Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS: We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS: Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P < 0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION: DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.

Endoscopic and percutaneous biliary interventions in patients with altered upper gastrointestinal anatomy-the Munich Multicenter Experience.

BACKGROUND: In patients with altered upper gastrointestinal anatomy, conventional endoscopic retrograde cholangiography is often not possible and different techniques, like enteroscopy-assisted or percutaneous approaches are required. Aim of this study was to analyze success and complication rates of these techniques in a large collective of patients in the daily clinical practice in a pre-endosonographic biliary drainage era. PATIENTS AND METHODS: Patients with altered upper gastrointestinal anatomy with biliary interventions between March 1st, 2006, and June 30th, 2014 in four tertiary endoscopic centers in Munich, Germany were retrospectively analyzed. RESULTS: At least one endoscopic-assisted biliary intervention was successful in 234/411 patients (56.9%)-in 192 patients in the first, in 34 patients in the second and in 8 patients in the third attempt. Success rates for Billroth-II/Whipple-/Roux-en-Y reconstruction were 70.5%/56.7%/49.5%. Complication rates for these reconstructions were 9.3%/6.5%/6.3%, the overall complication rate was 7.1%. Success rates were highest in patients with Billroth-II reconstruction where use of a duodenoscope was possible, complication rates were also highest in this scenario. Success rates were lowest in longer-limb anatomy like Roux-en-Y reconstruction. Percutaneous biliary drainages (PTBD) were inserted 268 times with substantially higher success (90.7%) as well as complication rates (11.6%) compared to the endoscopic approach. Compared to patients treated endoscopically, patients with PTBD had a lower performance status, more severe cholestasis and a significant higher rate of malignant underlying disease. CONCLUSION: In patients with altered upper gastrointestinal anatomy, success rates of endoscopic-assisted biliary interventions are lower compared to PTBD. Still, due to the beneficial complication rates of the endoscopic approach, this technique should be preferred whenever possible and in selected patients who still need to be defined in detail, repeated endoscopic attempts are useful to help achieve the desired result.

IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients.

BACKGROUND: For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients. METHODS: Prospectively collected serum samples of 17 EoE patients before and after 8 weeks of therapy with budesonide (1 mg BID) were analyzed for total and antigen-specific IgG4 and IgE levels. Also, immunohistochemical analysis of total and IgG4-positive plasma cells was performed on esophageal biopsies of these patients. In total, 14 GERD patients without histologic proof of eosinophilic infiltration were taken as a control group. RESULTS: Total IgG4 serum levels in EoE patients were significantly higher than in GERD patients (121.0 vs. 71.2 mg/dL; P=0.038) and decreased under budesonide therapy (121.0 vs. 104.2 mg/dL; P=0.019). IgE levels did not differ significantly between all groups. In EoE patients also a high number of esophageal IgG4-positive plasma cells was detected and significantly reduced under therapy (29.1 vs. 0.1 IgG4-positive cells; P<0.001). In GERD patients no relevant esophageal plasma cell infiltration could be seen. CONCLUSIONS: In EoE patients elevated systemic IgG4 serum levels compared with GERD patients can be seen and decrease under topical steroid therapy. Also, local IgG4 plasma cells expression is high in EoE, but not in GERD patients and normalize under therapy. These findings are further proof for a possible association of EoE with IgG4.

Comparison of cap-assisted endoscopy vs. side-viewing endoscopy for examination of the major duodenal papilla: a randomized, controlled, noninferiority crossover study.

BACKGROUND : Use of a side-viewing endoscope is currently mandatory to examine the major duodenal papilla; however, previous studies have used cap-assisted endoscopy for complete examination of the papilla. The aim of this study was to compare cap-assisted endoscopy with side-viewing endoscopy for examination of the major duodenal papilla. METHODS : This was a prospective, randomized, blinded, controlled, noninferiority crossover study. Patients were randomized to undergo either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted endoscopy followed by side-viewing endoscope. Photographs of the major duodenal papilla were digitally edited to mask the cap area before they were evaluated by three blinded external examiners. Our primary end point was complete visualization of the major duodenal papilla. Secondary end points were the ability to examine the mucosal pattern, the overview of the periampullary region, overall satisfaction, and time to locate the papilla. RESULTS : 62 patients completed the study. Complete visualization of the major duodenal papilla was achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 % with a two-sided 95 % confidence interval of -4.0 % to 7.3 %, which did not exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better scores regarding the examination of mucosal pattern and overall satisfaction, whereas side-viewing endoscopy had a better overview score (P < 0.001, P = 0.004, and P < 0.001, respectively). There was no relevant difference in the median times to locate the major duodenal papilla. CONCLUSION : Cap-assisted endoscopy and side-viewing endoscopy had similar success rates for complete visualization of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing endoscopy gives a better overview of the periampullary region.

