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Duodenal cancer is considered to be a small intestinal carcinoma in terms of clinicopathology. In Japan, there are no established treatment guidelines based on sufficient scientific evidence; therefore, in daily clinical practice, treatment is based on the experience of individual physicians. However, with advances in diagnostic modalities, it is anticipated that opportunities for its detection will increase in future. We developed guidelines for duodenal cancer because this disease is considered to have a high medical need from both healthcare providers and patients for appropriate management. These guidelines were developed for use in actual clinical practice for patients suspected of having non-ampullary duodenal epithelial malignancy and for patients diagnosed with non-ampullary duodenal epithelial malignancy. In this study, a practice algorithm was developed in accordance with the Minds Practice Guideline Development Manual 2017, and Clinical Questions were set for each area of epidemiology and diagnosis, endoscopic treatment, surgical treatment, and chemotherapy. A draft recommendation was developed through a literature search and systematic review, followed by a vote on the recommendations. We made decisions based on actual clinical practice such that the level of evidence would not be the sole determinant of the recommendation. This guideline is the most standard guideline as of the time of preparation. It is important to decide how to handle each case in consultation with patients and their family, the treating physician, and other medical personnel, considering the actual situation at the facility (and the characteristics of the patient).

Introduction: Few studies have focused on bleeding following endoscopic submucosal dissection (ESD) in surgically altered stomach. We aimed to reveal the bleeding risk in surgically altered stomach following ESD for early gastric cancer (EGC). Methods: We enrolled patients with ESD for EGC at 33 institutions between 2013 and 2016. In study 1, we evaluated bleeding risk following ESD in surgically altered stomach, compared with whole stomach. In study 2, we evaluated factors associated with bleeding following ESD in patients with surgically altered stomach. Results: Of 11,452 patients, 445 patients had surgically altered stomach with the bleeding rate following ESD of 4.9%. In study 1, the bleeding risk in surgically altered stomach was not significant (odds ratio [OR], 1.37; 95% confidence interval [CI], 0.87–2.17) in the multivariate logistic regression analysis. No significant results were obtained when the surgically altered stomach was subdivided into various types. In study 2, the multivariate logistic regression analysis revealed that independent risk factors for bleeding following ESD were ischemic heart disease (OR, 7.52; 95% CI, 2.00–28.25) and P2Y12 receptor antagonist (OR, 4.81; 95% CI, 1.21–19.14). Discussion/Conclusion: In this nationwide study, we found that the bleeding risk of surgically altered stomach following ESD for EGC did not significantly differ from that of whole stomach. The risk factors for ESD in patients with surgically altered stomach were ischemic heart disease and P2Y12 receptor antagonist.

Introduction: Risk prediction of gastric cancers is important to implement appropriate screening procedures. Although aberrant DNA methylation is deeply involved in gastric carcinogenesis, its induction by Helicobacter pylori, a strong gastric carcinogen, is unclear. Here, we analyzed the effect of H. pylori infection on the quantity of methylated DNA molecules in noncancerous gastric mucosae and examined its association with gastric cancer risk.Experimental Design: Gastric mucosae were collected from 154 healthy volunteers (56 H. pylori negative and 98 H. pylori positive) and 72 cases with differentiated-type gastric cancers (29 H. pylori negative and 43 H. pylori positive) by endoscopy. The numbers of DNA molecules methylated and unmethylated for eight regions of seven CpG islands (CGI) were quantified by quantitative PCR after bisulfite modification, and fractions of methylated molecules (methylation levels) were calculated.Results: Among healthy volunteers, methylation levels of all the eight regions were 5.4- to 303-fold higher in H. pylori positives than in H. pylori negatives (P < 0.0001). Methylation levels of the LOX, HAND1, and THBD promoter CGIs and p41ARC exonic CGI were as high as 7.4% or more in H. pylori–positive individuals. Among H. pylori–negative individuals, methylation levels of all the eight regions were 2.2- to 32-fold higher in gastric cancer cases than in age-matched healthy volunteers (P ≤ 0.01). Among H. pylori–positive individuals, methylation levels were highly variable, and that of only HAND1 was significantly increased in gastric cancer cases (1.4-fold, P = 0.02).Conclusions: It was indicated that H. pylori infection potently induces methylation of CGIs to various degrees. Methylation levels of specific CGIs seemed to reflect gastric cancer risk in H. pylori–negative individuals.

