Systemic inflammatory response and thrombosis due to alterations in the gut microbiota in COVID-19.

We thank Dr. Cienfuegos and colleagues for their comments on our recent publication "COVID-19, Coronavirus, SARS-CoV-2 and the small bowel". Cienfuegos et al. have treated several COVID-19 patients with thromboembolic complications, including bowel ischemia. The authors correctly highlight the importance of this complication in COVID-19 patients, which has also been documented in autopsy studies.

Wireless capsule endoscopy of the small intestine: a review with future directions.

PURPOSE OF REVIEW: Here, we review the clinical applications of small bowel capsule endoscopy. Moreover, we provide an outlook on the exceptional future developments of small bowel capsule endoscopy. We discuss clinical algorithms for diagnosis of small bowel diseases. Multiple studies have shown the potential of capsule endoscopy for identification of the bleeding source located in the small bowel and the increased diagnostic yield over radiographic studies. Capsule endoscopy could detect villous atrophy and severe complications in patients with nonresponsive celiac disease. In addition, small bowel capsule endoscopy was proven as a valid tool to diagnose polyps and tumors and Crohn's disease. SUMMARY: Major current clinical indications of capsule endoscopy in the small bowel include evaluation of obscure gastrointestinal bleeding, diagnosis and surveillance of small bowel polyps and tumors, celiac disease and Crohn's disease. Recent developments have also passed the way for small bowel capsule endoscopy to become a therapeutic instrument.

Learning curve of virtual chromoendoscopy for the prediction of hyperplastic and adenomatous colorectal lesions: a prospective 2-center study.

BACKGROUND: Computed virtual chromoendoscopy (CVC) enables high-definition imaging of mucosal lesions with improved tissue contrast. Previous studies have shown that CVC yields an improved detection rate of colorectal lesions. However, the learning curve for interpretation of CVC images is unknown. OBJECTIVE: To examine the learning curve of correctly identifying hyperplastic and adenomatous colorectal lesions by using CVC. DESIGN: Prospective, 2-center study. PATIENTS: Consecutive patients undergoing screening colonoscopy were included. CVC images were analyzed by using corresponding polypectomies as the reference standard followed by a prospective, double-blind review of i-scan images. METHODS: A training set containing 20 images with known histology was reviewed to standardize image interpretation, followed by a blind review of 110 unknown images. Overall, 4 endoscopists from 2 different endoscopy centers evaluated the images, which were obtained by 1 endoscopist using high-definition endoscopy with CVC. RESULTS: Patients were included in a prospective fashion. Seventy-seven of 110 colorectal lesions were adenomas and 33 were hyperplastic lesions. Mean diameter of colonic polyps was 4 mm (range, 2-20 mm). Overall accuracy for the group was 73.9% for lesions 1 to 22, 79.6% for lesions 23 to 44, 84.1% for lesions 45 to 66, 87.5% for lesions 67 to 88, and 94.3% for lesions 89 to 110. Accuracy of i-scan for prediction of polyp histology was not dependent on polyp size (≤5 mm, 6-10 mm, or > 10 mm). The ability to obtain high-quality images was stable over time, and high-quality images were constantly produced. LIMITATION: Post-hoc assessment. CONCLUSION: Accurate interpretation of CVC images for prediction of hyperplastic and adenomatous colorectal lesions follows a learning curve but can be learned rapidly.

Review article on current applications and future concepts of capsule endoscopy.

Since the advent of capsule endoscopy (CE) more than one decade has passed. During this time, extensive efforts have been made to proof the relevance of CE for diagnosis of various disease entities within the esophagus, small bowel, and colon. To date, the most common indications for CE are obscure gastrointestinal bleeding, Crohn's disease, polyposis syndromes and evaluation of patients with complicated celiac disease. In this review we will focus on the current clinical applications of CE for imaging of the esophagus, small bowel and colon and will additionally give an outlook on future concepts and developments of CE.

Gastro-oesophageal reflux disease is associated with up-regulation of desmosomal components in oesophageal mucosa.

