Duodenogastroesophageal Reflux Research Articles

Prevalence of bile reflux in gastroesophageal reflux disease patients not responsive to proton pump inhibitors

To determine the prevalence and characteristics of bile reflux in gastroesophageal reflux disease (GERD) patients with persistent symptoms who are non-responsive to medical therapy. Sixty-five patients (40 male, 25 female; mean age, 50 +/- 7.8 years) who continued to report symptoms after 8 wk of high-dose proton pump inhibitor (PPI) therapy, as well as 18 patients with Barrett's esophagus, were studied. All patients filled out symptom questionnaires and underwent endoscopy, manometry and combined pH-metry and bilimetry. There were 4 groups of patients: 22 (26.5%) without esophagitis, 24 (28.9%) grade A-B esophagitis, 19 (22.8%) grade C-D and 18 (21.6%) Barrett's esophagus. Heartburn was present in 71 patients (85.5%) and regurgitation in 55 (66.2%), with 44 (53%) reporting simultaneous heartburn and regurgitation. The prevalence of pathologic acid reflux in the groups without esophagitis and with grades A-B and C-D esophagitis was 45.4%, 66.6% and 73.6%, respectively. The prevalence of pathologic bilirubin exposure in these 3 groups was 53.3%, 75% and 78.9%, respectively. The overall prevalence of bile reflux in non-responsive patients was 68.7%. Pathologic acid and bile reflux was observed in 22.7% and 58.1% of non-esophagitic patients and esophagitic patients, respectively. The high percentage of patients poorly responsive to PPI therapy may result from poor control of duodenogastroesophageal reflux. Many patients without esophagitis have simultaneous acid and bile reflux, which increases with increasing esophagitis grade.

Prevalence of pathological duodenogastric reflux and the relationship between duodenogastric and duodenogastrooesophageal reflux in chronic gastrooesophageal reflux disease

The role of duodenogastric reflux in gastrooesophageal reflux disease is still controversial. (i) To determine the prevalence of pathological duodenogastric reflux (DGR) in gastrooesophageal reflux disease patients and (ii) to define the relationship between DGR and duodenogastrooesophageal reflux. We evaluated 92 patients referred for investigation of recurrent reflux symptoms after proton pump inhibitors (PPI) therapy. All the patients filled out symptom questionnaires and underwent endoscopy, oesophageal manometry and combined oesophagogastric pH and bilirubin monitoring. Endoscopy divided the 92 patients into four groups (group I: 25 nonoesophagitis patients, group II: 26 patients with grade A-B oesophagitis, group III: 21 patients with grade C-D oesophagitis and group IV: 20 patients with Barrett's oesophagus. Twenty-four of the 92 patients (26%) showed pathological DGR. Abnormal oesophageal bilirubin exposure was observed in 62 of the 92 patients (67.4%). Of the 62 patients with abnormal oesophageal bilimetry, 15 (24.2%) patients simultaneously showed pathological DGR. The gastric bilirubin exposure in patients with abnormal oesophageal, Bilitec tests did not differ from that in patients with normal oesophageal bilimetry (P>0.05). A weak correlation between oesophageal and gastric bilirubin exposure, both expressed as a percentage of time, was found (r=0.28; P<0.01). Pathological DGR is present in a little more than a quarter of patients with recurrent reflux and dyspeptic symptoms after PPI therapy. Excessive DGR is not a prerequisite for pathological oesophageal exposure to duodenal contents. Gastric bilirubin monitoring may be useful to choose the best surgical treatment for patients with reflux and dyspeptic symptoms refractory to PPI.

