Adherence to guideline recommendations for Barrett's esophagus (BE) surveillance endoscopies: Effects of dedicated BE endoscopy lists.

Background and study aims For non-dysplastic Barrett's Esophagus (BE) patients, guidelines recommend endoscopic surveillance every 3 to 5 years with four-quadrant random biopsies every 2 cm of BE length. Adherence to these guidelines is low in clinical practice. Pooling BE surveillance endoscopies on dedicated endoscopy lists performed by dedicated endoscopists could possibly enhance guideline adherence, detection of visible lesions, and dysplasia detection rates (DDRs). Patients and methods Data were used from the ACID-study (Netherlands Trial Registry NL8214), a prospective trial of BE surveillance in the Netherlands. BE patients with known or previously treated dysplasia were excluded. Guideline adherence, detection of visible lesions, and DDRs were compared for patients on dedicated and general endoscopy lists. Results A total of 1,244 patients were included, 318 on dedicated lists and 926 on general lists. Endoscopies on dedicated lists showed significantly higher adherence to the random biopsy protocol (85% vs. 66%, P <0.01) and recommended surveillance intervals (60% vs. 47%, P <0.01) compared to general lists. Detection of visible lesions (8.8% vs. 8.1%, P =0.79) and DDRs were not significantly different (6.9% and 6.6%, P =0.94). None (0.0%) of the patients scheduled on dedicated lists and 10 (1.1%) on general lists were diagnosed with esophageal adenocarcinoma ( P =0.07). In multivariable analysis, dedicated lists were significantly associated with biopsy protocol adherence and adherence to surveillance interval recommendations with odds ratios of 4.45 (95% confidence interval [CI] 2.07-9.57) and 1.64 (95% CI 1.03-2.61), respectively. Conclusions Dedicated endoscopy lists are associated with better adherence to the random biopsy protocol and surveillance interval recommendations.

[Surgery for colorectal cancer since the introduction of the Netherlands national screening programmeInvestigations into changes in number of resections and waiting times for surgery]. / Darmkankerchirurgie sinds het bevolkingsonderzoek.

OBJECTIVE: To investigate the impact of the Netherlands national colorectal cancer screening programme on the number of surgical resections for colorectal carcinoma and on waiting times for surgery. DESIGN: Descriptive study. METHOD: Data were extracted from the Dutch Surgical Colorectal Audit. Patients with primary colorectal cancer surgery between 2011-2015 were included. The volume and median waiting times for the years 2011-2015 are described. Waiting times from first tumor positive biopsy until the operation (biopsy-operation) and first preoperative visit to the surgeon until the operation (visit-operation) are analyzed with a univariate and multivariate linear regression analysis. Separate analysis was done for visit-operation for academic and non-academic hospitals and for screening compared to non-screening patients. RESULTS: In 2014 there was an increase of 1469 (15%) patients compared to 2013. In 2015 this increase consisted of 1168 (11%) patients compared to 2014. In 2014 and 2015, 1359 (12%) and 3111 (26%) patients were referred to the surgeon through screening, respectively. The median waiting time of biopsy-operation significantly decreased (ß: 0.94, 95%BI) over the years 2014-2015 compared to 2011-2013. In non-academic hospitals, the waiting time visit-operation also decreased significantly (ß: 0.89, 95%BI 0.87-0.90) over the years 2014-2015 compared to 2011-2013. No difference was found in waiting times between patients referred to the surgeon through screening compared to non-screening. CONCLUSION: There is a clear increase in volume since the introduction of the colorectal cancer screening programme without an increase in waiting time until surgery.

Long-term results of palliative stent placement for acute malignant colonic obstruction.

