Mucosal Biofilms Are an Endoscopic Feature of Irritable Bowel Syndrome and Ulcerative Colitis.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) and inflammatory bowel diseases result in a substantial reduction in quality of life and a considerable socioeconomic impact. In IBS, diagnosis and treatment options are limited, but evidence for involvement of the gut microbiome in disease pathophysiology is emerging. Here we analyzed the prevalence of endoscopically visible mucosal biofilms in gastrointestinal disease and associated changes in microbiome composition and metabolism. METHODS: The presence of mucosal biofilms was assessed in 1426 patients at 2 European university-based endoscopy centers. One-hundred and seventeen patients were selected for in-depth molecular and microscopic analysis using 16S ribosomal RNA gene amplicon-sequencing of colonic biopsies and fecal samples, confocal microscopy with deep learning-based image analysis, scanning electron microscopy, metabolomics, and in vitro biofilm formation assays. RESULTS: Biofilms were present in 57% of patients with IBS and 34% of patients with ulcerative colitis compared with 6% of controls (P < .001). These yellow-green adherent layers of the ileum and right-sided colon were microscopically confirmed to be dense bacterial biofilms. 16S-sequencing links the presence of biofilms to a dysbiotic gut microbiome, including overgrowth of Escherichia coli and Ruminococcus gnavus. R. gnavus isolates cultivated from patient biofilms also formed biofilms in vitro. Metabolomic analysis found an accumulation of bile acids within biofilms that correlated with fecal bile acid excretion, linking this phenotype with a mechanism of diarrhea. CONCLUSIONS: The presence of mucosal biofilms is an endoscopic feature in a subgroup of IBS and ulcerative colitis with disrupted bile acid metabolism and bacterial dysbiosis. They provide novel insight into the pathophysiology of IBS and ulcerative colitis, illustrating that biofilm can be seen as a tipping point in the development of dysbiosis and disease.

Fully Covered Self-Expanding Metal Stent vs Multiple Plastic Stents to Treat Benign Biliary Strictures Secondary to Chronic Pancreatitis: A Multicenter Randomized Trial.

BACKGROUND & AIMS: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients. METHODS: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events. RESULTS: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred. CONCLUSIONS: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.).

[Health status of endoscopy personnel in Austria]. / Gesundheitszustand des Endoskopiepersonals in Österreich.

BACKGROUND: Working in the field of endoscopy is associated with physical and psychological challenges, but we lack data as to whether it influences the health status of endoscopy personnel. The aim of the present survey was to evaluate the health status of endoscopy personnel in Austria and draw comparisons. METHOD: In 2019, a standardized questionnaire of Hogrefe Publishers and a self-designed SurveyMonkey questionnaire were sent online to doctors (n=326) and nursing staff (n=234) working in the field of gastrointestinal endoscopy in Austria. The response rate was 17.9%. The data were compared with those of a standard population, a similar previous survey from 2004, and national sick leave data. RESULTS: Compared to a standard population of identical age and gender distribution, endoscopy personnel in Austria have more health-related complaints. Compared to doctors, nursing staff experience greater adverse effects; foremost among these are fatigue and an excessive need for sleep (p=0.001), a heavy sensation in the legs (p=0.001), hypersensitivity to warmth (p<0.001) and cold (p=0.002). Nursing staff are somewhat more frequently on sick leave than doctors. The days of sick leave were higher than those in 2004, but markedly below the average figures in Austria. Lifestyle had little influence on the respondents' symptoms. CONCLUSION: The results of the survey showed that persons working in endoscopy have slightly greater health problems than the standard population. Nursing staff are affected more severely than doctors. These data may serve as a basis for targeted preventive measures.

Fully covered self-expanding metal stents for benign biliary stricture after orthotopic liver transplant: 5-year outcomes.

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.).

Long-term outcomes after temporary placement of a self-expanding fully covered metal stent for benign biliary strictures secondary to chronic pancreatitis.

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: NCT01014390.).

Transformed mucosa-associated lymphoid tissue lymphomas: A single institution retrospective study including polymerase chain reaction-based clonality analysis.

