[Cough from the perspective of a gastroenterologist]. / Husten aus gastroenterologischer Sicht.

Cough from the perspective of a gastroenterologist Abstract. Chronic cough can have numerous origins. The work-up of these conditions should always include a multidisciplinary approach to exclude other causes first (cardial, pulmonary, structural changes of pharynx and larynx, allergies, malignancy) before thinking of an upper GI pathology. Cough as an extra-esophageal manifestation of gastroesophageal reflux disease (GERD) is the most common gastroenterological condition. From a gastroenterologist's perspective eosinophilic esophagitis (EoE) and esophageal motility disorders are potential differential diagnosis. If other worrisome symptoms (weight loss, anemia, dysphagia) are present at the same time an endoscopic evaluation with esophago-gastro-duodenoscopy (EGD) should be performed first to exclude a malignancy. Hereby one should perform biopsies of the esophagus to exclude an eosinophilic esophagitis (EoE). If the macroscopic and histopathology results of the EGD are unremarkable a probatory trial of acid-suppressive therapy with proton pump inhibitors (PPIs) is the first-line therapeutic option. For non-responders to PPI-therapy functional diagnostics are the next step. With the help of ambulatory pH-impedance monitoring one can diagnose a non- erosive reflux disease and an esophageal hypersensitivity. An esophageal manometry can deliver relevant information about the physiological anti-reflux barrier and diagnose motility disorders of the esophagus. Surgical therapy (antireflux surgery) can be an option for selected patients with proven reflux associated cough refractory to medical therapy. The aim of this review is to give an overview over a possible diagnostic-therapeutic algorithm from a gastroenterologist's point of view to approach the symptom cough.

Comparison of videofluoroscopy and impedance planimetry for the evaluation of oesophageal stenosis: a retrospective study.

OBJECTIVES: To compare videofluoroscopy that included a tablet test with impedance planimetry (EndoFLIP®) for the evaluation of oesophageal stenosis in patients with dysphagia. METHODS: In 56 patients, videofluoroscopic examinations following the transit of a 14-mm tablet were retrospectively reviewed and correlated with impedance planimetry findings, a catheter-based method using impedance planimetry to display the oesophageal diameter estimates. Additional findings assessed were the occurrence of symptoms during tablet passage and evaluation of oesophageal motility. RESULTS: Impaction of the tablet occurred in 31/56 patients; nine showed a moderate delay (2-15 s), three a short delay (<2 s) and 13 no delay of tablet passage. Both methods showed a significant correlation between tablet impaction and oesophageal diameter <15.1 mm, as measured by impedance planimetry (p = 0.035). The feeling of the tablet getting stuck was reported by seven patients, six showing impaction of the tablet (four with an EndoFLIP-diameter < 13 mm, two with a diameter of 13-19 mm) and one showing delayed passage (EndoFLIP diameter of 17 mm). CONCLUSIONS: Videofluoroscopy and impedance planimetry correlate significantly regarding tablet impaction and residual oesophageal lumen. A standardized 14-mm tablet is helpful in demonstrating oesophageal strictures in dysphagic patients. Triggering of subjective symptoms provides valuable information during a videofluoroscopic study. KEY POINTS: • A 14-mm tablet can demonstrate oesophagogastric junction narrowing in patients with dysphagia. • Type of passage of a tablet enables estimation of oesophageal luminal diameter. • Videofluoroscopy and impedance planimetry correlate significantly regarding tablet impaction and residual oesophageal lumen.

Gastro-oesophageal reflux disease in type 2 diabetics: symptom load and pathophysiologic aspects - a retro-pro study.

