Mixed Reflux Research Articles

Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

BackgroundEsophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed.MethodsWe performed reflux surgery on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Some mice were also treated with omeprazole (1,400 ppm in diet), iron (50 mg/kg/m, i.p.), or gastrectomy plus iron. Mouse esophagi were harvested at 20, 40 or 80 weeks after surgery for histopathological analysis.ResultsAt week 20, we observed metaplasia in wild-type mice (5%, 1/20) and p53A135V mice (5.3%, 1/19). At week 40, metaplasia was found in wild-type mice (16.2%, 6/37), p53A135V mice (4.8%, 2/42), and wild-type mice also receiving gastrectomy and iron (6.7%, 1/15). Esophageal squamous cell carcinoma developed in INK4a/Arf+/- mice (7.1%, 1/14), and wild-type mice receiving gastrectomy and iron (21.4%, 3/14). Among 13 wild-type mice which were given iron from week 40 to 80, twelve (92.3%) developed squamous cell carcinoma at week 80. None of these mice developed esophageal adenocarcinoma.ConclusionSurgically induced gastroesophageal reflux produced esophageal squamous cell carcinoma, but not esophageal adenocarcinoma, in mice. Dominant negative p53 mutation, heterozygous loss of INK4a/Arf, antacid treatment, iron supplementation, or gastrectomy failed to promote esophageal adenocarcinoma in these mice. Further studies are needed in order to develop a mouse model of esophageal adenocarcinoma.

Does the Presence of a Hiatal Hernia Affect the Efficacy of the Reflux Inhibitor Baclofen During Add-On Therapy?

Reflux inhibitors, like the gamma-aminobutyric acid type B (GABA(B)) receptor agonist, baclofen, block transient lower esophageal sphincter relaxations (TLESRs) and are proposed as an add-on therapy in patients with proton pump inhibitor (PPI)-resistant gastroesophageal reflux. However, as other mechanisms of reflux become more important in the presence of a hiatal hernia (HH), the efficacy of reflux inhibitors to reduce acid and non-acid exposure may be hampered. Therefore, we compared the effect of baclofen in patients with no HH (-HH) and those with a large HH during PPI treatment. A total of 27 gastroesophageal reflux disease (GERD) patients on PPI were included; 16 had -HH and 11 had a large (> or =3 cm) HH (+HH). During PPI treatment, the effect of baclofen (3 x 20 mg) on acid and non-acid reflux was evaluated in a randomized, double-blind, placebo-controlled cross-over study. Reflux was measured during 24 h using combined esophageal impedance and pH-metry. The majority of reflux events consisted of both gaseous and liquid reflux with a significant increase in non-acid, mixed reflux episodes in +HH patients compared with those in -HH patients. Acid exposure time was in the normal range in both patient groups during both placebo and baclofen. In this study, baclofen significantly reduced the total number of reflux episodes with 36% in -HH patients and 43% in +HH patients, but did not change the number of acid reflux episodes or total acid exposure time. This study shows that baclofen is also effective in patients with GERD with +HH, further underscoring the potential of reflux inhibitors as treatment of GERD.

Reflux profile of Chinese gastroesophageal reflux disease patients with combined multichannel intraluminal impedance‐pH monitoring

To investigate the reflux profile of Chinese gastroesophageal reflux disease (GERD) patients with the aid of combined multichannel intraluminal impedance-pH (MII-pH) monitoring technique. Consecutive patients presented with GERD symptoms were enrolled to erosive esophagitis (EE) group, non-erosive reflux disease (NERD) group and functional heartburn (FH) group after upper endoscopy, combined MII-pH monitoring and rabeprazole test. Another 20 healthy controls (HC) were recruited. Sixty-four GERD patients (EE:20, NERD:22, FH:22, HC:20) were enrolled. There were more episodes of liquid reflux and proximal reflux in EE and NERD groups than that in FH and HC groups (P < 0.05). Patients in FH and HC groups had higher proportion of mixed reflux (P = 0.000). The percentage of acid reflux in EE and NERD was much higher, while there was a higher percentage of weakly acidic reflux in FH and HC (P = 0.000). No significant difference was found in MII-pH parameters between groups with and without response to rabeprazole test except recumbent percentage time of esophageal pH value below 4 and episodes of proximal reflux. Erosive esophagitis and NERD patients had more liquid and proximal reflux episodes than FH patients and healthy controls. Acid and liquid reflux was predominant in the former two groups, while weakly acidic and mixed reflux was predominant in the latter two groups.

