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Background Laparoscopic sleeve gastrectomy (LSG) has recently been considered for the surgical management of refractory gastroparesis. Our study aims to determine the efficacy of LSG as a new treatment modality for gastroparesis.Methods A multi-surgeon single institution retrospective chart review of patients who underwent LSG for refractory gastroparesis from September 2016-December 2017. Pre- and postoperative Patient Assessment of Upper Gastrointestinal Disorders-Symptoms Severity Index and/or Gastroparesis Cardinal Symptom Index (GCSI) questionnaires were reviewed. A telephone survey was conducted. Statistical analysis consisted of two-sample t test and utilized SAS v9.4. A P-value <.05 was considered significant.Results There were 10 patients included and 80% were women with an average age of 43 years (24-63). Mean Body Mass Index was 24.5 (16.8-39.6), and median gastric emptying at 4 hours was 50% (30-85). Etiology of gastroparesis was 50% idiopathic, 40% diabetic, and 10% postsurgical. 80% of patients had previously undergone gastric electrical stimulator implantation, 20% pyloric botox injections, and 1 patient jejunostomy tube placement. One patient required conversion from laparoscopic to open secondary to adhesions. Median length of stay was 5 days (2-13), and median follow-up was 13.3 months. 90% of patients were tolerating a regular diet at longest follow-up with significant improvement in self-reported symptoms. GCSI scores were 33.6 preoperatively and 14.9 postoperatively (P= .01).Discussion Our study adds to the literature examining the role of LSG in the treatment of gastroparesis. LSG has favorable outcomes at short-term follow-up for patients with refractory gastroparesis.

Electrical stimulation of the lower esophageal sphincter (LES) has been shown to improve outcomes in patients with gastroesophageal reflux disease (GERD) at 2 years. The aim of the study was to evaluate the safety and efficacy of LES stimulation in the same cohort at 3 years. GERD patients with partial response to PPI, with % 24-h esophageal pH < 4.0 for >5 %, with hiatal hernia <3 cm and with esophagitis ≤LA grade C were treated with LES stimulation in an open-label 2-year trial. All patients were on fixed stimulation parameter of 20 Hz, 220 μs, 5 mA delivered in twelve, 30-min sessions. After completing the 2-year open-label study, they were offered enrollment into a multicenter registry trial and were evaluated using GERD-HRQL, symptom diaries and pH testing at their 3-year follow-up. Fifteen patients completed their 3-year evaluation [mean (SD) age = 56.1 (9.7) years; men = 8] on LES stimulation. At 3 years, there was a significant improvement in their median (IQR) GERD-HRQL on electrical stimulation compared to both their on PPI [9 (6–10) vs. 1 (0–2), p= 0.001] and off PPI [22 (21–24) vs. 1 (0–2), p< 0.001]. Median 24-h distal esophageal acid exposure was significantly reduced from [10.3 (7.5–11.6) % at baseline vs. 3 (1.9–4.5) %, p< 0.001] at 3 years. Seventy-three % (11/15) patients had normalized their distal esophageal acid exposure at 3 years. Remaining four patients had improved their distal esophageal acid exposure by 39–48 % from baseline. All but four patients reported cessation of regular PPI use (>50 % of days with PPI use); three had normal esophageal pH at 3 years. There were no unanticipated device- or stimulation-related adverse events or untoward sensation reported during the 2- to 3-year follow-up. LES-EST is safe and effective for treating patients with GERD over long-term, 3-year duration. There was a significant and sustained improvement in esophageal acid exposure and reduction in GERD symptoms and PPI use. Further, no new GI side effects or adverse events were reported.