Supplementary Table S1 from High Levels of Aberrant DNA Methylation in Helicobacter pylori–Infected Gastric Mucosae and its Possible Association with Gastric Cancer Risk

Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume. Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching. A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups. The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD.

BACKGROUND AND AIM This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). METHODS We retrospectively reviewed 10,320 patients who underwent ESD for EGC during November 2013-October 2016. We evaluated overall bleeding rates and their inter-group differences. Factors associated with early/late (cut-off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated. RESULTS Overall, the post-ESD bleeding rate was 4.7% (489/10 320); the median time to post-ESD bleeding was 4 days. The post-ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1). CONCLUSION We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.

Introduction: An increase in the incidence of duodenal adenocarcinoma has been recently reported. However, little is known about the risk factors for duodenal adenocarcinoma, which are important for screening purposes. We, therefore, aimed to conduct a systematic review to identify risk factors for non-ampullary duodenal adenocarcinoma. Methods: A medical literature search was performed using electronic databases, including PubMed, Cochrane Library, Japan Medical Abstracts Society, and Web of Science. Studies that assessed the association between dietary habits, lifestyle behaviors, comorbidities, and non-ampullary duodenal adenocarcinoma were extracted. The Newcastle-Ottawa Scale was used to assess the risk of bias in individual studies, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the quality of evidence across studies included in this review. Results: Out of 1,244 screened articles, 10 were finally selected for qualitative synthesis. In the general population, no consistent risk factors were identified except for Helicobacter pylori positivity, which was considered a risk factor in 2 studies, but the quality of evidence was considered very low because of the high risk of bias. In patients with familial adenomatous polyposis (FAP), Spigelman stage IV at initial endoscopy was considered a consistent risk factor in 3 studies. Conclusions: There are currently limited data regarding risk factors for non-ampullary duodenal adenocarcinoma, and no conclusive risk factors were identified in the general population. However, in patients with FAP, Spigelman stage IV was identified as a consistent risk factor. Further studies are needed to improve diagnosis and support effective clinical management of this malignancy.

Background and Aim Percutaneous radiofrequency ablation (RFA) is a minimally invasive and curative local treatment for hepatocellular carcinoma (HCC). However, serious concerns remain regarding critical recurrences such as metastasis, dissemination, and/or seeding due to RFA. In August 2006, we introduced selective feeding artery ablation before tumor ablation to reduce the risk of critical recurrence by blocking tumor blood flow. The aim of the present study was to clarify whether feeding artery ablation before tumor ablation can reduce the risk of critical recurrence after RFA. Methods This study retrospectively analyzed 279 patients with primary, solitary, and hypervascular HCC ≤5 cm in diameter who were treated with RFA alone between April 2001 and August 2013. Critical recurrence was defined as intra‐ or extrahepatic metastasis, dissemination, or seeding that was difficult to treat radically. Results Of the 279 HCC patients, 157 patients were treated with conventional RFA alone, and 122 patients underwent RFA with prior feeding artery ablation. Although no significant differences were seen in the rates of local tumor progression‐free survival, overall recurrence‐free survival, or overall survival between a conventional RFA group and a prior feeding artery ablation group, significant differences were seen in rates of critical recurrence‐free survival and cancer‐specific survival (5‐year, 69 vs 81%, P = 0.01 and 76 vs 88%, P = 0.03, respectively). On multivariate analysis, prior feeding artery ablation, tumor diameter, and alpha‐fetoprotein were independent factors related to critical recurrence. Conclusions Feeding artery ablation before tumor ablation may reduce the risk of critical recurrence., To reduce the risk of critical recurrence such as metastasis, dissemination, and/or seeding, we conducted selective ablation of the feeding artery before tumor ablation. Our retrospective analysis of 279 patients with primary, solitary, hypervascular hepatocellular carcinoma ≤5 cm in diameter who were treated with radiofrequency ablation alone revealed that feeding artery ablation before tumor ablation could reduce the risk of critical recurrence.

