Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study.

OBJECTIVE: To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC. DESIGN: Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup. RESULTS: Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC. CONCLUSION: Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC. TRIAL REGISTRATION NUMBER: NCT03633617.

Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice - International Expert Recommendations.

BACKGROUND & AIMS: There are no studies or recommendations on optimal monitoring strategies for patients with eosinophilic esophagitis (EoE). Our objective was to develop guidance on how to monitor patients with EoE in routine clinical practice, on the basis of available clinical evidence and expert opinion. METHODS: A multidisciplinary, international group of EoE experts identified the following important 3 questions during several consensus meetings: why, by what means, and when to monitor patients with EoE. A steering committee was named, and 3 teams were formed to review literature and to formulate statements for each topic. In a Delphi survey, a level of agreement of ≥75% was defined as threshold value for acceptance. In a final conference, results were presented, critical points and comments on the statements were discussed, and statements were rephrased/rewritten if necessary. RESULTS: Eighteen EoE experts (14 adult and pediatric gastroenterologists, 2 pathologists and 2 allergists) with a median of 21.7 years in clinical practice, mostly academic or university-based, completed the Delphi survey, which included 11 statements and a proposed algorithm for monitoring patients with EoE. Each statement attained ≥75% agreement. Participants discussed and debated mostly about the statement concerning surveillance intervals for EoE patients with stable disease. CONCLUSIONS: It was concluded that effective maintenance treatment probably reduces the development of EoE complications, and regular, structured, and, under certain conditions, individualized clinical follow-up is recommended to assess disease activity while opening a window to monitoring side effects, adjusting therapy, and encouraging adherence to treatment. Follow-up should comprise symptom assessment and periodic or repeated endoscopy with histological assessment in specific EoE settings.

Barrett's Esophagus in Eosinophilic Esophagitis in Swiss Eosinophilic Esophagitis Cohort Study (SEECS).

INTRODUCTION: There is a complex interrelationship between gastroesophageal reflux disease (GERD) and eosinophilic esophagitis (EoE) potentially promoting the occurrence and modulating severity of each other reciprocally. Presence of Barrett's esophagus (BE) is a defining factor for the diagnosis of GERD. While several studies investigated the potential impact of concomitant GERD on the presentation and course of EoE, little was known with regards to BE in EoE patients. METHODS: We analyzed prospectively collected clinical, endoscopic, and histological data from patients enrolled in the Swiss Eosinophilic Esophagitis Cohort Study (SEECS) regarding differences between EoE patients with (EoE/BE+) versus without BE (EoE/BE-) and determined the prevalence of BE in EoE patients. RESULTS: Among a total of 509 EoE patients included in our analysis, 24 (4.7%) had concomitant BE with a high male preponderance (EoE/BE+ 83.3% vs. EoE/BE- 74.4%). While there were no differences in dysphagia, odynophagia was significantly (12.5 vs. 3.1%, p = 0.047) more common in EoE/BE+ versus EoE/BE-. General well-being at last follow-up was significantly lower in EoE/BE+. Endoscopically, we observed an increased incidence of fixed rings in the proximal esophagus in EoE/BE+ (70.8 vs. 46.3% in EoE/BE-, p = 0.019) and a higher fraction of patients with a severe fibrosis in the proximal histological specimen (8.7 vs. 1.6% in EoE/BE, p = 0.017). CONCLUSION: Our study reveals that BE is twice as frequent in EoE patients compared to general population. Despite many similarities between EoE patients with and without BE, the finding of a more pronounced remodeling in EoE patients with Barrett is noteworthy.

Efficacy and Safety of Cold Snare Polypectomy of Colorectal Polyps 10-15 mm with a Hybrid Snare: A Prospective Observational Pilot Study.

