Photodynamic therapy with polyhematoporphyrin for malignant biliary obstruction: A nationwide retrospective study of 150 consecutive applications.

BACKGROUND: Photodynamic therapy (PDT) is a palliative treatment for malignant biliary obstruction. OBJECTIVE: The objective of this article is to assess the feasibility and safety of this technique. METHODS: In this nationwide, retrospective study of prospectively collected clinical data, all patients treated with PDT using polyhematoporphyrin in Austria from March 2004 to May 2013 were included. Feasibility, adverse events, stent patency and mortality rates were investigated. RESULTS: Eighty-eight patients (54 male, 34 female, median age 69 years) underwent 150 PDT procedures at seven Austrian referral centers for biliary endoscopy. The predominant underlying disease was Klatskin tumor (79/88). All PDT procedures were feasible without technical issues. Cholangitis was the most frequent adverse event (21/88). Stent patency was 246 days (95% CI 203-289) median and was significantly longer for metal than for plastic stents (269 vs. 62 days, p < 0.01). The median survival was 12.4 months (95% CI 9.7-14.9 m) calculated from first PDT and 15.6 months (95% CI 12.3-18.7 m) calculated from initial diagnosis. In patients suffering from biliary tract cancer, Cox regression revealed the number of PDT treatment sessions as the only independent predictor of survival at a multivariate analysis (p = 0.048). CONCLUSION: PDT using polyhematoporphyrin was feasible and safe in this nationwide analysis. Survival data suggest a benefit of PDT in this unselected real-life patient population. Prospective trials comparing PDT to other palliative treatments will help to define its role in the management of malignant biliary obstruction. The study is registered at ClinicalTrials.gov number: NCT02504957.

A multicenter prospective study on the diagnostic performance of a new liquid rapid urease test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori (H. pylori) causes a diversity of gastric diseases. Rapid urease tests (RUT) are well established for the point-of-care, invasive diagnosis of H. pylori infection. The study aimed to evaluate the diagnostic performance of a new liquid RUT, the preOx-HUT, within a prospective cohort of treatment-naïve patients. METHODS: The multicenter prospective clinical trial was conducted at nine Austrian centers for gastrointestinal endoscopy. Patients referred for a diagnostic upper gastrointestinal endoscopy underwent gastric biopsy sampling for routine histological evaluation, and in parallel, the preOx-HUT. Histology served as reference standard to evaluate the diagnostic performance of the preOx-HUT. RESULTS: From January 2015 to January 2016, a total of 183 consecutive patients (54 males and 129 females, median age 50 years) were included. Endoscopy revealed pathological findings in 149/183 cases (81%), which were mostly gastritis (59%) and gastro-esophageal reflux disease (27%). H. pylori infection was detected by histology in 41/183 (22%) cases. In relation to histology, the preOx-HUT had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 80% and a negative predictive value of 96%. Performance of preOx-HUT was not affected significantly by concomitant PPI-use as present in 15% of cases (P = 0.73). CONCLUSIONS: This was the first study evaluating the preOx-HUT in a prospective, multicenter clinical setting. We found a high diagnostic accuracy for the point-of-care, invasive diagnostic test of H. pylori infection. Hence, this test may be a valuable diagnostic adjunct to the clinical presentation of patients with suspected H. pylori infection. Trial registration number EK 1548/2014, Name of registry: Register der Ethikkommission der Medizinischen Universität Wien, URL of registry: https://ekmeduniwien.at/core/catalog/2012/, Date of registration: 24.09.2014, Date of enrolment of the first participant to the trial: 15.01.2015.

Primary resistance of Helicobacter pylori is still low in Southern Austria.

