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Background and Aim: Colitis‐associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC. Methods: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score‐matched data. Results: A total of 1077 patients with UC‐CAC, 297 with CD‐CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score‐matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01). Conclusion: CAC, including early‐stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression. [ABSTRACT FROM AUTHOR]

Background: The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate "patients without gastritis" (defined as true A patients) from those "with gastritis." A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. Methods: Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the "pathologically-evaluated group" and "endoscopically-evaluated group," according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. Results: The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12–126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. Conclusion: The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development.Methods: We enrolled 22,736 patients aged 20-95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger-Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling. First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up.Results: Among the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer.Conclusions: The combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Serrated polyposis syndrome (SPS), a type of colorectal polyposis characterized by multiple serrated polyps, is associated with a high risk of colorectal carcinoma (CRC). This study aimed to clarify the clinicopathological characteristics of SPS in Japan. Methods: We investigated the clinicopathological characteristics of patients with SPS from the "Multicenter Study on Clinicopathological Characteristics of SPS (UMIN 000032138)" by the Colorectal Serrated Polyposis Syndrome (SPS) Study Group. In this study, patients were diagnosed with SPS based on the 2019 World Health Organization (WHO) SPS diagnostic criteria. Results: Ninety-four patients were diagnosed with SPS in 10 institutions between January 2001 and December 2017. The mean number (± standard deviation [SD]) of resected lesions per patient was 11.3 ± 13.8. The mean age at diagnosis of SPS was 63.3 ± 11.6 years, and 58 patients (61.7%) were male. Eighty-seven (92.6%) and 16 (17.0%) patients satisfied WHO diagnostic criteria I and II, respectively. Nine patients (9.6%) satisfied both criteria I and II. Carcinoma (T1–T4) were observed in 21 patients (22.3%) and 24 lesions. Of the 21 patients with CRC, 19 (90.4%) satisfied diagnostic criterion I, 1 (4.8%) satisfied diagnostic criterion II, and 1 (4.8%) satisfied diagnostic criteria I and II. There was no notable difference in the prevalence of CRC among patients who met diagnostic criterion I, II, and both I and II. Conclusions: Patients with SPS have a high risk of CRC and should undergo regular surveillance colonoscopy. Raising awareness of this syndrome is crucial. [ABSTRACT FROM AUTHOR]

Background: This postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. Methods: This multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab. Correlation of background characteristics with treatment-related adverse events (TRAEs) and tumor response was explored. Results: Overall, 654 patients were registered (safety analysis set, n = 650; effectiveness analysis set, n = 636; response evaluation set, n = 516). The incidences of all TRAEs and grade ≥ 3 TRAEs were 31.5 and 11.2%, respectively. TRAEs significantly correlated with the absence of peritoneal metastasis; C-reactive protein level < 1; prior G/GEJ cancer surgery; and past or concomitant pulmonary, thyroid, or renal disease (each p < 0.05). The incidence of TRAEs was significantly lower in patients with higher Glasgow prognostic scores (p < 0.05). No new safety signals were observed. Complete response, partial response, stable disease, and progressive disease were observed in 1.2, 10.1, 27.1, and 58.3% of the response evaluation set, respectively. Patients aged ≥ 65 years (13.9 vs 5.3%, p = 0.0083) and ≥ 75 years (18.8 vs 9.2%, p = 0.0036) showed a higher response rate than their younger counterparts. Conclusions: The real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent G/GEJ cancer were consistent with those observed in the phase 3 ATTRACTION-2 study. [ABSTRACT FROM AUTHOR]

Background: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. Aims: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. Methods: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. Results: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. Conclusion: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed. [ABSTRACT FROM AUTHOR]

Background: In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years.Methods: ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months.Results: The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients.Conclusions: ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis. [ABSTRACT FROM AUTHOR]

Background and Aim: The typical histology of Helicobacter pylori‐uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H. pylori‐uninfected patient and its prevalence in diffuse‐type gastric cancer (DGC) within Japan. Methods: We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H. pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA. Results: Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H. pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P < 0.01). Twenty‐two (6.4%) patients, including two with submucosal invasion, were negative for H. pylori and had mucosal SRCC component in the cancer lesions. Of the 259 SRCC cases (pure SRCC or SRCC + PDA), H. pylori‐uninfected cases had different clinicopathological characteristics compared with H. pylori‐positive cases. Particularly, the ratio of patients with submucosal invasive SRCC was significantly lower in the H. pylori‐uninfected gastric cancer group than in those with H. pylori infection. Conclusion: Helicobacter pylori‐uninfected gastric cancer is not rare among pure DGC patients in Japan. SRCC in patients without H. pylori infection is less likely to be invasive. [ABSTRACT FROM AUTHOR]

Objectives: A Japanese multicenter prospective cohort study examining endoscopic resection (ER) for early gastric cancer (EGC) has been conducted using a Web registry developed to determine the short‐term and long‐term outcomes based on absolute and expanded indications. We hereby present the short‐term outcomes of this study. Methods: All consecutive patients with EGC or suspected EGC undergoing ER at 41 participating institutions between July 2010 and June 2012 were enrolled and prospectively registered into the Web registry. The baseline characteristics were entered before ER, and the short‐term outcomes were collected at 6 months following ER. Results: Nine thousand six hundred and sixteen patients with 10 821 lesions underwent ER (endoscopic submucosal dissection [ESD]: 99.4%). The median procedure time was 76 min, and R0 resections were achieved for 91.6% of the lesions. Postoperative bleeding and intraoperative perforation occurred in 4.4% and 2.3% of the patients, respectively. Significant independent factors correlated with a longer procedure time (120 min or longer) were as follows: tumor size >20 mm, upper‐third location, middle‐third location, local recurrent lesion, ulcer findings, gastric tube, male gender, and submucosa. Histopathologically, 10 031 lesions were identified as common‐type gastric cancers. The median tumor size was 15 mm. Noncurative resections were diagnosed for 18.3% of the lesions. Additional surgery was performed for 48.6% (824 lesions) of the 1695 noncurative ER lesions with a possible risk of lymph node (LN) metastasis. Among them, 64 (7.8%) exhibited LN metastasis. Conclusions: This multicenter prospective study showed favorable short‐term outcomes for gastric ESD. [ABSTRACT FROM AUTHOR]

