[Dose-response effect of lansoprazole in patients with Zollinger-Ellison syndrome]. / Effet dose-réponse du lansoprazole chez des malades atteints d'un syndrome de Zollinger-Ellison.

Lansoprazole, a new substituted benzimidazole, is an effective acid proton pump inhibitor acting by inhibiting selectively H+/K+ ATPase of the gastric parietal cell. This study was performed to assess the effect of successive 30, 60, 90 and 120 mg dosages of lansoprazole in 4 patients suffering from Zollinger-Ellison syndrome. The basal gastric acid output was markedly inhibited in comparison with baseline values (mean maximal reduction: 87%; extremes: 75-99%) and was dose-related. Lansoprazole inhibited pepsin output globally with a dose range effect between 30 and 90 mg/day. The treatment induced a rapid relief of clinical symptoms. No biological abnormality was noted. These data proved that lansoprazole is efficient for treating gastric acid hypersecretion in patients suffering from ZES.

Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation.

Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients.

BACKGROUND: Liver metastases of endocrine tumors are of major prognostic significance. The various therapeutic approaches have given disappointing results; however, locoregional treatment has allowed transient control of hepatic tumor growth. METHODS: Twenty-four patients with liver metastases of endocrine tumors (mainly carcinoid tumors [n = 18] and gastrinomas [n = 5]) were included in a Phase II study of hepatic arterial chemoembolization (CE). Metastases were bilateral in all patients and invaded more than 50% of the liver in 12. They were synchronous of the primary tumor in 62.5% of the patients. Seventeen patients had not responded to previous intravenous chemotherapy. CE courses were performed every 3 months using an emulsion of 10 ml of iodized oil and doxorubicin 50 mg/m2 injected into tumor vessels, followed by CE arterial occlusion with gelatin sponge particles. Seventy-one CE courses were performed in 23 patients; there was one technical failure. RESULTS: Among patients with carcinoid tumors, disappearance of diarrhea and/or flushing was observed in 8 of 11. Serotonin and/or its metabolite 5-hydroxyindoleacetic acid levels decreased by more than 50% in 57% of the patients. The size of liver metastases decreased by at least 50% in 6 of 18 patients, i.e., in 33% (range, 12-54%). Two had complete responses. The median duration of the responses was 14 months (range, 6-40). Among patients with noncarcinoid tumors, minor response or stabilization occurred in three of five patients. Major side effects were bleeding peptic ulcer (one patient) and oligoanuric renal failure (one patient). Abdominal pain, fever, and increases in hepatic enzyme levels were common and transient. CONCLUSIONS: These results suggest that CE is effective in patients with liver metastases of endocrine tumors, mainly in carcinoids. In the latter, CE allows control of the carcinoid syndrome and regression or stabilization of the liver tumors in 80% of patients.

Raised concentrations of platelet activating factor in colonic mucosa of Crohn's disease patients.

Platelet activating factor (PAF-ACETHER or PAF) and precursors of platelet activating factor were investigated in 26 patients with acute Crohn's disease and in 10 healthy controls. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine, were determined in colonic mucosal biopsies in patients with acute Crohn's disease, during prednisolone therapy, and in remission. Biopsy specimens were submitted to histopathology examination and to phospholipid extraction. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute Crohn's disease and in remission as well as in controls. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher (p < 0.01) in Crohn's disease than in controls. There was no correlation between the level of colonic PAF-ACETHER and age, sex, Crohn's disease activity index, and biological parameters in sera. Although concentrations of colonic platelet activating factor content were higher (p < 0.01) when colonic mucosa displayed cell infiltration, they were neither related to the severity nor the type of inflammatory cells. Platelet activating factor decreases with prednisolone therapy and might return to normal concentrations in quiescent patients. Lyso platelet activating factor and alkyl acyl glycerophosphocholine were not significantly higher in Crohn's disease than in controls. These data suggest that platelet activating factor may be involved in the pathogenesis of Crohn's disease and that it could be used as a marker of the mucosal activity of the disease.

[Intravenous chemotherapy with streptozotocin and 5 fluorouracil for hepatic metastases of Zollinger-Ellison syndrome. A prospective multicenter study in 21 patients]. / Chimiothérapie intraveineuse par streptozotocine et 5 fluoro-uracile des métastases hépatiques du syndrome de Zollinger-Ellison. Etude prospective multicentrique chez 21 patients.

Twenty-one patients with liver metastasis of gastrinoma received intravenous streptozotocin (STZ: 500 mg/sqm.day) and 5 fluorouracil (5 FU: 400 mg/sqm.day) during 5 consecutive days every 6 weeks. Variations in tumor mass (TM) on CT scan and in serum gastrin levels were assessed every two courses. Treatment was continued if TM decreased or remained unchanged, and if severe renal toxicity of STZ was not observed. Three patients had a minor (25-50 percent decrease in TM) and transient response. Only one patient (5 percent) presented an objective response (greater than 50 percent) which lasted 55 months. TM remained unchanged in 28 percent and increased in 65 percent of cases. Changes in serum gastrin levels did not parallel those of TM. Nausea and/or vomiting (66 percent) was easily controlled by symptomatic treatment. Renal toxicity (24 percent), including one case of acute and transient renal failure due to accidental overdosing, was observed in 24 percent of cases. This prospective study does not confirm the efficacy of combined STZ-5 FU as previously suggested by retrospective data.

[Familial forms of endocrine tumors of the pancreas. Apropos of 4 cases in the same family]. / Formes familiales de tumeurs endocrines du pancréas. A propos de 4 observations dans une même famille.

Four cases of endocrine tumors of the pancreas and, more generally, of the diffuse endocrine system, are presented here. Included are all the data relative to the inherited character of the disease covering two generations. Two brothers had Zollinger-Ellison syndrome--one of them probably, the other one proven (first case recorded in France). Both patient's only sons are currently treated for endocrine tumor of the pancreas and Zollinger-Ellison syndrome, respectively.