BACKGROUND AND AIM Chronic pancreatitis (CP) leads to permanent impairment of exocrine and endocrine functions. The endoscopic ultrasonography (EUS)-based Rosemont classification plays an important role in diagnosing CP. However, it is based on subjective judgment. In contrast, EUS shear wave measurement (EUS-SWM) has been established to be a precise method for evaluating tissue hardness. This study aimed to evaluate the utility of EUS-SWM in diagnosing CP and determining exocrine and endocrine dysfunctions. METHODS We evaluated 40 patients who underwent EUS-SWM between January 2019 and January 2020. They were classified into the normal pancreas and early, probable, and definite CP groups following the Japan Pancreatic Society criteria. EUS-SWM value was compared between the normal pancreas group and the early, probable, and definite CP groups. The relationship between EUS-SWM value and exocrine/endocrine dysfunctions was also assessed. The cut-off value of EUS-SWM for diagnosing CP and exocrine/endocrine dysfunctions was investigated. RESULTS The EUS-SWM value was positively correlated with the Japan Pancreatic Society criteria stages. The probable and definite CP groups had significantly higher EUS-SWM values than the normal group. The areas under the receiver operating characteristic curve for the diagnostic accuracy of EUS-SWM for CP, exocrine dysfunction, and endocrine dysfunction were 0.92, 0.78, and 0.63, respectively. The cut-off values of 1.96, 1.96, and 2.34 for diagnosing CP, exocrine dysfunction, and endocrine dysfunctions had 83%, 90%, and 75% sensitivity, respectively, and 100%, 65%, and 64% specificity, respectively. CONCLUSIONS Endoscopic ultrasonography shear wave measurement provides objective assessment and can thus be an alternative diagnostic tool for diagnosing CP and exocrine/endocrine dysfunctions.

Objective Bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is a frequent adverse event after ESD. We aimed to develop and externally validate a clinically useful prediction model (BEST-J score: Bleeding after ESD Trend from Japan) for bleeding after ESD for EGC. Design This retrospective study enrolled patients who underwent ESD for EGC. Patients in the derivation cohort (n=8291) were recruited from 25 institutions, and patients in the external validation cohort (n=2029) were recruited from eight institutions in other areas. In the derivation cohort, weighted points were assigned to predictors of bleeding determined in the multivariate logistic regression analysis and a prediction model was established. External validation of the model was conducted to analyse discrimination and calibration. Results A prediction model comprised 10 variables (warfarin, direct oral anticoagulant, chronic kidney disease with haemodialysis, P2Y12 receptor antagonist, aspirin, cilostazol, tumour size >30 mm, lower-third in tumour location, presence of multiple tumours and interruption of each kind of antithrombotic agents). The rates of bleeding after ESD at low-risk (0 to 1 points), intermediate-risk (2 points), high-risk (3 to 4 points) and very high-risk (≥5 points) were 2.8%, 6.1%, 11.4% and 29.7%, respectively. In the external validation cohort, the model showed moderately good discrimination, with a c-statistic of 0.70 (95% CI, 0.64 to 0.76), and good calibration (calibration-in-the-large, 0.05; calibration slope, 1.01). Conclusions In this nationwide multicentre study, we derived and externally validated a prediction model for bleeding after ESD. This model may be a good clinical decision-making support tool for ESD in patients with EGC.

