Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Weight-Loss Endoscopy Trial: A Multicenter, Randomized, Controlled Trial Comparing Weight Loss in Endoscopically Implanted Duodenal-Jejunal Bypass Liners versus Intragastric Balloons versus a Sham Procedure.

INTRODUCTION: Obesity is associated with reduced life expectancy and various comorbidities. Surgical interventions are effective but accompanied by the risk of serious complications. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). A randomized, sham-controlled study comparing both procedures has not been undertaken so far. METHODS: We performed a randomized, patient- and assessor-blinded, controlled trial comparing weight loss in IB versus DJBL versus a sham procedure (2:2:1 ratio). Patients with a BMI >35 kg/m2 or >30 with obesity-related comorbidities were included. The IB was removed after 6 months and the DJBL after 12 months. The main objective was successful weight loss (>10% from baseline) 12 months after explantation of the devices. Secondary outcomes were changes in comorbidities, quality of life, and complications. RESULTS: Thirty-three patients were randomized. Recruitment has to be stopped suddenly in after the DJBL device lost its CE mark in Europe. In all, 11 patients received DJBL, 15 IB, and 7 were allocated to the sham group. Blinding was feasible in all patients. Weight decreased from baseline until explantation (DJBL: 129.4 ± 28.3 kg to 107.4 ± 16.7 kg; IB: 118.3 ± 22.8 kg to 107.4 ± 25.7 kg; sham: 134.6 ± 18.0 kg to 131.2 ± 14.3 kg), but patients regained weight almost to the baseline level 12 months after explantation. Only 1 patient in IB group reached the primary endpoint. Severe device-related complications were very rare. CONCLUSION: Endoscopic bariatric procedures failed to achieve effective weight loss 12 months after explantation of the devices. The results of this trial need to be interpreted with caution due to its early termination.

GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Comparison between traumatic and atraumatic over-the-scope clips in patients with duodenal ulcer bleeding: a retrospective analysis with propensity score-based matching.

BACKGROUND AND AIMS: Over-the-scope clips (OTSCs) substantially improved the endoscopic armamentarium for the treatment of severe GI bleeding and can potentially overcome limitations of standard clips. Data indicate a superiority of OTSCs in hemostasis as first- and second-line therapy. However, the impact of the OTSC designs, in particular the traumatic (-t) or atraumatic (-a) type, in duodenal ulcer bleeding has not been analyzed so far. METHODS: This was a retrospective analysis of a prospective collected database from 2009 to 2020 of 6 German endoscopic centers. All patients who underwent emergency endoscopy and were treated using an OTSC for duodenal ulcer bleeding were included. OTSC-t and OTSC-a patients were compared by the Fisher exact test, χ2 test, or Mann-Whitney U test as appropriate. A propensity score-based 1:1 matching was performed to obtain equal distribution of baseline characteristics in both groups. RESULTS: The entire cohort comprised 173 patients (93 OTSC-a, 80 OTSC-t). Age, gender, anticoagulant therapy, Rockall score, and treatment regimen had similar distributions in the 2 groups. However, the OTSC-t group showed significantly more active bleeding ulcers (Forrest Ia/b). Matching identified 132 patients (66 in both groups) with comparable baseline characteristics. Initial bleeding hemostasis (OTSC-a, 90.9%; OTSC-t, 87.9%; P = .82) and 72-hour mortality (OTSC-a, 4.5%; OTSC-t, 6.0%; P > .99) were not significantly different, but the OTSC-t group revealed a clearly higher rate of recurrent bleeding (34.9% vs 7.6%, P < .001) and necessity of red blood cell transfusions (5.1 ± 3.4 vs 2.5 ± 2.4 concentrates, P < .001). CONCLUSIONS: For OTSC use, the OTSC-a should be the preferred option for duodenal ulcer bleeding.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Diagnosis of esophageal motility disorders - Significance of the new Chicago classification v4.0]. / Diagnostik von Motilitätsstörungen des Ösophagus ­ Bedeutung der neuen Chicago-Klassifikation v4.0.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2021 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

[Therapy of esophageal motility disorders]. / Therapieoptionen von primären Motilitätsstörungen des Ösophagus.

Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice.

Over-the-scope-clips versus standard treatment in high-risk patients with acute non-variceal upper gastrointestinal bleeding: a randomised controlled trial (STING-2).

