Long-term oncological outcomes of endoscopic full-thickness resection after previous incomplete resection of low-risk T1 CRC (LOCAL-study): study protocol of a national prospective cohort study.

BACKGROUND: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization. METHODS/DESIGN: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate. DISCUSSION: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 ).

Switching from infliximab innovator to biosimilar in patients with inflammatory bowel disease: a 12-month multicentre observational prospective cohort study.

BACKGROUND: Infliximab biosimilars have become available for treatment of inflammatory bowel disease (IBD). However, data showing long-term safety and effectiveness of biosimilars in IBD patients are limited. AIM: To study prospectively the switch from infliximab innovator to biosimilar in an IBD cohort with 12 months follow-up to evaluate safety and effectiveness. METHODS: Adult IBD patients from two hospitals treated with infliximab innovator (Remicade; Janssen Biotech,  Horsham ,  Pennsylvania, USA) were switched to infliximab biosimilar (Inflectra; Hospira, Lake Forest, Illinois, USA) as part of routine care, but in a controlled setting. Blood samples were taken just before the first, second, fourth and seventh infusion of biosimilar. Infliximab trough levels, antibodies-to-infliximab (ATI), CRP and ESR were measured and disease activity scores were calculated. RESULTS: Our cohort consisted of 133 IBD patients (64% CD, 36% UC). Before switching we found widely varying infliximab levels (median 3.5 µg/mL). ATI were detected in eight patients (6%). Most patients were in remission or had mild disease (CD: 82% UC: 90%). After switching to biosimilar, 35 patients (26%) discontinued therapy within 12 months, mostly due to subjective higher disease activity (9%) and adverse events (AE, 9.8%). AE included general malaise/fatigue (n = 7), arthralgia (n = 2), skin problems (n = 2) and infusion reactions (n = 2). No differences in IFX levels, CRP, and disease activity scores were found between the four time points (P ≥ .0917). CONCLUSIONS: We found no differences in drug levels and disease activity between infliximab innovator and biosimilar in our IBD cohort, indicating that biosimilars are safe and effective. The high proportions of discontinuers were mostly due to elective withdrawal or subjective disease worsening.

Endoscopic mucosal resection (EMR) versus endoscopic submucosal dissection (ESD) for resection of large distal non-pedunculated colorectal adenomas (MATILDA-trial): rationale and design of a multicenter randomized clinical trial.

BACKGROUND: Endoscopic mucosal resection (EMR) is currently the most used technique for resection of large distal colorectal polyps. However, in large lesions EMR can often only be performed in a piecemeal fashion resulting in relatively low radical (R0)-resection rates and high recurrence rates. Endoscopic submucosal dissection (ESD) is a newer procedure that is more difficult resulting in a longer procedural time, but is promising due to the high en-bloc resection rates and the very low recurrence rates. We aim to evaluate the (cost-)effectiveness of ESD against EMR on both short (i.e. 6 months) and long-term (i.e. 36 months). We hypothesize that in the short-run ESD is more time consuming resulting in higher healthcare costs, but is (cost-) effective on the long-term due to lower patients burden, a higher number of R0-resections and lower recurrence rates with less need for repeated procedures. METHODS: This is a multicenter randomized clinical trial in patients with a non-pedunculated polyp larger than 20 mm in the rectum, sigmoid, or descending colon suspected to be an adenoma by means of endoscopic assessment. Primary endpoint is recurrence rate at follow-up colonoscopy at 6 months. Secondary endpoints are R0-resection rate, perceived burden and quality of life, healthcare resources utilization and costs, surgical referral rate, complication rate and recurrence rate at 36 months. Quality-adjusted-life-year (QALY) will be estimated taking an area under the curve approach and using EQ-5D-indexes. Healthcare costs will be calculated by multiplying used healthcare services with unit prices. The cost-effectiveness of ESD against EMR will be expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per recurrence free patient and as ICER showing additional costs per QALY. DISCUSSION: If this trial confirms ESD to be favorable on the long-term, the burden of extra colonoscopies and repeated procedures can be prevented for future patients. TRIAL REGISTRATION: NCT02657044 (Clinicaltrials.gov), registered January 8, 2016.

The effect of laparoscopic partial fundoplication on dysphagia, esophageal and lower esophageal sphincter motility.

