Predominant mucosal IL-8 mRNA expression in non-cagA Thais is risk for gastric cancer

AIM:To study gastric mucosal interleukine-8(IL-8) mRNA expression,the cytotoxin-associated gene A(cagA) mutation,and serum pepsinogen(PG)Ⅰ/Ⅱ ratio related risk in Thai gastric cancer.METHODS:There were consent 134 Thai non-cancer volunteers who underwent endoscopic narrow band imaging examination,and 86 Thais advance gastric cancer patients who underwent endoscopic mucosal biopsies and gastric surgery.Tissue samples were taken by endoscopy with 3 points biopsies.The serum PG Ⅰ,Ⅱ,and Helicobacter pylori(H.pylori) immunoglobulin G(IgG) antibody for H.pylori were tested by enzyme-linked immunosorbent assay technique.The histopathology description of gastric cancer and non-cancer with H.pylori detection was defined with modified Sydney Score System.Gastric mucosal tissue H.pylori DNA was extracted and genotyped for cagA mutation.Tissue IL-8 and cyclooxygenase-2(COX-2) mRNA expression were conducted by real time relative quantitation polymerase chain reaction.From 17 Japanese advance gastric cancer and 12 benign gastric tissue samples,all were tested for genetic expression with same methods as well as Thai gastric mucosal tissue samples.The multivariate analysis was used for the risk study.Correlation and standardized t-test were done for quantitative data,P value < 0.05 was considered as a statistically significant.RESULTS:There is a high non cagA gene of 86.8 per cent in Thai gastric cancer although there are high yields of the East Asian type in the positive cagA.The H.pylori infection prevalence in this study is reported by combined histopathology and H.pylori IgG antibody test with 77.1% and 97.4% of sensitivity and specificity,respectively.The serum PG Ⅰ/Ⅱ ratio in gastric cancer is significantly lower than in the non-cancer group,P = 0.045.The serum PG Ⅰ/Ⅱ ratio of less than 3.0 and IL-8 mRNA expression ≥ 100 or log 10 ≥ 2 are significant cut off risk differences between Thai cancer and non-cancer,P = 0.03 and P < 0.001,respectively.There is a significantly lower PGI/II ratio in Japanese than that in Thai gastric cancer,P = 0.026.Serum PG Ⅰ/Ⅱ ratio at cut off less than 3.0 and IL-8 mRNA expression Raw RQ > 100 or log 10 > 2 are significantly difference between Thai cancer group when compared to non-cancer group,P = 0.013 and P < 0.001,respectively.In the correlation study,low PG Ⅰ/Ⅱ ratio does not associate with chronic atrophic gastritis severity score in Thais non-cancer cases.However,there is a trend,but not significant convert correlation between IL-8 mRNA expression level and low PG Ⅰ/Ⅱ ratio in Thai positive H.pylori infection.The high expression of IL-8 gene demonstrates a poorer prognosis by stage and histology.CONCLUSION:Predominant gastric mucosal IL-8 mRNA expression level,H.pylori infection,and low PG Ⅰ/Ⅱ ratio are relative risks for Thai gastric cancer without correlation with cagA mutation.

胃癌预防亚太地区共识指南

背景与目的:胃癌是亚太地区的主要健康负担之一,但对其预防策略尚缺乏共识。本共识会议旨在评价预防胃癌的策略。方法:多学科专家组应用德尔菲(Delphi)法制订共识条文,提呈相关数据,对证据等级、推荐强度以及共识水平予以分级。结果:幽门螺杆菌(H.pylori)感染是非贲门胃腺癌必要但非充分的致病因子。盐的高摄入与胃癌强烈相关。新鲜果蔬对胃癌具有预防作用,但维生素和其他饮食补充并不能预防胃癌。H.pylori感染中的宿主-细菌相互作用导致不同类型的胃炎和胃酸分泌,从而决定疾病结局。胃癌阳性家族史是一个重要的危险因素。低血清胃蛋白酶原反映胃萎缩程度,可作为检出胃癌高危人群的标志物。H.pylori筛查和治疗被推荐作为减少高危人群胃癌危险性的一种策略,该策略在萎缩性胃炎发生前实施最为有效,但并不排除对胃癌高危人群的内镜监测。对胃癌低危人群不推荐行H.pylori筛查。H.pylori感染的一线治疗应遵循国家治疗指南。结论:高危人群中H.pylori筛查和根除策略可能会减少胃癌的发生率,本共识根据现有证据予以推荐。

