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Benralizumab, an interleukin-5 receptor blocker, significantly reduced absolute eosinophil counts and relieved symptoms in a small group of patients with hypereosinophilic syndrome. Adverse events were similar in the benralizumab group and the placebo group.

INTRODUCTION:The efficacy of texture and color enhancement imaging (TXI) in the novel light-emitting diode endoscopic system for polyp detection has not been examined. We aimed to evaluate the noninferiority of the additional 30-second (Add-30-s) observation of the right-sided colon (cecum/ascending colon) with TXI compared with narrow band imaging (NBI) for detecting missed polyps.METHODS:We enrolled 381 patients ≥40 years old who underwent colonoscopy from September 2021 to June 2022 in 3 institutions and randomly assigned them to either the TXI or NBI groups. The right-sided colon was first observed with white light imaging in both groups. Second, after reinsertion from hepatic flexure to the cecum, the right-sided colon was observed with Add-30-s observation of either TXI or NBI. The primary endpoint was to examine the noninferiority of TXI to NBI using the mean number of adenomas and sessile serrated lesions per patient. The secondary ones were to examine adenoma detection rate, adenoma and sessile serrated lesions detection rates, and polyp detection rates in both groups.RESULTS:The TXI and NBI groups consisted of 177 and 181 patients, respectively, and the noninferiorities of the mean number of adenomas and sessile serrated lesions per patients in the second observation were significant (TXI 0.29 [51/177] vs NBI 0.30 [54/181], P < 0.01). The change in adenoma detection rate, adenoma and sessile serrated lesions detection rate, and polyp detection rate for the right-sided colon between the TXI and NBI groups were not different (10.2%/10.5% [P = 0.81], 13.0%/12.7% [P = 0.71], and 15.3%/13.8% [P = 0.71]), respectively.DISCUSSION:Regarding Add-30-s observation of the right-sided colon, TXI was noninferior to NBI.

Although screening colonoscopy is effective in preventing distal colon cancers, effectiveness in preventing right-sided colon cancers is less clear. Previous studies have reported that retroflexion in the right colon improves adenoma detection. We aimed to determine whether a second withdrawal from the right colon in retroflexion vs. forward view alone leads to the detection of additional adenomas. Patients undergoing screening or surveillance colonoscopy were invited to participate in a parallel, randomized, controlled trial at two centers. After cecal intubation, the colonoscope was withdrawn to the hepatic flexure, all visualized polyps removed, and endoscopist confidence recorded on a 5-point Likert scale. Patients were randomized to a second exam of the proximal colon in forward (FV) or retroflexion view (RV), and adenoma detection rates (ADRs) compared. Logistic regression analysis was used to evaluate predictors of identifying adenomas on the second withdrawal from the proximal colon. A total of 850 patients (mean age 59.1±8.3 years, 59% female) were randomly assigned to FV (N=400) or RV (N=450). Retroflexion was successful in 93.5%. The ADR (46% FV and 47% RV) and numbers of adenomas per patient (0.9±1.4 FV and 1.1±2.1 RV) were similar (P=0.75 for both). At least one additional adenoma was detected on second withdrawal in similar proportions (10.5% FV and 7.5% RV, P=0.13). Predictors of identifying adenomas on the second withdrawal included older age (odds ratio (OR)=1.04, 95% confidence interval (CI)=1.01-1.08), adenomas seen on initial withdrawal (OR=2.8, 95% CI=1.7-4.7), and low endoscopist confidence in quality of first examination of the right colon (OR=4.8, 95% CI=1.9-12.1). There were no adverse events. Retroflexion in the right colon can be safely achieved in the majority of patients undergoing colonoscopy for colorectal cancer screening. Reexamination of the right colon in either retroflexed or forward view yielded similar, incremental ADRs. A second exam of the right colon should be strongly considered in patients who have adenomas discovered in the right colon, particularly when endoscopist confidence in the quality of initial examination is low.

ObjectiveTo determine if human colonic neuromuscular functions decline with increasing age.DesignLooking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35–91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35–60 years) groups.ResultsWith increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon.ConclusionIn ascending not descending colon, ageing impairs cholinergic function.

