Hierarchical contribution of individual lifestyle factors and their interactions on adenomatous and serrated polyp risk.

BACKGROUND: Individual colorectal polyp risk factors are well characterized; however, insights into their pathway-specific interactions are scarce. We aimed to identify the impact of individual risk factors and their joint effects on adenomatous (AP) and serrated polyp (SP) risk. METHODS: We collected information on 363 lifestyle and metabolic parameters from 1597 colonoscopy participants, resulting in over 521,000 data points. We used multivariate statistics and machine-learning approaches to assess associations of single variables and their interactions with AP and SP risk. RESULTS: Individual factors and their interactions showed common and polyp subtype-specific effects. Abdominal obesity, high body mass index (BMI), metabolic syndrome, and red meat consumption globally increased polyp risk. Age, gender, and western diet associated with AP risk, while smoking was associated with SP risk. CRC family history was associated with advanced adenomas and diabetes with sessile serrated lesions. Regarding lifestyle factor interactions, no lifestyle or dietary adjustments mitigated the adverse smoking effect on SP risk, whereas its negative effect was exacerbated by alcohol in the conventional pathway. The adverse effect of red meat on SP risk was not ameliorated by any factor, but was further exacerbated by western diet along the conventional pathway. No modification of any factor reduced the negative impact of metabolic syndrome on AP risk, whereas increased fatless fish or meat substitutes' intake mitigated its effect on SP risk. CONCLUSIONS: Individual risk factors and their interactions for polyp formation along the adenomatous and serrated pathways are strongly heterogeneous. Our findings may facilitate tailored lifestyle recommendations and contribute to a better understanding of how risk factor combinations impact colorectal carcinogenesis.

Prospective clinical cohort study: low incidence of Barrett esophagus but high rate of reflux disease at 5-year follow-up after sleeve gastrectomy versus Roux-en-Y gastric bypass.

BACKGROUND: Gastroesophageal reflux disease seems more frequent after laparoscopic sleeve gastrectomy (LSG) than Roux-en-Y gastric bypass (LRYGB). Retrospective case series have raised concerns about a high incidence of Barrett esophagus (BE) after LSG. OBJECTIVE: This prospective clinical cohort study compared the incidence of BE ≥5 years after LSG and LRYGB. SETTING: St. Clara Hospital, Basel, and University Hospital, Zürich, Switzerland. METHODS: Patients were recruited from 2 bariatric centers where preoperative gastroscopy is standard practice and LRYGB is preferred for patients with preexisting gastroesophageal reflux disease. At follow-up ≥5 years after surgery, patients underwent gastroscopy with quadrantic biopsies from the squamocolumnar junction and metaplastic segment. Symptoms were assessed using validated questionnaires. Wireless pH measurement assessed esophageal acid exposure. RESULTS: A total of 169 patients were included, with a median 7.0 ± 1.5 years after surgery. In the LSG group (n = 83), 3 patients had endoscopically and histologically confirmed de novo BE; in the LRYGB group (n = 86), there were 2 patients with BE, 1 de novo and 1 preexisting (de novo BE, 3.6% versus 1.2%; P = .362). At follow-up, reflux symptoms were reported more frequently by the LSG group than by the LRYGB group (51.9% versus 10.5%). Similarly, moderate-to-severe reflux esophagitis (Los Angeles grade B-D) was more common (27.7% versus 5.8%) despite greater use of proton pump inhibitors (49.4% versus 19.7%), and pathologic acid exposure was more frequent in patients who underwent LSG than in patients who underwent LRYGB. CONCLUSIONS: After at least 5 years of follow-up, a higher incidence of reflux symptoms, reflux esophagitis, and pathologic esophageal acid exposure was found in patients who underwent LSG compared with patients who underwent LRYGB. However, the incidence of BE after LSG was low and not significantly different between the 2 groups.

Early gastrogastric fistula after Roux-en-Y gastric bypass: successful fistula treatment with self-expandable endoscopic stent.

