Endoscopic submucosal dissection for early esophageal adenocarcinoma: low rates of metastases in mucosal cancers with poor differentiation

Background and aims Endoscopic resection (ER) is accepted as standard treatment for intramucosal esophageal adenocarcinoma (EAC) with well or moderate differentiation. Poor differentiation (PD) is judged as a risk factor for lymph node metastasis (LNM) and surgery is recommended. However, the evidence for this recommendation is weak. Study aim was to analyze the clinical course of patients after ER of EAC with PD. Patients and methods Patients undergoing endoscopic submucosal dissection for EAC were included from 16 German centers. Inclusion criteria were PD in the resection specimen, R0 resection and endoscopic follow-up. Primary outcome was the metastasis rate during follow-up. Analysis was performed retrospectively in a prospectively collected database. Results 25 patients with PD as single risk factor (group A) and 15 patients with PD and additional risk factors (submucosal invasion and/or lymphovascular invasion) were included. The metastasis rate was was 1/25 (4.0%; 95%CI 0.4-17.2) in group A and 3/15 (20.0%; 95%CI 6.0-44.4%) in group B, respectively (p=0.293). The rate of EAC-associated deaths was 1/25 (4%; 95%CI 0.4-17.2%) versus 3/15 (20%; 95%CI 6.0-44.4%) in group B (p=0.293) while the overall death rate was 7/25 (28.0%; 95%CI 13.5-47.3%) versus 3/15 (20%; 95%CI 6.0-44.4%) (p=0.715). Median follow-up was 30 months (IQR 15-53). Conclusions During long-term follow-up the risk of metastasis is low after ER of mucosal EAC with PD as single risk factor. A conservative approach seems justified in this small patient group. However, the treatment strategy has to be determined on an individualized basis until further prospective data are available

Risk factors and outcome in patients with primary sclerosing cholangitis with persistent biliary candidiasis

Background: Candidiasis is commonly observed in patients with primary sclerosing cholangitis (PSC), but the clinical risk factors associated with its presence have not been fully investigated. In this study, we aimed to analyse the incidence, risk factors, and transplantation-free survival in primary sclerosing cholangitis (PSC) patients with persistent biliary candidiasis. Methods: We retrospectively analysed patients diagnosed with PSC who were admitted to our department during 2002 to 2012. One-hundred fifty patients whose bile cultures were tested for fungal species were selected, and their clinical and laboratory parameters were investigated. The results of endoscopic retrograde cholangiography (ERC) and bile cultures were analysed using chart reviews. The cases of biliary candidiasis were sub-classified as transient or persistent. Results: Thirty out of 150 (20.0%) patients had biliary candidiasis. Although all patients demonstrated comparable baseline characteristics, those with biliary candidiasis showed significantly reduced transplantation-free survival (p < 0.0001) along with a markedly elevated frequency of cholangiocarcinoma (CCA) (p = 0.04). The patients were further sub-classified according to the transient (15/30) or persistent (15/30) nature of their biliary candidiasis. A subgroup analysis showed reduced survival with a greater necessity for orthotopic liver transplantation (OLT) only in patients with persistence of Candida (p = 0.007). The survival in the patients with transient biliary candidiasis was comparable to that in candidiasis-free patients. In a multivariate regression analysis that included Mayo risk score (MRS), sex, age, dominant stenosis, inflammatory bowel disease, autoimmune hepatitis overlap syndrome, and number of times ERC was performed, biliary candidiasis was an independent risk factor for reduced survival (p = 0.008). Risk factors associated with acquisition of biliary candidiasis were age at PSC diagnosis and number of ERCs. Conclusions: The persistence of biliary candidiasis is associated with markedly reduced transplantation-free survival in PSC patients. By contrast, actuarial survival in patients with transient biliary candidiasis approaches that for patients without any evidence of biliary candidiasis. Further studies on the treatment of persistent biliary candidiasis in patients with PSC are warranted

Cold versus hot snare endoscopic resection of large non-pedunculated colorectal polyps (randomized-controlled German CHRONICLE-trial)

