Mark Schoeman

Mechanisms of gastroesophageal reflux in ambulant healthy human subjects

BACKGROUND/AIMS Investigation of the motor events underlying gastroesophageal reflux has largely been confined to resting, recumbent subjects. The motor events associated with reflux during physical activity remain unknown. The aim of this study was to investigate the patterns of lower esophageal sphincter (LES) function underlying reflux in healthy subjects and the effect of exercise and physical activity on reflux mechanisms. METHODS LES pressure was recorded with a perfused sleeve sensor in 10 healthy subjects; intraluminal transducers recorded pressure in the stomach, esophagus, and pharynx, and pH was recorded 5 cm above the LES. Signals were stored in a portable data-logger. Recordings were made for 24 hours, including moderate physical activity, periods of rest and sleep, standardized meals, and standardized exercise. RESULTS Most reflux episodes (81 of 123; 66%) occurred in the 3 hours after food intake; only 2 episodes occurred during exercise. LES pressure was < or = 3 cm H2O in 79% of reflux episodes. Transient LES relaxation was the mechanism of reflux in 82% of episodes, irrespective of activity or body position, whereas swallow-related LES relaxations accounted for 13% and persistently absent LES pressure accounted for 1%. Straining occurred in only 20% of episodes. CONCLUSIONS In ambulant healthy subjects, accurate continuous recording of LES function is possible, reflux usually occurs during transient LES relaxations, and straining is not a major factor in the induction of reflux.

Motor events underlying gastro‐oesophageal reflux in ambulant patients with reflux oesophagitis

Abstract Information on the mechanism of gastro‐oesophageal reflux in patients with reflux disease is limited largely to studies in resting recumbent subjects. Evidence exists that both posture and physical activity may influence reflux. The aim of this study was to investigate reflux mechanisms in ambulant patients with reflux oesophagitis.

Delivery of radiofrequency energy to the lower oesophageal sphincter and gastric cardia inhibits transient lower oesophageal sphincter relaxations and gastro-oesophageal reflux in patients with reflux disease

Background and aims: Radiofrequency energy (RFe) treatment to the lower oesophageal sphincter (LOS) and gastric cardia is a new luminally delivered therapy proposed as an alternative treatment for gastro-oesophageal reflux disease (GORD). However, it is unclear how RFe achieves its antireflux effect. This study investigated the effects of RFe on mechanisms of spontaneous reflux in patients with GORD. Methods: Twenty patients with GORD underwent endoscopy, symptom evaluation, and combined postprandial oesophageal manometry and pH monitoring before and six months after RFe, and 24 hour ambulatory pH monitoring before and at six and 12 months after treatment. Results: RFe reduced the rate of postprandial transient LOS relaxations from 6.8 (5.7–8.1) (median (interquartile range) per hour to 5.2 (4.2–5.8) per hour (p<0.01), and increased mean basal LOS pressure from 5.2 (SEM 0.3) mm Hg to 8.0 (SEM 0.4) mm Hg (p<0.01). The number of reflux events was reduced from 10 (2–15.3)/3 hours to 5 (3.5–8.5)/3 hours (p<0.05) and there was an associated significant reduction in acid exposure time from 5.4% (0.4–14.7) to 3.9% (0.4–6.6) (p<0.05). RFe significantly reduced ambulatory oesophageal acid exposure from 10.6% (7.8–13.0) to 6.8% (3.1–9.1) (p<0.01) at six months and 6.3% (4.7–10.9) (p<0.05) at 12 months. All patients required acid suppressant medication for symptom control before RFe. Six months after treatment, 15 patients (75%) were in symptomatic remission and 13 (65%) at 12 months. Conclusions: RFe has significant effects on LOS function that are associated with improvement in the antireflux barrier. Uncontrolled clinical data also suggest a beneficial effect in the control of reflux symptoms in these patients.