M1859 Incidence of GERD Symptoms Among Patients Under Acute NSAIDs Treatment: Genius Study Preliminary Results

not responding (<50% improvement) to full dose PPI, pH-impedance ambulatory monitoring was performed on two occasions, off and on therapy, randomly, following stationarymanometry. Data obtained in 15 patients (F 11, mean age 47), showing a positive symptom-reflux association (SI and/or SAP), were compared to those of 27 NERD patients PPI-responders, with a positive SI and/or SAP (F 16, mean age 51). Reflux episodes were classified according to standardized protocols. Results: AET was pathological in 12/15 patients off PPI and in 1/15 patients on PPI. Overall, 2639 refluxes were analyzed; off therapy, non-responder patients, compared to responders, showed more frequent reflux episodes (mean 55±30 vs 37±16/24h), higher proportion of acidic (83±15 vs 68±12%) and of proximal refluxes (59±14 vs 34±9%), lower proportion of mixed (42±12 vs 55±14%) refluxes. During PPI therapy, in the non-responder patients, frequency of reflux episodes did not change, proportions of acidic decreased to 21%, weakly acidic refluxes increased to 79%; proportions of mixed (36±10%) and proximal refluxes (60±18%) remained unchanged. Analysis of gastric pH confirmed compliance and effectiveness of therapy in all patients. On therapy, in nonresponder patients, acidic, compared to weakly acidic reflux, was significantly associated with liquid-gas composition (OR 1.6 [1.13-2.26]) and with proximal extent (OR 1.6 [0.73.8]). No interaction between acidity, proximal extent and physical properties was observed in non-responder patients off PPI (OR 0.9 [0.6-1.4] and 1 [0.8-1.4]) and in PPI-responder patients (OR 1.2 [0.7-2.2] and 1 [0.7-1.6]). Conclusions: in PPI-resistant patients, during therapy, acidic content is associated with presence of gas and proximal spread of refluxate. It could be hypothesized that the interaction between chemical and physical properties are involved in the persistence of symptoms despite acid suppression in this subgroup of NERD patients.

W1841 Esophageal Acid Reflux and Respiratory Symptoms: Disparate Relationship in Asthmatic and Non-Asthmatic Patients

(esophageal aperistalsis and hypotonic LES). Nine patients (60%) had endoscopic esophagitis, whereas all fifteen showed gastroesophageal reflux at the 24h pH-MII recording. Analyzing the type of reflux, 2 patients showed a pure acid reflux, five (33%) a non-acid reflux and the other eight (53%) had a mixed reflux, both acid and non acid. Regarding lung involvement, images of interstitial pneumonia were detected in 6 out 15 (40%). The proximal extent of liquid refluxate into the esophagus was documented in three patients, all of them with interstitial pneumonia (p>0.05 by Fisher's exact test) Conclusions: the majority of SSc patients showed both acid and non acid GERD, and these findings might help for better tailoring medical treatment. Patients with proximal extent of liquid refluxate seem to be at risk of pulmonary involvement. These preliminary data need to be confirmed in a larger cohort of SSc patients.

