Jean-Marc Sabate

Iterative Cytoreductive Surgery Associated With Hyperthermic Intraperitoneal Chemotherapy for Treatment of Peritoneal Carcinomatosis of Colorectal Origin With or Without Liver Metastases

Introduction:The aim of this study was to evaluate the results of an aggressive strategy in patients presenting peritoneal carcinomatosis (PC) from colorectal cancer with or without liver metastases (LMs) treated with cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients and Methods:The population included 43 patients who had 54 CS+HIPEC for colorectal PC from 1996 to 2006. Sixteen patients (37%) presented LMs. Eleven patients (25%) presented occlusion at the time of PC diagnosis. Ascites was present in 12 patients (28%). Seventy-seven percent of the patients were Gilly 3 (diffuse nodules, 5–20 mm) and Gilly 4 (diffuse nodules>20 mm). The main endpoints were morbidity, mortality, completeness of cancer resection (CCR), and actuarial survival rates. Results:The CS was considered as CCR-0 (no residual nodules) or CCR-1 (residual nodules <5 mm) in 30 patients (70%). Iterative procedures were performed in 26% of patients. Three patients had prior to CS + HIPEC, 10 had concomitant minor liver resection, and 3 had differed liver resections (2 right hepatectomies) 2 months after CS + HIPEC. The mortality rate was 2.3% (1 patient). Seventeen patients (39%) presented one or multiple complications (per procedure morbidity = 31%). Complications included deep abscess (n = 6), wound infection (n = 5), pleural effusion (n = 5), digestive fistula (n = 4), delayed gastric emptying syndrome (n = 4), and renal failure (n = 3). Two patients (3.6%) were reoperated. The median survival was 38.4 months (CI, 32.8–43.9). Actuarial 2- and 4-year survival rates were 72% and 44%, respectively. The survival rates were not significantly different between patients who had CS + HIPEC for PC alone (including the primary resection) versus those who had associated LMs resection (median survival, 35.3 versus 36.0 months, P = 0.73). Conclusion:Iterative CS + HIPEC is an effective treatment in PC from colorectal cancer. The presence of resectable LMs associated with PC does not contraindicate the prospect of an oncologic treatment in these patients.

Advanced gastric cancer with or without peritoneal carcinomatosis treated with hyperthermic intraperitoneal chemotherapy: a single western center experience.

INTRODUCTION The aim of this article was to evaluate the role of hyperthermic intraperitoneal chemotherapy (HIPEC), associated or not to cytoreductive surgery (CS) in the treatment of different stages of advanced gastric cancer (AGC). PATIENTS AND METHODS Thirty seven patients with AGC who underwent 43 HIPEC from June 1992 to February 2007 were included. HIPEC used Mitomycin-C and Cisplatin for 60-90 min at 41-43 degrees C intra-abdominal temperature. The main endpoints were long-term survivals, morbidity and mortality rates. RESULTS Eleven patients had no demonstrable sign of PC and constituted the Prophylactic-group, while 26 patients had macroscopic PC (PC-group). Five patients were Gilly 1 or 2 (nodules <0.5 cm) and 21 Gilly 3 or 4 (nodules >or=0.5 cm). In the PC-group a complete curative CS was achieved before HIPEC in 8 (PC-curative subgroup) and a palliative HIPEC in 18 patients (PC-palliative subgroup). The overall 30-days mortality was 5% (2 patients). Two patients in the Prophylactic group died within 6 months after hospital discharge (overall mortality 11%). The estimated risk of death per procedure was 9%. Ten patients (27%) presented one or more complications. The median survival was 23.4 months in the Prophylactic group, and 6.6 months in the PC-group (p<0.05). The median survival in the PC-curative subgroup was 15 vs 3.9 months in the PC-palliative subgroup (p=0.007). The median survival according to Gilly classification was significantly different (Gilly 1&2 vs Gilly 3&4, 15 vs 4 months respectively, p=0.014). The global recurrence rates between the Prophylactic group and the PC-curative subgroup at 2years were 36% vs 50% respectively. The median delay to recurrence was 18.5 vs 9.7 months respectively. CONCLUSION HIPEC might be useful to improve the survival in selected patients with ACG only when a complete cytoreduction can be achieved. Despite encouraging data, prospective studies, based on larger cohorts of patients are required to assess the role of this procedure as a prophylactic treatment in patients with AGC.