INTRODUCTION: Cold snare polypectomy (CSP) is a safe and effective procedure for small colorectal polyps ≤9 mm. There are only limited data regarding CSP of larger neoplastic lesions. This study evaluated the efficacy and safety of CSP for polyps between 10 and 15 mm in size. METHODS: In this prospective single-arm observational pilot study, patients with a least one polyp 10-15 mm were included. These polyps were preferably removed by CSP using a dedicated hybrid snare. The primary outcome was the histological complete resection rate (CRR) determined by pathologically negative margins of the specimen and no neoplastic tissue obtained from biopsies of the resection site margin. Secondary outcomes were en bloc resection rate, failure of CSP, and incidence of adverse events. RESULTS: A total of 61 neoplastic polyps were removed from 39 patients. Overall CRR was 80.3% (49/61). CSP was feasible in 78.7% (48/61) of polyps and the CRR in this group was 85.4% (41/48). When CSP failed (13/61; 21.3%), lesions were successfully resected by immediate HSP using the same snare with a CRR of 61.5% (8/13) in this group. One patient presented delayed hemorrhage after HSP of a polyp but successful hemostasis was achieved with two hemoclips. No other adverse events occurred. No recurrence was seen on follow-up colonoscopy in cases with incomplete resected polyps. CONCLUSION: CSP seems to be efficient and safe in removing colorectal polyps up to 15 mm. A hybrid snare seems to be particularly advantageous for these polyps as it allows immediate conversion to HSP if CSP might fail in larger polyps. This trial is registered at ClinicalTrials.gov (NCT04464837).

[Treatment of eosinophilic esophagitis - advancements and perspectives]. / Therapie der eosinophilen Ösophagitis - Fortschritte und Perspektiven.

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.

Fluticasone Propionate Orally Disintegrating Tablet (APT-1011) for Eosinophilic Esophagitis: Randomized Controlled Trial.

BACKGROUND & AIMS: Topical steroids are effective treatments for eosinophilic esophagitis (EoE). The FLUTE (Fluticasone in EoE) trial evaluated safety and efficacy of APT-1011 (fluticasone propionate oral disintegrating tablet) vs placebo for treatment of EoE. METHODS: In this randomized, double-blind, placebo-controlled, dose-finding, phase 2b trial, 106 adults with EoE received 1 of 4 APT-1011 doses or placebo for a 12-week induction period and 40 weeks of maintenance. Primary outcome was histologic response (≤6 eosinophils per high-power field) at Week 12. Secondary outcomes included endoscopic features and dysphagia frequency. RESULTS: Histologic response rates were 0% for placebo, 80% for APT-1011 3 mg twice daily (BID), 67% for 3 mg at bedtime (HS), 86% for 1.5 mg BID, 48% for 1.5 mg HS (P < .001 for all groups vs placebo). At Week 12, mean Edema/Rings/Exudates/Furrows/Strictures (EoE Endoscopic Reference Score) total score (max, 9.0) improved from 4.5 to 2.3 for 3 mg BID, 5.3 to 2.1 for 3 mg HS, 4.6 to 1.7 for 1.5 mg BID, 5.3 to 2.9 for 1.5 mg HS vs 5.2 to 4.5 for placebo. Mean dysphagia frequency over 14 days improved from baseline to Week 12 with all active groups improving more than placebo. Improvements were sustained to Week 52. APT-1011 was safe and well-tolerated, with higher incidence of candidiasis noted at the higher twice daily doses. CONCLUSION: APT-1011 dosing regimens were superior for histologic and endoscopic responses, and for reduction in dysphagia frequency vs placebo. Based on the symptom improvement and assessment of adverse events together with the histologic response rate, 3 mg once daily at bedtime dose showed the most favorable risk-benefit profile. CLINICALTRIALS: gov, Number: NCT03191864.

