Increased rectal wall stiffness after prostate radiotherapy: relation with fecal urgency.

BACKGROUND: Late anorectal toxicity is a frequent adverse event of external beam radiotherapy (EBRT) for prostate cancer. The pathophysiology of anorectal toxicity remains unknown, but we speculate that rectal distensibility is impaired due to fibrosis. Our goal was to determine whether EBRT induces changes of rectal distensibility as measured by an electronic barostat and to explore whether anorectal complaints are related to specific changes of anorectal function. METHODS: Thirty-two men, irradiated for localized prostate carcinoma, underwent barostat measurements, anorectal manometry, and completed a questionnaire prior to and 1 year after radiotherapy. The primary outcome measure was rectal distensibility in response to stepwise isobaric distensions. In addition, we assessed sensory thresholds, anal pressures, and anorectal complaints. KEY RESULTS: External beam radiotherapy reduced maximal rectal capacity (227 ± 14 mL vs 277 ± 15 mL; P < 0.001), area under the pressure-volume curve (3212 ± 352 mL mmHg vs 3969 ± 413 mL mmHg; P < 0.005), and rectal compliance (15.7 ± 1.2 mL mmHg(-1) vs 17.6 ± 0.9 mL mmHg(-1) ; P = 0.12). Sensory pressure thresholds did not significantly change. Sixteen of the 32 patients (50%) had one or more anorectal complaints. Patients with urgency (n = 10) had a more reduced anal squeeze and maximum pressure (decrease 29 ± 11 mmHg vs 1 ± 7 mmHg; P < 0.05 and 31 ± 12 mmHg vs 2 ± 8 mmHg; P < 0.05 respectively) compared with patients without complaints, indicating a deteriorated external anal sphincter function. CONCLUSIONS & INFERENCES: Irradiation for prostate cancer leads to reduced rectal distensibility. In patients with urgency symptoms, anal sphincter function was also impaired.

Gut hormone profiles in critically ill neonates on extracorporeal membrane oxygenation.

OBJECTIVES: The objective of this study was to gain insight into the hormonal responses to enteral nutrition in critically ill newborns requiring venoarterial extracorporeal membrane oxygenation (ECMO) by analyzing plasma gut hormone levels of gastrin, cholecystokinin and peptide-YY in relation to enteral nutrition. METHODS: In 24 consecutive neonates treated with venoarterial ECMO intestinal hormone secretions were determined by radioimmunoassay at 2-day intervals. Twelve received parenteral nutrition only. In 12 enteral nutrition was introduced later. The findings in these patients were compared with those of 16 measurements in eight non-ECMO treated age-matched controls. Mixed model analysis of variance was used for statistical analysis. RESULTS: Concentrations of gastrin, cholecystokinin and peptide-YY were significantly higher in ECMO patients receiving enteral nutrition compared with ECMO patients who received parenteral nutrition (62, 3.8 and 59.4 pmol/L versus 46, 3.1 and 34.7 pmol/L, respectively). Overall, plasma hormone levels did not differ from those in age-matched controls. CONCLUSIONS: Intestinal hormone levels showed normal responses after introduction of enteral feeding, comparable with those in age-matched controls without ECMO. These results do not provide an argument for withholding enteral nutrition even in the most severely ill neonates on venoarterial ECMO.

Peptide YY release after colectomy in slow transit constipation.

BACKGROUND: The gut hormone peptide YY is abundant in the colonic mucosa. Circulating PYY inhibits gastrointestinal motility and decreases food intake. The aim was to determine whether colectomy decreases PYY release in patients with slow transit constipation. METHODS: Plasma PYY concentrations were measured in 10 patients with slow transit constipation before and 3-24 months after total abdominal colectomy with ileorectal anastomosis, and in 8 healthy controls. A liquid meal was infused intraduodenally to stimulate PYY release. RESULTS: Postprandial PYY significantly (P < 0.05) increased from a basal value of 15.6 +/- 1.8 pM to a peak of 71.2 +/- 11.6 pM after colectomy. Basal and postprandial plasma PYY concentrations were not significantly different from the results before surgery. Fasting, but not postprandial, plasma peptide YY after colectomy was significantly higher than that in healthy volunteers, 10.9 +/- 0.9 pM. CONCLUSION: Despite removal of a major source of PYY-secreting cells, colectomy with ileorectal anastomosis does not induce major impairment of PYY release in slow transit constipation.

Gastrointestinal hormone secretion after surgery in neonates with congenital intestinal anomalies during starvation and introduction of enteral nutrition.