AIMS: Gastro-oesophageal reflux disease (GERD) is associated with impaired epithelial barrier function. This study was aimed at investigating the role of desmosomal proteins in relation to GERD. METHODS AND RESULTS: Ninety-five patients with GERD-related symptoms (erosive, n = 51; non-erosive, n = 44) and 27 patients lacking those symptoms were included. Endoscopic and histological characterization of oesophagitis was performed according to the Los Angeles and Ismeil-Beigi criteria, respectively. Multiple biopsies were taken from the oesophageal mucosa of each patient. Gene expression analysis of plakoglobin, desmoglein-1, desmoglein-2 and desmoglein-3 was performed by quantitative real time (RT)-polymerase chain reaction and immunohistochemistry in the oesophageal mucosa. Routine histology revealed specific GERD-related alterations, such as dilatation of intercellular spaces (DIS), basal cell hyperplasia (BCH), and elongation of the papillae, in the oesophageal mucosa of patients with GERD, as compared with controls (all parameters: P < 0.05). All four genes and corresponding proteins were found to be up-regulated by between 1.7 and 8.1-fold (transcript level, P < 0.05; protein level, P < 0.05). Induced gene expression levels of plakoglobin, desmoglein-1 and desmoglein-2 correlated significantly with DIS and BCH. CONCLUSIONS: Taken together, the uniform up-regulation of desmosomal genes/proteins in the oesophageal mucosa of patients with GERD supports the concept of architectural and molecular changes in the desmosomal compartment in the pathogenesis of GERD.

Role of tight junction proteins in gastroesophageal reflux disease.

BACKGROUND: Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function that is regulated by cell-cell contacts. The aim of the study was to investigate the expression pattern of selected components involved in the formation of tight junctions in relation to GERD. METHODS: Eighty-four patients with GERD-related symptoms with endoscopic signs (erosive: n = 47) or without them (non-erosive: n = 37) as well as 26 patients lacking GERD-specific symptoms as controls were included. Endoscopic and histological characterization of esophagitis was performed according to the Los Angeles and adapted Ismeil-Beigi criteria, respectively. Mucosal biopsies from distal esophagus were taken for analysis by histopathology, immunohistochemistry and quantitative reverse-transcription polymerase chain reaction (RT-PCR) of five genes encoding tight junction components [Occludin, Claudin-1, -2, Zona occludens (ZO-1, -2)]. RESULTS: Histopathology confirmed GERD-specific alterations as dilated intercellular spaces in the esophageal mucosa of patients with GERD compared to controls (P < 0.05). Claudin-1 and -2 were 2- to 6-fold upregulation on transcript (P < 0.01) and in part on protein level (P < 0.015) in GERD, while subgroup analysis of revealed this upregulation for ERD only. In both erosive and non-erosive reflux disease, expression levels of Occludin and ZO-1,-2 were not significantly affected. Notably, the induced expression of both claudins did not correlate with histopathological parameters (basal cell hyperplasia, dilated intercellular spaces) in patients with GERD. CONCLUSIONS: Taken together, the missing correlation between the expression of tight junction-related components and histomorphological GERD-specific alterations does not support a major role of the five proteins studied in the pathogenesis of GERD.

The submucosal cushion does not improve the histologic evaluation of adenomatous colon polyps resected by snare polypectomy.

BACKGROUND & AIMS: Although the "submucosal cushion" technique or injection-assisted polypectomy (IAP) is often used to resect colon polyps, little is known on the influence of this technique on histologic interpretation. We aimed to evaluate whether the use of a submucosal cushion improves the histologic and margin evaluation of colon polyps. METHODS: Consecutive patients undergoing polypectomy with and without IAP were included. An experienced blinded gastrointestinal pathologist evaluated the specimens using standardized criteria. RESULTS: One hundred eleven sessile colon adenomas were analyzed (IAP, n = 65, standard, n = 46). Two-thirds of polyps ranged in size from 10 to 20 mm; the average polyp size was 13.2 mm for IAP and 9.9 mm for standard snare polypectomy (P = .001). The cautery degree, cautery amount, and margin evaluability, did not differ substantially with regard to the resection technique. For polyps ≥10-20 mm, the overall architecture quality was better in polyps resected with standard technique as compared with IAP. CONCLUSIONS: The utilization of IAP did not result in a better margin evaluability of the resected polyp. Overall, IAP does not result in a better histologic polyp evaluability.

Feasibility of endoscopic closure of an iatrogenic colon perforation occurring during colonoscopy.