Diagnostic Delay in Patients With Eosinophilic Esophagitis Has Not Changed Since the First Description 30 Years Ago: Diagnostic Delay in Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic progressive disease. Diagnostic delay (DD) is associated with increased risk of esophageal strictures and food impactions. We aimed to assess the evolution of DD since the first description of EoE in 1993 until 2021. METHODS: We analyzed data from patients prospectively included in the Swiss EoE database. DD was calculated as the time interval between the first occurrence of EoE symptoms and the confirmed diagnosis. DD was analyzed annually over time (1989-2021) and according to milestone publications in the field (1993: first description; 2007: first consensus recommendations; and 2011: updated consensus recommendations). In addition, a Cox proportional hazards model has been used to describe the relation between DD and covariates. RESULTS: Complete data of 1,152 patients (857 male [74%]; median age at diagnosis: 38 years, interquartile range: 28-49, range: 1-86) were analyzed. Overall, median DD was 4 years (interquartile range: 1-11, range, 0-56), with DD ≥ 10 years in 32% of the population. Over time, DD did not significantly change, neither annually nor according to release dates of milestone publications with a persistently stable fraction of roughly one-third of all patients with a DD of ≥10 years. Both ages at diagnosis ( P < 0.001, with an increase in DD up to the age of 31-40 years) and at symptom onset (younger patients had a longer DD; P < 0.001) were significantly associated with DD. DISCUSSION: DD has not changed since the first description of EoE almost 30 years ago and remains substantial. Even today, one-third of patients have a persistently high DD of ≥10 years. Substantial efforts are warranted to increase awareness for EoE and its hallmark symptom, solid food dysphagia, as an age-independent red-flag symptom among healthcare professionals and presumably the general population alike to lower risk of long-term complications.

Safety and efficacy of a novel resection system for direct endoscopic necrosectomy of walled-off pancreas necrosis: a prospective, international, multicenter trial.

BACKGROUND AND AIMS: Direct endoscopic necrosectomy (DEN) of walled-off pancreatic necrosis (WOPN) lacks dedicated instruments and requires repetitive and cumbersome procedures. This study evaluated the safety and efficacy of a new powered endoscopic debridement (PED) system designed to simultaneously resect and remove solid debris within WOPN. METHODS: This was a single-arm, prospective, multicenter, international device trial conducted from November 2018 to August 2019 at 10 sites. Patients with WOPN ≥6 cm and ≤22 cm and with >30% solid debris were enrolled. The primary endpoint was safety through 21 days after the last DEN procedure. Efficacy outcomes included clearance of necrosis, procedural time, adequacy of debridement, number of procedures until resolution, hospital stay duration, and quality of life. RESULTS: Thirty patients (mean age, 55 years; 60% men) underwent DEN with no device-related adverse events. Of 30 patients, 15 (50%) achieved complete debridement in 1 session and 20 (67%) achieved complete debridement within 2 or fewer sessions. A median of 1.5 interventions (range, 1-7) were required. Median hospital stay was 10 days (interquartile range, 22). There was an overall reduction of 91% in percent necrosis within WOPN from baseline to follow-up and 85% in collection volume. Baseline WOPN volume was positively correlated with the total number of interventions (ρ = .363, P = .049). CONCLUSIONS: The new PED system seems to be a safe and effective treatment tool for WOPN, resulting in fewer interventions and lower hospital duration when compared with published data on using conventional instruments. Randomized controlled trials comparing the PED system with conventional DEN are needed. (Clinical trial registration number: NCT03694210.).

Motorized spiral enteroscopy: results of an international multicenter prospective observational clinical study in patients with normal and altered gastrointestinal anatomy.

