Yutaka Asakuma

A New Prognostic Staging System for Hepatocellular Carcinoma: Value of the Biomarker Combined Japan Integrated Staging Score

Objectives: The Japan Integrated Staging (JIS) score has been reported to have good stratification ability in patients with hepatocellular carcinoma (HCC). However, the JIS score could not estimate malignant grade of HCC. The aim of this study was to evaluate the performance of a new staging system: the biomarker combined JIS (bm-JIS) which includes three tumor markers: α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP and des-γ-carboxy prothrombin with the conventional JIS score. Methods: A total of 1,924 HCC patients were included in this study. We compared their overall survival, the stratification ability and suitability as a prognostic model according to the bm-JIS score and the conventional JIS score. Results: There were significant differences between the survival curves for all bm-JIS scores. For the conventional JIS scores of 0, 1, 2 and 3, the survival curves differed greatly according to the bm-JIS score (p < 0.0001). The independent homogenizing ability and the stratification value of the JIS score and the bm-JIS score determined by the likelihood ratio test using the Cox proportional hazard regression model showed the bm-JIS score to have a higher value(χ2 = 717.348) than the JIS score (χ2 = 668.91). Conclusions: The bm-JIS score showed superior stratification ability and thus was found to be a better predictor of the prognosis than the conventional JIS score, especially for the patients with good prognosis.

Removal of diminutive colorectal polyps: A prospective randomized clinical trial between cold snare polypectomy and hot forceps biopsy

AIM To compare the efficacy and safety of cold snare polypectomy (CSP) and hot forceps biopsy (HFB) for diminutive colorectal polyps. METHODS This prospective, randomized single-center clinical trial included consecutive patients ≥ 20 years of age with diminutive colorectal polyps 3-5 mm from December 2014 to October 2015. The primary outcome measures were en-bloc resection (endoscopic evaluation) and complete resection rates (pathological evaluation). The secondary outcome measures were the immediate bleeding or immediate perforation rate after polypectomy, delayed bleeding or delayed perforation rate after polypectomy, use of clipping for bleeding or perforation, and polyp retrieval rate. Prophylactic clipping after polyp removal wasn’t routinely performed. RESULTS Two hundred eight patients were randomized into the CSP (102), HFB (106) and 283 polyps were evaluated (CSP: 148, HFB: 135). The en-bloc resection rate was significantly higher with CSP than with HFB [99.3% (147/148) vs 80.0% (108/135), P < 0.0001]. The complete resection rate was significantly higher with CSP than with HFB [80.4% (119/148) vs 47.4% (64/135), P < 0.0001]. The immediate bleeding rate was similar between the groups [8.6% (13/148) vs 8.1% (11/135), P = 1.000], and endoscopic hemostasis with hemoclips was successful in all cases. No cases of perforation or delayed bleeding occurred. The rate of severe tissue injury to the pathological specimen was higher HFB than CSP [52.6% (71/135) vs 1.3% (2/148), P < 0.0001]. Polyp retrieval failure was encountered CSP (7), HFB (2). CONCLUSION CSP is more effective than HFB for resecting diminutive polyps. Further long-term follow-up study is required.

Efficacy of treatment with rebamipide for endoscopic submucosal dissection-induced ulcers

AIM To prospectively compare the healing rates of endoscopic submucosal dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI) or rebamipide. METHODS We examined 90 patients with early gastric cancer who had undergone ESD. All patients were administered an intravenous infusion of the PPI lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45; PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were compared. RESULTS No significant differences were noted in patient age, underlying disease, tumor location, Helicobacter pylori infection rate, or ESD-induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%; rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions following ulcer healing were significantly higher in the PPI-treated group (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8-wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer bleeding or complications due to the drugs were observed in either treatment group. CONCLUSION The healing rate of ESD-induced ulcers was similar with rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective and prevents granulation lesions following ulcer healing.