BACKGROUND: Colon perforation is one of the most dreaded complications of colonoscopy. Traditionally, patients with a colon perforation have been treated surgically. Although there are several case reports documenting the usefulness of endoscopic closure of colon perforations, there are few current data evaluating the feasibility of endoscopic closure for an iatrogenic perforation on consecutive patients undergoing colonoscopy. OBJECTIVE: To assess the incidence of colon perforations and the utility of immediate endoscopic closure during colonoscopy. DESIGN: Retrospective, observational study. SETTING: Tertiary-care academic medical center. PATIENTS: All patients who underwent colonoscopy at 1 institution from June 2002 to December 2008 were identified. INTERVENTION: An attempt at immediate colon perforation closure by endoscopic means. MAIN OUTCOME MEASUREMENTS: Successful endoscopic closure of colon perforation. RESULTS: During the study period, a total of 8601 colonoscopies were performed (2472 therapeutic interventions, 28.7%). A total of 12 iatrogenic colon perforations occurred, yielding a rate of 1.4/1000. Five (41.7%) occurred during a diagnostic colonoscopy (0.8/1000), and 7 perforations (58.3%) occurred as the result of a therapeutic intervention (2.8/1000). Endoscopic closure of the perforation site was possible in 5 patients (42%). Seven patients were treated surgically (large defects [n = 3], including 1 failed endoscopic closure, difficult endoscope position [n = 2], stool contamination [n = 1], and endoscopist's inexperience with closure of mucosal defects [n = 1]). LIMITATION: Retrospective design. CONCLUSIONS: In this study, the incidence of colon perforations was 1.4/1000. Endoscopic closure of iatrogenic colon perforations was attempted in 50% of patients and was successful in 83%. All patients with successful endoscopic closure had lesions smaller than 10 mm.

Therapeutic double-balloon enteroscopy: a binational, three-center experience.

BACKGROUND/AIMS: There are few reports focusing on therapeutic small bowel endoscopy. The aim of this study was to analyze the results of therapeutic small bowel endoscopy in a large cohort of patients. METHODS: A retrospective study of a prospectively collected database comprising all patients undergoing diagnostic and therapeutic small bowel endoscopy in three centers. RESULTS: A total of 614 double-balloon enteroscopies were performed in 534 patients. The most common pathological findings were angiodysplasias and vascular lesions (n = 98, 18%), mucosal ulcers and erosions (n = 95, 17.8%), polyps and tumors (including patients with familiar polyposis syndrome such as Peutz-Jeghers syndrome, familiar adenomatous polyps syndrome, neurofibromatosis, adenocarcinoma, neuroendocrine tumors and gastrointestinal stromal tumors) (n = 52, 9.7%), and strictures (Crohn's disease, ischemia, tumors) (n = 12, 2.2%). The mean duration of therapeutic small bowel enteroscopy was 67 min (range 30-115) compared to 50 min (range 25-105) for diagnostic procedures (p < 0.05). A therapeutic small bowel endoscopy was performed in 121 patients (22%). Therapeutic procedures included argon plasma coagulation of vascular lesions (n = 73), polypectomy (n = 49), mucosectomy (n = 5), stricture dilation (n = 7), foreign body extraction (n = 7), injection of fibrin glue (n = 10), and clip placement (n = 5). There were a total of 5 complications (0.9%; paralytic ileus, n = 2, pancreatitis, n = 1, bleeding n = 2). No perforations or deaths occurred. CONCLUSION: Endoscopists performing double-balloon enteroscopy should be trained and prepared to provide therapeutic interventions for small bowel disorders including argon plasma coagulation, injection, hemoclipping, polypectomy, mucosectomy and foreign body extraction. Therapeutic small bowel endoscopy, albeit associated with complications in about 1% of cases, can be considered a relatively safe procedure.

Intercellular space volume is mainly increased in the basal layer of esophageal squamous epithelium in patients with GERD.

BACKGROUND/AIMS: At present, the dilation of esophageal intercellular spaces (ICS) is considered an early morphologic marker of acid damage in patients with GERD. Nevertheless, previous electron microscopic (EM) studies had focused only on the suprabasal layer of squamous epithelium or did not nearly specify which layer of squamous epithelium was studied. Therefore, we aimed to assess the volumetric amount of the ICS in all layers of SE in patients with GERD. METHODS: In this study, 48 patients were prospectively included (NERD = 18, ERD = 17; Barrett's esophagus = 5, controls = 8). All patients with ERD and NERD had typical reflux symptoms, as assessed by a valid GERD questionnaire. ICS volume was assessed by electron microscopy in the superficial, prickle cell, and basal layers of esophageal squamous epithelium using the method of Weibel. RESULTS: ERD was associated with increased ICS volume in the basal layer (LA-A, p = 0.038; LA-B, p = 0.005) and prickle cell layer (LA-A, p = 0.006; LA-B, p = 0.007) as compared to controls. Comparisons between NERD and ERD patients revealed more dilated ICS in the basal layer (LA-B, p = 0.007), prickle cell layer (LA-A, p = 0.008; LA-B, p = 0.001) and superficial layer (LA-B, p = 0.018) in patients with ERD. CONCLUSIONS: Not only the diameter but also the volume of the ICS is increased in patients with GERD. Furthermore, the dilation of ICS is present in all three layers of the SE, being more pronounced in the basal layer. These findings support the concept that the impairment of the esophagus begins in the deeper parts of the esophageal epithelium.