BACKGROUND : Motorized spiral enteroscopy (MSE) has been shown to be safe and effective for deep enteroscopy in studies performed at expert centers with limited numbers of patients without previous abdominal surgery. This study aimed to investigate the safety, efficacy, and learning curve associated with MSE in a real-life scenario, with the inclusion of patients after abdominal surgery and with altered anatomy. METHODS : Patients with indications for deep enteroscopy were enrolled in a prospective observational multicenter study. The primary objective was the serious adverse event (SAE) rate; secondary objectives were the diagnostic and therapeutic yield, procedural success, time, and insertion depth. Data analysis was subdivided into training and core (post-training) study phases at centers with different levels of MSE experience. RESULTS : 298 patients (120 women; median age 68, range 19-92) were enrolled. In the post-training phase, 21.5 % (n = 54) had previous abdominal surgery, 10.0 % (n = 25) had surgically altered anatomy. Overall, SAEs occurred in 2.3 % (7/298; 95 %CI 0.9 %-4.8 %). The SAE rate was 2.0 % (5/251) in the core group and 4.3 % (2/47) in the training group, and was not increased after abdominal surgery (1.9 %). Total enteroscopy was achieved in half of the patients (n = 42) undergoing planned total enteroscopy. In 295/337 procedures (87.5 %), the anatomical region of interest could be reached. CONCLUSIONS : This prospective multicenter study showed that MSE was feasible and safe in a large cohort of patients in a real-life setting, after a short learning curve. MSE was shown to be feasible in postsurgical patients, including those with altered anatomy, without an increase in the SAE rate.

A novel Cereblon E3 ligase modulator with antitumor activity in gastrointestinal cancer.

Targeted protein degradation offers new opportunities to inactivate cancer drivers and has successfully entered the clinic. Ways to induce selective protein degradation include proteolysis targeting chimera (PROTAC) technology and immunomodulatory (IMiDs) / next-generation Cereblon (CRBN) E3 ligase modulating drugs (CELMoDs). Here, we aimed to develop a MYC PROTAC based on the MYC-MAX dimerization inhibitor 10058-F4 derivative 28RH and Thalidomide, called MDEG-541. We show that a subgroup of gastrointestinal cancer cell lines and primary patient-derived organoids are MDEG-541 sensitive. Although MYC expression was regulated in a CRBN-, proteasome- and ubiquitin-dependent manner, we provide evidence that MDEG-541 induced the degradation of CRBN neosubstrates, including G1 to S phase transition 1/2 (GSPT1/2) and the Polo-like kinase 1 (PLK1). In sum, we have established a CRBN-dependent degrader of relevant cancer targets with activity in gastrointestinal cancers.

Endoscopic vacuum therapy in the upper gastrointestinal tract: when and how to use it.

BACKGROUND: Endoscopic vacuum therapy (EVT) has emerged as a novel treatment option for upper gastrointestinal wall defects. The basic principle of action of EVT entails evacuation of secretions, removal of wound debris, and containment of the defect. Furthermore, there is increasing evidence that EVT reduces interstitial edema, increases oxygen saturation, and promotes tissue granulation and microcirculation. Various devices, such as macroporous polyurethane sponge systems or open-pore film drains, have been developed for specific indications. Depending on the individual situation, EVT devices can be placed in- or outside the intestinal lumen, as a stand-alone procedure, or in combination with surgical, radiological, and other endoscopic interventions. PURPOSE: The aim of this narrative review is to describe the current spectrum of EVT in the upper gastrointestinal tract and to assess and summarize the related scientific literature. CONCLUSIONS: There is growing evidence that the efficacy of EVT for upper GI leakages exceeds that of other interventional treatment modalities such as self-expanding metal stents, clips, or simple drainages. Owing to the promising results and the excellent risk profile, EVT has become the therapy of choice for perforations and anastomotic leakages of the upper gastrointestinal tract in many centers of expertise. In addition, recent clinical research suggests that preemptive use of EVT after high-risk upper gastrointestinal resections may play an important role in reducing postoperative morbidity.

Management of eosinophilic esophagitis associated food impaction in Europe and the United States.