Electrical stimulation of the lower esophageal sphincter (LES) in gastroesophageal reflux disease (GERD) patients, using EndoStim®LES stimulation system (EndoStim BV, the Hague, Netherlands), enhances LES pressure, decrease distal esophageal acid exposure, improves symptoms, and eliminates the need in many patients for daily GERD medications. To evaluate, in a post hoc analysis, the effect of LES stimulation on proximal esophageal acid exposure in a subgroup of patients with abnormal proximal esophageal acid exposure. Nineteen patients (median age 54 years; IQR 47–64; men-10) with GERD partially responsive to proton pump inhibitors (PPI), hiatal hernia ≤3 cm, esophagitis ≤LA grade C underwent laparoscopic implantation of the LES stimulator. LES stimulation at 20 Hz, 215 μs, 5–8 m Amp sessions was delivered in 6–12, 30 min sessions each day. Esophageal pH at baseline and after 12-months of LES stimulation was measured 5 and 23 cm above the manometric upper border of LES. Total, upright and supine values of median (IQR) proximal esophageal pH at baseline were 0.4 (0.1–1.4), 0.6 (0.2–2.3), and 0 (0.0–0.2) %, respectively, and at 12 months on LES-EST were 0 (0–0) % (p= 0.001 total and upright; p= 0.043 supine comparisons). 24-hour distal esophageal acid exposure improved from 10.2 (7.6–11.7) to 3.4 (1.6–7.0) % (p= 0.001). Seven (37 %) patients had abnormal (>1.1 %) 24-hour proximal acid exposure at baseline; all normalized at 12 months (p= 0.008). In these 7 patients, total, upright, and supine median proximal acid exposure values at baseline were 1.7 (1.3–4.1), 2.9 (1.9–3.7), and 0.3 (0–4.9) %, respectively, and after 12 months of LES-EST were 0 (0–0.0), 0 (0–0.1), and 0 (0–0) % (p= 0.018 total and upright; p= 0.043 supine comparisons). Distal esophageal pH for this group improved from 9.3 (7.8–17.2) at baseline to 3.2 (1.1–3.7) % at 12-months (p= 0.043). There were no GI side effects such as dysphagia, gas-bloat or diarrhea or device or procedure related serious adverse events with LES-EST. There was also a significant improvement in their GERD-HRQL scores. LES-EST is associated with normalization of proximal esophageal pH in patients with GERD and may be useful in treating those with proximal GERD. The LES-EST is safe without typical side effects associated with traditional antireflux surgery.

Colonic inertia is a frustrating motility disorder to patients, clinicians, and pathologists. The pathogenesis is largely unknown. The aims of this study were to: (1) characterize the expression of smoothelin, a novel smooth muscle-specific contractile protein expressed only by terminally differentiated smooth muscle cells, in the normal gastrointestinal (GI) tract; and (2) determine whether smoothelin is aberrantly expressed in patients with colonic inertia. A total of 57 resections of the normal GI tract (distal esophagus to left colon) were obtained from patients without GI motor dysfunction. Sixty-one colon resections were obtained from patients with a clinical diagnosis of colonic inertia. Smoothelin immunostaining was conducted on full-thickness tissue sections. In the nondysmotile controls, strong and diffuse cytoplasmic staining for smoothelin was observed in both the inner circular and outer longitudinal layers of the muscularis propria (MP) throughout the entire GI tract. The muscularis mucosae (MM) and muscular vessel walls were either completely negative or only patchily and weakly stained. The 1 exception to this pattern was observed in the distal esophagus, in which the MM was also diffusely and strongly stained. In cases with colonic inertia, a moderate to marked reduction of smoothelin immunoreactivity was observed in 15 of 61 (24.6) colon resections, selectively seen in the outer layer of the MP. The data demonstrate that smoothelin is differentially expressed in the MP and MM of the normal GI tract and suggest that defective smoothelin expression may play a role in the pathogenesis of colonic inertia in a subset of patients.

High-resolution manometry (HRM) makes it possible to better evaluate spatial and temporal characteristics of esophageal motor function. This technology is revealing new observations regarding disordered motor function in esophageal diseases.

