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BACKGROUND Endoscopic submucosal dissection (ESD) has shown to be effective in management of colorectal neoplasm in the Asian countries, while its implementation in Western countries where endoscopic mucosal resection (EMR) is preferred is still debatable. AIM To compare the surgical, histological, and oncological outcomes between ESD and EMR in the treatment of colorectal polyps, with subgroup analysis comparing the efficacy of ESD and EMR between Japan and the rest of the world. METHODS Embase and Medline databases were searched from inception to October 2020 in accordance with PRISMA guidelines for studies comparing en bloc , complete resection, margin involvement, resection time, need for additional surgery, complications, and recurrence rate of ESD with EMR. RESULTS Of 281344 colorectal polyps from 21 studies were included. When compared to EMR, the pooled analysis revealed ESD was associated with higher en bloc and complete resection rate, and lower lateral margin involvement and recurrence. ESD led to increased procedural time, need for additional surgery, and perforation risk. No significant difference in bleeding risk was found between the two groups. Meta-regression analysis suggested only right colonic polyps correlated with an increased perforation risk in ESD. Confounders including polyp size and invasion depth did not significantly influence the en bloc and complete resection rate, bleeding risk and recurrence. In subgroup analysis, Japan performed better than the rest of the world in both ESD and EMR with perforation risk of 4% and 0.0002%, respectively, as compared to perforation risk of 8% and 1%, respectively, in reports coming from rest of the world. CONCLUSION ESD resulted in better resection outcomes and lower recurrence compared to EMR. With appropriate training, ESD is preferred over EMR as the first-line therapy for resection of colorectal polyps, without restricting to lesions greater than 20 mm and those with high suspicion of submucosal invasion.

Objective As there has been so far no consensus on the best endoscopic resection technique, a meta‐analysis was conducted to compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for treating rectal carcinoid tumors. Methods MEDLINE and EMBASE databases were searched for articles on the treatment of rectal carcinoid tumors using ESD vs EMR published up to October 2020 for outcomes including en bloc and complete resection, margin involvement, procedure time, requirement for additional surgery, bleeding, perforation and recurrence. Risk ratio and weighted mean differences were used for a DerSimonian and Laird random effects pairwise meta‐analysis. Single‐arm meta‐analyses of proportions and random effects meta‐regression analysis were also conducted. Results Twenty‐two studies involving 1360 rectal carcinoid tumors were included, in which 655 and 705 rectal carcinoid tumors were resected with ESD and EMR, respectively. The resection efficacy of ESD was comparable to that of EMR for tumors <10 mm. However, there were a significantly higher complete resection rate, and lower rates of vertical margin involvement and requirement for additional surgery using ESD than using EMR for tumors ≤20 mm. ESD had a longer procedure time and an increased likelihood of bleeding than EMR. Conclusions ESD is more effective in providing a curative treatment for rectal carcinoid tumors ≤20 mm in size as ESD can achieve a higher complete resection rate with lower vertical margin involvement than EMR. While they are suitable for treating rectal carcinoid tumors <10 mm as both techniques provide similar efficacy.