Eosinophilic esophagitis (EoE) is the most common cause of esophageal food impaction (EFI). Approaches to management of EFI due to EoE have not been well characterized. We conducted a web-based survey to understand approaches to management of EFI due to EoE among endoscopists. Questions focused on management of patients from presentation to post-endoscopy follow-up. The survey was administered to a list of eligible candidates provided by societies of gastroenterology. A total of 308 endoscopists completed the questionnaire. The majority (83%) practiced in Europe and treated adults (78%). Most agreed patients should be advised to seek emergency care (66%) within 1 to 2 hours (41% agreement). There was agreement that medications to induce vomiting should be avoided (84%) and that blood tests or imaging studies were usually not required before endoscopy. By contrast, there was more variability in the type of sedation recommended and the need for endotracheal intubation, especially when comparing more experienced with less experienced EoE-endoscopists. Overall, fewer than half (43%) respondents recommended obtaining esophageal biopsies during the initial endoscopy. However, there were significant differences in the proportion who recommended biopsies based on level of EoE-experience (25, 52, 77%, P < 0.001; less vs. moderate vs. very experienced) and comparing pediatric and adult endoscopists (32, vs. 79%, P < 0.001; adult vs. pediatric). There exists heterogeneity among endoscopists in recommendations to manage EFI in patients with EoE. These findings support development of clinical guidelines and new studies to clarify the rationale for best practices. Key summary: Established knowledge-The optimal management of patients with esophageal food impaction due to eosinophilic esophagitis from presentation at the emergency department to postendoscopy care is unclear. New findings-Considerable recommendation variation exists in the management of EFI in patients with EoE. Our findings provide a rationale for the creation of consensus practice guidelines and further study into best practices.

Anastomotic leakage following resection of the esophagus-introduction of an endoscopic grading system.

BACKGROUND: Malignant tumors of the esophagus are the sixth leading cause of cancer-related deaths worldwide. Postoperative leakage of the esophago-gastrostomy leads to mediastinal sepsis, which is still associated with a high morbidity and mortality rate. The aim of this study was to describe the endoscopic view of the different severity grades of an anastomotic leakage. METHODS: Patients Between June 2016 and September 2018, 144 patients were operated upon in the Department of Surgery, University of Munich, Germany. Among these patients, 34 (23.6%) presented with a leakage of the anastomosis. Endoscopy In this retrospective analysis, the focus is to describe different patterns of leakage of the anastomosis. RESULTS: We studied 34 patients in whom post-esophagectomy leakage of the anastomosis was detected and treated with an endoluminal vacuum sponge system. The leakage healed in 26 of 29 patients (success rate 89.7%). With the increasing severity of leakage, the treatment time and the in-hospital mortality correspondingly increased. Furthermore, the incidence of the development of a fistula to the tracheobronchial system increased with higher grades of leakage. CONCLUSIONS: Exact descriptions of leakage are necessary to compare the cases and to prove post-treatment improvement. This is, to our knowledge, the first publication to present a leakage grading score in patients after esophagectomy including reconstruction with a gastric tube. This new grading system needs to be tested in further analyses, with a special focus on prospective analysis.

Budesonide Orodispersible Tablets Maintain Remission in a Randomized, Placebo-Controlled Trial of Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder. Swallowed topical-acting corticosteroids are effective in bringing active EoE into remission. However, it is not clear whether these drugs are effective for long-term maintenance of remission. METHODS: We performed a double-blind trial to compare the efficacy and safety of 2 dosages of a budesonide orodispersible tablet (BOT) vs placebo in maintaining remission of EoE. Maintenance of remission was defined as absence of clinical and histologic relapse and no premature withdrawal for any reason. Two hundred and four adults with EoE in clinical and histologic remission, from 29 European study sites, were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. RESULTS: At end of treatment, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (P < .001 for both comparisons of BOT with placebo). Median time to relapse in the placebo group was 87 days. The frequency of adverse events was similar in the BOT and placebo groups. Morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. CONCLUSIONS: In a phase 3 trial, up to 48 weeks of treatment with BOT (0.5 mg or 1.0 mg twice daily) was superior to placebo in maintaining remission of EoE. Both dosages were equally effective and well tolerated. EudraCT number; 2014-001485-99; ClinicalTrials.gov number, NCT02434029.

