Standard-definition White-light,High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas:A Multicenter Randomized Controlled Trial

Objective This study aimed to compare the performance of standard-definition white-light endoscopy(SD-WL),high-definition white-light endoscopy(HD-WL),and high-definition narrow-band imaging(HD-NBI)in detecting colorectal lesions in the Chinese population.Methods This was a multicenter,single-blind,randomized,controlled trial with a non-inferiority design.Patients undergoing endoscopy for physical examination,screening,and surveillance were enrolled from July 2017 to December 2020.The primary outcome measure was the adenoma detection rate(ADR),defined as the proportion of patients with at least one adenoma detected.The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression.Results Out of 653 eligible patients enrolled,data from 596 patients were analyzed.The ADRs were 34.5%in the SD-WL group,33.5%in the HD-WL group,and 37.5%in the HD-NBI group(P=0.72).The advanced neoplasm detection rates(ANDRs)in the three arms were 17.1%,15.5%,and 10.4%(P=0.17).No significant differences were found between the SD group and HD group regarding ADR or ANDR(ADR:34.5%vs.35.6%,P=0.79;ANDR:17.1%vs.13.0%,P=0.16,respectively).Similar results were observed between the HD-WL group and HD-NBI group(ADR:33.5%vs.37.7%,P=0.45;ANDR:15.5%vs.10.4%,P=0.18,respectively).In the univariate and multivariate logistic regression analyses,neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL(HD-WL:OR 0.91,P=0.69;HD-NBI:OR 1.15,P=0.80).Conclusion HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients.It can be concluded that HD-NBI or HD-WL is not superior to SD-WL,but more effective instruction may be needed to guide the selection of different endoscopic methods in the future.Our study’s conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources,especially advanced imaging technologies.

Consensus on the digestive endoscopic tunnel technique

With the digestive endoscopic tunnel technique(DETT), many diseases that previously would have been treated by surgery are now endoscopically curable by establishing a submucosal tunnel between the mucosa and muscularis propria(MP). Through the tunnel, endoscopic diagnosis or treatment is performed for lesions in the mucosa, in the MP, and even outside the gastrointestinal(GI) tract.At present, the tunnel technique application range covers the following:(1)Treatment of lesions originating from the mucosal layer, e.g., endoscopic submucosal tunnel dissection for oesophageal large or circular early-stage cancer or precancerosis;(2) treatment of lesions from the MP layer, per-oral endoscopic myotomy, submucosal tunnelling endoscopic resection, etc.; and(3) diagnosis and treatment of lesions outside the GI tract, such as resection of lymph nodes and benign tumour excision in the mediastinum or abdominal cavity. With the increasing number of DETTs performed worldwide, endoscopic tunnel therapeutics, which is based on DETT, has been gradually developed and optimized. However, there is not yet an expert consensus on DETT to regulate its indications, contraindications, surgical procedure, and postoperative treatment.The International DETT Alliance signed up this consensus to standardize the procedures of DETT. In this consensus, we describe the definition, mechanism,and significance of DETT, prevention of infection and concepts of DETTassociated complications, methods to establish a submucosal tunnel, and application of DETT for lesions in the mucosa, in the MP and outside the GI tract(indications and contraindications, procedures, pre-and postoperative treatments, effectiveness, complications and treatments, and a comparison between DETT and other operations).