A 25-year-old patient underwent laparoscopic Roux-en-Y gastric bypass surgery with an initially uneventful postoperative course. Two weeks postoperatively, the patient presented with acute abdominal pain. CT scan revealed a gastrogastric fistula from the gastric pouch to the gastric remnant. Laparoscopic drainage was performed, and intraoperative endoscopy confirmed a large gastrogastric fistula. Due to intense adhesions between pouch and remnant, a closure by suture of the fistula was not possible. The fistula was initially treated with a fully covered metal stent. After multiple stent migrations despite clip attachment to the mucosa, the stent was changed to a partially covered metal stent. Fistula healing progress was documented every 2 weeks. After 10 weeks of stent treatment, fistula closure was accomplished.In conclusion, early fistula from the gastric pouch to the gastric remnant is a rare complication and can be managed with endoscopic stent placement.

Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals.

Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na+/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.

Determinants of fecal continence in healthy, continent subjects: a comprehensive analysis by anal manometry, rectal barostat and a stool substitute retention test.

BACKGROUND/AIMS: This study aimed to identify anal sphincter and rectal factors that determine anorectal filling sensations and continence during rectal filling in health. METHODS: Measurements of anorectal physiology were collected from 42 continent healthy subjects participating in a prospective trial. Rectal function and capacity were assessed by barostat. Anal sphincter functions were assessed by manometry. A validated stool substitute retention test was performed in which a viscous suspension was infused into the rectum at 60 ml/min to 1,500 ml. Multivariate regression was applied to identify physiologic factors that determine anorectal sensation and continence during rectal filling. RESULTS: The volume at which first awareness of rectal filling occurred associated with age (p < 0.03), rectal capacity (p < 0.06) and anal resting pressure (p < 0.003); urgency associated with rectal capacity (p < 0.0007), anal resting (p < 0.04) and squeeze pressure (p < 0.02); volume at first incontinence with rectal capacity (p < 0.0001) and squeeze pressure (p < 0.04) and the maximum volume retained were closely correlated with rectal capacity only (p < 0.0001). CONCLUSION: Anorectal filling sensations and continence in health require a rectal reservoir of adequate capacity and effective voluntary anal sphincter function. Complementary associations between continence, motor and sensory function indicate the presence of an adaptive mechanism that enables timely, appropriate responses to events that threaten fecal continence.

Effect of a prebiotic mixture on intestinal comfort and general wellbeing in health.

Specific carbohydrates, i.e. prebiotics such as fructo-oligosaccharide (FOS), are not digested in the small intestine but fermented in the colon. Besides beneficial health effects of an enhanced bifidobacteria population, intestinal gas production resulting from fermentation can induce abdominal symptoms. Partial replacement with slowly fermented acacia gum may attenuate side effects. The aim was to compare the effects of FOS with those of a prebiotic mixture (50 % FOS and 50 % acacia gum; BLEND) and a rapidly absorbed carbohydrate (maltodextrin) on general intestinal wellbeing, abdominal comfort and anorectal sensory function. Twenty volunteers (eight male and twelve female; age 20-37 years) completed this double-blind, randomised study with two cycles of a 2-week run-in phase (10 g maltodextrin) followed by 5 weeks of 10 g FOS or BLEND once daily, separated by a 4-week wash-out interval. Abdominal symptoms and general wellbeing were documented by telephone interview or Internet twice weekly. Rectal sensations were assessed by a visual analogue scale during a rectal barostat test after FOS and BLEND treatment. Both FOS and BLEND induced more side effects than maltodextrin. Belching was more pronounced under FOS compared with BLEND (P = 0.09 for females; P = 0.01 for males), and for self-reported general wellbeing strong sex differences were reported (P = 0.002). Urgency scores during rectal barostat were higher with FOS than BLEND (P = 0.01). Faced with a growing range of supplemented food products, consumers may benefit from prebiotic mixtures which cause fewer abdominal side effects. Sex differences must be taken in consideration when food supplements are used.

The effect of macronutrients on gastric volume responses and gastric emptying in humans: A magnetic resonance imaging study.

