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ZusammenfassungNeuroendokrine Tumoren des Gastrointestinaltrakts (GI-NET) sind selten. Die im Vergleich zu den mit hormonellen Syndromen assoziierten funktionellen Tumoren (Insulinom, Gastrinom) häufigeren nichtfunktionellen Tumoren verlaufen klinisch in der Regel bis in späte Stadien indolent. Die Therapie der GI-NET ist multimodal, wobei kurative Therapieansätze aus der vollständigen Entfernung des Tumorgewebes auf endoskopischem respektive chirurgischem Weg bestehen. Patienten in späten Tumorstadien profitieren von interventionell-radiologischen oder medikamentösen Therapieverfahren. Der vorliegende Artikel gibt einen praxisnahen Überblick über die Schlüsselaspekte der Therapie von gastrointestinalen NET in der täglichen gastroenterologischen Praxis mit Schwerpunkt auf endoskopischen Diagnose- und Therapieverfahren.

Background and Aims: Minimally invasive treatments of anastomotic benign biliary stricture (BBS) after orthotopic liver transplantation (OLT) include endoscopic placement of multiple plastic stents or fully covered self-expandable metal stents (FCSEMSs). No multiyear efficacy data are available on FCSEMS treatment after OLT. Methods: We prospectively studied long-term efficacy and safety of FCSEMS treatment in adults aged ≥18 years with past OLT, cholangiographically confirmed BBS, and an indication for ERCP with stent placement. Stent removal was planned after 4 to 6 months, with subsequent follow-up until 5 years or stricture recurrence. Long-term outcomes were freedom from stricture recurrence, freedom from recurrent stent placement, and stent-related serious adverse events (SAEs). Results: In 41 patients, long-term follow-up began after FCSEMS removal (n = 33) or observation of complete distal migration (CDM) (n = 8). On an intention-to-treat basis, the 5-year probability of remaining stent-free after FCSEMS removal or observation of CDM was 48.9% (95% confidence interval [CI], 33.2%-64.7%) among all patients and 60.9% (95% CI, 43.6%-78.2%) among 31 patients with over 4 months of FCSEMS indwell time. In 28 patients with stricture resolution at FCSEMS removal or observed CDM (median, 5.0 months indwell time), the 5-year probability of no stricture recurrence was 72.6% (95% CI, 55.3%-90%). Sixteen patients (39%) had at least 1 related SAE, most commonly cholangitis (n = 10). Conclusions: By 5 years after temporary FCSEMS treatment of post-OLT BBS, approximately half of all patients remained stent-free on an intention-to-treat basis. Stent-related SAEs (especially cholangitis) were common. FCSEMS placement is a viable long-term treatment option for patients with post-OLT BBS. (Clinical trial registration number: NCT01014390.), SCOPUS: ar.j, info:eu-repo/semantics/published

Background and Aims: Temporary single, fully covered self-expanding metal stent (FCSEMS) placement for benign biliary strictures (BBSs) associated with chronic pancreatitis (CP) may require fewer interventions than endotherapy with multiple plastic stents and may carry less morbidity than biliary diversion surgery. This study aimed to assess long-term outcomes in CP-associated BBSs after FCSEMS placement and removal. Methods: In this open-label, multinational, prospective study, subjects with CP and a BBS treated with FCSEMS placement with scheduled removal at 10 to 12 months were followed for 5 years after FCSEMS indwell. Kaplan-Meier analyses assessed BBS resolution and cumulative probability of freedom from recurrent stent placement to 5 years after FCSEMS indwell. Results: One hundred eighteen patients were eligible for FCSEMS removal. At a median of 58 months (interquartile range, 44-64) post-FCSEMS indwell, the probability of remaining stent-free was 61.6% (95% confidence interval [CI], 52.5%-70.7%). In 94 patients whose BBSs resolved at the end of FCSEMS indwell, the probability of remaining stent-free 5 years later was 77.4% (95% CI, 68.4%-86.4%). Serious stent-related adverse events occurred in 27 of 118 patients (22.9%); all resolved with medical therapy or repeated endoscopy. Multivariate analysis identified severe CP (hazard ratio, 2.4; 95% CI, 1.0-5.6; P = .046) and longer stricture length (hazard ratio, 1.2; 95% CI, 1.0-1.4; P = .022) as predictors of stricture recurrence. Conclusion: In patients with symptomatic BBSs secondary to CP, 5 years after placement of a single FCSEMS intended for 10 to 12 months indwell, more than 60% remained asymptomatic and stent-free with an acceptable safety profile. Temporary placement of a single FCSEMS may be considered as first-line treatment for patients with CP and BBSs. (Clinical trial registration number: NCT 01014390.), info:eu-repo/semantics/published

ZusammenfassungSeit 10 Jahren überblickt das Qualitätssicherungsprogramm „Benchmarking ERCP“ unter der Patronanz der Österreichischen Gesellschaft für Gastroenterologie und Hepatologie (ÖGGH) mit einjähriger Unterbrechung (2008) in Zusammenarbeit mit dem Institut für Angewandte Statistik der Johannes Kepler Universität Linz die Ergebnisqualität, Erfolgsrate und Patientensicherheit bei der ERCP in Österreich anhand von derzeit 28 319 gesammelten Untersuchungen.Die teilnehmenden Zentren mit unterschiedlicher ERCP-Frequenz und Untersucherzahl können so anhand des Vergleichs den gepoolten Benchmark-Daten individuelle Probleme in Hinblick auf Erfolgs-, Sondierungs- und Komplikationsraten (3,9 % Post-ERCP-Pankreatitiden, 3,8 % Blutungen, 0,6 % Perforationen, 1,2 % Cholangitiden, 1,0 % kardiopulmonale Komplikationen) erkennen und verbessern.