BACKGROUND: Endoscopic placement of self-expanding-metal-stents (SEMS) is widely performed as palliative treatment for acute malignant colonic obstruction. There is ongoing debate regarding risks and benefits associated with SEMS placement. This study aimed to evaluate long-term outcomes of palliative SEMS placement in patients presenting with acute malignant colonic obstruction. METHODS: A prospectively collected patient cohort (2005-2013) from a general teaching hospital was used. In this hospital, all consecutive patients presenting with acute malignant large bowel obstruction are treated with endoscopic SEMS placement. Only colon cancer patients who underwent palliative SEMS placement were selected. RESULTS: In total, 48 patients were included. The technical and short-term clinical success rates were 91 % (44/48) and 85 % (36/48), respectively. SEMS-related mortality occurred in 6/48 patients (13 %) (early n = 4, late n = 2) and was caused by SEMS-related perforation in all cases. The SEMS-related morbidity rate was 38 % (18/48) (early n = 7, late n = 11). Endoscopic re-intervention was performed 14 times and 13 patients eventually underwent surgical treatment during follow-up. The stoma-formation rate was 15 % (7/48). Long-term clinical success was 48 % (23/48). The estimated stent patency rate (95 % confidence interval) was 69 % (52-79) at 1 month, 54 % (37-66) at 6 months and 50 % (33-62) at 12 months. CONCLUSION: Palliative SEMS placement provides rapid relief of obstruction and avoids a stoma in most patients with acute colonic obstruction caused by incurable or inoperable colon cancer. However, these benefits should be weighed against mortality and morbidity related to SEMS placement.

Low morbidity and mortality after stenting for malignant bowel obstruction.

BACKGROUND: The difference in mortality between emergency and elective surgery for malignant colonic obstruction is more than 5% in healthy patients below the age of 65 and increases with age to around 20%. Emergency surgery can be avoided by endoscopic placement of a self-expandable metal stent (SEMS). AIM: To evaluate the effectiveness and safety of SEMS as 'bridge to surgery'. METHOD: Between January 2001 and July 2008, SEMS were placed for acute malignant colonic obstruction in 45 patients (median age 72 years, range 35-91). RESULTS: The procedure was technically successful in 43 patients (94%) with resolution of obstructive symptoms within 48 h in 87% of the patients. No perforations occurred during the procedure or while awaiting surgery. Two (4%) patients required a second endoscopic procedure. All patients underwent a single-stage surgical procedure. Postoperative mortality was 2.2% (n = 1). Histology showed advanced colorectal cancer (T3-4N1-2M0-1) in 75% of the patients. CONCLUSION: SEMS placement is a safe and effective procedure as bridge to surgery in patients presenting with colonic obstruction due to colorectal malignancy. This procedure carries a risk of serious complications well below that of the reported difference in mortality between emergency an elective surgery.

[The use of a self-expanding stent as palliation or before elective surgery in patients with obstructive colorectal carcinoma]. / Zelfexpanderende stent bij obstruerend colorectaal carcinoom als palliatie of als overbrugging naar electieve chirurgie.

OBJECTIVE: To evaluate the use of colorectal stents. DESIGN: Retrospective. METHOD: Data were collected on all patients treated at the Deventer Hospital, the Netherlands, between 1 April 1996 and 31 December 2003 in whom the placement of a self-expanding colorectal stent was attempted. Each patient's physician was contacted to inquire about the patient's status, including quality of life with the stent in situ. RESULTS: Stent placement was attempted in 57 patients as palliation (n = 45) or before elective surgery (n = 12). Of the 57 patients, 29 were men and 28 were women, and the mean age was 71 years (range: 46-94). All patients had colorectal carcinoma, except 1 patient with stenosis following ischaemic colitis. Passage of air and faeces occurred immediately after stent expansion in 55 of the 57 patients (96%). Perforation during stent placement occurred in 2 patients, who subsequently underwent colostomy. 4 additional patients required a colostomy due to stent migration within a few hours or days after placement (n = 3) or obstruction by tumor growth after 65 days (n = 1). Patients in the palliative group had an acceptable quality of life. Those who received a stent before elective surgery were able to undergo resection, did not require colostomy, and had no postoperative complications. One patient did not undergo surgery because of extensive metastases. CONCLUSION: A colorectal stent can be used in the palliative treatment of terminal patients with colorectal carcinoma before colostomy is considered. Experiences with stents before elective surgery were also positive.