It has been suggested that dysphagia is less common after partial versus complete fundoplication. The mechanisms contributing to postoperative dysphagia remain unclear. The objective of the present prospective study was to investigate esophageal motility and the prevalence of dysphagia in patients who have undergone laparoscopic partial fundoplication. Symptoms, lower esophageal sphincter (LES) characteristics and esophageal body motility were evaluated prospectively in 62 patients before and after laparoscopic partial fundoplication: 33 women and 29 men with a mean age of 44 +/- 1.5 years (range, 21-71). The patients filled in symptom questionnaires and underwent stationary and ambulatory manometry and 24-h pH-metry before and after operation. A small but significant increase in LES pressure from 14.8 +/- 0.9 to 17.8 +/- 0.8 mmHg was seen after laparoscopic partial fundoplication. Further, LES characteristics and esophageal body motility were not different post- versus preoperation. Three months after surgery, dysphagia was present in eight patients. No differences in LES characteristics or body motility were present between patients with and without dysphagia. Six months after the operation dysphagia was present in only three patients (3.2% mild and 1.6% severe dysphagia). Adequate reflux control was obtained in 85% of the patients. Laparoscopic partial fundoplication offers adequate reflux control without affecting esophageal body motility and with a very low incidence of postoperative dysphagia.

Comparison of two techniques for lower oesophageal sphincter manometry: sleeve and sphinctometer.

We have compared the sphinctometer with the water-perfused sleeve (gold standard) for measurement of lower oesophageal sphincter (LOS) characteristics by simultaneous recording. LOS pressure and transient LOS relaxations (TLOSR) measured by sleeve and sphinctometer in 11 healthy volunteers showed identical patterns. However, output of the sphinctometer was significantly (P < 0.01) lower than output of the sleeve. A total of 249 TLOSR were recorded. Of these, 176 TLOSR were identified by both sleeve and sphinctometer, 50 TLOSR were identified by sleeve alone and 23 TLOSR by sphinctometer alone. Due to the lower pressure output of the sphinctometer, 29 LOS relaxations did not reach criteria to qualify as TLOSRs. When TLOSR criteria were adjusted for sphinctometer pressure measurements, the number of TLOSRs identified by both sleeve and sphinctometer increased from 176 to 205. In conclusion, in healthy volunteers the sphinctometer registers TLOSR with results comparable with sleeve recording. However at low LOS pressures, the number of TLOSR is underscored by the sphinctometer.

Provocation of transient lower esophageal sphincter relaxations during continuous gastric distension.

BACKGROUND: Transient lower esophageal sphincter relaxations (TLESRs) are triggered by gastric distension. The aim of the study was to investigate TLESRs during controlled prolonged gastric distensions using the barostat technique. METHODS: Twelve healthy volunteers (4 M, 8 F, age range 19-42 years) were studied under fasting conditions with combined esophageal manometry (Dentsleeve) and gastric barostat. Randomized isobaric distensions at 0 (control), 10, 12 and 14 mmHg were performed each period for 30 min with 30-min recovery periods in between. RESULTS: The frequency of TLESR was significantly (P < 0.05) higher during all distension periods compared to control periods (4.0 +/- 0.4 TLESR/30 min versus 2.6 +/- 0.4 TLESR/30 min). The frequency of TLESR in the first 15-min period of distension was significantly (P < 0.001) higher compared to the second 15-min period pointing to adaptation (2.7 +/- 0.3 TLESR/15 min versus 1.3 +/- 0.2 TLESR/15 min, respectively). The frequency of TLESR correlated significantly with intragastric pressure (r = 0.47; P < 0.01) and wall tension (r = 0.48; P < 0.01), but not with intragastric volume. TLESR characteristics such as duration were not related to pressure or wall tension. CONCLUSIONS: Acute gastric distension increases the frequency of TLESR but adaptation occurs rapidly. The frequency of TLESR during distension is related to pressure and wall tension rather than to intragastric volume.

Prospective study of the effect of laparoscopic Nissen fundoplication on reflux mechanisms.