Prevalence and Predictive Factors of Non-Alcoholic Steatohepatitis (NASH) in Morbidly Obese Patients Undergoing Bariatric Surgery

Background: In patients with morbid obesity selected for bariatric surgery, previous studies have shown a prevalence of NASH varying from 2.6% to 91%. The prevalence of NASH and extensive fibrosis were studied in a prospective cohort of patients with morbid obesity requiring bariatric surgery, to identify predictive factors of NASH. Methods: From July 01 to Sept 02, every patient requiring bariatric surgery had a liver biopsy. The diagnosis of NASH was established using Lees criteria. Results: 92 patients (85 women, age 38 ± SEM 11 years) were analyzed. Mean BMI was 45.7 ± 5.1 kg/m2. 35 patients had lobular inflammation. 9 patients had steatosis associated with lobular necrotic and inflammatory foci and ballooning degeneration or pericellular fibrosis. No cirrhosis or extensive fibrosis was evidenced. The prevalence of NASH in this population was 9.8%. Waist/hips ratio and BMI were independent predictors of lobular inflammation, but only BMI was an independent factor of NASH in multivariate analysis. Conclusion: In this prospective cohort of patients at bariatric surgery, the prevalence of NASH was 9.8%. BMI was the only predictive factor for NASH.

The V249I polymorphism of the CX3CR1 gene is associated with fibrostenotic disease behavior in patients with Crohn's disease.

Objectives CX3CR1, the receptor of CX3CL1/fractalkine, is involved in regulation of inflammatory response and the CX3CR1-I249-M280 naturally occurring mutants are associated with altered binding to the ligand. Our aim was to evaluate the frequency of CX3CR1 V249I and T280M polymorphisms and NOD2/CARD15 mutations in Crohns disease patients and to search for a relationship with phenotype. Methods Clinical data were retrospectively collected. V249I and T280M polymorphisms of CX3CR1 gene and NOD2/CARD15 mutations (R702W, G908R, 3020InsC) were identified. Results Two hundred and thirty-nine patients (140 females, 39.7±14.1 years) were included. About 37.4% were heterozygous and 8.8% were homozygous for the V249I CX3CR1 polymorphism, 18.1% were heterozygous and 1.3% homozygous for the T280M CX3CR1 polymorphism and 35.9% had at least one of the three mutations of NOD2/CARD15. The T280M CX3CR1 polymorphism was not associated with any phenotype. In univariate analysis, stenosis was significantly associated with both V249I CX3CR1 polymorphism and 3020InsC NOD2/CARD15 mutations. In smoker patients carrying the CX3CR1 allele I249, there was a significant increase in the frequency of fibrostenosing disease [P=0.005, odds ratio (OR): 3.25] whereas this relationship disappeared in the group of nonsmokers (P=0.72). In multivariate analysis, 3020InsC NOD2/CARD15 mutations and the V249I CX3CR1 polymorphism were independent risk factors for intestinal stenosis (P=0.046, OR: 1.8 and P=0.044, OR: 2.4, respectively). Conclusion In Crohns disease, V249I CX3CR1 polymorphism is associated with intestinal strictures, particularly in smokers. This association is independent of CARD15 mutations.

Cytoreductive surgery associated to hyperthermic intraperitoneal chemoperfusion for desmoplastic round small cell tumor with peritoneal carcinomatosis in young patients.

PURPOSE Desmoplastic round small cell tumor (DRSCT) is a rare intraabdominal mesenchymal tissue neoplasm in young patients and spreads through the abdominal cavity. Its prognosis is poor despite a multimodal therapy including chemotherapy, radiotherapy, and surgical cytoreduction (CS). hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as an additional strategy in the treatment of peritoneal carcinomatosis; for this reason, we planned to treat selected cases of children with DRSCT using CS and HIPEC. METHODS Peritoneal disease extension was evaluated according to Gilly classification. Surgical cytoreduction was considered as completeness of cytoreduction-0 when no macroscopic nodule was residual; HIPEC was performed according to the open technique. RESULTS We described 3 cases: the 2 first cases were realized for palliative conditions and the last one was operated on with curative intent. There was no postoperative mortality. One patient was reoperated for a gallbladder perforation. There was no other complication related to HIPEC procedure. CONCLUSIONS Surgical cytoreduction and HIPEC provide a local alternative approach to systemic chemotherapy in the control of microscopic peritoneal disease in DRSCT, with an acceptable morbidity, and may be considered as a potential beneficial adjuvant waiting for a more specific targeted therapy against the fusion protein.

255 Aminosalicylates, Thiopurines and the Risk of Colorectal Cancer in Inflammatory Bowel Diseases: A Case-Control Study Nested in the CESAME Cohort

7-3589). There was no impact of years of 5ASA use on outcomes. Conclusion In study I we could not find evidence that 1 or 5 years of consecutive 5-ASA use was chemoprophylactic in IBD (in fact it tended to increase the risk). We could not discount that longer use might have been chemoprophylactic. In Study II with a longer duration of follow up and more CRC cases we could not discern that 5-ASA was chemoprophylactic. Overall, our results support the majority of studies to date that 5-ASA is not chemoprophylactic in IBD for CRC.

Efficacy of infliximab in Crohn's disease. Results of a retrospective multicenter study with a 15-month follow-up.