Endoscopic spectrum and practical classification of small bowel gastrointestinal stromal tumors (GISTs) detected during double-balloon enteroscopy.

Background and study aims Information about the endoscopic characterization of small bowel gastrointestinal tumors (GISTs) is limited. The aim of this case study was to describe the endoscopic spectrum of small bowel GISTs and to present a practical classification. Patients and methods Observational, retrospective, consecutive case series of patients with small bowel GIST. Results A total of 10 small bowel GISTs were found in patients (6 male, 4 female, mean age 52 years, range 28 to 68).). All patients presented with obscure gastrointestinal bleeding (overt, n = 8, occult, n = 2). Most GISTs were present in the proximal or middle small bowel (n = 7). The endoscopic tumor characteristics could be categorized as follows: submucosal round (n = 4), submucosal sessile (n = 2), and invasive/penetrating) (n = 4). The mucosa overlying the tumor was normal (n = 4), grooved (n = 3) or frankly ulcerated (n = 3). Tumor size ranged from 8 mm to 50 mm. Biopsy was negative in all patients with normal mucosa but showed tumor in all patients with ulcerations. Regardless of biopsy results, all patients were sent for surgery. Nine resections were carried out. One patient refused surgery. There were no complications of endoscopy in this cohort. Conclusion Our series shows that GISTs have a wider spectrum of endoscopic characteristics than previously described. The round type with normal overlying mucosa was equally prevalent as the grooved or ulcerated variant. Endoscopists should be aware of this wide spectrum of presentation of small bowel GIST.

Proteinase-activated receptor-2 in the pathogenesis of gastroesophageal reflux disease.

OBJECTIVES: The proteinase-activated receptor-2 (PAR-2) is activated by serine proteases and has been demonstrated to induce proinflammatory and neuroinflammatory effects. It is considered to alter transepithelial resistance and mediates visceral hypersensitivity. This study aimed to evaluate the expression of PAR-2 in human esophageal mucosa of patients with gastroesophageal reflux disease (GERD) in relation to mucosal alterations. METHODS: The study included 123 patients with GERD stratified to erosive reflux disease (n=50), non-erosive reflux disease (n=46), and reflux-negative patients as controls (n=27). Endoscopic and histopathological characterization was performed according to the Los Angeles classification and modified Ismail-Beigi criteria, respectively. PAR-2 expression was analyzed by quantitative reverse transcription (RT)-PCR and immunohistochemistry. The gene expression levels of interleukin (IL)-8 were determined by quantitative RT-PCR and correlated to PAR-2 expression in each patient. Performing in vitro studies, esophageal squamous cell lines (KYSE 150, KYSE 450) were incubated, adjusted to different pH (7.0, 6.0, and 5.0), and exposed to bile acids and PAR-2-activation peptide (SLIGKV-NH(2)). RESULTS: PAR-2 gene expression was 7- to 10-fold upregulated (P<0.0001) in the mucosa of patients with GERD and correlated positively with IL-8 expression and with histomorphological alterations (dilated intercellular spaces, papillary elongation, basal cell hyperplasia (BCH); P<0.01). Immunohistochemistry showed an intense staining of PAR-2 throughout all epithelial layers in patients with GERD compared with controls (P=0.0005). In vitro studies revealed a 1.5- to 20-fold induction of PAR-2 gene expression in esophageal squamous cells by acidified medium (P<0.01), but not by additional bile acids. The activation of PAR-2 leads to expression and secretion of IL-8. CONCLUSIONS: This study provides evidence of the functional importance of PAR-2-mediated pathways in the pathogenesis of GERD and GERD-associated mucosal alterations and inflammatory changes.