Objectives We report on a large prospective, multicentre clinical investigation on inter- and intrapatient genetic variability for antimicrobial resistance of Helicobacter pylori . Methods Therapy-naive patients ( n = 2004) who had undergone routine diagnostic gastroscopy were prospectively included from all geographic regions of Austria. Gastric biopsy samples were collected separately from antrum and corpus. Samples were analysed by histopathology and real-time PCR for genotypic resistance to clarithromycin and quinolones. Clinical and demographic information was analysed in relation to resistance patterns. Results H. pylori infection was detected in 514 (26%) of 2004 patients by histopathology and confirmed in 465 (90%) of 514 patients by real-time PCR. PCR results were discordant for antrum and corpus in 27 (5%) of 514 patients, indicating inhomogeneous infections. Clarithromycin resistance rates were 17% (77/448) and 19% (84/455), and quinolone resistance rates were 12% (37/310) and 10% (32/334) in antrum and corpus samples, respectively. Combination of test results per patient yielded resistance rates of 21% (98/465) and 13% (50/383) for clarithromycin and quinolones, respectively. Overall, infection with both sensitive and resistant H. pylori was detected in 65 (14%) of 465 patients. Conclusions Anatomically inhomogeneous infection with different, multiple H. pylori strains is common. Prospective clinical study design, collection of samples from multiple sites and microbiologic methods that allow the detection of coinfections are mandatory for collection of reliable data on antimicrobial resistance patterns in representative patient populations. (ClinicalTrials.gov identifier: NCT02925091).

Das Adenokarzinom des Osophagus weist weltweit sowie auch in Osterreich in den letzten Jahren eine steigende Inzidenz auf. Der groste Risikofaktor des Adenokarzinoms ist der sog. Barrett-Osophagus. Dessen Risikofaktoren sind mannliches Geschlecht, helle Hautfarbe, Ubergewicht, Rauchen, hoheres Alter, langjahriger Reflux und weniger ausgepragt auch die familiare Belastung. Ein generelles Screening der Allgemeinbevolkerung wird derzeit nicht empfohlen, fur Hochrisikogruppen scheint ein Screening dennoch sinnvoll. Immunhistochemische Marker, wie „trefoil factor 3“ (TFF3), SOX2 und p53, waren in Studien vielversprechend in der Risikostratifizierung eines Barrett-Osophagus. Fur den Pathologen scheint p53 derzeit von groster Relevanz zu sein. Fur die Surveillance gibt es Empfehlungen, die in einem Positionspapier der Europaischen Gesellschaft fur Gastrointestinale Endoskopie festgehalten sind. Weiters hat bei Vorliegen einer Dysplasie immer die Nachbefundung durch einen Referenzpathologen zu erfolgen. Die Therapie einer „high-grade Dysplasie“ (HGD) bzw. eines Fruhkarzinoms, in manchen Fallen auch einer „low-grade Dysplasie“ (LGD), erfolgt durch eine endoskopische Mukosaresektion (EMR) oder endoskopische Submukosadissektion (ESD) in Kombination mit einem ablativen Verfahren, wobei hier die Radiofrequenzablation (RFA) am besten untersucht ist. Doch auch nach RFA besteht das Risiko von Rezidiven, weshalb eine lebenslange Surveillance in noch nicht definierten Zeitabstanden erfolgen muss.

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

Photodynamic therapy (PDT) is a palliative treatment for malignant biliary obstruction.The objective of this article is to assess the feasibility and safety of this technique.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.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,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.

Neuroendocrine tumors of the gastrointestinal tract (GI-NET) are rare tumors. Functional tumors with hormonal syndromes (e. g., insulinoma, gastrinoma) are less common than non-functional tumors, which usually have an indolent course. Therapy for GI-NET is multimodal, including endoscopic or surgical procedures aiming at complete removal of tumor tissue. Patients in later stages may benefit from interventional radiology or medical therapy. This article gives an overview regarding the key aspects of GI-NET therapy in daily gastroenterology practice with emphasis on endoscopic diagnosis and therapy.Neuroendokrine Tumoren des Gastrointestinaltrakts (GI-NET) sind selten. Die im Vergleich zu den mit hormonellen Syndromen assoziierten funktionellen Tumoren (Insulinom, Gastrinom) häufigeren nichtfunktionellen Tumoren verlaufen klinisch in der Regel bis in späte Stadien indolent. Die Therapie der GI-NET ist multimodal, wobei kurative Therapieansätze aus der vollständigen Entfernung des Tumorgewebes auf endoskopischem respektive chirurgischem Weg bestehen. Patienten in späten Tumorstadien profitieren von interventionell-radiologischen oder medikamentösen Therapieverfahren. Der vorliegende Artikel gibt einen praxisnahen Überblick über die Schlüsselaspekte der Therapie von gastrointestinalen NET in der täglichen gastroenterologischen Praxis mit Schwerpunkt auf endoskopischen Diagnose- und Therapieverfahren.