A comparison of transnasal and transoral endoscopy with small-diameter endoscopes in unsedated patients

BACKGROUND The aim of this study was to compare use and tolerance of transnasal and transoral diagnostic endoscopy with small-diameter endoscopes in unsedated patients. METHODS Patients being seen for diagnostic endoscopy were randomly assigned to have an unsedated transnasal or transoral procedure. Two prototype narrow-diameter endoscopes (a 5.3 mm fiberoptic endoscope and a 5.9 mm videoendoscope) were used. RESULTS Of 170 patients (64 women and 106 men) enrolled, 86 underwent transoral and 84 underwent transnasal endoscopy. The procedure was successfully completed using the transoral route in 85 of 86 patients and using the transnasal route in 74 of 84 patients (p = 0.004). Sixteen patients experienced mild epistaxis after transnasal endoscopy. The larger videoendoscope, when compared with the fiberoptic endoscope, accounted for a significantly higher proportion of failures (8 of 41 vs. 2 of 43, p = 0.046) and cases of epistaxis (12 of 33 vs. 4 of 41, p = 0.007). The time taken for transoral endoscopy was shorter than the transnasal route (oral mean 13.7 +/- 0.5 minutes, nasal mean 15.2 +/- 0.6 minutes, p = 0.054). There was no difference between the 2 groups with respect to tolerance of the procedure. From the endoscopists perspective, the only statistically significant difference between the 2 groups was that endoscope insertion was easier by the oral route (p = 0.007). CONCLUSIONS Unsedated transnasal endoscopy with the videoendoscope was less successful compared with the transnasal fiberoptic instrument or when compared with either instrument passed transorally. Use of the larger diameter videoendoscope also resulted in significantly more epistaxis in the transnasal endoscopy group. Endoscopists find transoral introduction of the endoscope easier; this may reflect their relative unfamiliarity with the nasal route. Once intubation has been successfully achieved for either route, patient tolerance is the same.

Prospective randomized controlled trial of argon plasma coagulation ablation vs. endoscopic surveillance of patients with Barrett's esophagus after antireflux surgery.

BACKGROUND Argon plasma coagulation is one of several techniques used to ablate Barretts esophagus. This study assessed the efficacy and safety of argon plasma coagulation in the ablation of Barretts esophagus in patients who have undergone antireflux surgery. METHODS A total of 40 patients with Barretts esophagus who had undergone a fundoplication were entered into a prospective, randomized, unblinded study comparing argon plasma coagulation with endoscopic surveillance. Treatment was repeated until either no Barretts epithelium remained or a maximum of 6 treatment sessions. RESULTS One month after the final treatment, complete ablation was achieved in 12 patients. In the remaining 8, a reduction of over 95% was observed. One patient died at 9 months of an unrelated cause. At 1 year, one patient with residual Barretts epithelium regressed completely, while relapse of Barretts esophagus was seen in another because of fundoplication failure. Buried glands were observed in 35% patients at 1 month, but only 5% at 1 year. Dysplasia was never seen. In the surveillance group, partial regression was observed in 11 patients, and, in 3 with short-segment Barretts esophagus, regression was complete. The length of Barretts esophagus increased in two patients. Two had low-grade dysplasia initially, but this was not evident at 1 year. Overall, complete ablation was achieved in 12 of 19 (63%) patients in the ablation group and 3 of 20 (15%) in the surveillance group (p<0.01). CONCLUSIONS Argon plasma coagulation of Barretts esophagus is safe and effective. The effects are durable, and buried glands may resolve with time. Long-term follow-up is required to assess the impact of argon plasma coagulation on cancer risk.

Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation defect in the offspring

A case of a 29-year-old woman who has had two episodes both clinically and biochemically consistent with acute fatty liver of pregnancy is described. These episodes occurred in two successive pregnancies, and liver biopsy confirmed the diagnosis in the second pregnancy. Both pregnancies were managed by prompt fetal delivery; on both occasions this led to a complete biochemical resolution of the liver function abnormalities. Two healthy babies were delivered by ceasarian sections. This case is of particular importance because a rapidly progressive and devastating illness developed in both infants, leading to death at 6 1/2 and 6 months, respectively. The illness in both babies was characterized by wide-spread fatty infiltration of several vital organs and a failure of any treatment to influence the outcome of that illness. Studies suggested that the illness in the children was caused by a still ill-defined disorder of fatty acid oxidation. The biochemical disorder evidenced in this family is discussed, in an attempt to shed light on the etiology of acute fatty liver of pregnancy.

Impact of Endoscopic Suturing of the Gastroesophageal Junction on Lower Esophageal Sphincter Function and Gastroesophageal Reflux in Patients with Reflux Disease

OBJECTIVES:Plication of the gastroesophageal junction by endoscopic suturing has been reported to improve symptoms and reduce acid exposure in patients with gastroesophageal reflux disease (GERD). The mechanisms underlying these effects are not well defined. The aims of our study were to determine the impact of endoscopic suturing of the gastroesophageal junction on lower esophageal sphincter (LES) function in patients with GERD.METHODS:In 15 patients (7 males) with GERD (heartburn, % time esophageal pH < 4 greater than 4%, ± history of erosive esophagitis within 6 months), two plications were performed circumferentially 1 cm below the gastroesophageal junction. Endoscopy and combined postprandial esophageal manometry and pH monitoring were performed before and 6 months after treatment; 24-h ambulatory pH monitoring and symptom assessment were also performed before, and at 6 and 12 months after treatment.RESULTS:Six months after treatment, the rate of transient LES relaxations (tLESRs) was decreased by 37% (p < 0.05) and basal LES pressure had increased from 4.3 ± 2.2 mmHg to 6.2 ± 2.1 mmHg (p < 0.05). The rate of postprandial reflux events and acid exposure time were not altered. Endoscopic suturing significantly reduced 24-h esophageal acid exposure from 9.6% (9.0–12.1) to 7.4% (3.9–10.1) at 6 months, due predominantly to a reduction in upright acid exposure. The reduction in total 24-h acid exposure was sustained to 12 months. At repeat endoscopy, only one plication was evident in 6 patients (40%) at 6 months. Seven patients (47%) remained off medications at 6 and 12 months follow-up.CONCLUSIONS:In patients with GERD, endoscopic suturing of the gastroesophageal junction results in a reduction in the rate of tLESRs, and an increase in basal LES pressure. These changes in LES function result in only a modest reduction in gastroesophageal reflux.

Anorectal Dysfunction Increases with Time Following Radiation Therapy for Carcinoma of the Prostate

OBJECTIVES:To characterize the prevalence and pathophysiology of anorectal dysfunction up to 2 yr following radiation therapy (RT) for localized carcinoma of the prostate.METHODS:Thirty-eight patients, median age 68 (range 60–82) yr with localized prostate carcinoma randomly assigned to one of two radiation dose schedules, underwent evaluation of the following variables of anorectal function before RT, as well as 4–6 wk and 1 and 2 yr after its completion: (1) symptoms, (2) anorectal motility, (3) anorectal sensory function, and (4) anal sphincteric morphology.RESULTS:There was a persistent increase in anorectal symptoms after RT. At 2 yr, bowel frequency, urgency, and fecal incontinence were increased in 50%, 47%, and 26% of patients, respectively. After RT, there were progressive reductions of (1) basal anal pressures, (2) anal pressures in response to squeeze and increased intra-abdominal pressure, (3) rectal compliance, and (4) rectal volumes associated with sensory perception and the desire to defecate. The thickness of the external anal sphincter increased with time after RT. No difference was observed between the patients in the two radiation dose schedules.CONCLUSIONS:Anorectal dysfunction following RT for prostate carcinoma is an underestimated cause of morbidity, which progresses with time. The prevalence and pathophysiology of anorectal dysfunction is similar after treatment with two commonly used radiation dose schedules.

