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.

Relationships between transit time in man and in vitro fermentation of dietary fiber by fecal bacteria.

OBJECTIVE: To assess the effects of drug-induced changes in mean transit time (MTT) on the activity of human fecal flora in vitro. METHODS: The activity of fecal flora was estimated by the ability of a fecal inoculum to ferment a substrate (beet fiber) in vitro in a batch system for 24 h. The inoculum was collected from 8 healthy volunteers studied during three 3-week randomized periods, who received a controlled diet alone (control period) or the same diet with either cisapride or loperamide. Cisapride and loperamide were adjusted in order to halve and double MTT measured during the control period. At the end of each period, the percentage disappearance of the initial added substrate and the concentration and the profile of short-chain fatty acids (SCFAs), were determined. RESULTS: In the control period, the pH of the inoculum and SCFA concentration were inversely related to MTT (P=0.0001). Individual SCFA production was also significantly related to MTT (P<0.01). Cisapride-reduced transit time was associated with a significant rise in the concentrations of total SCFAs (P<0.05), propionic and butyric acids (P<0.05) and the percentage substrate disappearance (P<0.05). Inverse relations were observed during the loperamide period. Moreover, MTT was inversely related to the percentage substrate disappearance (P<0.001), SCFA production (P<0.001) and butyrate production (P<0.0005). CONCLUSION: Changes in MTT alter bacterial activity and modify the bacterial pathways affecting the proportion of individual SCFAs. European Journal of Clinical Nutrition (2000) 54, 603-609

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.

Relations between transit time, fermentation products, and hydrogen consuming flora in healthy humans.

BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases.

[Primary sclerosing cholangitis and systemic lupus erythematosus]. / Cholangite sclérosante primitive et lupus érythémateux systémique.

We report the association of primary sclerosing cholangitis and systemic lupus erythematosus in a 39 year-old man. Six months after a diagnosis of primary sclerosing cholangitis was established, the patient was hospitalized for a pleural effusion and acute pericarditis. Emergency pericardiocentesis, was required due to sudden cardiac tamponnade. Plasmatic anti-DNA and anti-nuclear antibodies were present. Treatment by steroids greatly improved symptoms. This clinical association suggests that some immune disorders may be common to the two diseases.

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)

Effects of high glucose concentration on survival and respiration of human endothelial cells.

To determine whether or not endothelial cell survival was decreased after incubation with high glucose concentrations in culture media, we studied the influence of D-glucose or L-glucose (a non-metabolizable stereoisomer of D-glucose) on cell survival using the trypan-blue exclusion test. Simultaneously, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assay was used to measure both the mitochondrial respiratory chain activity and cell viability. Respiratory chain activity per cell increased when D-glucose concentrations rose but at the same time trypan-blue excluded cells were decreased. Comparison with data in the literature showed that the MTT assay was not reliable for studies involving endothelial cell survival when glucose reduction was affected on these cells. It seems important to check MTT assay reliability carefully when it is used for drugs affecting glucose metabolism, or with other cell types.

[Reproducibility of orocecal transit time and hydrogen production measured by breath tests]. / Reproductibilité du temps de transit oro-caecal et de la production d'hydrogène mesurés par les tests respiratoires.

The hydrogen breath test after a lactulose oral load in the fasting period is currently used to measure mouth to cecum transit time (MCTT). However, the reproducibility of this test is poor, and normal values are very scattered. The aim of the study was to determine the reproducibility of hydrogen breath test for MCTT measurement and hydrogen production after administration of 2 disaccharides: lactulose and lactitol ingested in the fasting state and postprandial period. Twelve healthy volunteers (6 men and 6 women; mean age = 34.6 +/- 9.6 years) were studied eight times in a random order, each disaccharide being studied twice in the fasting state and twice in the postprandial period. In the later, lactulose or lactitol was ingested 30 min after a liquid meal completely absorbed (400 kcal; glucide: 55 p. 100, lipid: 30 p. 100, protein: 15 p. 100; 400 ml of Inkopeptide). The MCTT was significantly increased with both disaccharides in the postprandial period as compared with the fasting state (P less than 0.0001). There was nos significant correlation between the 2 measurements of the MCTT in the fasting state, in contrast, the 2 measurements of the MCTT were closely related in the fed state (r = 0.62, P less than 0.05, et r = 0.79, P less than 0.003 for lactulose and lactitol respectively). During both periods no significant difference was found in the MCTT between lactulose and lactitol. As well, hydrogen production did not differ between the 2 disaccharides, but was significantly increased in the postprandial period, and in non methane producers.(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.

Comparative continuous-indirect-calorimetry study of two carbohydrates with different glycemic indices.