Given the lack of consistent data regarding the clinico-pathological features and clonal lymphomagenesis of patients with mucosa-associated lymphoid tissue (MALT) lymphoma and histological transformation (HT), we have systematically analysed 379 patients (32% gastric, 68% extra-gastric; median follow-up 52 months) diagnosed with HT at the Medical University Vienna 1999-2017, and reassessed tissues of identified patients by polymerase chain reaction (PCR)-based clonality analysis. HT was documented in 12/379 patients (3·2%) and occurred at a median time of 22 months (range; 6-202 months) after diagnosis of MALT lymphoma. By PCR-based clonality analysis, we detected a clear-cut clonal relationship of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) in 8 of 11 analysed cases proving that the large majority of DLBCL following MALT lymphoma are clonally-related and constitute a real transformation. Interestingly, HT occurred within the first 2·5 years after diagnosis in patients with clonal relationship, whereas time to aggressive lymphoma was longer in patients identified as clonally-unrelated (most likely secondary) lymphoma (82-202 months), suggesting that HT is an early event in this disease. Survival of patients with HT was poor with 6/12 dying at 1·5-33 months after HT, however, patients with localized gastric transformation had a superior outcome with only 1/6 dying due to progression of lymphoma.

Treatment of mucosa associated lymphoid tissue lymphoma with a long-term once-weekly regimen of oral azithromycin: Results from the phase II MALT-A trial.

The macrolide clarithromycin has been reported as active for therapy of mucosa associated lymphoid tissue (MALT) lymphoma. Pharmacokinetic properties, however, require continuous daily intake over a prolonged period of time. As the macrolide azithromycin is characterized by a long half-life as well as potential antineoplastic activity in vitro, we have performed a phase II trial of long-term once-weekly oral azithromycin for treatment of MALT lymphoma. In a 2-stage-design, 16 patients (10 f/6 m) with histologically verified and measurable MALT lymphoma were included in the first phase of the trial, which could be expanded to a maximum of 46 patients depending on remissions in the first phase. Patients were given oral azithromycin 1500 mg once-weekly 4 times a month, and restaging was performed after 3 and 6 months. Two patients had gastric and 14 extragastric MALT lymphoma; 12/16 patients were treatment-naive and received azithromycin as first line treatment. Tolerance of this regimen was excellent, and 14/16 patients received 6 months of treatment as scheduled, while 1 patient each discontinued after 4 (progressive disease) and 1 cycle (personal reasons), respectively. The most commonly observed side effects were mild nausea (n = 8) and diarrhea (n = 4). Efficacy, however, was low as only 4/16 patients (25%) responded, with 2 complete and 2 partial remissions, 9 patients (56%) had stable disease, and 3 patients 19%) were rated as progressive disease. As the predefined activity of more than 7/16 patients responding was not reached, the study was stopped after 16 patients. Although long-term once-weekly oral azithromycin showed some antilymphoma activity, the response rate was below the predefined threshold of interest. However, based on our data, one cannot rule out suboptimal dosing in our study; attempts to study azithromycin at a different mode of application might be warranted in the future.

Outcomes after placement of a SX-ELLA oesophageal stent for refractory variceal bleeding-A national multicentre study.

BACKGROUND: Current guidelines favour the use of bleeding stents over balloon tamponade (BT) for refractory variceal bleeding (VB) from oesophageal varices. However, data on the efficacy and safety of self-expandable metal SX-ELLA Danis stents (SEMS) are limited. METHODS: Cirrhotic patients receiving SEMS for VB at four tertiary care centres were included in this retrospective multicentre study. Rates of failure-to-control bleeding (within 5 days) and bleeding-related mortality (6 weeks) were assessed. RESULTS: SEMS controlled VB in 79.4% (27/34) of patients. In the rest of patients, other rescue treatments including endoscopic band ligation (EBL, n = 3), SEMS renewed (n = 2) or Linton (n = 2) were applied; however, VB was only controlled in one patient. Early rebleeding within six weeks occurred in 17.6% (6/34) patients. Median SEMS dwell time was three (IQR:6) days. Overall n = 13/34 (38.2%) patients died with SEMS in situ. After SEMS removal, rebleeding and bleeding-related death occurred in n = 7 (35%) and n = 5 (14.7%) patients respectively. Only 32.4% (10/34) patients did not experience any rebleeding within six weeks after SEMS removal. Bleeding-related mortality was 47.1% (n = 16/34) and the median survival after SEMS placement was 2.1 months. Notably, no patient received an early transjugular intrahepatic portosystemic shunt (TIPS). The most common adverse events were stent dislocations (n = 13; 38.2%), while ulcers/necrosis of the oesophageal mucosa was seen in only four (11.8%) patients. CONCLUSION: SEMS controlled refractory VB in most patients. However, bleeding-related mortality remained high. While SEMS dislocations were frequent, ulcers/necrosis of the oesophagus was rare. Further studies should investigate whether the wider use of early TIPS reduces bleeding-related mortality after SEMS placement.