691 The Role of PPARγ Modulation in the Growth Inhibition of Hepatocellular Carcinoma Cells

Background: It has been reported that weakly acidic pharyngeal gas reflux is significantly increased in patients with reflux laryngitis. However, the diagnosis of reflux laryngitis is controversial. Therefore, we studied patients with chronic cough who responded to fulldose PPI therapy, in whom 24-hr pharyngoesophageal impedance and pH monitoring was performed. Methods: Ten patients with chronic cough responding to PPIs (CC)(24-74 yrs; 3F), 10 with GERD (GE)(20-73; 2F), and 10 healthy controls (C)(22-72; 4F) underwent ambulatory 24-hr concurrent pharyngoesophageal impedance and pH monitoring. Three types of new impedance/pH catheters (ZAI-S62C12E-14E, Sandhill Scientific Inc., CO) were used to detect esophagopharyngeal reflux with a Sleuth GER monitoring system. The subjects ate ad libitum and were instructed to record events such as coughing by using an event marker. Weakly acidic reflux was defined as a pH drop of more than 1 unit with a nadir pH > 4. The symptom association probability (SAP) method was used to analyze the relation between gastroesophageal reflux and cough. In 6 CC patients, 24-hr monitoring was repeated on treatment after 8 weeks full-dose PPI therapy. Symptoms were evaluated using Frequency scale for the symptoms of GERD (FSSG). Results: Weakly acidic pharyngeal gas reflux events were observed in 8 out of 10 CC patients, and were significantly increased in the CC versus GE or C groups (p<0.05). Acidic and weakly acidic esophagaopharyngeal reflux (EPR) events were only observed in CC patients and were always induced by swallowing and occurred during acid liquid or mixed reflux events in the proximal esophagus. Swallow-induced acidic and weakly acidic EPR was significantly increased in the CC versus GE or C groups (p<0.05). Among 10 CC patients, 9 had weakly acidic and/or acidic EPR events, while only one had pure non-acidic EPR events. This patient and 2 other CC patients showed a positive association between gastroesophageal reflux and cough on SAP analysis. In 6 CC patients, PPIs abolished swallow-induced weakly acidic and/or acidic reflux, while weakly acidic pharyngeal gas reflux events decreased significantly and symptoms improved significantly compared with before therapy (p<0.05). Conclusion: Most patients with chronic cough responding to PPIs had minor acidic gas reflux and/or swallow-induced weakly acidic and/or acidic reflux in the pharynx. A direct effect of acidic mist or acidic liquid refluxing into the pharynx was suggested to be the cause of their chronic cough. In some patients, symptoms may arise indirectly from gastroesophageal reflux via a vago-vagal reflex.

Normal Values of 24-Hour Combined Esophageal Multichannel Intraluminal Impedance and pH Monitoring in the Chinese Population

Background: There is a lack of data on combined esophageal multichannel intraluminal impedance and pH (MII-pH) monitoring in the Chinese population. Goals: To define the normal range and compare the parameters to those of the Western population. Study: Healthy volunteers were recruited and underwent 24-hour ambulatory combined MII-pH monitoring. Gastroesophageal reflux episodes were detected and characterized by pH (acidic, weakly acidic and weakly alkaline reflux) and composition (liquid, mixed and gas reflux). Results: Seventy healthy volunteers (male:female 33:37) were recruited. The median and 95th percentile number of the total reflux episodes over 24 h in the Chinese population was 40 and 75, respectively, whereas the corresponding numbers of acidic, weakly acidic and weakly alkaline reflux episodes were 22 and 54, 16 and 40, and 0 and 4, respectively. Among all reflux episodes 53.3% were acidic, 44.7% were weakly acidic, and 2% weakly alkaline. More than half (52.4%) of the reflux episodes were mixed, 37.2% were liquid, and 10.4% were gas. A total of 26.6% of reflux episodes reached 15 cm above the lower esophageal sphincter. Male gender was associated with an increased number of acid, liquid, mixed and proximal reflux episodes (p < 0.05). Conclusions: This study provides normal values for the Chinese population. Differences between genders in impedance parameters required caution during data interpretation. The number of reflux episodes in the Chinese population was similar to that in the Western population.

Bile and acid reflux in the pathogenesis of reflux oesophagitis in children

The aim of this study was to investigate the role of bile and acid reflux in the pathogenesis of reflux oesophagitis (RE) in children. A total of 44 patients aged 5-17 years with gastro-oesophageal reflux symptoms were enrolled. Simultaneous 24-h oesophageal Bilitec 2000 (Medtronic Instruments, Minneapolis, MN, USA) bilirubin monitoring and pH monitoring, in biopsy of oesophageal mucosa by gastro-endoscopy, were performed in all patients. According to the diagnostic criteria of pathological acid reflux and pathological bile reflux, 10 of 44 cases (22.7%) had acid reflux, 10 (22.7%) had isolated bile reflux, 16 (36.4%) had mixed acid and bile reflux, and the other eight (18.2%) had no reflux. Significant difference was observed in the ratio of different patterns of reflux between the RE group (26 cases) and the non-erosive reflux disease (NERD) group (18 cases) (chi(2) = 9.096, P < 0.01). All the parameters of acid reflux in the RE group were higher significantly than that in the NERD group (P < 0.05 or P < 0.01). A total of 20 out of 26 cases (76.9%) with RE had oesophageal acid reflux as against six out of 18 cases (33.3%) in patients with NERD (P < 0.01). The difference of each parameter of bile reflux had not reached significance between the two groups. Mixed reflux is the predominant form of reflux in the causation of oesophageal mucosal injury in children. Isolated bile reflux also plays a role in the development of RE, although only in patients without acid reflux.

