Jan Willem A. Straathof

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

ObjectiveAfter 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.MethodsWe 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.ResultsMinimal 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.ConclusionsPost-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.

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 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-1CCK, and 3) 1.0 IDU ⋅ kg-1 ⋅ h-1CCK. 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-1CCK 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-1CCK was significantly increased over saline (363 ± 44 vs. 195 ± 34 ml; P < 0.01) but not during 0.5 IDU ⋅ kg-1 ⋅ h-1CCK (195 ± 14 ml; not significant). During both isovolumetric and isobaric distensions, 1.0 IDU ⋅ kg-1 ⋅ h-1CCK significantly ( P < 0.05) increased proximal gastric compliance compared with saline. However, 0.5 IDU ⋅ kg-1 ⋅ h-1CCK had no significant effect on gastric compliance. During volume distensions, but not during fixed pressure distensions, 1.0 IDU ⋅ kg-1 ⋅ h-1CCK significantly ( P < 0.05) reduced visceral perception. These results suggest that in humans CCK may have a physiological role in regulating proximal gastric mechanics.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.

Therapeutic drug monitoring of infliximab in inflammatory bowel disease patients in a teaching hospital setting: results of a prospective cohort study.

Objective Therapeutic drug monitoring (TDM) of infliximab (IFX) is not routinely implemented in our clinical practice. We therefore carried out a prospective cohort study measuring IFX trough levels in our total inflammatory bowel disease (IBD) population in relation to remission. Methods Patient demographics, and medication and clinical history were collected from the electronic hospital information system. Blood was drawn at one time point for the determination of IFX trough levels and antibodies to IFX (ATI). Disease activity indices [Crohn’s disease activity index (CDAI) and the Truelove–Witts disease activity index (TWDAI) for Crohn’s disease and ulcerative colitis, respectively] and quality-of-life scores (Visual Analog Scale) were obtained. Results We included 107 patients. IFX levels varied from less than 0.02 to 21.9 &mgr;g/ml. The median IFX level was 2.8 &mgr;g/ml [interquartile range (IQR) 1.37–5.13]. The IFX level was associated significantly with remission (P=0.007). The median IFX level was 3.9 &mgr;g/ml (IQR 1.9–6.53) in patients in remission and 2.1 &mgr;g/ml in patients with active disease (IQR 0.77–4.38) (P=0.074). Receiver operating charecteristic curve analysis indicated a cutoff value of 2.18 &mgr;g/ml for CD and 6.26 &mgr;g/ml for UC. Eleven patients (10.3%) had developed ATI. The appearance of ATI was associated with the disappearance of IFX [relative risk: 2.2 (95% confidence interval: 1.368–3.610) P<0.0001], but not with relapse. The presence of ATI induced more infusion reactions [relative risk: 11.7 (95% confidence interval: 2.74–49.60) P<0.001]. Conclusion TDM of IFX in IBD outpatients in a teaching hospital setting showed large interindividual differences in IFX trough levels. Despite this, we still found a significant association between remission and IFX trough levels. We determined cutoff values for both IBD modalities. IFX trough levels were not detectable in a significant proportion of IBD patients; TDM is indicated to identify this group of patients.

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. Eur J Gastroenterol Hepatol 12:419‐424

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.

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 swallowinduced 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 mg/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.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.

Comparison of two techniques for lower esophageal sphincter manometry: Dentsleeve and sphinctometer

We have compared the sphinctometer with the water-perfused sleeve (gold standard) for meas- urement of lower oesophageal sphincter (LOS) char- acteristics 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 under- scored by the sphinctometer.