This article has an accompanying continuing medical education activity on page e15. Learning Objective: upon completion of this activity, participants should be able to discuss the indications to use self-expandable metal stents (SEMS) for management of benign biliary strictures, identify patients at high-risk and low-risk for migration of these stents after placement, and understand the risks and benefits of fully-covered, self-expandable metal stents (FCSEMS) versus plastic stents for management of chronic pancreatitis. BACKGROUND & AIMS: Fully covered self-expanding metal stents (FCSEMS) are gaining acceptance for the treatment of benign biliary strictures. We performed a large prospective multinational study to study the ability to remove these stents after extended indwell and the frequency and durability of stricture resolution. METHODS: In a nonrandomized study at 13 centers in 11 countries, 187 patients with benign biliary strictures received FCSEMS. Removal was scheduled at 10-12 months for patients with chronic pancreatitis or cholecystectomy and at 4-6 months for patients who received liver transplants. The primary outcome measure was removal success, defined as either scheduled endoscopic removal of the stent with no removal-related serious adverse events or spontaneous stent passage without the need for immediate restenting. RESULTS: Endoscopic removal of FCSEMS was not performed for 10 patients because of death (from unrelated causes), withdrawal of consent, or switch to palliative treatment. For the remaining 177 patients, removal success was accomplished in 74.6% (95% confidence interval [CI], 67.5%-80.8%). Removal success was more frequent in the chronic pancreatitis group (80.5%) than in the liver transplantation (63.4%) or cholecystectomy (61.1%) groups (P = .017). FCSEMS were removed by endoscopy from all patients in whom this procedure was attempted. Stricture resolution without restenting upon FCSEMS removal occurred in 76.3% of patients (95% CI, 69.3%-82.3%). The rate of resolution was lower in patients with FCSEMS migration (odds ratio, 0.22; 95% CI, 0.11-0.46). Over a median follow-up period of 20.3 months (interquartile range, 12.9-24.3 mo), the rate of stricture recurrence was 14.8% (95% CI, 8.2%-20.9%). Stent-or removal-related serious adverse events, most often cholangitis, occurred in 27.3% of patients. There was no stent-or removal-related mortality. CONCLUSIONS: In a large prospective multinational study, removal success of FCSEMS after extended indwell and stricture resolution were achieved for approximately 75% of patients.

Background and Aims Accurate diagnosis of small gastric subepithelial tumors (SETs) is essential to assess their malignant potential. Endoscopic unroofing has been reported to yield sufficient tissue samples for histologic evaluation. This study aimed to evaluate the safety, diagnostic yield, and potential therapeutic effects of this technique over time. Methods This retrospective analysis of prospectively collected clinical data identified patients who underwent endoscopic unroofing at the Medical University of Vienna from January 2003 to December 2012. Demographic data, indications for endoscopic unroofing, intraprocedural adverse events, hospital stay, histologic results, and follow-up procedures were reviewed. Results A total of 14 patients (7 men; 7 women; median age, 70 years; range, 51-95 years) underwent endoscopic unroofing of 14 gastric SETs with a mean diameter of 26 ± 13 mm at EUS. In 9 of 14 cases, endoscopic unroofing was done exclusively for diagnostic purposes; in the remaining cases, it was performed with therapeutic intent because of bleeding from the gastric SETs. Unroofing was technically successful in 13 of 14 cases and revealed 8 cases of GI stromal tumor (GIST) and 1 case each of leiomyoma, fibroid polyp, glomus tumor, pancreatic rest, and nondiagnostic material at histology. Intraprocedural bleeding was the only adverse event (4 cases) and could be managed endoscopically. A follow-up EUS was available (median, 8 months) for 10 of the 14 patients. Notably, most patients showed complete regression of their gastric SETs after unroofing (on white light and EUS), including the glomus tumor, the leiomyoma, and 6 of the 8 cases of GIST. Conclusions Endoscopic unroofing was safe and had a very favorable diagnostic yield in this study. Unexpectedly, it led to complete regression in most gastric SETs. Although it is not an oncologically curative treatment, endoscopic unroofing can be a valuable option to treat local adverse events in patients unfit for surgical therapy. (Clinical trial registration number: NCT02587923.)

Background and aim After liver transplantation, the endoscopic approach has become the standard treatment modality for biliary complications. Aim of this study was to compare primary endoscopic with primary surgical management. Patients and methods A retrospective review on 1188 consecutive liver transplant patients between 1989 and 2009 was performed. Management strategies (endoscopic, surgical or combined approach) were evaluated for treatment success as well as patient survival. Results Biliary complications after liver transplantation were diagnosed in 211 (18%) patients. Initial endoscopic approach (N = 162, 77%) was successful in 97 of 162 (60%) patients. In 80% of patients, success was achieved within a median of four ERCPs. Sixty-one patients (38%) were referred to surgery after non-successful ERCP. Initial surgical approach was performed in 49/211 patients (23%) with successful management in 38/49 (78%) of patients. Patients presenting with intraluminal objects needed a significantly higher number of ERCPs to reach treatment success (median 3 versus 2 interventions, p = 0.001) but had an equal endoscopic success rate (p = 0.427). Patients with successful endoscopic treatment showed lower mortality compared to patients with primary surgical treatment (p = 0.029). Conclusions Endoscopic management should be considered as the primary approach for biliary complications after liver transplantation.