Chronic pancreatitis: relation between function and morphology.

BACKGROUND: In our department, we routinely use a combined exocrine-endocrine function test to evaluate the pancreatic function in chronic pancreatitis i.e. urinary para amino benzoic acid (PABA) recovery and pancreatic polypeptide secretion in response to a meal and glucose tolerance test. AIM: To study the relationship between changes in morphology and exocrine/endocrine function in patients with chronic pancreatitis. PATIENTS AND METHODS: In 103 patients with chronic pancreatitis seen by our department for evaluation of pancreatic function between 1989 and 1999, we retrospectively analysed the correlation between morphology (Cambridge-score) and function. Furthermore the differences in presentation, function and morphology between patients with alcohol-induced chronic pancreatitis and idiopathic chronic pancreatitis were evaluated. RESULTS: Significant correlation were found for both PABA recovery and pancreatic polypeptide secretion with morphologic score, respectively r = -0.205 (P = 0.037) and r = -0.209 (P = 0.031), but not with endocrine function. The correlation between morphology and PABA recovery or pancreatic polypeptide secretion was observed in the subgroup with alcohol-induced chronic pancreatitis but not in those with idiopathic chronic pancreatitis. Pain is a prominent symptom of chronic pancreatitis. Pain was more frequent and more severe in patients suffering from chronic pancreatitis caused by alcohol or idiopathy. CONCLUSIONS: Morphology and exocrine function correlate in patients with alcohol-induced chronic pancreatitis but not in patients with chronic pancreatitis. When compared to patients with chronic pancreatitis of idiopathic origin, patients with alcoholic origin show differences in presentation and morphology but not in function.

Gall bladder dysmotility: a risk factor for gall stone formation in hypertriglyceridaemia and reversal on triglyceride lowering therapy by bezafibrate and fish oil.

BACKGROUND AND AIM: The aim of this study was to unravel the mechanisms responsible for the increased risk of gall stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride lowering therapy by bezafibrate and fish oil on determinants of cholelithiasis (biliary lipid composition and gall bladder motility) in HTG patients. PATIENTS AND METHODS: Gall bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between nine HTG patients and 10 age, sex, and body mass index matched normolipidaemic controls. The effects of bezafibrate and fish oil in HTG patients were studied in a randomised cross over trial. RESULTS: HTG patients showed 14-fold higher serum triglyceride (TG) levels than controls. Biliary lipid composition, fasting gall bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p<0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68% and -51% v baseline, respectively; both p<0.01). Fasting CCK levels were not affected whereas CCK induced gall bladder emptying increased during bezafibrate (+29%; p<0.001) and tended to increase on fish oil therapy (+13%; p=0.07). Postprandial gall bladder motility improved on bezafibrate and fish oil (+47 and +25% v baseline, respectively; both p<0.02) at least partly due to increased gall bladder sensitivity to CCK (both p<0.05 v baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p

Effects of very long chain versus long chain triglycerides on gastrointestinal motility and hormone release in humans.

Fish oil (a very long chain triglycerides, VLCT) has received much attention because of its favorable metabolic properties; however, its effect on gastrointestinal function has not been studied. We investigated the effects of intraduodenally administered VLCT on gut-hormone release [cholecystokinin (CCK), neurotensin, peptide YY (PYY)], gallbladder emptying, antroduodenal motility, and small bowel transit time (SBTT) in comparison to intraduodenal administration of saline and long chain triglycerides (LCT, corn oil) in nine healthy volunteers. Gallbladder contraction duration was significantly shorter after VLCT than after LCT (138 +/- 16 min vs 233 +/- 38 min, P < 0.05). Both fats induced a fed motility pattern, while SBTT was not significantly altered. CCK secretion was significantly reduced after VLCT compared to LCT (36 +/- 12 pM x 120 min vs 78 +/- 15 pM x 120 min, P < 0.05), whereas PYY and neurotensin release were not significantly different. In conclusion, effects of triglycerides on CCK and gallbladder motility appear to be chain-length dependent, in contrast to the effects on distal gut-hormone release and intestinal motility and transit, which appear to be chain-length independent.

