M. Fujishiro - Academia.edu (original) (raw)

Papers by M. Fujishiro

Journal of Gastroenterology and Hepatology, 2021

Alimentary pharmacology & therapeutics, 2014

Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduo... more Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respect...

Japanese Journal of Clinical Oncology, 2000

Background: The aim was to determine the maximum tolerated dose (MTD) and recommended dose of iri... more Background: The aim was to determine the maximum tolerated dose (MTD) and recommended dose of irinotecan hydrochloride (CPT-11) in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC). Methods: Etoposide was administered continuously at 25 mg/m 2 /day for 14 days. The initial dose of CPT-11 was 40 mg/m 2 given as a 90 min intravenous infusion on days 1, 8 and 15 and the dose escalation of CPT-11 was planned in increments of 20 mg/m 2 until severe or lifethreatening toxic effects were observed. Results: Nine refractory or advanced LC patients (eight at level 1, one at level 2) were entered in this study, of whom two at level 1 were not assessable for toxicity because of patient's refusal and progressive disease. One treatment-related death due to pulmonary toxicity and one patient with hypotension who needed catecholamine for more than 48 h were observed at level 1, a CPT-11 dose of 40 mg/m 2. The MTD of CPT-11 was 40 mg/m 2. Therapeutic efficacy could be assessed in seven patients, of whom two achieved a partial response. Conclusions: This regimen was too toxic and the recommended dose was outside the levels in this study. One has to consider pulmonary toxicity when using CPT-11, especially for patients previously treated with cytotoxic agents for which pulmonary toxicity has been reported.

European Journal of Clinical Nutrition, 2010

Objectives: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter... more Objectives: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). Methods: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. Results: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P ¼ 0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the highintake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. Conclusions: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

Digestive Endoscopy, 2009

Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard tre... more Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard treatments for early esophageal cancer, as well as for early gastric cancer in Japan, but standardization of the knowledge is still incomplete. The final goal to perform ESD is not to resect the lesion in an en bloc fashion, but to save the patient from esophageal cancer‐related death. Thus, the indications should be considered based on the entire patient, not just the target lesion itself, and pre‐, peri‐ and postoperative management of the patient is also very important, as well as technical aspects of ESD. In terms of the techniques of ESD, owing to refinement of the procedural strategy, invention of the devices, and the learning curve, acceptable safety and favorable middle‐term efficacy have been obtained. We believe that ESD will become a standard treatment for early esophageal cancer not only in Japan but also worldwide in the near future.

Clinical Gastroenterology and Hepatology, 2007

BACKGROUND & AIMS The clinical outcomes for endoscopic submucosal dissection (ESD), a novel e... more BACKGROUND & AIMS The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endoluminal surgery for gastrointestinal neoplasm in the colorectum, are reported. METHODS ESD was performed on 186 consecutive patients with 200 colorectal epithelial neoplasms who had preoperative diagnoses of mucosal or slight submucosally invasive neoplasms. In addition, these could be of large size, with submucosal fibrosis, or located on an intestinal fold. The therapeutic efficacy and safety were assessed. RESULTS The targeted lesions consisted of 102 adenomas, 72 noninvasive carcinomas, and 26 invasive carcinomas. Seven lesions (3.5%) were histologically considered to be at substantial risk for nodal metastasis after ESD. The rate of en bloc resection was 91.5% (183/200), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 70.5% (141/200). Two lesions (1%) required emergency colonoscopies as a result of hematochezia after ESD. Eleven (5.5%) immediate perforations that occurred during ESD were successfully managed conservatively, but 1 (0.5%) delayed perforation required laparotomy. Two multiple-piece resections of 111 tumors (1.8%), which were successfully followed by colonoscopy (median follow-up, 18 months; range, 12-60 months), were found as locally recurrent tumors 2 and 21 months after ESD. No lymph node or distant metastasis was detected in 77 patients with noninvasive or invasive carcinoma (median follow-up, 24 months; range, 6-74 months). CONCLUSIONS ESD is applicable in the colorectum with promising results. However, when considering the risks and benefits, piecemeal endoscopic resection or colorectal resection might be more appropriate for some subgroups of large flat neoplasms or those with submucosal fibrosis.