Corticosteroid therapy in ulcerative colitis:Clinical response and predictors

AIM:To evaluate clinical response to initial corticosteroid(CS) treatment in Chinese ulcerative colitis patients(UC) and identify predictors of clinical response.METHODS:Four hundred and twenty-three UC patients who were initially treated with oral or intravenous CS from 2007 to 2011 were retrospectively reviewed at eight inflammatory bowel disease centers in China,and 101 consecutive cases with one-year follow-up were analyzed further for clinical response and predictors.Short-term outcomes within one month were classified as primary response and primary non-response.Longterm outcomes within one year were classified as prolonged CS response,CS dependence and secondary non-response.CS refractoriness included primary and secondary non-response.Multivariate analyses were performed to identify predictors associated with clinical response.RESULTS:Within one month,95.0%and 5.0%of the cases were classified into primary response andnon-response,respectively.Within one year,41.6%of cases were assessed as prolonged CS response,while49.5%as CS dependence and 4.0%as secondary nonresponse.The rate of CS refractoriness was 8.9%,while the cumulative rate of surgery was 6.9%within one year.After multivariate analysis of all the variables,tenesmus was found to be a negative predictor of CS dependence(OR=0.336;95%CI:0.147-0.768;P=0.013)and weight loss as a predictor of CS refractoriness(OR=5.662;95%CI:1.111-28.857;P=0.040).After one-month treatment,sustained high Sutherland score(≥6)also predicted CS dependence(OR=2.347;95%CI:0.935-5.890;P=0.014).CONCLUSION:Tenesmus was a negative predictor of CS dependence,while weight loss and sustained high Sutherland score were strongly associated with poor CS response.

Genetic diagnosis strategy of hereditary non-polyposis colorectal cancer

AIM: To study the characteristics of mismatch repair gene mutation of Chinese hereditary non-polyposis colorectal cancer (HNPCC) and hMLH1 gene promoter methylation, and to improve the screening strategy and explore the pertinent test methods. METHODS: A systematic analysis of 30 probands from HNPCC families in the north of China was performed by immunohistochemistry, microsatellite instability (MSI), gene mutation and methylation detection. RESULTS: High frequency microsatellite instability occurred in 25 probands (83.3%) of HNPCC family. Loss of hMLH1 and hMSH2 protein expression accounted for 88% of all microsatellite instability. Pathogenic muta-tion occurred in 14 samples and 3 novel mutational sites were discovered. Deletion of exons 1-6, 1-7 and 8 of hMSH2 was detected in 3 samples and no large fragment deletion was found in hMLH1. Of the 30 probands, hMLH1 gene promoter methylation occurred in 3 probands. The rate of gene micromutation detection combined with large fragment deletion detection was 46.7%-56.7%. The rate of the two methods in combination with methylation detection was 63.3%. CONCLUSION: Scientific and rational detection strategy can improve the detection rate of HNPCC. Based on traditional molecular genetics and combined with epigenetics, multiple detection methods can accurately diagnose HNPCC.

Advances in the study of Lynch syndrome in China

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers due to inherited mutations in mismatch repair(MMR) genes. During the last decades, therehave been great advances in research on Chinese Lynch syndrome. This review mainly focuses on the genetic basis, clinicopathologic features, diagnosis, intervention,chemoprevention, and surveillance of Lynch syndrome in China. In addition to frequently altered MMR genes, such as MLH1, MSH2, MSH6, and MLH3,other MMR-associated genes, such as those encoding human exonuclease 1, transforming growth factor βreceptor 2, and alanine aminopeptidase, metastasisassociated protein 2, adenomatosis polyposis coli down-regulated 1, and hepatic and glial cell adhesion molecule have also been implicated in Chinese Lynch syndrome. Most Chinese researchers focused on the clinicopathologic features of Lynch syndrome, and it is noticeable that the most frequent extracolonic tumor in northeast China is lung cancer, which is different from other areas in China. The Chinese diagnostic criteria for Lynch syndrome have been established to identify gene mutation or methylation. With regard to chemoprevention, celecoxib may be effective to prevent polyps relapse in Lynch syndrome carriers. Additionally,a colonoscopy-based surveillance strategy for the prevention and early detection of neoplasms in Lynchsyndrome carriers has been proposed.