Effect of oral anticoagulant treatment on markers for calcium and bone metabolism.

Vitamin K-dependent proteins regulate blood coagulation as well as bone growth and calcification. Here, we have compared the effects of oral anticoagulants on circulating vitamin K-dependent proteins and on markers for calcium and bone metabolism. Patients with a clinical indication for antithrombotic therapy were randomized into three groups and treated with either aspirin, regular-intensity anticoagulation [target international normalized ratio (INR) values: 2.5-3.5] or low-intensity anticoagulation (target INR values: 1.1-1.6). At the start and after 1 year of treatment, various biochemical markers were assessed. Both the circulating levels and the degree of carboxylation of the various gamma-carboxyglutamate (Gla)-containing proteins were affected differently by oral anticoagulant treatment. Circulating osteocalcin was more sensitive to poor vitamin K status than other Gla proteins. From the fact that - except for osteocalcin - neither markers for osteoblast nor osteoclast function were affected by oral anticoagulant treatment, we conclude that bone turnover remained unaltered, which is indicative of an unchanged rate of bone loss. Whether the long-term production of undercarboxylated bone Gla proteins may have a negative effect on the quality of bone (e.g. bone strength) cannot be concluded from this study.

Differences in cholecystokinin release and gallbladder contraction between emulsified and nonemulsified long-chain triglycerides.

BACKGROUND: Fat is a potent stimulus of cholecystokinin (CCK) release. Apart from lipolysis, fatty acid chain length, and saturation, emulsification may also determine the magnitude of CCK release. METHODS: We have studied the effect of emulsification of soybean oil on CCK and pancreatic polypeptide (PP) release (radioimmunoassay [RIA]) and gallbladder motility (ultrasonography). Six healthy subjects were studied on three separate occasions in random order during (1) intraduodenal administration of emulsified long-chain triglycerides (LCT) (6 mmol/h for 120 minutes); (2) equimolar amounts of nonemulsified LCT with addition of emulsifier; and (3) saline with emulsifier (control). RESULTS: Intraduodenal administration of both nonemulsified LCT and emulsified LCT induced significant (p < .05) increases in plasma CCK and PP levels and reductions in gallbladder volume. However, compared with nonemulsified LCT, emulsified LCT resulted in a readier and significantly stronger CCK release (212+/-62 pmol/L per 120 minutes vs 36+/-7 pmol/L per 120 minutes; p < .05); PP release (2034+/-461 pmol/L per 120 minutes vs 671+/-106 pmol/L per 120 minutes; p < .05); and gallbladder contraction (77%+/-2% vs 41%+/-7%; p < .05). No significant alterations were observed in plasma CCK or PP levels and gallbladder volume during administration of saline with emulsifier. CONCLUSIONS: Intraduodenal administration of a low-dose emulsified LCT more potently stimulates CCK and PP release and gallbladder contraction in comparison to equimolar amounts of nonemulsified LCT. These findings point to an important role for solubilization of LCT in determining the magnitude of CCK release from the intestine.

Antroduodenal motility and small bowel transit during continuous intraduodenal or intragastric administration of enteral nutrition.