Despite the widespread use of endoscopic submucosal dissection (ESD) for early gastric cancer, post-ESD bleeding remains a significant problem. Intragastric pH plays an important role in intragastric bleeding. Because gastric acid secretion contributes to intragastric pH, both the presence or absence of Helicobacter pylori infection and the degree of gastric mucosal atrophy may affect bleeding. The present study aimed to clarify the relationship between post-ESD bleeding and the degree of gastric mucosal atrophy based on H. pylori infection status.We included 8170 patients who underwent ESD for early gastric cancer at 33 hospitals in Japan from November 2013 to October 2016. We analyzed the risk factors contributing to post-ESD bleeding.There were 3935 H. pylori-positive patients and 4235 H. pylori-negative patients. A nonsevere degree of gastric mucosal atrophy was an independent risk factor for post-ESD bleeding in H. pylori-negative patients (odds ratio: 1.51, P = 0.007), but not in H. pylori-positive patients (odds ratio: 0.91, P = 0.600). Further, in H. pylori-negative, but not H. pylori-positive, patients, the rate of post-ESD bleeding increased in a stepwise manner for patients continuing antithrombotic drug use, patients who withdrew antithrombotic drug use, and antithrombotic drug nonusers.Nonsevere gastric mucosal atrophy was a risk factor for post-ESD bleeding in early gastric cancer in H. pylori-negative patients but not in H. pylori-positive patients.

Detective flow imaging endoscopic ultrasonography (DFI-EUS) provides a new method to image and detect fine vessels and low-velocity blood flow without using ultrasound contrast agents. The aim of this study was to evaluate the utility of DFI-EUS for pancreatobiliary lesions and lymph nodes. Between January 2019 and January 2020, 53 patients who underwent DFI-EUS, e-FLOW EUS, and contrast-enhanced EUS were enrolled. The ability of DFI-EUS and e-FLOW EUS to detect vessels was compared with that of contrast-enhanced EUS. This article describes the DFI technique along with our first experience of its use for vascular assessment of pancreatobiliary lesions. Vessels were imaged in 34 pancreatic solid lesions, eight intraductal papillary mucinous neoplasms (IPMNs), seven gall bladder lesions, and four swollen lymph nodes. DFI-EUS (91%) was significantly superior to e-FLOW EUS (53%) with respect to detection of vessels (p < 0.001) and for discrimination of mural nodules from mucous clots in IPMN and gallbladder lesions from sludge (p = 0.046). Thus, DFI-EUS has the potential to become an essential tool for diagnosis and vascular assessment of various diseases.

OBJECTIVES Post-operative bleeding is the most common adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Patients taking antithrombotic agents has increased. We evaluated the influence of antithrombotic agents on delayed bleeding in ESD for EGC. METHODS This was a post hoc analysis of nationwide, multicenter, retrospective cohort study in Japan. Altogether, 11,452 patients who underwent ESD for EGC in 33 institutions between November 2013 and October 2016 were enrolled. The primary outcome was the incidence of delayed bleeding in patients with or without antithrombotic agents. The secondary outcome was the incidence of delayed bleeding in those who took each antithrombotic agent and the cessation status of its use compared with each matched pair of patients. We used propensity matching and inverse probability of treatment weighting (IPTW) analyses. RESULTS There were 1353 matched pairs of patients. The incidence of delayed bleeding was 2.8% and 10.7% in those without and with antithrombotic agents, respectively (odds ratio [OR] 4.15, 95% confidence interval [CI] 2.88-5.99; P

Continuous duodenal levodopa/carbidopa intestinal gel delivery by a gastrostomy infusion system improves control of Parkinson’s disease. The overall complication rates of percutaneous endoscopic gastrojejunostomy were reported to be 41% and 59% for immediate and delayed adverse events, respectively. A 72-year-old woman underwent percutaneous endoscopic gastrojejunostomy using the delivery system noted above. Abdominal pain and vomiting occurred 3 months later. Esophagogastroduodenoscopy showed a longitudinal ulcer extending from the lower gastric body to the ileum end, with small intestinal telescoping. Colonoscopy showed a large bezoar of food residue that was attached around the tip of the tube, reaching the ascending colon, which may have acted as an anchor. Thus, the gastric antrum and small intestine were shortened with telescoping. This complication was resolved by crushing the bezoar with forceps during colonoscopy and can be prevented by consuming a fiber-free diet and periodic exchanges of the tube using esophagogastroduodenoscopy.