Curriculum for ERCP and endoscopic ultrasound training in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement.

The European Society of Gastrointestinal Endoscopy (ESGE) has recognized the need to formalize and enhance training in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS). This manuscript represents the outcome of a formal Delphi process resulting in an official Position Statement of the ESGE and provides a framework to develop and maintain skills in ERCP and EUS. This curriculum is set out in terms of the prerequisites prior to training; recommended steps of training to a defined syllabus; the quality of training; and how competence should be defined and evidenced before independent practice. 1: Trainees should be competent in gastroscopy prior to commencing training. Formal training courses and the use of simulation in training are recommended. 2: Trainees should keep a contemporaneous logbook of their procedures, including key performance indicators and the degree of independence. Structured formative assessment is encouraged to enhance feedback. There should be a summative assessment process prior to commencing independent practice to ensure there is robust evidence of competence. This evidence should include a review of a trainee's procedure volume and current performance measures. A period of mentoring is strongly recommended in the early stages of independent practice. 3: Specifically for ERCP, all trainees should be competent up to Schutz level 2 complexity (management of distal biliary strictures and stones > 10 mm), with advanced ERCP requiring a further period of training. Prior to independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 300 cases, a native papilla cannulation rate of ≥ 80 % (90 % after a period of mentored independent practice), complete stones clearance of ≥ 85 %, and successful stenting of distal biliary strictures of ≥ 90 % (90 % and 95 % respectively after a mentored period of independent practice). 4: The progression of EUS training and competence attainment should start from diagnostic EUS and then proceed to basic therapeutic EUS, and finally to advanced therapeutic EUS. Before independent practice, ESGE recommends that a trainee can evidence a procedure volume of > 250 cases (75 fine-needle aspirations/biopsies [FNA/FNBs]), satisfactory visualization of key anatomical landmarks in ≥ 90 % of cases, and an FNA/FNB accuracy rate of ≥ 85 %. ESGE recognizes the often inadequate quality of the evidence and the need for further studies pertaining to training in advanced endoscopy, particularly in relation to therapeutic EUS.

Aspergillus fumigatus cholangitis in a patient with cholangiocarcinoma: case report and review of the literature.

Aspergillus spp. cholangitis is an uncommon presentation of invasive aspergillosis. Only few cases are described in the literature affecting severely immunocompromised patients or patients following biliary surgery. Especially, invasive aspergillosis in non-haematological patients is associated with high mortality rates, caused by atypical presentations, which is associated with a delay in diagnosis and therapy. We report a 72-year-old man with primary diagnosis of cholangiocarcinoma and stent implantation by endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression who developed severe cholangitis with invasive aspergillosis. The patient had no history of prior hospitalisation, no immunosuppressive therapy and no preceding biliary surgery. Furthermore, in this exceptional case of extrapulmonary aspergillosis, there were no signs of pulmonary involvement. From the literature review, only three cases of Aspergillus cholangitis could be identified. Clinical manifestations of invasive aspergillosis can be variable and classical risk factors such as immunosuppression are not mandatorily present. Clinical awareness of these rare cases is of vital importance for initiation of correct therapy.

Endoscopic and percutaneous biliary interventions in patients with altered upper gastrointestinal anatomy-the Munich Multicenter Experience.