Proton pump inhibitor influence on reflux in Barrettʼs oesophagus

It is important to identify factors responsible for the development of Barrett's oesophagus (BO). The effect of proton pump inhibitors (PPIs) on oesophageal clearance of both acid and alkaline reflux in these patients is uncertain and studies comparing BO patients and healthy controls (HCs) have not been performed earlier. Two groups of patients were studied: 18 HCs and 12 BO patients. Oesophageal motility, acid reflux and duodenogastro-oesophageal reflux (DGOR) were measured using a three-pressure transducer catheter with an antimony pH tip, connected to a sodium ion selective electrode. All patients were studied both on and off PPIs. Without PPI therapy, BO patients had significantly more upright and supine acid reflux and upright DGOR compared with HCs. During acid reflux, HC demonstrated more peristalsis than BO [HC, % peristalsis=64 (9), BO=53 (8), P<0.01], but this was not seen during DGOR. [HC, % peristalsis=68 (14), BO=56 (11)]. In Barrett's patients, DGOR was significantly reduced with PPIs [off PPI, % upright DGOR=61 (17), on PPIs=19 (15), P<0.01], and no oesophageal motility differences were seen compared with results without PPIs. HCs demonstrate better oesophageal motility compared with BO patients to prevent acid and alkaline reflux. When acid reflux occurred, HCs had better coordinated motility to remove it. This increased coordination did not occur during DGOR, suggesting different stimulation mechanisms. PPI reduced DGOR in BO patients, without any change in oesophageal motility.

Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces

Background:Severe duodeno-gastro-oesophageal reflux (DGOR) is a risk factor for oesophagitis and Barrett’s oesophagus. Patients with non-erosive reflux disease (NERD) have a slight increase in DGOR. Patients with gastro-oesophageal reflux disease...

Multivariate analysis of the association of acid and duodeno-gastro-oesophageal reflux exposure with the presence of oesophagitis, the severity of oesophagitis and Barrett’s oesophagus

Background:Exposure to acid and duodeno-gastro-oesophageal reflux (DGOR) both increase with oesophageal lesions in gastro-oesophageal reflux disease (GORD). It is unknown whether DGOR exposure is an independent risk factor for oesophageal...

Duodenogastroesophageal reflux and its effect on extraesophageal tissues: A review

We conducted a literature review to identify elements of duodenogastroesophageal reflux (DGER)--namely pancreatic fluids, hydrochloric acid, pepsin, and bile--as to the effects each has when refluxed to the extraesophageal structures. Further, we wished to acquaint clinicians with the possibilities that, in addition to hydrochloric acid, the other components of DGER are likewise contributing to disease in the extraesophageal areas. Our review included studies that have indicated reflux of the above mentioned components of DGER to the pharynx, larynx, tracheobronchial tree, oral cavity, nasopharynx, nose and sinuses, eustachian tube, and middle ear. Findings demonstrate that injury to the upper aerodigestive tract can occur from a variety of substances secreted from the stomach and duodenum. Treatment for DGER is nonspecific. We conclude that patients with an incomplete response to acid suppression may have significant involvement of pepsin, bile, or both. Future studies are needed to clarify the importance of these elements and to suggest more precise treatments.

899 Transformation of Benign Barrett's Epithelial Cells By Repeated Acid and Bile Exposure Over 22-65 Weeks: An in-Vitro Model of Metaplasia to Neoplasia By Environmental Factors