Comparison of Ultrasound and Fluoroscopically Guided Percutaneous Transhepatic Biliary Drainage.

BACKGROUND: Percutaneous transhepatic biliary drainage (PTBD) plays a significant role especially in the palliation of an endoscopically inaccessible biliary system. Since a standard technique of PTBD is not defined, we compared a fluoroscopically guided technique (F-PTBD) with an ultrasound (US-PTBD) guided approach. PATIENTS AND METHODS: Procedure characteristics, success-rates and complication-rates of the different PTBD techniques were compared in patients who underwent PTBD between October 1, 2006, and -December 31, 2014. RESULTS: In 195 patients, 251 PTBDs (207 F-PTBDs, 44 US-PTBDs) were performed. F-PTBDs were mostly inserted from the right and US-PTBDs from the left. Patient age, gender and physical status were comparable in both techniques. There was no difference regarding overall procedure success (90%/86.4%), overall interventional complication rates (10.6%/9.1%), fluoroscopy times, intervention times or sedatives dosages. However, major complications were only encountered in F-PTBDs. There was a higher success rate for F-PTBD vs. US-PTBD from the right side (91.9 vs. 75%; p = 0.033) and a trend towards a higher success rate for US guidance from the left side (82.9 vs. 95.8%; p = 0.223). CONCLUSIONS: For drainage of the right biliary system F-PTBD seems superior over the US-PTBD technique used in this study. However, major complications can occur more frequently in F-PTBD.

Management of occluded self-expanding biliary metal stents in malignant biliary disease.

BACKGROUND: Occlusion of self-expanding metal stents (SEMS) in malignant biliary obstruction occurs in up to 40% of patients. This study aimed to compare the different techniques to resolve stent occlusion in our collective of patients. METHODS: Patients with malignant biliary obstruction and occlusion of biliary metal stent at a tertiary referral endoscopic center were retrospectively identified between April 1, 1994 and May 31, 2014. The clinical records were further analyzed regarding the characteristics of patients, malignant strictures, SEMS, management strategies, stent patency, subsequent interventions, survival time and case charges. RESULTS: A total of 108 patients with biliary metal stent occlusion were identified. Seventy-nine of these patients were eligible for further analysis. Favored management was plastic stent insertion in 73.4% patients. Second SEMS were inserted in 12.7% patients. Percutaneous transhepatic biliary drainage and mechanical cleansing were conducted in a minority of patients. Further analysis showed no statistically significant difference in median overall secondary stent patency (88 vs. 143 days, P = 0.069), median survival time (95 vs. 192 days, P = 0.116), median subsequent intervention rate (53.4% vs. 40.0%, P = 0.501) and median case charge (€5145 vs. €3473, P = 0.803) for the treatment with a second metal stent insertion compared to plastic stent insertion. In patients with survival time of more than three months, significantly more patients treated with plastic stents needed re-interventions than patients treated with second SEMS (93.3% vs. 57.1%, P = 0.037). CONCLUSIONS: In malignant biliary strictures, both plastic and metal stent insertions are feasible strategies for the treatment of occluded SEMS. Our data suggest that in palliative biliary stenting, patients especially those with longer expected survival might benefit from second SEMS insertion. Careful patient selection is important to ensure a proper decision for either management strategy.

Endoluminal Sphincter Augmentation with the MUSE™ System and GERDX™ System in the Treatment of Gastroesophageal Reflux Disease: A New Impact?

