Incomplete resection of colorectal neoplasia decreases the efficacy of colonoscopy. Conventional resection (CR) of polyps, performed in a gas-distended colon, is the current standard, but incomplete ...resection rates of approximately 2% to 30% for nondiminutive (>5 mm), nonpedunculated lesions are reported. Underwater resection (UR) is a novel technique. The aim of this study was to determine the incomplete resection rates of colorectal lesions removed by UR versus CR.
In a randomized controlled trial, patients with small (6-9 mm) and large (≥10 mm) nonpedunculated lesions were assigned to CR (gas-distended lumen) or UR (water-filled, gas-excluded lumen). Small lesions in both arms were removed with a dedicated cold snare. For CR, large lesions were removed with a hot snare after submucosal injection. For UR, large lesions were removed with a hot snare without submucosal injection. Four-quadrant biopsy samples around the resection sites were used to evaluate for incomplete resection.
Four hundred sixty-two eligible polyps (248 UR vs 214 CR) from 255 patients were removed. Incomplete resection rates for UR and CR were low and did not differ (2% vs 1.9%, P = .91). UR was performed significantly faster for lesions ≥10 mm in size (10-19 mm, 2.9 minutes vs 5.6 minutes, P < .0001); ≥20 mm, 7.3 minutes vs 9.5 minutes, P = .015).
Low incomplete resection rates are achievable with UR and CR. UR is effective and safe with the advantage of faster resection and potential cost savings for removal of larger (≥10 mm) lesions by avoiding submucosal injection. As an added approach, UR has potential to improve the cost-effectiveness of colonoscopy by increasing efficiency and reducing cost while maintaining quality. (Clinical trial registration number: NCT02889679.)
Display omitted
Retinoic acid (RA) is used to treat leukemia and other cancers through its ability to promote cancer cell differentiation. Strategies to enhance the anticancer effects of RA could deepen and broaden ...its beneficial therapeutic applications. In this study, we describe a receptor cross-talk system that addresses this issue. RA effects are mediated by RAR/RXR receptors that we show are modified by interactions with the aryl hydrocarbon receptor (AhR), a protein functioning both as a transcription factor and a ligand-dependent adaptor in an ubiquitin ligase complex. RAR/RXR and AhR pathways cross-talk at the levels of ligand-receptor and also receptor-promoter interactions. Here, we assessed the role of AhR during RA-induced differentiation and a hypothesized convergence at Oct4, a transcription factor believed to maintain stem cell characteristics. RA upregulated AhR and downregulated Oct4 during differentiation of HL-60 promyelocytic leukemia cells. AhR overexpression in stable transfectants downregulated Oct4 and also decreased ALDH1 activity, another stem cell-associated factor, enhancing RA-induced differentiation as indicated by cell differentiation markers associated with early (CD38 and CD11b) and late (neutrophilic respiratory burst) responses. AhR overexpression also increased levels of activated Raf1, which is known to help propel RA-induced differentiation. RNA interference-mediated knockdown of Oct4 enhanced RA-induced differentiation and G(0) cell-cycle arrest relative to parental cells. Consistent with the hypothesized importance of Oct4 downregulation for differentiation, parental cells rendered resistant to RA by biweekly high RA exposure displayed elevated Oct4 levels that failed to be downregulated. Together, our results suggested that therapeutic effects of RA-induced leukemia differentiation depend on AhR and its ability to downregulate the stem cell factor Oct4.
Retinoic acid(RA), an embryonic morphogen, regulates cell differentiation. Endocytosis regulates receptor signaling that governs such RA-directed cellular processes. Vacuolin-1 is a small molecule ...that disrupts endocytosis, motivating interest in its effect on RA-induced differentiation/arrest. In HL-60 myeloblastic-leukemia cells, RA causes differentiation evidenced by a progression of cell-surface and functional markers, CD38, CD11b, and finally reactive oxygen species(ROS) production and G1/0 cell cycle arrest in mature cells.
We found that Vacuolin-1 enhanced RA-induced CD11b, ROS and G1/0 arrest, albeit not CD38. Enhanced CD11b expression was associated with enhanced activation of Focal Adhesion Kinase(FAK). Adding vacuolin-1 enhanced RA-induced tyrosine phosphorylation of FAK, Src Family Kinases(SFKs), and the adaptor protein, SLP-76, expression of which is known to drive RA-induced differentiation. Depleting CD11b cripples late stages of progressive myeloid differentiation, namely G1/0 arrest and inducible ROS production, but not expression of CD38. Loss of NUMB, a protein that supports early endosome maturation, affected RA-induced ROS and G1/0 arrest, but not CD38 expression.
Hence there appears to be a novel CD11b/FAK/LYN/SLP-76 axis subject to endosome regulation which contributes to later stages of RA-induced differentiation. The effects of vacuolin-1 thus suggest a model where RA-induced differentiation consists of progressive stages driven by expression of sequentially-induced receptors.
