the tyrosine kinase receptor KIT. Overall 5-year survival after surgical resection of GIST is approximately 60%. However, these tumours span a wide clinical spectrum from benign to highly malignant. Prognostic factors have recently been identified for GIST and include tumour size, mitotic rate and other minor factors. At present, surgery is the standard treatment for primary resectable GIST. Benign GIST have an excellent prognosis after primary surgical treatment, with over 90% 5-year survival. While recurrent or malignant GIST, which are resistant to radiotherapy and chemotherapy, had until recently an extremely poor prognosis even after surgical resection, with median survival of 12 months. The development of a tyrosine kinase inhibitor has changed the management of unresectable malignant cases. This new tyrosine kinase inhibitor, imatinib mesylate, which inhibits the c-kit receptor, has proved highly effective against GIST and has improved survival in metastatic GIST. This paper reviews the literature and our experience of GIST, including: diagnosis, pathology, treatment and prognosis.

Algorithms↗