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The prevalence, clinical profiles and management of gastroenteropancreatic endocrine tumours (GEP) in France are not known. From August 1, 2001 to September 1, 2002, standardized records on patients with GEP were prospectively completed in 87 participating centres. The total group amounted to 668 patients (median age: 56 years, range: 12-89). WHO performance status was 0/1 for 80.2% of patients. The primary sites were the small bowel and colon (288), pancreas (211), unknown (77), stomach (33), non-digestive primary sites (24), appendix (20), rectum-anus (12), and oesophagus or cardia (3). GEP were functional in 260 patients (39%). Most pancreatic tumours were non-functional (72%). Metastatic disease was observed in 73.4% of cases. Most tumours (85.8%) were well or moderately differentiated. Somatostatin receptor scintigraphy was performed in only 55% of patients. The following treatment modalities were employed: resection of primary tumour: 66%; systemic chemotherapy: 41%; somatostatin analogues: 44 and 26% for GEP of small intestine and pancreas, respectively; interferon: 12%, and intra-arterial hepatic (chemo)embolization in 23 and 15% of GEP arising from the midgut and pancreas, respectively. Despite their low prevalence, well-differentiated GEP represent a significant and heterogeneous clinical group, which warrants improved medical education, referral to expert centres at an early stage, and the design of prospective therapeutic trials., ((c) 2008 S. Karger AG, Basel.)

Background and Study Aims: Duodenal stenting has become a popular treatment in cases of malignant stenosis. However, a prospective evaluation of the efficacy and morbidity of this procedure has not been performed. A prospective multicenter study of duodenal stenting was conducted by the Société Française d'Endoscopie Digestive (SFED)., Patients and Methods: A total of 51 patients were selected (mean age 72), the majority (69%) having pancreatic adenocarcinoma. Palliative treatment was chosen because of irresectability (61.2%), inoperability (18.4%), or both (20.4 %). Enteral Wallstent prostheses were used, and the patients were followed up on day 3, after 1 month, and then every month, with weight measurement, and symptomatic and laboratory evaluation., Results: One prosthesis was sufficient in 46 patients. Stent positioning and deployment were correct in 50/51 patients (98%). Twenty patients also underwent biliary stenting in addition to the duodenal stenting. On day 3, 43 patients (84%) were able to tolerate soft solids or a full diet. Six complications were attributed to stenting: three intestinal hemorrhages, two cases of peritonitis due to bowel perforation, and one case of septicemia, and these led to five deaths (mortality 9.8%). Stent dysfunction was observed in 12 cases (23.5%) after a mean delay of 75 days, comprising 11-malignant obstructions and one migration: a new stent was inserted inside the first one and was effective in eight cases; and no treatment was given in the other four patients because of their clinical state. The median survival was 71.5 days., Conclusions: Palliative endoscopic treatment of malignant duodenal stenosis using metallic prostheses is highly feasible, even with associated biliary stenting. Symptomatic improvement is fast. However, the mortality and the obstruction rate are high, suggesting that a prospective trial comparing this treatment with surgery is still required.

Background: The objective of this phase III study was to compare the safety and efficacy of FLP (modulation of 5-FU (Fluorouracil) by folinic acid or leucovorin (LV) and cisplatin vs. FP (5-FU combined with Cisplatin) as a first line chemotherapy in advanced oesophageal, gastric and pancreatic cancer., Patients and Methods: 232 patients with measurable lesions were randomised to receive at the first cycle either FP (arm A: 5-FU 800 mg/m2/d in continuous infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2), or FLP (arm B: LV, 100 mg/m2/d in bolus 5 days, followed by 5-FU 350 mg/m2/d in 1 h infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2). In case of no grade 3-4 haematological and diarrhoea toxicity, the dose of 5-FU was increased to 1000 mg/m2/d and 400 mg/m2/d in the two arms respectively, for the subsequent cycles until disease progression., Results: The distribution of primary tumours was: 19 squamous cell carcinoma of the oesophagus, 19 oesophageal adenocarcinoma, 91 gastric and 97 pancreatic adenocarcinoma. Safety remained acceptable and comparable in the two arms except for the severe grade 3-4 mucositis, which was lower in arm B (4.5 vs. 16.4%, p < 0.009). Efficacy in terms of tumour response and survival was similar in the two arms, showing an objective response rate (after external review) of 18.6% (95% confidence interval (CI) 11.4-25.8%) in arm A vs. 15% (95% CI 8.5-21.6%) in arm B, an overall median survival of 24 weeks in arm A vs. 24.7 in arm B (p = 0.83) and a progression-free median survival of 12.4 weeks vs. 12.1 in arms A and B, respectively (p = 0.91)., Conclusion: The FLP regimen is substantially equivalent to FP in terms of safety and quality of life, as well as for antitumour efficacy in these carcinomas; the only slight advantage of FLP in this study concerns mucositis. Based on these results, FLP could be used as an alternative to FP when appropriate.