OBJECTIVES: We determined primary and secondary resistance rates of H. pylori in different regions of Austria and potential bacterial and host factors associated with resistance. METHODS: In a prospective multicentre study H. pylori was cultivated from biopsies and susceptibility testing was performed according to EUCAST. Resistance to clarithromycin and levofloxacin was determined by sequencing of the resistance-determining regions of 23S rRNA and gyrA genes. cagA, vacA and babA2 genotypes were determined. RESULTS: A total of 1266 patients were included. 178 isolates were cultured: 128 from patients without prior eradication therapy, 50 from patients after failed eradication. Primary resistance to clarithromycin, levofloxacin and metronidazole were 17.2%, 9.4% and 10.2%, respectively. Secondary resistance to clarithromycin, levofloxacin and metronidazole were 64%, 18% and 44%, respectively. Prior eradication was associated with a higher risk of clarithromycin as well as metronidazole resistance (OR=8.1; 95% CI 3.8-17.1 and OR 5.7; 95% CI 2.5-13, respectively). CONCLUSION: Primary resistance to both clarithromycin and levofloxacin was markedly lower in Southern Austria than recently reported.

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), and neuromuscular and vascular hamartoma (NMVH): two sides of the same coin?

Multifocal stenosing enteritis, not related to Crohn's disease or drug intake, has been described under two different terms: "cryptogenic multifocal ulcerous stenosing enteritis" (CMUSE) and "neuromuscular and vascular hamartoma" (NMVH). We present three new cases of this condition and argue that the two terms reflect the same disease entity. Although etiology and pathogenesis of the disease remain largely unclear, obliterative vascular changes may play an important role.

Evolving patterns in the diagnosis of reactive gastropathy: data from a prospective Central European multicenter study with proposal of a new histologic scoring system.

Histologic examination of gastric biopsies is crucial for determining the cause of gastritis. This prospective multicenter study was undertaken to investigate different histologic parameters arguing in favor or against the diagnosis of reactive gastropathy and to correlate findings with patient's symptoms and endoscopic findings. A total of 1123 individuals aged 15-93 years participated in a prospective multicenter study (histoGERD trial). Diagnosis of Helicobacter gastritis was made following the Updated Sydney System. Diagnosis of reactive gastropathy was based upon Dixon's parameters of foveolar hyperplasia, smooth muscle fibers in the lamina propria and vasodilatation and congestion of mucosal capillaries. Including paucity of acute and chronic inflammatory cells in analysis, a new score with visual analog scales for the diagnosis of reactive gastropathy was developed. All three histologic parameters in favor of the diagnosis of reactive gastropathy were positively associated with the endoscopic diagnosis of gastritis (p < 0.001), yet negatively with Helicobacter infection (p < 0.001). In contrast, presence of acute and chronic inflammatory cells in lamina propria was positively associated with Helicobacter infection (p < 0.001), yet not with the endoscopic diagnosis of gastritis. Our score demonstrated strong association between histologic and endoscopic diagnoses (p < 0.001), yet not with patient's symptoms. In conclusion, our data prove foveolar hyperplasia, smooth muscle fibers and vasodilatation and congestion as key histologic parameters for the diagnosis of reactive gastropathy. The proposed score may enhance the diagnostic accuracy. It should be validated in future studies.

Validation study of the Esohisto consensus guidelines for the recognition of microscopic esophagitis (histoGERD Trial).

In patients with gastroesophageal reflux disease (GERD), histology is generally believed to be a tool of limited diagnostic value. Our study aimed to assess the prevalence of microscopic esophageal lesions as defined by the Esohisto consensus guidelines, which have proven high interobserver agreement in previous studies. In the prospective Central European multicenter histoGERD trial, we recruited 1071 individuals (576 females and 495 males; median age, 53 years; range, 15-93 years) undergoing gastroscopy for nonselected reasons. Biopsy material was systematically sampled from above and below the gastroesophageal junction. Overall, histologic diagnosis of mild and severe esophagitis was made in 423 (39.5%) and 296 (27.6%) individuals, respectively, whereas the squamous mucosa of 352 individuals (32.9%) was normal upon histology or showed only insignificant findings. Proliferative changes of the squamous epithelium, in particular basal cell layer hyperplasia, papillary elongation, and intercellular space dilation, were more common than inflammatory cell infiltration. The presence of microscopic esophagitis was associated with male sex (P = .009), patients' symptoms (P = .003), history of proton pump inhibitor intake (P < .001), and the endoscopic diagnosis of esophagitis (P < .001). Notably, among the 450 patients with no endoscopic signs of esophagitis (Los Angeles Category N), 41.8% and 17.1% were identified with mild and severe (microscopic) esophagitis, respectively, indicating higher sensitivity of histologic diagnosis. In conclusion, our data illustrate the value of histology in the workup of patients with reflux disease. We suggest that biopsies should routinely be obtained when patients undergo upper gastrointestinal endoscopy for evaluation of GERD and may particularly be beneficial in patients with nonerosive reflux disease.