Abstract This study determined the effect of low-frequency and high-frequency gastric electrical stimulation (GES) on canine lower esophageal sphincter (LES) pressure and also evaluated the effect of such stimulation on neurohumoral factors that modulate LES pressure. Eight dogs were fitted with stimulation wires along the greater curvature of the stomach. A sleeve device measured LES pressure before, during, and after GES, and regulatory peptides were measured during fasting and after a meal. A consistent and significant rise in LES pressure was observed during GES, and it was sustained after GES was discontinued. Plasma concentration and area under the curve of pancreatic polypeptide, motilin, gastrin and neurotensin were not affected by GES. We conclude that acute low- and high-frequency GES significantly increases LES pressure. This effect may not be modulated by efferent vagal activity or release of regulatory peptides.

Gastric electrical stimulation (GES) was shown to improve symptoms in patients with gastroparesis. However, the underlying mechanisms remain unclear. This study assessed the influence of various patterns of GES on fasting and postprandial gastric acid secretion and 24-hr gastric pH. Eight healthy dogs were studied and we found that in the fasting state, low-frequency, long-pulse (6/12-cpm, 375-msec, 4-mA) GES at the proximal stomach significantly inhibited the secretion of gastric juice (P< 0.05). No such effect was observed during GES (6/12 cpm) at the distal stomach. In the postprandial period, low-frequency, long-pulse GES at both proximal and distal sites and at both frequencies did not significantly affect gastric acid secretion. High-frequency, short-pulse GES, investigated for obesity (21 Hz, 8 mA, and 250 μsec, with 2 secs on, 3 sec off), at the proximal and distal stomach did not significantly affect the 24-hr gastric pH profile. In conclusion, GES with various stimulation parameters, and at various sites, has little effect on gastric acid secretion. The clinical effects induced by GES at these parameters may not be related to their effect on gastric acid homeostasis.

Objective:It has been reported that electrical stimulation at the distal stomach can disrupt intrinsic gastric electrical activity and delay gastric emptying. Gastric dysrhythmia and impaired gastric emptying are associated with upper gastrointestinal symptoms and weight loss. The purpose of this study was to evaluate the effect of low‐frequency/long‐pulse gastric electrical stimulation (GES), at proximal and distal stomach, on canine gastric emptying, food intake, and body weight. Research Methods and Procedures:Eight dogs were surgically implanted with four pairs of electrodes along the greater curvature and a gastric tube at the dependent part of the stomach. Liquid gastric emptying at baseline, during proximal and distal GES at 6 cycles per minute, was assessed first by a dye dilution technique. Proximal and distal GES were then randomly delivered during feeding for 10 consecutive days, and food intake and body weight were recorded daily. Results:There was no significant difference in gastric emptying parameters among the various sessions. The mean daily food consumption was significantly reduced during both sessions of GES, resulting in significant immediate weight loss. Percentage weight loss was comparable between both sessions of GES. Discussion:Short‐term GES significantly reduced canine food intake and weight. This effect may not be related to changes in gastric emptying. GES may have a potential role in the treatment of obesity.

We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case–control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 ± 0.8 in IBS subjects and 2.2 ± 1.0 in controls (P< 0.000001). The duration of phase III was 305 ± 123 sec in IBS subjects and 428 ± 173 in controls (P< 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P< 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.

Growth factors, such as epidermal growth factor (EGF), are known to protect upper gut mucosa against irritants and to enhance healing of ulcerative lesions in animal models. A number of salivary growth factors are found in human saliva. The aim of this study was to determine if salivary growth factors and cytokines are deficient in patients with esophagitis or with Barrett's metaplasia. Fifteen healthy subjects, eight patients with esophagitis, and 13 patients with Barrett's metaplasia were included. Salivary concentration of EGF, FGF, IL-1, and IL-6 were measured during esophageal saline and hydrochloric acid perfusion and in the postprandial state. There was no statistically significant difference in the concentration of EGF or cytokines among the three study groups in each experimental condition or among the three experimental conditions in each group. FGF basic could not be detected in saliva. In conclusion, these findings do not support the hypothesis that a deficiency in salivary growth factors or cytokines plays a significant role in the development of mild to moderate reflux esophagitis or Barrett's metaplasia.

