The PRSS3P2 and TRY7 deletion copy number variant modifies risk for chronic pancreatitis.

BACKGROUND: PRSS1 and PRSS2 constitute the only functional copies of a tandemly-arranged five-trypsinogen-gene cluster (i.e., PRSS1, PRSS3P1, PRSS3P2, TRY7 and PRSS2) on chromosome 7q35. Variants in PRSS1 and PRSS2, including missense and copy number variants (CNVs), have been reported to predispose to or protect against chronic pancreatitis (CP). We wondered whether a common trypsinogen pseudogene deletion CNV (that removes two of the three trypsinogen pseudogenes, PRSS3P2 and TRY7) might be associated with CP causation/predisposition. METHODS: We analyzed the common PRSS3P2 and TRY7 deletion CNV in a total of 1536 CP patients and 3506 controls from France, Germany, India and Japan by means of quantitative fluorescent multiplex polymerase chain reaction. RESULTS: We demonstrated that the deletion CNV variant was associated with a protective effect against CP in the French, German and Japanese cohorts whilst a trend toward the same association was noted in the Indian cohort. Meta-analysis under a dominant model yielded a pooled odds ratio (OR) of 0.68 (95% confidence interval (CI) 0.52-0.89; p = 0.005) whereas an allele-based meta-analysis yielded a pooled OR of 0.84 (95% CI 0.77-0.92; p = 0.0001). This protective effect is explicable by reference to the recent finding that the still functional PRSS3P2/TRY7 pseudogene enhancers upregulate pancreatic PRSS2 expression. CONCLUSIONS: The common PRSS3P2 and TRY7 deletion CNV was associated with a reduced risk for CP. This finding provides additional support for the emerging view that dysregulated PRSS2 expression represents a discrete mechanism underlying CP predisposition or protection.

Prognostic factors associated with upper gastrointestinal bleeding based on the French multicenter SANGHRIA trial.

Background and study aims Prognostic and risk factors for upper gastrointestinal bleeding (UGIB) might have changed overtime because of the increased use of direct oral anticoagulants and improved gastroenterological care. This study was undertaken to assess the outcomes of UGIB in light of these new determinants by establishing a new national, multicenter cohort 10 years after the first. Methods Consecutive outpatients and inpatients with UGIB symptoms consulting at 46 French general hospitals were prospectively included between November 2017 and October 2018. They were followed for at least for 6 weeks to assess 6-week rebleeding and mortality rates and factors associated with each event. Results Among the 2498 enrolled patients (mean age 68.5 [16.3] years, 67.1 % men), 74.5 % were outpatients and 21 % had cirrhosis. Median Charlson score was 2 (IQR 1-4) and Rockall score was 5 (IQR 3-6). Within 24 hours, 83.4 % of the patients underwent endoscopy. The main causes of bleeding were peptic ulcers (44.9 %) and portal hypertension (18.9 %). The early in-hospital rebleeding rate was 10.5 %. The 6-week mortality rate was 12.5 %. Predictors significantly associated with 6-week mortality were initial transfusion (OR 1.54; 95 %CI 1.04-2.28), Charlson score > 4 (OR 1.80; 95 %CI 1.31-2.48), Rockall score > 5 (OR 1.98; 95 %CI 1.39-2.80), being an inpatient (OR 2.45; 95 %CI 1.76-3.41) and rebleeding (OR 2.6; 95 %CI 1.85-3.64). Anticoagulant therapy was not associated with dreaded outcomes. Conclusions The 6-week mortality rate remained high after UGIB, especially for inpatients. Predictors of mortality underlined the weight of comorbidities on outcomes.

Efficacy and safety of panitumumab in a cohort of patients with metastatic colorectal cancer in France: PANI OUEST, a post-EMA-approval descriptive study with a geriatric oncology focus.