The coagulation protein tissue factor (TF) regulates inflammation and angiogenesis via its cytoplasmic domain in infection, cancer and diabetes. While TF is highly abundant in the heart and is implicated in cardiac pathology, the contribution of its cytoplasmic domain to post-infarct myocardial injury and adverse left ventricular (LV) remodeling remains unknown. Methods: Myocardial infarction was induced in wild-type mice or mice lacking the TF cytoplasmic domain (TF∆CT) by occlusion of the left anterior descending coronary artery. Heart function was monitored with echocardiography. Heart tissue was collected at different time-points for histological, molecular and flow cytometry analysis. Results: Compared with wild-type mice, TF∆CT had a higher survival rate during a 28-day follow-up after myocardial infarction. Among surviving mice, TF∆CT mice had better cardiac function and less LV remodeling than wild-type mice. The overall improvement of post-infarct cardiac performance in TF∆CT mice, as revealed by speckle-tracking strain analysis, was attributed to reduced myocardial deformation in the peri-infarct region. Histological analysis demonstrated that TF∆CT hearts had in the infarct area greater proliferation of myofibroblasts and better scar formation. Compared with wild-type hearts, infarcted TF∆CT hearts showed less infiltration of proinflammatory cells with concomitant lower expression of protease-activated receptor-1 (PAR1) - Rac1 axis. In particular, infarcted TF∆CT hearts displayed markedly lower ratios of inflammatory M1 macrophages and reparative M2 macrophages (M1/M2). In vitro experiment with primary macrophages demonstrated that deletion of the TF cytoplasmic domain inhibited macrophage polarization toward the M1 phenotype. Furthermore, infarcted TF∆CT hearts presented markedly higher peri-infarct vessel density associated with enhanced endothelial cell proliferation and higher expression of PAR2 and PAR2-associated pro-angiogenic pathway factors. Finally, the overall cardioprotective effects observed in TF∆CT mice could be abolished by subcutaneously infusing a cocktail of PAR1-activating peptide and PAR2-inhibiting peptide via osmotic minipumps. Conclusions: Our findings demonstrate that the TF cytoplasmic domain exacerbates post-infarct cardiac injury and adverse LV remodeling via differential regulation of inflammation and angiogenesis. Targeted inhibition of the TF cytoplasmic domain-mediated intracellular signaling may ameliorate post-infarct LV remodeling without perturbing coagulation.

Early detection of liver graft fibrosis is crucial for risk stratification to identify patients for liver biopsy and timely treatment. However, diagnostic accuracy of noninvasive tests (NITs) remains unclear. Thus, this study sought to evaluate diagnostic accuracy of NITs in assessing liver allograft fibrosis and compare the differences in specificities and sensitivities among NITs. Medline and Embase databases were searched to include articles on diagnostic tests in liver transplantation (LT) patients with fibrosis. A meta‐analysis on diagnostic test accuracy was conducted in a random‐effects model. Sensitivities and specificities among the diagnostic tests were compared, and threshold values were calculated where applicable. A total of 25 articles were included. Vibration‐controlled transient elastography (VCTE) met the minimum diagnostic accuracy requirements, yielding sensitivity, specificity, and diagnostic odds ratios of 0.9 (CI, 0.8‐1.0), 0.9 (CI, 0.8‐1.0), and 379.6 (CI, 45.8‐1728.7), respectively. In the threshold assessment, the optimal cutoff was 9.30 kPa with a sensitivity, specificity, and area under the curve of 0.7 (CI, 0.5‐0.9), 0.9 (CI, 0.8‐0.9), and 0.9 (CI, 0.8‐0.9), respectively. For significant fibrosis, acoustic radiation force impulse (ARFI) was superior to FibroTest (LabCorp [Burlington, NC]) and magnetic resonance elastography (MRE) in sensitivity. VCTE was superior to FibroTest in specificity. For advanced fibrosis, ARFI was superior to the Fibrosis‐4 Index (FIB‐4) in sensitivity. VCTE was superior to the AST to Platelet Ratio Index (APRI), MRE, and FIB‐4 in specificity. In cirrhosis, VCTE was superior to APRI in specificity (P = 0.004) with comparable sensitivity. This study demonstrates the potential of VCTE and ARFI as diagnostic tools for fibrosis in LT recipients compared with blood‐based NITs, which were shown to be less optimal.