Secretory phospholipase A 2 is required to produce histologic changes associated with gastroduodenal reflux in a murine model

The earliest response of esophageal mucosa to gastric reflux is the development of oxidative damage and inflammation. These processes contribute to the development of metaplasia known as Barrett's esophagus, as well as the progression to malignancy. Secretory phospholipase A(2) is a mediator of inflammation with levels that are increased in Barrett's metaplasia and carcinoma when compared with levels in normal samples. Our goal is to determine the role of secretory phospholipase A(2) in the development of reflux-associated changes in the esophageal mucosa. Secretory phospholipase A(2)-deficient mice (C57BL/6, n = 5) and mice known to express high levels of secretory phospholipase A(2) (BALB/c, n = 5) underwent side-to-side surgical anastomosis of the first portion of the duodenum and gastroesophageal junction, allowing exposure of esophageal mucosa to duodenal and gastric contents duodeno-gastroesophageal anastomosis. Control animals (n = 5) of each strain underwent laparotomy with esophagotomy and repair. Tissue was frozen in embedding medium. Hematoxylin and eosin staining and Ki67 and secretory phospholipase A(2) immunohistochemistry were used to evaluate esophageal tissue and its response to duodeno-gastroesophageal anastomosis. Immunofluorescent staining confirmed the absence of secretory phospholipase A(2) in C57BL/6 mice and its presence in BALB/c mice. Hematoxylin and eosin staining demonstrated significant thickening of the esophageal mucosa in response to gastroesophageal reflux in the presence of secretory phospholipase A(2). Mice known to express high levels of secretory phospholipase A(2) also demonstrated increased numbers of proliferating cells. Secretory phospholipase A(2)-deficient mice were immune to the early changes induced by mixed reflux. The presence of secretory phospholipase A(2) appears necessary for early histologic changes produced by exposure of the esophagus to gastroduodenal contents. This enzyme is identified as a promising target for evaluation of mechanisms of carcinogenesis and chemoprevention of esophageal carcinoma.

Characteristics of Symptomatic Reflux Episodes on Acid Suppressive Therapy

Persistent symptoms on acid suppressive therapy are due to either acid or nonacid gastroesophageal reflux (GER) episodes or are not related to reflux. To compare physical and chemical characteristics of GER episodes associated with symptoms in patients on acid suppressive therapy. Patients with persistent symptoms on acid suppressive therapy underwent combined impedance-pH monitoring. Reflux episodes were classified as acid if nadir pH was <4.0, and nonacid if it remained at >/=4.0, separated into liquid-only or mixed (liquid-gas), and considered to reach the proximal esophagus if liquid was present 15 cm above the lower esophageal sphincter (LES). Reflux episodes were considered symptomatic if patients recorded a symptom within 5 min after the reflux episode. Risk factors of symptomatic reflux episodes were identified using multivariable generalized estimating equations (GEEs). One hundred twenty patients (85 women, median age 54 yr, range 18-85 yr) recorded 3,547 reflux episodes (84.3% nonacid, 50.6% mixed), of which 468 (13.2%) were symptomatic. Based on multivariable GEE analysis with episode-level symptom status (symptomatic vs nonsymptomatic) as the outcome variable, reflux episode acidity was not significantly associated with symptoms (P= 0.40). Mixed reflux episodes were significantly associated with symptoms relative to liquid-only episodes (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.19-1.87, P= 0.0005), as were reflux episodes reaching the proximal esophagus compared with those reaching the distal esophagus only (OR 1.28, 95% CI 1.06-1.55, P= 0.012). The majority of reflux episodes on acid suppressive therapy are asymptomatic. Reflux episodes extending proximally and having a mixed (liquid-gas) composition are significantly associated with symptoms, irrespective of whether pH is acid (<4) or nonacid (>/=4).