Performance of the Glasgow-Blatchford score in predicting clinical outcomes and intervention in hospitalized patients with upper GI bleeding

BACKGROUND Data regarding the utility of the Glasgow-Blatchford bleeding score (GBS) in hospitalized patients with upper GI hemorrhage are limited. OBJECTIVE To evaluate the performance of the GBS in predicting clinical outcomes and the need for interventions in patients with upper GI hemorrhage. DESIGN Prospective observational study. SETTING Single, tertiary-care endoscopic center. PATIENTS Between July 2010 and July 2012, 888 consecutive hospitalized patients managed for upper GI hemorrhage were entered into the study. INTERVENTION GBS and Rockall scores. MAIN OUTCOME MEASUREMENTS GBS and Rockall scores were prospectively calculated. The performance of these scores to predict the need for interventions and outcomes was assessed by using a receiver operating characteristic curve. RESULTS Endoscopy was performed in 708 patients (80%). A total of 286 patients (40.3%) required endoscopic therapy, and 29 patients (3.8%) underwent surgery. GBS and post-endoscopy Rockall scores (post-E RS) were superior to pre-endoscopy Rockall scores in predicting the need for endoscopic therapy (area under the curve [AUC] 0.76 vs 0.76 vs 0.66, respectively) and rebleeding (AUC 0.71 vs 0.64 vs 0.57). The GBS was superior to Rockall scores in predicting the need for blood transfusion (AUC 0.81 vs 0.70 vs 0.68) and surgery (AUC 0.71 vs 0.64 vs 0.51). Patients with GBS scores ≤ 3 did not require intervention. LIMITATIONS Subjective decision making as to need for endoscopic therapy and blood transfusion. CONCLUSION Compared with post-E RS, the GBS was superior in predicting the need for blood transfusion and surgery in hospitalized patients with upper GI hemorrhage and was equivalent in predicting the need for endoscopic therapy, rebleeding, and death. There are potential cutoff GBS scores that allow risk stratification for upper GI hemorrhage, which warrant further evaluation.

Randomized Trial of Argon Plasma Coagulation Versus Endoscopic Surveillance for Barrett Esophagus After Antireflux Surgery : Late Results

Objective:To determine the efficacy of endoscopic argon plasma coagulation (APC) for ablation of Barrett esophagus. Summary Background Data:APC has been used to ablate Barrett esophagus. However, the long-term outcome of this treatment is unknown. This study reports 5-year results from a randomized trial of APC versus surveillance for Barrett esophagus in patients who had undergone a fundoplication for the treatment of gastroesophageal reflux. Methods:Fifty-eight patients with Barrett esophagus were randomized to undergo either ablation using APC or ongoing surveillance. At a mean 68 months after treatment, 40 patients underwent endoscopy follow-up. The efficacy of treatment, durability of the neosquamous re-epithelialization, and safety of the procedure were determined. Results:Initially, at least 95% ablation of the metaplastic mucosa was achieved in all treated patients. At the 5-year follow-up, 14 of 20 APC patients continued to have at least 95% of their previous Barrett esophagus replaced by neosquamous mucosa, and 8 of these had complete microscopic regression of the Barrett esophagus. Five of the 20 surveillance patients had more than 95% regression of their Barrett esophagus, and 4 of these had complete microscopic regression (1 after subsequent APC treatment). The length of Barrett esophagus shortened significantly in both study groups, although the extent of regression was greater after APC treatment (mean 5.9–0.8 cm vs. 4.6–2.2 cm). Two patients who had undergone APC treatment developed a late esophageal stricture, which required endoscopic dilation, and 2 patients in the surveillance group developed high-grade dysplasia during follow-up. Conclusions:Regression of Barrett esophagus after fundoplication is more likely, and greater in extent, in patients who undergo ablation with APC. In most patients treated with APC the neosquamous mucosa remains stable at up to 5-year follow-up. The development of high-grade dysplasia only occurred in patients who were not treated with APC.