To bridge the gap between the long-term intake of proton pump inhibitors (PPIs) and the potential risks of laparoscopic fundoplication, a number of endoscopic procedures for the treatment of gastro-esophageal reflux disease (GERD) have been developed over the past 30 years. Because of the minimally invasive approach, short operative time, and efficacy in selected patients, endoluminal sphincter augmentation appears to be highly attractive. However, most early devices have proven to be unsafe or failed to provide long-term symptom relief. Accordingly, products for endoluminal sphincter augmentation have undergone several modifications to achieve an increased lower esophageal sphincter (LES) baseline pressure to re-establish the LES as an efficacious anti-reflux barrier. This paper reviews and discusses the two latest products for endoluminal sphincter augmentation, the MUSE™ device (Medigus, Ltd., Omer, Israel) and the GERDX™ system (G-SURG GmbH, Seeon-Seebruck, Germany). While the currently available literature has proven their effectiveness in principle, long-term results are lacking. Further studies and developments are necessary to determine whether these two new devices will truly impact GERD therapy.

Mortality Risk for Acute Cholangitis (MAC): a risk prediction model for in-hospital mortality in patients with acute cholangitis.

BACKGROUND: Acute cholangitis is a life-threatening bacterial infection of the biliary tract. Main focus of this study was to create a useful risk prediction model that helps physicians to assign patients with acute cholangitis into different management groups. METHODS: 981 cholangitis episodes from 810 patients were analysed retrospectively at a German tertiary center. RESULTS: Out of eleven investigated statistical models fit to 22 predictors, the Random Forest model achieved the best (cross-)validated performance to predict mortality. The receiver operating characteristics (ROC) curve revealed a mean area under the curve (AUC) of 91.5 %. Dependent on the calculated mortality risk, we propose to stratify patients with acute cholangitis into a high and low risk group. The mean sensitivity, specificity, positive and negative predictive value of the corresponding optimal cutpoint were 82.9 %, 85.1 %, 19.0 % and 99.3 %, respectively. All of these results emerge from nested (cross-)validation and are supposed to reflect the model's performance expected for external data. An implementation of our risk prediction model including the specific treatment recommendations adopted from the Tokyo guidelines is available on http://www2.imse.med.tum.de:3838/ . CONCLUSION: Our risk prediction model for mortality appears promising to stratify patients with acute cholangitis into different management groups. Additional validation of its performance should be provided by further prospective trails.

Emergency video capsule endoscopy in patients with acute severe GI bleeding and negative upper endoscopy results.

BACKGROUND: In mid-GI bleeding, video capsule endoscopy (VCE) shows the best diagnostic yield for ongoing overt bleeding. To date, the utility of VCE in acute severe GI bleeding has been analyzed rarely. OBJECTIVE: To evaluate the impact of VCE when performed on patients with acute severe GI bleeding immediately after an initial negative upper endoscopy result. DESIGN: Prospective study. SETTING: Tertiary-care center. PATIENTS: Patients with melena, dark-red or maroon stool, hemodynamic instability, drop of hemoglobin level ≥2 g/dL/day, and/or need of transfusion ≥2 units of packed red blood cells per day were included. INTERVENTIONS: After a negative upper endoscopy result, emergency VCE was performed by immediate endoscopic placement of the video capsule into the duodenum. MAIN OUTCOME MEASUREMENTS: Rate of patients in whom emergency VCE correctly guided further diagnostic and therapeutic procedures. RESULTS: Upper endoscopy showed the source of bleeding in 68 of 88 patients (77%). In the remaining 20 patients (23%), emergency VCE was performed, which was feasible in 19 of 20 patients (95%; 95% confidence interval [CI], 75%-99%). Emergency VCE correctly guided further diagnostic and therapeutic procedures in 17 of 20 patients (85%; 95% CI, 62%-97%) and showed a diagnostic yield of 75% (95% CI, 51%-91%). LIMITATIONS: Single-center study, small sample size. CONCLUSION: In patients with acute severe GI bleeding and negative upper endoscopy results, emergency VCE can be useful for the immediate detection of the bleeding site and is able to guide further therapy. (Clinical trial registration number: NCT01584869.)

Drainage-related Complications in Percutaneous Transhepatic Biliary Drainage: An Analysis Over 10 Years.