BACKGROUND/AIMS: The Bretagne-Pays de la Loire cancer observatory, an oncology network created by the French Ministry of Health, is specifically dedicated to assess the use of new targeted anticancer therapies in routine practice. In line with the French National Cancer III program, our cancer network set up a real-life cohort, which is independent of the pharmaceutical industry, for patients with colorectal cancer to monitor patient safety and quality of care and promote pharmacovigilance. MATERIALS AND METHODS: Panitumumab monotherapy was assessed in 243 patients with wild-type Kirsten rat sarcoma who were treated for metastatic colorectal cancer (mCRC) between July 2008 and December 2010 after prior chemotherapy using oxaliplatine and irinotecan. This was a post-European medicine agency marketing (EMA-M) study Results: This study shed light on the best practices, strategic adaptations, clinical results (treatment objective responses, 13%; progression free survival, 2.99 months [2.73-3.15]; and overall survival, 6.8 months [5.49-8.38]) as well as expected or unexpected (grade 3 or 4: 11.5%) secondary effects in the phase IV panitumumab treatment of mCRC. CONCLUSION: Our results are similar to those by Amado whose phase III study led to obtaining EMA-M for panitumumab and tend to confirm the antitumor activity of this antiepidermal growth factor receptor antibody in the treatment of mCRC. In addition, our results opened avenues to further assessment of panitumumab use as monotherapy as well as its benefit-risk ratio while taking into account the patients' general and clinical characteristics. In 2012, the French National Authority for Health appended these data to the panitumumab transparency committee report.

[Treatment of squamous cell carcinoma of the pancreas with gemcitabine]. / Traitement d'un carcinome épidermoïde primitif du pancréas par gemcitabine.

Primary squamous cell carcinoma of the pancreas is a rare tumor. We report a case of a 49 years old patient with a metastatic squamous cell carcinoma of the pancreas. Histological diagnosis was established by echoguided biopsy of the liver. Due to that, we cannot be sure that this tumor was not adenosquamous with a metastatic component from only the squamous part of the lesion. Two types of chemotherapy have been performed. The first one was radiochemotherapy with an association of 5FU and cisplatinum. Gemcitabin was the second one. An objective response was obtained with gemcitabin and the patient's health improved. To our knowledge, this has never had been reported beforehand. However the prognosis of this cancer remains poor. Overall survival was 8 months.

Epidemiology and long term survival of gastric carcinoma in the French district of Finistere between 1984 and 1995.

OBJECTIVES: The aims of this study were to evaluate trends in incidence, clinical characteristics, treatment regimen and prognosis of gastric carcinoma in the area of Finistere (France) during a 12-year period. METHODS: Between 1984 and 1995, the Finistere Registry of GastroIntestinal Tract Tumors listed 2 139 patients with gastric carcinoma in a population of 838 627 inhabitants. Curative resection and operative mortality were analyzed by logistic regression. Prognostic factors were determined using the Kaplan-Meier method and the Cox model. RESULTS: When comparing the second period (1990-1995) to the first period (1984-1989) we observed: a) a decrease of standardized incidence (13.2 vs. 15.6/100 000 inhabitants/year in males and 5.4 vs. 7.0/100 000 inhabitants/year in females); b) a significant increase of linitis plastica (21.4% vs. 10.9%) and infiltrative tumors (53.1 vs. 31.2%) (P<0.0001); c) no variation in tumor stage at diagnosis; d) a significant increase in curative resection (65.7% vs. 45.0%; P<0.0001); e) no variation in operative mortality; f) the absence of improvement of survival rate; the latter was 29% at 2 years, 19% at 5 years and 11% at 10 years during the second period. Multivariate analysis showed that the main prognostic factors of gastric carcinoma were age, tumor stage and the type of surgical procedure. CONCLUSION: This study showed a decrease in the incidence of gastric carcinoma over time and an increase of linitis plasticia and infiltrative forms. Despite improvement in management of patients, the global prognosis of gastric carcinoma did not improve significantly over a 12-year period of observation.