OBJECTIVES To evaluate prescription practices and response to infliximab treatment for Crohns disease (CD). PATIENTS AND METHODS The files of CD patients treated with at least one infusion of infliximab treated in gastroenterology units belonging to university teaching hospitals of the Parisian hospitals group (Assistance Publique-Hôpitaux de Paris (AP-HP) during the year 2000 were analyzed retrospectively. RESULTS One hundred and thirty-seven patients (36.0 +/- 12.7 years, 92 females) from 12 centers were studied. Indication for treatment was fistulae or perianal disease in 39% of patients, active Crohns disease in 45% and mixed conditions in 16%. Mean follow-up was 15.2 +/- 7.2 months. The overall response rate was 85%. No predictive factor of sustained remission could be identified. The mean time to relapse was to 3.9 +/- 3.1 months. Thirty-eight patients were on maintenance therapy at the end of the follow up; 37% exhibiting progressive lost of response to treatment. Immunosuppressive therapy was added to infliximab in 78% of cases but response to infliximab was not modified by addition of immunosuppressive drugs. Adverse events, most frequently minor, were noted in 23% of the patients. CONCLUSION This retrospective study confirms the efficacy and safety of infliximab in CD.

Food consumption and dietary intakes in 36,448 adults and their association with irritable bowel syndrome: Nutrinet-Santé study:

Introduction: Diet plays an important role for patients with irritable bowel syndrome (IBS). The aim of this study was to compare the diets in terms of food consumption and nutrient intake between subjects with IBS and controls in a large French population. Methods: This study included 36,448 subjects from the Nutrinet-Santé cohort study, who completed a questionnaire pertaining to functional bowel disorders based on the Rome III criteria. Dietary data were obtained from at least three self-administered 24 h records via the internet. Association between IBS and diet was evaluated by comparison tests controlled for gender, age and total energy intake (ANCOVA tests). Results: Subjects included were mainly women (76.9%) and the mean age was 50.2 ± 14.2 years. Among these individuals, 1870 (5.1%) presented with IBS. Compared to healthy controls, they had significantly lower consumption of milk (74.6 versus 88.4 g/day; p < 0.0001), yogurt (108.4 versus 115.5 g/day; p = 0.001), fruits (192.3 versus 203.8 g/day; p < 0.001), and higher soft non-sugared beverages (1167.2 versus 1122.9 ml/day; p < 0.001). They had higher total energy intake (2028.9 versus 1995.7 kcal/day; p < 0.001), with higher intakes of lipids (38.5 versus 38.1% of total energy intake; p = 0.001) and lower intakes of proteins (16.4 versus 16.8% of total energy intake; p < 0.0001), as well as micronutrients (calcium, potassium, zinc and vitamins B2, B5 and B9, all p < 0.0001). Conclusions: In this large sample, these findings suggest that dietary intake of subjects suffering from IBS differs from that of control subjects. They may have adapted their diet according to symptoms following medical or non-medical recommendations.

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn’s Disease

BACKGROUND & AIMS: Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn’s disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn’s perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. METHODS: We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn’s disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case‐control study in which participants were matched for age and sex. RESULTS: Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn’s lesions at cohort entry, 2 developed anal squamous‐cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient‐years for anal squamous‐cell carcinoma, 0.38 per 1000 patient‐years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient‐years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn’s disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient‐years and of rectal cancer was 0.21 per 1000 patient‐years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune‐suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18‐551.51; P = .03). CONCLUSIONS: In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn’s disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

Association between self-reported vegetarian diet and the irritable bowel syndrome in the French NutriNet cohort

Background There is growing interest in using diet counselling in the management of patients with irritable bowel syndrome (IBS). Among new emerging diets, vegetarian diets (VD) seem to be experiencing an important popularity, partly because of their alleged health benefits. A recent study performed among a rural Indian population showed that predominant VD could be associated with IBS. Objective This cross-sectional study aimed at assessing the association between the VD and IBS, among a large French cohort, the NutriNet-santé study. Methods Subjects participating in the NutriNet-Santé cohort study completed a questionnaire based on Rome III criteria (N = 41,682). Anthropometrics, socio-demographical and lifestyle data, including VD, were collected prior to the completion of Rome III questionnaire via self-administered questionnaires. Association between VD and IBS and its subtypes was investigated through multivariate logistic regression. Results The included subjects were mainly women (78.0%) and the mean age was 49.8±14.3 years. Among these individuals, 2,264 (5.4%) presented an IBS, and 805 (1.9%) reported a VD. Overall, VD was not associated with IBS or subtypes. A stable VD (i.e. self-declared at least three times) was associated with IBS (aOR 2.60 95%CI [1.37–4.91]), IBS mixed (aOR 2.97 95%CI [1.20–7.36]) and IBS diarrhoea (aOR 2.77 95%CI [1.01–7.59]). Conclusions This study suggests that a long term VD could be associated with IBS. Nevertheless, further studies are needed to confirm these results, and investigate the multiple aspects of the vegetarian diet, possibly related to the IBS.