Background and aims: Barrett's esophagus (BE) is regarded as pre-malignant condition of esophagus. The exact pathomechanisms responsible for the development Barrett's adenocarcinoma (BA) are still poorly understood. There is an evidence that the development of BE is a consequence of a chronic duodenogastroesophageal reflux disease (DGER) and ongoing inflammation in injured area of esophageal mucosa. The aims of the study were; 1) analysis of NFκB activity in human BE biopsies and influence of bile acids (DCA and UDCA) on its transactivation in BA cell line (OE-19 cells); 2) Implication of CDX-2 in BE development and the influence of bile acids on CDX-2 expression in OE-19 cell line; 3) Influence of siRNA-RelA (siRNA against NFκB) and a NFκB inhibitor (MG-132) on COX-2 and CDX-2 expressions in OE-19 cell line induced by bile salts. Material and Methods: CDX-2 and COX-2 was analysed in human biopsies from the normal esophagus mucosa and BE at mRNA and protein level by qRT-PCR and Western blot, respectively. Additionally, activity of NFκB in BE was assessed by ELISA. In separate In Vitro experiments, OE-19 cells were incubated with or without bile salts (DCA or UDCA, 100μM or 300μM) in neutral pH in the presence of MG-132 or after transfection with siRNA-RelA. The apoptosis rate was evaluated by FACS. The expression of COX-2 and CDX-2 was analyzed at mRNA and protein level by quantitative RT-PCR and immunoblot. Results: BE demonstrated a significant upregulation of CDX-2 and COX-2 expressions and elevated activity of NFκB as compared to normal esophagus. DCA compared to UDCA stronger stimulated COX-2 and CDX-2 expression in OE-19 cells. Both MG-132 and transfection with siRNA-RelA attenuated the increase in COX-2 and CDX-2 expression after treatment of the cells with DCA and induced higher rate of apoptosis. Conclusions: Bile salts are involved development of Barrett's metaplasia probably via direct stimulation of COX-2 and CDX2. These effects are mediated by increased activation of NFκB Thus, targeted therapy against NFκB may have beneficial preventive effect on the development of Barrett's adenocarcinoma.

Esôfago de Barrett: aspectos fisiopatológicos e moleculares da seqüência metaplasia-displasia-adenocarcinoma - artigo de revisão

The Barrett's esophagus (BE) is defined as endoscopically visible columnar mucosa at the distal esophagus, of any extension, proved to harbor intestinal metaplasia on biopsy, highlighted by the presence of goblet cells. BE denotes long-standing gastroesophageal reflux disease (GERD) and is an important risk factor for the development of esophageal adenocarcinoma (EAC). Therefore, these patients must be on follow-up, in order to diagnose cancer early. BE patients have frequent alterations in esophageal physiologyc studies. Alkaline duodenogastroesophageal reflux seems to have important role. The development BE occurs in steps, initially with formation of cardiac type mucosa subsequent intestinalization. Futher progression can follow a sequence, from low grade dysplasia, to high grade dysplasia and esophageal adenocarcinoma. Current follow-up is based on the presence of dysplasia. It has limitations, grouping patients heterogeneously. Different steps of carcinogenesis have been studied looking for an ideal prognostic marker. Uncontrolled proliferative activity, apoptosis inhibition, angiogenesis, tissue invasion and metastases formation are all implicated in cancer origin. Some cycle cell molecules have been studied in BE, such as retinoblastoma protein, ciclins, kinase dependent ciclins and cell cycle inhibitors. The P53 protein is one of the most investigated in the metaplasia-adenocarcinoma progression. Growth Factors, apoptotic proteins, telomers and DNA ploidy have also been searched. Increased proliferative activity has been implicated in Barrett's carcinogenesis and the Ki-67 antigen, through imunohistochemical analysis, has become the the method of choice. Present in the nucleus, it is found in proliferative cells only. Some studies suport association between Ki-67 activity and the metaplasia-dysplasia-adenocarcinoma sequence.The results, however, are inconclusive and research should follow this way.

Effect of Roux-en-Y gastric bypass in obese patients with Barrett’s esophagus: attempts to eliminate duodenogastric reflux