BACKGROUND: Laparoscopic Nissen fundoplication effectively reduces acid reflux and reflux symptoms. Little is known about the effect on reflux mechanisms, especially on transient lower oesophageal sphincter relaxations (TLOSRs). METHODS: Twenty-seven patients were studied prospectively before and after laparoscopic Nissen fundoplication, by simultaneous recording of pH and lower oesophageal sphincter (LOS) characteristics using sleeve manometry. In all of the 27 patients the operation was judged successful, based on major improvement or resolution of reflux symptoms and acid reflux. Vagus nerve integrity was studied indirectly by the secretion of pancreatic polypeptide (PP) in response to insulin-induced hypoglycaemia. RESULTS: After fundoplication basal LOS pressure increased significantly from mean(s.e.m.) 13(1) to 22(1) mmHg (P < 0.001). Laparoscopic Nissen fundoplication significantly decreased the frequency of TLOSR in the fasting period from mean(s.e.m.) 2.5(0.5) to 0.6(0.2) per h, and in the postprandial period from 4.0(0.4) to 1.3(0.3) per h (P < 0.01). The percentage of TLOSRs associated with reflux also decreased significantly from 24(10) to 0(0) per cent in the fasting period and from 42(6) to 12(6) per cent in the postprandial period, before and after fundoplication respectively (P < 0.01). After operation the PP response was abnormal in three patients, pointing to vagus nerve dysfunction. Postoperative TLOSR frequency and LOS pressure were no different between patients with and without vagus nerve dysfunction. CONCLUSION: Laparoscopic Nissen fundoplication significantly increased fasting and postprandial LOS pressure and significantly decreased the rate of TLOSR. This resulted in a significant reduction in oesophageal acid exposure but postprandial LOS characteristics were preserved.

Does Helicobacter pylori gastritis affect motor function of proximal stomach in dyspeptic patients?

The role of Helicobacter pylori infection in proximal gastric motor function and its relation to symptoms in patients with functional dyspepsia is still unclear. We prospectively studied 26 patients with dyspepsia, no structural abnormalities found during endoscopy and biopsy-proven Helicobacter pylori-positive gastritis before and three months after Helicobacter pylori treatment. We used an 11-item score list to evaluate symptoms, gastric biopsies for histology, and a gastric barostat (isobaric inflation-deflation) for proximal gastric motility. Minimal distending pressure (MDP), mean gastric volume at operating pressure, AUC of inflation-deflation cycles, and hysteresis (difference in AUC during inflation and AUC during deflation) were calculated. After three months, Helicobacter pylori was eradicated in 96% of patients. MDP, mean gastric volume at operating pressure, gastric compliance, and hysteresis did not change significantly. Aggregate symptom score as well as histology scores in antrum and corpus decreased significantly. Reduction in postprandial pain correlated with a change in hysteresis (r = 0.567, P < 0.01), but other symptoms did not. Reduction of corpus inflammatory activity correlated with changes in hysteresis (r = 0.604, p < 0.005), suggesting that the stomach attains it original shape faster when inflammation is reduced. These observations suggest that inflammatory changes or release of inflammatory substances associated with Helicobacter pylori infection may influence proximal gastric motor characteristics.

Provocation of transient lower esophageal sphincter relaxations by gastric distension with air.

OBJECTIVES: Transient lower esophageal sphincter relaxations (TLESRs) are the major mechanism permitting not only gastroesophageal reflux but also venting of air from the stomach. Triggering of TLESRs is provoked by gastric distension. Antireflux surgery is associated with impaired ability to belch. It is not known whether a reduced capacity to belch results from postoperative reduction in TLESRs. METHODS: We studied the occurrence of TLESRs, common cavities (indicator for gas gastroesophageal reflux), and belching after standardized acute gastric distension by air insufflation (750 ml). Control subjects (n = 10), patients with gastroesophageal reflux disease (GERD) (n = 22), and patients after fundoplication (n = 24) were studied. LES and esophageal motilities were recorded with perfusion manometry. RESULTS: Gastric distension with air significantly (p < 0.05) increased TLESR frequency in controls (1.6+/-0.3 to 3.5+/-1.0 per 20 min), GERD patients (1.2+/-0.3 to 3.1+/-0.5 per 20 min), and patients after fundoplication (0.5+/-0.1 to 1.8+/-0.6 per 20 min). Postfundoplication the number of TLESRs was significantly reduced (p < 0.05) both under fasting conditions and after air insufflation. The number of common cavities and belches after gastric air distension also was significantly reduced (p < 0.05) after fundoplication: 2.3+/-0.6 versus 4.7+/-0.4 in controls and 4.1+/-0.4 in GERD patients. About half of the common cavities occurred during TLESRs, and half during other mechanisms. An impaired ability to belch in daily life correlated with an impaired belching response during the test. An impaired ability to belch occurred only in patients with complete fundoplication and not in patients with partial fundoplication and was associated with a reduced number of common cavities after gastric air insufflation. CONCLUSIONS: Short-lasting gastric air distension 1) provokes TLESRs but does not differentiate GERD patients from controls, 2) reveals impaired belching capacity in patients after complete fundoplication, and 3) shows that common cavities do not exclusively occur during TLESRs.