Six healthy young men were studied by indirect calorimetry for 6 h after eating a meal composed of glucose or manioc starch (equivalent to 50 g dextrose). Blood was drawn every 30 min for 6 h to measure plasma glucose, free fatty acid (FFA), and insulin concentrations. The glycemic index of the starch was 57%. Plasma insulin and glucose concentrations were significantly higher from 150 to 210 min and FFA concentrations remained significantly lower from 210 to 360 min after starch than after glucose. Carbohydrate oxidation rose from a similar initial concentration for glucose and starch, to a constant concentration until 200 min before becoming significantly higher for the starch load until the end of the test. Total glucose oxidation was significantly higher with starch. Total fat oxidation did not differ after the two loads. A negative correlation was found between glucose oxidation and plasma FFA concentrations. Use of low-glycemic-index carbohydrates increases carbohydrate oxidation because of lower plasma FFA concentrations and fat oxidation.

[Measurement of gastric emptying, intestinal transit time and colonic filling by scintiscan in healthy subjects]. / Mesure de la vidange gastrique, du temps de transit intestinal et du remplissage colique par scintigraphie chez le sujet sain.

A scintigraphic technique allowing combined measurements of gastric emptying, small intestinal transit time and colonic filling was developed and its reproducibility assessed in 8 healthy volunteers. Each subject underwent four tests: a) two were performed in the fasting state (99mTc labelled water, added to lactulose), b) two in the postprandial state (balanced meal, 1,750 kJ, included pellets labelled with 111In, the gut transit of which being nearly the same as dietary fibers). Intestinal transit was modeled using linear operators (expressed as a convolution product). In fasting state (lactulose), orocecal transit time of water was 109 +/- 60 min and 89 +/- 36 min (m +/- DS) for the first and second tests, respectively. In the postprandial state, values were 297 +/- 37 min and 293 +/- 43 min respectively for the pellets. Small bowel transit times were 135 +/- 70 and 103 +/- 40 min respectively in fasting state for water, and 209 +/- 47 and 209 +/- 29 min respectively in postprandial state for the pellets. Determination of residual variance showed that reproducibility of the test was better in the postprandial state than in the fasting state. Water orocecal transit times measured using this technique and lactulose orocecal transit time measured using hydrogen breath test were strongly correlated (r = 0.98, n = 12, P less than 0.01). This isotopic method provides a reproducible assessment of gastric emptying, small bowel transit, and colonic filling and could represent a reliable and non invasive tool for further physiological and pharmacological studies.

[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.

[Lactase deficiency and lactose intolerance-related symptoms in adult healthy subjects from western France]. / Déficit en lactase et symptômes d'intolérance au lactose dans une population adulte saine originaire de l'ouest de la France.

The prevalence of lactase deficiency (LD) and lactose intolerance is not well known in France. Using breath hydrogen and methane analysis after 50 g oral lactose load, we investigated the prevalences of LD, lactose intolerance, and methane producer status in 102 healthy adults born in western France, and we examined the relationships between these parameters and the daily milk consumption. In 10 subjects with LD and lactose intolerance, we studied the reproducibility of the lactose hydrogen breath test results for the diagnosis of LD and lactose intolerance and estimated the quantity of lactose malabsorbed in comparison with the lactulose hydrogen breath test. The prevalence of LD was 23.4 percent and symptoms of lactose intolerance were observed in 50 percent of the 24 subjects with LD. The daily milk consumption was not significantly different in the 24 subjects with LD and in the 78 subjects without LD (281 +/- 197 vs 303 +/- 217 ml/24 h). The prevalence of methane producer status was 42.1 percent. The symptomatic group of lactose malabsorbers (n = 12) was characterized by a shorter lactose mouth to caecum transit time (39 +/- 20 vs 88 +/- 48 min; P less than 0.05), and more marked hydrogen production (6.1 +/- 2.3 vs 3.4 +/- 2.4 10(3) ppm.min; P less than 0.04). In the 10 subjects with LD and lactose intolerance, the hydrogen breath test was reproducible for diagnosis of LD and lactose intolerance, and for hydrogen production. The quantity of lactose malabsorbed was 60 percent. In France, symptoms of lactose intolerance are not severe and do not affect the daily consumption of milk and dairy products.

[Intestinal obstruction and pregnancy. Diagnostic and therapeutic approach. Apropos of 3 cases]. / Occlusion intestinale et grossesse. Démarche diagnostique et thérapeutique. A propos de 3 cas.

The etiological diagnosis of obstruction is difficult during pregnancy. The authors report 3 cases of this rare association: obstruction due to adhesions [1], volvulus of the transverse colon on a common mesentery [1] and obstruction due to an appendix abscess [1]. Complementary investigations, obviously limited under these circumstances, were based on plain abdominal X-rays, repeated if necessary. The diagnosis must be made early and appropriate treatment given in order to ensure a good materno-fetal prognosis as was obtained in these 3 cases.