BACKGROUND: Gastrointestinal intolerance is observed more frequently during intraduodenal (ID) tube feeding than during intragastric (IG) feeding, possibly because it evokes a stronger gastrointestinal response and accelerates small bowel transit. We have investigated whether the accelerated small bowel transit during ID feeding results from alterations in antroduodenal motility pattern. DESIGN: The effect of IG and ID infusion of a polymeric diet (Nutrison, 125 kcal h-1) on antroduodenal motility, small bowel transit time (SBTT) and gastrointestinal hormone release was studied in nine healthy subjects. These subjects were studied on three occasions for 6 h during fasting, continuous IG or ID feeding. RESULTS: Phase III recurrence time was significantly prolonged during IG feeding compared with fasting (240 +/- 51 vs. 136 +/- 24 min; P < 0.05). None of the subjects had recurrence of phase III during ID feeding; the fed motor pattern remained present. Parameters of fed motility (mean amplitude and motility index) were not significantly different between IG and ID feeding, although the frequency of antral and duodenal contractions was lower during ID than during IG feeding. SBTT was significantly accelerated during ID compared with IG feeding and with fasting (58 +/- 8 vs. 73 +/- 9 and 83 +/- 10 min respectively; P < 0.05). Plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels were significantly higher during ID than during IG feeding. Peptide YY (PYY) levels were significantly higher during ID than during fasting, but not during IG feeding CONCLUSIONS: During intraduodenal feeding, a fed motility pattern is preserved, whereas during intragastric feeding transition from a fed to a fasting motor pattern is observed in over 50% of the subjects. These differences may be related to augmented hormone release during intraduodenal feeding.

Effect of intragastric or intraduodenal administration of a polymeric diet on gallbladder motility, small-bowel transit time, and hormone release.

OBJECTIVE: During postpyloric tube feeding, GI intolerance is observed more frequently than during prepyloric feeding, possibly by evoking a stronger GI response. METHODS: We investigated the effect of intragastric and intraduodenal administration of a polymeric diet (125 kcal/h) on gallbladder motility (by ultrasonography), duodeno-cecal transit time (by lactulose H2 breath test), and GI hormone release (including cholecystokinin, pancreatic polypeptide, and gastrin). Six healthy subjects (two male, four female; mean age 22 yr, range 18-27 yr) were studied on two separate occasions in random order during 6 h of continuous administration of the diet through either the gastric or duodenal port of a two-lumen tube. RESULTS: Intraduodenal feeding resulted in a more rapid contraction of the gallbladder, from 32 +/- 4 to 23 +/- 4 cm3 at 10 min (p < 0.05), reaching a minimum of 6 +/- 1 cm3, in contrast to intragastric feeding (31 +/- 4 to 19 +/- 3 cm3 at 60 min, p < 0.05; minimum 14 +/- 1 cm3). The gallbladder remained contracted during the 6-h study period during both intraduodenal and intragastric feeding. Small-bowel transit time was significantly accelerated during intraduodenal compared with intragastric feeding (51 +/- 12 vs 81 +/- 9 min; p = 0.003). Plasma cholecystokinin secretion was significantly (p < 0.05) increased during intraduodenal compared with intragastric feeding (848 +/- 107 vs 279 +/- 89 pmol x L(-1) x 360 min). The same was true for pancreatic polypeptide secretion. However, gastrin release was significantly (p < 0.05) higher during intragastric feeding. CONCLUSIONS: Intraduodenal feeding elicited a stronger GI response than intragastric feeding, as demonstrated by accelerated small-bowel transit time, more rapid and stronger gallbladder contractions, and increased cholecystokinin and pancreatic polypeptide release. Gastrin release, on the other hand, was stronger during intragastric feeding.

Prospective study of the effect of the Belsey Mark-IV fundoplication on reflux mechanisms.

BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism permitting gastroesophageal reflux (GER). Little information is available on how anti-reflux surgery affects reflux mechanisms, especially TLESRs. We evaluated the effects of partial fundoplication (Belsey Mark IV) on reflux mechanisms. METHODS: Sixteen patients were prospectively studied before and after Belsey Mark-IV operation by endoscopy, 24-h esophageal pH-metry, and simultaneous recording of pH and lower esophageal sphincter (LES) characteristics by sleeve manometry. RESULTS: The operation was successful in 14 of 16 patients (87%). Fasting and postprandial reflux decreased significantly (P < 0.01) after the operation. Partial fundoplication significantly (P < 0.05) decreased the number of TLESRs per hour in the fasting and postprandial period from 3.2+/-0.4 and 5.6+/-0.5 to 1.7+/-0.3 and 2.8+/-0.4, respectively. The percentage of TLESRs associated with reflux also decreased significantly (P < 0.05). Basal LES pressure increased from 14.7+/-2.1 mmHg to 17.9+/-2.6 mmHg (not significant). CONCLUSIONS: Partial fundoplication controls GER through a reduction in the number of TLESRs and by decreasing the number of relaxations associated with reflux.