BACKGROUND/PURPOSE: Gastrointestinal hormones modulate gut function in response to enteral nutrition. Infants with a congenital intestinal anomaly with loss of bowel length either pre-or postnatal, who are on total parenteral nutrition for prolonged periods after surgery, are especially prone to a disturbed secretion of gut hormones. The aim of this study was to determine whether circulating gut hormones were altered in these patients and to collect baseline data for future studies in short bowel patients using different enteral substrates. METHODS: Gastrin, cholecystokinin, and peptide YY were measured in 14 operated neonates who had a congenital intestinal anomaly during starvation and introduction of enteral nutrition. None of the neonates had a short bowel. Fourteen neonates who underwent surgery for other major congenital anomalies served as age-matched controls. Gut hormones were measured with radioimmunoassays. RESULTS: Postprandial gut hormone values were higher than basal gut hormone values within both groups. Compared with the controls, postprandial gastrin and cholecystokinin were significantly higher in the patients. CONCLUSIONS: Neonates with a congenital intestinal anomaly in the absence of a short bowel have a similar secretion pattern of gastrointestinal hormones as neonates with a structurally normal intestinal tract, both during starvation and enteral nutrition.

Effect of two breakfasts, different in carbohydrate composition, on hunger and satiety and mood in healthy men.

OBJECTIVE: To study the effect of simple vs complex carbohydrates (SCHO and CCHO respectively) containing breakfasts on blood parameters, hunger and satiety and mood. DESIGN: A 2-day, open, randomised, cross-over trial. SUBJECTS: A total of 26 male subjects (34+/-6 y; BMI 23.4+/-2.2 kg m(-2)). MEASUREMENTS: Blood glucose, insulin, triacylglycerols (TG), free fatty acids (FFA) and cholecystokinin (CCK) were determined repeatedly for 4 h on both test days after a breakfast containing SCHO or CCHO. Feelings of hunger and satiety were determined at similar time points as well. Mood state was examined 3 h after breakfast consumption. RESULTS: Consumption of a SCHO breakfast resulted in higher glucose and insulin levels at 30 min after breakfast consumption. TG at 180 min, and FFA at 180 and 240 min were higher after SCHO breakfast than after CCHO breakfast. Satiety scores were higher after CCHO breakfast consumption for the first 90 min after intake. Furthermore, the item 'fatigue' was scored higher after SCHO breakfast than after CCHO breakfast intake. CONCLUSION: Consumption of a CCHO breakfast is favourable in comparison to a SCHO breakfast, because of the lower perception of 'fatigue' and the higher degree of satiety after consumption.

Tumour necrosis factor alpha antibody affects gastrin release in Crohn disease.

BACKGROUND: Gastrin plays an important role in the regulation of gastric acid secretion in humans. Tumour necrosis factor alpha (TNF-alpha) stimulates gastrin release from antral G cells in vitro. The aim was to determine whether gastrin release decreases in patients with Crohn disease treated with monoclonal antibody to TNF-alpha. METHODS: Twenty-five consecutive patients with Crohn disease (10 M, 15 F; 18 with fistulas) were treated with a single intravenous infusion of the monoclonal antibody to TNF-alpha, infliximab, at a dose of 5 mg/kg. Basal and bombesin stimulated gastrin was measured after an overnight fast immediately before and 2 weeks after infliximab. Helicobacter pylori status was determined by serology. RESULTS: Twenty-two patients were H. pylori-negative. Basal plasma gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS). Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59) pmol/L (P < 0.005) 2 weeks after infliximab. CONCLUSION: Gastrin release in response to bombesin decreases in patients with Crohn disease treated with infliximab.

Tumour Necrosis Factor Alpha Antibody Affects Gastrin Release in Crohn Disease.

BACKGROUND: Gastrin plays an important role in the regulation of gastric acid secretion in humans. Tumour necrosis factor alpha (TNF-α) stimulates gastrin release from antral G cells in vitro. The aim was to determine whether gastrin release decreases in patients with Crohn disease treated with monoclonal antibody to TNF-α. METHODS: Twenty-five consecutive patients with Crohn disease (10 M, 15 F; 18 with fistulas) were treated with a single intravenous infusion of the monoclonal antibody to TNF-α, infliximab, at a dose of 5 mg/kg. Basal and bombesin stimulated gastrin was measured after an overnight fast immediately before and 2 weeks after infliximab. Helicobacter pylori status was determined by serology. RESULTS: Twenty-two patients were H. pylori-negative. Basal plasma gastrin was 21 (16-26) pmol/L before and 19 (15-25) pmol/L after infliximab (NS). Bombesin stimulated gastrin decreased from 49 (40-62) pmol/L before to 36 (33-59) pmol/L (P < 0.005) 2 weeks after infliximab. CONCLUSION: Gastrin release in response to bombesin decreases in patients with Crohn disease treated with infliximab.