Clinical Gastroenterology and Hepatology, 2007

Background & Aims: The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endo... more Background & Aims: The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endoluminal surgery for gastrointestinal neoplasm in the colorectum, are reported. Methods: ESD was performed on 186 consecutive patients with 200 colorectal epithelial neoplasms who had preoperative diagnoses of mucosal or slight submucosally invasive neoplasms. In addition, these could be of large size, with submucosal fibrosis, or located on an intestinal fold. The therapeutic efficacy and safety were assessed. Results: The targeted lesions consisted of 102 adenomas, 72 noninvasive carcinomas, and 26 invasive carcinomas. Seven lesions (3.5%) were histologically considered to be at substantial risk for nodal metastasis after ESD. The rate of en bloc resection was 91.5% (183/200), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 70.5% (141/200). Two lesions (1%) required emergency colonoscopies as a result of hematochezia after ESD. Eleven (5.5%) immediate perforations that occurred during ESD were successfully managed conservatively, but 1 (0.5%) delayed perforation required laparotomy. Two multiple-piece resections of 111 tumors (1.8%), which were successfully followed by colonoscopy (median follow-up, 18 months; range, 12-60 months), were found as locally recurrent tumors 2 and 21 months after ESD. No lymph node or distant metastasis was detected in 77 patients with noninvasive or invasive carcinoma (median follow-up, 24 months; range, 6-74 months). Conclusions: ESD is applicable in the colorectum with promising results. However, when considering the risks and benefits, piecemeal endoscopic resection or colorectal resection might be more appropriate for some subgroups of large flat neoplasms or those with submucosal fibrosis.

Cancer Epidemiology, Biomarkers & Prevention, 2008

Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recogniti... more Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen test are unclear, test-positive and test-negative subjects were investigated in a longitudinal cohort study. Methods: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on “atrophy-positive” and “atrophy-negative” criteria used for cancer screening was investigated. Results: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, ≤70 ng/mL; pepsinogen I/II ratio, ≤3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive v...

Acta Gastro Enterologica Belgica, 2021

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SA... more Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has become a global pandemic. The human-tohuman transmission of SARS-CoV-2 occurs primarily through droplets, aerosols, and direct contact. Endoscopy is performed at a short physical distance between an endoscopist and patient, which increases the risk of SARS-CoV-2 transmission to the endoscopist through contact with body fluids and exposure to droplets due to vomiting, retching, and coughing during endoscopic procedures (1). Gastrointestinal endoscopic procedures generate aerosols, which mandates the use of appropriate personal protective equipment (PPE) (1,2). To further reduce the risk of viral infection during endoscopy, additional infection protection is needed to assist PPE from not only the side of endoscopists but also the side of patients (3). Various infection prevention devices, such as a reusable plastic cube barrier, have been reported (3); however, we focused on ...

Nihon Naika Gakkai Zasshi, 1998

Hepato-gastroenterology

Systemic chemotherapy for pancreatic adenocarcinoma, at present, has been of limited value in cli... more Systemic chemotherapy for pancreatic adenocarcinoma, at present, has been of limited value in clinical practice and only a small portion of patients obtains meaningful palliation. We retrospectively examined 96 patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy to determine factors predictive of tumor response. None of the patients had received any prior anti-cancer treatment except for pancreatectomy. Of these 96 patients, 5 patients (5.2%) showed partial response but none showed complete response. There was no responder with a performance status of 2 or 3, serum albumin level less than 3.5 g/dL, serum total bilirubin level equal to or more than 2.0 mg/dL, or peritoneal dissemination. Response rates tended to be higher in the subgroups of female patients, those with serum albumin level > or = 3.5 g/dL and those with serum carcinoembryonic antigen level < 10 ng/mL, although there were no significant differences. Patients with a poor performance...

Journal of gastroenterology, 1999

Although epidemiological studies strongly suggest an association between Helicobacter pylori infe... more Although epidemiological studies strongly suggest an association between Helicobacter pylori infection and gastric carcinogenesis via a multistage process, a causal link between them has not been demonstrated. We evaluated the endoscopic and histological changes of gastric adenoma, which is considered a premalignant condition, after eradication of H. pylori. Thirty-five H. pylori-infected patients with gastric adenoma were treated with triple therapy (lansoprazole 30mg/day, clarithromycin 400mg/day, and amoxicillin 1500 mg/day) for 1 week. Of these 35 patients, 30 (86%) exhibited no H. pylori by culture or histology after the therapy. Of the 30 gastric adenomas, 7 decreased in size endoscopically; three gastric adenomas especially showed apparent remission, although histological cure in these three patients was not apparent. Our results suggest that removal of H. pylori infection may only mask a gastric adenoma endoscopically owing to the change around the gastric mucosa.

