Treatment of supragastric belching with cognitive behavioral therapy improves quality of life and reduces acid gastroesophageal reflux.

OBJECTIVES: Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. METHODS: Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. RESULTS: Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31 patients were shown to have a reduction in SGB by >50%. In patients with increased AET at baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after: 140 (80-210) mm, P<0.0001). CONCLUSIONS: Cognitive behavioral therapy reduced the number of SGB and improved social and daily activities. Careful analysis of MII-pH allows identification of a subgroup of GERD patients with acid reflux predominantly driven by SGB. In these patients, CBT can reduce esophageal acid exposure.

Anatomy and physiology of the esophageal body.

The primary role of the esophagus is to propel swallowed food or fluid into the stomach and to prevent or clear gastroesophageal reflux. This function is achieved by an organized pattern that involves a sensory pathway, neural reflexes, and a motor response that includes esophageal tone, peristalsis, and shortening. The motor function of the esophagus is controlled by highly complex voluntary and involuntary mechanisms. There are three different functional areas in the esophagus: the upper esophageal sphincter, the esophageal body, and the LES. This article focused on anatomy and physiology of the esophageal body.

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis.

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.

Aetiology of running-related gastrointestinal dysfunction. How far is the finishing line?

30 to 65% of long distance runners experience gastrointestinal (GI) symptoms related to exercise. Several hypotheses have been postulated; however, the aetiology and pathophysiology are far from clear. The mechanical effect of running on the viscera must be involved in the development of GI symptoms in this sport. Reduction of splanchnic blood flow due to visceral vasoconstriction is another widely supported theory; nevertheless, it does not explain many of the clinical findings. Examination of the GI tract during exercise is a difficult task, and measurements of both orocaecal and whole-gut transit time have shown equivocal results. GI hormones, and especially prostaglandins, may be of crucial importance for the production of symptoms. Intestinal absorption, secretion and permeability may also be altered during exercise, provoking intestinal dysfunction. Factors such as stress, diet, dehydration, infections and other factors need to be analysed in order to present a global view of the hypotheses regarding the aetiology of this common and often overlooked problem.

The role of gastrointestinal endoscopy in long-distance runners with gastrointestinal symptoms.

BACKGROUND: Exercise-related gastrointestinal symptoms are not uncommon among athletes. The occurrence of gastrointestinal bleeding has been reported, especially in long-distance runners. We studied gastrointestinal mucosal damage, using gastrointestinal endoscopy, in competitive long-distance runners. Gastrointestinal blood loss and anaemia before and after running were also assessed. METHODS: Sixteen competitive long-distance runners (all men; age range 16-19 years) participated in the study. All runners completed a symptom questionnaire prior to a 20 km race. Stool occult blood and haematological studies (haemoglobin, haematocrit, serum iron, total iron-binding capacity [TIBC] and ferritin) were performed before and immediately after the race. Gastrointestinal endoscopy was performed to assess macroscopic changes. Colonoscopy was also performed on the patients who had positive stool occult blood before or after the race. RESULTS: Gastrointestinal symptoms were frequently experienced by the runners. Gastritis (n = 16), oesophagitis (n = 6) and gastric ulcer (n = 1) were found at gastroscopy. Colonoscopy was performed on four patients who had positive stool occult blood. One had multiple erosions at the splenic flexure and one had a rectal polyp. Five runners had anaemia, and all of these had at least one endoscopic lesion (three gastritis, two oesophagitis and one multiple erosion at the splenic flexure). There were significant changes in the following haematological parameters after the race: iron (decreased, P = 0.02), ferritin (decreased, P = 0.001) and TIBC (increased, P = 0.00005). CONCLUSIONS: Gastrointestinal symptoms and gastrointestinal mucosal damage are prevalent among long-distance runners. Prior to treatment, gastrointestinal endoscopy should be considered in long-distance runners with gastrointestinal symptoms and/or anaemia.

The effect of pH change on the gastric emptying of liquids measured by electrical impedance tomography and pH-sensitive radiotelemetry capsule.