Background Dieulafoy lesions consist of aberrant submucosal arteries, which can cause severe GI bleeding. The predominant location of Dieulafoy lesions is the upper GI tract. Objective To our best knowledge, this is the first systematic study on the frequency of bleeding from Dieulafoy lesions in the small bowel and the efficacy of enteroscopic therapy regarding primary hemostasis and long-term follow-up. Design Multicenter, retrospective, observational study. Setting Nine Austrian centers doing double-balloon enteroscopy or single-balloon enteroscopy. Patients This study involved 284 consecutive patients who were referred for double-balloon enteroscopy or single-balloon enteroscopy because of suspicion of mid-GI bleeding. Intervention A total of 317 double-balloon enteroscopy and 78 single-balloon enteroscopy procedures were performed in 284 patients with suspected mid-GI bleeding. Main Outcome Measurements Demographic, clinical, procedural, and outcome data were collected. Results A Dieulafoy lesion in the small bowel was identified as the source of mid-GI bleeding in 3.5% of patients, with a mean of 1.5 enteroscopy sessions required per diagnosis. In 9 cases the Dieulafoy lesion was found by enteroscopy from an oral approach, and in 1 patient the lesion was found by an anal approach. In all patients primary endoscopic hemostasis was successful. Eight of 10 patients were free from rebleeding episodes (median follow-up 14.5 months, interquartile range 10.0-17.5 months). In 2 of 10 patients, rebleeding occurred, and a surgical intervention was necessary. Limitations Retrospective study. Conclusion Bleeding from Dieulafoy lesions of the small bowel seems to occur more frequently than previously estimated. Most of these lesions are located in the proximal jejunum and can be managed successfully by enteroscopy. After successful endoscopic hemostasis, rebleeding episodes occur in only 20% of patients.

Enteropathy-associated T cell lymphoma (EATL) is a rare disease with a dismal prognosis. Due to the low efficacy of chemotherapy and the poor performance status of patients failing first line, no data on second line therapy exist. A retrospective analysis of 19 patients with EATL at our institution identified six patients (31%) undergoing second line chemotherapy after CHOP-like regimens. Three patients had progressive disease (PD) during first line therapy, while the other three patients showed relapse after an initial complete remission (CR). The time from the last cycle of first line chemotherapy to second line therapy was 1-62 months. Two patients received ifosfamide, carboplatin and etoposide (ICE), two were given fludarabine and cyclophosphamide (FC) and one each had dexamethasone, cisplatin and cytarabine (DHAP) and cladribine chemotherapy. One patient progressed after one course of cladribine, while two patients developed intestinal perforation and died after one course of ICE and DHAP, respectively. Three patients achieved a CR lasting 4, +7 and +64 months, with two being alive without evidence of disease. Our data again confirm the poor prognosis of patients with EATL. A small subset of patients, however, apparently benefits from initiation of second line chemotherapy.

Environmental factors of the modern Western lifestyle may trigger Crohn's disease (CD) in susceptible individuals. Because such factors could be part of ingested matter, we intended to improve intestinal Crohn's lesions by exclusion thereof.At first we tested a highly restricted diet (based on spelt bread and red meat, both derived from intensively monitored organic farming) in 5 pilot cases. In a subsequent controlled trial, 18 patients with mild-to-moderate CD were randomly assigned to receive either this active diet or a control diet (low-fiber, low-fat, and high-carbohydrate). Mucosal improvement was assessed by magnetic resonance imaging (MRI) and endoscopy. Secondary endpoints included sonography, the Crohn's Disease Activity Index (CDAI), and the Inflammatory Bowel Disease Questionnaire (IBDQ).Four of 5 pilot patients showed significant improvement within 4 weeks. From 18 patients in the controlled trial, 8 were randomized to the active and 10 to the control group; 4 decided to quit immediately after dietary counseling, 3 in the active and 1 in the control group (P = 0.183). At 6 weeks MRI and endoscopy showed improvement of intestinal lesions in 3 of 4 assessable patients of the active group and 1 of 9 patients of the control group (P = 0.027). Sonography showed improvement in 4 of 5 patients of the active group and in 1 of 8 assessable patients of the control group (P = 0.016). CDAI and IBDQ improved in both groups to a similar extent.Ingested matter as part of the modern Western lifestyle may cause persistence of intestinal Crohn's lesions.

Background and study aims: Endoscopic treatment of active gastrointestinal bleeding often remains difficult, and considerable technical expertise is required. Our aim was to assess the efficacy and safety of endoscopic hemostasis with a liquid combination of bovine activated factors IIa/VIIa/IXa/Xa (SeraSeal). Methods: Patients with active gastrointestinal bleeding were prospectively included. In group A, 5 mL of bovine activated factors IIa/VIIa/IXa/Xa was topically applied via catheters to the bleeding site as initial hemostasis; group B received a similar application but as rescue therapy after failure of conventional endoscopic hemostasis. Results: In group A, bleeding was stopped by the agent in 15 /22 patients (68 %) and by conventional endoscopic hemostasis in 5 of the other 7, with coiling and surgery required for definitive hemostasis in 2. In group B, the addition of the agent definitively stopped bleeding in 13 /15 patients (87 %), with hemostasis in the remaining 2 achieved with fibrin glue. Rebleeding was observed in 1 patient. Conclusions: Our proof of concept study suggests that the use of bovine activated factors IIa/VIIa/IXa/Xa might be a safe and effective addition to current endoscopic hemostatic strategies, but further studies are necessary. ClinicalTrials.gov identifier: NCT02349490

Patients with gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma require lifelong endoscopic follow-up. This study aimed to establish and evaluate confocal laser endomicroscopy (CLE) criteria for gastrointestinal MALT lymphoma.This prospective trial was conducted after IRB approval at the Medical University of Vienna. Twenty-four consecutive patients (14 males and 10 females, median age 65 years) referred for staging or follow-up of (former) gastrointestinal MALT lymphoma underwent endosonography (EUS) and CLE including white light endoscopy (WLE) and conventional biopsy sampling of the upper gastrointestinal tract. CLE criteria of the disease were based on the first five patients with histologically proven MALT lymphoma. All CLE datasets were reviewed separately by two CLE experts. The diagnostic modalities were compared using conventional histology as the gold standard.Sixty-two percentages had a positive diagnosis of MALT lymphoma based on histology. The sensitivity was 80 % for EUS (0.51-0.95), 100 % for WLE (0.75-1) and 93 % for CLE (0.66-1); the specificity was 67 % for EUS (0.31-0.91), 23 % for WLE (0.04-0.60) and 100 % for CLE (0.63-1). The agreement with histology was moderate for EUS (kappa 0.47, p = 0.02), fair for WLE (kappa 0.26, p = 0.06) and almost perfect for CLE (kappa 0.91, p 0.01). Expert evaluation identified all but one case of MALT lymphoma with excellent interobserver agreement (kappa 0.89, p 0.01). In the case missed by CLE, MALT lymphoma involvement was restricted to deep tissue structures.Despite minor technical limitations, CLE is a promising alternative to conventional biopsy sampling in patients with gastrointestinal MALT lymphoma. CLINICALTRIALS.NCT01583699.