Summary Living donor liver transplantation (LDLT) is increasing, yet gaps exist in the understanding of psychological wellbeing of donors after liver transplant. This meta‐analysis seeks to evaluate the incidence and risk factors for donor‐related depression after liver transplantation. A search was conducted on Medline and Embase database. Articles assessing incidence of depression in LDLT donors were included. Incidence was pooled after Freeman–Turkey double‐arcsine transformation. For risk factors, dichotomous variables were analyzed with generalized linear model, while a conventional meta regression with logit transformation was conducted for continuous variables. Of 1069 abstracts, 40 articles underwent full‐text review. Seventeen articles were included. The pooled incidence of depression among 1888 LT donors was 7.66% (CI: 4.47–12.80%). Depression rates were significantly higher in Asian compared to Western studies (RR: 1.73, CI: 1.19–2.52, P = 0.0039). Female gender (P < 0.001), Caucasian ethnicity (P = 0.047), employment status (P < 0.001) and lower education levels (P = 0.044) were significantly associated with depression. Donor relationship with recipients was not a significant risk factor. LDLT remains a core aspect of the treatment of end‐stage liver disease. However, the high depression rates after LT suggest that there remains room for improvement in the care of donors’ mental health post‐transplant.

IntroductionCoagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. This study aims to assess the association between plasma tissue factor activity and LV remodeling in post-AMI patients.MethodsWe studied 228 patients with AMI and 57 healthy subjects. Patients with AMI were categorized into two age- and sex-matched groups: patients with adverse LV remodeling or reverse LV remodeling, defined by an increase or decrease, respectively, in LV end systolic volume by ≥15% over 6 months. TF activity was measured in plasma collected at baseline (within 72 hours of revascularization), 1 month and 6 months post-AMI. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess the impact of various clinical variables on TF activity in post-AMI.ResultsPlasma TF activity in post-AMI patients at baseline (29.05 ± 10.75 pM) was similar to that in healthy subjects but fell at 1 month (21.78 ± 8.23, p&lt;0.001) with partial recovery by 6 months (25.84 ± 8.80, p&lt;0.001) after AMI. Plasma TF activity at 6 month post-AMI was better restored in patients with reverse LV remodeling than those with adverse LV remodeling (27.35 ± 7.14 vs 24.34 ± 9.99; p=0.009) independent of gender, age and relevant cardiovascular risk factors.ConclusionsPlasma TF activity decreased after AMI but was better restored at 6 months in patients with reverse LV remodeling. The clinical significance of changes in post-AMI plasma TF activity needs further investigation.

Background and study aims Evidence from recent trials comparing conventional endoscopic mucosal resection (EMR) to underwater EMR (UEMR) have matured. However, studies comparing UEMR to endoscopic submucosal dissection (ESD) are lacking. Hence, we sought to conduct a comprehensive network meta-analysis to compare the efficacy of UEMR, ESD, and EMR. Methods Embase and Medline databases were searched from inception to December 2020 for articles comparing UEMR with EMR and ESD. Outcomes of interest included rates of en bloc and complete polyp resection, risk of perforation and bleeding, and local recurrence. A network meta-analysis comparing all three approaches was conducted. In addition, a conventional comparative meta-analysis comparing UEMR to EMR was performed. Analysis was stratified according to polyp sizes (< 10 mm, ≥ 10 mm, and ≥ 20 mm). Results Twenty-two articles were included in this study. For polyps ≥ 10 mm, UEMR was inferior to ESD in achieving en bloc resection (P = 0.02). However, UEMR had shorter operating time for polyps ≥ 10 mm (P < 0.001), and ≥20 mm (P = 0.019) with reduced perforation risk for polyps ≥ 10 mm (P = 0.05) compared to ESD. In addition, en bloc resection rates were similar between UEMR and EMR, although UEMR had reduced recurrence for polyps ≥ 10 mm (P = 0.013) and ≥ 20 mm (P = 0.014). UEMR also had shorter mean operating than EMR for polyps ≥ 10 mm (P < 0.001) and ≥ 20 mm (P < 0.001). Risk of bleeding and perforation with UEMR and EMR were similar for polyp of all sizes. Conclusions UEMR has demonstrated technical and oncological outcomes comparable to ESD and EMR, along with a desirable safety profile. UEMR appears to be a safe and effective alternative to conventional methods for resection of polyps ≥ 10 mm.