Gastrointestinal Involvement in Patients with Mantle Cell Lymphoma: A Single Center Experience of Eighty-Five Patients.

BACKGROUND: The frequency of endoscopically apparent gastrointestinal tract (GI) involvement in patients with mantle cell lymphoma (MCL) at diagnosis is thought to be in the range of 30%. While reports on GI involvement in MCL patients exist, most series lack a strict GI assessment due to the often asymptomatic nature of GI involvement. Owing to the standardized staging routine at our institution including GI assessment at diagnosis, we have analyzed the rate and prognostic impact of GI involvement in MCL. METHODS: In this retrospective single-center evaluation, we have investigated GI involvement in 85 consecutive patients with MCL. All data were collected from clinical records. RESULTS: MCL with and without endoscopically detectable GI involvement was reported in 29 (34%) patients and 56 patients (66%), respectively. The colon was involved in 21 (72%) and the stomach in 8 (28%). Eight of 29 patients (28%) had symptomatic GI involvement, and the primary diagnosis had been established in the GI tract in 3/29 (10%) of our patients. No statistical differences could be observed between both groups in terms of gender (p = 0.474), Eastern Cooperative Oncology Group (0.428), and MCL international prognostic index (0.543). Overall survival was longer in patients with GI involvement (116.0 vs. 74 months), but not statistically significant (p = 0.825). CONCLUSIONS: In our single center cohort, we did not find a clinical impact of GI involvement on the clinical course of MCL and no GI complications occurred during chemotherapy in these patients. As most patients were also asymptomatic, these data argue against a routine GI assessment in patients diagnosed with MCL.

Rifaximin Reduces the Number and Severity of Intestinal Lesions Associated With Use of Nonsteroidal Anti-Inflammatory Drugs in Humans.

The intestinal microbiota might contribute to enteropathy associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed-release antibiotic formulation (rifaximin-extended intestinal release [EIR]) prevents the development of intestinal lesions in subjects taking daily NSAIDs. Sixty healthy volunteers (median age, 26 y; 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days. Subjects were assessed by videocapsule endoscopy at baseline and after 2 weeks of treatment. The primary end point was the proportion of subjects developing at least 1 small-bowel mucosal break at week 2. Secondary end points were the change in the mean number of mucosal lesions and the number of subjects with large erosions and/or ulcers after 14 days of exposure. We detected mucosal breaks in 20% of subjects given rifaximin and in 43% of subjects given placebo (P = .05 in the post hoc sensitivity analysis). None of the subjects in the rifaximin group developed large lesions, compared with 9 subjects in the placebo group (P < .001). Our findings indicate that intestinal bacteria contribute to the development of NSAID-associated enteropathy in human beings. Clinical trial no: EudraCT 2013-000730-36.

Immunohistochemical expression of cereblon and MUM1 as potential predictive markers of response to lenalidomide in extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma).