BACKGROUND AND STUDY AIMS Strictures are a substantial cause of morbidity in patients with Crohn's disease. Endoscopic balloon dilation is a therapeutic option in limited strictures to avoid intestinal surgery, although there have been few reports regarding the long-term outcome. PATIENTS AND METHODS Balloon dilation was scheduled for 46 patients (26 women, 20 men; median age 34) with Crohn's-associated symptomatic and radiographically confirmed intestinal stenosis. The study plan envisaged up to four consecutive treatments within the first 2 months until relief of symptoms, and thereafter dilations depending on clinical requirements. RESULTS Dilation was not possible in seven of the 46 patients (15 %), due to technical problems (n = 2), internal fistulas (n = 3), or absence of a stenosis (n = 2). Thirty-nine patients received at least one treatment. The site of obstruction was the ileocolonic anastomosis in 23 of the 39 patients (59 %) and surgically untreated areas in 16 patients (41 %). After the initial dilation series (median 1, interquartile range 1-2), strictures were traversed in 37 of the 39 patients (95 %). During a median follow-up period of 21 months (range 3-98 months), 24 of the 39 patients (62 %) underwent a repeat intervention, including 12 (31 %) with repeat dilation, 11 (28 %) with surgical resection, and one patient who received an intestinal stent. The cumulative percentages of patients without a repeat intervention or surgery at 6, 12, 24, and 36 months were 68 %, 48 %, 36 %, and 31 %, and 97 %, 91 %, 84 % and 75 %, respectively. Two perforations and one case of severe bleeding were seen in the 73 dilation procedures (4 %) performed. CONCLUSIONS Endoscopic balloon dilation is a safe and effective method that allows surgery to be avoided in approximately 75 % of patients with Crohn's-associated short intestinal strictures. However, recurrent symptoms frequently make it necessary to repeat the procedure.

Cobalamin deficiency is a common finding. In the elderly the prevalence is 10-20%, but only 5-10% of these are clinically symptomatic. Typical clinical symptoms include macrocytic anemia, neuropsychiatric symptoms and glossitis. In many cases this triad is lacking, however. The serum cobalamin assay is the best first line test, but the results must be carefully interpreted, since a normal level does not exclude deficiency. Markers of cobalamin activity, such as serum homocysteine or methylmalonic acid may be helpful in this situation. The main cause of cobalamin deficiency is atrophic gastritis. It is either caused by an autoimmune process which leads to achlorhydria and severe intrinsic factor deficiency ("classical pernicious anemia") or by atrophic gastritis from other causes, in particular helicobacter pylori infection. In the latter cases the lack of gastric acid does not allow separation of cobalamin from proteins, but intrinsic factor, although low, is sufficient for cobalamin protection (food cobalamin malabsorption). Helicobacter pylori eradication may cure some of these patients. While in food cobalamin malabsorption syndrome small doses of oral cobalamin are effective, parenteral therapy or high oral doses are required for treatment of pernicious anemia. While almost all patients respond hematologically, only half of the patients with neurological signs, and a small minority of psychiatric patients respond to treatment. Patients with pernicious anemia and atrophic gastritis have a greatly increased long-term risk for gastric carcinoids.

It is a basic interest of Man to look inside and understand the human body. This interest dates back to prehistoric times and is nowadays of diagnostic relevance in sick patients. It has led to the development of a variety of imaging methods for medical purposes within the 20th century. Among these, ultrasound is exceptionally appealing to both doctors and patients because of the wide variety of organs that can be investigated and because of its safety. The user, at any level, needs both theoretical knowledge and technical skills in its use. Various sites from the upper gastrointestinal tract to the anus are nowadays accessible by ultrasound. This review discusses the instruments for the sonographic evaluation of the gastrointestinal tract and gives an overview of their current applications.

Background: Diffuse large B-cell lymphoma (DLBCL) of the stomach is a relatively common disease. Recently, chemotherapy consisting of doxorubicin, cyclophosphamide, vincristine and prednisone (CHOP) has been reported as effective treatment for early-stage gastric DLBCL. Given the fact that the application of the CD20 antibody rituximab (R) in addition to CHOP has improved outcomes in nodal DLBCL, we have analysed our experience with application of R-CHOP in patients with early-stage gastric DLBCL. Patients and methods: Patients with histologically verified early-stage gastric DLBCL undergoing treatment with R-CHOP for initial management were analysed. Results: Fifteen patients received a total of 79 cycles, with a median of six cycles per patient. All patients responded to therapy, 13 had a complete remission (CR) (87%) and two (13%) a partial remission. All patients in CR, except one who died unrelated to lymphoma, have remained so with a median follow-up of 15 months (range 4 –42) after treatment. Subjective tolerance was moderate, and toxicities were mainly haematological, including leukocytopenia WHO grade 3 and 4 in 10 and five patients each. The addition of rituximab to the standard CHOP regimen did not appear to significantly increase toxicity. Conclusions: Our data indicate that R-CHOP is an effective regimen for management of early-stage gastric DLBCL. However, given the excellent results with CHOP alone in such patients, the value of adding rituximab to standard CHOP remains to be determined in a randomised trial.