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID‐19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID‐19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID‐19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID‐19; (ii) practical protective equipment for medical personnel depending on the risk for COVID‐19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow‐up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID‐19. [ABSTRACT FROM AUTHOR]

Background: We aimed to clarify the long-term outcomes of patients with T1 colorectal carcinoma (CRC) after endoscopic resection (ER) and surgical resection.Methods: We examined T1 CRC patients treated during 1992-2008 and who had ≥5 years of follow-up. Patients who did not meet the curative criteria after ER according to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines were defined as "non-endoscopically curable" and classified into three groups: ER alone (Group A: 121 patients), additional surgery after ER (Group B: 238 patients), and surgical resection alone (Group C: 342 patients). Long-term outcomes and predictors of recurrence were analyzed.Results: Of the 882 patients with T1 CRC, 701 were non-endoscopically curable. Among these patients, recurrence and 5-year overall survival (OS) rates were 0.6 and 91.1%, respectively. In Groups A, B, and C, recurrence rates were 5.0, 5.5, and 3.8%, OS rates were 79.3, 92.4, and 91.5% (p < 0.01), and 5-year disease-free survival (DFS) rates were 98.1, 97.9, and 98.5%, respectively. Thirty-two patients experienced local recurrence or distant/lymph node metastasis (Group A: 6; Group B: 13; Group C: 13) and 14 patients died of primary CRC (Group A: 3; Group B: 7; Group C: 4). Age ≥65 years, protruded gross type, positive lymphatic invasion, and high budding grade were significant predictors of recurrence in non-endoscopically curable patients.Conclusions: Our findings supported the JSCCR criteria for endoscopically curable T1 CRC. ER for T1 CRC did not worsen the clinical outcomes of patients who required additional surgical resection. [ABSTRACT FROM AUTHOR]

Background: The lower rectum close to the dentate line has distinct characteristics, making endoscopic submucosal dissection (ESD) of tumors challenging. We assessed clinical outcomes of ESD for such patients with hemorrhoids.Methods: Sixty-four patients (mean age, 68 years) underwent ESD for anorectal tumors close to the dentate line. We divided patients into those with (Group A, 45 patients) and without hemorrhoids (Group B, 19 patients). We examined en bloc and histological en bloc resection rates, procedure time, complication rates, and postoperative prognosis after ESD.Results: The mean tumor size was 43 mm. Histologic diagnoses were adenoma (42 %, 27/64), carcinoma in situ (44 %, 28/64), and T1 carcinoma (14 %, 9/64). There was no significant difference in en bloc resection (93 %, 42/45 vs. 95 %, 18/19) or postoperative bleeding rates (16 %, 7/45 vs. 11 %, 2/19) between Groups A and B, respectively. The mean procedural durations were 120 and 124 min, respectively, in Groups A and B. No perforations occurred. There was no significant difference in postoperative anal pain rate between Groups A (18 %, 8/45) and B (16 %, 3/19), and it resolved within a few days in all cases. There was one case of stricture in Group B. Two patients with T1 carcinoma underwent additional surgery, one underwent chemotherapy, and five had no additional treatment. No recurrence occurred during the follow-up period of 38 months.Conclusions: ESD is safe and effective for anorectal tumors close to the dentate line in patients with hemorrhoids. [ABSTRACT FROM AUTHOR]

Background: Although Japanese guidelines proposed by the Japan Gastroenterological Endoscopy Society for endoscopic submucosal dissection (ESD) for colorectal tumors recommend continued use of low-dose aspirin (LDA), this strategy is controversial. It was our practice to interrupt LDA therapy 5-7 days before ESD until December 2010, when we instituted the new guidelines and performed ESD without interrupting LDA therapy. The aim of the present study was to confirm the validity of the noninterrupted use of LDA inpatients undergoing ESD for colorectal tumors.Methods: We studied 582 consecutive patients with 609 colorectal tumors who underwent ESD at Hiroshima University Hospital between January 2006 and July 2014. The patients comprised three groups: LDA-interrupted group (13 patients with 13 colorectal tumors), LDA-continued group (28 patients with 31 colorectal tumors), and no anticoagulant/antiplatelet group (541 patients with 565 colorectal tumors).Results: The en bloc resection rate was 100% (13/13) in the LDA-interrupted group and 90.3% (28/31) in the LDA-continued group. Incidences of poor bleeding control during the procedure and bleeding after the procedure were 7.7% (1/13) and 15.4% (2/13) of patients, respectively, in the LDA-interrupted group, and 3.2% (1/31) and 16.1% (5/31) of patients, respectively, in the LDA-continued group. No patients experienced ischemic events in the perioperative period.Conclusions: Our data suggest that continued use of LDA increased the risk of bleeding after ESD for colorectal tumors compared with nonuse of anticoagulant/antiplatelets. No significant difference was seen between the LDA-continued group and the LDA-interrupted group. [ABSTRACT FROM AUTHOR]

Purpose: Pulverized konjac glucomannan (PKGM) is a natural biologically active compound extracted from konjac, a Japanese traditional food. In the present study, we investigated the role of PKGM in intestinal immunity in a mouse model of oxazolone (OXA)-induced colitis. Methods: C57BL/6(B6) mice were fed PKGM or control food from 2 weeks before the induction of OXA colitis. Body weight change, colon length, and histological change in the colon were examined. The mononuclear cells were purified from colon and stimulated with PMA/ionomycin. The levels of TNF-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-13 from the supernatant were measured by ELISA. Results: Oral administration of PKGM prevented the body weight loss and shortening of colon length associated with OXA-induced colitis. Histological analysis revealed that the colonic inflammation was improved by the administration of PKGM. The levels of IL-4 and IL-13, the critical inflammatory cytokines in OXA colitis, derived from mononuclear cells from the lamina propria of the colon were significantly suppressed by PKGM administration. PKGM-fed mice showed a significantly lower IL-4/IFN-γ ratio in the colonic lamina propria compared with that in control-fed mice. Fluorescence-activated cell sorting analysis revealed that natural killer (NK) 1.1 T cells in the liver were significantly decreased in PKGM-fed mice. Finally, the preventive role of PKGM in OXA-induced colitis was not observed in invariant natural killer T cell-deficient mice. Conclusions: PKGM ameliorated OXA-induced colitis in mice. This effect is associated with a decreased population of NK1.1 T cells and induction of Th1-polarized immune responses. [ABSTRACT FROM AUTHOR]