The effects of macronutrients on gastric volume changes, emptying, and gastrointestinal symptoms are incompletely understood. Three liquid meals of 500 ml (fat emulsion, 375 kcal; protein solution, 375 kcal; glucose solution, 400 kcal) were infused into the stomach of 12 healthy volunteers on three occasions. Studies were performed in seated body position using an open-configuration magnetic resonance imaging (MRI) system. MRI imaging sequences, assessing stomach and meal volumes, were performed prior to and at times t = 0, 3, 6, 9, 12, 15, 25, 35, 45, 60, 75, and 90 min after meal administration. Areas under the curve for the early emptying phase (0-15 and 0-45 min) were calculated, and characteristics of the volume curves were analyzed by a gastric emptying model. Gastrointestinal symptoms were assessed by a self-report scale. Initial (t = 0 min) and early postprandial gastric volumes were highest for glucose because of lower initial emptying. However, in the early emptying phase the characteristics of the volume curves for stomach and meal were uniform for all macronutrients. Perceptions of fullness and satiety were linearly associated with postprandial gastric volumes, but not with macronutrient composition. Isovolumic macronutrient meals modulate gastric volume response by initial meal emptying patterns. Macronutrient specific accommodation responses, as shown in barostat studies, are not reflected as gastric volume responses under noninvasive conditions.

Quantification of distal antral contractile motility in healthy human stomach with magnetic resonance imaging.

PURPOSE: To quantify healthy postprandial: 1) propagation, periodicity, geometry, and percentage occlusion by distal antral contraction waves (ACWs); and 2) changes in ACW activity in relationship to gastric emptying (GE). MATERIALS AND METHODS: Using 1.5-T MR scanner, nine healthy fasted volunteers were examined in the right decubitus position after ingestion of 500 mL of 10% glucose (200 kcal) with 500 microM Gd-DOTA. Total gastric (TGV) and meal volumes (MV) were assessed every five minutes for 90 minutes, in and interspersed with dynamic scan sequences (duration: 2.78 minutes) providing detailed images of distal ACWs. RESULTS: TGV increased by 738+/-38 mL after ingestion (t0), subsequently decreasing in parallel to GE. The mean GE rate and half-emptying time were 24+/-3 mL/5 minutes and 71+/-6 minutes, respectively. Accompanying ACWs reached a periodicity of 23+/-2 seconds at t35 and propagated at an unvarying speed of 0.27+/-0.01 cm/second. Their amplitude of 0.70+/-0.08 cm was constant, but the width decreased along the antral wall by 6+/-2%/cm (P=0.003). ACWs were nonocclusive (percentage occlusion 58.1+/-5.9%, t0 at the pylorus) with a reduction in occlusion away from the pylorus (P<0.001). No propagation and geometry characteristics of ACWs correlated with the changes of MV (mL/5 minutes; R2<0.05). CONCLUSION: Our results indicate that ACWs are not imperative for emptying of liquids. This study provides a detailed quantitative reference for MRI inquiries into pharmacologically- and pathologically-altered gastric motility.

Efficacy and safety of botulinum toxin a injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure: a prospective randomized study.

OBJECTIVES: To evaluate the efficacy and safety of botulinum toxin A injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure (CAF). METHODS: Fifty outpatients with CAF were randomized to receive either a single botulinum toxin injection (30 IU Botox) or topical nitroglycerin ointment 0.2% b.i.d. for 2 wk. If the initial therapy failed, patients were assigned to the other treatment group for a further 2 wk. If CAF still showed no healing at wk 4, patients received combination therapy of botulinum toxin and nitroglycerin for 4 additional wk. Persisting CAF at wk 8 was treated according to the investigator's decision. Healing rates, symptoms, and side effects of the therapy were recorded at wk 2, 4, 8, 12, and 24 after randomization. RESULTS: The group initially treated with nitroglycerin showed a higher healing rate of CAF (13 of 25, 52%) as compared with the botulinum toxin group (6 of 25, 24%) after the first 2 wk of therapy (p < 0.05). At the end of wk 4, CAF healed in three additional patients, all receiving nitroglycerin after initial botulinum toxin injection. Mild side effects occurred in 13 of 50 (26%) patients, all except one were on nitroglycerin. CONCLUSIONS: Nitroglycerin ointment was superior to the more expensive and invasive botulinum toxin injection for initial healing of CAF, but was associated with more but mild side effects.