The stomach is the most common site of primary extranodal lymphoma. Virtually all cases are of B-cell lineage, including extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and diffuse large B-cell lymphomas. While secondary gastric involvement from nodal mantle cell lymphoma (MCL) or in the course of primary intestinal MCL (lymphomatous polyposis) have been described, primary gastric MCL has not been reported so far. A 74-year-old man with a 14 year-history of Crohn's disease was admitted at a general hospital due to epigastric pain refractory to therapy with proton-pump inhibitors. Endoscopy disclosed a large polypoid tumor with an ulcerated surface at the greater curvature of the gastric antrum. Endosonography demonstrated the tumor to be limited to the stomach with only local lymph node involvement. Histology of gastric biopsies revealed a dense atypical lymphoid infiltrate composed of small to medium sized cells with slightly irregular nuclear contours. Immunohistochemichally, the cells were positive for CD20, CD79a, CD43 and cyclin D1, but negative for CD3, CD5 and bcl-6. They stained for IgM and showed lambda-light chain restriction. Fluorescent in situ hybridisation studies showed the presence of the t(11;14) characteristic for MCL. No further evidence of lymphoma was found on extensive clinical staging. Following chemotherapy the patient is disease free at 24 months after diagnosis. This is the first case of a primary localized gastric MCL. The lack of CD5 expression underscores the importance of performing thorough immunohistochemical studies, particularly to exclude MALT lymphoma.

Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) arises in lymphoid tissue acquired through chronic antigenic stimulation as exemplified by Helicobacter pylori. Secondary development of gastric cancer, however, is thought to be a rare event. The detection of a signet ring cell carcinoma during follow-up endoscopy after successful therapy of MALT lymphoma in a patient with Sjögren's syndrome prompted us to analyse the frequency of subsequent gastric cancer in patients with underlying autoimmune disease (AD).Patients with early stage MALT lymphoma and an underlying AD were evaluated for the occurrence of a secondary gastric cancer during the course of follow-up. Data analysed included the type of AD, stage of MALT lymphoma, H. pylori status, treatment for MALT lymphoma and response, follow-up, the presence of a secondary cancer, and time to development of cancer. In all patients, histologic samples were reassessed for the extent of gastritis, presence of intestinal metaplasia or focal atrophy at the time of lymphoma diagnosis.A total of eight patients with overt AD at the time of diagnosis of MALT lymphoma were identified. All patients were women aged between 56 and 77 years; 5 had Sjögren's syndrome, 2 had autoimmune thyroiditis (1 along with psoriasis) and 1 suffered from polymyalgia rheumatica. All patients had early stage MALT lymphoma restricted to the mucosa and submucosa at the time of diagnosis, and the presence of H. pylori was found in all cases. Two of these patients achieved complete remission (CR) of the lymphoma following H. pylori eradication, while six were judged unresponsive and underwent chemotherapy, resulting in CR in all cases. One patient died from stroke while being in CR for 2 months following chemotherapy. Two patients (25%) developed early cancer limited to the gastric mucosa while being in CR from lymphoma for 9 and 27 months, respectively, and underwent partial gastrectomy. Final staging of gastric cancer revealed pT1pN0M0 in both cases. Of the remaining 5 cases, 1 patient had a local lymphoma relapse 18 months after CR and was salvaged with radiotherapy. In the remaining 4 patients, no evidence of lymphoma recurrence or a second malignancy has been found so far by regular follow-up every 3 months for a time-span between 52 and 63 months after initial diagnosis.Patients with concurrent MALT lymphoma and an underlying autoimmune condition show not only an impaired response to H. pylori eradication but might also be at increased risk for the development of gastric cancer. In view of this, such patients should be followed closely by regular endoscopies after remission of MALT lymphoma.

Background: Endoscopic ultrasound (EUS) is considered the best technique for local staging of primary gastric lymphomas. Its role in the follow up of patients with gastric lymphoma following organ conserving strategies has not been established. Aim: To compare endosonographic response assessment with results of histological evaluation. Patients and methods: Thirty three patients with primary gastric lymphomas underwent pretreatment EUS and were followed endosonographically every 3–6 months after administration of organ conserving treatment modalities. A wall thickness of ≤4 mm with preserved five layer structure and the absence of suspicious lymph nodes was defined as endosonographic remission. Decrease in wall thickness, increase in echogenicity, and regression of lymph nodes were tested for their value to predict histological remission. Results: A total of 158 endosonographies were performed (median 4; range 2–12). Within a median follow up period of 15 months (range 3–48), 27 (82%) patients achieved complete histological remission while endosonographic remission was found in 21 (64%) patients. Eighteen patients achieved both forms of remission, with endosonographic remission occurring later (35.1 (11–212.9) weeks v 17.6 (11–97.9) weeks; median (range); p Conclusions: In view of the inferior accuracy of EUS when compared with histology, gastroscopy with biopsy seems sufficient for the routine follow up of patients with gastric lymphoma.