A 68-year-old man with epigastric pain was admitted for acute pancreatitis and obstructive jaundice caused by Primary pancreatic malignant lymphoma. Computed tomography showed diffuse enlargement of the whole pancreas and dilation of the main pancreatic duct and bile duct. Endoscopic retrograde cholangiopancreatography was performed to decompress these dilated ducts. After two courses of chemotherapy, follow-up computed tomography incidentally revealed migration of the pancreatic duct stent, which had perforated the contralateral duodenal wall to enter the peritoneal cavity. In the present case, pancreatic duct stent deviation was attributed to tumor shrinkage resulting from chemotherapy. In addition, stent migration into the peritoneal cavity occurred due to repeated mechanical manipulation of the pancreatic duct stent, presumably leading to partial ulceration of the duodenal wall and delayed wound healing during chemotherapy. This case may provide valuable information on the migration of pancreatic duct stents as a rare, stent-related late complication during chemotherapy.

Information on whether there is a relationship between hospital volume and bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is limited. This study aimed to compare the bleeding rates after ESD for EGC according to the hospital volume.Patients who underwent ESD for EGC at 33 institutions in Japan between November 2013 and October 2016 were included in this multicenter retrospective study. Hospital volume was categorized into three groups, based on the average annual number of ESD procedures: low- and medium-volume group (LMVG), high-volume group (HVG), and very high-volume group (VHVG). The bleeding rate after ESD for EGC was compared between the three hospital volume groups after propensity score matching.A total of 10,320 patients, including 2797 patients in the LMVG, 4646 patients in the HVG, and 2877 patients in the VHVG, were identified. Propensity score matching yielded 2002 patients in each hospital volume group, with an improved balance of confounding variables between the three groups. The bleeding rates in the LMVG, HVG, and VHVG were 4.3%, 3.7%, and 4.9%, respectively, and no significant difference was noted between the three groups.The bleeding rate after ESD for EGC did not differ between hospitals in Japan. The finding indicated that ESD for EGC is equally feasible across Japanese hospitals of different volumes regarding bleeding after ESD.

Additional file 1. Protocol of WHICH study ver. 7.

Additional file 2. Statistical analysis plan.

Background and aims Endoscopic resection of nonampullary duodenal adenoma is often challenging, and its technique has not yet been standardized. To overcome the practical difficulty of conventional endoscopic mucosal resection, underwater endoscopic mucosal resection (UEMR) was recently developed; therefore, we investigated the effectiveness and safety of UEMR for nonampullary duodenal adenoma. Methods A multicenter, prospective cohort study was conducted at 21 institutions in Japan. We enrolled patients with no more than 2 nonampullary duodenal adenomas ≤20 mm in size, who were scheduled to undergo UEMR. After UEMR, follow-up endoscopies were scheduled at 2 and 12 months after the procedure, and biopsy specimens were taken from the post-UEMR scars. The primary endpoint was the proportion of patients with histologically proven nonrecurrence at follow-up endoscopy and biopsy. Results A total of 155 patients with 166 lesions underwent UEMR. One patient with a non-neoplastic lesion in the resected specimen and 10 patients with 10 lesions who were lost to follow-up were excluded. Finally, 144 patients with 155 lesions who received all follow-up endoscopies were analyzed for the primary endpoint. The proportion of patients with proven nonrecurrence was 97.2% (n = 140 of 144; 95% confidence interval, 92.8%–99.1%) which exceeded the predefined threshold value (92%). Two cases of delayed bleeding (1.2%) occurred and they were successfully managed by clips. All recurrences were successfully treated by additional endoscopic treatment. Conclusions This multicenter, prospective cohort study demonstrated effectiveness and safety of UEMR for nonampullary duodenal adenomas ≤20 mm in size. (University Hospital Medical Network Clinical Trials Registry, Number: UMIN000030414 ).

