Surgical outcome in gastro-esophageal reflux disease patients with inadequate response to proton pump inhibitors

Laparoscopic fundoplication (LF) has been shown to be effective in treatment of patients with gastro-esophageal reflux disease (GERD) requiring long-term medical therapy. Its effectiveness in patients with poor response to proton pump inhibitors (PPIs) has been questioned. We prospectively followed 445 patients with proven GERD inadequately controlled on PPI (up to 120 mg/day) and 274 GERD patients with good response to PPIs (20–120 mg/day) after LF. Patients in both groups underwent 24 h pH testing, esophageal manometry, symptom score evaluation, and quality-of-life (QOL) assessment (SF-36) before and at 6 months, 2 years, and 5 years after surgery. LF was associated with a marked improvement in percentage acid reflux, lower esophageal sphincter pressure, and symptom control in both groups of patients; however, the poor responders to PPIs also had a significant improvement in both physical and mental health component of the QOL assessment. Laparoscopic fundoplication provides an excellent symptom control for GERD patients, even those who have responded inadequately to large doses of PPIs. GERD patients who respond poorly to PPI therapy have significantly lowered physical and mental health QOL scores. Laparoscopic fundoplication in this group of patients leads to marked improvement of both components of QOL by 2 years after surgery.     

Efficacy of once-daily esomeprazole treatment in patients with laryngopharyngeal reflux evaluated by 24-hour pH monitoring.

OBJECTIVE: Laryngopharyngeal reflux (LPR) is generally treated with twice-daily proton-pump inhibitor (PPI) therapy. In this study, the efficacy of esomeprazole 40 mg once-daily together with lifestyle modifications was determined by repeated 24-hour pH monitoring. STUDY DESIGN AND SETTING: A prospective study. Forty-nine patients with suspected LPR underwent 24-hour pH monitoring. Twenty-seven of 49 patients with measurable abnormal proximal reflux reflected by a reflux area index (RAI)>6.3 were treated with esomeprazole 40 mg every day, and a second pH study was performed. RESULTS: In 22 of 27 patients, everyday PPI treatment reduced the RAI. Four of 5 patients with no RAI reduction reported on symptomatic relief. CONCLUSION: In a considerable number of patients with suspected LPR, pH monitoring reveals no abnormal proximal reflux. Esomeprazole 40 mg every day together with lifestyle modifications could reach adequate acid suppression in a large number of patients. Symptom improvement is also reported by patients without measurable effects of therapy.     

Early referral for 24-h esophageal pH monitoring may prevent unnecessary treatment with acid-reducing medications

Background

Gastroesophageal reflux disease (GERD) affects nearly 25 % of adults; however, an objective diagnosis is rarely established. We hypothesized that patients’ symptoms and response to acid-reducing therapy are poor predictors of the outcome of 24-h esophageal pH monitoring.

Methods

A review of 24-h esophageal pH monitoring studies performed at an ambulatory tertiary care center between 2004 and 2011 was performed. Demographics, type of GERD symptoms, and duration and response to acid-reducing medications before referral for pH monitoring were collected. DeMeester score, symptom sensitivity index (SSI), and symptom index (SI) were tabulated and compared with the patients’ symptoms and response to medical therapy.

Results

One hundred patients were included. Of all reported symptoms, only heartburn was more common in patients with positive DeMeester scores, but there were no correlations between any symptoms and SSI or SI scores. Sixty-nine percent of patients with esophageal symptoms had a positive DeMeester score compared with only 29 % of patients with extraesophageal symptoms (P < 0.01). Esophageal symptoms and endoscopic evidence of GERD significantly increased the likelihood of having a positive DeMeester score, but they had no influence on SSI or SI scores. There was no correlation between response to acid-reducing medications and DeMeester, SSI, or SI scores. A total of 536 person-years of acid-reducing medications were prescribed to the study population, of which 151 (28 %) were prescribed to patients who had a negative pH study.

Conclusions

Extraesophageal symptoms and response to empiric trials of acid-reducing medications are poor predictors of the presence of GERD and the DeMeester score is more likely to identify GERD in patients who met other empiric diagnostic criteria than SSI or SI. Early referral for 24-h esophageal pH monitoring may avoid lengthy periods of unnecessary medical therapy.     