Background: Endosonography has been reported as the method of choice for local staging of patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT)-type. As endosonography is still restricted to specialized centers, we have investigated the use of spiral computed tomography of the abdomen with water-filling of the stomach (hydro-spiral CT) for enhanced contrast in patients with gastric lymphoma. Patients and Methods: Patients with a histological verified diagnosis of gastric lymphoma of MALT-type were included in this prospective series. All patients underwent routine staging procedures including endosonography of the upper GI-tract carried out by a single individual. In addition, patients were subjected to hydro-spiral CT either before or after endosonography within a maximal time span of 4 weeks. Results of hydro-spiral CT were compared to those of the endosonographic evaluation and histological work-up of biopsy specimens. Results: A total of 14 patients with primary gastric lymphoma of MALT-type (3 with a high-grade component) were studied prospectively. All patients underwent hydro-spiral CT before initiation of treatment, and 2 patients were also studied following chemotherapy. In the pretherapeutic setting, hydro-spiral CT identified gastric lymphoma in 8 patients, while a false negative result was seen in 6 patients. In addition, the localization of the lymphoma within the stomach was divergent between CT and endosonography in 1 patient. In the 2 patients who were also studied after therapy, CT showed unchanged thickening of the stomach wall in spite of normalization in the endosonographic assessment as well as the histologic evaluation. Conclusion: Our results demonstrate the superiority of endosonography over hydro-spiral CT for the staging and follow-up of patients with gastric lymphoma, who should therefore be managed at centers where endosonography is available.

Background To follow-up clinical and biochemical features in patients with Crohn's disease (CD) of the upper gastrointestinal (GI) tract and to evaluate the impact of different therapeutics on the outcome of these patients. Methods 32 CD patients with endoscopically and histologically proven CD of the upper GI tract were included into this retrospective study. Gastroduodenal and intestinal permeability tests, inflammatory parameters, Crohn's Disease Activity Index (CDAI), and upper gastrointestinal complaint profile were sequentially assessed. These parameters were assessed at the beginning and followed up during therapies with antisecretory drugs, mesalamine, prednisolone, and azathioprine. Results Symptoms responded to antisecretory drugs. Gastroduodenal permeability increased under mesalamine. Gastroduodenal and intestinal permeability as well as CDAI decreased under prednisolone. Under azathioprine, gastroduodenal and intestinal permeability, CDAI, and C-reactive protein decreased.

PURPOSE: It has become increasingly clear that nonsteroidal anti-inflammatory drugs may cause damage not only to the upper gastrointestinal tract but also to the small and large intestine. Although the colon may be readily investigated by endoscopy, drug-induced lesions are not well known, probably because they are considered to occur only rarely. In the present study we describe endoscopic, histologic, and gross characteristics of nonsteroidal anti-inflammatory drug-induced colonic damage. Furthermore, pathogenetic mechanisms and therapeutic options are discussed. METHODS: The histories of all patients diagnosed as having nonsteroidal anti-inflammatory drug colitis during the last two years at the department of gastroenterology or the department of pathology at our hospital were reviewed. Endoscopic, histologic, and gross pathologic findings were systematically recorded. In addition, data on duration and type of nonsteroidal anti-inflammatory drug intake and time from onset of symptoms to diagnosis were collected. Therapy and outcome of our patients, if available, are reported. RESULTS: During the study period 11 patients were diagnosed as having nonsteroidal anti-inflammatory drug colitis. Most patients presented with diarrhea with or without blood loss and complained about diffuse abdominal pain. Endoscopy revealed flat ulcers in the entire colon being more severe in the right colon in the three cases with acute onset of diarrhea. In four cases concentric “diaphragm-like” strictures were seen, all located in the right colon. In the remainder endoscopy showed nonspecific erosions and was normal in one patient. Histology revealed findings similar to ischemic colitis. Additionally, in two cases collagenous colitis was found. Diclofenac slow release was the most commonly involved drug. The median time from onset of symptoms to diagnosis was 1.8 (range, 0–11.5) years. CONCLUSIONS: Nonsteroidal anti-inflammatory drug colitis is a clinically significant disease, which may present with diarrhea, anemia, and nonspecific abdominal complaints. Careful history taking, together with awareness of endoscopic and histologic findings, allows a timely diagnosis of this disease.

Background Helicobacter pylori has been recognised as a major gastric pathogen. Many techniques to identify infection have been developed, including histology and culture as invasive tests and the urea breath test as non-invasive technology. Recently, another non-invasive test based on the detection of H. pylori antigens in stool specimens was introduced. Aim To evaluate the sensitivity and specificity of this novel enzyme-linked immunosorbent assay for detection of H. pylori infection in comparison with histology. Methods Stool specimens of 72 consecutive patients who had gastroscopy with biopsy at our endoscopy unit were collected and frozen at -20 degrees C until further processing. H. pylori status was determined as part of the routine histological work-up. In a second step, histology slides were reviewed by a pathologist who specialized in gastrointestinal pathology. Stool samples were tested for the presence of H. pylori antigen using the PREMIER H. pylori Stool Antigen Test. Sensitivity and specificity of routine histopathology and the H. pylori Stool Antigen Test were determined using the diagnosis of the expert gastrointestinal histopathologist as gold standard. Results Routine histopathology resulted in a sensitivity of 90% and specificity of 92% in the diagnosis of H. pylori. These results compare well with the results of the H. pylori Stool Antigen Test that revealed a sensitivity of 80% and a specificity of 98%. Conclusion The H. pylori Stool Antigen Test is a promising non-invasive test for the detection of H. pylori infection.

Mucosa associated lymphoid tissue lymphoma of the stomach is associated with Helicobacter pylori (HP) infection in the large majority of patients [1]. Following initial pilot studies, large scale t...

