The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors.

OBJECTIVE: Somatostatin analogs are the first-line drugs for controlling hormone-mediated symptoms of carcinoid tumors. Prospective and retrospective studies have suggested that somatostatin analogs also have antiproliferative activity. The octapeptide lanreotide is available in sustained-release form, obviating the need for daily injections. METHODS: A total of 46 patients were enrolled in this open, prospective, phase II trial. They received lanreotide 30 mg i.m. every 14 days for 6 months when they had symptomatic carcinoid tumors, and lanreotide 30 mg i.m. every 10 days if they had nonsymptomatic tumors. Nonsymptomatic tumors were progressive before the start of the study. Tumor size was assessed every 3 months by means of computed tomography. The assessment was centralized and was made by an external panel. RESULTS: In all, 30 patients had symptomatic neuroendocrine tumors and 16 had asymptomatic neuroendocrine tumors. Five patients in the group with symptomatic tumors and two in the group with nonsymptomatic tumors were considered not to be evaluable. The mean duration of treatment was 12 months in the group with symptomatic tumors and 13 months in the other group. Among the 39 evaluable patients, two objective responses were obtained, giving an objective response rate of 5% (one in the group with symptomatic tumors and one in the other group). Nineteen patients had no significant increase in their tumor size for a mean of 9.5 months. CONCLUSIONS: Lanreotide is safe and well tolerated in patients with carcinoid tumors. It seems to have both symptomatic and antitumoral effects in this setting.

Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients.

BACKGROUND: Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome. The octapeptide lanreotide is available in slow release form, which could eliminate the necessity of twice a day injections as with octreotide. PATIENTS AND METHODS: 39 patients with carcinoid syndrome were included in a prospective multicentre study. Patients received lanreotide 30 mg intramuscularly every 14 days for six months. The number and intensity of flushing episodes and bowel movements, urinary 5 hydroxy-indolacetic acid (5 HIAA) concentrations, and variations of tumour mass were recorded. RESULTS: After one month of treatment, flushing episodes (median (range)) decreased significantly (3 (0.3-24) episodes per day v 1 (0-15), p = 0.04) and completely resolved in 39% of the patients. A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea. Urinary 5 HIAA concentrations were unchanged in 57% of the patients and decreased in 18%. After six months of treatment, the actuarial proportions of patients with at least a 50% decrease in the number of flushing episodes and bowel movements were 54% and 56%, respectively. Forty two per cent of the patients who were treated for six months had at least a 50% reduction in 5 HIAA values. No clear signs of regression of tumours were seen in any of the patients. Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25% of the patients. Biliary lithiasis appeared in two patients after six months of lanreotide. CONCLUSION: Lanreotide, 30 mg intramuscularly every other week, is an effective and convenient treatment in patients with the carcinoid syndrome.

Neurotensin and oxyntomodulin-(30-37) potentiate PYY regulation of gastric acid and somatostatin secretions.

The present study was designed to investigate, in cats provided with both a gastric fistula and a denervated fundic Heidenhain pouch, the effect of peptide YY (PYY) on pentagastrin-stimulated gastric acid and somatostatin secretions and to determine whether neurotensin (NT) and the COOH-terminal octapeptide of oxyntomodulin [Oxm-(30-37)] would modify these secretions. Intravenous infusion of PYY (0.1 nmol.kg-1.h-1), NT (15 nmol.kg-1.h-1), or Oxm-(30-37) (60 nmol.kg-1.h-1) did not affect basal acid secretion. However, they significantly inhibited pentagastrin-stimulated gastric acid output up to 50% (P < 0.01) in the main stomach. Furthermore, they significantly increased gastric somatostatin release by +750, +1,700, and +600% over basal level (P < 0.01) for (in nmol.kg-1.h-1) 0.1 PYY, 15 NT, and 60 Oxm-(30-37), respectively. On the other hand, the effects of 0.1 nmol.kg-1.h-1 PYY were potentiated by subthreshold doses of NT (5 nmol.kg-1.h-1) or Oxm-(30-37) (15 nmol.kg-1.h-1). These findings suggest that there could be a cooperation between the three peptides in the intestinal regulation of gastric secretions.

Effects of colonic fermentation on respiratory gas exchanges following a glucose load in man.