Comparative Study of Clarithromycin- versus Metronidazole-Based Triple Therapy as First-Line Eradication for Helicobacter pylori

Introduction: Clarithromycin (CAM)-based triple therapy comprising proton pump inhibitors and amoxicillin is administered as first-line eradication treatment against Helicobacter pylori infection. However, the eradication rate achieved with CAM-based triple therapy has decreased to <80% owing to the emergence of CAM-resistant strains. This prospective randomized study aimed to compare the efficacy of CAM-based and metronidazole (MNZ)-based triple therapy in terms of H. pylori eradication. Methods:H. pylori-positive patients were treated with CAM-based triple therapy comprising esomeprazole and amoxicillin (EAC group) or with MNZ-based triple therapy comprising esomeprazole and amoxicillin (EAM group). Results:H. pylori eradication rates achieved in the intention-to-treat (ITT) and per protocol (PP) analyses were 70.6 and 72.7%, respectively, in the EAC group. Eradication rates obtained via ITT and PP analyses were 91.7 and 94.3%, respectively, in the EAM group. In the EAC group, eradication rates were significantly lower in patients harboring CAM-resistant strains than in those harboring CAM-sensitive strains. In contrast, eradication rates were comparable between patients harboring CAM-resistant strains and those harboring CAM-sensitive strains in the EAM group. Conclusion: MNZ-based triple therapy consisting of esomeprazole and amoxicillin is superior to CAM-based triple therapy containing esomeprazole and amoxicillin as first-line eradication treatment against H. pylori.

Heat shock protein 27 expression is inversely correlated with atrophic gastritis and intraepithelial neoplasia.

BackgroundIntestinal-type gastric carcinomas progress through several sequential steps, including atrophic gastritis, intestinal metaplasia, dysplasia, and cancer.AimWe investigated heat shock protein 27 (HSP27) expression in gastric neoplasia and background gastric mucosa to assess its involvement in gastric carcinogenesis.MethodsWe used real-time quantitative polymerase chain reaction to examine HSP27 expression in gastric neoplasias and background gastric mucosae of 30 patients with intraepithelial neoplasias and in gastric mucosae of 30 patients without gastric neoplasia. Immunohistochemical staining was performed on 30 advanced gastric cancer tissues.ResultsHSP27 expression was negatively associated with atrophic gastritis. HSP27 expression in the background gastric mucosa of neoplasia-bearing patients was significantly lower than in the mucosa of those without gastric neoplasia. In tumor necrosis factor α-treated gastric cancer cells, HSP27 knockdown increased cell death and accumulation of the reactive oxygen species that link inflammation to cancer. Poorly differentiated tumors most frequently had high HSP27 levels. Dedifferentiation of cancer cells is associated with an epithelial–mesenchymal transition (EMT) signaling pathway. In gastric cancer MKN-1 cells, HSP27 knockdown upregulated E-cadherin and downregulated vimentin and smooth muscle actin, but this did not occur in MKN-74 cells.ConclusionHSP27 expression in gastric mucosae is inversely correlated with intraepithelial neoplasia, a probable precursor to gastric cancer, and HSP27 expression in cancer is positively correlated with poor differentiation.

Clinical Analysis of Esophageal Stricture in Patients Treated with Intralesional Triamcinolone Injection after Endoscopic Submucosal Dissection for Superficial Esophageal Cancer

Introduction: Endoscopic submucosal dissection (ESD) has been widely used in the resection of superficial esophageal cancers. Since its use has been extended to cases involving large esophageal tumors occupying nearly the whole or the whole circumference of the lumen, the occurrence of esophageal stricture has increased. Although endoscopic injection of triamcinolone (TA) is widely used for the prevention of postoperative stricture, a significant number of patients still develop stricture after TA injection therapy. Methods: We performed a retrospective study to identify the clinical parameters that predispose post-ESD patients to esophageal stricture after TA injection therapy. Results: A total of 207 patients who were diagnosed with superficial esophageal cancer and subsequently underwent ESD were enrolled in this study. Among these patients, 53 patients and 57 lesions bearing mucosal defects covering greater than two-thirds of the esophageal circumference after ESD were treated with TA injection therapy. The rate of esophageal stricture was found to be highest in cases involving mucosal defects that covered more than seven-eighths of the circumference. Conclusion: Endoscopic TA injection is not sufficient for preventing esophageal stricture in patients bearing mucosal defects covering more than seven-eighths of the esophageal circumference after ESD.