Lenalidomide is an active agent for the treatment of MALT lymphoma. Recently, high expression levels of cereblon (CRBN) and MUM1 have been associated with better response rates in multiple myeloma treated with lenalidomide. However, there are no data on CRBN and MUM1 expression in MALT lymphoma. In the current study, we have systematically investigated a potential correlation of CRBN/MUM1 immunohistochemical expression and response to lenalidomide-based therapy in a series of 46 patients with MALT lymphoma treated at the Medical University Vienna 2009 to 2014. In total, 28% (13/46) of biopsy specimens derived from gastric tissues, while 72% (33/46) originated from extragastric MALT lymphoma. In terms of CRBN, 54% showed high expression (CRBN+, ≥50% positive cells); the remaining 46% were classified as low expression (CRBN-). In contrast to other reports, there was a non-significant trend towards worse response rates in CRBN+ (68% versus 86%, P = 0.161). Relapse rates (P = 0.592) and PFS (P = 0.306) did not differ between CRBN+/CRBN-, but all 3 patients progressing on lenalidomide were CRBN+ and both patients completely lacking CRBN expression responded to treatment. Concerning MUM1, 62% were MUM1-negative (MUM1-) and 38% positive (MUM1+). There was no difference in response to lenalidomide by MUM1-status (MUM1+ 71% versus MUM1- 79%, P = 0.546) and also relapse rates (P = 0.828) and PFS (P = 0.681) did not differ. Interestingly, a subgroup analysis of gastric lymphoma revealed a significantly better PFS for CRBN- and MUM1- patients, respectively (both P < 0.05). To conclude, there was no significant difference in response to lenalidomide between patients with low or high expression of CRBN/MUM1 in a general population of MALT lymphoma, and immunohistochemical CRBN/MUM1 assessment cannot be recommended in the clinical routine.

A pilot phase II study of ofatumumab monotherapy for extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) lymphoma.

These are the final results of the Ofatumumab in MALT lymphoma study (O-MA 1), a pilot phase II trial evaluating the capacity and safety of ofatumumab to induce objective responses in patients with Helicobacter pylori eradication refractory or extragastric MALT lymphoma. Ofatumumab was given at 4 weekly doses (1000 mg) followed by 4 doses at 2-month intervals starting at week 8. According to protocol, a total of 16 patients were recruited (median age 69 years; range 38-85). Thirty one percent (5/16) of patients had primary gastric MALT lymphoma while the remaining 69% (11/16) presented with extragastric manifestations. Seventy-five percent (12/16) had localized lymphoma and 4 patients disseminated disease. The overall response rate to treatment with ofatumumab was 81% (13/16), with the median time to best response being 5.5 months. In detail, 50% (8/16) achieved complete remission; 31% (5/16), partial remission; and 19% (3/16), disease stabilization as best response. However, 1 patient with gastric lymphoma and complete remission at second restaging had a relapse at final assessment but ongoing complete remission during further follow-up. Tolerability was excellent accept low-grade infusion reactions occurring in 86% (14/16). At a median follow-up time of 25 months only 1 patient has relapsed suggesting durable responses in the majority of patients. This pilot trial shows clearly that ofatumumab is active and safe for the treatment of MALT lymphoma.

Radiofrequency ablation in patients with large cervical heterotopic gastric mucosa and globus sensation: Closing the treatment gap.

BACKGROUND AND AIM: Symptomatic cervical heterotopic gastric mucosa, also known as cervical inlet patch (CIP), may present in various shapes and causes laryngopharyngeal reflux (LPR). Unfortunately, argon plasma coagulation, standard treatment of small symptomatic CIP, is limited in large CIP mainly because of concerns of stricture formation. Therefore, we aimed to investigate radiofrequency ablation (RFA), a novel minimally invasive ablation method, in the treatment of CIP focusing on large symptomatic patches. METHODS: Consecutive patients with macroscopic and histological evidence of large (≥20 mm diameter) heterotopic gastric mucosa were included in this prospective trial. Primary outcome was complete macroscopic and histological eradication rate of CIP. Secondary outcome measures were symptom improvement, quality of life, severity of LPR and adverse events. RESULTS: Ten patients (females, n = 5) underwent RFA of symptomatic CIP. Complete histological and macroscopic eradication of CIP was observed in 80% (females, n = 4) of individuals after two ablations. Globus sensations significantly improved from median visual analog scale score 8 (5-9) at baseline to 1.5 (1-7) after first ablation and 1 (1-2) after final evaluation (P < 0.001). Mental health scores significantly increased from 41.4 (± 8.5) to 54.4 (± 4.4) after RFA (P = 0.007). LPR improved significantly (P = 0.005) with absence of strictures after a mean follow up of 1.9 (± 0.5) years. CONCLUSIONS: This is the first study on RFA focusing on therapy of large symptomatic heterotopic gastric mucosa. Hereby, we demonstrate that this new technique can be successfully implemented in patients where treatment was limited so far (NCT03023280).