Background Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer,... more Background Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation. Objective To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels. Design Patients with early gastric cancer, aged 40-80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment. Results Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1-2, 2-3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1. Conclusions Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.

Surgical Endoscopy, 2006

Background: There are few published data on the discrimination ability of endoscopic ultrasonogra... more Background: There are few published data on the discrimination ability of endoscopic ultrasonography (EUS) among each subdivision of T1 cancer, and overdiagnosis is an unsolved problem that eventually causes overtreatment. The purpose of this study was to verify whether our treatment strategy incorporating EUS realizes a tailored patient management of T1 esophageal cancer. Methods: This study comprised 20 esophageal cancer patients undergoing 12-to 20-MHz miniprobes for T staging and a 7.5-MHz dedicated echoendoscope for N staging. Initial therapy constituted endoscopic submucosal dissection (ESD) for endosonographically nodenegative, mucosal, or slight submucosal cancers and a primary esophagectomy with three-field lymphadenectomy for deeper cancers. If the ESD specimen revealed no cancer involvement of the muscularis mucosa, the patients entered a follow-up program; otherwise, they were advised to undergo a subsequent esophagectomy and three-field lymphadenectomy. Results: Perfect discrimination accuracy was achieved among T1, T2, and T3 cancers. Whether cancer depth was up to the slight submucosal layer or deeper was correctly differentiated in 12 of 14 T1 cancers (86%). EUS categorized all patients correctly into candidates for either ESD or surgery. The pathological cancer depth of the resected specimens revealed that no patients experienced unnecessary overtreatment. Conclusions: A higher frequency miniprobe is useful for the detailed evaluation of cancer depth, contributing to decision making for treatment options of T1 esophageal cancer. A miniprobe and echoendoscope in combination with ESD provide an appropriately tailored management plan on an individual basis, avoiding unnecessary treatment or indicating radical surgery.

Endoscopy, 2006

We have previously reported that gastric ulcers artificially created by endoscopic submucosal dis... more We have previously reported that gastric ulcers artificially created by endoscopic submucosal dissection (ESD) would heal within 8 weeks regardless of size and location. The details of the healing process remain unclear, and we aimed to clarify the mechanism by histopathological investigation. 21 post-ESD ulcers were examined histopathologically, using surgically resected specimens from patients who had subsequently undergone gastrectomy due to submucosal invasion and/or lymphovascular infiltration by the tumor. The grade of ulcer, appearance of regenerative mucosa, scar formation, and extent of fibrosis were evaluated. Fibrosis and wall thickening were observed from 2 weeks after ESD, but regenerative mucosa was not observed until 5 weeks. Among 12 patients who underwent gastrectomy later than 8 weeks after ESD, a mucosal defect was still observed in two patients. In these two patients the lesion was associated with severe fibrosis due to previous peptic ulcer or submucosal invasion by the lesion. Size reduction in these ulcers occurs by contraction in the early phase, then regenerative mucosa covers the remaining mucosal defect within 8 weeks. If there is fibrosis under the lesion before ESD, there is a possibility that the artificially created ulcer will not heal within 8 weeks.

Endoscopy, 2006

Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointes... more Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 degrees C, the mean white blood cell count was 9733/mm3, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Endoscopy, 2009

Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection... more Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection of large gastrointestinal tumors. However, this technique has disadvantages such as a long intervention time, complexity of the procedure, and a higher rate of complications. The primary aims of the study were to show the feasibility of ESD in the pig colon and to evaluate a new ESD technique comprising the use of a newly developed hybrid knife for colon procedures combining RF (radiofrequency) application and a distance-dependent water-jet application. ESD was conducted at three different locations in the colon according to the computer-generated randomization list, using either the standard technique (injection needle, flex knife, and hook knife as therapeutic instruments and DRY CUT and SWIFT COAG as RF currents), or the new ESD technique (hybrid knife as the therapeutic instrument combined with the new cutting mode ENDO CUT D) in 12 healthy pigs. The perforation and bleeding rates were documented and statistically analyzed. Intervention time, resected specimen size, thermal and mechanical damage of the resection bed, and number of instrument changes required were also recorded. A total of 16 and 18 ESD procedures were performed by the standard and new techniques, respectively. Complete en bloc resection was achieved in all cases. The standard ESD technique showed a perforation rate of 25 % (4/16) whereas the new ESD technique resulted in a 5.5 % perforation rate (1/18) ( P = 0.035); bleeding rates were similar. The new ESD technique was significantly safer compared with the standard ESD technique. A new ESD technique for the successful en bloc resection in thin-walled regions such as pig colon has been described. This procedure is as effective as the standard procedure but is easier to handle and significantly safer.