To assess the effect of Roux-en-Y gastric bypass (RYGB) at a tertiary referral Center of Excellence for bariatric surgery on the length and presence of dysplasia in morbidly obese patients with Barrett's esophagus (BE). Esophageal reflux of gastroduodenal contents (acid, bile) contributes to the development of BE and progression in the dysplasia-carcinoma sequence. Obese patients have a high prevalence of gastroesophageal reflux and might be at an increased risk of developing BE and esophageal adenocarcinoma. The effect of eliminating duodenogastroesophageal reflux on BE is not known. We performed a retrospective review of all patients with pre-existing, biopsy-proven, long-segment (>3 cm) BE undergoing RYGB at our institution. Only patients with >1 year of endoscopic, biopsy-controlled follow-up (mean 34 mo) were included. Five patients (3 men and 2 women) were identified. The mean +/- standard error of the mean preoperative length of BE was 6 +/- 2 cm; 2 patients had low-grade dysplasia and 1 indeterminate dysplasia. At the postoperative follow-up (>1 yr) examinations, the length of BE had decreased in 4 patients; the overall length was 2 +/- 1 cm; and only 1 patient had dysplasia. All patients experienced a decrease in the length of BE (n = 4), complete disappearance of BE (n = 2), or improvement in the degree of dysplasia (n = 3). The body mass index had decreased from 43 +/- 4 kg/m(2) to 33 +/- 3 kg/m(2), and all experienced subjective improvement in reflux symptoms postoperatively. RYGB resulted in complete or partial regression of BE in 4 of 5 patients and improvement in reflux symptoms in all. Our results suggest that RYGB might be the procedure of choice in morbidly obese patients with BE requiring surgical treatment for gastroesophageal reflux disease.

Ingestion of thioproline suppresses rat esophageal adenocarcinogenesis caused by duodenogastroesophageal reflux

Duodenogastroesophageal reflux causes esophageal adenocarcinoma in rats without the use of a carcinogen. This etiology is unclear, but may be associated with endogenous nitrosation in the gastrointestinal tract. Thioproline (TPRO) is an effective nitrite-trapping agent and blocks endogenous nitrosation. We investigated how ingested TPRO affected esophageal adenocarcinogenesis in rats with duodenogastroesophageal reflux (DGER) or gastroesophageal reflux (GER). A series of 200 male Fischer 344 rats received surgery to induce reflux of duodenogastric contents or gastric contents alone into the esophagus. The rats were separated into two divisions according to the surgical procedure employed (DGER or GER), and each division was further subdivided into two groups: one group was fed a special diet (CRF-1 containing 0.5% of TPRO); the other group was fed a standard diet (CRF-1). The rats were given no carcinogen and sacrificed at ten-week intervals from the 25th to the 45th week after surgery. Pathological examination was carried out using hematoxylin-eosin or immunohistochemical staining. Erosion, regenerative thickening, basal cell hyperplasia and columnar-lined epithelium (CLE) were found in both groups of the DGER rats. Adenocarcinoma (AC) appeared only in the DGER rats sacrificed at 35 and 45 weeks following surgery. The incidence of AC at the 45th week was significantly lower in the group of rats fed the diet containing TPRO, as compared to those fed the standard diet, whereas the incidences of CLE were the same for both groups. iNOS protein and nitrotyrosine protein were identified in the CLE and macrophages of the DGER group using immunohistochemical staining. There were no remarkable pathological changes in the esophagi of the rats which underwent the GER procedure. In conclustion, TPRO has an inhibitory effect on esophageal reflux-induced adenocarcinogenesis in rats in that it prevents the progression from CLE to AC.

Stratification and symptom characteristics of non‐erosive reflux disease based on acid and duodenogastroesophageal reflux

The subgroups and symptom characteristics of non-erosive reflux disease (NERD) based on acid and duodenogastroesophageal reflux may be different in Chinese patients to Western patients. This study aimed to explore the stratification and symptom characteristics of patients with NERD. Patients with typical heartburn and/or acid regurgitation symptoms were enrolled. Each patient filled out a questionnaire. An upper gastrointestinal endoscopy was performed for each patient followed by simultaneous ambulatory 24-h esophageal pH and Bilitec (bilirubin) monitoring. A symptom index (SI) of > or =50% was considered to be positive. Eighty-two consecutive NERD patients were evaluated. Abnormal (NERD pH+) and normal (NERD pH-) 24-h pH tests were found in 24 (29.3%) and 58 (70.7%) patients, respectively. Among 42 NERD pH- patients who reported heartburn symptoms during monitoring, SI was positive in 19 (45.2%) patients (NE-SI+) and negative in 23 (54.8%) patients (NE-SI-). Pathological duodenogastroesophageal reflux (DGER) was found in 43 (52.4%) patients. No significant differences were noted regarding the prevalence of other upper gastrointestinal symptoms, except for acid regurgitation in NERD pH+ and NERD pH- groups. Additionally, no significant differences were seen in the prevalence of other symptoms, except for chest pain, in groups with pathological and normal DGER. The proportion of NERD patients with pathological acid reflux was somewhat lower than that reported in Western countries. The role of DGER in NERD may be important. It is difficult to differentiate whether NERD patients have pathological acid or bile reflux according to symptoms.