Persistent acid and bile reflux in asymptomatic patients with Barrett esophagus receiving proton pump inhibitor therapy

HYPOTHESIS: Symptom control does not reflect elimination of abnormal acid reflux or abnormal bile reflux in patients with long-segment Barrett esophagus receiving proton pump inhibitors (PPIs). DESIGN: Prospective survey. SETTING: University hospital. PATIENTS: Thirty-two patients with long-segment Barrett esophagus who were asymptomatic with PPIs. MAIN OUTCOME MEASURES: Twenty-four-hour ambulatory pH and bile reflux monitoring while continuing PPIs. RESULTS: Abnormal acid reflux (pH <4 for 11.9% [interquartile range, 6.8%-19.6%) of 24 hours] persisted in 15 patients (47%) who could not be distinguished from those with normal acid reflux (pH <4 for <4.5% of 24 hours) by any endoscopic, manometric, or therapeutic characteristic. Abnormal bile reflux (absorbance >0.14 for 8.7% [interquartile range, 3.9%-8.7%] of 24 hours) was detected in 11 (48%) of 23 patients, such that both normal bile reflux (absorbance >0.14 for <1.8% of 24 hours) and normal acid reflux were observed in only 8 patients (35%). There was no association between abnormal acid reflux and abnormal bile reflux. CONCLUSIONS: Despite symptom control with PPIs, both acid reflux and bile reflux were controlled in only one third of patients. Posttherapeutic monitoring of acid and bile reflux is recommended in future clinical trials of PPI treatment vs laparoscopic antireflux surgery.     

Effect of proton pump inhibitors on glycemic control in patients with diabetes

Gastrin is a linear peptide hormone which is secreted mostly in the stomach pyloric antrum G cells. Although the main role of this hormone is the promotion of the secretion of gastric acid from the stomach parietal cells, gastrin can also behave as a growth factor and stimulate gastric cell proliferation. It is also reported that gastrin promotes β cell neogenesis in the pancreatic ductal complex, modest pancreatic β cell replication, and improvement of glucose tolerance in animal models, in which the remodeling of pancreatic tissues is promoted. These findings suggest the possibility that gastrin has the potential to promote an increase of β cell mass in pancreas, and therefore that gastrin may improve glucose tolerance. Proton pump inhibitors(PPIs) are wildly used clinically for the therapy of gastro-esophageal reflex disease, gastritis due to excess stomach acid, and gastric ulcers. PPIs indirectly elevate serum gastrin levels via a negative feedback effect. Recent evidence has revealed the beneficial effect of PPIs on glycemic control especially in patients with type 2 diabetes mellitus(T2DM), probably via the elevation of the levels of serum gastrin, although the detailed mechanism remains unclear. In addition, the beneficial effects of a combination therapy of gastrin or a PPI with a glucagon-like peptide-1 receptor agonist on glycemic control in animal models have been demonstrated. Although PPIs may be possible candidates for a new approach in the therapy of diabetes, a prospective, longterm, randomized, double-blind, placebo-controlled study is needed to establish the effect of PPIs on glycemic control in a large number of patients with T2 DM.     

Effectiveness of pembrolizumab in patients with urothelial carcinoma receiving proton pump inhibitors