Endoscopy, 2006

Background and aim: Endoscopic submucosal dissection (ESD) of gastric stromal tumors is becoming ... more Background and aim: Endoscopic submucosal dissection (ESD) of gastric stromal tumors is becoming increasingly common. However, there have been few studies analyzing the therapeutic efficacy and safety of this technique on large (≥ 3 cm) gastric stromal tumors (LGSTs). The aim of this study was to determine the feasibility of ESD for the removal of LGSTs and to investigate the clinical safety and efficacy of ESD for this indication. Methods: A retrospective analysis was carried out on 82 patients with LGSTs who underwent an ESD. Data on therapeutic outcomes and follow-up were collected for an analysis of the rates of en block resection and complete resection. A logistic regression model was used to identify potential risk factors for ESD-related complications, and a receiver operating characteristic (ROC) curve was generated for qualifying independent risk factors. Results: En bloc resection was achieved in 81 lesions (98.8%), and complete resection was achieved in 80 lesions (97.6%). The rates of intraoperative and postoperative bleeding were 6.1% and 3.7%, respectively. The accidental perforation rate was 12.2%, the postoperative perforation rate was 3.7%, the intentional perforation rate was 28.0%, and the postoperative infection rate was 12.2%. There was no postoperative mortality. LGSTs originating from the deep muscularis propria (MP) layer (OR = 4.905, 95% CI: 1.362-17.658, P = 0.015), located at the gastric fundus (OR = 4.927, 95% CI:1.308-18.558, P = 0.018) and with an irregular shape (OR = 4.842, 95% CI: 1.242-18.870, P = 0.023) increased the rate of complications. The prediction model that incorporated these factors demonstrated an area under the ROC curve of 0.77 (95% CI: 0.66-0.89). No tumor recurrence or distant metastasis was observed during the follow-up period, which ranged from 6-36 months.

Journal of Gastroenterology and Hepatology, 2021

Alimentary pharmacology & therapeutics, 2014

Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduo... more Few studies have evaluated the effects of rabeprazole on low-dose aspirin (LDA)-induced gastroduodenal injuries. To conduct a randomised, double-blind, triple-dummy, active-controlled, multicentre trial, named the PLANETARIUM study, to assess the efficacy, dose-response relationship and safety of rabeprazole for peptic ulcer recurrence in Japanese patients on long-term LDA therapy. Eligible patients had a history of endoscopically confirmed peptic ulcers and were receiving long-term LDA (81 or 100 mg/day) therapy for cardiovascular or cerebrovascular protection. Subjects were randomly segregated into three groups receiving rabeprazole 10 mg once daily (standard dose in Japan), rabeprazole 5 mg once daily, or teprenone (geranylgeranylacetone; mucosal protective agent commercially available in Japan) 50 mg three times per day as an active control. The primary endpoint was recurrence of peptic ulcers over 24 weeks. Among 472 randomised subjects, 452 subjects (n = 151, 150, 151, respect...

Japanese Journal of Clinical Oncology, 2000

Background: The aim was to determine the maximum tolerated dose (MTD) and recommended dose of iri... more Background: The aim was to determine the maximum tolerated dose (MTD) and recommended dose of irinotecan hydrochloride (CPT-11) in combination with a 14-day continuous infusion of etoposide in patients with refractory advanced lung cancer (LC), especially small cell lung cancer (SCLC). Methods: Etoposide was administered continuously at 25 mg/m 2 /day for 14 days. The initial dose of CPT-11 was 40 mg/m 2 given as a 90 min intravenous infusion on days 1, 8 and 15 and the dose escalation of CPT-11 was planned in increments of 20 mg/m 2 until severe or lifethreatening toxic effects were observed. Results: Nine refractory or advanced LC patients (eight at level 1, one at level 2) were entered in this study, of whom two at level 1 were not assessable for toxicity because of patient's refusal and progressive disease. One treatment-related death due to pulmonary toxicity and one patient with hypotension who needed catecholamine for more than 48 h were observed at level 1, a CPT-11 dose of 40 mg/m 2. The MTD of CPT-11 was 40 mg/m 2. Therapeutic efficacy could be assessed in seven patients, of whom two achieved a partial response. Conclusions: This regimen was too toxic and the recommended dose was outside the levels in this study. One has to consider pulmonary toxicity when using CPT-11, especially for patients previously treated with cytotoxic agents for which pulmonary toxicity has been reported.