Magnifying endoscopy in upper gastroenterology for assessing lesions before completing endoscopic removal

Any prognosis of gastrointestinal (GI) cancer is closely related to the stage of the disease at diagnosis.Endoscopic submucosal dissection (ESD) and en bloc endoscopic mucosal resection (EMR) have been performed as curative treatments for many early-stage GI lesions in recent years.The technologies have been widely accepted in many Asian countries because they are minimally invasive and supply thorough histopathologic evaluation of the specimens.However,before engaging in endoscopic therapy,an accurate diagnosis is a precondition to effecting the complete cure of the underlying malignancy or carcinoma in situ.For the past few years,many new types of endoscopic techniques,including magnifying endoscopy with narrow-band imaging (MENBI),have emerged in many countries because these methods provide a strong indication of early lesions and are very useful in determining treatment options before ESD or EMR.However,to date,there is no comparable classification equivalent to "Kudo's Pit Pattern Classification in the colon",for the upper GI,there is still no clear internationally accepted classification system of magnifying endoscopy.Therefore,in order to help unify some viewpoints,here we will review the defining optical imaging characteristics and the current representative classifications of microvascular and microsurface patterns in the upper GI tract under ME-NBI,describe the accurate relationship between them and the pathological diagnosis,and their clinical applications prior to ESD or en bloc EMR.We will also discuss assessing the differentiation and depth of invasion,defying the lateral spread of involvement and targeting biopsy in real time.

Feasibility and safety of endoscopic submucosal dissection for lower rectal tumors with hemorrhoids

AIM: To evaluate the feasibility and safety of endoscopic submucosal dissection(ESD) for lower rectal lesions with hemorrhoids.METHODS: The outcome of ESD for 23 lesions with hemorrhoids(hemorrhoid group) was compared with that of 48 lesions without hemorrhoids extending to the dentate line(non-hemorrhoid group) during the same study period. RESULTS: Median operation times(ranges) in the hemorrhoid and non-hemorrhoid groups were 121(51-390) and 130(28-540) min. The en bloc resection rate and the curative resection rate in the hemorrhoid group were 96% and 83%, and they were 100% and 90% in the non-hemorrhoid group, respectively. In terms of adverse events, perforation and postoperative bleeding did not occur in both groups. In terms of the clinical course of hemorrhoids after ESD, the rate of complete recovery of hemorrhoids after ESD in lesions with resection of more than 90% was significantly higher than that in lesions with resection of less than 90%.CONCLUSION: ESD on lower rectal lesions with hemorrhoids could be performed safely, similarly to that on rectal lesions extending to the dentate line without hemorrhoids. In addition, all hemorrhoids after ESD improved to various degrees, depending on the resection range.

Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics

Hepatitis B virus(HBV) infection is major global issue, because chronic HBV infection is strongly associated with liver cancer. HBV spread worldwide with variousmutations and variations. This variability, called quasispecies, is derived from no proof-reading capacity of viral reverse transcriptase. So far, thousands of studies reported that the variety of genome is closely related to the geographic distribution and clinical characteristics. Recent technological advances including capillary sequencer and next generation sequencer have made in easier to analyze mutations. The variety of HBV genome is related to not only antigenicity of HBs-antigen but also resistance to antiviral therapies. Understanding of these variations is important for the development of diagnostic tools and the appropriate therapy for chronic hepatitis B. In this review, recent publications in relation to HBV mutations and variations are updated and summarized.

