Incidence and management of colonoscopic perforations: 8 years' experience

AIM： To review the experience of a major medical teaching center with diagnostic and therapeutic colonoscopies and to assess the incidence and management of related colonic perforations. METHODS： All colonoscopies performed between January 1994 and December 2001 were studied. Data on patients, colonoscopic reports and procedure-related complications were collected from the departmental computerized database. The medical records of the patients with post procedural colonic perforation were reviewed. RESULTS： A total of 12 067 colonoscopies were performed during the 8 years of the study. Seven colonoscopic perforations （4 females, 3 males） were diagnosed （0.058%）. Five occurred during diagnostic and two during therapeutic colonoscopy. Six were suspected during or immediately after colonoscopy. All except one had signs of diffuse tenderness and underwent immediate operation with primary repair done in 4 patients. No deaths were reported. CONCLUSION： Perforation rate during colonoscopy is low. Nevertheless, it is a serious complication and its early recognition and treatment are essential to optimize outcome. In patients with diffuse peritonitis early operative intervention makes primary repair a safe option.

Mucin gene expression in bile of patients with and without gallstone disease,collected by endoscopic retrograde cholangiography

AIM： To investigate the pattern of mucin expression and concentration in bile obtained during endoscopic retrograde cholangiography （ERC） in relation to gallstone disease.METHODS： Bile samples obtained at ERC from 29 consecutive patients, 17 with and 12 without gallstone disease were evaluated for mucin content by gel filtration on a Sepharose CL-4B column. Dot blot analysis for bile mucin apoproteins was performed with antibodies to Mucin 1 （MUC1）, MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score （0-3） was used as a measure of antigen expression.RESULTS： MUCl, MUC2, MUC3, MUCSAC, MUC5B and MUC6 were demonstrated in 34.4%, 34.4%, 51.7%, 51.7%, 55.1% and 27.5% of bile samples, respectively.The staining intensity scores were 0.62 ± 0.94, 0.58 ± 0.90, 0.79 ± 0.97, 1.06 ± 1.22, 1.20 ± 2.26 and 0.41 ± 0.73, respectively. Mean mucin concentration measured in bile by the Sepharose CL-4B method was 22.8 ± 24.0 mg/mL （range 3.4-89.0 mg/mL）. Mean protein concentration was 8.1 ± 4.8 mg/mL （range 1.7-23.2 mg/mL）.CONCLUSION： High levels of MUC3, MUC5AC and MUC5B are expressed in bile aspirated during ERC examination. A specific pattern of mucin gene expression or change in mucin concentration was not found in gallstone disease.

Efficiency of bowel preparation for capsule endoscopy examination:A meta-analysis

Good preparation before endoscopic procedures is essential for successful visualization. The small bowel is difficult to evaluate because of its length and complex configuration. A meta-analysis was conducted of studies comparing small bowel visualization by capsule endoscopy with and without preparation. Medical data bases were searched for all studies investigating the preparation for capsule endoscopy of the small bowel up to July 31, 2007. Studies that scored bowel cleanness and measured gastric and small bowel transit time and rate of cecum visualization were included. The primary endpoint was the quality of bowel visualization. The secondary endpoints were transit times and proportion of examinations that demonstrated the cecum, with and without preparation. Meta-analysis was performed with StatDirect Statistical software, version 2.6.1 (http:// statsdirect.com). Eight studies met the inclusion criteria. Bowel visualization was scored as "good" in 78% of the examinations performed with preparation and 49% performed without (P < 0.0001). There were no significant differences in transit times or in the proportion of examinations that demonstrated the cecum with and without preparation. Capsule endoscopy preparation improves the quality of small bowel visualization, but has no effect on transit times, or demonstration of the cecum.