BACKGROUND: Procedure-related complications of percutaneous transhepatic biliary drainage (PTBD) have been well documented in the literature. However, relatively restricted data are available concerning drainage-related complication rates in long-term PTBD therapy. The present retrospective study evaluated the extent and the nature of drainage complications during PTBD therapy and associated risk factors for these complications. PATIENTS AND METHODS: Between June 1997 and May 2007, a total of 385 patients with PTBD were identified by analyzing the PTBD database and hospital charts, with a total of 2468 percutaneous biliary drainages being identified. RESULTS: Among the identified patients, 243 (63%) had malignant and 142 (37%) had benign bile duct strictures. At least 1 drainage-related complication was observed in 40% of the patients. With respect to the total number of drains, prosthesis complications occurred in 23%. Occlusion, dislocation, and cholangitis were the most common complications observed during PTBD therapy. Risk factors for cholangitis and occlusion were malignant disease, prior occurrence of complications, and bilateral drainage. Proximal stenosis of the biliary system was close to significant. CONCLUSIONS: Drainage-related complications are a major problem in PTBD therapy. The risk factors for occlusion and cholangitis discovered in this study can help to refine individual strategies to reduce the rate of these drainage complications.

Fungal "colonisation" is associated with increased mortality in medical intensive care unit patients with liver cirrhosis.

OBJECTIVES: Patients with liver cirrhosis are at increased risk for fungal infections. However, distinction of fungal colonisation (FC) and invasive mycoses is difficult. Aim of this study was to analyse the impact of FC on mortality of cirrhotic ICU-patients. METHODS: Retrospective mortality analysis of a prospectively maintained database on 120 cirrhotic patients with and without FC. Comparison to 120 noncirrhotic controls matched for APACHE-II (24.9 ± 3.7 vs. 25.0 ± 2.6; p = 0.263). RESULTS: About 69/120 (58%) of patients with cirrhosis had FC. These patients had significantly higher APACHE-II score and mortality compared to cirrhotic patients without FC (27 ± 3 vs. 23 ± 4, p < 0.001; 78 vs. 35%, p < 0.001). In multivariate analysis, FC was independently (p = 0.047) associated to mortality. Mortality of noncirrhotic patients with FC (14/31; 45.2%) was not different to noncirrhotic controls without FC [28/89 (31.2%; p = 0.168)]. Similarly, in multivariate analysis of noncirrhotics, APACHE-II (p < 0.001), but not FC, was independently associated to mortality. Multiple regression analysis of all 240 cirrhotic and noncirrhotic patients demonstrated that APACHE-II (p < 0.001), cirrhosis (p = 0.001) and FC (p = 0.049) were independently associated with mortality. CONCLUSION: Fungal "colonisation" is independently associated to mortality in cirrhotic ICU-patients. Early antimycotic therapy should be considered in critically ill cirrhotic patients with FC.

Treatment of eosinophlic esophagitis with swallowed topical corticosteroids.

Eosinophilic esophagitis (EoE) is an emerging chronic local immune-mediated disease of the esophagus. Beside proton pump inhibitors and food-restriction-diets swallowed topical corticosteroids (STC) can be offered as a first line therapy according to current guidelines. This review describes the background and practical management of STCs in EoE. So far, mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications "off label". Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85% - an orodispersible tablet of budesonide has been approved as the first "in label" medication for EoE in Europe in June 2018. Whereas it was shown that disease remission induction of EoE by STCs is highly effective, there is still a lack of data regarding long-term and maintenance therapy. However, current studies on STC maintenance therapy add some movement into the game.

Sorbitol malabsorption in patients with abdominal discomfort.

BACKGROUND: The role of sorbitol malabsorption in patients with functional abdominal discomfort has not been finally clarified yet. Therefore, aim of this study was to evaluate the clinical significance of sorbitol malabsorption, diagnosed by sorbitol hydrogen breath testing in these patients. METHODS: Data of all patients referred to our hospital for hydrogen breath testing between May 1st, 2013 and December 31st, 2014 were retrospectively collected and analyzed. Patients with confirmed sorbitol malabsorption completed a symptom-based questionnaire before and after nutritional counseling. RESULTS: Five hundred and ten patients with functional abdominal discomfort (65.5% female, 34.5% male; mean age 45±16.4 years) were referred to our hospital for hydrogen breath testing. H2-sorbitol breath tests were performed in 252 of these patients. In 122 of them (48%), sorbitol-malabsorption was diagnosed. In 66 of these patients (54%), the results of the symptom-based questionnaire showed a significant improvement of the frequency of abdominal discomfort (P<0.001) and of the influence of these symptoms on daily life (P<0.001) after sorbitol testing/nutritional counseling. CONCLUSIONS: Sorbitol malabsorption is a common finding in patients with functional abdominal discomfort. Dietary intervention positively affects abdominal symptoms in these patients.