BACKGROUND: Information about gastro-oesophageal reflux disease (GERD) in patients with Diabetes mellitus type 2 (T2D) is scarce, although the incidence of both disorders is increasing. METHODS: This "retro-pro" study compared 65 T2D patients to a control group of 130 age- and sex-matched non-diabetics. GERD was confirmed by gastroscopy, manometry, pH-metry and barium swallow. RESULTS: In patients with T2D compared to controls, dysphagia (32.3% vs. 13.1%; p = 0.001) and globus sensation (27.7% vs. 13.8%; p = 0.021) were found more frequently, whereas heartburn (76.9% vs. 88.5%; p = 0.046) and regurgitation (47.7% vs. 72.3%; p= 0.001) were predominant in non-diabetics. Despite higher body mass indices (31.1 ± 5.2 vs. 27.7 ± 3.7 kg/m²; p < 0.001), hiatal hernia was less frequent in T2D patients compared to controls (60.0% vs. 90.8%, p < 0.001). Lower oesophageal sphincter (LES) pressure was higher in patients with T2D (median 10.0 vs. 7.2 mmHg, p = 0.016). DeMeester scores did not differ between the groups. Helicobacter pylori infections were more common in T2D patients (26.2% vs. 7.7%, p = 0.001). Barrett metaplasia (21.5% vs. 17.7%), as well as low- (10.8% vs. 3.8%) and high-grade dysplasia (1.5% vs. 0%) were predominant in T2D patients. CONCLUSIONS: T2D patients exhibit different GERD symptoms, higher LES pressures and a decreased prevalence of hiatal hernia than non-diabetics, which may be related to worse oesophageal motility and, thus, a more functional rather than anatomical cause of GERD. Low-grade dysplasia was more than twice as high in T2D than in non-diabetics patients. TRIAL REGISTRATION: Ethics committee of the Medical University of Vienna, IRB number 720/2011.

Intraoperative assessment of esophagogastric junction distensibility during per oral endoscopic myotomy (POEM) for esophageal motility disorders.

BACKGROUND: Per oral endoscopic myotomy (POEM) is a novel treatment for esophageal motility disorders such as achalasia. To date, the extent of the myotomy has been determined based on the subjective assessment of the endoscopist. We hypothesized that the real-time measurement of esophagogastric junction (EGJ) distensibility using a novel functional lumen-imaging probe would enable objective evaluation of POEM. METHODS: Patients diagnosed with achalasia disorders electively underwent POEM. Using impedance planimetry with a transorally inserted functional lumen-imaging probe (EndoFLIP), cross-sectional areas (CSA) and distensibilities at the EGJ were measured intraoperatively immediately before and after the transoral myotomy (n = 4). All patients completed their 6-month follow-up and two patients had repeat distensibility tests at this time. Four healthy volunteers served as a control group. RESULTS: POEM was successfully performed in all patients (4/4). Premyotomy measurements (40-ml fill mode) showed a median diameter of 6.5 mm (range = 5.2-7.9 mm) at the narrowest location of the EGJ and was 10.1 mm (7.3-13.2 mm) following POEM. CSA increased from 41.5 mm(2) (20-49 mm(2)) to 86 mm(2) (41-137 mm(2)) at a similar median intraballoon pressure (40.3 vs. 38.6 mmHg). The increased EGJ distensibility (DI, 1.0 vs. 2.4 mm(2)/mmHg) was comparable to that of healthy volunteers (2.7 mm(2)/mmHg). CONCLUSION: Functional lumen distensibility measures show that POEM can result in an immediate correction of the nonrelaxing lower esophageal sphincter, which appears similar to that of healthy controls. Intraoperative EGJ profiling may be an important tool to objectively guide the needed extent and completeness of the myotomy during POEM.

Gastroesophageal Junction and Pylorus Distensibility Before and After Sleeve Gastrectomy-pilot Study with EndoFlipTM.

Sleeve gastrectomy (SG) is the most frequently performed bariatric surgical intervention worldwide. Gastroesophageal reflux disease (GERD) is frequently observed after SG and is a relevant clinical problem. This prospective study investigated the gastroesophageal junction (GEJ) and pyloric sphincter by impedance planimetry (EndoFlipTM) and their association with GERD at a tertiary university hospital center. Between January and December 2018, patients undergoing routine laparoscopic SG had pre-, intra-, and postoperative assessments of the GEJ and pyloric sphincter by EndoFlipTM. The distensibility index (DI) was measured at different volumes and correlated with GERD (in accordance with the Lyon consensus guidelines). Nine patients were included (median age 48 years, preoperative BMI 45.1 kg/m2, 55.6% female). GERD (de novo or stable) was observed in 44.4% of patients one year postoperatively. At a 40-ml filling volume, DI increased significantly pre- vs. post-SG of the GEJ (1.4 mm2/mmHg [IQR 1.1-2.6] vs. 2.9 mm2/mmHg [2.6-5.3], p VALUE=0.046) and of the pylorus (6.0 mm2/mmHg [4.1-10.7] vs. 13.1 mm2/mmHg [7.6-19.2], p VALUE=0.046). Patients with postoperative de novo or stable GERD had a significantly increased preoperative DI at 40 ml of the GEJ (2.6 mm2/mmHg [1.9-3.5] vs. 0.5 mm2/mmHg [0.5-1.1], p VALUE=0.031). There was no significant difference in DI at 40 mL filling in the preoperative pylorus and postoperative GEJ or pylorus. In this prospective study, the DI of the GEJ and the pylorus significantly increased after SG. Postoperative GERD was associated with a significantly higher preoperative DI of the GEJ but not of the pylorus.