Inflammatory bowel disease among first generation immigrants in Israel:A nationwide epi-Israeli Inflammatory Bowel Disease Research Nucleus study

BACKGROUND Israel has a high rate of Jewish immigration and a high prevalence of inflammatory bowel disease(IBD).AIM To compare IBD prevalence in first-generation immigrants vs Israel-born Jews.METHODS Patients with a diagnosis of IBD as of June 2020 were included from the validated epi-IIRN(Israeli IBD Research Nucleus)cohort that includes 98%of the Israeli population.We stratified the immigration cohort by IBD risk according to country of origin,time period of immigration,and age group as of June 2020.RESULTS A total of 33544 patients were ascertained,of whom 18524(55%)had Crohn’s disease(CD)and 15020(45%)had ulcerative colitis(UC);28394(85%)were Israel-born and 5150(15%)were immigrants.UC was more prevalent in immigrants(2717;53%)than in non-immigrants(12303,43%,P<0.001),especially in the<1990 immigration period.After adjusting for age,longer duration in Israel was associated with a higher point prevalence rate in June 2020(high-risk origin:Immigration<1990:645.9/100000,≥1990:613.2/100000,P=0.043;intermediate/low-risk origin:<1990:540.5/100000,≥1990:192.0/100000,P<0.001).The prevalence was higher in patients immigrating from countries with high risk for IBD(561.4/100000)than those originating from intermediate-/low-risk countries(514.3/100000;P<0.001);non-immigrant prevalence was 528.9/100000.CONCLUSION Lending support to the environmental effect on IBD etiology,we found that among immigrants to Israel,the prevalence of IBD increased with longer time since immigration,and was related to the risk of IBD in the country of origin.The UC rate was higher than that of CD only in those immigrating in earlier time periods.

H pylori recurrence after successful eradication

Recurrence of H pylori after eradication is rare in developed countries and more frequent in developing countries. Recrudescence (recolonization of the same strain within 12 mo after eradication) rather than reinfection (colonization with a new strain, more than 12 mo after eradication) is considered to be responsible for most of the cases. This observation was confirmed only in developed countries, while in developing countries a recent meta-analysis demonstrated a high rate of reinfection. The proportion of H pylori annual recurrence was 2.67% and 13.00% in developed and developing countries, respectively. Nested meta-analysis (only cases with a longer follow-up and a negative 13CUBT a year after eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54] and 12.00% (RR, 0.92) in developed and developing countries, respectively. These findings support the notion that in developed countries many cases of recurrence are due to recrudescence within the first year after eradication, with a 46% drop in the recurrence rate after the first year post eradication, while in developing countries reinfection is more pronounced, and continue at the same rate since eradication. A different approach for follow-up after H pylori eradication is probably needed in patients of developing countries, since reinfection is highly prevalent.

Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer

Colorectal cancer （CRC） is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsateUite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracilbased chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DNA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.

MUC1 and colorectal cancer pathophysiology considerations

Several lines of evidence point towards a biological role of mucin and particularly MUC1 in colorectal cancer. A positive correlation was described between mucin secretion, proliferation, invasiveness, metastasis and bad prognosis. But, the role of MUC1 in cancer progression is still controversial and somewhat confusing. While Mukherjee and colleagues developed MUC1-specific immune therapy in a CRC model, Lillehoj and coinvestigators showed recently that MUC1 inhibits cell proliferation by a β-catenin-dependent mechanism. In carcinoma cells the polarization of MUC1 is lost and the protein is over expressed at high levels over the entire cell surface. A competitive interaction between MUC1 and E-cadherin, through β-catenin binding, disrupts E-cadherin-mediated cell-cell interactions at sites of MUC1 expression. In addition, the complex of MUC1-β-catenin enters the nucleus and activates T-cell factor/leukocyte enhancing factor 1 transcription factors and activates gene expression. This mechanism may be similar to that just described for DCC and UNC5H, which induced apoptosis when not engaged with their ligand netrin, but mediate signals for proliferation, differentiation or migration when ligand bound.

MicroRNAs as a potential prognostic factor in gastric cancer

AIM:To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer.METHODS:The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available.Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples,preserving the small RNA fraction.Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection.The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR).Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group,n=14,31%) and those who did not (good-prognosis group,n=31,69%).RESULTS:Three miRs,miR-451,miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P<0.0002,0.0027 and 0.0046 respectively).High expression of each miR was associated with poorer prognosis for both recurrence and survival.Using miR-451,the positive predictive value for non-recurrence was 100% (13/13).The expression of the differential miRs was verified by qRT-PCR,showing high correlation to the microarray data and similar separation into prognosis groups.CONCLUSION:This study identified three miRs,miR-451,miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer.Of these,miR-451 had the strongest prognostic impact.