Predictors and characteristics of angioectasias in patients with obscure gastrointestinal bleeding identified by video capsule endoscopy.

BACKGROUND: In obscure gastrointestinal bleeding, angioectasias are common findings in video capsule endoscopy (VCE). OBJECTIVE: The objective of this study was to identify predictors and characteristics of small bowel angioectasias. METHODS: Video capsule examinations between 1 July 2001 and 31 July 2011 were retrospectively reviewed. Patients with obscure gastrointestinal bleeding were identified, and those with small bowel angioectasia were compared with patients without a definite bleeding source. Univariate and multivariable statistical analyses for possible predictors of small bowel angioectasia were performed. RESULTS: From a total of 717 video capsule examinations, 512 patients with obscure gastrointestinal bleeding were identified. Positive findings were reported in 350 patients (68.4%) and angioectasias were documented in 153 of these patients (43.7%). These angioectasias were mostly located in the proximal small intestine (n = 86, 56.6%). Patients' age >65 years (odds ratio (OR) 2.15, 95% confidence interval (CI) 1.36-3.38, p = .001) and overt bleeding type (OR 1.89, 95% CI 1.22-2.94, p = .004) were identified as significant independent predictors of small bowel angioectasia. CONCLUSION: Angioectasias are the most common finding in VCE in patients with obscure gastrointestinal bleeding. They are mostly located in the proximal small bowel and are associated with higher age and an overt bleeding type.

Endoscopic ultrasound-guided tissue sampling of small subepithelial tumors of the upper gastrointestinal tract with a 22-gauge core biopsy needle.

Background and study aims The optimal approach to small subepithelial tumors (SETs) of the upper gastrointestinal tract remains inconclusive. The aim of this study was to evaluate endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for less invasive tissue sampling of small SETs of the upper gastrointestinal tract. Patients and methods In this prospective observational study patients with small ( ≤ 3 cm) SETs of the upper gastrointestinal tract were eligible and underwent EUS-FNB with a 22-gauge core biopsy needle. The main outcome measure was the diagnostic yield. The number of obtained core biopsies was also assessed. Results Twenty patients were included. The mean SET size was 16 mm (range 10 - 27 mm). EUS-FNB was technically feasible in all cases and no complications were observed. The diagnostic yield was 75 %. Core biopsy specimens were obtained in only 25 % of cases. Conclusion EUS-FNB with a 22-gauge core biopsy needle of small SETs can achieve a definite diagnosis in the majority of cases. However, because core samples cannot regularly be obtained, EUS-FNB seems not to be convincingly superior to standard EUS-FNA in this setting.

pH/multichannel impedance monitoring in patients with laryngo-pharyngeal reflux symptoms - Prediction of therapy response in long-term follow-up.

BACKGROUND AND STUDY AIM: Optimal therapy concepts in patients with laryngo-pharyngeal reflux (LPR) are still under discussion. Aim of this study was to evaluate long term symptom relief according to results in combined pH/multichannel impedance (MII) monitoring to predict therapy response and symptom relief during long term follow-up. PATIENTS AND METHODS: In patients with predominant LPR symptoms, pH/MII monitoring and subsequent proton pump inhibitor (PPI) therapy were evaluated retrospectively after a minimum follow-up period of 36months. Patients were asked to complete symptom based questionnaires. RESULTS: 45 patients were evaluated and classified according to results of pH/MII. Twenty one patients showed a pathological finding in pH/MII. These patients reported significantly higher LPR-symptom intensity scores and a significantly higher LPR symptom-induced impairment of everyday life scores compared to patients with normal pH/MII monitoring at baseline and at follow-up. PPI associated symptom relief was significantly higher in patients with pathologic pH/MII monitoring (p=0.003). CONCLUSION: In conclusion, combined pH/MII monitoring can reliably predict therapy response to PPIs in LPR patients. With negative results, PPI therapy should be avoided. This approach should be assessed in future prospective clinical trials.