Basal and fat-stimulated plasma peptide YY levels in celiac disease.

The distal gut hormone peptide YY (PYY) mediates feedback inhibition of gastric acid secretion, gastrointestinal motility, and pancreatic enzyme output. To investigate the influence of maldigestion on PYY, we determined plasma PYY levels in patients with celiac disease under basal conditions and in response to intraduodenal fat. Basal PYY was increased in untreated celiac patients (N = 13) compared to patients on a gluten free diet (N = 9) [15.6 (11.8-27.0) pM vs 12.2 (10.1-13.1) pM; P < 0.05] and compared to control subjects (N = 15) [9.5 (8.3-10.4) pM; P < 0.001]. Integrated PYY in response to intraduodenally infused predigested fat (1071+/-293 pM 80 min) was significantly (P < 0.05) greater than in response to undigested fat (322+/-223 pM 80 min) in six untreated celiacs. Plasma concentrations of PYY and cholecystokinin were strongly correlated (r = 0.79; P < 0.001). We conclude that basal PYY levels in untreated celiac disease are elevated, that predigestion of fat enhances PYY release in these patients, and that PYY secretion is correlated with CCK release.

Effect of circulating peptide YY on gallbladder emptying in humans.

BACKGROUND: To further establish its role in the ileal brake mechanism, we determined the effect of the distal gut hormone peptide YY (PYY) on gallbladder motility and plasma gut hormones during the cephalic phase of meal stimulation. METHODS: Eight healthy volunteers were studied in a randomized crossover design, with or without intravenous infusion of a physiological dose of PYY. On each occasion, subjects underwent modified sham feeding followed by real feeding. RESULTS: PYY reduced gallbladder emptying in response to modified sham feeding from 23 +/- 5% to 5 +/- 7% (P < 0.01) and integrated plasma pancreatic polypeptide from 2337 +/- 397 pmol/L x 90 min to 903 +/- 232 pmol/L x 90 min (P < 0.01). PYY enhanced plasma cholecystokinin in response to real feeding from 53 +/- 9 pmol/L x 90 min to 82 +/- 17 pmol/L x 90 min (P < 0.05), but did not significantly affect maximum gallbladder emptying and tended to decrease plasma pancreatic polypeptide. CONCLUSION: Circulating PYY suppresses the cephalic phase of postprandial gallbladder emptying, but not meal stimulated maximum emptying. The results support the hypothesis that the effect of PYY on gallbladder emptying is mediated by vagal-dependent rather than cholecystokinin-dependent pathways.

Effect of subtotal colectomy on gastric emptying of a solid meal in slow-transit constipation.

BACKGROUND: Idiopathic slow-transit constipation is considered a panenteral disease in which patients may have delayed gastric emptying. The effects of total abdominal colectomy and ileorectal anastomosis on upper gut motility are unknown. The aim of this study was to evaluate gastric emptying in patients with idiopathic slow-transit constipation before and after subtotal colectomy. METHODS: Gastric emptying of a solid meal was studied by scintigraphic technique in 11 patients with idiopathic slow-transit constipation. The total colonic transit time was more than 72 hours in all patients studied, with delay in transit in all segments of the colon. The gastric emptying test was repeated 3 to 6 months after total abdominal colectomy and ileorectal anastomosis in ten of these patients. Before and after surgery, patients filled out a questionnaire to record upper gut symptoms. RESULTS: Solid gastric emptying was delayed (T1/2 > upper limit of normal) in 7 of 11 patients with idiopathic slow-transit constipation. Gastric emptying T1/2 was almost similar before and after surgery. Mean +/- standard deviation was 142 +/- 91 minutes before surgery and 146 +/- 67 minutes after surgery. Symptoms of vomiting and belching improved significantly after surgery. Symptoms of nausea, bloating, and pyrosis also decreased, but these changes failed to reach statistical significance. CONCLUSION: Despite a reduction in upper gut symptoms, total abdominal colectomy and ileorectal anastomosis does not improve delayed gastric emptying in patients with idiopathic slow-transit constipation.

Effect of rectal distension on gallbladder emptying and circulating gut hormones.