Membrane-bound mucins and mucin terminal glycans expression in idiopathic or Helicobacter pylori, NSAID associated peptic ulcers

AIM: To determine the expression of membrane-bound mucins and glycan side chain sialic acids in Helicobacter pylori (H. pylori)-associated, non-steroidal inflammatory drug (NSAID)-associated and idiopathic-gastric ulcers.

Gastric mucin expression in Helicobacter pylori-related, nonsteroidal anti-inflammatory drug-related and idiopathic ulcers

AIM: To determine the pattern of secreted mucin expression in Helicobacter pylori (H. pylori)-related, nonsteroidal anti-inflammatory drug (NSAID)-related and idiopathic gastric ulcers. METHODS: We randomly selected 92 patients with H. pylori-associated (n = 30), NSAID-associated (n = 18), combined H. pylori and NSAID-associated gastric ulcers (n = 24), and patients with idiopathic gastric ulcers (n = 20). Immunohistochemistry for T-cell CD4/CD8, andfor mucin 5AC (MUC5AC) and mucin 6 (MUC6), was performed on sections of the mucosa from the ulcer margin. Inflammation score was assessed according to the Sydney system. RESULTS: MUC5AC was expressed on the surface epithelium (98.9%) and neck glands (98.9%) with minimal expression in the deep glands (6.5%). MUC6 was strongly expressed in the deep glands (97.8%), variable in the neck glands (19.6%) and absent in the surface epithelium (0%). The pattern of mucin expression in idiopathic ulcer margins was not different from the expression in ulcers associated with H. pylori, NSAIDs, or combined H. pylori and NSAIDs. CD4/CD8 ratio was higher in H. pylori-positive patients (P = 0.009). Idiopathic ulcers are associated with hospitalized patients and have higher bleeding and mortality rates. CONCLUSION: Idiopathic ulcers have a unique clinical profile. Gastric mucin expression in idiopathic gastric ulcers is unchanged compared with H. pylori and/or NSAID-associated ulcers.

服用小剂量阿司匹林的无症状患者的内镜检查结果

Aspirin is widely used for its antiplatelet activity, but it harbors a risk of severe adverse gastrointestinal effects, such as bleeding and perforation, espe cially in elderly people. Our aim to assess the prevalence of upper gastrointest inal lesions and the effect of aspirin on the gastrointestinal mucosa in asympto matic subjects taking minid- ose aspirin (100 to 325 mg per day) for more than 3 mon- ths. A prospective, open design was used. Patients attending the ophthalmology and cardiology outpatient clinics who had a medical history of more than 3 mont hs of regular aspirin consumption were referred for esophagogastroduodenoscopy(E GD). Of the 90 patients referred for EGD, 44 were symptomatic (epigastric pain o r dyspepsia) and were excluded from the study. The 46 asymptomatic patients incl uded 22 men and 24 women of mean age 70 ±10 years (range, 36 to 87 years); 32% were current or former smokers. Mean daily aspirin dose was 129.34 ±76.61 mg. O nly 24%were taking a gastroprotective agent. EGD revealed ulcer or erosions in 47.83%of the patients: erosive gastroduodenitis in 13 patients,gastric ulcer in 14, duodenal ulcer in 2, and gastric and duodenal ulcers in 2. Urease test for Helicobacter pylori infection was positive in 26%. Univariate and multivariate analysis revealed no factor other than aspirin predictive of a positive endoscop - y.Minidose aspirin treatment is associated with a high prevalence of ulceratio ns of the stomach and duodenum.