Factors associated with residual gastroesophageal reflux disease symptoms in patients receiving proton pump inhibitor maintenance therapy

AIM To elucidate the factors associated with residual gastroesophageal reflux disease(GERD) symptoms in patients receiving proton pump inhibitor(PPI) maintenance therapy in clinical practice.METHODS The study included 39 GERD patients receiving maintenance PPI therapy. Residual symptoms were assessed using the Frequency Scale for Symptoms of GERD(FSSG) questionnaire and the Gastrointestinal Symptom Rating Scale(GSRS). The relationships between the FSSG score and patient background factors, including the CYP2C19 genotype, were analyzed.RESULTS The FSSG scores ranged from 1 to 28 points(median score: 7.5 points), and 19 patients(48.7%) had a score of 8 points or more. The patients' GSRS scores were significantly correlated with their FSSG scores(correlation coefficient = 0.47, P < 0.005). In erosive esophagitis patients, the FSSG scores of the CYP2C19 rapid metabolizers(RMs) were significantly higher than the scores of the poor metabolizers and intermediate metabolizers(total scores: 16.7 ± 8.6 vs 7.8 ± 5.4, P < 0.05; acid reflux-related symptom scores: 12 ± 1.9 vs 2.5 ± 0.8, P < 0.005). In contrast, the FSSG scores of the CYP2C19 RMs in the non-erosive reflux disease patients were significantly lower than those of the other patients(total scores: 5.5 ± 1.0 vs 11.8 ± 6.3, P < 0.05; dysmotility symptom-related scores: 1.0 ± 0.4 vs 6.0 ± 0.8, P < 0.01). CONCLUSION Approximately half of the GERD patients receiving maintenance PPI therapy had residual symptoms associated with a lower quality of life, and the CYP2C19 genotype appeared to be associated with these residual symptoms.

Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic favors such as hypoxia-inducible factor 1 alpha (HIF-1alpha and vascular endothelial growth factor (VEGF).METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after theoccurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF.RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry.HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis.CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.

Gastric plexiform fibromyxoma resected by endoscopic submucosal dissection after observation of chronological changes:A case report

A 66-year-old man was diagnosed with a gastric submucosal tumor. Endoscopic ultrasound(EUS) revealed an iso/hypoechoic mass in the third layer. No malignant cells were detected in a histological examination. Yearly follow-up endoscopy and EUS showed the slow growth of the tumor. Endoscopic submucosal dissection(ESD) was performed and a glistening tumor was resected. The lesion showed a multinodular plexiform growth pattern consisting of spindle cells with an abundant fibromyxoid stroma that was rich in small vessels. The tumor was diagnosed as plexiform fibromyxoma(PF) by immunohistochemistry. Although difficulties are associated with reaching a diagnosis preoperatively, chronological changes on EUS may contribute to the diagnosis of PF. ESD may also be useful in the diagnosis and treatment of PF.

Esophageal diverticulum exposed during endoscopic submucosal dissection of superficial cancer

Endoscopic submucosal dissection(ESD) is now widely accepted as a strategy to treat superficial esophageal neoplasms.The rate of adverse events,such as perforation,has been decreasing with the improvement of devices and techniques.In this paper,we report a case of esophageal cancer that had a diverticulum under cancerous epithelium.The diverticulum was not detected during preoperative examination,and led to perforation during the ESD procedure.Our case shows that,although rare,some diverticula can exist underneath the mucosal surface without obvious depression.If there is any sign of hidden diverticula during ESD,surgeons should proceed with caution or,depending on the case,the procedure should be discontinued to avoid adverse events.

Efficacy of forced coagulation with low high-frequency power setting during endoscopic submucosal dissection

AIM To investigated the hemostatic ability of the S and F1-10 methods in clinical and ex vivo studies.METHODS The hemostatic abilities of the two methods were analyzed retrospectively in all six gastric endoscopic submucosal dissection cases. The treated vessel diameter, compressed vessel frequency, and bleeding frequency after cutting the vessels were noted by therecorded videos. The coagulation mechanism of the two power settings was evaluated using the data recording program and histological examination on macro-and microscopic levels in the ex vivo experiments using porcine tissues.RESULTS F1-10 method showed a significantly better hemostatic ability for vessels ≥ 2 mm in diameter and a trend of overall better coagulation effect, evaluated by the bleeding rate after cutting the vessels. F1-10 method could sustain electrical current longer and effectively coagulate the tissue wider and deeper than the S method in the porcine model.CONCLUSION F1-10 method is suggested to achieve a stronger hemostatic effect than the S method in clinical procedures and ex vivo models.