BACKGROUND: Abnormalities of upper gut motility, including a delay of gastric emptying and small bowel transit, found in patients with constipation may be secondary to factors originating in the colon or rectum as a result of faecal stasis. The aim was to determine if stimulation of mechanosensory function by rectal distension affects postprandial gallbladder emptying and release of gastrointestinal peptides participating in control of upper gut motility. MATERIALS AND METHODS: Eight healthy volunteers were studied with an electronic barostat and a plastic bag positioned in the rectum. Intrabag pressure was maintained at minimal distension pressure + 2 mmHg on one occasion and on a pressure that induced a sensation of urge on the other. Gallbladder volume and plasma concentrations of cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY (PYY) were measured before and after ingestion of a 450-kcal mixed liquid meal. RESULTS: Rectal distension enhanced maximum gallbladder emptying from 66 +/- 7% to 78 +/- 5% (P < 0.05). Distension tended to increase integrated plasma PYY from 77 +/- 30 pM min to 128 +/- 40 pM min in the first hour after the meal (P = 0.08) and it suppressed integrated plasma PP from 1133 +/- 248 pM min to 269 +/- 284 pM min in the second hour (P < 0.05). Integrated plasma CCK concentrations were not significantly affected. CONCLUSION: Mechanosensory stimulation of the rectum enhances postprandial gallbladder emptying and influences postprandial release of gut hormones involved in the regulation of gastrointestinal motility in healthy subjects. These mechanisms may play a role in the pathogenesis of the upper gastrointestinal motor abnormalities observed in constipated patients.

Plasma cholecystokinin, plasma peptide YY and gallbladder motility in patients with slow transit constipation: effect of intestinal stimulation.

BACKGROUND/AIM: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation. METHODS: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls. RESULTS: Fasting levels of plasma cholecystokinin (3.1+/-0.2 vs. 2.4+/-0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4+/-1.4 vs. 8.9+/-0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60-90 min), incremental cholecystokinin (p<0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0-60 min), incremental plasma cholecystokinin (251+/-20 pM.min) and peptide YY (1,146+/-186 pM. min) in patients were almost similar to control values (262+/-22 and 901+/-166 pM. min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying. CONCLUSION: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.

Role of circulating peptide YY in the inhibition of gastric acid secretion by dietary fat in humans.

BACKGROUND: Intestinal fat inhibits gastric acid secretion and induces release of peptide YY (PYY) into the circulation. The aim of this study was to further establish the role of circulating PYY in the inhibition of gastric acid secretion by intraduodenal fat. METHODS: Plasma PYY concentrations and gastrin-stimulated gastric acid output were measured in response to intravenous infusion of PYY in eight healthy men. The results were compared with those obtained after intraduodenal administration of dietary fat. RESULTS: Plasma PYY concentrations increased by 8.1 +/- 1.8 pmol/l (P < 0.005) in response to the lower and by 13.5 +/- 2.5 pmol/l (P < 0.005) in response to the higher PYY dose. These increments were comparable to those observed after intraduodenal fat (10.3 +/- 2.4 pmol/l). Intraduodenal fat significantly inhibited (P < 0.005 versus control) gastrin-stimulated gastric acid secretion by 74% +/- 6%, but neither the lower (3% +/- 7%; NS) nor the higher PYY dose (1% +/- 10%; NS) induced any change in gastric acid output. PYY was biologically active, as reflected by a significant delay (P = 0.04) of orocaecal transit time. CONCLUSION: Release of PYY into the circulation is not responsible for inhibition of gastrin-stimulated gastric acid secretion by dietary fat.

Sympathoadrenal activation and the dumping syndrome after gastric surgery.

Dumping symptoms suggest concomitant sympathoadrenal activation. To evaluate the relation between dumping symptoms and postprandial plasma catecholamine changes, standardized dumping-provocation tests with use of oral glucose were performed for 16 gastric surgery patients with dumping, for 14 gastric surgery patients without dumping, and for 14 healthy control patients. Early dumping symptoms were present for all patients with dumping, and late symptoms developed in three patients with dumping after glucose ingestion. Patients without dumping and healthy control patients had slight complaints or no complaints. Systolic and diastolic blood pressure remained unaffected for the three groups. Positive breath-hydrogen tests, heart rate increments, and reactive plasma glucose decrements were present for patients with dumping and for patients without dumping, but not for control patients. Plasma noradrenaline and adrenaline increased for patients with dumping and for patients without dumping, but not for control patients. The noradrenaline increment was higher for patients with dumping (98%) than for patients without dumping (78%; p <0.05). The noradrenaline increment was related to the dumping score and to the heart rate increment for the first hour after glucose ingestion, whereas the adrenaline increment was related to the plasma glucose decrement for the third hour. Therefore, dumping symptoms clearly are accompanied by postprandial sympathoadrenal activation, but sympathoadrenal activation cannot account completely for development of dumping symptoms.