BACKGROUND & AIMS: Gastric histology is not well studied in patients with Crohn's disease. The aim of this study was to analyze the histological appearance of gastric mucosa in patients with Crohn's disease. METHODS: In a prospective study, biopsy specimens taken from the antrum and body of 75 patients with known Crohn's disease of the large and/or small bowel and 200 Crohn's disease-free controls were evaluated by histology and immunohistochemistry. RESULTS: Helicobacter pylori-associated gastritis was found in 25 patients with Crohn's disease (33.3%) and 78 controls (39%). In H. pylori-negative patients with Crohn's disease, a characteristic type of gastritis was found in antral biopsy specimens of 36 patients (48%) and in body biopsy specimens of 18 patients (24%). It was characterized by a focal infiltration of CD3+ lymphocytes, CD68R+ histiocytes, and, in 80% of cases, of granulocytes. Granulomas were found in 11 patients. Overall, granulomas and/or focally enhanced gastritis were observed in 76% of H. pylori-negative patients with Crohn's disease and in 0.8% of controls. There were no correlations between the occurrence of focally enhanced gastritis and clinical and laboratory findings. CONCLUSIONS: Focally enhanced gastritis is common in Crohn's disease. Its recognition should guide the clinician into further investigations in patients not yet known to have Crohn's disease. (Gastroenterology 1997 Mar;112(3):698-706)

Minimal chronic inactive gastritis is regularly observed in routine histopathology. Presently, it is not clear whether this type of gastritis should be regarded as a histopathological entity or a normal variant. The similarity to lesions observed after H.pylori eradication prompted us to look for an association between minimal chronic inactive gastritis and status post H.pylori eradication. In a prospective study of 110 consecutive patients undergoing upper gastrointestinal endoscopy, at least two mucosal biopsies were taken from the gastric antrum and body. Gastritis was classified according to the Sydney System. Antibodies to H.pylori were determined serologically by immunofluorescence test, ELISA, and complement binding reaction. A status post eradication of H.pylori was revealed by medical history and/or positive serology; H.pylori gastritis was found in 39.1%, reactive gastritis in 12.7%, and minimal chronic inactive gastritis in 29.1%. In 19.1% a combination of reactive/ minimal chronic gastritis was diagnosed according to morphology. Status post eradication was observed significantly more often in cases with minimal chronic inactive gastritis (43.8%) than in cases with reactive gastritis (7.1%, p < 0.004). Furthermore, positive ELISA and/or status after eradication was found in 50% of the cases with minimal chronic inactive gastritis (p < 0.005 vs reactive gastritis), in 42.9% of the cases with mixed reactive/chronic inactive gastritis (p < 0.03 vs reactive gastritis), and in 7.1% of the cases with reactive gastritis. Lymphoid aggregates, considered another sign of former H.pylori presence, were found significantly more often in minimal chronic inactive gastritis than in reactive gastritis (50% versus 7.1%, p < 0.005). Minimal chronic inactive gastritis is significantly associated with both positive H.pylori serology and status post eradication and is, therefore, an indicator of pre-existing H.pylori gastritis.

Background and study aims: The MiroCam is a new video capsule device offering a higher frame rate and a longer battery life-expectancy. We aimed to quantify its clinical impact and performed a randomized head-to-head comparison with the EndoCapsule device with respect to the rate of complete small-bowel examinations, diagnostic yield in the small bowel, and capsule transit time. Patients and methods: Patients referred for video capsule endoscopy because of obscure gastrointestinal bleeding, chronic diarrhea, and anemia of unknown origin were randomly assigned to swallow either the MiroCam first, followed by the EndoCapsule 2 hours later, or vice versa. All videos were analyzed by two independent investigators. Results: A total of 50 patients (median age 61, range 21 – 84) were included. Complete small-bowel examination was achieved in 48 /50 patients using the MiroCam and 45 /50 using the EndoCapsule (96 % vs. 90 %, odds ratio [OR] 2.67, 95 % confidence interval [CI] 0.49 – 14.45; P = 0.38). There was diagnostic yield in the small bowel for 25 /50 patients using the MiroCam and 24 /50 using the EndoCapsule (50 % vs. 48 %, OR 1.08, 95 %CI 0.49 – 2.37; P > 0.99). However, the findings were concordant in 68 % only (kappa = 0.50). The combined diagnostic yield was 58 %. Even solitary findings had a relevant clinical impact during a 6-month follow-up. Conclusion: In this direct comparison the MiroCam and EndoCapsule devices were not statistically different with regard to their rates of complete small-bowel examinations or diagnostic yield. Their moderate concordance, mainly caused by missed pathological findings, which affected both devices, needs consideration in clinical practice.

Mucosa-associated lymphoid tissue (MALT) lymphomas are B cell neoplasms which commonly affect the gastrointestinal (GI) tract. Gastrointestinal MALT lymphomas rarely show plasmacytic differentiation (PCD), and limited data on the potential influence of the anti-CD20 antibody rituximab (R) on PCD exist in the current literature. We have retrospectively analyzed patients with GI MALT lymphomas treated with R-containing regimens because restaging is routinely performed by repeated biopsies with pathohistological response assessment. Twenty-one patients with GI MALT lymphoma were identified to have undergone R-containing therapy. In 19 patients, the lymphoma originated in the stomach, while the colon was the primarily affected organ in two cases. Four patients received R monotherapy and 17 combinations of R with various chemotherapeutic agents. Only two patients with gastric MALT lymphoma had PCD before initiation of therapy. In 7 of 19 patients (37%) without PCD at diagnosis, restaging revealed PCD after or while on treatment with R-containing regimens. Out of these seven patients, only one patient had a complete response as opposed to 10/12 without PCD. These data suggest that R or R-containing treatment regimens may not optimally eradicate the plasma cell component and thus lead to PCD in patients with GI MALT lymphoma. In view of this, rebiopsy and histological re-assessment appear mandatory in patients failing/relapsing after R-containing regimens.