Barostat measurement of rectal compliance and capacity.

PURPOSE: Fecal continence requires relaxation of the rectal wall and a reservoir of adequate capacity. Rectal compliance provides an assessment of rectal wall stiffness; however, compliance is also affected by rectal capacity. We developed and validated a barostat measurement of rectal capacity. By accounting for variation in rectal capacity, we aimed to improve the inconsistent relationship between rectal compliance, sensation, and continence reported in the literature. METHOD: Barostat measurements of rectal compliance and capacity were validated in 41 healthy, continent subjects. Slow staircase (0-40 mmHg) and rapid phasic (12-40 mmHg) distentions were performed on two separate days, filling sensations were assessed by visual analog score. A stool substitute retention test of rectal filling sensation and continence was performed. RESULTS: Variance of volume measurements decreased with pressure comparing conditioning vs. index distentions, staircase vs. phasic distentions, and measurements on different days (all P < 0.001). Correction for rectal capacity measured at 40 mmHg reduced the "normal range" of compliance measurements (P < 0.01) but not vice versa. Compared with unadjusted volume measurements, normalized rectal volume (percentage filling relative to rectal capacity) improved the description of rectal sensation visual analog score (P < 0.01). Rectal capacity correlated with filling sensations and the volume retained on retention testing (P < 0.01). CONCLUSION: Barostat measurements of rectal capacity at 40 mmHg are highly reproducible and not affected by distention protocol. The assessment of rectal capacity complements that of rectal compliance. Correction for rectal capacity provides an assessment of rectal wall stiffness independent of rectal geometry and improves the association of barostat volume measurements with rectal sensitivity and continence.

The effects of loperamide on continence problems and anorectal function in obese subjects taking orlistat.

UNLABELLED: Continence problems during treatment with orlistat (a lipase inhibitor) are caused when susceptible patients are exposed to increased volumes of loose, fatty stool. AIM: To investigate the dose-response effects of loperamide on continence and anorectal function in subjects susceptible to continence problems on orlistat. METHOD: Ten obese subjects enterred a randomized controlled, double-blind study of loperamide at placebo, 2, 4, and 6 mg/day in a factorial design. Continence problems during orlistat treatment were self-assessed by patient diary. Anorectal function and continence were assessed by barostat, manometry, and retention testing. RESULTS: Loperamide increased stool consistency with dose (p = 0.07) and this effect reduced continence problems during orlistat treatment (p < 0.05). A bell-shaped dose-response relationship was present with anal sphincter function (p < 0.01) and anorectal sensitivity (p < 0.01). CONCLUSION: Loperamide has beneficial effects on stool consistency and continence in obese subjects taking orlistat. The effect on stool consistency appeared more important than effects on anorectal function.

Significance of incidental 18F-FDG accumulations in the gastrointestinal tract in PET/CT: correlation with endoscopic and histopathologic results.