European Journal of Clinical Nutrition, 2010

Objectives: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter... more Objectives: We investigated the correlation between Japanese apricot (JA) intake and Helicobacter pylori-related chronic atrophic gastritis (CAG). Methods: A questionnaire was administered and serum anti-H. pylori IgG antibodies measured in 1358 asymptomatic adults. The subjects were divided into high-intake and low-intake groups. Histological and serological evaluation of H. pylori-related CAG was performed in 68 non-elderly volunteers. Results: The H. pylori-negative rate did not differ significantly between the high-intake and low-intake groups. Mean antibody titers were lower in the high-intake group, but the difference was not significant. There was no significant difference in the rate of H. pylori infection on the basis of JA intake when subjects were stratified by age. Among H. pylori-positive non-elderly subjects, antibody titers were significantly lower in the high-intake group (P ¼ 0.041). Endoscopic tissue biopsy from the 68 volunteers showed less H. pylori bacterial load and mononuclear infiltration irrespective of gastric site in the high-intake group. In the highintake group, antral neutrophil infiltration was significantly less pronounced and corporal atrophy was less extensive. Serological evaluation using serum PG levels also confirmed these histopathological data. Conclusions: Our findings strongly indicate a preventive effect of JA intake on CAG by inhibiting H. pylori infection and reducing active mucosal inflammation.

Digestive Endoscopy, 2009

Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard tre... more Endoscopic submucosal dissection (ESD) has gradually gained acceptance as one of the standard treatments for early esophageal cancer, as well as for early gastric cancer in Japan, but standardization of the knowledge is still incomplete. The final goal to perform ESD is not to resect the lesion in an en bloc fashion, but to save the patient from esophageal cancer‐related death. Thus, the indications should be considered based on the entire patient, not just the target lesion itself, and pre‐, peri‐ and postoperative management of the patient is also very important, as well as technical aspects of ESD. In terms of the techniques of ESD, owing to refinement of the procedural strategy, invention of the devices, and the learning curve, acceptable safety and favorable middle‐term efficacy have been obtained. We believe that ESD will become a standard treatment for early esophageal cancer not only in Japan but also worldwide in the near future.

Clinical Gastroenterology and Hepatology, 2007

BACKGROUND & AIMS The clinical outcomes for endoscopic submucosal dissection (ESD), a novel e... more BACKGROUND & AIMS The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endoluminal surgery for gastrointestinal neoplasm in the colorectum, are reported. METHODS ESD was performed on 186 consecutive patients with 200 colorectal epithelial neoplasms who had preoperative diagnoses of mucosal or slight submucosally invasive neoplasms. In addition, these could be of large size, with submucosal fibrosis, or located on an intestinal fold. The therapeutic efficacy and safety were assessed. RESULTS The targeted lesions consisted of 102 adenomas, 72 noninvasive carcinomas, and 26 invasive carcinomas. Seven lesions (3.5%) were histologically considered to be at substantial risk for nodal metastasis after ESD. The rate of en bloc resection was 91.5% (183/200), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 70.5% (141/200). Two lesions (1%) required emergency colonoscopies as a result of hematochezia after ESD. Eleven (5.5%) immediate perforations that occurred during ESD were successfully managed conservatively, but 1 (0.5%) delayed perforation required laparotomy. Two multiple-piece resections of 111 tumors (1.8%), which were successfully followed by colonoscopy (median follow-up, 18 months; range, 12-60 months), were found as locally recurrent tumors 2 and 21 months after ESD. No lymph node or distant metastasis was detected in 77 patients with noninvasive or invasive carcinoma (median follow-up, 24 months; range, 6-74 months). CONCLUSIONS ESD is applicable in the colorectum with promising results. However, when considering the risks and benefits, piecemeal endoscopic resection or colorectal resection might be more appropriate for some subgroups of large flat neoplasms or those with submucosal fibrosis.