Colorectal endoscopic submucosal dissection ( ESD) has become common in recent years. Suitable lesions for endoscopic treatment include not only early colorectal carcinomas but also many types of precarcinomatous adenomas. It is important to establish practical guidelines in which the preoperative diagnosis of colorectal neoplasia and the selection of endoscopic treatment procedures are properly outlined, and to ensure that the actual endoscopic treatment is useful and safe in general hospitals when carried out in accordance with the guidelines. In cooperation with the Japanese Society for Cancer of the Colon and Rectum, the Japanese Society of Coloproctology, and the Japanese Society of Gastroenterology, the Japan Gastroenterological Endoscopy Society has recently compiled a set of colorectal ESD/endoscopic mucosal resection ( EMR) guidelines using evidence-based methods. The guidelines focus on the diagnostic and therapeutic strategies and caveat before, during, and after ESD/ EMR and, in this regard, exclude the specific procedures, types and proper use of instruments, devices, and drugs. Although eight areas, ranging from indication to pathology, were originally planned for inclusion in these guidelines, evidence was scarce in each area. Therefore, grades of recommendation were determined largely through expert consensus in these areas. [ABSTRACT FROM AUTHOR]

Background and Aim Double-balloon endoscopy ( DBE) has enabled direct, detailed examination of the entire small bowel with interventional capabilities. Although its usefulness is recognized, efficacy and safety have not been extensively evaluated by prospective multicenter studies. To evaluate the efficacy and safety of DBE carried out by expert and non-expert endoscopists, a prospective, multicenter study was conducted in five university hospitals and a general hospital in Japan. Methods A total of 120 patients who underwent 179 procedures were enrolled in the study. Experts carried out 129 procedures and non-experts carried out 50 procedures. Primary and secondary end points were evaluation of safety, the rate of achievement of procedural objectives, namely, identification of a new lesion, detailed examination to establish a therapeutic strategy, or exclusion of significant lesions by total enteroscopy, and rate of successful examination of the entire small bowel and evaluation of safety. Results Overall rate of achievement of procedural objectives was 82.5% (99/120). Overall success rate for examination of the entire small bowel was 70.8% (34/48). Incidence of adverse events was 1.1% (a mucosal injury and an episode of pyrexia in two of 179 examinations). No severe adverse events were encountered. There were no significant differences in any of the outcome measures comparing expert and non-expert operators. Conclusions DBE is effective and safe for patients with suspected small bowel diseases, and can be safely carried out even by a non-expert under the supervision of an expert, following a simple training program. [ABSTRACT FROM AUTHOR]

Objectives: Recent reports indicated that reduced SLC22A7 (a gene-encoding organic anion transporter 2) expression in noncancerous liver tissue predicts hepatocellular carcinoma (HCC) recurrence after curative resection. Our study aimed to elucidate the association between SLC22A7 expression and HCC development in chronic hepatitis C patients. Methods: HCC recurrence after local ablation therapy and SLC22A7 expression in noncancerous liver tissue were analyzed in 20 patients. Subsequently, the association between de novo HCC development and SLC22A7 expression was examined at baseline in 38 hepatitis C patients without HCC who subsequently developed HCC as well as in 76 hepatitis C patients who did not develop HCC and were matched for age, gender and stage of fibrosis. Results: In the patients whose HCC had been cured, reduced SLC22A7 expression in noncancerous liver tissue was significantly associated with a high incidence of multifocal HCC recurrence. In patients without HCC at baseline, cumulative incidence of de novo HCC development was significantly higher with a reduced SLC22A7 expression than with a normal expression (p = 0.01). This difference remained significant among patients without known risk factors for HCC like age and advanced fibrosis. Conclusion: Reduced SLC22A7 expression in the liver indicates a significant risk for HCC development in chronic hepatitis C, independently of other risk factors. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

SUMMARY Precise estimation of the capacity for right-turn traffic (comparable to left-turn traffic in the USA) is of great importance to determine signal phasing schemes at signalized intersections in Japan, where the left-hand driving rule is valid. However, in most signal timing procedures across the world, the lost time of right-turn traffic is simply determined by the duration of intergreen intervals and thus lacks considerations of various signal phasing and driver behavior. Meanwhile, sneakers per cycle are usually applied to account for the number of drivers completing right turns during the effective red portion of the clearance-and-change intervals. As a result, an initial cycle length must be hypothesized in order to assess the total number of sneakers within the analysis period. Consequently, a time-consuming iterative calculation process often becomes necessary. Therefore, the present study aims to develop a new lost time estimation method for right-turn traffic to overcome the aforementioned drawbacks. Lost times of right-turn traffic under three conventional phasing plans are theoretically formulated on the basis of a time-space diagram and shock-wave theory. The new method is validated using field data, with case studies of its application in the signal timing procedure. Results indicated that the proposed method is capable of offering more accurate estimation than conventional approaches, which leads to shorter cycle length and simplifies signal timing process by eliminating an iterative check to determine the number of sneakers. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, 'Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Conventional endoscopic resection (CER) for early colorectal neoplasia (CRN) is widely accepted as a minimally invasive treatment. Endoscopic submucosal dissection (ESD) was developed in Japan to resect larger lesions, but ESD was not covered by the Japanese national health insurance until April 2012. In addition, treatment strategies vary considerably among medical facilities. To evaluate the current situation in Japan regarding endoscopic treatment of CRNs measuring ≥20 mm, we conducted a prospective multicenter study at 18 medium-volume and high-volume specialized facilities in cooperation with the Japan Society for Cancer of the Colon and Rectum (JSCCR). Methods: The JSCCR conducted a multicenter, observational study of all patients treated by CER and ESD of CRNs measuring ≥20 mm. Results: From October 2007 to December 2010, CERs and ESDs were performed on 1,845 CRNs (CERs 1,029; ESDs 816). Lesions diagnosed as protruded, flat, and depressed totaled 541, 1224, and 48, respectively. En bloc resection rates and mean procedure times for CER/ESD were 56.9 %/94.5 % ( P < 0.01) and 18 ± 23 min/96 ± 69 min, respectively. The average ESD procedure time was 129 ± 83 min in the ≥40-mm group. As lesion size increased, the CER en bloc resection rate decreased significantly (trend P < 0.01), but the ESD en bloc resection rate remained over 93 %. Perforation and delayed bleeding rates of CER/ESD were 0.8 %/1.6 % ( P < 0.05) and 2 %/2.2 % ( P = 0.3), respectively. Conclusions: The en bloc resection rate for ESD was significantly higher than for CER, although complication rates were fairly low. Despite a longer procedure time, safety of colorectal ESD has improved in various facilities in Japan. However, ESD for lesions measuring ≥40 mm must be performed by experienced endoscopists due to the longer procedure time. [ABSTRACT FROM AUTHOR]