Effect of medium- and long-chain triglycerides on lower esophageal sphincter pressure: role of CCK.

Fat meals are known to decrease lower esophageal sphincter (LES) pressure, possibly through postprandial CCK release. Dietary fat consists mainly of long-chain triglycerides (LCT), which potently stimulate CCK secretion. This effect contrasts with that of medium-chain triglycerides (MCT), which do not induce CCK release. We recorded LES pressure and gallbladder volume in six healthy subjects on five separate occasions during intraduodenal administration of 1) saline control, 2) LCT, 3) MCT, 4) LCT during intravenous infusion of the CCK receptor antagonist loxiglumide, and 5) MCT together with loxiglumide. LES pressure decreased significantly during administration of both LCT and MCT. Loxiglumide completely prevented the reduction in LES pressure during intraduodenal LCT, but not during intraduodenal MCT. Gallbladder volume decreased during LCT, but not during MCT. It is concluded that intraduodenal administration of equimolar amounts of both LCT and MCT significantly reduces LES pressure. The effect of LCT on LES pressure is mediated by CCK. The effect of MCT is not dependent on CCK, since MCT does not release CCK and loxiglumide does not prevent the MCT-induced reduction in LES pressure.

Gallbladder motility and cholecystokinin secretion during continuous enteral nutrition.

OBJECTIVES: During total parenteral nutrition, gallbladder motility is impaired, resulting in sludge and stone formation. Little is known about gallbladder motility during prolonged enteral nutrition. METHODS: We studied gallbladder motility during continuous enteral nutrition (CEN) in nine hospitalized patients with active inflammatory bowel disease. The patients received a polymeric diet (2000 kcal/24 h) by CEN through a nasogastric tube for a prolonged period. Gallbladder volumes were obtained daily by ultrasonography, starting from day 0 (before CEN) and on 7 consecutive days during CEN. At days 0, 1, 4, and 7, the gallbladder response to i.v. cholecystokinin (CCK-33; 0.5 Ivy Dog unit/kg/h) was studied. Plasma CCK levels were determined at regular intervals by radioimmunoassay. RESULTS: No significant differences were observed on day 0 between patients and a group of nine healthy control subjects in fasting gallbladder volumes (19.4 +/- 2.3 and 19.6 +/- 2.4 cm3, respectively) and gallbladder contraction during CCK infusion (56 +/- 14% and 69 +/- 7%, respectively). During CEN, from day 1 to day 7, mean gallbladder volume remained significantly (p < 0.05) reduced compared with fasting gallbladder volume, and mean plasma CCK levels remained significantly (p < 0.05) increased compared with fasting levels. Although gallbladder volume was significantly reduced during CEN, the gallbladder contractile response to CCK was not affected; at days 1, 4, and 7, gallbladder contraction was 36-57%. CONCLUSIONS: During CEN, 1) gallbladder volume is significantly reduced and plasma CCK levels are significantly increased, 2) these effects are sustained over time (7 days), and 3) the gallbladder remains responsive to exogenous CCK. These results indicate that gallbladder contractility and gallbladder responsiveness to CCK are preserved during prolonged CEN in patients with inflammatory bowel disease.

Do patients with systemic sclerosis have abnormal gallbladder function?

