Shigenaga Matsui

Estimation of malignant potential of GI stromal tumors by contrast-enhanced harmonic EUS (with videos)

BACKGROUND Contrast-enhanced harmonic EUS (CEH-EUS) is a new sonographic technique that uses US contrast agents and depicts intratumoral vessels in real time. OBJECTIVE To evaluate whether assessment of tumor vascularity by CEH-EUS can predict the preoperative malignancy risk of GI stromal tumors (GISTs). DESIGN Prospective study to observe GIST vascularity. SETTING Kinki University School of Medicine. PATIENTS Between June 2007 and September 2009, 76 consecutive patients suspected of having subepithelial lesions underwent CEH-EUS. INTERVENTION CEH-EUS was performed by using a prototype echoendoscope in an extended pure harmonic detection mode. MAIN OUTCOME MEASUREMENTS Resected GIST specimens in 29 patients who underwent surgical resection were divided into high-grade (n=16) and low-grade (n=13) malignancy groups based on mitotic activity. The abilities of EUS-guided FNA and CEH-EUS to diagnose the malignant potential were compared. The sensitivities with which contrast-enhanced multidetector CT, power-Doppler EUS, and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs also were compared. RESULTS CEH-EUS identified irregular vessels and thereby predicted GIST malignancies with a sensitivity, specificity, and accuracy of 100%, 63%, and 83%, respectively. Diagnosis of high-grade malignancy GISTs by EUS-guided FNA had a sensitivity, specificity, and accuracy of 63%, 92%, and 81%, respectively. Contrast-enhanced multidetector CT, power-Doppler EUS, and CEH-EUS detected intratumoral vessels in high-grade malignancy GISTs with sensitivities of 31%, 63%, and 100%, respectively (P<.05). LIMITATIONS A single center was involved in this study. CONCLUSIONS CEH-EUS successfully visualized intratumoral vessels and may play an important role in predicting the malignancy risk of GISTs.

Association of Gankyrin and Stemness Factor Expression in Human Colorectal Cancer

BackgroundIt is widely accepted that the adenoma-carcinoma sequence represents the process by which most colorectal cancers (CRCs) arise. Although gankyrin is overexpressed in CRC tissues, its roles in the initiation step of colorectal carcinogenesis remain largely unexplored.AimWe investigated the expression of gankyrin and stemness factors in human colorectal adenomas, precancerous lesions, as well as CRC tissues to assess its involvement in colorectal carcinogenesis.MethodsExpression of several molecules including gankyrin and certain stemness factors was compared in 50 pairs of adenoma and surrounding normal mucosa using real-time quantitative polymerase chain reaction and in 30 CRC tissues using immunohistochemistry.ResultsIn CRC specimens, expression of CD133, a cancer stem cell marker, was significantly correlated with gankyrin expression. Gankyrin knockdown decreased the expression of vascular endothelial growth factor (VEGF) and stemness factors such as Nanog and Oct-4 in colorectal cancer cells. Expression of gankyrin and these stemness factors was significantly higher in adenomas than in the surrounding normal mucosa. Importantly, a significant correlation was observed between the expression of gankyrin, VEGF, and Nanog in colorectal adenomas.ConclusionIn CRC development, gankyrin would control stem cell behavior by regulating the expression of stemness factors.

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.

Intrahepatic huge hematoma due to rupture of small hepatocellular adenoma: a case report.