Backgrounds: Gastrointestinal (GI) toxicity is an undesirable effect of nonsteroidal anti-inflammatory drugs (NSAIDs). We conducted a multicenter study in Japan to clarify the GI risk grade in patients with NSAID-induced GI bleeding. Methods: Patients with emergent endoscopic hemostasis by nonvariceal bleeding were registered from 36 hospitals in Hiroshima. In cases with NSAID use, the GI risk grade (low, moderate, or high) was evaluated, and concomitant drugs were investigated. We asked 79 gastroenterologists and 234 orthopedists what concomitant drugs they would prescribe to 3 simulated patients. Results: A total of 1,350 patients were registered. NSAIDs were used in 278 cases (21%). Concerning the risk grade in each patient, the largest group was the moderate-risk group (203 patients; 73%), while the high-risk group comprised 10% of all NSAID users with bleeding. A proton pump inhibitor (PPI) or misoprostol was administrated to only 20 patients (7%). A small number of the gastroenterologists and orthopedists who responded to the questionnaire would prescribe PPI or misoprostol to simulated patients with short-term loxoprofen use. Conclusions: In NSAID users with GI bleeding, the moderate-risk group was the largest group for GI toxicity in Japan. In these cases, PPI or misoprostol was not commonly medicated in clinical practice. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) allows for en bloc tumor resection irrespective of the size of the lesion. In Japan, ESD has been established as a standard method for endoscopic ablation of malignant tumors in the upper gastrointestinal tract. Although the use of colorectal ESD has been gradually spreading with the development of numerous devices, ESD has not yet been fully established as a standard therapeutic method for colorectal lesions. Currently, colorectal ESD is performed as an 'advanced medical treatment' without national health insurance coverage. With the recent accumulation of numerous cases, the safety and simplicity of colorectal ESD have improved remarkably. Currently in Japan, a prospective multicenter cohort study organized by the Japan Gastroenterological Endoscopy Society is ongoing to clarify the safety and efficacy of colorectal ESD to obtain remuneration from national health insurance. In this report, we showed the outcome regarding safety and efficacy of colorectal ESD through a review of the published work. Of 2719 cases with colorectal ESD at 13 institutions, the complete en bloc resection and perforation rates were 82.8% (61-98.2%, 2082/2516) and 4.7% (1.4-8.2%, 127/2719), respectively. Additional surgery for perforation was very rare because perforations were tiny enough to be closed endoscopically by clips in most of the cases and treated conservatively. In the near future, colorectal ESD will be a common therapeutic method for early colorectal carcinoma. [ABSTRACT FROM AUTHOR]

Use of a Dual knife has become commonplace for endoscopic submucosal dissection (ESD) of colorectal tumors at Hiroshima University Hosipital. A Hook knife has been also used in combination with the Dual knife, depending on the location of the lesion. We have had recent opportunities to use a scissors-type SB knife Jr. We retrospectively compared outcomes of colorectal ESD performed with the Dual knife in combination with the SB knife Jr versus the Hook knife. In conclusion, although the Hook knife was shown to be a very useful auxiliary device for colorectal ESD, the SB knife Jr. yielded better results than the Hook knife in terms of complete en block resection and avoidance of perforation. Use of the Dual knife with the SB Knife Jr shows good potential for improving complete en bloc resection rate and safety of technically difficult colorectal ESD. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a major cause of death in Japan, where it accounts for the largest number of deaths from malignant neoplasms in women and the third largest number in men. Many new treatment methods have been developed over the last few decades. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer (JSCCR Guidelines 2010) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment, and to deepen mutual understanding between health-care professionals and patients by making these Guidelines available to the general public. These Guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these Guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. As a result of the discussions held by the Guideline Committee, controversial issues were selected as Clinical Questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here we present the English version of the JSCCR Guidelines 2010. [ABSTRACT FROM AUTHOR]

Background: The 2010 Japanese Gastric Cancer Association guidelines for the treatment of submucosal invasive gastric cancer (SM-GC) specify size 30 mm or less, differentiated-dominant histology, lack of vessel involvement, and submucosal invasion of less than 500 μm (SM1) as expanded criteria for curative endoscopic resection. Our purpose in this study was to confirm the validity of the expanded indications for curative endoscopic submucosal dissection (ESD) of SM-GC. Methods: The study subjects were 173 patients with SM-GC resected by ESD at Hiroshima University Hospital between April 2002 and September 2010, including 99 patients for whom 3-plus years' follow-up information was available. Post-ESD outcomes were compared between cases of SM1-GC that met the expanded ESD criteria, those that did not, and SM2-GC cases. Results: Complete resection was achieved for 93.2% of the SM1-GCs that met the expanded criteria. There was neither metastasis to lymph nodes or other organs nor local recurrence among the SM1-GCs. Disease-specific survival did not differ significantly between patients that were simply followed up after ESD and those that were treated by additional surgical resection. Conclusions: Our outcome data support the clinical validity of ESD without additional surgical resection for SM1-GCs that meet the expanded criteria. [ABSTRACT FROM AUTHOR]