Introduction: Clinically significant serrated lesions (SL) may contribute to colon cancers (AJG 2012;107:1315-30) through a pathway unrelated to the adenoma-cancer sequence (CGH 2016;14:105659). ...These often subtle and non-polypoid lesions include sessile serrated adenomas/polyps, traditional serrated adenomas and hyperplastic polyps in the proximal colon, and missed lesions may account for interval cancers in proximal colon. Table 1 shows the impact of various combinations of cap (C), water exchange (WE) and chromoendoscopy with indigo carmine added to water (CE) on detection rate (DR) of various lesions (adenomas, serrated lesions) in proximal colon. We hypothesize that cap-assisted total water with chromoendoscopy (CATWCE) can further improve proximal adenoma detection (ADR) and clinically significant serrated lesions detection rate (SLDR) in screening and surveillance colonoscopy. Methods: Retrospective analysis of performance improvement observations in two consecutive series. Colonoscopy was performed with a transparent cap attached to tip of high definition colonoscope (Olympus PCF-H190L). Examination with CATW was performed with plain water and CATWCE used a 0.002 % indigocarmine solution. Air button was turned off. Water was infused and exchanged to remove debris on scope insertion until cecum was reached. Air pockets were suctioned. Water was used on scope withdrawal to facilitate examination and underwater polypectomy with forceps, cold or hot snares. Water was suctioned at dependent locations and tallied. No air was used for either method. Results: A total of 250 patients (125 per group) were included. Patients demographics (age, BMI) were comparable (Table 2). There were more patients for surveillance in CATW and screening in CATWCE. Total amount of water infused/suctioned were comparable. Cecal intubation time and success rate were comparable but withdrawal time was longer for CATWCE. Compared with CATW, CATWCE has significantly higher proximal < 5 mm ADR (67% vs 60% respectively, p< 0.05), and proximal SLDR (33% vs 17%, respectively, p< 0.05) Conclusion: Limitations: Retrospective analysis of non-randomized consecutive series of Veterans, single operator. Conclusion: Combined cap-assisted total water and chromoendoscopy (CATWCE) significantly improved proximal (< 5 mm) ADR and proximal SLDR in screening and surveillance colonoscopy. The role of CATWCE in colorectal cancer prevention including interval cancers deserves further evaluation in a prospective RCT
Blood transfusion practices for acute upper gastrointestinal hemorrhage have changed over time. Restrictive strategies, which gave way to more liberal approaches for the greater part of the 20
...century, have again gained traction as emerging research suggests restricting transfusion is associated with similar, or possibly better outcomes in UGI bleeding. In a large, retrospective cohort study from an integrated health care system in Taiwan, Chen, et al., report the association between early blood transfusion and clinical outcomes in patients presenting to the emergency department with UGI bleeding, and these findings are discussed in the context of current knowledge and practice.
Airway mucus plugs are frequently identified on CT scans of patients with COPD with a smoking history without mucus-related symptoms (ie, cough, phlegm silent mucus plugs).
In patients with COPD, ...what are the risk and protective factors associated with silent airway mucus plugs? Are silent mucus plugs associated with functional, structural, and clinical measures of disease?
We identified mucus plugs on chest CT scans of participants with COPD from the COPDGene study. The mucus plug score was defined as the number of pulmonary segments with mucus plugs, ranging from 0 to 18, and categorized into three groups (0, 1-2, and ≥ 3). We determined risk and protective factors for silent mucus plugs and the associations of silent mucus plugs with measures of disease severity using multivariable linear and logistic regression models.
Of 4,363 participants with COPD, 1,739 had no cough or phlegm. Among the 1,739 participants, 627 (36%) had airway mucus plugs identified on CT scan. Risk factors of silent mucus plugs (compared with symptomatic mucus plugs) were older age (OR, 1.02), female sex (OR, 1.40), and Black race (OR, 1.93) (all P values < .01). Among those without cough or phlegm, silent mucus plugs (vs absence of mucus plugs) were associated with worse 6-min walk distance, worse resting arterial oxygen saturation, worse FEV1 % predicted, greater emphysema, thicker airway walls, and higher odds of severe exacerbation in the past year in adjusted models.
Mucus plugs are common in patients with COPD without mucus-related symptoms. Silent mucus plugs are associated with worse functional, structural, and clinical measures of disease. CT scan-identified mucus plugs can complement the evaluation of patients with COPD.
To investigate the performance of Dual-AI Deep Learning Platform in detecting unreported pulmonary nodules that are 6 mm or greater, comprising computer-vision (CV) algorithm to detect pulmonary ...nodules, with positive results filtered by natural language processing (NLP) analysis of the dictated report.
Retrospective analysis of 5047 chest CT scans and corresponding reports. Cases which were both CV algorithm positive (nodule ≥ 6 mm) and NLP negative (nodule not reported), were outputted for review by 2 chest radiologists.
The CV algorithm detected nodules that are 6 mm or greater in 1830 (36.3%) of 5047 cases. Three hundred fifty-five (19.4%) were unreported by the radiologist, as per NLP algorithm. Expert review determined that 139 (39.2%) of 355 cases were true positives (2.8% of all cases). One hundred thirty (36.7%) of 355 cases were unnecessary alerts-vague language in the report confounded the NLP algorithm. Eighty-six (24.2%) of 355 cases were false positives.
Dual-AI platform detected actionable unreported nodules in 2.8% of chest CT scans, yet minimized intrusion to radiologist's workflow by avoiding alerts for most already-reported nodules.
PDF
