Phase II study of oxaliplatin, fluorouracil, and folinic acid in locally advanced or metastatic gastric cancer patients.

PURPOSE: To evaluate the efficacy and safety of an oxaliplatin, fluorouracil (5-FU), and folinic acid (FA) combination in patients with metastatic or advanced gastric cancer (M/AGC). PATIENTS AND METHODS: Of the 54 eligible patients with measurable or assessable M/AGC, 53 received oxaliplatin 100 mg/m(2) and FA 400 mg/m(2) (2-hour intravenous infusion) followed by 5-FU bolus 400 mg/m(2) (10-minute infusion) and then 5-FU 3,000 mg/m(2) (46-hour continuous infusion) every 14 days. RESULTS: Patients (69% male, 31% female) had a median age of 61 years (range, 31 to 75 years), 89% had a performance status of 0 or 1, 70% had newly diagnosed disease, and 87% had metastatic disease. All had histologically confirmed adenocarcinoma. With a median of three involved organs, disease sites included the lymph nodes (67%), stomach (65%), and liver (61%). A median of 10 cycles per patient and 468 complete cycles were administered. Best responses in the 49 assessable patients were two complete responses and 20 partial responses, giving an overall best response rate of 44.9%. Eight patients underwent complementary treatment with curative intent (six with surgery and two with chemoradiotherapy). Median follow-up, time to progression, and overall survival were 18.6 months, 6.2 months, and 8.6 months, respectively. Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and anemia occurred in 38%, 19%, 4%, and 11% of patients, respectively, and febrile neutropenia occurred in six patients (one episode each). Grade 3 peripheral neuropathy occurred in 21% of patients (oxaliplatin-specific scale). Seven patients withdrew because of treatment-related toxicity. CONCLUSION: This oxaliplatin/5-FU/FA regimen shows good efficacy and an acceptable safety profile in M/AGC patients, and may prove to be a suitable alternative regimen in this indication.

Endoscopic ultrasonography immediately prior to laparoscopic cholecystectomy: a prospective evaluation.

BACKGROUND AND STUDY AIMS: In patients who are highly likely to have common bile duct (CBD) stones, it seems necessary to image the biliary tract before laparoscopic cholecystectomy, and endoscopic ultrasonography (EUS) is one way of doing this. The aim of this study was to compare immediate preoperative EUS to intraoperative cholangiography for imaging the CBD and for the diagnosis of CBD stones, in a population with a high risk of choledocholithiasis (as assessed by clinical, biochemical, and ultrasound criteria). PATIENTS AND METHODS: From January 1993 to August 1995, EUS was carried out in the operating room in 50 patients (11 men, 39 women; mean age 57 years) before laparoscopic cholecystectomy for symptomatic choledocholithiasis. A diagnosis of CBD stones by EUS or intraoperative cholangiography was always confirmed by instrumental exploration. An absence of stones in the CBD was established by a negative EUS and intraoperative cholangiography, as well as normal findings at clinical monitoring three months after laparoscopic cholecystectomy. RESULTS: EUS visualized the CBD in 100% of cases. Intraoperative cholangiography was successful in 94% of cases (n = 47 of 50), and after conversion to open laparotomy in eight patients. CBD stones were found in 12 patients (24%). The sensitivity, specificity, and positive and negative predictive values for EUS were 100%, 97%, 92%, and 100%, respectively. CONCLUSIONS: Immediate preoperative EUS may make it possible to select the best form of treatment in patients with CBD stones, avoiding inappropriate laparoscopic instrumental CBD exploration.

[A new hereditary cause of portal vein thrombosis: the abnormal resistance to activated protein C by the Arg 506-->Gln mutation of the gene of factor V]. / Une nouvelle cause héréditaire de thrombose portale: la résistance anormale à la protéine C activée par mutation Arg506-->Gln du gène du facteur V.

We report 2 cases of portal vein thrombosis associated with a single point mutation in the factor V gene that replaces arginine in residue 506 with glutamine. This mutation induces abnormal resistance to anticoagulant activity of activated protein C and increases the risk of deep vein thrombosis. Both patients had a personal and familial history of deep vein thrombosis. Intraabdominal neoplasia or infection, myeloproliferative disorder, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria and coagulation inhibitor deficiency (antithrombin, proteins C and S) were excluded by exhaustive investigation. However, an abnormal resistance to activated protein C was found, and DNA analysis showed the factor V Arg506 to Gln mutation in both cases. Anticoagulant treatment was begun. A study of family history made in one case, showed the same genetic disease in one of the relatives. Resistance to activated protein C with factor V gene mutation should be investigated in patients with portal vein thrombosis. A study of family history, and anticoagulant treatment are justified for symptomatic patients.

Measurement of gastric intramucosal pH in patients with cirrhosis and portal hypertensive gastropathy.

OBJECTIVES: Patients with cirrhosis often have gastric mucosal lesions associated with portal hypertension. Microvascular changes due to portal hypertension may cause mucosal ischaemia. The decrease in intramucosal pH is used as an index of this condition. In this study we compared the gastric intramucosal pH in patients with cirrhosis and portal hypertension and in control group. METHODS: Estimates of pH were calculated using the Henderson-Hasselbalch equation, assuming that measured concentrations of CO2 in the gastric lumen (pCO2) and of HCO3- in arterial blood represented intramucosal CO2 and intramucosal HCO3- concentrations, respectively. Tonometer measurements of intragastric CO2, validated in vitro, were made in patients treated by famotidine (10 mg.h-1 continuous infusion) to suppress gastric acid secretion and minimize CO2 production from luminal gastric bicarbonate. Intramucosal pH was determined in 19 control patients (mean age: 50.2 years) and in 25 patients with cirrhosis and portal hypertensive gastropathy (mean age: 54.2 years). In the patients with cirrhosis the severity of mucosal and parietal abnormalities induced by portal hypertension were graded according to endoscopic score from 0 to 9 and endoscopic ultrasonography score from 0 to 3. RESULTS: The mean endoscopic and ultrasonographic scores were 5.0 and 1.8 respectively. The median gastric intramucosal pH of patients with cirrhosis (7.42; range: 7.36 to 7.53) was similar to that of the controls (7.42; range: 7.33-7.51). A positive correlation was found between intramucosal pH and severity of portal hypertensive gastropathy, in the antrum, but not in the fundus. CONCLUSION: These findings do not support the hypothesis that gastric mucosal lesions are the consequence of ischaemia in patients with cirrhosis.