UNLABELLED: This study was undertaken to identify the clinical value of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with (18)F-FDG PET/CT. METHODS: The reported database of 3,281 patients who underwent partial-body (18)F-FDG PET/CT scans from April 2001 to September 2003 was reviewed. Patients with incidental (18)F-FDG accumulations in the GIT that were associated with concomitant abnormal soft-tissue density or wall thickening on the native CT were evaluated. Incidental PET/CT findings were correlated with endoscopic and histopathologic results. RESULTS: According to our selection criteria, 98 (3%) of the 3,281 patients had an IDL of the GIT on (18)F-FDG PET/CT. Correlative endoscopic findings were available in 69 (70%) of 98 patients. Of these, 13 patients (19%) were harboring newly occurring cancers of the GIT in addition to preexisting aerodigestive tract tumors (n = 12) and malignant melanoma (n = 1). Twenty-nine (42%) patients were identified with precancerous lesions, such as advanced colonic adenomas (n = 27), Barrett's esophagus (n = 1), and intestinal metaplasia of the gastric mucosa (n = 1). Inflammatory and other benign GIT lesions were detected in 12 (17%) and 6 (8%) patients, respectively. In 9 (13%) patients, PET/CT was false-positive, showing normal findings in subsequent endoscopic examinations. In 20 (28%) of 69 patients, PET/CT findings had a relevant impact on the clinical management. Twenty-nine (30%) of the 98 patients were not subject to a further endoscopic examination because of the extent and nature of the primary tumor (n = 17), loss to follow-up (n = 7), death shortly after PET (n = 3), and patient unwillingness (n = 2). CONCLUSION: Although IDLs of the GIT on (18)F-FDG PET/CT scans are found only in about 3% of cases, they are associated with a substantial risk of an underlying cancerous or precancerous lesion. Early identification of these occult lesions may have a major impact on the patients' management and outcome.

The physical properties of rectal contents have effects on anorectal continence: insights from a study into the cause of fecal spotting on orlistat.

PURPOSE: The intermittent loss of oil or stool ("spotting") is an adverse effect that occurs in patients taking orlistat; the pathophysiology is unknown. This study was designed to investigate the local effects of orlistat, free fatty acids, and the effects of the physical properties of rectal contents on anorectal function and continence. METHODS: Anorectal physiology and continence function were assessed in ten healthy patients after the application of four test enemas: 1) high-viscosity stool substitute, 2) stool substitute with free fatty acid, 3) low-viscosity oil with placebo, 4) oil with orlistat. Rectal function and capacity were assessed by barostat techniques. Anal resting pressure, squeeze pressure, and squeeze duration were assessed by manometry. A retention test was performed using the same enemas as a quantitative assessment of continence. RESULTS: Orlistat and free fatty acid had no adverse effects on anorectal function or continence. For each enema, the maximum volume retained correlated with rectal capacity (r = 0.85; P < 0.01). Continence during rectal filling was better maintained for high-viscosity stool substitute than low-viscosity oil enemas (P < 0.03). Patients able to maintain effective squeeze pressure retained more of the low-viscosity enemas than those with short squeeze duration (P < 0.01); in contrast, the volume retained of high-viscosity enemas was unaffected by anal sphincter function. CONCLUSIONS: The physical properties of rectal contents, rectal capacity, and voluntary anal sphincter function have effects on continence function in healthy patients. The occurrence of spotting may depend on both intrinsic anorectal function and the effects of orlistat on the volume and physical properties of stool.

Magnetic resonance imaging for the in vivo evaluation of gastric-retentive tablets.

PURPOSE: To develop a magnetic resonance imaging (MRI) technique for assessing in vivo properties of orally ingested gastric-retentive tablets under physiologic conditions. METHODS: Tablets with different floating characteristics (tablet A-C) were marked with superparamagnetic Fe3O4 particles to analyze intragastric tablet position and residence time in human volunteers. Optimal Fe3O4 concentration was determined in vitro. Intragastric release characteristic of one slow-release tablet (tablet D) was analyzed by embedding gadolinium chelates (Gd-DOTA) as a drug model into the tablet. All volunteers underwent MRI in the sitting position. Tablet performance was analyzed in terms of relative position of tablet to intragastric meal level (with 100% at meal surface), intragastric residence time (min) and Gd-DOTA distribution volume (% of meal volume). RESULTS: Intragastric tablet floating performance and residence time of tablets (tablet A-D) as well as the intragastric Gd-DOTA distribution of tablet D could be monitored using MRI. Tablet floating performance was different between the tablets (A, 93%(95 - 9%); B, 80%(80 - 68%): C, 38%(63 - 32%); p < 0.05). The intragastric distribution volume of Gd-DOTA was 19.9% proximally and 35.5% distally. CONCLUSIONS: The use of MRI allows the assessment of galenic properties of orally ingested tablets in humans in seated position.