Duodenogastro-Esophageal Reflux in Children with Refractory Gastro-Esophageal Reflux Disease

To determine the role of duodenogastro-esophageal reflux (DGER) in the pathogenesis of refractory gastro-esophageal reflux disease (GERD) in children. Twenty-two patients (12 boys, mean age, 13.2 years) with GERD symptoms that persisted on omeprazole (1 mg/kg) underwent upper gastrointestinal endoscopy and barium x-ray, 24-hour pH and DGER (Bilitec) monitoring, and a 13C octanoic acid gastric emptying breath test. Patients presented mainly with epigastric pain, regurgitation, and nausea. Endoscopy revealed persistent esophagitis in 15 patients (68%). Pathologic acid and DGER exposure were present in 12 (55%) and 15 (68%) children, respectively, with combined pathologic reflux in 10 (45%). Acid exposure did not differ according to the presence of esophagitis, but patients with grade II esophagitis had significantly higher DGER exposure than those without esophagitis (9.1 +/- 5.3% vs 26.7 +/- 10.9% of the time, P < .05). Gastric emptying rate was not associated to acid or DGER exposure or persisting esophagitis. Symptoms improved after adding a prokinetic drug to the proton pump inhibitor therapy or referral for surgery (n = 5). DGER may play a role in the pathophysiology of proton pump inhibitor-refractory GERD and esophagitis in children.

Simultaneous adeno- and squamous cell carcinoma with different phenotypic profiles in a rat model of chronic gastroesophageal reflux

The aim of our study was to investigate the incidence of duodeno-gastroesophageal reflux-induced malignant transformation in a series of duodeno-esophageal anastomosis operations in rats. This surgical method provides a model for reflux-induced esophageal pathologies, without carcinogen administration. The study design included the follow-up of 31 cases. Thirty weeks of duodeno-gastroesophageal reflux disease significantly increased the risk of the development of Barrett's esophagus, and reflux-induced esophageal adenocarcinoma formation was evident in four animals. In one of these particular cases, a superficial squamous cell cancer was noted in close vicinity to the adenocarcinoma formation. For further analysis, a detailed immunohistochemical staining protocol was used. The immunophenotypes revealed cyclin D1 expression (nuclear positivity in 35% of all the squamous cells), p53 protein accumulation (50% nuclear positivity), with a low expression of cox-2, and negative c-erbB2 staining in the squamous carcinoma cells. The specialized intestinal metaplasia and mucinous adenocarcinoma cells exhibited exclusively diffuse cox-2 positivity (90% of all glandular cells) and weak focal c-erbB2 (5%) staining, without cyclin D1 expression or p53 protein accumulation. Real-time polymerase chain reaction was applied to quantify the abundance of p53, cyclin D1 and cox-2 mRNAs in this biopsy. The most dramatic changes were observed in the level of expression of cyclin D1 (a 9.08-fold expression as compared with the non-treated esophagus samples), while the p53 and cox-2 gene expressions were increased by 1.61 and 2.45-fold, respectively, relative to the non-treated samples. The results afford evidence of the simultaneous activation of more than one possible carcinogenetic pathway in experimental gastroesophageal reflux disease. Synchronous neoplasm formation with different growth pattern characteristics is a rarity in humans, and this phenomenon suggests that the presented model is a suitable means of mimicking the whole spectrum of human gastroesophageal reflux disease pathology.