Usefulness of a novel slim type Flush Knife-BT over conventional Flush Knife-BT in esophageal endoscopic submucosal dissection

AIM To investigated the usefulness of a novel slim type balltipped Flush Knife (Flush Knife-BTS) over ball-tipped Flush Knife (Flush Knife-BT) in functional experiments and clinical practice.METHODS In order to evaluate the functionality of Flush KnifeBTS, water aspiration speed, resistance to knife insertion through the scope, and waterjet flushing speed were compared between Flush Knife-BTS and BT. In clinical practice, esophageal endoscopic submucosal dissection (ESD) performed using Flush Knife-BTS or BT by an experienced endoscopist between October 2015 and January 2016 were retrospectively reviewed. The treatment speed and frequency of removing and reinserting the knife to aspirate fluid and air during ESD sessions were analyzed.RESULTS Functional experiments revealed that water aspiration speed by the endoscope equipped with a 2.8-mm working channel with Flush Knife-BTS was 7.7-fold faster than that with conventional Flush Knife-BT. Resistance to knife insertion inside the scope with a 2.8-mm working channel was reduced by 40% with FlushK nife-BTS. The waterjet flushing speed was faster with the use of Flush Knife-BT. In clinical practice, a comparison of 6 and 7 ESD using Flush Knife-BT and BTS, respectively, revealed that the median treatment speed was 25.5 mm2/min (range 19.6-30.3) in the BT group and 44.2 mm2/min(range 15.5-55.4) in the BTS group (P = 0.0633). However, the median treatment speed was significantly faster with Flush Knife-BTS when the resection size was larger than 1000 m2(n = 4, median 24.2 mm2/min, range 19.6-27.7 vs n = 4, median 47.4 mm2/min, range 44.2-55.4, P = 0.0209). The frequency of knife replacement was less in the BTS group (median 1.76 times in one hour, range 0-5.45) than in the BT group (7.02 times in one hour, range 4.23-15)(P = 0.0065).CONCLUSION Our results indicate that FlushK nife-BTS enhances the performance of ESD, particularly for large lesions, by improving air and fluid aspiration and knife insertion during ESD and reducing the frequency of knife removal and reinsertion.

Visceral Fat Accumulation Is Associated with Increased Mortality Rate after Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma

Aim: Transcatheter arterial chemoembolization (TACE) is thought to be a safe and effective treatment for hepatocellular carcinoma (HCC). However, in some HCC patients, it potentially shortens survival due to liver damage. We aimed to identify independent factors to predict overall survival of HCC after TACE. Methods: We included a total of 96 consecutive HCC patients who underwent TACE at Kobe University Hospital. Areas of skeletal muscle and fat tissue were measured by computed tomography (CT) scan before TACE. We divided the patients into two groups in terms of the presence or absence of 1-year mortality after TACE. Factors associated with 1-year mortality after TACE were assessed by multivariate analyses, and the optimal cut-off values were evaluated using a propensity score. Results: Multivariate analyses showed that visceral fat accumulation on CT was an independent factor associated with 1-year mortality after TACE (p = 0.033). There were no differences in skeletal muscle area and subcutaneous and intermuscular fat area between the two groups. Cut-off values for visceral fat area associated with 1-year mortality after TACE were defined as 33.3 cm2/m2 for males and 24.4 cm2/m2 for females. Conclusions: High visceral fat area was a prognostic factor associated with increased mortality rate in HCC patients undergoing TACE. Using this value, 1-year mortality risk after TACE would be better estimated before the day TACE was performed.