Long-term safety and activity of cladribine in patients with extranodal B-cell marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) lymphoma.

The purine analogue 2-chloro-deoxyadenosine (2-CDA, cladribine) +/- rituximab has been successfully tested in mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) patients. However, studies using cladribine in other indications have reported the potential for prolonged hematological side effects and secondary hematologic and non-hematologic malignancies. To date, there have been no data on long-term effects of cladribine in MALT lymphoma patients. We have analyzed a large number of 49 patients treated with cladribine at our institution 1997-2011. All patients were treated within clinical trials and had undergone a standardized follow-up protocol minimizing a potential bias in the detection of late sequels and relapses. After a median follow-up time of 61 months (interquartile range: 43-72) for 49 analyzed patients, 35 (71%) are alive, while 14 (29%) have died. In the entire collective, three cases (6%) of prolonged pancytopenia including manifest myelodysplastic syndrome in one patient (2%), three cases (6%) of secondary lymphoid malignancies, and five cases (10%) of non-hematologic cancers were documented. In terms of outcome, 42/49 (86%) patients responded to cladribine-containing treatment, and only 10/42 (24%) responding patients needed further treatment after a median time to progression of 14 months (interquartile range, 8-34). Currently, 25/35 (71%) patients being alive are in ongoing complete remission and 2/35 (6%) in ongoing stable disease, respectively. Eight patients (23%) are free of lymphoma after second-line therapy, with the median overall survival not having been reached. Our data suggest that cladribine might be safely applied in patients with MALT lymphoma, also in terms of long-term toxicities. These data also confirm the potential of cladribine to induce durable remissions. Copyright © 2015 John Wiley & Sons, Ltd.

Pediatric gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) and European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) Guideline Executive summary.

This Executive summary of the Guideline on pediatric gastrointestinal endoscopy from the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) refers to infants, children, and adolescents aged 0 - 18 years. The areas covered include: indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; endoscopic management of corrosive ingestion and stricture/stenosis; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography, and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease (IBD) have been dealt with in other Guidelines and are therefore not mentioned in this Guideline. Training and ongoing skill maintenance will be addressed in an imminent sister publication.

Paediatric Gastrointestinal Endoscopy: European Society for Paediatric Gastroenterology Hepatology and Nutrition and European Society of Gastrointestinal Endoscopy Guidelines.

This guideline refers to infants, children, and adolescents ages 0 to 18 years. The areas covered include indications for diagnostic and therapeutic esophagogastroduodenoscopy and ileocolonoscopy; endoscopy for foreign body ingestion; corrosive ingestion and stricture/stenosis endoscopic management; upper and lower gastrointestinal bleeding; endoscopic retrograde cholangiopancreatography; and endoscopic ultrasonography. Percutaneous endoscopic gastrostomy and endoscopy specific to inflammatory bowel disease has been dealt with in other guidelines and are therefore not mentioned in this guideline. Training and ongoing skill maintenance are to be dealt with in an imminent sister publication to this.

Delayed Efficacy After Treatment With Lenalidomide or Thalidomide in Patients With Mucosa-Associated Lymphoid Tissue Lymphoma.