BACKGROUND: In patients with altered upper gastrointestinal anatomy, conventional endoscopic retrograde cholangiography is often not possible and different techniques, like enteroscopy-assisted or percutaneous approaches are required. Aim of this study was to analyze success and complication rates of these techniques in a large collective of patients in the daily clinical practice in a pre-endosonographic biliary drainage era. PATIENTS AND METHODS: Patients with altered upper gastrointestinal anatomy with biliary interventions between March 1st, 2006, and June 30th, 2014 in four tertiary endoscopic centers in Munich, Germany were retrospectively analyzed. RESULTS: At least one endoscopic-assisted biliary intervention was successful in 234/411 patients (56.9%)-in 192 patients in the first, in 34 patients in the second and in 8 patients in the third attempt. Success rates for Billroth-II/Whipple-/Roux-en-Y reconstruction were 70.5%/56.7%/49.5%. Complication rates for these reconstructions were 9.3%/6.5%/6.3%, the overall complication rate was 7.1%. Success rates were highest in patients with Billroth-II reconstruction where use of a duodenoscope was possible, complication rates were also highest in this scenario. Success rates were lowest in longer-limb anatomy like Roux-en-Y reconstruction. Percutaneous biliary drainages (PTBD) were inserted 268 times with substantially higher success (90.7%) as well as complication rates (11.6%) compared to the endoscopic approach. Compared to patients treated endoscopically, patients with PTBD had a lower performance status, more severe cholestasis and a significant higher rate of malignant underlying disease. CONCLUSION: In patients with altered upper gastrointestinal anatomy, success rates of endoscopic-assisted biliary interventions are lower compared to PTBD. Still, due to the beneficial complication rates of the endoscopic approach, this technique should be preferred whenever possible and in selected patients who still need to be defined in detail, repeated endoscopic attempts are useful to help achieve the desired result.

[Treatment of eosinophilic esophagitis - advancements and perspectives]. / Therapie der eosinophilen Ösophagitis ­ Fortschritte und Perspektiven.

In recent years significant progress has been made in the treatment of eosinophilic esophagitis (EoE), especially in the area of topical corticosteroids. Novel EoE-specific formulations have been developed and first approvals have been obtained for induction and maintenance of remission in adult EoE patients with the orodispersible budesonide tablet in Germany and other European and non-EU countries. A novel budesonide oral suspension is currently under priority review by the FDA for first approval in the U.S. In contrast, the scientific evidence on the efficacy of proton pump inhibitors remains limited. Moreover, new biologicals have been identified which showed promising results in phase 2 trials and are now being studied in phase 3. This article aims to summarize and discuss recent advances and perspectives in the treatment of EoE.

Efficacy of Budesonide Orodispersible Tablets as Induction Therapy for Eosinophilic Esophagitis in a Randomized Placebo-Controlled Trial.

BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE. METHODS: We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily). RESULTS: At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent. CONCLUSIONS: In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

IgG4 is Elevated in Eosinophilic Esophagitis but Not in Gastroesophageal Reflux Disease Patients.

BACKGROUND: For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients. METHODS: Prospectively collected serum samples of 17 EoE patients before and after 8 weeks of therapy with budesonide (1 mg BID) were analyzed for total and antigen-specific IgG4 and IgE levels. Also, immunohistochemical analysis of total and IgG4-positive plasma cells was performed on esophageal biopsies of these patients. In total, 14 GERD patients without histologic proof of eosinophilic infiltration were taken as a control group. RESULTS: Total IgG4 serum levels in EoE patients were significantly higher than in GERD patients (121.0 vs. 71.2 mg/dL; P=0.038) and decreased under budesonide therapy (121.0 vs. 104.2 mg/dL; P=0.019). IgE levels did not differ significantly between all groups. In EoE patients also a high number of esophageal IgG4-positive plasma cells was detected and significantly reduced under therapy (29.1 vs. 0.1 IgG4-positive cells; P<0.001). In GERD patients no relevant esophageal plasma cell infiltration could be seen. CONCLUSIONS: In EoE patients elevated systemic IgG4 serum levels compared with GERD patients can be seen and decrease under topical steroid therapy. Also, local IgG4 plasma cells expression is high in EoE, but not in GERD patients and normalize under therapy. These findings are further proof for a possible association of EoE with IgG4.