Multilayered epithelium at the gastroesophageal junction is a marker of gastroesophageal reflux disease: data from a prospective Central European multicenter study (histoGERD trial).

Multilayered epithelium is defined as hybrid epithelium with characteristics of both squamous and columnar epithelia. Our aim was to evaluate the clinicopathological significance of the lesion by relating its presence to various histological and clinical and/or endoscopic features indicating gastroesophageal reflux disease (GERD). A total of 1,071 individuals participated in a prospective cross-sectional study (576 females and 495 males; median age 53 years). Biopsy material was systematically sampled from the gastroesophageal junction. The histological diagnosis of esophagitis was made according to the Esohisto consensus guidelines. The endoscopic diagnosis of esophagitis was made according to the modified Los Angeles classification and the diagnosis of Barrett's esophagus according to Prague's C & M criteria, respectively. Multilayered epithelium was identified in 103 (9.6 %) individuals, frequently within or adjacent to the ducts of esophageal glands. Its presence was associated with increasing age (p < 0.001), high BMI (p = 0.026), hiatal hernia (p < 0.001), and the endoscopic diagnoses of esophagitis (p = 0.002) and Barrett's esophagus (p < 0.001). Upon histology, multilayered epithelium was associated with features of the squamous epithelium indicating GERD, particularly intercellular space dilation (p = 0.005), and presence of cardiac mucosa (<0.001). For intestinal metaplasia, a trend was noted (p = 0.094). In conclusion, multilayered epithelium was observed in about every tenth individual undergoing upper gastrointestinal endoscopy. The association with histological and clinical features indicating GERD advocates the lesion as a promising new marker for reflux esophagitis. The association with cardiac mucosa and Barrett's esophagus suggests multilayered epithelium to be an intermediate step in the development of columnar metaplasia and, ultimately, Barrett's esophagus.

Changing prevalence patterns in endoscopic and histological diagnosis of gastritis? Data from a cross-sectional Central European multicentre study.

BACKGROUND AND AIMS: Traditionally, Helicobacter infection is considered to be the most common cause of gastritis. In the cross-sectional Central European histoGERD trial, we assessed the prevalence of different types of gastritis, correlating histological and endoscopic diagnoses. METHODS: A total of 1123 individuals participated in an observational multicentre study. Endoscopists classified individuals as positive or negative for gastritis and rendered the putative cause. Pathologists evaluated biopsy specimens based upon the Updated Sydney System. RESULTS: Histological diagnosis of gastritis was made in 639 (56.9%) participants. In all, 210 (18.7%) individuals were diagnosed with Helicobacter gastritis, 215 (19.1%) with post Helicobacter gastritis, 234 (20.8%) with reactive gastropathy, 26 (2.3%) with autoimmune gastritis, and 6 (0.5%) with focally enhanced gastritis related to Crohn's disease. In 46 out of 639 (7.2%) individuals diagnosed with gastritis, combinations of different histological subtypes were noted the most common being reactive gastropathy and post Helicobacter gastritis. Endoscopic diagnosis of gastritis was made in 534 (47.6%) individuals. CONCLUSIONS: Reactive gastropathy was more common than active Helicobacter gastritis, and the majority of cases attributable to Helicobacter infection were no longer ongoing, i.e. post Helicobacter gastritis. Agreement between histological and endoscopic diagnoses was better in reactive gastropathy than in Helicobacter gastritis.

Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial).

AIMS: The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD). METHODS AND RESULTS: One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P < 0.001) indicative of GORD, intestinal metaplasia (P < 0.001), and an endoscopic diagnosis of oesophagitis (P < 0.001). No association with an endoscopic diagnosis of Barrett's oesophagus or with gastric pathology, particularly Helicobacter infection, was observed. CONCLUSIONS: Cardiac mucosa is a common finding in biopsy specimens taken from the gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion.

Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications.

BACKGROUND: Biliary radiofrequency ablation (RFA) using the Habib™ EndoHBP catheter is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to assess the feasibility and safety of this technique. METHODS: In this nationwide retrospective study of prospectively collected clinical data, all patients treated by biliary RFA in Austria between November 2010 and December 2012 were included. Procedure-related complications, adverse events within 30 days post-intervention, stent patency, and mortality rates were investigated. RESULTS: A total of 58 patients (31 male, 27 female, median age 75 years) underwent 84 RFA procedures at 11 Austrian referral centers for biliary endoscopy. The predominant underlying condition was Klatskin tumor (45 of 58 cases). All 84 RFA procedures were feasible without technical problems. A partial liver infarction was induced by RFA in a 49-year-old Klatskin tumor patient. During 30 days after each RFA procedure, five cases of cholangitis, three cases of hemobilia, two cases of cholangiosepsis, and one case each of gallbladder empyema, hepatic coma, and newly diagnosed left bundle branch block occurred. Median stent patency after last electively performed RFA was 170 days (95 % CI 63-277) and was almost significantly different between metal and plastic stenting (218 vs. 115 days; p = 0.051). Median survival was 10.6 months (95 % CI 6.9-14.4) from the time of the first RFA in each patient and 17.9 months (95 % CI 10.3-25.6) from the time of initial diagnosis. CONCLUSIONS: Except for one severe interventional complication (hepatic infarct), RFA presented as a technically feasible and safe therapeutic option for the palliative treatment of malignant biliary obstruction. The good results of stent patency and survival in this study should be proven in prospective (controlled) trials to further quantify the efficacy of this promising new technique.

Pancreatic acinar cells--a normal finding at the gastroesophageal junction? Data from a prospective Central European multicenter study.

Pancreatic acinar cells are a well-recognized finding at the gastroesophageal junction, but their histogenesis and biological significance are unclear. From the prospective Central European multicenter histoGERD trial, we recruited 1,071 individuals undergoing gastroscopy for various non-selected reasons. Biopsy material was systematically sampled from the gastroesophageal junction and from the stomach. The study aimed to assess the prevalence of pancreatic acinar cells and to relate their presence to various histologic and clinical features. Overall, pancreatic acinar cells were observed in 184 (17.2%) participants. Individuals diagnosed with pancreatic acinar cells were slightly younger than those without (median 50 vs. 53 years; p = 0.009). There was no association with patients' symptoms and/or complaints or with an endoscopic diagnosis of esophagitis or Barrett's esophagus. Regarding histology, pancreatic acinar cells were not associated with features of the squamous epithelium indicating reflux disease, such as basal cell hyperplasia, papillary elongation, dilation of intercellular spaces, and inflammatory cell number, but were associated with the presence of cardiac mucosa (p < 0.001), oxyntocardiac mucosa (p < 0.001), and intestinal metaplasia (p = 0.038), respectively. No association with Helicobacter pylori infection or diagnosis of gastritis was noted. In conclusion, pancreatic acinar cells are a common finding at the gastroesophageal junction, and no association with either reflux disease (histologically or endoscopically) or diagnosis of gastritis was observed. These data suggest a congenital rather than an acquired (metaplastic) origin of pancreatic acinar cells at the gastroesophageal junction. This questions the term "pancreatic acinar metaplasia" which is currently widely used for their diagnosis.