Abstract: Diabetes mellitus affects various organs, including the gastrointestinal tract. The stomach is commonly affected, and symptoms related to the upper GI tract are frequently reported. Management of diabetic gastropathy involves dietary modifications, pharmacological agents, and occasionally, alternative feeding methods.

We performed esophageal investigations in 20 patients suffering from noncardiac chest pain in order to assess the diagnostic value of short-versus long-term manometric and pH studies. Patients had baseline esophageal manometry with two provocative tests: a Bernstein test and an intravenous injection of edrophonium. On a separate occasion they had a 24-hr ambulatory esophageal pH and motility recording. The Bernstein test provoked chest pain in two patients, while edrophonium injection did not elicit pain in any of the patients. The ambulatory pH study helped to establish the esophagus as the likely source of pain in one patient, and the ambulatory motility one in another. In our experience, ambulatory pH and motility recordings have a low diagnostic yield in the evaluation of patients with noncardiac chest pain.

Sphincter of Oddi dysfunction (SOD) is associated with abdominal pain and is treated by sphincterotomy. Of 215 patients who underwent biliary sphincterotomy for SOD in our institution, 26 reported no improvement and 25 of those were found to have pancreatic sphincter dysfunction and subsequently underwent pancreatic septotomy. Nine patients remained symptomatic after the second intervention. Six of those nine patients, and seven of the 16 patients who improved after the septotomy, agreed to undergo an ambulatory duodenojejunal (DJ) manometry. DJ manometry was abnormal in four of the six symptomatic patients but only in one of seven patients who became asymptomatic after endoscopic treatment. We conclude that the persistence of symptoms after endoscopic ablation of the biliary and pancreatic sphincters is associated with abnormal intestinal motility, which may explain in part the lack of response to the endoscopic treatment.

Abstract: Cisapride improves reflux esophagitis and enhances esophageal acid clearance. To test the effect of cisapride on salivary production, we enrolled 14 healthy volunteers in a double-blind, randomized, placebo-controlled study. Subjects received cisapride, 10 mgper os four times a day, or placebo for three days. Saliva, collected during fasted and fed states, was analyzed for volume and buffer capacity. Buffer capacity was expressed as the volume of 0.01 N HCl needed to titrate 1 ml of saliva to pH 6.1. Both volume and buffer capacity significantly increased during the fed state as compared to the fasted on both cisapride and placebo. Cisapride significantly enhanced the postprandial salivary volume and buffer capacity compared to placebo: 29.6±11.3 ml vs 22.9±9.5 ml and 1.07±0.31 vs 0.89±0.28, respectively (P<0.0001). Cisapride's enhancement of salivary flow rate and buffer capacity in the fed state may be another mechanism by which it exerts its beneficial effect in patients with reflux esophagitis.