Colonic fermentation produces short-chain fatty acids (SCFA). In humans, the amount of energy produced from the oxidation of these compounds is unknown and could modify the metabolic utilization of energetic fuels (eg, carbohydrates and lipids). If it were so, the equations used to evaluate the oxidation of nutrients from indirect calorimetry data should include the contribution of SCFA, which is not usually the case. Indeed, this fermentation process is usually considered as a minor and neglected energetic pathway. In this study, we have addressed the reliability of this assumption. Six normal subjects received orally either 50 g glucose or 50 g glucose plus 20 g lactulose. Their respiratory gas exchanges, breath hydrogen, methane, and 13CO2 concentrations, and plasma glucose, insulin, and free fatty acid (FFA) concentrations were monitored for 8 hours. CO2 production and breath hydrogen concentration were significantly greater with lactulose. No differences in oxygen consumption, breath 13CO2 production, or plasma concentrations of blood glucose, FFA, and insulin could be found between the two experiments. This suggests that the fermentation process induced by lactulose generates extra fuels going through an oxidation pathway. Therefore, the classic equations used to calculate carbohydrate and lipid oxidation and energy expenditure (EE) from indirect calorimetry data are probably not valid when fermentation is taking place. Indeed, in this experiment we could have overestimated glucose oxidation (12.5%) if the fermentation process were not considered. In conclusion, colonic fermentation in humans of nondigestible carbohydrates produces energetic substrates that could be used and oxidized as energetic fuels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Barret's esophagus and acid gastroesophageal reflux. Two-channel pH-metric measurements and manometric study]. / Endobrachyoesophage et reflux gastro-oesophagien acide. Enregistrements pH-métriques étagés et étude manométrique.

Although the pathogenic role of gastroesophageal reflux in Barrett's esophagus (BE) is now widely accepted, the pattern of pH profile in the esophagus of patients with BE is not well documented. The aim of this study was to assess the severity and "extent" of acid exposure in patients with BE using an automated single or two-channel 24-hour pH monitoring system. Eighteen patients with histologically proven BE were compared with 3 other groups: a) 100 patients with clinical symptoms and pHmetrically proven acid reflux divided in 2 sub-groups: 38 patients without esophagitis at endoscopy, and 62 patients with esophagitis (Savary-Miller classification; grade I: n = 24, grade II: n = 27, grade III: n = 8, grade IV: n = 3) and b) 9 healthy volunteers. In 17 patients with BE, and in 14 patients with reflux and healthy volunteers, 2 electrodes were placed 5 (electrode E1) and 10 cm (electrode E2) above the lower esophageal sphincter. In the other patients, pH was monitored using a single pH electrode (E1) only. The mucosal acid exposure at E1 (percentage of time below pH 4 on total period, day and night), the number of reflux episodes longer than 5 min were significantly higher in the BE group when compared with the other groups. The number of patients with abnormal acid exposure at E2 was significantly higher (P less than 0.01) in the BE group (15/17 cases) than in the reflux group (5/14 cases). The mean duration of acid reflux was significantly longer in BE than in other groups at both recording sites.(ABSTRACT TRUNCATED AT 250 WORDS)

["Cholethorax" revealing injury to the common bile duct after celioscopic cholecystectomy]. / "Choléthorax" révélateur d'une plaie de la voie biliaire principale après cholécystectomie per-coelioscopique.

The case-report describes the unusual formation of a bilious pleural effusion or "cholethorax" revealing a common bile duct injury secondary to laparoscopic cholecystectomy. Pleural drainage led to a diagnostic ERCP. Subsequently a Roux en Y hepatico-jejunostomy allowed a satisfactory outcome.

Human intestine epithelial cell acetyl- and butyrylcholinesterase.

The epithelial cells of the human intestine exhibit a cholinesterase activity which is restricted to the apex of the villi. This activity displays a maximum in the colon and a minimum in the jejunum. Contrary to most of the studied vertebrates, the human cells present both acetylcholinesterase and butyrylcholinesterase activities, acetylcholinesterase being predominant in all the intestinal segments: duodenum, jejunum, ileum and colon. Like in the other vertebrates, only globular forms are identified by sucrose gradient centrifugation. However, the simultaneous presence, on the one hand of three globular forms (G1, G2 and G4) and, on the other hand of soluble as well as detergent-soluble molecular species seems to be a particular feature of the human cells.

[Perineal clamping of the everted rectum in conservative coloproctectomy. Experimental and clinical results]. / L'agrafage périnéal du rectum éversé dans la coloproctectomie conservatrice. Résultats expérimentaux et cliniques.