BackgroundThe association of concurrent proton pump inhibitor (PPI) use with treatment outcome of metastatic urothelial carcinoma (UC) remains controversial.Materials and methodsWe retrospectively analyzed the records of 227 patients with platinum-treated metastatic UC treated with pembrolizumab. The primary outcome was overall survival (OS). Immune progression-free survival (iPFS) and objective response per immune response evaluation criteria in solid tumors were also compared. Inverse probability of treatment weighting (IPTW)-adjusted multivariable Cox regression models and an IPTW-adjusted multivariable logistic regression model were used to evaluate the oncological outcomes. Furthermore, the heterogeneity of the treatment effect on OS was examined using interaction terms within the IPTW-adjusted univariate Cox regression models.ResultsOverall, 86 patients (37.9%) used PPIs. After weighting, no significant differences in patient characteristics were observed between PPI users and non-users. PPI use was significantly associated with a shorter OS (hazard ratio [HR]: 2.02, 95% confidence interval [CI]: 1.28–3.18, P = 0.003) and iPFS (HR: 1.70, 95% CI: 1.23–2.35, P = 0.001). Although not statistically significant, PPI use was associated with objective response as well (OR: 0.61, 95% CI: 0.36–1.02, P = 0.06). The interaction analyses showed that the effect of PPI significantly decreased with age (HR: 0.97, 95% CI: 0.93–1.00, P[interaction] = 0.048) and was increased in males (HR: 2.97, 95% CI: 1.10–8.05, P[interaction] = 0.032).ConclusionsPPI use was significantly associated with worse survival of patients with metastatic UC treated with pembrolizumab. Furthermore, the results suggested that its effects decreased with age and was increased in males.     

慢性肾脏病患者24小时动态血压的特点分析

目的采用24h动态血压监测的方法,分析慢性肾脏病（CKD）不同分期患者24h动态血压特点。方法将152例CKD患者分为5组：CKD1期组（A组）15例;CKD2期组（B组）29例;CKD3期组（C组）42例;CKD4期（D组）组34例;CKD5期组（E组）32例。所有患者均无糖尿病、非肾脏替代治疗。采用携带式的动态血压检测仪测定各组患者动态血压参数和昼夜节律。结果①随着肾功能下降,24h、日间和夜间平均收缩压越来越高;②CKD患者总体非杓型血压比例为81．6o,4,肾功能下降组（CKD2～5期）非杓型血压比例显著高于肾功能正常组（CKD1期）;③夜间收缩压与24h尿蛋白定量呈正相关（r=0．427,P〈0．01）,与。肾小球滤过率（GFR）呈负相关（r=-0．352,P〈0．05）。结论CKD患者的血压非杓型节律现象比较普遍,并随着肾功能下降,其发生率逐渐升高;夜间收缩压与尿蛋白排泄、肾功能有相关性。     

A randomized controlled trial of laparoscopic nissen fundoplication versus proton pump inhibitors for treatment of patients with chronic gastroesophageal reflux disease: One-year follow-up

A randomized controlled trial conducted in patients with gastroesophageal reflux disease compared optimized medical therapy using proton pump inhibitor (n = 52) with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1 year. The primary end point was frequency of gastroesophageal reflux dis-ease symptoms. Surgical patients had improved symptoms, pH control, and overall quality of life health index after surgery at 1 year compared with the medical group. The overall gastroesophageal reflux disease symptom score at 1 year was unchanged in the medical patients, but improved in the surgical patients. Fourteen patients in the medical arm experienced symptom relapse requiring titration of the proton pump inhibitor dose, but 6 had satisfactory symptom remission. No surgical patients required additional treatment for symptom control. Patients controlled on long-term proton pump inhibitor therapy for chronic gastroesophageal reflux disease are excellent surgical candidates and should experience improved symptom control after surgery at 1 year.     

贲门癌术后近期24小时食管pH监测

为了解贲门癌切除术后患者胃食管反流的具体情况,探讨现行手术方法对胃食管反流的影响,评价体位改变对减少胃食管反流的效果,作者对３０例贲门癌患者在术后１３～１８天进行了２４小时食管ｐＨ监测。结果显示：（１）贲门癌患者术后２４小时食管ｐＨ各项监测指标均高于正常（Ｐ＜０．０１）,但只有６０％的患者有典型胃食管反流症状;（２）胸内吻合与腹内吻合、套入式吻合与围巾式吻合相比,监测结果无显著差别（Ｐ＞０．０５）;（３）术后上身抬高３０°仰卧的患者,监测指标均明显低于对照组（Ｐ＜０．０１）。由此得出结论：（１）贲门癌患者术后普遍存在胃食管反流;（２）上身抬高可明显减少胃食管反流;（３）目前常用的一些手术吻合方法不能减少胃食管反流;（４）尽管某些患者没有反流的典型症状,胃食管反流仍存在。     