OBJECTIVE: To determine gallbladder motility in patients with systemic sclerosis. DESIGN: Case control study. SETTING: University hospital, out-patient department of rheumatology. PATIENTS: Ten patients with systemic sclerosis according to the criteria of the American Rheumatism Association with documented involvement of the gastrointestinal tract and 10 healthy controls matched for age, sex and body mass index. INTERVENTION: Cephalic vagal cholinergic simulation by modified sham feeding and hormonal stimulation by infusion of cholecystokinin. MEASUREMENTS: Gallbladder volume obtained by ultrasonography and determination of plasma cholecystokinin concentrations. RESULTS: Fasting gallbladder volumes were not significantly different between patients with systemic sclerosis and controls (19.6 +/- 1.9 cm3 and 23.3 +/- 2.9 cm3, respectively, mean plus or minus standard error of the mean). Neither were there significant differences in reduction of gallbladder volume in response to modified sham feeding (35 +/- 4% and 33 +/- 4%, respectively) nor during cholecystokinin infusion (56 +/- 4% and 60 +/- 6%, respectively). The increase in plasma cholecystokinin levels during infusion was not different in the two groups. CONCLUSION: Gallbladder motility in patients with systemic sclerosis is preserved in response to both cholinergic and hormonal stimulation, even when other gastrointestinal motor disturbances are present. These results suggest that patients with systemic sclerosis are not at increased risk for cholelithiasis because of gallbladder dysmotility.

Effect of antrectomy and truncal vagotomy on erythromycin induced pancreatic polypeptide secretion.

Erythromycin, a motilin agonist, enhances gastrointestinal motility but also stimulates endogenous pancreatic polypeptide (PP) secretion. We investigated whether the effect of erythromycin on PP release is dependent on (1) prokinetic activity of erythromycin generated from the antrum and (2) the long vagus nerve since erythromycin acts via cholinergic neurons. Erythromycin induced PP secretion was determined in 14 patients with antrectomy (6 patients with Billroth I type anastomosis, 8 patients with Billroth II type anastomosis), in 6 patients with truncal vagotomy and pyloroplasty but without gastric resection and in 8 healthy controls. Plasma PP levels in response to erythromycin (3 mg/kg i.v.) were determined at regular intervals for 180 min. Erythromycin induced a significant increase in plasma PP in the control subjects from 22 +/- 4 pmol/l (basal) to 49 +/- 4 pmol/l at 10 min. In the patients with truncal vagotomy plasma PP secretion after erythromycin was significantly (P < 0.05) increased (peak increment vs. basal: 98 +/- 10 pmol/l vs. 27 +/- 2 pmol/l) and prolonged compared to controls. In the patients with antrectomy no significant increases in plasma PP over basal were observed after erythromycin infusion. It is concluded that erythromycin stimulates PP secretion in healthy controls. The PP response to erythromycin is exaggerated after truncal vagotomy but absent after antrectomy indicating that the antrum is essential for erythromycin induced PP secretion.

Effect of erythromycin on gallbladder emptying in patients with antrectomy or truncal vagotomy.

OBJECTIVES: Erythromycin, a motilin-like agent, stimulates gallbladder contraction in healthy control subjects. Because the action of erythromycin is cholinergic dependent and possibly related to premature phase III migrating motor complex activity in the antrum, we investigated the effect of erythromycin on gallbladder volume in six patients with truncal vagotomy without gastric resection and 14 patients with antrectomy (6 with Billroth I anastomosis, 8 with Billroth II anastomosis), and we compared the results obtained with those in eight healthy controls. In addition, the effect of meal ingestion on gallbladder volume was studied. METHODS: Gallbladder volumes, measured with ultrasonography, were determined every 15 min for 180 min after erythromycin infusion (3 mg/kg i.v.), as well as 30 and 60 min after meal ingestion. RESULTS: Basal gallbladder volumes were not significantly different among the four groups. Erythromycin induced a significant (p < 0.01-0.05) gallbladder contraction of maximal 46 +/- 6% in the controls, 49 +/- 9% in the patients with truncal vagotomy, and 38 +/- 7% in the patients with antrectomy and Billroth I anastomosis. In the patients with antrectomy and Billroth II anastomosis, no significant reduction in gallbladder volume after erythromycin was observed. Meal-induced gallbladder contraction was normal in all patients, including those with Billroth II anastomosis. CONCLUSIONS: These results indicate that neither the long vagus nerve nor the antrum is essential for erythromycin-induced effects on the gallbladder. Because no significant reduction in gallbladder volume in response to erythromycin was observed in the patients with antrectomy and Billroth II anastomosis, we suggest that duodenojejunal anatomical integrity is essential for erythromycin-induced gallbladder contraction.