Hiatal hernia, Barrett's esophagus, and long-term symptom control after laparoscopic fundoplication for gastroesophageal reflux.

BACKGROUND: The aim of this study was to determine the long-term symptom control after laparoscopic fundoplication for gastroesophageal reflux disease (GERD), and possible prognostic factors. METHODS: A cohort of 271 patients, operated on at a university hospital from 1996 through 2002, was eligible for evaluation after a median interval of 102 months (range = 12-158). The time between surgery and recurrence of reflux symptoms (i.e., time to treatment failure) served as the end point for statistical analysis. Putative risk factors for symptom recurrence were analyzed by univariate analysis and by using Cox's multiple-hazards regression. RESULTS: According to Kaplan-Meier estimates, the rate of reflux symptom recurrence was 15 % after 108 months, 11 % in cases without intestinal metaplasia, but 43 % in patients with long-segment (≥ 3 cm) Barrett's esophagus (BE; p < 0.0001). Reflux symptoms recurred in 22 % of cases with a hiatal hernia (HH) ≥ 3 cm before operation, but only in 7 % with smaller or absent HH (p = 0.005). Multivariate analysis revealed a relative risk of 6.6 (CI = 3.0-13.0) for long-segment BE and 3.0 (CI = 1.7-10.1) for HH ≥ 3 cm. A strong statistical interaction was found between HH ≥ 3 cm and long-segment BE: the small group (n = 18) of cases exhibiting both risk factors had an exaggerated recurrence rate of 72 % at 108 months. CONCLUSIONS: Laparoscopic fundoplication for symptomatic GERD provided a long-lasting abolition of reflux symptoms in 231 of 271 (85 %) patients. HH ≥ 3 cm and long-segment BE were shown as independent prognostic factors favoring recurrence.

Chicago Classification update (v4.0): Technical review of high-resolution manometry metrics for EGJ barrier function.

Esophagogastric junction (EGJ) barrier function is of fundamental importance in the pathophysiology of gastroesophageal reflux disease. Impaired EGJ barrier function leads to excessive distal esophageal acid exposure or, in severe cases, esophagitis. Hence, proposed high-resolution manometry (HRM) metrics assessing EGJ integrity are clinically important and were a focus of the Chicago Classification (CC) working group for inclusion in CC v4.0. However, the EGJ is a complex sphincter comprised of both crural diaphragm (CD) and lower esophageal sphincter (LES) component, each of which is subject to independent physiological control mechanisms and pathophysiology. No single metric can capture all attributes of EGJ barrier function. The working group considered several potential metrics of EGJ integrity including LES-CD separation, the EGJ contractile integral (EGJ-CI), the respiratory inversion point (RIP), and intragastric pressure. Strong recommendations were made regarding LES-CD separation as indicative of hiatus hernia, although the numerical threshold for defining hiatal hernia was not agreed upon. There was no agreement on the significance of the RIP, only that it could localize either above the LES or between the LES and CD in cases of hiatus hernia. There was agreement on how to measure the EGJ-CI and that it should be referenced to gastric pressure in units of mmHg cm, but the numerical threshold indicative of a hypotensive EGJ varied widely among reports and was not agreed upon. Intragastric pressure was endorsed as an important metric worthy of further study but there was no agreement on a numerical threshold indicative of abdominal obesity.

Histopathology of the endoscopic esophagogastric junction in patients with gastroesophageal reflux disease.