At present, there are many narrow band imaging (NBI) magnifying observation classifications for colorectal tumor in Japan. To internationally standardize the NBI observation criteria, a simple classification system is required. When a colorectal tumor is closely observed using the recent high-resolution videocolonoscope, a pit-like pattern on the tumor can be observed to a certain degree without magnification. In the symposium we could have a consensus that we will name the pit-like pattern as 'surface pattern.' Using the NBI system, the microvessels on the tumor surface can also be recognized to a certain degree. When the NBI system is used, the structure is emphasized, and consequently, the surface pattern can be recognized easily. Recently, an international cooperative group was formed and consists of members from Japan, the USA and Europe, which is named as the Colon Tumor NBI Interest Group. This group has developed a simple category classification (NBI international colorectal endoscopic [NICE] classification), which classifies colorectal tumors into types 1−3 even by closely observing colorectal tumors using a high-resolution videocolonoscope (Validation study is now ongoing by Colon Tumor NBI Interest Group.). The key advantage of this is simplification of the NBI classification. Although the magnifying observation is the best for getting detailed NBI findings, both close observation and magnifying observation using the NICE classification might give almost similar results. Of course the NICE classification can be used more precisely with magnification. In this report we also refer the issues on NBI magnification, which should be solved as early as possible. [ABSTRACT FROM AUTHOR]

Colorectal cancer is one of the complications of ulcerative colitis (UC) and the risk of cancer increases as the duration of the disease becomes longer. Surveillance colonoscopy has been considered to be important for the early detection and early treatment of colorectal cancer, especially in longstanding UC. Because it is not always easy to detect neoplastic lesions in UC endoscopically, guidelines recommend the use of step biopsy in surveillance, in which either 4 biopsy specimens for every 10 cm or a total of 33 or more biopsy specimens are obtained. However, it has been pointed out that a step biopsy obtaining several tens of biopsy specimens may not be an ideal method in terms of invasiveness to the patient or medical cost. Instead of step biopsy, recent studies report the usefulness of target biopsy, in which biopsy tissues are obtained only from regions suspected of neoplasia. Therefore, the Research Group for Intractable Inflammatory Bowel Disease of the Ministry of Health, Labour and Welfare of Japan has initiated a randomized controlled study to compare the efficacy of step biopsy and target biopsy. The present article gives an introduction to this ongoing randomized controlled trial in Japan. [ABSTRACT FROM AUTHOR]

Bleeding, perforation, and residual/local recurrence are the main complications associated with colonoscopic treatment of colorectal tumor. However, current status regarding the average incidence of these complications in Japan is not available. We conducted a questionnaire survey, prepared by the Colorectal Endoscopic Resection Standardization Implementation Working Group, Japanese Society for Cancer of the Colon and Rectum (JSCCR), to clarify the incidence of postoperative bleeding, perforation, and residual/local recurrence associated with colonoscopic treatment. The total incidence of postoperative bleeding was 1.2% and the incidence was 0.26% with hot biopsy, 1.3% with polypectomy, 1.4% with endoscopic mucosal resection (EMR), and 1.7% with endoscopic submucosal dissection (ESD). The total incidence of perforation was 0.74% (0.01% with the hot biopsy, 0.17% with polypectomy, 0.91% with EMR, and 3.3% with ESD). The total incidence of residual/local recurrence was 0.73% (0.007% with hot biopsy, 0.34% with polypectomy, 1.4% with EMR, and 2.3% with ESD). Colonoscopic examination was used as a surveillance method for detecting residual/local recurrence in all hospitals. The surveillance period differed among the hospitals; however, most of the hospitals reported a surveillance period of 3-6 months with mainly transabdominal ultrasonography and computed tomography in combination with the colonoscopic examination. [ABSTRACT FROM AUTHOR]

In order to understand the current use of endoscopic submucosal dissection (ESD) for the treatment of colorectal tumors in Japan, we administered a questionnaire survey to 1356 institutions all over the country. The subject of the survey was colorectal ESD performed from January 2000 to September 2008. Among the 1356 institutions, 391 (28.8%) responded to the questionnaire, and colorectal ESD was currently being performed in 194 institutions. The 194 institutions were almost equally distributed in Japan, that is, colorectal ESD has been performed all over the country. Among these 194 institutions, the procedure had been performed in 100 or more cases in 22 (11.3%) institutions and in 50–99 cases in 18 institutions (9.3%). The knives used in colorectal ESD were the Hook knife, Flush knife, and Flex knife. The average time required for colorectal ESD was 92.2 min, the rate of complete en bloc resection was 83.8%, the perforation rate was 4.8%, and no case of death from complications was reported. [ABSTRACT FROM AUTHOR]

Aim: Regarding the assessment of colonic lesions, important differences between Japan and the Western world have emerged during the last decade. The aim of this study was to compare the clinical outcomes of the same equipment when used in Japan or in France. Method: Chromoscopy has not been extensively accepted in the West, in contrast to the wide acceptance in Japan which is probably due to the national screening programme for early gastric cancer. With the development of narrow-band imaging (NBI) we might expect a more generalized approach to the clinical use of various classifications. Narrow band imaging might be an important step towards virtual chromoscopy. A total of 48 patients were examined with back-to-back colonoscopy, using a non-sequential (EXERA II, Olympus Medical Systems Corp., Tokyo, Japan) endoscope, and a sequential endoscope (LUCERA, Olympus Medical Systems Corp.). Results: Education differences also play a role in the evaluation of the clinical outcome of the endoscopy. In Japan, detailed classification of the morphology of the detected lesion is done as a preliminary characterization step before the treatment decision. In the West a treatment decision immediately leads to the therapeutic outcome (non-neoplastic or neoplastic; removed or not). This study showed clearly that, with the same equipment, we obtained identical results for image quality of image in Japan and France. Non-Japanese endoscopists could achieve the same results as Japanese colleagues if knowledge of the minute classification is more widely accepted. Conclusion: While the differences in the evaluation of the clinical outcome are mostly cultural, the analysis of endoscopic imaging indicates that the LUCERA and EXERA series provide the same clinical benefit. [ABSTRACT FROM AUTHOR]