Effect of somatostatin on lower esophageal sphincter characteristics in man.

BACKGROUND: Somatostatin (SST) is known for its inhibitory effect on the gastrointestinal tract. Transient lower esophageal sphincter relaxations (TLESR), low or absent LES pressure (LESP) and swallow-induced LES relaxations are the most important reflux mechanisms. METHODS: We have studied the effect of somatostatin on lower esophageal sphincter (LES) characteristics in man. Nine healthy volunteers participated in four experiments performed in random order and double-blind during continuous infusion of somatostatin (250 microg/h) or saline (control) under fasting and postprandial conditions. Esophageal motility was measured with sleeve manometry combined with pH metry. RESULTS: Under fasting conditions LESP was not influenced by somatostatin. Ingestion of the carbohydrate meal significantly (P < 0.01) decreased LESP. During continuous somatostatin infusion the postprandial decrease in LESP did not occur; LESP was even significantly (P < 0.05) increased over basal levels. Somatostatin did not significantly influence TLESR frequency, neither under basal conditions, nor postprandially. The residual pressure during swallow-induced LES relaxation was significantly (P < 0.05) increased by somatostatin. CONCLUSION: In humans somatostatin prevents postprandial reduction in LESP, does not affect TLESR, but inhibits swallow-induced LES relaxation.

Effect of modified sham feeding and insulin-induced hypoglycemia on function of the proximal stomach.

BACKGROUND/AIM: Animal experiments have shown that vagal cholinergic stimulation causes an increase in proximal gastric tone, but little is known about the effect of vagal stimulation on proximal gastric motor function in humans. Vagal cholinergic stimulation can be elicited by modified sham feeding (MSF) or by insulin-induced hypoglycemia. The aim of our study was to investigate the effect of MSF and insulin-induced hypoglycemia on the motor and sensory function of the proximal stomach in humans. METHODS: Eight healthy volunteers participated in random order in three experiments: (A) control experiment, (B) MSF and (C) intravenous insulin injection. Intragastric volume was recorded with a barostat set at a constant preselected pressure level (MDP + 2 mm Hg). Pancreatic polypeptide (PP) secretion was measured as an indicator of cholinergic tone. RESULTS: PP secretion increased significantly after both MSF (p<0.05) and insulin administration (p<0.01). No changes in intragastric volume were seen after MSF, while intragastric volume increased significantly in response to insulin-induced hypoglycemia when compared to control (290+/-43 vs. 148+/-24 ml; p<0.01). No differences in perception scores were seen between the three experiments. CONCLUSIONS: Vagal cholinergic stimulation by MSF has no effect on the motor function of the proximal stomach, while insulin-induced hypoglycemia causes a relaxation of the proximal stomach.

Effect of L-arginine on lower oesophageal sphincter motility in man.

OBJECTIVE: Inhibitory responses of the lower oesophageal sphincter (LOS) are mediated via an L-arginine/nitric oxide (NO) pathway. L-arginine is known as the precursor of NO. We have studied the effect of intravenous L-arginine on LOS motility in man. DESIGN: Twelve healthy subjects participated in a double-blind, placebo-controlled randomized study. METHODS: We investigated the effect of continuous infusion of L-arginine (500 mg/kg body weight/120 min) in six subjects under fasting conditions. Six other subjects were studied under postprandial conditions. LOS pressure (LOSP), swallow-induced LOS relaxations and transient lower oesophageal sphincter relaxations (TLOSR) were measured with sleeve manometry combined with pH metry. The meal consisted of a carbohydrate-high fat meal. Blood samples were taken before and after administration of L-arginine or saline to determine plasma levels of amino acids, cholecystokinin and gastrin. RESULTS: Plasma levels of arginine and citrulline significantly (P < 0.05) increased during L-arginine infusion. L-arginine did not affect plasma hormone levels. Under fasting conditions, LOSP and TLOSR were not influenced by L-arginine. Ingestion of the carbohydrate-high fat meal significantly decreased LOSP. L-arginine did not significantly influence TLOSR frequency, either under fasting conditions or postprandially. CONCLUSIONS: These results suggest that in humans under fasting or postprandial conditions intravenous infusion of L-arginine does not influence LOS motility.