Cronkhite-Canada syndrome polyps infiltrated with IgG4-positive plasma cells

Cronkhite-Canada syndrome(CCS) is a rare but serious protein-losing enteropathy, but little is known about the mechanism. Further more, misdiagnosis is common due to non-familiarity of its clinical manifestation. A 40-year-old male patient was admitted to our hospital because of diarrhea and hypogeusia associated with weight loss for 4 mo. On physical examination, skin pigmentation, dystrophic nail changes and alopecia were noted. He had no alike family history. Laboratory results revealed low levels of serum albumin(30.1 g/L, range: 35.0-55.0 g/L), serum potassium(2.61 mmol/L, range: 3.5-5.5 mmol/L) and blood glucose(2.6 mmol/L, range: 3.9-6.1 mmol/L). The erythrocyte sedimentation rate was elevated to 17 mm/h(range: 0-15 mm/h). X-ray of chest and mandible was normal. The endoscopic examination showed multiple sessile polyps in the stomach, small bowel and colorectum. Histopathologic examination of biopsies obtained from those polyps showed hyperplastic change, cystic dilatation and distortion of glands with inflammatory infiltration, eosinophilic predominance and stromal edema. Immune staining for IgG 4 plasma cells was positive in polyps of stomach and colon. The patient was diagnosed of CCS and treated with steroid, he had a good response to steroid. Both histologic findings and treatment response to steroid suggested an autoimmune mechanism underling CCS.

Immunoglobulin G4-related autoimmune pancreatitis and sialadenitis: A case report

Immunoglobulin G4(Ig G4)-related disease is a rare systemic diseases. A 67-year-old male presented at our institution with mild upper abdominal pain and jaundice for 20 d. Laboratory results revealed high levels of Ig G4(15.4 g/L,range: 0.08-1.4 g/L). Computed tomography(CT) showed significant enlargement of the entire pancreas and a capsule-like low-density rim surrounding the whole pancreas. Positron emission tomography/CT revealed increased uneven metabolism of the entire pancreas. Both magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed stenosis of the distal common bile duct and proximal main pancreatic duct,and dilation of the proximal common bile duct and extra- and intra-hepatic bile ducts. He was diagnosed with Ig G4-related autoimmune pancreatitis. The patient was treated with prednisone for 14 mo. The patient responded well to prednisone but upon cessation of the corticosteroid developed enlargement of the submandibular gland. The patient's serum Ig G4 was elevated at 23.9 g/L. It is important to maintain treatment,so the patient was again treated with prednisone and had a good response. Follow-up of Ig G4-related disease is thus necessary.

Candidate colorectal cancer predisposing gene variants in Chinese early-onset and familial cases

AIM: To investigate whether whole-exome sequencing may serve as an efficient method to identify known or novel colorectal cancer(CRC) predisposing genes in early-onset or familial CRC cases.METHODS: We performed whole-exome sequencing in 23 Chinese patients from 21 families with nonpolyposis CRC diagnosed at ≤ 40 years of age, or from multiple affected CRC families with at least 1 firstdegree relative diagnosed with CRC at ≤ 55 years of age.Genomic DNA from blood was enriched for exome sequences using the Sure Select Human All Exon Kit, version 2(Agilent Technologies) and sequencing was performed on an Illumina Hi Seq 2000 platform.Data were processed through an analytical pipeline to search for rare germline variants in known or novel CRC predisposing genes.RESULTS: In total, 32 germline variants in 23 genes were identified and confirmed by Sanger sequencing.In 6 of the 21 families(29%), we identified 7 mutations in 3 known CRC predisposing genes including MLH1(5 patients), MSH2(1 patient), and MUTYH(biallelic, 1 patient), five of which were reported as pathogenic.Inthe remaining 15 families, we identified 20 rare and novel potentially deleterious variants in 19 genes, six of which were truncating mutations.One previously unreported variant identified in a conserved region of EIF2AK4(p.Glu738_Asp739insA rgA rg) was found to represent a local Chinese variant, which was significantly enriched in our early-onset CRC patient cohort compared to a control cohort of 100 healthy Chinese individuals scored negative by colonoscopy(33.3% vs 7%, P < 0.001).CONCLUSION: Whole-exome sequencing of early-onset or familial CRC cases serves as an efficient method to identify known and potential pathogenic variants in established and novel candidate CRC predisposing genes.