The records of all patients who had dudenojejunal manometry (DJM) from 1989 to 1995 were retrospectively reviewed. We evaluated the main symptoms of the patients, the indication for the study, its result, and the impact on therapy and management. One hundred sixteen patients out of 154 were included in the study, of whom 96 were women and 20 were men, with a mean age of 41.2 years. Twenty-five had perfused tube studies, and 91 had prolonged ambulatory recordings. Forty-one patients were referred for evaluation of abdominal pain, 34 for chronic constipation, 24 for nausea and vomiting, 8 for pseudoobstruction, and the remaining 9 for other reasons. All patients had appropriate endoscopic, radiographic, or scintigraphic studies prior to manometry. Forty-seven (40.5%) had abnormal manometry: 20 of 41 (48.8%) for abdominal pain, 7 of 34 (20.6%) for chronic constipation, 10 of 24 (41.7%) for nausea and vomiting, 5 of 8 (62.5%) for pseudoobstruction, and 5 of 9 (55.6%) for the miscellaneous group. The various subgroups did not have specific patterns of motor abnormalities. In 22 patients (18.9%) manometry helped in the choice of therapy: in 15 patients by affecting surgical approach, particularly in the constipation group, and in 7 patients by affecting feeding options and prokinetic agents. Detection of motor abnormalities was helpful in patients with severe symptoms thought to have functional disease even when no specific therapy was rendered. Thus, DJM was abnormal in ⅖ patients referred for evaluation of suspected motility disorders. It directly affected therapy in approximately ⅕ patients, particularly in those with constipation. It is helpful in the management of patients even when specific therapy is not rendered, particularly in those with abdominal pain. The modest impact on specific therapy is related to limited availability of effective prokinetic drugs and the limited specificity and predictive value of tests results.

We studied a group of six patients with clinical, radiological, and/or manometric features of severely abnormal gastrointestinal motility. Symptoms suggestive of esophageal, small bowel, or colonic involvement were present from 1 1/2 to 40 years. All patients had elevated antinuclear antibody (ANA) titers. None had clinical or radiographic features suggestive of progressive systemic sclerosis or other connective tissue diseases. Two patients had pathologic examinations of intestinal specimens, and these did not show changes suggestive of progressive systemic sclerosis. We conclude that patients with severe gastrointestinal motility disorders can have elevated ANA titers without features of progressive systemic sclerosis or other connective tissue diseases.

Radiation-induced esophagitis can cause substantial morbidity. Experiments in lab animals have shown that pretreatment with indomethacin protects the esophagus from radiation damage. We conducted a prospective, double-blind, randomized trial of naproxen vs placebo in patients undergoing thoracic radiation therapy for lung cancer. Twenty-eight patients were enrolled, of which 26 completed the study. Sixteen patients were given a short course of radiation (30 Gy/10 fractions/2 weeks), and 10 patients were given a longer course and a larger dose (40–50 Gy/25 fractions/5 weeks). Half of the irradiated patients were treated with naproxen, 375 mg, taken orally twice a day, and half were given an identical placebo. All patients were given ranitidine 300 mg, taken orally once a day. Study drugs were taken throughout the course of radiation. Endoscopy with esophageal biopsies and brushings was performed before and on the last day of treatment. Patients kept a daily diary for symptom scoring. Symptoms such as chest pain, dysphagia, odynophagia, and/or heartburn were reported in 15 patients from both subgroups, resulting in diet restriction to liquids only in eight patients and requiring temporary discontinuation of radiation therapy in one of them. Approximately half the patients in each subgroup developed esophagitis, usually mild and usually limited to the proximal esophagus. Severity of symptoms was not proportional to the severity of esophagitis. Candidiasis was documented in eight patients, but only four had symptoms that were severe in one. We conclude that acute radiation injury to the esophagus is observed in approximately half the patients receiving radiation therapy and can result in substantial morbidity. Treatment with a prostaglandin inhibitor, naproxen, was not protective. Esophagitis may be complicated by esophageal candidiasis, but its contribution to the patient's morbidity is unclear.

To assess the efficacy of misoprostol in the treatment of patients with severe chronic constipation, nine such patients were enrolled in a double-blind, randomized, crossover study of misoprostol (1200 µg/day) or placebo, that lasted three weeks. During this period each patient received the drug for one week and placebo for another with a week washout period in between. A colonic transit study, using radiopaque markers, was performed during each of the treatment weeks, while the number of stools and their total weight was recorded by each patient for the appropriate periods. Colonic transit time was significantly and consistently decreased by misoprostal compared to placebo [66 hr±10.2 vs 109.4 hr±8.1 (P=0.0005)]. Misoprostrol significantly increased the total stool weight per week [976.5 g±288.8 vs 434.6 g±190.5 (P=0.001)] and also significantly increased the number of stools per week compared to placebo [6.5±1.3 vs 2.5±0.11 (P=0.01)]. The incidence of abdominal pain was similar in both groups. We concluded that misoprostol, during a short trial period, proved effective in increasing the frequency and weight of bowel movements and decreasing colonic transit time in patients with severe chronic constipation. It may be used as a therapeutic measure to treat such patients.