Assessment of respiratory symptoms with dual pH monitoring in patients with gastro-oesophageal reflux disease

BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a commonly underestimated aetiological factor in patients with respiratory symptoms. In this study, acid reflux in healthy volunteers and patients with GORD with and without respiratory symptoms was investigated by dual pH monitoring. METHODS: Thirty healthy volunteers and 43 patients with GORD underwent oesophageal manometry and dual pH monitoring with one probe in the proximal and one in the distal oesophagus. Nineteen of the 43 patients complained of respiratory symptoms. RESULTS: There were no differences in proximal probe measurements between volunteers and patients without respiratory symptoms. Patients with GORD and respiratory symptoms had a higher prevalence of abnormally high exposure to gastric juice and more reflux episodes in the proximal oesophagus compared with patients with GORD and no respiratory symptoms. Some 17 of 19 patients with GORD and respiratory symptoms showed deteriorated oesophageal body motility. CONCLUSION: Dual pH monitoring is feasible and well tolerated, and provides an objective means of evaluating patients with GORD and respiratory symptoms. Prolonged exposure of the proximal oesophagus to gastric juice and disorders of oesophageal body motility seem to be responsible for the development of respiratory symptoms.     

Esophageal manometry and 24-hour pH monitoring to evaluate laparoscopic Lind fundoplication in gastroesophageal reflux disease.

Laparoscopic and thoracoscopic techniques have provided a new dimension in the correction of functional disorders of the esophagus. Therapeutic success, however, depends on the confirmation of esophageal disease as a cause of the symptoms, on understanding the basic cause of dysfunction and on identifying the surgical patient. This study is a retrospective study of patients submitted to surgery using the Lind procedure for gastroesophageal reflux disease (GERD). The purpose of this study is to establish the value of the routine use of esophageal manometry and 24-hour pH monitoring in order to select patients and perform pre and postoperative functional evaluation. Forty-one patients (68.3%) had a hypotonic lower esophageal sphincter. The average pressure was 9.2 mm Hg preoperatively and 15.2 mm Hg postoperatively, with an increase of 6.0 mm Hg. This increase was 8.8 mm Hg in hypotonics and 4.3 mm Hg in the normotonics. There was a certain degree of hypomotility of the esophageal body in 14 patients (23.3%) and, of this group, 4 (28.5%) improved postoperatively. Pathological acid reflux was found in 51 cases (85.0%) by pH monitoring. The mean of the preoperative DeMeester score was 31.4, later dropping to 3.2. Esophageal manometry and 24-hour pH monitoring are effective methods for revealing the level of functional modification established by anti-reflux surgery and for helping to objectively perform the selection.     

Cost-effectiveness of proton pump inhibitors versus laparoscopic Nissen fundoplication for patients with gastroesophageal reflux disease: a systematic review of the literature

Background  

Gastroesophageal reflux disease is a common condition in Western countries. It is unknown whether medical or surgical treatment is more cost-effective. This study was conducted to determine whether laparoscopic Nissen fundoplication or treatment by proton pump inhibitors is the most cost-effective for gastroesophageal reflux disease in the long term.     

Esophageal manometry and 24-hour pH monitoring in the diagnosis of pulmonary aspiration secondary to gastroesophageal reflux.

