Jochen Weigt

Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn

Proton pump inhibitor (PPI)‐refractory heartburn may be due to persistent gastro‐oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non‐erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI‐refractory patients is uncertain.

Jackhammer esophagus: high-resolution manometry and therapeutic approach using peroral endoscopic myotomy (POEM).

We present the first report on peroral endoscopic myotomy (POEM) in the treatment of jackhammer esophagus. A 34-year-old female patient was newly diagnosed with a jackhammer esophagus. After failure of medical treatment, the patient underwent POEM procedure for myotomy of the spastic segment. Postoperatively, a mild emphysema and pneumothorax occurred that required drainage and antibiotic therapy until full recovery. Discharge was possible after 5 days. Six months later, she presented with recurrent but mild pain due to a remnant spastic segment proximal to the myotomy. Endoscopic balloon dilation was performed twice within 6 weeks with full symptomatic relief of pain and mild symptoms of dysphagia.

Helicobacter pylori but not gastrin is associated with the development of colonic neoplasms

Recent studies have suggested that Helicobacter pylori (H. pylori) constitutes a risk for the development of colonic neoplasia. Hypergastrinemia can be induced by H. pylori infection, and gastrin can act as putative promoter of colorectal carcinogenesis. Aim of our study was to assess whether H. pylori infection and/or increased serum gastrin levels are associated with the occurrence of colonic neoplasms. For this, we reviewed prospectively collected data of 377 patients with a minimum age of 50 years who underwent colonoscopy. H. pylori and CagA status were determined by serology. Serum gastrin levels were measured in fasting state by commercially available assay. In H. pylori infected patients (n = 138; 36.6%), the overall prevalence of colonic neoplasms was more frequent compared to H. pylori negative patients (n = 239; 63.4%) (OR = 2.73, 95% CI: 1.76–4.24). H. pylori infection occurred more frequently in patients with hyperplastic polyps (OR = 2.66, 95% CI: 1.23–5.74) and adenomas presenting with low grade intraepithelial neoplasia (IEN) (OR = 1.85, 95% CI: 1.14–2.99). Attributable risk for adenomas with high grade IEN and colorectal adenocarcinoma (n = 14) was not assessed due to the low number of cases. The expression of CagA was also associated with an increased risk for colonic neoplasms (OR = 2.25, 95% CI: 1.29–3.94). Hypergastrinemia did not increase the risk for any colonic neoplasms and there was no difference in basal serum gastrin levels between H. pylori positive and negative patients. In conclusion, H. pylori infection, including CagA expression is associated with an increased risk for the development of colonic neoplasm.

Influence of Helicobacter pylori on gastric regulation of food intake.

Purpose of reviewTo evaluate the influence of Helicobacter pylori infection on the gastric regulation of food intake and body weight. Recent findingsH. pylori infection leads to a decrease of circulating ghrelin through a reduction of ghrelin-producing cells in the gastric mucosa and increases the amount of gastric leptin with no effect on circulating leptin levels. Eradication of H. pylori reverses the abnormal regulation of gastric hormone secretion. This finding is suggested to favor weight gain after H. pylori eradication and points to the potential effect of H. pylori in the pathophysiology of obesity. SummaryH. pylori has an influence on the release of gastric hormones and therefore plays a role in the regulation of body weight, hunger and satiety.

Identification of Clinical and Laboratory Markers for Predicting Eosinophilic Esophagitis in Adults