Citrate phosphate buffer liquid adjusted to different pH values was used to investigate the gastric emptying profiles in human using simultaneous monitoring by electrical impedance tomography (EIT) and pH sensitive radiotelemetry capsule. No interference was observed between the two methods during data acquisition periods. A positive correlation between methods from the pooled data was demonstrated. Statistical moments analysis demonstrated a significant delay in the onset of gastric emptying and also the mean gastric residence time of the pH 3 buffer liquid (34.7-46.7 min) when compared with pH 7 buffer liquid (14.4-22.5 min). These data suggest that the negative feedback gastrin related response to acidity of the liquid was high. However, incorporation of an acid suppression compound (ranitidine), as part of the control study showed that the EIT imaging of this buffer could be successfully performed under normal physiological conditions. When 450 ml pH 7 buffer liquid was measured, no significant difference in gastric emptying rate was observed. This study demonstrated that, citrate phosphate buffers can be used as an alternative test liquid for EIT monitoring, and that pH has a systematic effect on gastric emptying and the lag phase.

Pelvic bioelectrical impedance measurements to detect rectal filling.

Anorectal sensory deficits are an important cause of defecatory disorders and are also a reason for evacuatory difficulties in patients undergoing total anorectal reconstruction. A method to detect rectal filling would be beneficial in such patients. We have investigated the feasibility of detecting rectal filling in vitro and in vivo by measuring changes in pelvic impedance. In vitro, a model of the pelvis was constructed using a cylindrical plastic tank filled with an electrolyte solution (conductivity 3 mS cm(-1)). Conductive Visking tubing representing the rectum was suspended in the tank and incrementally filled with artificial faeces. An impedance meter detected changes in voltage on rectal filling when an alternating current of 2 mA was passed at eight frequencies (4.8 to 612 kHz). In vivo, changes in pelvic bioelectrical impedance upon retrograde and antegrade rectal filling with artificial faeces were evaluated in three pigs, four electrodes being implanted in the pelvis. Impedance measurements accurately detected 'rectal' volume changes in vitro (n = 10, p < 0.0001; Kruskal Wallis), but not in vivo (n = 68, p = 0.48; Kruskal Wallis). This was probably due to extreme sensitivity of the detecting device to movement, a problem that needs to be resolved before this technique could be used in man.

Objective evaluation of small bowel and colonic transit time using pH telemetry in athletes with gastrointestinal symptoms.

BACKGROUND: Gastrointestinal (GI) disturbances are often reported by long distance runners and are more common in women, particularly after prolonged high intensity exercise. OBJECTIVES: To determine whether these symptoms could be associated with alterations in GI motility. METHODS: Small bowel and colonic transit were measured using pH telemetry in a group of 11 female athletes (age 22 to 53 years), six of whom experienced lower GI symptoms during exercise. Subjects participated in two experimental sessions: a control measurement, where small bowel transit was estimated during a rest period (R) of six hours; and an exercise session (E), where small bowel transit was measured during a one hour period of high intensity exercise (cross country running) at >70% VO(2)max. Colonic transit was estimated indirectly from determinations of whole gut transit time by radio-opaque marker. RESULTS: Small bowel transit time was 3.5 to 10.6 h (R) and 3.0 to 8.7 h (E) in asymptomatic athletes, versus 4.0 to 6.6 h (R) and 4.6 to 7.3 h (E) in symptomatic athletes (NS). Colonic transit time was 35.0 to 62.5 h (R) and 30.5 to 70.9 h (E) in asymptomatic athletes versus 20.4 to 42.9 h (R) and 21.5 to 67.2 h (E) in symptomatic athletes (NS). CONCLUSIONS: Small bowel and colonic transit times were similar in the two groups in the rest and exercise sessions. The diarrhoea seen in this study did not result from accelerated colonic transit. Other mechanisms must be sought.

[Therapeutic effectiveness of 131I-MIBG on malignant pheochromocytoma--results of long-term follow-up].

The therapeutic response of 131I-MIBG was evaluated in 4 patients with malignant pheochromocytoma who had been treated with 131I-MIBG and followed-up over 5 years. The patients were 2 men and 2 women with ages ranging from 41 to 69 years old (mean 53 years). The primary tumors in 3 of 4 patients had been resected four to eight years before 131I-MIBG treatment. One patient was diagnosed as adrenal pheochromocytoma, and two were retroperitoneal paraganglioma. And in one patient, the resection of primary mediastinal tumor was not performed due to the adhesion to pericardium but the diagnosis of paraganglioma was obtained by biopsy of bone lesion. All patients showed the clear accumulation of 131I-MIBG in tumor on scintigraphy. The number of doses of 131I-MIBG ranged from one to three times with 3.7 GBq per administration and a cumulative activity from 3.7 to 11.1 GBq. Treatment effect was obvious in one patient with lung, bone, and lymph node metastases whose cumulated absorbed dose with 11.1 GBq of 131I-MIBG exceeded over 150 Gy. At the present time, the duration of survival since the beginning of initial 131I-MIBG therapy is over 5 yrs. The other three patients, however, showed little effects, and died with the disease in 2.6 to 4.1 years after the initial 131I-MIBG therapy. 131I-MIBG will become a promising agent for therapy in patients with malignant pheochromocytoma with high degree of accumulation.