BACKGROUND: Discrepancy exists between the endoscopic (rugal folds) and the histopathologic (oxyntic mucosa) definition of proximal stomach. We compared endoscopy and histopathology of the esophagogastric junction in patients with gastroesophageal reflux disease. METHODS: A total of 102 consecutive patients (60 women) with gastroesophageal reflux disease prospectively underwent endoscopy including multilevel biopsy sampling at the level of the rise of rugal folds (level 0), and also 0.5 cm and 1.0 cm distal and 0.5 cm and > or = 1 cm proximal to this point. Columnar lined esophagus (CLE) was cataloged according to the histopathologic Paull-Chandrasoma classification and esophagitis according to the endoscopic Los Angeles classification. Hiatal hernia was diagnosed if the endoscopic rugal folds commenced > or = 2 cm above the diaphragm; competency of the esophagogastric valve was graded according to the Hill classification. RESULTS: All patients had histopathologic CLE with maximal presence at level 0 (97%) and a decrease towards proximal and distal biopsy levels (level -0.5 cm, 81%; level -1.0, 28%; level + 0.5 cm, 40%; level + 1.0 cm, 18%). Histopathologic CLE (distance between CLE-positive biopsy levels) was longer than endoscopic CLE (P < 0.001). All 19 patients with intestinal metaplasia (18.6%) were identified from 4-quadrant biopsies obtained at the squamocolumnar junction and at 0.5 cm distal from it. Persons with intestinal metaplasia were significantly older, had increased frequency of endoscopic hiatal hernia, higher Hill grade and presence of endoscopic CLE (P < 0.05); no significant difference was observed regarding sex, endoscopic esophagitis or length of endoscopic and histopathologic CLE (P > 0.05). None of the patients had dysplasia or carcinoma. CONCLUSIONS: In patients with gastroesophageal reflux disease the esophagogastric junction cannot be identified by endoscopy but requires histopathology of multilevel biopsies. The squamocolumnar junction harbors the highest yield of intestinal metaplasia.

Radiologic, endoscopic, and functional patterns in patients with symptomatic gastroesophageal reflux disease after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is considered the gold standard in treatment of morbid obesity and gastroesophageal reflux disease (GERD). Resolution of GERD symptoms is reported to be approximately 85% to 90%. OBJECTIVE: To evaluate patients with persistent GERD symptoms after RYGB and to identify contributing factors. SETTING: University hospital, cross-sectional study. METHODS: Data of patients evaluated for persistent GERD with a history of RYGB between January 2012 and December 2015 were reviewed. GERD was assessed with questionnaires, endoscopy, 24-hour pH-impendance manometry, and barium swallow. RESULTS: Of 47 patients, 44 (93.6%) presented with typical GERD, 18 (38.3%) with obstruction, 8 (17%) with pulmonary symptoms, and 21 (44.7%) with pain. The interval between RYGB and evaluation was a median of 3.8 years (range .8-12.6); median patient age was 36.5 years (19.1-67.2). Median body mass index was 30.3 kg/m2 (20.3-47.2). Pouch gastric fistulas were seen in 2 (5.1%), enlarged pouches in 5 (10.6%), and hiatal hernias in 25 patients (53.2%). Twelve (23.4%) had esophagitis>Los Angeles (LA) grade B. Manometry was performed in 45 (95.7%) and off-proton pump inhibitor 24-hour pH-impedance-metry in 44 patients (94.6%). Seventeen patients (37.8%) had esophageal hypomotility or aperistalsis; hypotensive lower esophageal sphincter was seen in 26 patients (57.8%). Increased esophageal acid exposure (>4% pH<4) was found in 27 (61.4%), an increased number of reflux episodes (>53) in 30 patients (68.2%). Symptoms were deemed as functional in 6 (12.8%). CONCLUSION: The evaluation for persistent GERD after RYGB revealed a high percentage of hiatal hernias, hypotensive lower esophageal sphincter, and severe esophageal motility disorders. These findings might have an influence on hiatal hernia closure concomitant with RYGB and the role of pH manometry in the preoperative bariatric assessment.

Histopathology of columnar-lined esophagus in patients with gastroesophageal reflux disease.