Hepatocellular adenoma sometimes causes intraperitoneal hemorrhage. It is, however, rare for small hepatocellular adenoma to cause intrahepatic huge hemorrhage without intraperitoneal bleeding. Here we describe such a rare case of hepatocellular adenoma with huge intrahepatic hemorrhage in a 25-year-old female, who had taken oral contraceptives for the last 2 weeks. She was admitted to our hospital with a sudden onset of right-upper-quadrant abdominal pain and temporally fell in shock state. Plain CT depicted low density area measuring more than 13 cm in diameter in the right lobe of the liver. Huge tumor was also suggested by abdominal ultrasound, contrast enhanced CT, magnetic resonance imaging (MRI) and angiography. The patient was diagnosed as intrahepatic rupture of hepatic tumor. Because of the risk of re-hemorrhage and malignancy, she underwent right hepatic lobectomy. Histopathologial examination of the resected specimen showed a typical small hepatocellular adenoma with the surrounding huge hematoma in the liver. The case presented here is very rare but seems to be suggestive to the natural course and management of hepatocellular adenoma.

Involvement of heat shock protein a4/apg-2 in refractory inflammatory bowel disease.

Background:Expression of heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, is induced by several forms of stress. The physiological and pathological functions of HSPA4 in the intestine remain to be elucidated. Methods:We assessed HSPA4 expression and function by generating HSPA4-deficient mice and using 214 human intestinal mucosa samples from patients with inflammatory bowel disease (IBD). Results:In the colonic mucosa of patients with IBD, a significant correlation was observed between the expression of HSPA4 and antiapoptotic protein Bcl-2, a T-cell–derived cytokine IL-17 or stem cell markers, such as Sox2. In refractory ulcerative colitis, a condition associated with increased cancer risk, expression of HSPA4 and Bcl-2 was increased in inflammatory cells of colonic mucosae. HSPA4 was overexpressed both in cancer cells and immune cells of human colorectal cancers. Patients with high expression of HSPA4 or Bmi1 showed significantly lower response rates upon subsequent steroid therapy as compared with patients with low expression of each gene. HSPA4-deficient mice exhibit more apoptosis and less expression of IL-17/IL-23 in inflammatory cells and less number of Sox2+ cells after administration of dextran sodium sulfate than control mice. Transduction of HspaA4+/− bone marrow into wild-type mice reduced the immune response. Conclusions:Upregulation of Bcl-2 and IL-17 by HSPA4 would control apoptosis of inflammatory cells and immune response in the gut, which might develop treatment resistance in IBD. HSPA4 and Bmi1 would be a useful biomarker for refractory clinical course and a promising approach for a therapeutic strategy in patients with IBD.

Comparison of argon plasma coagulation and paravariceal injection sclerotherapy with 1% polidocanol in mucosa-fibrosing therapy for esophageal varices