Twenty-three consecutive patients who had persistent respiratory symptoms of unexplained etiology were evaluated to determine the presence of gastroesophageal reflux (GER) and its relationship to their respiratory complaints. Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures and the characteristics of the peristaltic waves in the proximal and distal esophagus were determined. Esophageal acid exposure 5 cm and 20 cm above the LES was measured using a pH probe with two antimony sensors. Aspiration was diagnosed when respiratory symptoms occurred during or within 3 minutes after a reflux episode, recorded at both levels of the esophagus. Based on these criteria, 12 patients were considered nonaspirators (group A), and 11 were categorized as aspirators (group B). Aspirators had: (1) lower LES pressure (6.1 +/- 3.1 versus 12 +/- 4.8 mm Hg, p less than 0.01); (2) decreased amplitude of peristalsis in the proximal esophagus (34 +/- 16 versus 59 +/- 21 mm Hg, p less than 0.01) and distal esophagus (46 +/- 25 versus 91 +/- 28 mm Hg, p less than 0.01), and higher incidence of simultaneous, nonperistaltic waves (30% versus 4%); and (3) lower UES pressure (44 +/- 23 versus 74 +/- 38 mm Hg). Impaired peristalsis in aspirators caused a higher acid exposure (11.4% +/- 8.0% versus 1.0% +/- 0.7% of time pH less than 4, p less than 0.01) and delayed clearance (5.5 +/- 6.5 versus 0.7 +/- 0.4 min) in the proximal esophagus. Our study shows that, in patients with respiratory symptoms of unexplained etiology, esophageal manometry and 24-hour pH monitoring will identify a subgroup of true aspirators. These patients suffer from a panesophageal motor dysfunction that affects all three barriers to aspiration: the LES, the esophageal "pump mechanism," and the UES.     

Quantification of duodenogastric reflux in gastroduodenal peptic ulcer and in gastric operation patients, using a 24-h gastric pH measurement as a quantification technique

Twenty-four-hour gastric pH measurement was used to study duodenogastric reflux. To differentiate between gastric hyposecretion and duodenogastric reflux, we also measured bile acid concentrations in the gastric juice, and regarded pH increases to above 4 as possible episodes of reflux. The procedure was used in 60 patients, divided into the following groups: (1) control group (ten patients); (2) duodenal ulcer (ten patients); (3) type 1 gastric ulcer (five patients); (4) type 3 gastric ulcer (five patients); (5) bilateral truncal vagotomy plus pyloroplasty (ten patients); (6) truncal vagotomy plus Billroth I partial gastrectomy (ten patients); and (7) truncal vagotomy plus Billroth II partial gastrectomy (ten patients). The amount of reflux (areas of pH greater than 4) in the type 1 gastric ulcer and Billroth I and Billroth II groups was significantly greater than that found in the control, duodenal ulcer, type 3 gastric ulcer and truncal vagotomy plus pyloroplasty groups. The mean concentration of total bile acids was also greater in the gastrectomized patients than in the rest of the groups studied. In the type 1 gastric ulcer group the mean bile acid concentration was similar to that of the control group.     

Pharyngeal pH measurements in patients with respiratory symptoms before and during proton pump inhibitor therapy.

BACKGROUND: Pharyngeal pH monitoring is a diagnostic tool used to identify Gastroesophageal reflux disease (GERD) as an etiology of respiratory symptoms. We performed pharyngeal pH monitoring on 14 patients with respiratory symptoms thought to be induced by GERD. METHODS: Symptoms and pH monitoring (esophageal and pharyngeal) were assessed prior to and 3 months after the initiation of double-dose proton pump inhibitor therapy. RESULTS: Symptoms included cough, hoarseness, and throat clearing. Ten patients had at least one episode of pharyngeal reflux (PR+) and 4 patients had no pharyngeal reflux (PR-). Pharyngeal reflux episodes in PR+ patients decreased from 3.5 to 0.9 (P <0.05) per day with 8 of 10 (80%) patients having elimination or reduction of such episodes. Eight of 9 PR+ patients (89%) with suppressed pharyngeal reflux on medical therapy had resolution of respiratory symptoms. Three of 4 PR- patients (75%) had persistent symptoms on medical therapy. CONCLUSIONS: Proton pump inhibitor therapy improves clinical symptoms and decreases pharyngeal reflux episodes in patients with respiratory symptoms related to GERD. Direct measurement of pharyngeal pH is helpful in the identification of patients likely to respond to antireflux therapy.     

A randomized controlled trial of laparoscopic Nissen fundoplication versus proton pump inhibitors for the treatment of patients with chronic gastroesophageal reflux disease (GERD): 3-year outcomes

Background  

A randomized controlled trial (RCT) investigated patients with gastroesophageal reflux disease (GERD) who were stable and symptomatically controlled with long-term medical therapy to compare ongoing optimized medical therapy with laparoscopic Nissen fundoplication (LNF).