^(13)C-尿素呼气试验对幽门螺杆菌根除成功的检测:对5885例以色列患者的研究

Helicobacter pylori (Hp) infection is highly prevalent in many countries and may cause gastritis, peptic ulcer disease, gastric cancer, and lymphoma. Successful eradication depends on the specific treatment used, patient compliance, and Hp antibiotic resistance. The primary aim was to characterize groups of patients with one or more failures of Hp eradication treatment. The secondary aim was to evaluate the factors that influence eradication failure. Between April 1, 1998, and December 31, 2001, 5885 patients were studied for the success of Hp eradication with the 13C- urea breath test ( 13C- UBT): 5442 after one course of treatment (Group I), 380 after two courses (Group II), and 63 after three courses (Group Ⅲ ). The 13C- UBT was positive in 27.8% , 37.4% , and 47.6% of patients in Groups Ⅰ , Ⅱ , and Ⅲ , respectively (PI- II = 0.000, PⅡ - Ⅲ = 0.126). A combination of omeprazole, amoxicillin, and clarithromycin (OAC) was used in 31.3% , 27.4% , and 7.9% of Groups I, Ⅱ , and Ⅲ , respectively, and a combination of omeprazole, amoxicillin, and metronidazole (OAM) in 15.2% , 28.9% , and 28.6% , respectively. Regimens that contained clarithromycin were used in decreasing order in Groups Ⅰ , Ⅱ , and Ⅲ , and regimens containing metronidazole, bismuth, or tetracycline, in increasing order. The only good prognostic factor for successful eradication was Israeli origin, while European- American and Asian- African origin, recurrence of symptoms, a history of duodenal ulcer, and chronic proton pump inhibitor (PPI) use did not favor successful eradication. Our results suggest that origin, history of peptic disease, and chronic PPI use are predictors of eradication failure.

Mucin expression and the pancreas:A systematic review and meta-analysis

AIM To assess mucin expression in pancreatic premalignant and malignant states, and to establish its role as a prognostic marker.METHODS English Medical literature searches were conducted for "mucin" and "pancreas". Observational studies were included. Meta-analysis was performed by using Comprehensive meta-analysis software. Pooled odds ratios and 95%CIs were calculated. RESULTS Out of 949 eligible papers we found 20 according to the inclusion criteria, including 4262 patients, published till May 31, 2016. Mucin expression increased in pancreatic lesions with OR 10.206(95%CI: 4.781-21.781, P < 0.0001). Measure of heterogeneity was high: Q = 296.973, df(Q) = 55.00, I2 = 81.48%. We found a significant increase in the expression of MUC2, MUC4 and MUC5 AC, 13.39, 118.43 and 13.91 times respectively, in pancreatic lesion in comparison with normal pancreatic tissue, and decreased expression of MUC5 B.CONCLUSION Mucin expression may serve as prognostic marker for transformation of intraductal papillary mucinous neoplasms to ductal adenocarcinoma, for aggressiveness of the pancreatic tumor, and as targets for potential therapy.

Effect of the transcutaneous electrical stimulation system on esophageal-acid exposure in patients non-responsive to once-daily proton-pump inhibitor:proof-of-concept study

Background:Gastroesophageal reflux disease(GERD)is a common disorder.Overall,≤35%of GERD patients fail the standard dose of proton-pump-inhibitor(PPI)treatment.Due to the high prevalence and low satisfaction rate with treatment failure,there is an unmet need for new treatment.Our aim was to evaluate whether the use of the transcutaneous electrical stimulation system(TESS)can reduce esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI.Methods:We enrolled 10 patients suffering from heartburn and regurgitation with an abnormal esophageal-acid exposure(off PPIs)who failed standard-dose PPI.After the placement of a wireless esophageal pH capsule,all patients were treated with TESS.The primary end point was the reduction in the baseline(pretreatment)24-hour percent total time pH<4 and/or DeMeester score by 50%.Results:Seven GERD patients(five females and two males,aged 49.3610.1 years)completed the study.At baseline,the mean percent total time pH<4 was 12.064.9.Following TESS,the mean percent total time pH<4 dropped to 5.563.4,4.562.6,3.762.9,and 4.462.5 on Days 1,2,3,and 4,respectively.At baseline,the mean DeMeester score was 39.0618.5.After TESS,the mean DeMeester score dropped to 15.869.2,13.266.8,11.269.4,and 12.066.8 on Days 1,2,3,and 4,respectively.Conclusion:TESS is a safe and potentially effective modality in reducing esophageal-acid exposure in GERD patients unresponsive to standard-dose PPI.A larger and prospective controlled study is needed to verify these preliminary results.