Clinical Gastroenterology and Hepatology, 2007

Background & Aims: The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endo... more Background & Aims: The clinical outcomes for endoscopic submucosal dissection (ESD), a novel endoluminal surgery for gastrointestinal neoplasm in the colorectum, are reported. Methods: ESD was performed on 186 consecutive patients with 200 colorectal epithelial neoplasms who had preoperative diagnoses of mucosal or slight submucosally invasive neoplasms. In addition, these could be of large size, with submucosal fibrosis, or located on an intestinal fold. The therapeutic efficacy and safety were assessed. Results: The targeted lesions consisted of 102 adenomas, 72 noninvasive carcinomas, and 26 invasive carcinomas. Seven lesions (3.5%) were histologically considered to be at substantial risk for nodal metastasis after ESD. The rate of en bloc resection was 91.5% (183/200), and en bloc resection with tumor-free lateral/basal margins (R0 resection) was 70.5% (141/200). Two lesions (1%) required emergency colonoscopies as a result of hematochezia after ESD. Eleven (5.5%) immediate perforations that occurred during ESD were successfully managed conservatively, but 1 (0.5%) delayed perforation required laparotomy. Two multiple-piece resections of 111 tumors (1.8%), which were successfully followed by colonoscopy (median follow-up, 18 months; range, 12-60 months), were found as locally recurrent tumors 2 and 21 months after ESD. No lymph node or distant metastasis was detected in 77 patients with noninvasive or invasive carcinoma (median follow-up, 24 months; range, 6-74 months). Conclusions: ESD is applicable in the colorectum with promising results. However, when considering the risks and benefits, piecemeal endoscopic resection or colorectal resection might be more appropriate for some subgroups of large flat neoplasms or those with submucosal fibrosis.

Cancer Epidemiology, Biomarkers & Prevention, 2008

Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recogniti... more Background: Gastric cancer screening using the pepsinogen filter test is receiving wide recognition in Japan owing to convenience, freedom from discomfort or risk, efficiency, and economy. Because the long-term outcomes of cancer development in extensive atrophic gastritis detected by pepsinogen test are unclear, test-positive and test-negative subjects were investigated in a longitudinal cohort study. Methods: Subjects comprised 5,209 middle-aged men with measured serum pepsinogen levels who were followed for 10 years. Cancer development based on “atrophy-positive” and “atrophy-negative” criteria used for cancer screening was investigated. Results: During the study, 63 cases of cancer developed in the cohort, representing an incidence rate of 125 per 100,000 person-years. Pepsinogen test screening using the most widely used atrophy-positive criterion (pepsinogen I, ≤70 ng/mL; pepsinogen I/II ratio, ≤3.0) displayed 58.7% sensitivity, 73.4% specificity, and 2.6% positive predictive v...

Acta Gastro Enterologica Belgica, 2021

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SA... more Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) has become a global pandemic. The human-tohuman transmission of SARS-CoV-2 occurs primarily through droplets, aerosols, and direct contact. Endoscopy is performed at a short physical distance between an endoscopist and patient, which increases the risk of SARS-CoV-2 transmission to the endoscopist through contact with body fluids and exposure to droplets due to vomiting, retching, and coughing during endoscopic procedures (1). Gastrointestinal endoscopic procedures generate aerosols, which mandates the use of appropriate personal protective equipment (PPE) (1,2). To further reduce the risk of viral infection during endoscopy, additional infection protection is needed to assist PPE from not only the side of endoscopists but also the side of patients (3). Various infection prevention devices, such as a reusable plastic cube barrier, have been reported (3); however, we focused on ...

Nihon Naika Gakkai Zasshi, 1998

Hepato-gastroenterology

Systemic chemotherapy for pancreatic adenocarcinoma, at present, has been of limited value in cli... more Systemic chemotherapy for pancreatic adenocarcinoma, at present, has been of limited value in clinical practice and only a small portion of patients obtains meaningful palliation. We retrospectively examined 96 patients with metastatic pancreatic adenocarcinoma undergoing systemic chemotherapy to determine factors predictive of tumor response. None of the patients had received any prior anti-cancer treatment except for pancreatectomy. Of these 96 patients, 5 patients (5.2%) showed partial response but none showed complete response. There was no responder with a performance status of 2 or 3, serum albumin level less than 3.5 g/dL, serum total bilirubin level equal to or more than 2.0 mg/dL, or peritoneal dissemination. Response rates tended to be higher in the subgroups of female patients, those with serum albumin level > or = 3.5 g/dL and those with serum carcinoembryonic antigen level < 10 ng/mL, although there were no significant differences. Patients with a poor performance...