Therapeutic effects of Tiaozhong Granule on esophagus mucous membrane in rats with mixed reflux esophagitis and the mechanisms

To explore the mechanism of Tiaozhong Granule (TZG), a compound traditional Chinese herbal medicine, in treating rats with mixed reflux esophagitis. Fifty-eight SD rats were randomly divided into untreated group (n=12), sham-operated group (n=10), TZG-treated group (n=12), Banxia Xiexin Decoction (BXXXD)-treated group (n=12) and cisapride-treated group (n=12). Mixed reflux esophagitis was induced by esophago-duodenum end-to-side anastomosis. Four weeks later, the rats were orally administered twice daily for 12 days. Pathological changes of esophagus mucous membrane were observed by using HE staining. The expressions of proliferating cell nuclear antigen (PCNA) and p53 in the esophagus tissue were detected by immunohistochemical SABC method. Spectrophotometric method was used to detect the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum. Compared with the untreated group, pathological changes of esophagus mucous membrane were relieved in different degrees in TZG-treated group, BXXXD-treated group and cisapride-treated group. Content of MDA and expressions of PCNA and p53 were obviously decreased in the three treated groups (P<0.01), and the activities of SOD and GSH-Px were significantly increased in the three treated groups (P<0.05, P<0.01). TZG had better effects than cisapride in decreasing the content of MDA and increasing the activities of SOD and GSH-Px (P<0.05). TZG was better in aspect of reducing the expressions of PCNA and p53 than BXXXD and cisapride tablets (P<0.05). Tiaozhong Granule can treat mixed reflux esophagitis in rats, and its action mechanisms may be associated with decreasing the expressions of PCNA and p53 in esophagus mucous membrane, reducing the content of MDA and increasing the activities of SOD and GSH-Px in serum.

T1983 Short Duration of Acid Exposure Sensitizes the Esophagus to Perception of Weakly Acidic and Mixed Reflux in Non-Erosive Reflux Disease (NERD) Patients

T1983 Short Duration of Acid Exposure Sensitizes the Esophagus to Perception of Weakly Acidic and Mixed Reflux in Non-Erosive Reflux Disease (NERD) Patients

Effects of Tiaozhong granule on experimental mixed reflux esophagitis in rats

Effects of Tiaozhong granule on experimental mixed reflux esophagitis in rats

Retinoids, bile acids and PPARs in Barrett’s oesophagus

Intestinal metaplasia of the oesophagus (Barrett’s oesophagus) is the most important risk factor for oesophageal adenocarcinoma. Although the role of mixed bile and acid gastro-oesophageal reflux is well established, the...

Presence of gas in the refluxate enhances reflux perception in non-erosive patients with physiological acid exposure of the oesophagus

Objective:The mechanisms underlying symptoms in gastro-oesophageal reflux disease, particularly in non-erosive reflux disease (NERD), remain to be fully elucidated. Weakly acidic reflux and the presence of gas in the refluxate...

VS13P THE IMPACT OF THE ESCHAR TRIAL ON CLINICAL PRACTICE

The ESCHAR trial, published June 2004, showed that patients with venous ulceration who had superficial or mixed superficial and segmental deep venous reflux had a decreased likelihood of recurrent ulceration if they were treated with superficial venous surgery. This prompted us, firstly, to review our service to see if we were following this level one evidence; secondly to estimate how many of our patients could benefit from adopting this practice.Method Retrospective audit of all patients attending a nurse‐led ulcer clinic for a 6 month period between June and December 2004.Results 163 patients attended during the audit period. Data were retrieved for 146. Of these only 54 (37%) had purely venous ulceration on clinical assessment, of whom 31 had a venous duplex scan. 21 patients had superficial only, or mixed superficial and deep reflux; 8 had no reflux; 2 had deep reflux only. Of these 21 patients who could potentially be suitable for superficial venous surgery, 1 had deep venous occlusion, 4 patients refused surgery, 4 were considered unsuitable for surgery on medical grounds, 7 were not assessed for surgery, only 3 patients were awaiting superficial venous surgery.Conclusion Despite the publication of evidence supporting superficial venous surgery in selected patients only 3/146 (2%) patients attending our clinic were listed for venous surgery. However 7/21 (33%) were not assessed for treatment. This study demonstrates the inertia in adopting “best evidence” into clinical practice. Even so the numbers of leg‐ulcer patients likely to benefit from surgery appears surprisingly small.