Helicobacter pylori ( H. pylori) infection plays an important role in gastric carcinogenesis. We conducted a systematic review concerning gastric cancer development after H. pylori eradication therapy. In total 15 papers matched our criteria, the results were reviewed. The H. pylori eradication therapy statistically diminished the prevalence of clinical gastric cancer by approximately one-third. The studies from Japan supported this conclusion; however, studies from overseas reported conflicting results. The differences in these conclusions lie in the diagnostic ability of endoscopic examination, since the clinical stage was quite different between these studies. Gastric cancer that developed after eradication revealed a mainly intestinal type histology and depressed-type appearance. The following are possible reasons for reduced gastric cancer: (1) eradication therapy inhibits the new occurrence of gastric cancer, (2) eradication regresses or inhibits the growth of gastric cancer, and (3) eradication interferes with the discovery of gastric cancer. Considering the biological nature of cancer cell proliferation, a sufficiently long-term follow-up may clarify the effect of eradication therapy on inhibition of the development (not discovery) of gastric cancer and reduction of gastric cancer-related mortality. [ABSTRACT FROM AUTHOR]

The article focuses on the findings of a study concerning the role of Artemia and mussel as food for cultured middle-stage Japanese spiny lobster physollomata Panulirus japonicus. Researchers used stable nitrogen isotope analysis in estimating the relative assimilation of Artemia and mussel gonad by cultured phyllosomata. The study indicated that the analysis of stable nitrogen isotope ratios is a very important and useful diagnostic tool in estimating the relative assimilation rates of different food items.

Endoscopic submucosal dissection (ESD) allows en bloc resection of a lesion, irrespective of the size of the lesion. ESD has been established as a standard method for the endoscopic ablation of malignant tumors in the upper gastrointestinal (GI) tract in Japan. Although the use of ESD for colorectal lesions has been studied via clinical research, ESD is not yet established as a standard therapeutic method for colorectal lesions because colorectal carcinoma has unique pathological, organspecific characteristics that differ radically from those of the esophagus and stomach, and scope handling and control is more difficult in the colorectum than in the upper GI tract. Depending on the efficacy of endoscopic mucosal resection (EMR) and the clinicopathological characteristics of the colorectal tumor, the proposed indications for colorectal ESD are as follows: (1) lesions difficult to remove en bloc with a snare EMR, such as nongranular laterally spreading tumors (particularly the pseudodepressed type), lesions showing a type Vi pit pattern, and large lesions of the protruded type suspected to be carcinoma; (2) lesions with fibrosis due to biopsy or peristasis; (3) sporadic localized lesions in chronic inflammation such as ulcerative colitis; and (4) local residual carcinoma after EMR. Colorectal ESD is currently in the development stage, and a standard protocol will be available in the near future. We hope that colorectal tumors will be efficiently treated by a treatment method appropriately selected from among EMR, ESD, and surgical resection after precise preoperative diagnosis based on techniques such as magnifying colonoscopy. [ABSTRACT FROM AUTHOR]

Background and Aim: Many studies have shown that Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers and gastric carcinoma in adults. However, little is known about these associations in the younger population. The aim of this study was to clarify endoscopic and histological findings in H. pylori-positive young adults. Methods: Two hundred consecutive outpatients younger than 29 years old undergoing esophago-gastroduodenal endoscopy at four hospitals between 2001 and 2002 were eligible for this study. At endoscopy, three biopsy specimens were obtained from the mid-antrum, the angulus and the mid-corpus. Endoscopic and histological interpretations were based on the updated Sydney System. H. pylori infection was determined by histology and serology. Results: The rates of H. pylori infection were 1.2% (1/86) in normal, 95.8% (46/48) in gastritis, 97.8% (45/46) in duodenal ulcers, 100% (17/17) in gastric ulcers, and 100% (3/3) in gastric carcinomas. Endoscopic findings in 112 H. pylori-positive patients were 25 normal (22.3%), 38 atrophy (33.9%), 18 erosion (16.1%), and 31 nodularity (27.7%). Histological findings of H. pylori-positive patients in the anturm revealed mononuclear cell and neutrophil infiltration in 100%, and atrophy in 27.7%. Histological findings of H. pylori-positive patients in the corpus revealed mononuclear cell infiltration in 75%, neutrophil infiltration in 60.7%, and atrophy in 28.6%. Conclusions: The study shows that H. pylori infection is strongly associated with chronic gastritis and peptic ulcers, and that histological corpus gastritis was found with high frequency in Japanese young adults. [ABSTRACT FROM AUTHOR]

Recently it has become very important to diagnose more precisely the invasion depth of submucosal carcinoma prior to endoscopic mucosal resection (EMR) whether selecting lesion is with or without indications for EMR. This study aimed to evaluate the usefulness of high-frequency ultrasound probes (HFUP) for preoperative diagnosis of vertical invasion depth<1000 µm or not in superficial and sessile type submucosal colorectal carcinomas. Twenty-seven cases of superficial and sessile type submucosal colorectal carcinoma were examined with high-frequency ultrasound probes (HFUP; 15 or 20 MHz radial-scan ultrasound probes; Olympus Optical, Tokyo, Japan and Fujinon Omiya, Saitama, Japan) at Hiroshima University Hospital and analyzed. Diagnostic accuracy was confirmed by comparing the ultrasonic with the pathologic vertical invasion depth of specimens resected either by EMR or surgical resection. Histologic depth of submucosal invasion was defined as the distance from muscularis mucosae measured microscopically with a micrometer. When muscularis mucosae in the tumor could not be detected, we measured the invasion depth from the surface of the carcinoma to the apex of the deepest invasive portion. As a result, invasion depth between ultrasonic image and histologic findings showed a significantly close correlation. HFUP diagnosis was demonstrated as useful in determining the distance of vertical invasion and for planning a therapeutic strategy against submucosal colorectal carcinomas. [ABSTRACT FROM AUTHOR]