Do acid and bile reflux into the esophagus simultaneously? Temporal relationship between duodenogastro‐esophageal reflux and esophageal pH

Duodenogastro-esophageal reflux (DGER) is an important factor in the pathogenesis of reflux esophagitis. Animal studies have demonstrated that the injurious effect of duodenal juice components depends on pH. The purpose of the present study was to investigate the temporal relationship between DGER and esophageal pH. Seventy-six children with symptoms of gastro-esophageal reflux disease (27 without, 31 with mild, 18 with severe esophagitis) underwent 24 h simultaneous esophageal pH and bilirubin monitoring with Bilitec 2000. The recordings were analyzed for (i) pH at the beginning of DGER episodes; (ii) relative duration of DGER in eight defined pH intervals of 1 pH unit; and (iii) differences in relative duration of DGER between the three groups of children. DGER episodes most frequently began at pH between 6 and 7. DGER was present in the esophagus across the spectrum of esophageal pH, with the biggest relative duration between pH 3 and 5. However, in children without esophagitis relative duration of DGER was longest between pH 5 and 6, in children with mild esophagitis between pH 4 and 5, while in those with severe esophagitis it was between pH 2 and 4 (P < 0.001). DGER appears across the whole esophageal pH spectrum. The more severe the esophagitis, the lower the pH at which DGER occurs, resulting in simultaneous damaging effects of acid and duodenal juice components.

ACG Practice Guidelines: Esophageal Reflux Testing

Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Issues regarding the utilization of conventional, catheter-based pH monitoring are discussed. Improvements in the interpretation of esophageal pH recordings through the use of symptom-reflux association analyses as well as limitations gleaned from recent studies are reviewed. The clinical utility of pH recordings in the proximal esophagus and stomach is examined. Newly introduced techniques of duodenogastroesophageal reflux, wireless pH capsule monitoring and esophageal impedance testing are assessed and put into the context of traditional methodology. Finally, recommendations on the clinical applications of esophageal reflux testing are presented.

Biliary reflux and non-acid reflux are two distinct phenomena: A comparison between 24-hour multichannel intraesophageal impedance and bilirubin monitoring

Objective. Duodenogastroesophageal reflux (DGER) can greatly increase microscopic and macroscopic esophageal mucosal damage caused by acid. The aim of this study was simultaneously to assess the chemical composition of DGER by detecting bilirubin in the refluxate by means of Bilitec and describe its pH and physical properties by impedance monitoring, in order to prove that non-acid reflux and biliary reflux are two distinct phenomena. Material and methods. Twenty patients with gastroesophageal reflux disease (GERD) with symptoms refractory to conventional proton-pump inhibitor (PPI) therapy or with atypical GERD symptoms were included in the study. All patients underwent upper gastrointestinal endoscopy and simultaneous Bilitec and intraeosophageal impedance (IIM) and pH monitoring. In the majority of patients (16/20), the tests were performed while assuming a standard PPI dose. Results. Pathological bilirubin exposure, as defined by intraesophageal bilirubin absorbance above 0.14 for more than 3.9% of the time, was present in 9 cases, 6 of them with normal values of non-acid reflux, as detected by IIM. A pathological non-acid reflux, as defined by an IIM showing a percentage time with non-acid reflux greater than 1.4%, was observed in 5 patients, 2 of whom had no pathological biliary reflux, as detected by Bilitec. No correlation was found between the two indices, as expressed by an r-value of −0.12 (p>0.05). Conclusions. Our study confirms that biliary reflux and non-acid reflux as detected by Bilitec and by IIM, respectively, are two distinct phenomena that require different techniques in order to be assessed in humans.

Strong activation of PAR-2 receptors: A common trigger for the development of gastrointestinal adenocarcinomas?

Helicobacter pylori infection is considered to be an important factor in the development of gastric cancer, while duodenogastroesophageal reflux is claimed to be the main cause of development of esophageal adenocarcinoma. A pronounced activation of PAR-2 receptors may be a common denominator in triggering the development of these cancers, and possibly pancreatic and colonic cancers as well. Evidence supporting such a concept is presented.

