Esophageal duplication cysts: a clinical practice review.

Esophageal duplication represents one of the most common types of bronchopulmonary foregut malformations. These rare congenital anomalies occur secondary to embryological aberrations between the 4th and 8th weeks of gestation. In order to be classified as an esophageal cyst a mediastinal cyst must have a close proximity with the esophagus, be lined by alimentary (squamous epithelium) or tracheobronchial mucosa and covered by two smooth muscle layers. These rare anomalies are often asymptomatic during adulthood. However, they can cause symptoms in early childhood, generally during the first 2 years of life. Variations in location, size, presence or absence of heterotopic mucosa, will dictate the clinical presentation. Dysphagia, food impaction, persistent cough and chest pain are common clinical presentations. Imaging studies including esophagram, computed tomography (CT) and magnetic resonance imaging (MRI) can provide key findings to reach the diagnosis. Nonetheless, endoscopic evaluation, particularly endoscopic ultrasound (EUS) is the most valuable tool to determine whether this lesion is cystic versus solid and or if there are abnormal mucosal findings. Needle biopsies are controversial but can help with drainage and to rule out malignant transformation. Therapeutic options include endoluminal drainage. However, more definitive therapies include surgical excision. Open and minimally invasive (laparoscopic and thoracoscopic) techniques have been demonstrated to be safe and effective at completely removing these lesions. Recently, robotic-assisted resections have gained more attention with case reports and series reporting excellent outcomes.

Five-Year Experience with Transcystic Laparoscopic Common Bile Duct Exploration.

Background: Common bile duct (CBD) stones associated with cholecystitis can be treated by single-stage CBD exploration at the time of cholecystectomy or a two-stage approach with endoscopic stone extraction before or after cholecystectomy. The ideal management remains a matter of debate. The aim of this study is to analyze our outcomes with transcystic laparoscopic common bile duct exploration (LCBDE). Material and Methods: A retrospective review of patients who underwent transcystic LCBDE between 2015 and 2019 was performed. Results: A total of 106 patients underwent transcystic LCBDE over 5 years. We performed 1192 laparoscopic cholecystectomies with cholangiograms from March 2015 to December 2019. Fifteen patients had a preoperative endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones seen on magnetic resonance cholangiopancreatography that during laparoscopic cholecystectomy with intraoperative cholangiogram (IOC), there were stones and/or sludge found in the CBD, which required clearance through a transcystic approach. Of the 91 patients who did not have a preoperative ERCP, clearance of the CBD was successful through a transcystic approach in 78 patients (86%). In the 13 patients that intraoperative clearance was not achieved (n = 13, 14%), a postoperative ERCP was performed. A total of 28 patients underwent either pre- or postoperative ERCP (n = 28, 26%). Choledochotomy was not performed in any of the patients. The mean operative time was 127 minutes (127 ± 48). The mean hospital length of stay (LOS) was 4 days (3.9 ± 2.8) with a median LOS of 3 days. Complications observed include wound infection (n = 2, 2%), pancreatitis after ERCP (n = 1, 1%), pneumonia (n = 1, 1%), and right hepatic duct injury (n = 1, 1%). Conclusion: Transcystic LCBDE is an effective and safe option for treatment of CBD stones. While a transcystic approach does not guarantee clearance of the CBD, it avoids the morbidity associated with a choledochotomy and can often prevent patients from having to undergo an additional procedure.

Endoluminal management of benign bronchoesophageal fistula.

The ideal management of bronchoesophageal fistulas is a debated topic. While open surgical repair remains the most definitive treatment, not all patients are fit for surgery. In this communication, we present a patient who developed a bronchoesophageal fistula 1 year after an Ivor Lewis esophagectomy that involved the native oesophagus and right mainstem bronchus. Endoluminal vacuum therapy was successful at closing this benign bronchoesophageal fistula.

A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect.

Cancer cells possess aberrant proteomes that can arise by the disruption of genes involved in physiological protein degradation. Here we demonstrate the presence of promoter CpG island hypermethylation-linked inactivation of DERL3 (Derlin-3), a key gene in the endoplasmic reticulum-associated protein degradation pathway, in human tumours. The restoration of in vitro and in vivo DERL3 activity highlights the tumour suppressor features of the gene. Using the stable isotopic labelling of amino acids in cell culture workflow for differential proteome analysis, we identify SLC2A1 (glucose transporter 1, GLUT1) as a downstream target of DERL3. Most importantly, SLC2A1 overexpression mediated by DERL3 epigenetic loss contributes to the Warburg effect in the studied cells and pinpoints a subset of human tumours with greater vulnerability to drugs targeting glycolysis.

Drosophila CTCF tandemly aligns with other insulator proteins at the borders of H3K27me3 domains.

Several multiprotein DNA complexes capable of insulator activity have been identified in Drosophila melanogaster, yet only CTCF, a highly conserved zinc finger protein, and the transcription factor TFIIIC have been shown to function in mammals. CTCF is involved in diverse nuclear activities, and recent studies suggest that the proteins with which it associates and the DNA sequences that it targets may underlie these various roles. Here we show that the Drosophila homolog of CTCF (dCTCF) aligns in the genome with other Drosophila insulator proteins such as Suppressor of Hairy wing [SU(HW)] and Boundary Element Associated Factor of 32 kDa (BEAF-32) at the borders of H3K27me3 domains, which are also enriched for associated insulator proteins and additional cofactors. RNAi depletion of dCTCF and combinatorial knockdown of gene expression for other Drosophila insulator proteins leads to a reduction in H3K27me3 levels within repressed domains, suggesting that insulators are important for the maintenance of appropriate repressive chromatin structure in Polycomb (Pc) domains. These results shed new insights into the roles of insulators in chromatin domain organization and support recent models suggesting that insulators underlie interactions important for Pc-mediated repression. We reveal an important relationship between dCTCF and other Drosophila insulator proteins and speculate that vertebrate CTCF may also align with other nuclear proteins to accomplish similar functions.