Effects of Helicobacter pylori infection on endocrine and exocrine mucosal functions in the upper gastrointestinal tract.

BACKGROUND: Helicobacter pylori infection affects the concentration of regulatory peptides such as gastrin, somatostatin and cholecystokinin and the concentration and activity of glutathione and glutathione S-transferases in the gastric mucosa. METHODS: Literature review. RESULTS: Although some of these peptides have been known since the beginning of this century, their action has changed since the discovery of H. pylori infection in 1983. Chronic infection with H. pylori might lead to an increased risk in developing gastric cancer. Glutathione S-transferases are involved in the cellular detoxification of xenobiotics and other toxic compounds. Since there is a close inverse relationship between the activity of glutathione S-transferase and incidence of malignancies in the gastrointestinal tract, the possible relation between H. pylori infection and activity of glutathione S-transferases in the gastric mucosa is discussed. CONCLUSION: The effect of H. pylori infection on regulatory peptides and glutathione/glutathione S-transferases might play a role in the development of neoplastic changes of the H. pylori-infected gastric mucosa.

Abnormalities of upper gut motility in patients with slow-transit constipation.

OBJECTIVE: To further delineate motor activity of the upper gastrointestinal tract in patients with slow-transit constipation. DESIGN: A prospective study comparing healthy volunteers with patients with a clinical diagnosis of slow-transit constipation. METHODS: Eighteen patients with clinical diagnosis of slow-transit constipation and 10 healthy controls were included in the study. Fasting antroduodenal motility was measured by perfusion manometry for at least one complete cycle of the migrating motor complex or a maximum of 300 min. Oesophageal manometry, gastric emptying and orocaecal transit time measurements were also performed. RESULTS: At least one complete cycle of the migrating motor complex was observed in all controls, but in only nine patients (P < 0.01 versus control). The migrating motor complex cycle was incomplete (n = 5) or phase 3 activity was absent (n = 4) in the other patients. The incidence of clustered contractions was significantly increased in slow-transit constipation (P = 0.05 versus controls). The area under the contraction curve during late phase 2 (1509+/-296 mmHg x s) in patients with a complete cycle was significantly smaller than that in controls (2997+/-614 mmHg x s; P = 0.05). Orocaecal transit time was not significantly different among patients and controls, but oesophageal motility was abnormal in five of 18 patients and gastric emptying was abnormal in eight of 15 patients. CONCLUSION: Abnormalities of upper gut motility occur frequently in patients with slow-transit constipation. Interdigestive antroduodenal motility is characterized by (i) absence or prolonged duration of the migrating motor complex, (ii) an increased number of clustered contractions, or (iii) a decreased motility during late phase 2 of the migrating motor complex.

Impaired release of peptide YY in patients with proctocolectomy and ileal pouch-anal anastomosis.

BACKGROUND: Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels. METHODS: Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects. RESULTS: Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 +/- 0.3 versus 9.3 +/- 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 +/- 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 +/- 66 pM*180min versus 3194 +/- 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001). CONCLUSION: PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous PYY.

The nondigestible fat sucrose polyester does not stimulate gallbladder emptying in humans.

BACKGROUND: We determined the effect of oral ingestion of sucrose polyester, which was approved as a fat replacer in the United States, on gallbladder motility and on the release of cholecystokinin, the hormone that mediates gallbladder emptying. OBJECTIVE: Our objective was to measure effects of sucrose polyester on gallbladder emptying and cholecystokinin release. DESIGN: Eight healthy volunteers (3 men and 5 women) drank 60 mL sucrose polyester, digestible fat, or saline solution in a balanced crossover design on 3 separate days. RESULTS: Mean (+/-SEM) gallbladder emptying, when integrated over time, was low in response to both sucrose polyester (-150 +/- 214 mL x 120 min) and saline solution (-89 +/- 123 mL x 120 min). In contrast, there was marked emptying in response to digestible fat (1069 +/- 253 mL x 120 min). Sucrose polyester did not affect plasma cholecystokinin concentrations (-9.3 +/- 15.0 pmol x 120 min/L), whereas digestible fat resulted in a significant increase (89.5 +/- 44.8 pmol x 120 min/L, P = 0.014) compared with saline solution (-3.0 +/- 13.8 pmol x 120 min/L). CONCLUSIONS: Ingestion of sucrose polyester, in contrast with digestible fat, did not stimulate gallbladder emptying or release of cholecystokinin.