BACKGROUND AND AIMS: The question of whether an endoscopically normal-appearing esophagogastric junction should be biopsied in patients with gastroesophageal reflux disease is controversial. We have addressed this issue using endoscopy and histopathology. METHODS: A total of 114 consecutive patients (58 males) with symptoms of gastroesophageal reflux disease prospectively underwent endoscopy, including biopsy sampling from the esophagogastric junction. Endoscopically visible columnar-lined esophagus was defined by the presence of gastric-type mucosa above the level of the rise of the gastric folds. Histopathology was conducted using the Paull-Chandrasoma classification. RESULTS: Of the 114 patients, 85 (74.6%) had endoscopically visible columnar-lined esophagus of length < or =0.5 cm (n = 82), 1 cm (n = 2) and 7 cm (n = 1); 29 patients (25.4%) had a normal endoscopic junction. All patients had histopathologic columnar-lined esophagus. Intestinal metaplasia and low-grade dysplasia was identified in 26 (22.8%) and 5 (4.4%) individuals, respectively, and was not statistically different in endoscopically normal vs. abnormal junction (P = 0.408 for intestinal metaplasia, P = 0.775 for low grade dysplasia). Intestinal metaplasia was independent from endoscopic esophagitis (P = 0.398) and hiatal hernia (P = 0.405). CONCLUSIONS: Columnar-lined esophagus cannot be excluded by endoscopy. In patients with gastroesophageal reflux disease, biopsy sampling of normal-appearing junction is recommended for histopathologic exclusion of intestinal metaplasia and low-grade dysplasia.

Videoendoscopy and histopathology of the esophagogastric junction in patients with gastroesophageal reflux disease.

BACKGROUND AND AIMS: During endoscopy the stomach is considered to rise at the level of the 'gastric' folds; however, anatomical studies have demonstrated that the proximal gastric folds may in fact be esophageal. This prospective study was designed to assess the histopathology of endoscopically visible proximal gastric folds in patients with gastroesophageal reflux disease. METHODS: 35 consecutive patients (20 males) with gastroesophageal reflux disease underwent video endoscopy, including biopsy sampling from the endoscopically visible esophagogastric junction (0 cm, 0.5 cm and 1.0 cm distal to the rise of gastric folds and 0.5 cm and 1.0 cm proximal to it). Endoscopy was digitally recorded and reviewed for assignment of biopsy level. Columnar-lined esophagus and esophagitis were cataloged according to the Paull-Chandrasoma histopathologic classification and the Los Angeles endoscopic classification. RESULTS: Endoscopy: Normal endoscopic esophagogastric junction was seen in 11 (31%) patients and visible columnar-lined esophagus < or = 0.5 cm in 24 (69%). HISTOLOGY: Columnar-lined esophagus extended 1.0 cm in 22.8% of patients and 0.5 cm in 51.4%, distal to the rise of the gastric folds. In all patients columnar-lined esophagus was interposed between squamous epithelium and gastric oxyntic mucosa. Thus, so-called gastric folds contained mucosa of esophageal origin in all patients. Intestinal metaplasia (Barrett esophagus) was detected in eight (22.9%) patients. CONCLUSIONS: Endoscopy cannot exclude histopathologic columnar-lined esophagus within gastric rugae. Thus, visible 'gastric' folds should not be used for definition of the esophagogastric junction but as a reference landmark for biopsy sampling during endoscopy.

Modern GERD treatment: feasibility of minimally invasive esophageal sphincter augmentation.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common chronic disease requiring adequate treatment since it represents one major cause of development of Barrett's esophagus and eventually carcinoma. Novel laparoscopic magnetic sphincter augmentation for GERD was evaluated prospectively. PATIENTS AND METHODS: A total of 23 patients with GERD underwent minimally invasive implantation of LINX™ Reflux Management System. Primary outcome measures were overall feasibility, short-term procedure safety and efficacy. Secondary GERD-related quality of life was assessed. RESULTS: All implantations were performed without serious adverse events. A significant decrease in all major GERD complaints were found: heartburn: 96%-22% (p<0.001); bloating: 70%-30% (p=0.006); respiratory complaints: 57%-17% (p=0.039); sleep disturbance: 65%-4% (p<0.001). A four-week follow-up reduction of ≥50% of proton pump inhibitor (PPI) dose was achieved in over 80% of patients. Self-limiting difficulty in swallowing was found in 70% within four weeks. One patient required for endoscopic dilation. GERD-related quality of life improved significantly. CONCLUSION: LINX™ implantation is a standardized, technically simple, safe and well-tolerated expeditious procedure.