Harimoto N, Shimada M, Aishima S, Kitagawa D, Itoh S, Tsujita E, Maehara S, Taketomi A, Tanaka S, Shirabe K, Maehara Y. The role of heat shock protein 27 expression in hepatocellular carcinoma in Japan: special reference to the difference between hepatitis B and C. Liver International 2004: DOI:10.1111/j.1478-3231.2004.0927.x. © Blackwell Munksgaard 2004 A recent report showed that heat shock protein (HSP)-27 expression was related to histological grade and survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to examine the effect of expression of HSP-27 on clinicopathological variables in Japanese patients with HCC. An immunohistochemical study for HSP-27 was performed on 60 HCC cases using a monoclonal anti-HSP-27 antibody. We divided 60 patients into two groups, patients with a low expression of HSP-27 ( n=34) and those with a high expression of HSP-27 ( n=26). Forty patients tested positive for the hepatitis C virus (HCV) antibody and 20 tested positive for the hepatitis B surface antigen. There appeared to be no relationship between HSP expression and clinicopathologic factors and no differences were observed between the high expression group and the low expression group. In the hepatitis B virus (HBV) group ( n=20), HSP-27 expression correlated significantly with prognosis, disease-free survival (DFS) and overall survival. High expression was significantly associated with poor prognosis in the HBV group. In contrast, patients with a high expression tended to have a good prognosis in the HCV group ( n=40): DFS and overall survival. This study showed the possibility that HSP-27 plays different roles in HBV- and HCV-associated HCCs. [ABSTRACT FROM AUTHOR]

We report two cases of granulomatous gastritis that resolved completely with Helicobacter pylori eradication. Two Japanese women, one 61 years old and one 58 years old, presented to our hospital with epigastralgia. Endoscopy revealed multiple shallow ulcerative lesions in the gastric corpus of both patients. Biopsy specimens demonstrated acute and chronic inflammation with multiple small, noncaseating granulomas at the level of the foveolar isthmi—the junction between the pits and the glands. Both specimens were positive for Helicobacter pylori. No other causes of organic granulomatous disease could be found. Both patients were diagnosed as having isolated granulomatous gastritis and were given triple therapy for Helicobacter pylori eradication, with their fully informed consent. The granulomatous gastritis resolved after successful Helicobacter pylori eradication therapy. This report describes a possible association between isolated granulomatous gastritis and Helicobacter pylori infection. To our knowledge, this is the first report describing isolated granulomatous gastritis successfully treated by triple therapy (Helicobacter pylori eradication therapy). [ABSTRACT FROM AUTHOR]

Background and aims: Recent genomic characterization of gastric cancer (GC) by sequencing has revealed a large number of cancer-related genes. Research to characterize the genomic landscape of cancer has focused on established invasive cancer to develop biomarkers for therapeutic or diagnostic targets, and nearly all GC reports have been about advanced GC. The aim of this study is to identify recurrently mutated genes in non-invasive GC and, in particular, the driver mutations that are associated with the development of GC. Methods and results: We performed whole-exome sequencing of 19 fresh frozen specimens of differentiated-type non-invasive GC and targeted sequencing for 168 genes of 30 formalin-fixed paraffin-embedded archival specimens of differentiated-type non-invasive GC. We found that TP53 and LRP1 are significantly associated with non-invasive GC. It has been reported that LPR1 is associated with CagA autophagy in gastric mucosa. Therefore, we downloaded RNA sequence data for gastric cancer from the The Cancer Genome Atlas (TCGA) Genomic Data Commons Data Portal and examined the differences in LRP1 gene expression levels. The expression level was significantly lower in cases without LRP1 mutation than in cases with LRP1 mutation. Based on these results, fluorescent immunostaining for CagA was performed for 49 of the above samples to evaluate CagA accumulation within the cancerous tissue. Accumulation of CagA was significantly greater when an LRP1 mutation was present than without a mutation. Conclusion: These data suggest that LRP1 mutation is an important change promoting the transformation of gastric mucosa to GC early in the carcinogenesis of cancer. [ABSTRACT FROM AUTHOR]

The article examines several cases of gastroenterological malpractice in Japan.It has been found out that lengthy diagnostic delay coupled with advanced disease at the time of final diagnosis has resulted to claims of negligence. Various medical complications associated with endoscopy has also been reported. Based from the cases examined, the process of informed consent is an important tool for reducing malpractice risk.

A letter to the editor is presented regarding the changes in malpractice claims in Japanese gastroenterological practice.

In order to verify the actual condition of endoscopic treatment of colorectal stenosis in Japan, 16 institutions participating in the Endoscopy Forum Japan participated in a survey with questionnaires concerning the number of stenting cases, the number of ballooning cases, the number of transanal ileus-tube insertion cases, the technical success rate, and complications, and so on. Treatment with a stent was conducted in 31.2% of the institutions for malignant lesions and in 25.0% of the institutions for benign lesions. Ballooning was conducted in 12.5% of the institutions for malignant lesions and in 62.5% of the institutions for benign lesions. Transanal ileus-tube insertion was conducted in 81.1% of the institutions for malignant lesions and in 18.7% of the institutions for benign lesions. The therapeutic success rate was excellent with each therapeutic technique and reached 86–100%. Complications included perforation and bleeding. [ABSTRACT FROM AUTHOR]

Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0–2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3–49·3), median overall survival periods were 2·93 years (95% CI 2·60–3·79) and 2·74 years (95%CI 2·26–3·21), respectively (hazard ratio 0·90 [95% CI 0·71–1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88–1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC. • Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma. • There is no clear consensus regarding the optimal chemotherapeutic agent for use in TACE. • Few studies have compared agents used for TACE. • Cisplatin is not significantly superior to epirubicin in TACE for patients with HCC. [ABSTRACT FROM AUTHOR]