New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal pH metry in extraesophageal gastroesophageal reflux disease.

AIM: To determine the laryngeal H+K+-ATPase and pharyngeal pH in patients with laryngopharyngeal reflux (LPR)-symptoms as well as to assess the symptom scores during PPI therapy. METHODS: Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area (immunohistochemistry and PCR analysis). Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase. Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed. The pH values were assessed in the aerosolized environment of the oropharynx (DxpH Catheter) and compared to a subsequently applied combined pH/MII measurement. RESULTS: Twenty patients with LPR symptoms were included. In only one patient, the laryngeal H+K+-ATPase was verified by immunohistochemical staining. In another patient, real-time RT-PCR for each H+K+-ATPase subunit was positive. Fourteen out of twenty patients had pathological results in DxpH, and 6/20 patients had pathological results in pH/MII. Four patients had pathological results in both functional tests. Nine out of twenty patients responded to PPIs. CONCLUSION: The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms. Alternative hypotheses for the pathomechanism are needed. The role of pharyngeal pH-metry remains unclear and its use can only be recommended for patients in a research study setting.

Prucalopride reduces the number of reflux episodes and improves subjective symptoms in gastroesophageal reflux disease: a case series.

INTRODUCTION: Treatment of persistence to proton pump inhibitors or non-acid reflux episodes in patients with gastroesophageal reflux disease is challenging. Prucalopride, a selective high affinity serotonin (5-HT4) receptor agonist, might offer a possible new therapeutic alterative. CASE PRESENTATIONS: We report four chronically constipated female gastroesophageal reflux disease-patients with reflux symptoms and an increased number of reflux episodes in combined esophageal pH and multichannel impedance monitoring treated with prucalopride (2mg per day). Symptoms were persistent to proton pump inhibitors and ranitidine. Gastroesophageal reflux was detected by pH or multichannel impedance (MII) monitoring. Numbers of all reflux episodes as well as non-acid reflux episodes were reduced in all of our patients. The objective findings were concordant with subjective reports of symptom relief. There were no major adverse events in any patient during therapy with prucalopride. CONCLUSION: Administration of prucalopride showed promising results in the treatment of persisting or weakly and/or non-acid reflux episodes in our case series in four constipated patients. Therefore, prucalopride can be regarded as a possible therapeutic option in the treatment of standard proton pump inhibitor-persistent reflux in the chronically constipated patient. However, further prospective trials are needed to prove our findings.

Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors.

AIM: To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease (GERD) and the response to proton pump inhibitor (PPI) therapy. METHODS: Retrospectively, 683 consecutive patients suspected for GERD who underwent pH-metry/impedance measurement (pH/MII) were analyzed. All patients had previously undergone standard PPI treatment (e.g., pantoprazole 40 mg/d or comparable). Four hundred sixty patients were at least 10 d off PPIs (group A), whereas 223 patients were analyzed during their ongoing PPI therapy (group B). In addition, all patients completed a standardized symptom- and lifestyle-based questionnaire, including the therapeutic response to previous PPI trials on a 10-point scale. Uni- and multivariance analyses were performed to identify criteria associated with positive therapeutic response to PPIs. RESULTS: In group A, positive predictors (PPs) for response in empirical PPI trials were typical GERD symptoms (heartburn and regurgitation), a positive symptom index (SI) and pathological results in pH/MII, along with atypical symptoms, including hoarseness and fullness. In group B, regular alcohol consumption was associated with the therapeutic response. The PPs for pathological results in pH/MII in group A included positive SI, male gender, obesity, heartburn and regurgitation. In group B, the PPs were positive SI and vomiting. Analyzing for positive SI, the PPs were pathological pH and/or MII, heartburn regurgitation, fullness, nausea and vomiting in group A and pathological pH and/or MII in group B. CONCLUSION: Anamnestic parameters (gender, obesity, alcohol) can predict PPI responses. In non-obese, female patients with non-typical reflux symptoms, pH/MII should be considered instead of empirical PPIs.