A Rat Surgical Model of Esophageal Metaplasia and Adenocarcinoma-Induced by Mixed Reflux of Gastric Acid and Duodenal Contents

Recent clinical data have revealed that mixed reflux (MR) of gastric acid and duodenal contents frequently occurs in patients with gastroesophageal reflux disease and a progressive increase of MR occurs with increasing severity across gastroesophageal reflux disease. Herein we report a novel rat surgical model in which esophageal metaplasia and adenocarcinoma develop as complications of MR. The model was created by performing an esophagojejunostomy and a gastrojejunostomy 5 mm proximal to the esophagojejunal anastomosis in 40 rats. Severe inflammatory and proliferative changes, high prevalence of esophageal metaplasia (78%), and adenocarcinoma (50%) were observed in the lower part of the esophagus of rats 20 weeks after surgery. The resulting esophageal lesions resembled those described in humans and supported a progression from intestinal metaplasia to dysplasia and, ultimately, esophageal adenocarcinoma. Such a model may provide a useful tool in study of human reflux-induced carcinogenesis.

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.

Le reflux biliaire duodéno-gastrique et gastro-œsophagien

This study reviews current data regarding duodenogastric and gastroesophageal bile reflux-pathophysiology, clinical presentation, methods of diagnosis (namely, 24-hour intraluminal bile monitoring) and therapeutic management. Duodenogastric reflux (DGR) consists of retrograde passage of alkaline duodenal contents into the stomach; it may occur due to antroduodenal motility disorder (primary DGR) or may arise following surgical alteration of gastoduodenal anatomy or because of biliary pathology (secondary DGR). Pathologic DGR may generate symptoms of epigastric pain, nausea, and bilious vomiting. In patients with concomitant gastroesophageal reflux, the backwash of duodenal content into the lower esophagus can cause mixed (alkaline and acid) reflux esophagitis, and lead, in turn, to esophageal mucosal damage such as Barrett's metaplasia and adenocarcinoma. The treatment of DGR is difficult, non-specific, and relatively ineffective in controlling symptoms. Proton pump inhibitors decrease the upstream effects of DGR on the esophagus by decreasing the volume of secretions; promotility agents diminish gastric exposure to duodenal secretions by improving gastric emptying. In patients with severe reflux resistant to medical therapy, a duodenal diversion operation such as the duodenal switch procedure may be indicated.

Multichannel Intraluminal Impedance and pH (MII-pH) in Functional Heartburn (FH)

Purpose: Patients with heartburn and regurgatation but normal endoscopy and 24hour pH have FH. Causes of FH are uncertain but include a false negative pH study, sensitivity to minute amounts of acid, non acid and gas reflux. 24 hour MII-pH allows examination of each of these potential causes. AIMS 1.Determine potential causes of FH symptoms. 2.Determine the clinical usefulness of MII-pH testing in these patients. Methods: 29 consecutive FH patients age 48 years (29–71 yrs), 22 F, off PPIs for 2 weeks underwent 24hour MII-pH, noting heartburn and regurgation.The catheter dectected pH 5cm above the LES and impedance at 6 sites throughout the esophagus.The following parameters were studied: Acid reflux (pH<4), Minor acid reflux (ph drop >1 log unit but pH remains >4), Non acid reflux (pH change of <1 log unit with pH>4), Type of reflux (liquid, gas or mixed). Symptoms occurring within 180sec of a reflux event were considered related to the reflux. The Symptoms Index (SI) was caculated if 4 or more symptoms occurred during a study and considered + if 50% or more. All studies were hand read. Results: 1) 8 patients (28%) had a + SI and therefore FH. 2) 4 patients (14%) had a + 24 hour pH test despite an initial negative study and had GERD. 3) 5 patients (17%) had a -SI and therefore no evidence of FH as defined. 4)12 patients (41%) had < 4 symptoms during the exam. Liquid, gas and mixed reflux were equally divided amongest the 98 total reflux episodes in the 8 FH patients. The table shows causes of reflux, SI of acid reflux and SI of all reflux in the 8 FH patients.Table: Patients with FHConclusions: 1) Minor acid/non acid reflux is a frequent cause of symptoms in FH (50/98 episodes). 2) 28% (8 of 29) had FH (+SI). 5 of these 8 (62.5%) would have had -SI without MII-ph testing and would have been missed. 3) 24 hour MII-pH was useful in determining whether FH was or wasn't present in almost half of all patients (48%) (+SI based on total reflux, -SI and original false −24hour pH). 4) 41% of patients had too few symptoms during the exam to properly catogorize. 5) Liquid, gas and mixed reflux were equally symptomatic in these FH patients.