Journal of gastroenterology, 1999

Although epidemiological studies strongly suggest an association between Helicobacter pylori infe... more Although epidemiological studies strongly suggest an association between Helicobacter pylori infection and gastric carcinogenesis via a multistage process, a causal link between them has not been demonstrated. We evaluated the endoscopic and histological changes of gastric adenoma, which is considered a premalignant condition, after eradication of H. pylori. Thirty-five H. pylori-infected patients with gastric adenoma were treated with triple therapy (lansoprazole 30mg/day, clarithromycin 400mg/day, and amoxicillin 1500 mg/day) for 1 week. Of these 35 patients, 30 (86%) exhibited no H. pylori by culture or histology after the therapy. Of the 30 gastric adenomas, 7 decreased in size endoscopically; three gastric adenomas especially showed apparent remission, although histological cure in these three patients was not apparent. Our results suggest that removal of H. pylori infection may only mask a gastric adenoma endoscopically owing to the change around the gastric mucosa.

Background Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer,... more Background Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation. Objective To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels. Design Patients with early gastric cancer, aged 40-80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment. Results Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1-2, 2-3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1. Conclusions Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.

Surgical Endoscopy, 2006

Background: There are few published data on the discrimination ability of endoscopic ultrasonogra... more Background: There are few published data on the discrimination ability of endoscopic ultrasonography (EUS) among each subdivision of T1 cancer, and overdiagnosis is an unsolved problem that eventually causes overtreatment. The purpose of this study was to verify whether our treatment strategy incorporating EUS realizes a tailored patient management of T1 esophageal cancer. Methods: This study comprised 20 esophageal cancer patients undergoing 12-to 20-MHz miniprobes for T staging and a 7.5-MHz dedicated echoendoscope for N staging. Initial therapy constituted endoscopic submucosal dissection (ESD) for endosonographically nodenegative, mucosal, or slight submucosal cancers and a primary esophagectomy with three-field lymphadenectomy for deeper cancers. If the ESD specimen revealed no cancer involvement of the muscularis mucosa, the patients entered a follow-up program; otherwise, they were advised to undergo a subsequent esophagectomy and three-field lymphadenectomy. Results: Perfect discrimination accuracy was achieved among T1, T2, and T3 cancers. Whether cancer depth was up to the slight submucosal layer or deeper was correctly differentiated in 12 of 14 T1 cancers (86%). EUS categorized all patients correctly into candidates for either ESD or surgery. The pathological cancer depth of the resected specimens revealed that no patients experienced unnecessary overtreatment. Conclusions: A higher frequency miniprobe is useful for the detailed evaluation of cancer depth, contributing to decision making for treatment options of T1 esophageal cancer. A miniprobe and echoendoscope in combination with ESD provide an appropriately tailored management plan on an individual basis, avoiding unnecessary treatment or indicating radical surgery.

Endoscopy, 2006

We have previously reported that gastric ulcers artificially created by endoscopic submucosal dis... more We have previously reported that gastric ulcers artificially created by endoscopic submucosal dissection (ESD) would heal within 8 weeks regardless of size and location. The details of the healing process remain unclear, and we aimed to clarify the mechanism by histopathological investigation. 21 post-ESD ulcers were examined histopathologically, using surgically resected specimens from patients who had subsequently undergone gastrectomy due to submucosal invasion and/or lymphovascular infiltration by the tumor. The grade of ulcer, appearance of regenerative mucosa, scar formation, and extent of fibrosis were evaluated. Fibrosis and wall thickening were observed from 2 weeks after ESD, but regenerative mucosa was not observed until 5 weeks. Among 12 patients who underwent gastrectomy later than 8 weeks after ESD, a mucosal defect was still observed in two patients. In these two patients the lesion was associated with severe fibrosis due to previous peptic ulcer or submucosal invasion by the lesion. Size reduction in these ulcers occurs by contraction in the early phase, then regenerative mucosa covers the remaining mucosal defect within 8 weeks. If there is fibrosis under the lesion before ESD, there is a possibility that the artificially created ulcer will not heal within 8 weeks.