Proton-Pump Inhibitor Therapy in Patients with Gastro-Oesophageal Reflux Disease

Proton-pump inhibitor (PPI) failure in gastro-oesophageal reflux disease (GORD) patients has become the main reason for referral of these patients to gastroenterology specialists. It is estimated that 30% of GORD patients requiring a PPI once daily will experience treatment failure. Patients with non-erosive reflux disease are the most common GORD-related group in which once-daily PPI therapy fails. Various mechanisms have been suggested to underlie PPI failure in GORD patients. The most pertinent include weakly acidic reflux, duodenogastro-oesophageal reflux, visceral hyperalgesia, delayed gastric emptying, psychological co-morbidity and concomitant functional bowel disorders, as well as others. Because of the importance of PPI failure as a target for future drug development, further understanding of the most relevant underlying mechanisms is needed.

Bile reflux measurement and its contribution to the severity of reflux esophagitis

Gastroesophageal reflux disease (GERD) may occur with acid, bile or in a mixed form. Endoscopic injury and mucosal metaplasia are a known sequelae to pathological GERD. The aim of the study was to determine the contribution of acid and duodenogastroesophageal reflux to endoscopic severity in patients with GERD and Barrett's esophagus (BE). Ninety-one patients complaining of reflux symptoms were studied with upper gastrointestinal endoscopy and graded to nonerosive reflux disease (NERD), erosive reflux disease (ERD) and BE. Esophageal manometry and simultaneous ambulatory 24-h esophageal pH and bilirubin monitoring (Bilitec 2000) were performed in all patients. Seventy-one patients (78.0%) had ERD (Savary-Miller (grade I-III), 11 patients (12.1%) had NERD and 9 patients (9.9%) had BE, which were suspected endoscopically and diagnosed by histological esophageal biopsy. Combined 24-h esophageal bilirubin and pH monitoring revealed the following: 39 patients (42.9%) had mixed acid and bile reflux, 16 (17.6%) had pathological acid reflux alone, 18 (19.8%) had bile reflux alone and 18 patients (19.8%) showed no evidences of abnormal reflux. The percentage of the total time of the bilirubin absorbance > 0.14 in 71 patients with ERD was (8.18+/-11.28%) and in 9 patients with BE was (15.48+/-30.48%), which was significantly greater than that in 11 patients with NERD (4.48+/-8.99%), P<0.05 and P=0.01 respectively. All the BE patients had abnormal esophageal bile reflux (bile alone (3 patients)); and mixed bile and acid (6 patients)); 44 of 71 patients (61.97%) with ERD had abnormal esophageal bile reflux (alone (13 patients) and mixed bile and acid (31 patients)); meanwhile, 15 of them (21.2%) had abnormal acid exposure alone. Despite 11 patients having NERD, four patients (36.4%) had abnormal esophageal bile reflux and two of them had mixed reflux of bile with acid. We believe that the Bilitec method reliably identifies the presence of bilirubin and quantitatively detects the duodenogastroesophageal reflux of bile. Mixed reflux (acid and bile) is the chief pattern of reflux in our GERD patients. Bile reflux either alone or along with acid reflux contributes to the severity of erosive and nonerosive reflux diseases as well as in BE.

Proton‐pump inhibitor failure/resistance: Proposed mechanisms and therapeutic algorithm

AbstractProton‐pump inhibitor (PPI) failure has become more prevalent with the increasing use of PPI as the first‐line agent in the treatment of gastroesophageal reflux disease (GERD). The underlying mechanisms are diverse and may overlap. The commonly available investigations are limited in their capacity in identifying the underlying cause for PPI failure. Multichannel intraluminal impedance with 24‐h pH sensors may be useful to identify non‐acid or duodenogastroesophageal reflux in selected cases. The management strategy for PPI failure is largely empirical. Patients who have symptomatic failure on normal dose of PPI shall try double dose PPI. Failing that, empirical treatment with transient lower esophageal sphincter relaxation reducers or pain modulators can be tried. Better understanding of the pathophysiology and mechanisms for PPI failure will help to improve the management of this rising problem.