Effective antiretroviral therapy (ART) dramatically reduces AIDS-related complications, yet the life expectancy of long-term ART-treated HIV-infected patients remains shortened compared to that of uninfected controls, due to increased risk of non-AIDS related morbidities. Many propose that these complications result from translocated microbial products from the gut that stimulate systemic inflammation--a consequence of increased intestinal paracellular permeability that persists in this population. Concurrent intestinal immunodeficiency and structural barrier deterioration are postulated to drive microbial translocation, and direct evidence of intestinal epithelial breakdown has been reported in untreated pathogenic SIV infection of rhesus macaques. To assess and characterize the extent of epithelial cell damage in virally-suppressed HIV-infected patients, we analyzed intestinal biopsy tissues for changes in the epithelium at the cellular and molecular level. The intestinal epithelium in the HIV gut is grossly intact, exhibiting no decreases in the relative abundance and packing of intestinal epithelial cells. We found no evidence for structural and subcellular localization changes in intestinal epithelial tight junctions (TJ), but observed significant decreases in the colonic, but not terminal ileal, transcript levels of TJ components in the HIV+ cohort. This result is confirmed by a reduction in TJ proteins in the descending colon of HIV+ patients. In the HIV+ cohort, colonic TJ transcript levels progressively decreased along the proximal-to-distal axis. In contrast, expression levels of the same TJ transcripts stayed unchanged, or progressively increased, from the proximal-to-distal gut in the healthy controls. Non-TJ intestinal epithelial cell-specific mRNAs reveal differing patterns of HIV-associated transcriptional alteration, arguing for an overall change in intestinal epithelial transcriptional regulation in the HIV colon. These findings suggest that persistent intestinal epithelial dysregulation involving a reduction in TJ expression is a mechanism driving increases in colonic permeability and microbial translocation in the ART-treated HIV-infected patient, and a possible immunopathogenic factor for non-AIDS related complications.

ObjectiveAccurate differentiation between Crohn's disease (CD) and UC is important to ensure early and appropriate therapeutic intervention. We sought to identify proteins that enable differentiation between CD and UC in children with new onset IBD.DesignMucosal biopsies were obtained from children undergoing baseline diagnostic endoscopy prior to therapeutic interventions. Using a super-stable isotope labeling with amino acids in cell culture (SILAC)-based approach, the proteomes of 99 paediatric control and biopsies of patients with CD and UC were compared. Multivariate analysis of a subset of these (n=50) was applied to identify novel biomarkers, which were validated in a second subset (n=49).ResultsIn the discovery cohort, a panel of five proteins was sufficient to distinguish control from IBD-affected tissue biopsies with an AUC of 1.0 (95% CI 0.99 to 1.0); a second panel of 12 proteins segregated inflamed CD from UC within an AUC of 0.95 (95% CI 0.86 to 1.0). Application of the two panels to the validation cohort resulted in accurate classification of 95.9% (IBD from control) and 80% (CD from UC) of patients. 116 proteins were identified to have correlation with the severity of disease, four of which were components of the two panels, including visfatin and metallothionein-2.ConclusionsThis study has identified two panels of candidate biomarkers for the diagnosis of IBD and the differentiation of IBD subtypes to guide appropriate therapeutic interventions in paediatric patients.

Little is known about the correlation between the polyp detection rate (PDR) and the adenoma detection rate (ADR) in individual colonic segments. The adenoma-to-polyp detection rate quotient (APDRQ) has been utilized in retrospective study as a constant to estimate ADR from PDR. It has been previously stated that diminutive polyps in the rectum are more likely to be non-adenomatous, compared with more proximal segments, yet the APDRQ uses data from the entire colon. We sought to characterize and compare ADR and PDR in each colonic segment, estimate ADR using the conversion factor, APDRQ, and assess the correlation between estimated and actual ADR for each colonic segment. As part of a quality improvement program, a retrospective chart review was conducted of all outpatient colonoscopies performed by 20 gastroenterologists between 1 October 2010 and 31 March 2011 at a single academic tertiary-care referral center. PDR, ADR, and the APDRQ were calculated for each gastroenterologist, using data from the entire colon and then for each colonic segment separately. Actual ADR was compared with estimated ADR based on the measured APDRQ. During 1,921 colonoscopies, 2,285 polyps were removed; 1,122 (49%) were adenomas. The mean (s.d.) PDR for the group was 49% (12.4%) (range, 16-64%). The mean (s.d.) ADR was 31% (7.4%) (range, 13-42%). PDR and ADR correlated well in segments proximal to the splenic flexure, but diverged in distal segments. ADR was significantly higher in the right colon (17.1%) than in the left (13.5%) (P=0.001). The correlation between estimated and actual ADR using the APDRQ was significantly higher in the right colon (r=0.95 (95% confidence interval (CI), 0.87-0.98)) than in the left (r=0.59 (95% CI, 0.17-0.83)) (P<0.05). Although PDR and ADR correlate well in segments proximal to the splenic flexure, they do not correlate well in the left colon. Caution should be exercised when using PDR as a surrogate for ADR if data from the rectum and sigmoid are included.