Randomised clinical trial: pregabalin attenuates the development of acid-induced oesophageal hypersensitivity in healthy volunteers - a placebo-controlled study.

BACKGROUND: Acid infusion in humans induces primary and secondary oesophageal hypersensitivity. The effects of pregabalin, a centrally-acting modulator of voltage-sensitive calcium channels, on development of acid-induced oesophageal hypersensitivity remain unknown. AIM: To study the effects of pregabalin on development of secondary oesophageal hypersensitivity in healthy humans. METHODS: Placebo-controlled, double-blind, randomised, cross-over study of 15 healthy volunteers (six women, age 21-56 years). After oesophageal manometry, baseline pain thresholds (PTs) to proximal oesophageal electrical stimulation were determined using bipolar ring electrodes. A 30-min infusion of HCl was performed in the distal oesophagus followed by PT measurements at 30 and 90 min. This protocol was repeated after administration of pregabalin (dosing schedule: 75 mg twice daily for 3 days then 150 mg twice daily for 1 day and then 150 mg on the morning of study) or placebo. RESULTS: T0 PTs were similar in patients after receiving placebo or pregabalin [mean (s.d.) 32.9 mA (20.5) vs. 34.1 (15.7), P = 0.42]. Pregabalin reduced development of acid-induced hypersensitivity in the proximal oesophagus at 30 min [mean change in PT (C.I.) placebo -6.2 mA (-11.3 to +1.3) vs. pregabalin +0.20 mA (-2.7 to +3.3)] and 90 min [placebo -3.7 mA (-10.0 to +2.0) vs. pregabalin +0.7 mA (-4.7 to 7.3)] overall P = 0.001. Pregabalin reduced median visual analogue scale score for acid-induced pain (1/10 vs. placebo 3/10, P = 0.027). CONCLUSIONS: Pregabalin attenuates development of secondary hypersensitivity in the proximal oesophagus after distal oesophageal acidification; it may thus have a role in treatment of patients with proven oesophageal pain hypersensitivity.

The effect of different types of exercise on gastro-oesophageal reflux.

Sportsmen and women frequently experience abdominal and chest pain during exertion. The symptoms could be cardiac but may be caused by gastro-oesophageal reflux (GOR). The aim of our study was to investigate the effect of the two activities on GOR in 17 fit, healthy adults. GOR, assessed by intraoesophageal pH, was recorded on portable monitoring equipment before, during and after rowing and running. GOR was also measured after a light meal to simulate pre-training hydration. Three studies were performed: rowing, fasted running, and post-prandial running. GOR was infrequent before exercise, being seen in only 2 subjects. However, GOR was induced in 70% of rowers, 45% of fasted runners, and 90 % of fed runners during and immediately after exercise. The presence of food in the stomach greatly increased the amount of reflux during post-prandial running, (p < 0.006 against control) but reflux was also significantly higher in those who refluxed during fasted running (p < 0.03) and rowing (p < 0.08). There was no statistical difference in the amount of GOR between the two exercise periods. This study shows that both running and rowing induce significant amounts of GOR in a normally asymptomatic group of athletes. GOR should be considered in the investigation of exertional chest pain in patients attending a sports clinic.

Relationship between symptom response and oesophageal acid exposure after medical and surgical treatment for gastro-oesophageal reflux disease.

BACKGROUND: The relationship between symptom severity and objective evidence of gastro-oesophageal reflux disease (GORD) after medical and surgical treatment has recently been questioned. This study aimed to compare the symptomatic and physiological response (as measured by pHmetry) to the treatment of GORD by proton pump inhibitors (PPIs) and by laparoscopic antireflux surgery, and to examine the relationship between the patient's subjective and objective response to treatment of GORD. METHODS: Seventy patients underwent 24-h oesophageal pH measurement and DeMeester symptom assessment (for heartburn and regurgitation, grade 0-3) while off medical treatment, while taking PPIs and after laparoscopic fundoplication. RESULTS: The median percentage total time with oesophageal pH < 4 off treatment, during medical treatment and after fundoplication was 9.5, 4.3 and 0.5 per cent respectively. After medical treatment 30 patients became asymptomatic although 18 of these still had pathological reflux on pH testing. Of the 19 patients who remained symptomatic after surgery only two had pathological acid reflux. CONCLUSION: The symptomatic response of patients to either PPIs or antireflux surgery is a poor indicator of successful treatment in terms of reduced lower oesophageal acid exposure. A high proportion of patients whose symptoms are improved by PPIs still have pathological levels of acid reflux. Conversely, most patients who complain of reflux symptoms after antireflux surgery have no evidence of residual reflux on pHmetry.