OBJECTIVE: Acute non-variceal upper gastrointestinal bleeding (NVUGIB) is managed by standard endoscopic combination therapy, but a few cases remain difficult and carry a high risk of persistent or recurrent bleeding. The aim of our study was to compare first-line over-the-scope-clips (OTSC) therapy with standard endoscopic treatment in these selected patients. DESIGN: We conducted a prospective, randomised, controlled, multicentre study (NCT03331224). Patients with endoscopic evidence of acute NVUGIB and high risk of rebleeding (defined as complete Rockall Score ≥7) were included. Primary endpoint was clinical success defined as successful endoscopic haemostasis without evidence of recurrent bleeding. RESULTS: 246 patients were screened and 100 patients were finally randomised (mean of 5 cases/centre and year; 70% male, 30% female, mean age 78 years; OTSC group n=48, standard group n=52). All but one case in the standard group were treated with conventional clips. Clinical success was 91.7% (n=44) in the OTSC group compared with 73.1% (n=38) in the ST group (p=0.019), with persistent bleeding occurring in 0 vs 6 in the OTSC versus standard group (p=0.027), all of the latter being successfully managed by rescue therapy with OTSC. Recurrent bleeding was observed in four patients (8.3%) in the OTSC group and in eight patients (15.4%) in the standard group (p=0.362). CONCLUSION: OTSC therapy appears to be superior to standard treatment with clips when used by trained physicians for selected cases of primary therapy of NVUGIB with high risk of rebleeding. Further studies are necessary with regards to patient selection to identify subgroups benefiting most from OTSC haemostasis. TRIAL REGISTRATION NUMBER: NCT03331224.

Photochemical Internalization of Gemcitabine Is Safe and Effective in Locally Advanced Inoperable Cholangiocarcinoma.

BACKGROUND: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA). METHODS: The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy. RESULTS: Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose. CONCLUSION: Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.

Case report - Selective internal radiation therapy (SIRT) in a patient with hyperinsulinemic hypoglycemia due to a metastatic insulinoma with late onset of endocrine activity.

Insulinomas are the most common functioning pancreatic neuroendocrine tumors (NET), which can lead to hyperinsulinemic hypoglycemia. In advanced metastatic stages of the disease, the prognosis is poor. Patients with hormonally active insulinomas primarily present with features of neuroglycopenia. Transformation from a nonfunctional to a functional NET is rare. Here, we present a case of a 59-year-old male adult with a metastatic insulinoma and late onset of endocrine activity. Besides medical treatment with Diazoxide and small frequent feedings, continuous intravenous glucose application was eventually required to avoid hypoglycemia. Furthermore, we show that selective internal radiation therapy (SIRT) can be an effective therapeutic approach for symptom reduction in advanced metastatic disease.

[Interventional endoscopic treatment in acute pancreatitis]. / Interventionelle endoskopische Therapie bei akuter Pankreatitis.

BACKGROUND: Acute pancreatitis (AP) represents a frequent gastrointestinal diseases. Approximately 80% of patients have a mild course of the disease and conservative treatment is sufficient; however, 20% of patients develop a severe AP with local and systemic complications. This article focuses on the currently recommended endoscopic management of severe AP. OBJECTIVE: Classification of AP by the revised Atlanta classification and the occurrence of local or systemic complications. Summary of current evidence with respect to endoscopic management. MATERIAL AND METHODS: Inspection of the current literature from specialist journals and current guidelines. RESULTS: The AP is classified as mild, moderate or severe based on systemic (hypotension, renal failure, lung failure) and/or local complications, such as acute peripancreatic fluid collections (APFC), peripancreatic pseudocysts (PPC), acute necrotic collections (ANC) and walled-off necrosis (WON). In recent years the staged endoscopic treatment of infected ANC, WON and PPC has become established. The initial step is the endoscopic ultrasound-guided puncture and drainage with plastic or lumen-apposing metal stents. For solid components or insufficient drainage, a transgastric endoscopic necrosectomy is recommended. The treatment of severe AP requires an interdisciplinary management in specialized centers and regular re-evaluation of the therapeutic efficacy. CONCLUSION: Interventional endoscopy has become established as the standard for treatment of severe AP.

NUPR1 preserves insulin secretion of pancreatic ß-cells during inflammatory stress by multiple low-dose streptozotocin and high-fat diet.

Obesity is associated with dyslipidemia and subclinical inflammation that promotes metabolic disturbances including insulin resistance and pancreatic ß-cell dysfunction. The nuclear protein, transcriptional regulator 1 (NUPR1) responds to cellular stresses and features tissue protective properties. To characterize the role of NUPR1 in endocrine pancreatic islets during inflammatory stress, we generated transgenic mice with ß-cell-specific Nupr1 overexpression (ßNUPR1). Under normal conditions, ßNUPR1 mice did not differ from wild type (WT) littermates and display normal glucose homeostasis and ß-cell mass. For induction of inflammatory conditions, mice were treated with multiple low-dose streptozotocin (mld-STZ) and/or fed a high-fat diet (HFD). All treatments significantly worsened glycaemia in WT mice, while ßNUPR1 mice substantially preserved insulin secretion and glucose tolerance. HFD increased ß-cell mass in all animals, with ßNUPR1 mice tending to show higher values. The improved outcome of ßNUPR1 mice was accompanied by decreased NF-κB activation and lymphocyte infiltration in response to mld-STZ. In vitro, isolated ßNUPR1 islets preserved insulin secretion and content with insignificantly low apoptosis during culture stress and IL-1ß exposure. These findings suggest that NUPR1 plays a vital role in the protection of ß-cells from apoptosis, related degradation of insulin storages and subsequent secretion during inflammatory and obesity-related tissue stress.

[Barrett-Screening: Rational, current concepts and perspectives]. / Barrett-Screening: rationale, aktuelle Konzepte und Perspektiven.

Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness - 8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people "at risk", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials.

Endoscopic full-thickness transoral outlet reduction with semicircumferential endoscopic submucosal dissection.

BACKGROUND: Endoscopic full-thickness transoral outlet reduction (efTOR) is a therapeutic option to reduce a dilated gastrojejunal anastomosis (GJA) after Roux-en-Y gastric bypass (RYGB). Mucosal ablation with argon plasma coagulation (APC) is usually performed to achieve tissue adaptation. However, rupture of sutures before scarring can lead to recurrent dilatation of the GJA. Here, we describe efTOR with a semicircumferential endoscopic submucosal dissection (ESD-efTOR) as an alternative to APC-efTOR. METHODS: We enrolled 41 patients with comparable baseline characteristics (APC-efTOR 26; ESD-efTOR 15). The main objectives were reduction in the GJA diameter and in ruptured sutures. Technical success, complications, total weight loss (TWL), and percentage of total and excess weight loss (%TWL and %EWL) at 3 and 12 months, were assessed. RESULTS: ESD-efTOR resulted in significantly fewer ruptured sutures (20 % vs. 69 %; P = 0.004) and a greater reduction in the GJA (major 20 % vs. 0 %; minor 54 % vs. 37 %; no reduction 13 % vs. 58 %; P = 0.02) after 3 months. Technical efficacy, examination time, and rate of complications were comparable. CONCLUSIONS: ESD-efTOR resulted in a significantly greater reduction in the GJA diameter and a lower risk of ruptured sutures compared with APC-efTOR.

In-depth characterization of the Wnt-signaling/ß-catenin pathway in an in vitro model of Barrett's sequence.

BACKGROUND: An altered Wnt-signaling activation has been reported during Barrett's esophagus progression, but with rarely detected mutations in APC and ß-catenin (CTNNB1) genes. METHODS: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3ß was performed in an in vitro cell culture model of Barrett's esophagus. Representing the Barrett's sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. RESULTS: A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett's metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1-10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. CONCLUSION: Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett's esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett's progression and the underlying pathological mechanisms.

[Barrett-Screening: Rational, current concepts and perspectives]. / Barrett-Screening: Rationale, aktuelle Konzepte und Perspektiven.

Though showing an increasing incidence over the past 20 years, esophageal adenocarcinoma (EAC) remains a rather uncommon cancer (i. e., compared to colorectal and gastric cancer). Once detected, the prognosis of this cancer entity is still very poor. Hence, in spite of some unfavorable prerequisites to systematic screening, the development of a screening concept for Barrett's esophagus (BE) and EAC seems worthwhile. Nowadays, screening for BE and EAC is based on conventional endoscopy, mostly conducted individually in patients with reflux complaints (gastroesophageal reflux disease-GERD). Biopsies are taken obligatorily and are the centerpiece of diagnosis and scheduling of surveillance. So far, endoscopy is the diagnostic gold standard, but it is expensive and obviously lacks effectiveness-8 of 10 cases of EAC are not detected in endoscopic screening (and surveillance) but by an opportunistic first-time endoscopy. Therefore, new methods for BE/EAC screening are strongly desirable. Research must be concentrated to favor procedures applicable for a screening of the population in a primary care setting. For that, the first step needs to consist of identifying a subgroup of people "at risk", which in a second step can be risk assessed and followed up by endoscopy and biopsy. From all screening variants, which have been actually tested in clinical application and experimental research, biomarker-based techniques seem to be most promising. Among those-under the aspect of costs and practicability-the Cytosponge, in addition with a panel of biomarkers, seemed to be promising in clinical trials.

Successful endoscopic recanalization of complete pharyngoesophageal obstruction after therapy of head and neck cancer.

BACKGROUND: Neopharyngeal obstruction after therapy of head and neck cancer is a frequent and clinically challenging problem without evidence-based guideline recommendations. CASE: We present two cases of complete esophageal obstruction after treatment for head and neck cancer. Due to complete obstruction of long distance stricture standard dilatation procedures were impossible to perform. In both cases, recanalization was achieved by combining an antegrade with a retrograde maneuver. In one patient endoscopic cutting with a papillotome was needed. CONCLUSION: Even in complex cases of post-therapeutic stenosis an endoscopic approach may offer a feasible alternative to surgical therapy, especially in the subset of frail patients.

Severe ileocecal inflammatory syndrome in adult patients with cystic fibrosis.

The relevance of gastrointestinal manifestations of cystic fibrosis (CF) is increasing due to an improved life expectancy. We report on 2 adult patients with prior lung transplantation who presented with a severe inflammatory disorder of the ileocecal region. One patient underwent ileocecal resection; the second patient died after emergency surgery for intestinal perforation. Both cases did not show typical signs of CF-related distal intestinal obstruction syndrome or extensive fibrosing colonopathy. However, the clinical and histopathological findings revealed CF-induced inflammatory alterations of the intestinal mucosa. Thus, these cases illustrate a further CF-related bowel disorder, which can be especially relevant in long-term CF survivors.