Endoscopy, 2006

Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointes... more Endoscopic submucosal dissection (ESD) is a novel technique used for the treatment of gastrointestinal neoplasia. One of its major limitations, however, is the complication of perforation. We included in our study all the cases of perforation that occurred during ESD procedures for gastrointestinal epithelial neoplasia between February 2000 and February 2005. Clinical outcomes after perforation were investigated. Perforation was experienced at 27 lesions in 27 patients (four in the esophagus, fourteen in the stomach, seven in the colon, and two in the rectum). Fibrosis under the lesions was confirmed histologically in seven patients (26 %). Immediate closure using endoclips was performed in all patients except for three asymptomatic patients in whom a stomach perforation was first noticed when free air was noticed on a radiograph the morning after the ESD procedure. Air accumulation was detected radiographically in 21 patients (78 %). The mean duration of antibiotic treatment was 6.7 days and the patients were fasted for a mean period of 5.3 days. The mean maximum body temperature was 37.3 degrees C, the mean white blood cell count was 9733/mm3, and the mean C-reactive protein level was 5.0 mg/dl. All the patients were discharged well from the ward after a mean time of 12.1 days after ESD, and no recurrence caused by tumor spread from the perforation occurred in any patient after a median follow-up period of 36 months (range 9 - 52 months). Successful nonsurgical management after ESD complicated by perforation is a highly feasible option if intensive conservative treatments are used following immediate endoscopic closure of the perforation.

Endoscopy, 2009

Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection... more Endoscopic submucosal dissection (ESD) is a promising therapeutic technique for en bloc resection of large gastrointestinal tumors. However, this technique has disadvantages such as a long intervention time, complexity of the procedure, and a higher rate of complications. The primary aims of the study were to show the feasibility of ESD in the pig colon and to evaluate a new ESD technique comprising the use of a newly developed hybrid knife for colon procedures combining RF (radiofrequency) application and a distance-dependent water-jet application. ESD was conducted at three different locations in the colon according to the computer-generated randomization list, using either the standard technique (injection needle, flex knife, and hook knife as therapeutic instruments and DRY CUT and SWIFT COAG as RF currents), or the new ESD technique (hybrid knife as the therapeutic instrument combined with the new cutting mode ENDO CUT D) in 12 healthy pigs. The perforation and bleeding rates were documented and statistically analyzed. Intervention time, resected specimen size, thermal and mechanical damage of the resection bed, and number of instrument changes required were also recorded. A total of 16 and 18 ESD procedures were performed by the standard and new techniques, respectively. Complete en bloc resection was achieved in all cases. The standard ESD technique showed a perforation rate of 25 % (4/16) whereas the new ESD technique resulted in a 5.5 % perforation rate (1/18) ( P = 0.035); bleeding rates were similar. The new ESD technique was significantly safer compared with the standard ESD technique. A new ESD technique for the successful en bloc resection in thin-walled regions such as pig colon has been described. This procedure is as effective as the standard procedure but is easier to handle and significantly safer.

Endoscopy, 2006

Background and aim: Endoscopic submucosal dissection (ESD) of gastric stromal tumors is becoming ... more Background and aim: Endoscopic submucosal dissection (ESD) of gastric stromal tumors is becoming increasingly common. However, there have been few studies analyzing the therapeutic efficacy and safety of this technique on large (≥ 3 cm) gastric stromal tumors (LGSTs). The aim of this study was to determine the feasibility of ESD for the removal of LGSTs and to investigate the clinical safety and efficacy of ESD for this indication. Methods: A retrospective analysis was carried out on 82 patients with LGSTs who underwent an ESD. Data on therapeutic outcomes and follow-up were collected for an analysis of the rates of en block resection and complete resection. A logistic regression model was used to identify potential risk factors for ESD-related complications, and a receiver operating characteristic (ROC) curve was generated for qualifying independent risk factors. Results: En bloc resection was achieved in 81 lesions (98.8%), and complete resection was achieved in 80 lesions (97.6%). The rates of intraoperative and postoperative bleeding were 6.1% and 3.7%, respectively. The accidental perforation rate was 12.2%, the postoperative perforation rate was 3.7%, the intentional perforation rate was 28.0%, and the postoperative infection rate was 12.2%. There was no postoperative mortality. LGSTs originating from the deep muscularis propria (MP) layer (OR = 4.905, 95% CI: 1.362-17.658, P = 0.015), located at the gastric fundus (OR = 4.927, 95% CI:1.308-18.558, P = 0.018) and with an irregular shape (OR = 4.842, 95% CI: 1.242-18.870, P = 0.023) increased the rate of complications. The prediction model that incorporated these factors demonstrated an area under the ROC curve of 0.77 (95% CI: 0.66-0.89). No tumor recurrence or distant metastasis was observed during the follow-up period, which ranged from 6-36 months.