The study of small bowel motility in humans iscommonly done by one of two techniques: short-termrecording in a stationary patient or long-term recordingin an ambulatory patient. To compare the diagnostic yield of short- and long-term manometricstudies of small intestinal motility, we reviewed allprolonged records performed in our center over theyears. Long-term studies that included less than 6 hr of recording during fasting or less than 5 hrduring sleep and short-term studies using the perfusedtube technique were excluded, leaving 91/121 tracingssuitable for review. We analyzed the first 3 hr of the fasting period and the first 2 hr of thepostprandial period on one occasion and the wholetracing on another; the fasting, postprandial and sleepperiod were analyzed separately. This allowed us to compare short and long recording sessions inthe same patient. The two analyses agreed in 81/91 ofthe cases. In 7/10 patients a study was diagnosed asabnormal in the short recording but was considered normal after review of the long recording,while the opposite occurred in the remaining three.Periods of sleep and fasting contributed similarly tothe change in diagnosis. In another 6 patients withequivocal abnormalities during the short period, the longperiod helped to establish the diagnosis of normalitywith confidence. Most of the improvement in thelong-term study came from extension of the studiesduring fasting to 6-7 hr from 3 hr. Long-term recordsof small bowel motility, including study during sleepenhance the diagnostic accuracy of the test. Accuracycan be improved also simply by prolonging the recording during fasting.

A high frequency of celiac disease is reported in patients with collagenous colitis. Limited information is available on the frequency of celiac disease in lymphocytic colitis. The aim of our study was to determine the prevalence of celiac disease in microscopic colitis (collagenous and lymphocytic colitis). Patients were identified from a pathology registry of microscopic colitis from 1987 to 1999. Pathology reports and medical records were reviewed for previous small bowel biopsies and/or celiac serology. We identified 113 patients with microscopic colitis, and 46 patients underwent a small bowel biopsy and/or celiac serology. Of these, 27 patients had lymphocytic colitis (63 female; age, 58.6 ± 16.2 years) and 19 patients had collagenous colitis (79 female; age, 61.8 ± 13.6 years). Small bowel biopsy alone was performed in 28 of 46 patients, celiac serology alone was performed in 10, and both small bowel biopsy and celiac serology were performed in 8. Celiac disease was identified in 4 patients by small bowel histology; all had lymphocytic colitis (4 of 27 patients, 15). This frequency of celiac disease is significantly higher than the highest reported U.S. prevalence of celiac disease (4/1,000 individuals;p< 0.01). There is a high frequency of celiac disease in patients with lymphocytic colitis. Given the importance of the early detection of celiac disease, it should be excluded in all patients with lymphocytic colitis, particularly if diarrhea does not respond to conventional treatment.

Small bowel diverticulosis is a rare disease that is usually associated with recurrent pseudo-obstruction, bacterial overgrowth, and malabsorption. The more severe complications include hemorrhage and perforation. There is evidence to suggest that this entity is a result of small bowel motor dysfunction. For this reason, it has been associated with disorders in which a myopathic or neuropathic process is involved, such as scleroderma. The majority of patients with jejunal diverticulosis do not require surgery and can be managed medically. We report a case of jejunal diverticulosis in a 63-year-old gentleman who presented with symptoms of pseudo-obstruction. Ambulatory duodenojejunal manometry revealed several abnormalities suggestive of small bowel motor dysfunction. Enteroclysis, however, did not find evidence of mechanical obstruction, and the patient had marked improvement with cisapride and antibiotics.