Objectives: The aim of this study was to evaluate the possibility of subsequent resection of locally advanced pancreatic adenocarcinoma after chemotherapy and external-beam radiotherapy., Patients and Methods: Between January 1996 and January 2001, 33 consecutive patients (18 males and 15 women, mean age 63 years) with locally advanced PA were treated with chemotherapy and concurrent external-beam radiotherapy. Radiotherapy delivered 45-50.4 Gy, in a classical manner (N=27) or on a split-course (N=6). Chemotherapy was made of 5FU by continuous infusion for all patients during 5 weeks and cisplatin at the 1st and 5th weeks (N=22). Tumor resectability was reassessed at the end of the chemoradiotherapy; surgical resection of tumour was attempted in patients whose tumor demonstrated reduction in size, and supplementary radiotherapy of 10 to 15 Gy was delivered to the others., Results: Thirty-nine percent of patients experienced grade 3 acute toxicity. WHO criteria response to chemoradiotherapy four weeks after the end of treatment were: 4 partial responders (12%), 6 minor responders (18%), 14 stable disease (42%), 9 progression (28%). Ten patients underwent exploratory laparotomy, in one case vascular encasement did not allow for tumor resection, and in another patient, there was peritoneal carcinomatosis. In the 8 remaining patients, surgical (R0) resection was possible. In one patient histological examination showed fibrosis with no residual tumour. After a median follow-up period of 40 months, median survival was 16 months (66% and 37% of survival at 1 and 2 years respectively). In operated and non-operated patients, survival rates at 24 months were 73% and 12.5% respectively. At 1 year, 80% of the patients treated with radiochemotherapy developed recurrence, metastatic recurrence in 88%. Initial laparotomy, split course radiotherapy were poor outcome factors whereas chemotherapy appears to be a favorable outcome factor., Conclusion: Subsequent resection of locally advanced pancreatic adenocarcinoma is possible after chemoradiotherapy allowing for a prolonged survival in some patients.

Aim of the Study: To detect hereditary non-polyposis colorectal cancer (HNPCC) patients with a strategy combining clinical selection (patient age at onset of cancer less than 50 years or family history of HNPCC tumors) and microsatellite instability typing plus immunohistochemistry, leading to mismatch repair (MMR) germline mutation analysis., Methods: Tumors were screened for microsatellite instability (MSI) and for hmlh1 and hmsh2 immunohistochemical expression. Germline mutation analysis was performed to search for MLH1 and MSH2 mutations in patients with MSI-High and MSI-Low tumors., Results: 197 adenocarcinomas were studied: 164 patients were< or =50 years old, 33 were older than 50 years but had a family history of HNPCC tumors. Fifty tumors (25.4%) were MSI-High, 10 were MSI-Low (5.1%), and 130 were MS-Stable (66%). MSI typing was inconclusive in 7 (3.5%). Immunohistochemistry screening was performed on 165 tumors: sensitivity was 63.6%, specificity was 99%. Germline mutation analysis was performed in 33/60 MSI-High or Low tumors: 23 mutations were noted (70% of the tested patients)., Conclusion: This proposed strategy of determining microsatellite instability in young colorectal cancer patients or in patients with a family history of HNPCC tumors led to an increased frequency in the detection of MMR germline mutations.