'The tropics in our bathroom': chronic diarrhoea after return from the tropics.

Interest in imported tropical diseases has increased with the rising number of travellers to the tropics. This is especially true in the case of tropical gastroenterologic disorders. The causative organisms of chronic diarrhoea are different from those causing acute diarrhoea. Bacteria are relatively unusual; parasites, e.g. Entamoeba histolytica or Giardia lamblia or an opportunistic parasitic infestation associated with an HIV infection are more likely. Furthermore, non-infectious causes, such as postinfective tropical malabsorption, lactase deficiency or coeliac disease have to be considered. Today, elderly people often undertake a journey to the tropics; in these cases the diarrhoea may be associated not only with an increased susceptibility to tropical bowel infections but also with causes previously present, such as diverticulosis, carcinoma or inflammatory bowel disease. The classification of chronic diarrhoea following a visit to the tropics is essentially the same as that for acute diarrhoea: diarrhoea with and without fever and with and without blood. In addition, malabsorption is an important feature of chronic diarrhoea.

Effect of cholecystokinin on lower oesophageal sphincter pressure and transient lower oesophageal sphincter relaxations in humans.

The effect of cholecystokinin (CCK) on the lower oesophageal sphincter (LOS) pressure, frequency of transient LOS relaxations, and the number of reflux episodes was investigated in six healthy subjects. LOS pressure was recorded on four separate occasions during continuous intravenous infusion of either saline or CCK-33 in doses of 0.25, 0.5, or 1.0 Ivy Dog units per kg body weight per hour (IDU.kg-1.h-1) for 90 minutes. Plasma CCK concentrations did not change during saline infusion, but increased significantly from 2.5 (0.3) pmol/l to steady state levels of 4.0 (0.4) pmol/l, 6.1 (0.4) pmol/l, and 9.3 (0.9) pmol/l respectively starting from 30 minutes. LOS pressure did not change significantly during infusion of saline or of CCK-33 at doses of 0.25 or 0.5 IDU.kg-1.h-1. However, a significant (p < 0.05) reduction in LOS pressure to a minimum level of 12 (4) mm Hg at 30 minutes compared with basal level (18 (4) mm Hg) and compared with saline was observed during infusion of CCK-33 at a dose of 1.0 IDU.kg-1.h-1. In addition, oesophageal motility and pH were recorded simultaneously in these six subjects on two separate occasions one hour before (fasting) and three hours during administration of a gastric load (dextrose 5%, pH 3) combined with continuous intravenous infusion of saline or CCK-33 at a dose of 1.0 IDU,kg-1.h-1. Plasma CCK concentrations did not change during the gastric load combined with saline, but increased significantly to a steady state level of 10.8 (0.8) pmol/l during intravenous infusion of CCK. The number of transient LOS relaxations increased significantly in the first hour during administration of the gastric load compared with fasting levels, both during saline infusion (fasting: 1.7 (0.6)/h, 1st hour: 4.3 (1.2)/h) and during CCK infusion (fasting: 1.7 (0.5)/h, 1st hour: 3.8 (0.7)/h). In the second and third hours the number of transient LOS relaxations fell to fasting levels in both experiments. No significant differences were observed in the number and type of transient LOS relaxations, mechanism of gastro-oesophageal reflux, or duration of acid exposure between the two experiments. It is concluded that in healthy subjects infusion of CCK-33 in a dose of 1.0 IDU.kg-1.h-1 significantly reduces LOS pressure but does not affect the frequency of transient LOS relaxations or acid exposure time during a continuous liquid gastric load.