The first year follow-up after colorectal adenoma polypectomyis important: A multiple-center study in symptomatichospital-based individuals in China

The recurrence of colorectal adenoma(CRA)is high.Although there are guidelines for colonoscopy surveillance after polypectomy in other countries,little is known about its recurrence rate and recurrence peak,especially in China.The aim of the present research is to investigate how long after polypectomy follow-up should take and to analyze risk factors of recurrence.1208 patients who received polypectomies fromfive clinical research centers in four regions of China(Shanghai,Guangzhou,Nanjing and Beijing)were included.They were divided into 4 groups:group A(follow-up≤1 year after poly-pectomy),group B(follow-up 2–3 years after polypect-omy),group C(follow-up 4–5 years after polypectomy),and group D(follow-up>5 years after polypectomy).The sex,age,adenoma location,size,number,and pathological characteristics were compared.On the whole,the recur-rence rate was 59.46%in group A,61.09%in group B,78.07%in group C,and 87.12%in group D,which indicated an increased tendency with a prolonged follow-up duration.There was a significant difference between group A and C or D,and between group B and C or D(P<0.01),but there was no statistical difference between group A and B.Additionally,the recurrent patients in thefirst year had a recurrence rate of 97.33%in thefirst three years(59.46/61.09),which means that the peak of recurrence was almost entirely concentrated in thefirst year.The recurrence rate was higher in males and the elder.The risk factors included multiple numbers,villous feature,high-grade dysplasia of medium or smaller size and location in the distal colon.In conclusion,the peak of recurrence was almost totally concentrated in thefirst year;meanwhile,thefirst year follow-up is of critical importance in China.It may not be necessary to do the follow-up examination during the second and third years,but after three years,another colonoscopy should be undertaken.

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients:a multicenter randomized-controlled trial

Background:Data from single-center experience or small sample-sized studies have shown that chromoendoscopy(CE)might be superior to white-light endoscopy(WLE)for dysplasia surveillance in ulcerative colitis(UC)patients.We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies(WLT),WLE with random biopsies(WLR),and dye-based CE with targeted biopsies(CET)in UC patients.Methods:Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms(WLT,WLR,and CET).Only high-definition endoscopy was used in all three groups.The patients were followed up by annual endoscopy with biopsies through December 2017.Results:With a median follow-up time of 55 months,a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set:WLT(n=43),WLR(n=40),and CET(n=39).A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients.WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT(8.1%and 9.7%vs 1.9%;P=0.014 and 0.004,respectively).WLR obtained more biopsied samples than WLT and CET(16.465.1 vs 4.361.4 and 4.361.4;both P<0.001).During the second half of the follow-up(37-69 months),CET could identify more colonoscopies that diagnosed dysplasia than WLT(13.3%vs 1.6%,P=0.015)and showed a trend for increasing the detection rate compared with WLR(13.3%vs 4.9%,P=0.107).Conclusions:For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC,CET appeared to be more effective thanWLT and less tedious than WLR.CET was found to be particularly useful when a long-term(>3 years)follow-up was conducted for dysplasia surveillance.The trial was registered on www.chictr.org.cn(ChiCTR1900023689).

Renal Artery Pseudoaneurysm Rupturing into the Small Intestine Causing Gastrointestinal Bleeding

A 21-year-old man was hospitalized with intermittent melena for 6 months. The patient was placed with a renal artery stent because of a let1 renal pseudoaneurysnl caused by trauma one year ago. Gastroscopy revealed traces of dark red blood in the lower segment of the duodenum, and enteroscopy revealed a large, purplish-red mass at the junction between the duodenum and jejunum [Figure 1]. The surface structure of the mass was unclear, and the mass was soft and appeared pedicled.

Over-the-scope Clip System for Wound Closure after Endoscopic Resection of an Esophageal Submucosal Tumor：A Case Report

To the Editor：Esophageal leiomyomas are the most common benign primary tumors of the esophagus and the common esophageal subepithelial lesions.The methods of treatment for esophageal submucosal lesions include surgical enucleation,endoscopic submucosal dissection,endoscopic enucleation,and submucosal tunneling with endoscopic removal （STER）.Courses of treatment for esophageal leiomyomas are related to a variety of factors,including tumor size,location,morphology,and the patient＆#39;s symptoms. The size and location of the tumor are the key factors in the selection of excision methods.With the development of endoscopic technology,the more endoscopic resection techniques have been proven to be feasible for tumors originating from muscularis propria,such as endoscopic full-thickness resection and the over-the-scope clipping device system （OTSC）. OTSC is used for primary or rescue therapy for patients who undergoing closure of perforations or leaks.