Background and aims Endoscopic mucosal resection (EMR) is standard therapy for non-pedunculated colorectal polyps ≥20mm. Recently, it has been suggested that polyp resection without current (cold resection) may be superior to the standard technique using cutting/coagulation current (hot resection) by reducing adverse events (AE), but evidence from a randomized trial is missing. Methods In this randomized-controlled multicentric trial involving 19 centers, non-pedunculated colorectal polyps ≥20mm were randomly assigned to cold or hot EMR. Primary outcome was major AE (perforation or post-endoscopic bleeding). Among secondary outcomes major AE subcategories, postpolypectomy-syndrome and residual adenoma were most relevant. Results Between 2021 and 2023, 396 polyps in 363 patients (48.2% female) were enrolled for the intention-to-treat analysis. Major AE occurred in 1.0 % in the cold and in 7.9% in the hot group (p=0.001; Odds ratio [OR] 0.12 [95%-CI: 0.03-0.54]). Rates for perforation and post-endoscopic bleeding were significantly lower in the cold group with 0% vs. 3.9% (p=0.007) and 1.0% vs. 4.4% (p=0.040). Postpolypectomy-syndrome occurred with similar frequency (3.1% vs. 4.4%, p=0.490). After cold resection, residual adenoma was found more frequently, with 23.7% vs. 13.8% (p=0.020; OR 1.94 [95%-CI: 1.12-3.38]). In multivariable analysis, lesion diameter of ≥4cm was an independent predictor both for major AE (OR 3.37) and residual adenoma (OR 2.47), and high-grade dysplasia/cancer for residual adenoma (OR 2.92). Conclusion Cold resection of large non-pedunculated colorectal polyps appears considerably safer than hot EMR, however at the cost of a higher residual adenoma rate. Further studies have to confirm to which extent polyp size and histology can determine an individualized approach (Trial number: DRKS00025170)

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

Identification of biomarkers for exposure of human oral mucosa to heavy metals or polycyclic aromatic hydrocarbons

Menschliche Mundschleimheut wurde ex-vivo gegenüber Schwermetallen (Blei) oder polyzyklischen aromatischen Kohlenwasserstoffen (Benzopyren) für Zeiten von 5Min. bis 360Min exponiert. Immunhistochemisch wurdne im Anschluss Marker für Apoptose, oxitaven und nitrogenen Stress untersucht. Hierbei zeigten sich jeweils charakteristische Veränderungen für aktive Caspase-3, 3-Nitrotyrosine und 8-epi-PGF2alpha. Proben von Rauchern wurden mit Nichtraucherproben verglichen und zeigten verminderte Werte für oxidativen und nitrogenen Stress.In this study samples of human oral mucosa were ex-vivo exposed to lead or benzopyrene to further investigate the influence of heavy metals and polycyclic aromatic hydrocarbons on apoptosis and generation of oxidative and nitrosative stress in human oral mucosa. Immunhistochemical staining was done for active-caspase-3, 8-epi-PGF2a and 3-nitrotyrosine as biomarkers for apoptosis as well as oxidative and nitrosative stress. Samples obtained from smokers where furthermore compared to non-smokers' samples. Activation of apoptosis and generation of oxidative and nitrosative stress already occured in oral mucosa cells after short-term, one-time exposure to lead or benzopyrene and is not limited to chronic exposure. In smokers' samples there seems to be a reduced generation of reactive oxygen or nitrogen species after exposure to benzopyrene

A novel device for the endoscopic management of buried bumper syndrome

Background Buried bumper syndrome (BBS) is a complication of percutaneous endoscopic gastrostomy (PEG) in which the internal bumper is overgrown by the gastric mucosa. Apart from loss of patency of the PEG tube, the buried bumper may evoke symptoms such as abdominal pain or peritubular leakage. While the management of an incompletely buried bumper is fairly straightforward, this is not the case for a completely buried bumper. Different approaches to remove completely buried bumpers have been described, including endoscopic knife- or papillotome-based techniques. However, these devices are used off-label and the procedures can be laborious. Methods The Flamingo device has recently been introduced as the first tool specifically designed to remove a completely buried bumper. Results We describe the technique and our first experience in five patients with a completely (n=4) or almost completely (n=1) buried bumper. Fast and save removal of the buried bumper was obtained in all patients. Conclusion We believe that this device has the potential to become the standard first-line tool for the management of completely buried bumpers

Slow ventricular tachycardia presenting with acute liver failure

Objectives: Cardiac hepatopathy is an important differential diagnosis of acute liver failure. Slow ventricular tachycardia (slow VT) is a ventricular tachycardia (VT), in which heart rate is below the typical frequency of VT. We here report a case of acute liver failure in a patient with slow VT. Methods: The 64-year old male patient with history of cardiac pacemaker implantation for complete atrioventricular block was referred to our intensive care unit because of acute liver failure. Results: Workup identified cardiac failure as cause of hepatopathy; however, reason for cardiac failure remained unknown even after left heart catheterization with coronary angiography. Finally, the analysis of cardiac pacemaker recordings led to the diagnosis of slow VT. This could not be terminated with either electric cardioversion or pharmacological treatment, and the patient died of cardiac failure. Conclusion: Diagnosis of VT can be challenging if occurring at unexpected slow heart rates. Analysis of pacemaker recordings could help to make the diagnosis of slow VT

Additional file 1 of Comparative proteomics reveals different protein expression in platelets in patients with alcoholic liver cirrhosis

Additional file 1. 2D gel of healthy control. Exemplary two-dimensional gel of a healthy control