Background: The diagnosis of eosinophilic esophagitis (EoE) and differentiation from gastroesophageal reflux disease (GERD) is potentially challenging and is based upon clinical signs and endoscopic and histological features. In order to alert the endoscopist to consider EoE in patients with esophageal symptoms before performing esophagogastroduodenoscopy, we aimed to identify a set of clinical and laboratory markers for predicting EoE. Methods: The study included 43 patients with either EoE (n = 23) or GERD (n = 20). The diagnosis of EoE was based on International Consensus Criteria. Age, gender, weight loss, history of atopy, dysphagia, history of food impaction, proton pump inhibitor (PPI) refractory heartburn, odynophagia, peripheral eosinophilia, and serum IgE were analyzed. Each symptom or sign was classified as ‘0’ (absent, normal) or ‘1’ (present, elevated), individually analyzed and statistically evaluated among the two groups of patients. Logistic regression analysis was carried out to identify a clinically applicable marker constellation to differentiate EoE from GERD. Results: Univariate analysis identified 6 out of the 10 variables to be significant between both groups. A stepwise procedure of logistic regression led to a model in which 3 out of the initial 10 items were found to be relevant for differentiating GERD and EoE. Derived from this model, an optimal differentiation was achieved by using the following simplified equation: peripheral eosinophilia + history of food impaction + PPI refractory heartburn leading to a maximal value of 3 (1 + 1 + 1). Based on a cut-off value of ≧2, sensitivity and specificity for diagnosing EoE were 91 and 100%, respectively. Conclusion: A defined set of markers including two clinical features and one laboratory parameter is highly predictive of EoE and thus allows physicians to distinguish EoE from GERD even before upper gastrointestinal endoscopy is performed.

Multichannel intraluminal impedance and pH-metry for investigation of symptomatic gastroesophageal reflux disease.

Background: Combined multichannel intraluminal impedance and pH-metry (MII-pH) is a technique that enables monitoring of gastroesophageal reflux independent of its acidity. Aim: To investigate the utility of MII-pH in the clinical investigation of patients with gastroesophageal reflux disease (GERD) symptoms. Methods: 32 consecutive patients underwent 24-hour ambulatory MII-pH. 16 patients were on PPI (PPI+) therapy and 16 were taking no acid-suppressive medication (PPI–). We investigated the pattern of reflux by means of acid and nonacid reflux and the relation to typical and atypical symptoms. In addition, we investigated the symptom association by using the symptom index. Results: Symptom-related acid reflux was higher in the PPI+ group (33 vs. 25%) and symptom-related nonacid reflux was higher in the PPI– group (36 vs. 21%). The association between type of symptoms and the association to reflux is highly significant (p < 0.001) in the PPI– group. In this group the association of acid reflux is more likely to correlate with typical symptoms and the association of nonacid reflux is more likely to be associated with atypical symptoms. Conclusions: These data show that nonacid reflux can be associated with symptoms in patients with GERD symptoms. The diagnostic value of MII-pH is independent of PPI therapy.

A multicenter study on the role of direct retrograde cholangioscopy in patients with inconclusive endoscopic retrograde cholangiography.

BACKGROUND AND STUDY AIMS Direct retrograde cholangioscopy (DRC) may improve the diagnostic and therapeutic yield of endoscopic retrograde cholangiography (ERC) but safety, feasibility, and outcome are unknown. PATIENTS AND METHODS All consecutive patients who underwent DRC at three tertiary endoscopy centers for inconclusive findings at ERC were included in this retrospective analysis. Ultraslim endoscopes (FujiFilm EG 530NP; Olympus GIF XP180; GIF N180) were used by the peroral route for intubating all accessible bile ducts. Success rate, usefulness in diagnosis and therapy, and safety of DRC were assessed in terms of technical and clinical parameters and therapeutic vs. diagnostic indication. RESULTS DRC was performed in 130 cases (89 patients). CO2 insufflation and an anchoring balloon were used in 66.9% and 97.7% of cases, respectively. Intubation of the papilla was successful in 115 of 130 (88.5%) cases, and the aim of the DRC investigation was accomplished in 105 cases (80.8%). DRC-guided biopsies were taken in 53 cases (40.8%), and a therapeutic intervention was performed in 32 cases (24.6%). The initial diagnosis was revised by DRC in 18 of 69 patients (26.1%) with indeterminate biliary stricture. Complications were observed in 10 cases (7.7%), including cholangitis (n=2; 1.5%), bleeding (n=2; 1.5%), and pain, hypoxia, bradyarrhythmia, air embolism, and perforation of an intrahepatic and an extrahepatic bile duct (1 each; 0.8%). There was no mortality associated with DRC. CONCLUSIONS DRC was successfully performed for the diagnosis and treatment of biliary disease that had eluded diagnosis with conventional ERC. DRC impacted on clinical decision making. The complication rate was low and similar to other cholangioscopy techniques.

Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer

Evaluation of: Valle J, Wasan H, Palmer DH et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N. Engl. J. Med. 362, 1273–1281 (2010). Biliary tract cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy has not been established yet. The evaluated article reports on the first Phase III randomized controlled multicenter trial (ABC-02 trial) on palliative chemotherapy for biliary tract cancer. A total of 410 patients with locally advanced or metastatic cholangiocarcinoma, gallbladder cancer or ampullary cancer were included to receive either cisplatin followed by gemcitabine or gemcitabine alone for up to 24 weeks. The primary end point was overall survival and the secondary end point was progression-free survival. The median overall survival was 11.7 months in the cisplatin plus gemcitabine group and 8.1 months in the gemcitabine only group. The median progression-free survival was 8.0 months in the cisplatin plus gemcitabine group and 5.0 months in the gemcitabine-only group (p < 0.001). Adverse events were comparable in the two groups. Cisplatin plus gemcitabine, compared with gemcitabine alone, was associated with a significant survival advantage without an increase in substantial toxicity.

Oxyntic gastric atrophy in Helicobacter pylori gastritis is distinct from autoimmune gastritis

Aim To assess characteristics of oxyntic gastric atrophy (OGA) in autoimmune gastritis (AIG) compared with OGA as a consequence of Helicobacter pylori infection. Methods Patients undergoing oesophagogastroduodenoscopy from July 2011 to October 2014 were prospectively included (N=452). Gastric biopsies were obtained for histology and H. pylori testing. Serum gastrin-17 (G17), pepsinogen (PG) I, PGII and antibodies against H. pylori and cytotoxin-associated gene A protein were determined in all patients. Antibodies against parietal cells and intrinsic factor were determined in patients with advanced (moderate to severe) OGA. Areas under the receiver operating characteristic curves (AUCs) were calculated for serum biomarkers and compared with histology. Results Overall, 34 patients (8.9%) had advanced OGA by histology (22 women, age 61±15 years). Current or past H. pylori infection and AIG were present in 14/34 and 22/34 patients, respectively. H. pylori-negative AIG patients (N=18) were more likely to have another autoimmune disease (OR 6.3; 95% CI 1.3 to 29.8), severe corpus atrophy (OR 10.1; 95% CI 1.9 to 54.1) and corpus intestinal metaplasia (OR 26.9; 95% CI 5.3 to 136.5) compared with H. pylori-positive patients with advanced OGA. Antrum atrophy was present in 39% of H. pylori-negative AIG patients. The diagnostic performance of G17, PG I and PGI/II was excellent for AIG patients (AUC=0.83, 0.95 and 0.97, respectively), but limited for H. pylori-positive patients with advanced OGA (AUC=0.62, 0.75 and 0.67, respectively). Conclusions H. pylori-negative AIG has a distinct clinical, morphological and serological phenotype compared with advanced OGA in H. pylori gastritis.

Metastatic Disease in the Stomach

Background: Gastric metastases are rare and represent a late and progressed stage of malignant disease. This review highlights epidemiological, clinical and endoscopic findings as well as therapeutic strategies for metastatic disease of the stomach. Summary: The clinical presentation of gastric metastases is highly unspecific. The endoscopic appearance of gastric metastases is heterogeneous, but the most prevalent findings are solitary and submucosal lesions in the gastric wall. The most prevalent primary tumor spreading to the stomach is breast cancer, followed by renal cell cancer and many others. In general, gastric metastases occur in a late stage of malignant disease and frequently indicate short survival. Specific therapy for gastric metastases does not exist and is mainly performed with chemotherapy according to the primary tumor. Compared with other metastatic diseases, gastric metastases of renal cell cancer and breast cancer need distinct consideration. Gastric metastasis of these cancers presents with a better prognosis, as patients with these conditions can be offered effective chemotherapeutic treatment. Key Message: Gastric metastatic disease is a rare clinical presentation. The pathophysiology of gastric metastatic seeding is not well understood. Practical Implications: In the course of malignant disease the presence of gastric metastases should be taken into account if mucosal or submucosal gastric lesions are present. Therapy in general depends on the primary tumor.