Background Ascending colon cancer is a subtype of colorectal cancer (CRC), the most common malignant tumor globally. The appendix has been considered to be a vestigial organ and appendectomy is the most routine management of acute appendicitis. However, limited studies have examined the association between appendectomy and the invasion of ascending colon cancer. Methods In this retrospective study, 880 cases of ascending colon cancer were selected. The preoperative and postoperative clinicopathological features were retrospectively studied. Logistic regression was performed and the propensity score matching (PSM) method was used to adjust for confounding factors. Results In total of 880 patients, 133 patients had a history of appendectomy. Patients with a history of appendectomy exhibited a higher proportion of number of lymph node metastasis (LNM) ( P  = 0.047), T4 stage (P  = 0.025), N1 stage ( P  = 0.037), N2 stage ( P  = 0.045), M1 stage ( P  = 0.008), stage III ( P  = 0.047), and stage IV ( P  = 0.003). The model following PSM revealed that a history of appendectomy was associated with an increased risk of LNM and M1. In 747 patients without a history of appendectomy, 568 patients (76.0%) were diagnosed with chronic appendicitis pathologically. Patients with chronic appendicitis had significantly smaller tumor sizes ( P  = 0.012), reduced lymphovascular invasion (LVI) ( P  = 0.001), fewer poorly differentiated tumors ( P  = 0.012,), a lower number of LNM ( P  = 0.020), less frequent T4 stage tumors ( P  = 0.023), and a decreased incidence of N2 stage disease ( P  = 0.035). Conclusions Appendectomy is associated with a higher aggressiveness of subsequent ascending colon cancer, particularly regarding LNM. Chronic appendicitis has been linked to a decrease in tumor invasion of ascending colon cancer.

Objective The purpose of this paper is to determine whether sites of distant recurrence are associated with specific locations of primary disease in colon cancer. Methods A cohort including all patients ( n  = 947) undergoing a segmental colonic resection for colon cancer at our center (2004–2011) comparing site-specific metastatic presentation and recurrence rates, as well as their respective multivariable American Joint Committee on Cancer (AJCC) stage-adjusted hazard ratios ( m HR). Results Right-sided colectomies ( n  = 557) had a lower overall metastasis rate (24.8 % vs. 31.8 %; P  = 0.017; m HR = 1.24 [95% CI: 0.96–1.60]; P  = 0.011) due to significantly lower pulmonary metastasis in follow-up (2.7 % vs. 9 %; P  < 0.001; m HR = 0.32 [95% CI: 0.17–0.58]; P  = 0.001) and lower overall liver metastasis rate (15.6 vs. 22.1 %; P  = 0.012; m HR = 0.74 [95% CI: 0.55–0.99]; P  = 0.050). Left colectomies ( n  = 127) had higher rates of liver metastasis during follow-up (9.4 % vs. 4.8 %; P  = 0.029; m HR = 1.64 [95% CI: 0.86–3.15]; P  = 0.134). Sigmoid resections ( n  = 238) had higher baseline rates of liver metastasis (17.1 % vs. 11.3 %; P  = 0.015) and higher cumulative rates of lung (12.2 % vs. 5.4 %; P  < 0.001; m HR = 2.26 [95 % CI: 1.41–3.63]; P  = 0.001) and brain metastases (2.3 % vs. 0.6 %; P  = 0.033; m HR = 4.03 [95% CI: 1.14–14.3]; P  = 0.031). Other sites of metastasis, including the (retro) peritoneum, omentum, ovary, and bone, did not yield significant differences. Conclusions Important variations in site-specific rates of metastatic disease exist within major resection regions of colon cancer. These variations may be important to consider when evaluating options for adjuvant treatment and surveillance after resection of the primary disease.

Delayed hemorrhage is an infrequent, but serious complication of colonoscopic polypectomy. Large size is the only polyp-related factor that has been unequivocally proven to increase the risk of delayed bleeding. It has been suggested that location in the right hemi-colon is also a risk factor. The objective of this study was to determine whether polyp location is an independent risk factor for delayed post-polypectomy hemorrhage. A retrospective case-control study was conducted in two university hospitals and two community hospitals. Thirty-nine cases and 117 controls were identified. In multivariate analysis, size and location were found to be independent polyp-related risk factors for delayed type hemorrhage. The risk increased by 13% for every 1 mm increase in polyp diameter (odds ratio (OR) 1.13, 95% confidence interval (CI) 1.05-1.20, P<0.001). Polyps located in the right hemi-colon had an OR of 4.67 (1.88-11.61, P=0.001) for delayed hemorrhage. Polyps in the cecum seemed to be especially at high risk in univariate analysis (OR 13.82, 95% CI 2.66-71.73), but this could not be assessed in multivariate analysis as the number of cases was too small. Polyp type (sessile or pedunculated) was not a risk factor. Polyp location in the right hemi-colon seems to be an independent and substantial risk factor for delayed post-polypectomy hemorrhage. A low threshold for preventive hemostatic measures is advised when removing polyps from this region.