Endoscopic treatment of tracheoesophageal fistula using the over-the-scope-clip system

An 84-year-old man with dysphagia was referred to our hospital for examination. The patient’s medical history included endoscopic submucosal dissection for superficial esophageal cancer 2 years previously. Gastrointestinal endoscopy revealed an esophageal foreign body, a pressthrough pack (PTP) (Fig. 1A). The PTP was successfully removed endoscopically. After extraction of the PTP, the patient presented with continuous fever and a cough. Gastrointestinal endoscopy and fluoroscopy revealed a tracheoesophageal fistula in the esophagus (Fig. 1B,C). The tracheoesophageal fistula was endoscopically closed with the Over-The-Scope Clip (OTSC) system (Fig. 2A). The patient’s symptoms were immediately improved. Gastrointestinal endoscopy after 2 months revealed a scar with complete fistula closure (Fig. 2B). The management of tracheoesophageal fistulas is associated with high morbidity and mortality and remains an interdisciplinary challenge. For patients with benign tracheoesophageal fistulas, treatment is always initially supportive, followed by definitive surgical correction [1]. The OTSC system is a new technique that is becoming established as a reliable method for the endoscopic closure of fistulas, bleeds, perforations and other gastrointestinal lesions [2]. The major benefits of the OTSC are its speed and ease of

A Case of Type II Enteropathy-Associated T-Cell Lymphoma in a Patient With Ulcerative Colitis

A Case of Type II Enteropathy-Associated T-Cell Lymphoma in a Patient With Ulcerative Colitis

Magnifying Narrow Band Imaging (NBI) for the Diagnosis of Localized Colorectal Lesions Using the Japan NBI Expert Team (JNET) Classification

Objective: The Japan NBI Expert Team (JNET) proposed a new narrow band imaging (NBI) classification system for colorectal tumors in June 2014. In this classification system, types 1, 2A, 2B, and 3 correspond to hyperplastic polyps (HPs) including sessile serrated polyps (SSPs), low-grade dysplasia (LGD), high-grade dysplasia (HGD) to shallow submucosal invasive (SM-s) carcinomas, and deep submucosal invasive (SM-d) carcinomas, respectively. Methods: To validate this system, we performed a retrospective image evaluation study, in which 199 colorectal tumors previously assessed by NBI magnifying endoscopy were classified by 3 blinded experienced colonoscopists using the JNET system. The results were compared with the final pathological diagnoses to determine the JNET classifications accuracy. The interobserver agreement was calculated, and the intraobserver agreement was assessed after 6 months. Results: The final pathological diagnoses identified 14 HPs/SSPs, 127 LGDs, 22 HGDs, 19 SM-s carcinomas, and 17 SM-d carcinomas. The respective sensitivities, specificities, positive predictive value, negative predictive value, and accuracies were as follows: Type 1, 85.7, 99.5, 92.3, 98.9, and 98.5%; Type 2A, 96.0, 81.9, 90.3, 92.1, and 90.9%; Type 2B, 75.6%, 90.5, 67.3, 93.4, and 87.4%; and Type 3, 29.4%, 100, 100, 93.8, and 94.0%. The interobserver agreement and the intraobserver agreement were moderate (κ value: 0.52) and excellent (κ value: 0.88), respectively. Lesions presenting as Type 2B during NBI comprised a range of colorectal tumors, including HGDs, SM-s, and SM-d. Conclusions: The JNET classification was useful for the diagnosis of HPs/SSPs, LGDs, and SM-d, but not SM-s lesions. For low-confidence cases, magnified chromoendoscopy is recommended to ensure correct diagnoses.

Risk Factors for Postoperative Bleeding in Endoscopic Submucosal Dissection of Colorectal Tumors

Background: Colonoscopic removal of adenomatous polyps or early cancer prevents death from colorectal cancer. Endoscopic submucosal dissection (ESD), which enables endoscopists to perform en bloc resection of flat or depressed colorectal tumors >20 mm, has recently been introduced and become a standard procedure in Japan. Although postoperative bleeding (POB) is a major complication associated with ESD, risk factors for POB have not been fully identified. Methods: A total of 451 patients (509 lesions) who underwent colorectal ESD were retrospectively analyzed to identify clinical parameters associated with POB. Results: POB occurred in 14 patients, and 7 of them had received antithrombotic therapy before ESD. Uni- and multivariate analyses revealed that antithrombotic therapy and rectal tumor location were strongly associated with POB following colorectal ESD. The incidence of POB was higher in patients on heparin bridge therapy (HBT) for the replacement of antithrombotic therapy than in patients with no HBT. Four of 7 patients (57.1%) on antithrombotic therapy experienced POB from the rectal lesions. Conclusion: Antithrombotic therapy and rectal lesions result in a higher POB incidence after colorectal ESD.