Effect of gastrin on proximal gastric motor function in humans.

UNLABELLED: The present study was performed to investigate the effect of gastrin on proximal gastric motor and sensory function. Ten healthy volunteers participated in three experiments performed in random order during: (A) continuous intravenous infusion of saline (control) or (B) gastrin (15 pmol kg-1 h-1) reaching postprandial serum gastrin levels or (C) gastrin infusion (15 pmol kg-1 h-1) preceded by acute acid inhibition with intravenous omeprazole. Proximal gastric function was evaluated using a barostat with stepwise pressure and volume distensions and volume measurements during set pressure (MDP + 2 mmHg). Gastrin significantly increased the intragastric volume compared to control during MDP + 2 mmHg (276 +/- 39 mL vs. 159 +/- 9 mL; P < 0.01) and reduced phasic slow volume wave frequency (from 1.4 +/- 0.1 to 0.7 +/- 0.1 per min; P < 0.01). During isobaric distensions gastrin increased gastric compliance (42 +/- 4 mL mmHg-1 vs. 31 +/- 3 mL mmHg-1; P < 0.05). These effects of gastrin infusion were completely abolished by pretreatment with omeprazole. Symptom perception decreased during gastrin infusion and was more dependent on pressure and wall tension than on volume. IN CONCLUSION: gastrin may have a role in regulating proximal gastric mechanics by inducing fundic relaxation and increasing gastric wall compliance. The effect of gastrin is dependent on acid secretion.

Motor and sensory function of the proximal stomach in reflux disease and after laparoscopic Nissen fundoplication.

OBJECTIVE: After Nissen fundoplication, dyspeptic symptoms such as fullness and early satiety develop in >30% of patients. These symptoms may result from alterations in proximal gastric motor and sensory function. METHODS: We have evaluated proximal gastric motor and sensory function using an electronic barostat in 12 patients after successful laparoscopic Nissen fundoplications (median follow-up; 12 months). Twelve age- and gender-matched patients with severe gastroesophageal reflux disease (GERD) and 12 healthy volunteers served as controls. Studies were performed in the fasting state and after meal ingestion. Gastric emptying tests were performed in all patients. Vagus nerve integrity was measured by the response of pancreatic polypeptide (PP) to insulin hypoglycemia. RESULTS: Minimal distending pressure and proximal gastric compliance were not significantly different between post-Nissen patients, GERD patients, and healthy controls. Postprandial relaxation of the stomach, however, was significantly (p < 0.05) reduced post-Nissen (267 +/- 34 ml), compared with controls (400 +/- 30 ml) and GERD (448 +/- 30 ml). Postprandial relaxation was significantly (p < 0.01) prolonged in GERD patients. Postprandial relaxation of the stomach correlated with gastric emptying of solids (r = 0.62; p = 0.01). Gastric emptying of solids became significantly (p < 0.05) faster after fundoplication. Postprandial fullness was significantly (p < 0.05) increased in the operated patients. CONCLUSIONS: Post-Nissen patients have a significantly reduced postprandial gastric relaxation and significantly accelerated gastric emptying, which may explain postoperative dyspeptic symptoms. The abnormalities result from fundoplication and not from vagus nerve injury or reflux per se, because in reflux patients gastric relaxation and gastric emptying are prolonged.

Effects of somatostatin on proximal gastric motor function and visceral perception.

BACKGROUND: Somatostatin affects gastrointestinal motility and secretion and visceral sensation, but little is known about its effects on the proximal stomach. AIM: To evaluate the effects of somatostatin on proximal gastric motor function and perception of symptoms. METHODS: Six healthy subjects participated in two experiments performed in random order during continuous intravenous infusion of saline or somatostatin (250 microg/h). Proximal gastric motor function was evaluated using a barostat. We performed pressure and volume distensions and a barostat procedure (minimal distending pressure + 2 mmHg). Symptoms were evaluated at regular intervals using visual analogue scales (VAS). RESULTS: Neither minimal distending pressure nor gastric fundal tone were significantly different between somatostatin and saline. Pressure-volume curves during distensions were not influenced by somatostatin. However, phasic volume waves were significantly (P < 0.001) reduced by somatostatin, and somatostatin significantly (P < 0.05) reduced symptom perception of fullness and abdominal pressure during stepwise distensions.