We report a prospective randomized multicenter trial that tested the efficacy of combining ursodeoxycholic acid and norfloxacin in the prevention of polyethylene stent clogging in patients with obstructive jaundice due to an unresectable malignancy at the level of the common bile duct. After insertion of a 10-Fr straight polyethylene stent, patients were allocated to receive oral treatment with ursodeoxycholic acid and norfloxacin, or conservative treatment. The primary outcome measure was stent blockage within six months. Thirty-three patients (group I) received ursodeoxycholic acid and norfloxacin, and 29 received conservative treatment (group II). At six months, cumulative stent patency rate did not differ significantly between group I (47+/-11%, mean +/- SE, median 149 days) and group II patients (24+/-10%, mean +/- SE, median 100 days, P = 0.23, log-rank test). Four stents were clogged by ursodeoxycholic acid. Survival did not differ between the two groups. Combined therapy with ursodeoxycholic acid and norfloxacin failed to improve stent patency. Moreover, ursodeoxycholic acid can cause stent obstruction.

Background: Thrombocytopenia occurred in a woman given alpha interferon for chronic hepatitis C without cirrhosis. Both central thrombocytopenia, clearly demonstrated, and peripheral thrombocytopenia, probably of autoimunne origin, were involved., Case Report: A 55-year-old woman with active chronic hepatitis C (Metavir score A2, F2) was given alpha interferon. One month after treatment onset, she developed thrombocytopenia (32 G/L). A second bone marrow aspirate and osteomedullary biopsy evidenced megalokaryocytes and the platelet count responded to polyvalent immunoglobulins. Five months after discontinuing interferon, the platelet count progressively returned to normal., Discussion: Central thrombocytopenia is classically described in patients given interferon and usually appears during the first weeks of treatment. In our case, the central mechanism was clearly demonstrated by the bone marrow aspirate and osteomedullary biopsy findings at a time when the platelet count was 32 G/L. A peripheral immunological participation was more difficult to prove but was strongly suggested by the persistence of thrombocytopenia despite the interruption of the interferon and the efficacy of immunoglobulins.

Objectives: We report the efficacy of alteplase (a recombinant tissue plasminogen activator) with heparin or heparin alone in the treatment of acute thrombosis of the portal venous system., Methods: Ten consecutive patients with acute portal venous system thrombosis were studied. Five patients were treated with alteplase and heparin, and the remaining 5 patients, who were asymptomatic or had a contraindication to alteplase, were treated with heparin alone., Results: In 3 of the 5 patients treated with alteplase, ultrasonography showed total resolution of the thrombus; the remaining 2 had partial resolution of the thrombus. In 4 of the 5 patients treated with heparin alone, ultrasonography showed total resolution of the thrombus, and no change in one. No bleeding occurred., Conclusion: Treatment with heparin can result in complete recanalisation of acute portal venous system thrombosis. These data suggest that combined therapy with systemic alteplase does not increase the efficacy of heparin.

A case of obstructive intramural hematoma of the esophagus post variceal sclerotherapy is reported in a 44-year-old man who presented retrosternal pain and complete dysphagia. Endoscopy showed a bluish submucosal mass occupying the esophageal lumen. Diagnosis was confirmed by Computed Tomography. A favorable outcome was observed with symptomatic treatment.

A variety of prodromal symptoms of viral hepatitis (urticaria, fever, arthralgias, headache, polyradiculonevritis) are attributed to A, B, C, D or E hepatitis only when jaundice appears, and because they disappear with it. Spectacular extrahepatic symptoms (polyarteritis nodosa, cryoglobulinemia, glomerulonephritis, marrow aplasia...) may be associated with B or C hepatitis without any liver symptom. Some of the extrahepatic symptoms observed during chronic hepatitis C therapy with interferon (thyroid dysfunctions, cutaneo-mucous lichen) may be related to the immunomodulatory effects of interferon rather than to virus C itself.