Technical alternatives in conservative proctocolectomy are presently investigated to improve the safety and the functional results of the operation. Abdominal transection of the rectum is not always satisfactory in this procedure. A new technique of stapled anastomosis is described: after full mobilization and eversion of the rectum, this latter is closed using a linear stapler and cut immediately above the anal canal via a perineal access; a 18 cm long J pouch is constructed and the anastomosis is stapled using the new premier EEA instrument through the staple line of the previously transected anorectal junction. This technique has been evaluated in dogs (N = 10): colo-anal anastomosis was easy, quick, and safe to perform. Clinical, radiological and gross results have confirmed the quality of these circular stapled anastomoses through an inverting linear suture of the anorectal junction. Clinical experience is actually based on 7 patients operated since January 1989 (proctocolitis: 3, polyposis: 4). The value of the technique was confirmed with ileostomy closure at 3 months for the 7 patients and good functional results. This method has several advantages: 1) to retain all of the anal canal, 2) to avoid prolonged anal dilatation, 3) to perform a rapid and safe stapled anastomosis.

[Pseudo-angina pain of esophageal origin. Results of functional study and value of the balloon distention test]. / Douleurs pseudo-angineuses d'origine oesophagienne. Résultats de l'exploration fonctionnelle et intérêt du test de distension mécanique par ballonnet.

In patients with angina-like chest pain, the diagnostic value of esophageal investigations has not been definitively established. The aim of this study was to assess the diagnostic value of different esophageal investigations in 45 patients (group I) with angina-like chest pain for which a cardiac origin had been previously excluded. These investigations included esophageal manometry, Bernstein test, edrophonium test, balloon distention test, and 24-hour pH monitoring (with event marker). These patients were compared to two control groups: a) 9 subjects with documented coronary disease (group IIa), and b) 9 healthy volunteers (group IIb). Abnormal results were observed in 37 patients in group I (82 percent), and in 4 patients in group IIa (44 percent). In group I, manometry was abnormal in 29 percent of patients and pH monitoring in 41 percent; provocative tests were positive in 10 percent, 15 percent, and 38 percent for the Bernstein test, edrophonium test, and balloon distention test respectively. Esophageal origin of the pain was shown to be likely in 36 percent of patients in group I. These results confirm the high incidence of functional abnormalities of esophagus in patients with angina-like chest pain. They also confirm the diagnostic value of the different provocative tests and especially the balloon distention test.

[Therapeutic problems caused by rupture of large hepatic adenoma with central location. Apropos of 3 cases]. / Problèmes thérapeutiques liés aux ruptures de volumineux adénomes hépatiques de siège central. A propos de 3 observations.

We report three cases of young female patients (26, 30, 36 years) with intraperitoneal hemorrhage associated with a rupture of a liver cell adenoma. Their topography was central or with central extension. Three patients had taken oral contraceptives, for a period of 10 years, before diagnosis in two cases and for only three weeks in the remaining patient. The diagnosis of hemoperitoneum from a liver tumor was established on initial symptoms and ultra sonographic examination. Angiography and CT were the most valuable investigations. The control of hemorrhage was obtained by hepatic artery ligation (2 cases) and angiographic embolization (1 case). We observed one patient with liver adenomatosis, uncommon lesion consisting of numerous adenomas in an otherwise normal hepatic parenchyma. In emergency major hepatic resection for an adenoma, in central localization, is too a high risk procedure for a benign tumor. Control of hemorrhage should be the aim of treatment, best achieved by alternative treatment, such as hepatic artery ligation of angiographic embolization, highly effective in our experience. Resection may be delayed for a residual tumor.

[Conservative coloproctectomy: the advantages of a circular trans-suture staple anastomosis after linear stapling of the everted rectum. Preliminary results]. / Coloproctectomie conservatrice: avantages d'une anastomose circulaire agrafée trans-suturaire, après agrafage linéaire du rectum retourné. Résultats préliminaires.

Technical alternatives in conservative proctocolectomy are presently investigated to improve the functional results of the operation. To avoid 2 difficult steps in the procedure, mucosectomy and transanal manual suturing, is of interest to retain the entire and canal and to reduce anal stretching duration. A new technique of stapled anastomosis is described: after full mobilization and eversion of the rectum, this latter is closed using a linear stapler and cut immediately above the anal canal; a 18 cm long J pouch is constructed and the anastomosis is stapled using the new premium EEA instrument*. Clinical experience begun in 1989 january, concerns 6 patients (2 U.C., 4 polyposis): at this time, 5 of these had their ileostomy closed, functional results being under evaluation. This method allows 1) to retain all the anal canal, 2) to avoid prolonged anal dilatation, 3) to perform a rapid and safe stapled anastomosis.