To the Editor: Endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) are widely used for esophageal varices treatment. However, recurrence of esophageal varices has sometimes been observed after these treatments. Especially, a high rate of recurrence associated with EVL1 was reported. In Japan, therefore, in addition to these treatments, mucosafibrosing therapy, by paravariceal injection sclerotherapy, was performed for complete disappearance of esophageal varices.2 In this study, we evaluated the efficacy, complications, and recurrence of esophageal varices after mucosa-fibrosing therapy with argon plasma coagulation (APC) compared with these features after paravariceal injection sclerotherapy using 1% polidocanol (PD). The study was retrospective. Forty-nine patients with esophageal varices exhibiting the red color sign (high-risk group,3 according to the criteria of the Japan Society for Portal Hypertension and Esophago-Gastric varices4) were evaluated. In the initial sessions, we performed endoscopic injection sclerotherapy (EISL),5 and immediately after the EISL procedure, EVL was also performed for esophageal varices (EISL/EVL therapy). One week after the initial EISL/EVL therapy, all patients underwent follow-up endoscopy. The patients with esophageal varices greater than F2 volume underwent additional EVL therapy. The additional EVL therapy was performed until the volume of varices became less than F1 volume. After the sessions, the patients with esophageal varices of F1 or F0 volume underwent mucosafibrosing therapy with APC or 1% PD. The 49 patients were divided into two groups; (1) the APC group and (2) the 1% PD group, in which patients received mucosa-fibrosing therapy by paravariceal injection sclerotherapy of 1% PD. APC therapy was performed only when the APC equipment was available (i.e., in April 1999, February 2000, March 2000, and October 2001; the equipment was rented from AMCO; during these periods 1% PD therapy was not performed). All data values are expressed as means SD. Statistical analysis to compare unpaired variables was performed using two-tailed Student’s t-test. The 2 test or Fisher’s exact test was used to compare categorical data. Intervals until the first recurrence were plotted by the Kaplan-Meier method, and compared by Wilcoxon test. A P values of less than 0.05 was considered statistically significant. The characteristics of the two groups are shown in Table 1. Thirteen of 15 patients in the APC group and 30 of 34 patients in the 1% PD group received prophylactic treatment. All candidates for prophylactic treatment were regarded as being at high risk for variceal hemorrhage. Four patients in the APC group (stage II, 3; stage III, 1) and 11 patients in the 1% PD group (stage I, 2; stage II, 9) had concomitant hepatoma. No significant differences of characteristics were found between the two groups. Endoscopic APC (gas flow, 1.6 l/min; power setting, 50W) was used to promote circumferential fibrosis of the esophageal mucosa from the esophagogastric junction to 5cm proximally (Fig. 1A–D). After the treatment, patients underwent endoscopy every 3 months until the end of follow-up. We defined recurrence as being greater than F1 volume or the appearance of the red color sign. Comparisons of the results of the APC group and the 1% PD group are shown in Table 2. There was no significant difference in the number of O-rings or in the volume of 5% ethanolamine oleate with iopamidol (5% EOI) between the two groups. The number of treatment sessions required to eradicate the varices was significantly lower in the APC group than in the 1% PD group (total, 2.2 0.5 vs 2.8 0.5; mucosa-fibrosing therapy, 1.1 0.3 vs 1.6 0.6; P 0.05). The 1and 2-year cumulative recurrencefree rates in the APC group (93.3% and 84%) were not This article is based on a study first reported in the Japanese Journal of Portal Hypertension (2002;8:180–4) by S Matsui, M Kudo, R Nakaoka, and M Shiomi. “Effect of mucosa-fibrosing therapy with argon plasma coagulation on esophageal varices”. Table 1. Characteristics of patients

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.

Computer-Aided Diagnosis Based on Convolutional Neural Network System for Colorectal Polyp Classification: Preliminary Experience

Background and Aim: Computer-aided diagnosis (CAD) is becoming a next-generation tool for the diagnosis of human disease. CAD for colon polyps has been suggested as a particularly useful tool for trainee colonoscopists, as the use of a CAD system avoids the complications associated with endoscopic resections. In addition to conventional CAD, a convolutional neural network (CNN) system utilizing artificial intelligence (AI) has been developing rapidly over the past 5 years. We attempted to generate a unique CNN-CAD system with an AI function that studied endoscopic images extracted from movies obtained with colonoscopes used in routine examinations. Here, we report our preliminary results of this novel CNN-CAD system for the diagnosis of colon polyps. Methods: A total of 1,200 images from cases of colonoscopy performed between January 2010 and December 2016 at Kindai University Hospital were used. These images were extracted from the video of actual endoscopic examinations. Additional video images from 10 cases of unlearned processes were retrospectively assessed in a pilot study. They were simply diagnosed as either an adenomatous or nonadenomatous polyp. Results: The number of images used by AI to learn to distinguish adenomatous from nonadenomatous was 1,200:600. These images were extracted from the videos of actual endoscopic examinations. The size of each image was adjusted to 256 × 256 pixels. A 10-hold cross-validation was carried out. The accuracy of the 10-hold cross-validation is 0.751, where the accuracy is the ratio of the number of correct answers over the number of all the answers produced by the CNN. The decisions by the CNN were correct in 7 of 10 cases. Conclusion: A CNN-CAD system using routine colonoscopy might be useful for the rapid diagnosis of colorectal polyp classification. Further prospective studies in an in vivo setting are required to confirm the effectiveness of a CNN-CAD system in routine colonoscopy.

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.