Electrically stimulated smooth muscle neosphincter.

BACKGROUND: Most patients undergoing total anorectal reconstruction suffer some degree of incontinence despite the incorporation of an electrically stimulated gracilis neosphincter. As smooth muscle has the ability to maintain prolonged contraction without fatigue, the aim of this study was to assess the feasibility of developing an electrically stimulated smooth muscle neosphincter. METHODS: Electrical stimulation of the rabbit colon was performed via intramural wire electrodes using a constant voltage DC stimulator. Contractile activity was recorded by serosal strain gauges and an intraluminal pressure probe. RESULTS: Basal colonic pressure was 4-13 (median 11) cmH2O. Peak pressures generated by stimulated contractions (10 V, 1 ms, 10 Hz) ranged from 14 to 37 (median 26, n = 36) cmH2O and were significantly higher than those with spontaneous contractions (P = 0.005). During continuous stimulation contractions lasted for 45-96 (median 74) s. Intermittent stimulation using trains of electrical pulses of 1-2-min duration at 1-2-min intervals produced repeated contractions. Alternative contractions were produced when intermittent electrical stimulation was performed at two sites alternately with two pairs of electrodes more than 2.5 cm apart, producing a sustained high-pressure zone. CONCLUSION: An electrically stimulated smooth muscle neosphincter is feasible. It has potential applications in the management of faecal incontinence.

An ambulant porcine model of acid reflux used to evaluate endoscopic gastroplasty.

BACKGROUND: There is a lack of suitable models for testing of therapeutic procedures for gastro-oesophageal reflux disease. Endoscopic sewing methods might allow the development of a new less invasive surgical approach to treatment of gastrointestinal disorders. AIMS: To develop an animal model of gastro-oesophageal reflux for testing the efficacy of a new antireflux procedure, endoscopic gastroplasty, performed at flexible endoscopy without laparotomy or laparoscopy. METHODS: At endoscopy a pH sensitive radiotelemetry capsule was sewn to the oesophageal wall, 5 cm above the lower oesophageal sphincter, in six large white pigs. Ambulant pH recordings (48-96 hours; total 447 hours) were obtained. The median distal oesophageal pH was 6.8 (range 6.4-7.3); pH was less than 4 for 9.3% of the time. After one week, endoscopic gastroplasty was performed by placing sutures below the gastro-oesophageal junction, forming a neo-oesophagus of 1-2 cm in length. Postoperative manometry and pH recordings (24-96 hours; total 344 hours) were carried out. RESULTS: Following gastroplasty, the median sphincter pressure increased significantly from 3 to 6 mm Hg and in length from 3 to 3.75 cm. The median time pH was less than 4 decreased significantly from 9.3% to 0.2%. CONCLUSIONS: These are the first long term measurements of oesophageal pH in ambulant pigs. The finding of spontaneous reflux suggested a model for studying treatments of reflux. Endoscopic gastroplasty increased sphincter pressure and length and decreased acid reflux.

Antireflux operations at flexible endoscopy using endoluminal stitching techniques: an experimental study.

BACKGROUND: Three antireflux operations-gastroplasty, fundoplication, and anterior gastropexy-were developed for performance at flexible endoscopy without laparotomy or laparoscopy. METHODS: An endoscopic sewing machine mounted on a standard gastroscope, endoscopic knotting devices, overtube, and nylon thread were used to perform these operations in adult beagle dogs. RESULTS: Gastroplasty (n = 10) was accomplished by suturing the anterior and posterior wall of the stomach to create a gastric tube (neoesophagus) along the lesser curve. An anatomic arrangement similar to fundoplication (n = 6) was achieved by invaginating the esophagus and fixing it to the stomach 2 cm distal to the cardioesophageal junction. Anterior gastropexy (n = 6) was performed using a technique similar to that used in creating percutaneous gastrostomies. There was no mortality. Ninety percent of sutures were seen at repeat endoscopy at 4 to 8 week intervals. The gastroplasty group was selected for more extensive evaluation. Manometry using a three-channel perfused catheter system before and after the procedures showed an increase in the lower esophageal sphincter pressure (preoperative median 4.6 mm Hg; post-operative median 13.33 mm Hg, p = 0.008) and cardiac yield pressures (preoperative median 10 mm Hg; postoperative median 19 mm Hg, p = 0.007). CONCLUSIONS: This study demonstrates the feasibility of performing antireflux operations at flexible endoscopy, without laparoscopy or laparotomy, by use of endoluminal suturing techniques.