Photochemotherapy mediated by hematoporphyrin derivative in gastroenterology.

While results concerning photodynamic treatments of cancers in pneumology or dermatology have been published regularly, few works have been devoted to gastroenterology. Twenty-seven non-operable patients bearing various G.I. tumors of less than 40 mm dia. have been treated by PDT for palliative purpose to appreciate the local efficacy of a single treatment. Before July, 1985, the parameters of treatment were 2.5 mg/kg of HPD injected intravenously for theoretical power of delivered laser light (630 mm) 300 mW. After July, 1985, HPD was injected at the dose of 5 mg/kg and the laser dose was 400 mW. A normalization of grip biopsies was observed on 12 patients (6 squamous cell carcinomas, 6 adenocarcinomas), transient in 3 cases. Our main finding is that PDT seems able to destroy significant volumes of tumor by itself although subsequent biopsies proved negative in very few cases. This method remains to be compared to others less sophisticated than the YAG laser.

[Hormone immunocytochemical studies of 46 endocrine tumors of the pancreas in 24 patients]. / Etudes immunocytochimiques hormonales de quarante-six tumeurs endocrines du pancréas chez 24 malades.

The aim of this retrospective study was to correlate the results of hormonal immunocytochemistry of 46 endocrine tumors to the corresponding clinical syndromes in 24 patients. They were divided as following: 14 cases of insulinoma, 3 cases of Zollinger-Ellison syndrome, 1 case of glucagonoma, 1 case of carcinoid syndrome and 5 cases without any obvious endocrine manifestations. Each tumor was tested with anti-insulin, anti-glucagon, anti-pancreatic polypeptide, anti-vasoactive intestinal peptide, anti-gastrin immune sera according to the peroxidase-antiperoxidase method. The presence of insulin was proved in 13 of 14 cases of insulinomas and the presence of gastrin in 2 of 3 cases of Zollinger-Ellison syndrome. Among the 5 asymptomatic cases, a somatostatinoma and a vipoma were individualized. More than 50 p. 100 of the tumors showed plurihormonal secretion with one predominantly secreted hormone responsible for the clinical syndrome. This study demonstrated the diversity of the hormonal secretion by some tumors and their metastasis in the same patient. Malignant insulinomas correspond either to poorly secreting tumors or to plurihormonal tumors secreting gastrin and glucagon as well.

[Ogilvie's syndrome: results of endoscopic exsufflation in a series of 29 cases]. / Syndrome d'Ogilvie: résultats de l'exsufflation endoscopique dans une série de 29 cas.

The aim of this study was to assess the value of endoscopic decompression of the colon in a series of 29 patients affected with Ogilvie's syndrome. During the first period (1980-1982), 14 patients were treated by colonoscopic decompression alone. During the second period (1982-1985), 15 endoscopic decompressions were systematically completed by intubation of the colon. The tube was removed after 2 to 13 days. Whatever the procedure, endoscopic decompression was successfully achieved in all cases. The death rate (8/29) and number of cecostomies (2/29) were similar in the two groups of patients. Only one death was directly related to Ogilvie's syndrome itself, whereas 7 patients died from other severe underlying diseases. However, colonic dilatation recurred in 6 patients in the first group and in one patient in the second group (p less than 0.05). No complications due to the endoscopic procedures occurred in this series. It may be concluded that endoscopic treatment of Ogilvie's syndrome is a safe and effective procedure. Our results also suggest that colonoscopic intubation should be used prophylactically in order to avoid recurrences, frequently observed after simple endoscopic decompression.

[The role of the argon laser in the treatment of condylomata acuminata of the anal margin and canal]. / Place du laser argon dans le traitement des condylomes acuminés de la marge et du canal anal.

Condyloma acuminata of the anal margin or anal canal raise therapeutic problems as soon as they become important. In this study, we report the results obtained by 24 patients after Argon-ion laser therapy. This laser, the beam of which is mainly absorbed by haemoglobin allowed us to cure 91,7 percent of our patients. This results was obtained in one (14 patients) or two sessions (10 patients) with at least 3 months as follow-up. Furthermore we can notice the excellent quality of cicatrization and the complete lack of incidents during or after the treatment. So argon laser could be a new kind of treatment used preferentially in extensive genital warts.