The incidence of chronic alcoholism among the non-medical staff of a hospital was evaluated in an occupational health service context. Three criteria were sought routinely: suspicion by history of excessive alcohol intake, typical findings by physical examination, and suggestive behavioural changes reported by work colleagues. Gamma glutamyl transpeptidase levels and mean corpuscular volume were measured when one of these three criteria existed. The diagnosis of chronic alcoholism was made when two criteria were found or when only one criterion existed but accompanied by laboratory abnormalities. The incidence of chronic alcoholism was 6.2 per cent among male staff and 0.6 among female staff. It appeared to be less than in the population as a whole. The selective and non-systematic use of laboratory investigations and the frequent absence of indication to the occupational health physician of behavioural problems were sources of bias which probably contributed to underestimation of the incidence of chronic alcoholism among employees of the Orleans Regional Hospital Group. Provision of information to all staff is essential in order to explain the behavioural changes associated with chronic alcoholism and the usefulness of reporting employees showing evidence of such changes to the occupational physician. This enables medico-social diagnosis and the early care of those with early chronic alcohol abuse.

Strong inhibition of acid secretion could be able to decrease gastric and duodenal ulcer early rebleeding. OBJECTIVE--The aim of this double blind randomized trial was to compare early rebleeding rates of 2 groups of patients treated with ranitidine (600 mg/day) or lansoprazole (60 mg/day) per os for 6 consecutive days. METHODS--Seventy five patients with a high risk of rebleeding (clinical and endoscopical criteria) were included in this trial. These ulcers were Ia (n = 10), Ib (n = 20), IIa (n = 13), IIb (n = 32) in Forrest classification. RESULTS--Nineteen out of 75 patients rebled (25.3%): 11 out of 37 (30%) and 8 out of 38 (21%) in the ranitidine and lansoprazole groups respectively. Rates of rebleeding were 10%, 12.5%, 36% and 29% respectively in the ulcers grade Ia (previously treated with endoscopic sclerosis), Ib, IIa and IIb in the Forest classification. CONCLUSION--The rates of rebleeding were not statistically different in the 2 groups of treatment. The high rebleeding rates observed with Forrest IIa and IIb and duodenal ulcers support the need of haemostatic endoscopic therapy associated to antisecretory treatment in such patients.

Radiation hazards to operators performing retrograde endoscopic cholangio-pancreatographies (RECP) have been investigated. The principles and central elements of French medical radioprotection legislation are recalled. Doses received by the operators, over a one month period representative of their usual work, were measured in two ways: by using a ionisation chamber and with thermoluminescent detectors worn by the staff. Extrapolated to 12 months, the results were inferior to the annual reglementary dose limit: whole body < 1.2 mSv (against 50 mSv), eye lens = 38.4 mSv (against 150 mSv). Further means for reducing dose levels are proposed.

The present study is based on the registry of digestive cancers set up for the French department of Côte-d'Or (455,727 residents). Large bowel cancer represents half of the gastrointestinal tract cancers recorded in the course of 2 years (1976-1977). The crude annual incidence rate was 52.2 per 100,000 for males, 41.7 per 100,000 for females. The age-standardized incidence rate for cancer of the rectum is one of the highest reported. The incidence rates for cancer of the colon are in the intermediate range. Half of the large bowel cancers were rectal cancers, nearly always adenocarcinoma. Coexisting benign polyps were seen in 21% of the cases at the time of diagnosis of carcinoma and were more common in males than in females. 54% of cancers of the colon and 62% of cancers of the rectum underwent curative surgery.

The registry of digestive tract cancers set up for the department of Cote d'Or (455, 727) was used to study primary liver cancer. The crude annual incidence rate was 10.4 per 100 000 for males, 2.3 per 100 000 for females. Among other cancer registries annual age standardized rates: 7.6 per 100 000 in males, 1.4 per 100 000 in females are in the intermediate range, close to the figure reported in Geneva and higher than incidence rates reported elsewhere in Europe. Most cancers were hepatocullular carcinomas (83%). Significant etiological factors were the sex ratio (5, 4), alcoholic cirrhosis associated with primary liver cancer in 61% of the patients. The one year crude survival rate was 8%.