BACKGROUND: The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have both been tested for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, with lenalidomide, in particular, showing promising activity. However, long-term results are missing. Because of the late-onset remissions registered in individual patients, we have systemically analyzed the patients treated with IMiDs at our institution for long-term results. METHODS: Within the present retrospective analysis, we identified 25 patients who had been treated with lenalidomide (n = 18) or thalidomide (n = 7) and were available for long-term assessments of outcome. All patients were followed up according to a standardized follow-up protocol. RESULTS: Of the 25 patients, 7 (28%) experienced delayed-onset responses without further treatment (thalidomide, n = 2; lenalidomide, n = 5). In 4 patients (16%), the initial outcome switched to a better result (partial remission [PR] to complete remission [CR], n = 1; stable disease [SD] to PR, n = 1; SD to CR, n = 1; and PD to CR, n = 1) after a median time of 19.5 months (range, 10.9-32.0). Furthermore, 2 patients showed ongoing shrinkage of the target lesion for 47.4+ and 43.5+ months, respectively, and 1 patient had durable disease stabilization for 16.2+ months. The median time to the best response for all responding patients (13 of 25; 53%) was 7.3 months (interquartile range [IQR], 5.6-22.5). After a median follow-up of 46 months (IQR, 32.0-58.5), 23 of 25 patients (92%) were alive. CONCLUSION: Our findings suggest that late-onset remissions might be a common phenomenon in the use of IMiDs for the treatment of MALT lymphoma. Thus, sufficient follow-up time after treatment before the initiation of further therapy appears crucial to assess the full effect of therapy and avoid unnecessary overtreatment. IMPLICATIONS FOR PRACTICE: The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have been tested for the treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, with lenalidomide showing promising activity. However, long-term results are missing. The present findings suggest that late-onset remissions and delayed responses could be a common phenomenon with IMiD use for MALT lymphoma. Using a standardized restaging protocol to ensure concise follow-up data, these findings suggest it is of major importance to ensure a sufficient follow-up time after treatment with these compounds and before initiation of further treatment lines, because nearly one third of treated patients showed further improvement during prolonged follow-up.

Gender Aspects in Extranodal Marginal Zone B-Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue: Does Sex Matter?

OBJECTIVES: Gender-related aspects have been investigated in a variety of tumor entities including results on sex-specific differences in non-Hodgkin lymphoma. However, there are no data on gender differences in mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: We have analyzed 327 patients treated between 1999 and 2015 with a median follow-up time of 55.2 months. RESULTS: There was a female predominance, with 197 female (60.2%) and 130 male patients (39.8%, female-to-male ratio 1.5). The mean age was comparable between female and male patients (61.2 vs. 61.7 years, p = 0.777). Female patients less frequently had gastric MALT lymphoma (31.5 vs. 39.2%), but this was not statistically significant (p = 0.149). Extragastric manifestations were equally distributed, except for parotid (p = 0.003) and breast lymphoma (n = 8, 100% female) showing a female predominance. This was most likely related to a higher rate of active autoimmune disorders in women (35.6 vs. 11.0%, p < 0.001). ß2-Microglobulin elevation at diagnosis occurred more often in female patients (42.8 vs. 26.0%; p = 0.008). However, this did not translate into a worse progression-free survival for female (56.0 months, 95% CI 30.1-81.9) versus male patients (49.0 months, 95% CI 25.4-72.5, p = 0.433). Overall survival did not differ between groups. CONCLUSION: Our data show surprisingly little differences between female and male patients with MALT lymphoma. Both sexes appeared to have well-balanced clinical features and an identical prognosis.

Prevalence of clarithromycin-resistant Helicobacter pylori strains in gastric mucosa-associated lymphoid tissue lymphoma patients.

Gastric MALT lymphoma is closely associated with Helicobacter pylori infection. Bacterial eradication therapy comprising clarithromycin is the first-line treatment in gastric MALT lymphoma patients. However, antimicrobial resistance to clarithromycin has been increasing in Europe, and thus far, it has not been examined in gastric MALT lymphoma patients. Based upon histopathological investigation, 17 adult gastric MALT lymphoma patients were identified to be related with H. pylori infection between 1997 and 2014. Detection of H. pylori infection in these patients and clarithromycin susceptibility testing were performed by 23S rRNA gene real-time PCR. Twelve of the patients were confirmed with H. pylori infection by real-time PCR. Among these patients, only two were found to be infected with clarithromycin-resistant H. pylori strain. In one of them, both the clarithromycin-resistant and sensitive genotype were detected. The rate of clarithromycin resistance was 15.4 %. Clarithromycin resistance pattern in gastric MALT lymphoma patients is under the predictions since a previous study performed in Central Europe revealed a rate of 36.6 % in Austria. Considering the low antimicrobial resistance rate, clarithromycin is still an option in gastric MALT lymphoma management.

A retrospective study on the safety, diagnostic yield, and therapeutic effects of endoscopic unroofing for small gastric subepithelial tumors.

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.).