Automated quantitative analysis of nocturnal jejunal motor activity identifies abnormalities in individuals and subgroups of patients with slow transit constipation.

OBJECTIVE: Small bowel dysmotility has previously been demonstrated in some patients with slow transit constipation (STC), suggesting a generalized intestinal disorder. However, no study has addressed whether the incidence of small intestinal dysfunction differs between subgroups of patients in this heterogeneous population. Using appropriate methodology, we aimed to determine prospectively the proportion of individuals with abnormal small bowel motility, and to assess whether heterogeneity in terms of pattern of colonic transit delay (based on (111)In diethylene-triamine-pentaacetic acid (DTPA) isotope scintigraphy), or mode of onset (based on clinical history) is of importance. METHODS: Thirty-seven patients with STC underwent 24-h ambulatory jejunal manometry; data were compared with those obtained in 38 healthy controls. Automated quantitative analysis of seven variables of the nocturnal migrating motor complex was performed, to assess whether differences existed between groups, and whether individual patients had evidence of small intestinal dysmotility, defined as two or more measures of migrating motor complex variables outside the normal range. Four variables differed significantly between STC patients and controls: in phase III, propagation was slower, duration was longer, and contraction amplitude was higher; in phase II, contraction frequency was increased. Seven of 24 patients with a generalized pattern of colonic transit delay had abnormal small bowel motility compared with none of 13 with a left-sided delay (p < 0.04). These included four patients with chronic idiopathic symptoms and three with acquired symptoms. Approximately one third of patients with a generalized delay in colonic transit had evidence of jejunal enteric neuromuscular dysfunction. Individual patients with a left-sided colonic delay did not satisfy the criteria for nocturnal small bowel dysmotility, but as a group, some differences were noted from controls. In contrast to previous reports, evidence of generalized enteric dysmotility may be present irrespective of the mode of onset.

Delayed gastric emptying in human immunodeficiency virus infection: correlation with symptoms, autonomic function, and intestinal motility.

Gastric emptying may be delayed in HIV infection. We aimed to characterize the pattern of gastric emptying in HIV seropositive subjects and correlate the findings with symptoms, as well as to identify possible etiological factors. Solid gastric emptying was measured using scintigraphy in 54 HIV seropositive subjects and 12 HIV seronegative controls. Gastrointestinal symptoms were evaluated using a standardized numerical score, and autonomic function was assessed using spectral analysis of heart rate variability. Fasting and postprandial duodenojejunal activity was recorded using strain gauge manometry catheters. Gastric emptying rate, but not lag phase, was significantly delayed in HIV-infected subjects, particularly those with enteric infections and more advanced disease. Delayed gastric emptying did not correlate with symptoms, autonomic dysfunction, or small intestinal motility. In conclusion, abnormalities found in autonomic function and gastric emptying in HIV infection are multifactorial in nature. The contribution of upper gastrointestinal motor dysfunction to gastric symptoms in such individuals is unclear.

Compliance measurement of lower esophageal sphincter and esophageal body in achalasia and gastroesophageal reflux disease.

Little is known about the effect of achalasia and gastroesophageal reflux disease (GERD) on compliance of the esophageal body and the lower esophageal sphincter (LES). Twenty-two patients with achalasia, 14 with GERD, and 14 asymptomatic volunteers were assessed. Recording apparatus consisted of a specially developed PVC bag tied to a compliance catheter, a barostat, and a polygraph. Intrabag pressures were increased incrementally while the bag volume was recorded. In each subject, pressure-volume graphs were constructed for both the esophageal body and LES and the compliance calculated. In achalasia, compliance of the esophageal body was significantly higher (P < 0.01) than in controls, whereas LES compliance was similar. Patients with GERD had a highly compliant LES in comparison to both controls and to patients with achalasia (P < 0.01 and P < 0.001, respectively); however there was no difference in their esophageal body compliance. In conclusion, foregut motility disorders can cause changes in organ compliance that are detectable using a barostat and a suitably designed compliance bag. Further measurement of compliance may provide clues to the pathogenesis of these disorders.