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

OBJECTIVE: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis. METHODS: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy < or = 3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects. RESULTS: Patients with Barrett's esophagus had significantly increased acid reflux time (p < 0.01-0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (p < 0.01-0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis. CONCLUSION: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.

Effect of CCK on proximal gastric motor function in humans.

We have studied the effect of CCK on proximal gastric motor function in humans. Seven healthy volunteers participated in three experiments performed in random order during continuous intravenous infusion of 1) saline (control), 2) 0.5 IDU.kg-1.h-1 CCK, and 3) 1.0 IDU.kg-1.h-1 CCK. Proximal gastric mechanics were measured by an electronic barostat, and abdominal symptoms were scored by visual analog scales. Infusion of 0.5 and 1.0 IDU.kg-1.h-1 CCK resulted in plasma CCK levels (RIA) in the postprandial range. CCK induced gastric relaxation; at 2 mmHg above intra-abdominal pressure the intragastric volume during 1.0 IDU.kg-1.h-1 CCK was significantly increased over saline (363 +/- 44 vs. 195 +/- 34 ml; P < 0.01) but not during 0.5 IDU.kg-1.h-1 CCK (195 +/- 14 ml; not significant). During both isovolumetric and isobaric distensions, 1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) increased proximal gastric compliance compared with saline. However, 0.5 IDU.kg-1.h-1 CCK had no significant effect on gastric compliance. During volume distensions, but not during fixed pressure distensions, 1.0 IDU.kg-1.h-1 CCK significantly (P < 0.05) reduced visceral perception. These results suggest that in humans CCK may have a physiological role in regulating proximal gastric mechanics.

Effect of gastrin-17 on lower esophageal sphincter characteristics in man.

We studied the effect of gastrin-17 on lower esophageal sphincter (LES) characteristics in man. Nine healthy volunteers participated in two experiments performed in random order during continuous infusion of saline (control) or gastrin-17 (15 pmol/kg/hr). LES pressure (LESP) and transient lower esophageal sphincter relaxations (TLESR), as most the important reflux mechanism, were measured with intraesophageal sleeve manometry combined with pH metry. Infusion of gastrin-17 resulted in plasma gastrin levels comparable to those reached after a mixed meal. During continuous gastrin infusion, LESP decreased significantly (P < 0.05) compared to control. The rate and duration of TLESR was not influenced by gastrin-17. Gastroesophageal reflux and the number of TLESR associated with reflux were significantly (P < 0.05) increased during gastrin infusion. These results suggest that in humans gastrin at physiological postprandial plasma concentrations decreases LESP, does not influence TLESR, but increases the percentage of TLESR associated with reflux.

Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.

The relationships between gastric emptying and intragastric distribution of glucose and oral glucose tolerance were evaluated in 16 healthy volunteers. While sitting in front of a gamma camera the subjects drank 350 ml water containing 75 g glucose and 20 MBq 99mTc-sulphur colloid. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide were obtained at--2, 2,5,10,15,30,45,60,75,90,105,120 and 150 min. Gastric emptying approximated a linear pattern after a short lag phase (3.3 +/- 0.8 min). The 50% emptying time was inversely related to the proximal stomach 50% emptying time (r = -0.55, p < 0.05) and directly related to the retention in the distal stomach at 120 min (r = 0.72, p < 0.01). Peak plasma glucose was related to the amount emptied at 5 min (r = 0.58, p < 0.05) and the area under the blood glucose curve between 0 and 30 min was related to the amount emptied at 30 min (r = 0.58, p < 0.05). In contrast, plasma glucose at 120 min was inversely related to gastric emptying (r = -0.56, p < 0.05) and plasma insulin at 30 min (r = -0.53, p < 0.05). Plasma insulin at 120 min was inversely related (r = -0.65, p < 0.01) to gastric emptying. The increase in plasma gastric inhibitory polypeptide at 5 min was related directly to gastric emptying (r = 0.53, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)