Since the 1990s, Akoya oyster disease (AOD) associated with reddish browning of the soft tissues and mortality of cultured pearl oyster, Pinctada fucata (Gould), has been occurring in the western part of Japan. Although transmission experiments suggested that the disease is infectious, the causative agent has not been identified. Previous studies suggested that a member of the Spirochaeta cause AOD, and Candidatus Maribrachyspira akoyae was proposed as the putative causative agent. However, difficulties in culturing the putative causal bacterium have hindered research on AOD. In this study, we developed a quantitative PCR assay to examine the spatial-temporal colonization patterns of Spirochaeta in pearl oysters. Spirochete genes were abundant in the mantle, adductor muscle, and hemolymph of oysters but scarce in the gill, crystalline style, hemocytes, heart, and digestive glands. Spirochete genes were detected in the hemolymph 2 weeks after infection, and their number increased with time and mortality. The Spirochaeta genes identified in the hemolymph of pearl oysters reared in culturing fields changed with variations in water temperature, and the number of Spirochaeta genes increased or decreased at approximately 20 °C. Hence, the bacterium was thought to grow at water temperatures above 20 °C. These results are consistent with those of infection tests and epidemiologic studies of the distribution and seasonal changes in AOD pathogens and support the hypothesis that a spirochete causes AOD. • We developed a quantitative PCR assay for genes thought to be derived from putative causative agent of Akoya oyster disease. • Gene copy number was high in the mantle, adductor muscle, and hemolymph. • Gene in hemolymph was detected 2 weeks after infection and continued to increase with time and mortality. • Spirochaeta is thought to grow at water temperatures above 20 °C. • Results of this study support the hypothesis that the Spirochaeta cause AOD. [ABSTRACT FROM AUTHOR]

Background and Aims: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes and explored new indications and curability criteria., Methods: We analyzed data from a Japanese multicenter, prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines) into elderly-high (>10% estimated metastatic risk) and elderly-low (EL-L) (≤10% estimated metastatic risk)., Results: In total, 3371 patients with 3821 EGCs were included; endoscopic submucosal dissection was the prominent treatment choice. Among them, 3586 lesions met the guidelines' ER indications, and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm and 96.0%, 64.0%, and 18.0%, respectively, for those >3 cm. Curative ER and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates after curative ER and elderly-high were 0.3% (95% confidence interval [CI], 0.2-0.6) and 3.5% (95% CI, 2.0-5.7), respectively. After EL-L, the rate was 0.9% (95% CI, 0.2-3.5) even without subsequent treatment., Conclusions: The usefulness of endoscopic submucosal dissection for elderly EGC patients was confirmed by their clinical outcomes. Lesions of ≤3 cm and EL-L emerged as new ER indication and curability criteria, respectively. (Clinical trial registration number: UMIN000005871.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This study was supported by a grant for Clinical Cancer Research from the Japanese Ministry of Health, Labor, and Welfare (H21-022); a grant from Daiwa Securities Health Foundation (H24-16); and grants for the National Cancer Center Research and Development from the Japanese Ministry of Health, Labor, and Welfare (25-A-12, 28-K-1, 29-A-13, and 2021-A-18)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: Narrow-band imaging (NBI) contributes to real-time optical diagnosis and classification of colorectal lesions. The Japan NBI Expert Team (JNET) was introduced in 2011. The aim of this study was to explore the diagnostic accuracy of JNET when applied by European and Japanese endoscopists not familiar with this classification., Methods: This study was conducted by 36 European Society of Gastrointestinal Endoscopy (ESGE) and 49 Japan Gastroenterological Endoscopy Society (JGES) non-JNET endoscopists using still images of 150 lesions. For each lesion, nonmagnified white-light, nonmagnified NBI, and magnified NBI images were presented. In the magnified NBI, the evaluation area was designated by region of interest (ROI). The endoscopists scored histological prediction for each lesion., Results: In ESGE members, the sensitivity, specificity, and accuracy were respectively 73.3%, 94.7%, and 93.0% for JNET Type 1; 53.0%, 64.9%, and 62.1% for Type 2A; 43.9%, 67.7%, and 55.1% for Type 2B; and 38.1%, 93.7%, and 85.1% for Type 3. When Type 2B and 3 were considered as one category of cancer, the sensitivity, specificity, and accuracy for differentiating high-grade dysplasia and cancer from the others were 59.9%, 72.5%, and 63.8%, respectively. These trends were the same for JGES endoscopists., Conclusion: The diagnostic accuracy of the JNET classification was similar between ESGE and JGES and considered to be sufficient for JNET Type 1. On the other hand, the accuracy for Types 2 and 3 is not sufficient; however, JNET 2B lesions should be resected en bloc due to the risk of cancers and JNET 3 can be treated by surgery due to its high specificity., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan., Methods: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum., Results: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA., Conclusions: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis., (© 2024. The Author(s).)

Background: Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria., Methods: Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis., Results: Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28 days., Conclusions: Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy., (© 2024. Japanese Society of Gastroenterology.)

Purpose: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA., Methods: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests., Results: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively., Conclusion: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

Background and Aims: Many patients have endoscopic evidence of recurrent Crohn's disease [CD] at 1 year after intestinal resection. These lesions predict future clinical recurrence. We endoscopically evaluated postoperative anastomotic lesions in CD patients from a large cohort of postoperative CD patients., Methods: We retrospectively enrolled CD patients who underwent surgical resection between 2008 and 2013 at 19 inflammatory bowel disease [IBD]-specialist institutions. The initial analyses included patients who underwent ileocolonoscopy ~1 year after intestinal resection. Follow-up analyses assessed any changes in the endoscopic findings over time. We evaluated the postoperative endoscopic findings, which were classified into four categories [no lesion, mild, intermediate, severe] at the sites of the anastomotic line and peri-anastomosis., Results: In total, 267 CD patients underwent postoperative ileocolonoscopy. Postoperative anastomotic lesions were widely detected in index ileocolonoscopy [61.0%] and were more frequently detected in follow-up ileocolonoscopy [74.9%]. Endoscopic severity also increased. Patients with intermediate or severe peri-anastomotic or anastomotic line lesions at the index ileocolonoscopy required significantly more interventions, including endoscopic dilatation or surgery, than patients with mild lesions or no lesions., Conclusions: Frequent anastomotic lesions were observed at the postoperative index ileocolonoscopy. These gradually increased for subsequent ileocolonoscopy, even in the biologic era. Regarding lesions on the anastomotic line, intermediate lesions on the anastomotic line [e.g. irregular or deep ulcers] might be considered recurrent disease, and mild lesions [e.g. linear superficial ulcers] might be considered non-recurrent disease. Prospective studies are needed to resolve this issue, including treatment enhancement., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)