Colonoscopy is currently considered the optimal method to detect colorectal neoplasia; however, some adenomas remain undetected. While indigo carmine staining with a dye-spray catheter has demonstrated promising results for reducing the miss rate, we investigated the oral indigo carmine method. The aim of this study was to determine whether oral indigo carmine intake before standard colonoscopy increases the adenoma (and adenocarcinoma) detection rate (ADR) or the mean number of adenomas per patient (MAP).The oral indigo carmine method was performed from April 2018 to July 2020 in two hospitals. Data were collected in a prospective manner and compared to the conventional group whose data were collected retrospectively and consecutively from January 2016 to March 2018. All data were anonymized.Among the 704 patients included, colonoscopies were completely performed in 693 patients (347 in the indigo group). The ADR did not significantly differ between the groups: 42.3% vs. 40.3% (indigo vs. conventional group; odds ratio: 1.13; 95% confidence interval: 0.9-1.33,The routine use of oral indigo carmine does not lead to a higher ADR despite the higher MAP.

OBJECTIVES Detective flow imaging for endoscopic ultrasonography (DFI?EUS) is a new imaging modality developed for detecting fine vessels without using ultrasound contrast agents. This study aimed to evaluate its utility by comparing it with a type of directional power Doppler (eFLOW) for subepithelial lesions (SELs). METHODS Between January 2019 and January 2020, 28 patients with SELs undergoing DFI?EUS and eFLOW?EUS were enrolled. DFI?EUS and eFLOW?EUS assessing the vascularity in SELs were compared in terms of the rates of identification of intratumoral vessels. We also investigated how large vessels were depicted in both modalities based on surgical specimens as well as the detection rates of intratumoral vessels in gastrointestinal stromal tumors (GISTs) and non?GISTs using either DFI?EUS or eFLOW?EUS. RESULTS Among 28 patients, 23 with pathological confirmation by EUS?guided fine?needle aspiration biopsy (EUS?FNAB) specimens were included. Of those 23 patients, the 10 who underwent surgical resection were selected for analysis. The rate of detection of intratumoral vessels in SELs was significantly higher on DFI?EUS (80%) than on eFLOW?EUS (30%) (P\xA0=\xA00.03). Comparison with surgical specimens revealed that detection rate for vessels with maximum size of less 1000\xA0μm was higher in DFI?EUS (66%) than that in eFLOW?EUS (0%). GIST patients had significantly higher positive rates (90%) of intratumoral vessels than non?GIST patients (31%) on DFI in 23 cases including EUS?FNAB specimens (P\xA0=\xA00.045). CONCLUSIONS Detective flow imaging?EUS is more sensitive for depicting intratumoral vessels than eFLOW?EUS. Evaluation of intratumoral vessels on DFI?EUS is useful for identifying GISTs without contrast agents.

Background 18F-fluorodeoxyglucose (18F-FDG) uptake in hepatocellular carcinoma (HCC) is significantly associated with early recurrence and survival after curative surgical resection. However, there are no reports regarding the relationship between 18F-FDG uptake and outcomes after radiofrequency ablation (RFA). A prospective cohort study was conducted to evaluate the prognostic value of 18F-FDG positron emission tomography (PET) in HCC patients after RFA. Methods A total of 121 consecutive patients with primary HCC (≤3 tumors, of diameter ≤ 3 cm) without vascular invasion on imaging were examined by 18F-FDG-PET computed tomography prior to RFA. An HCC with a component of 18F-FDG uptake visibly stronger than that of surrounding liver was defined as 18F-FDG-PET positive. Results The median follow-up period was 1267 days. There were 110 18F-FDG-PET negative and 11 positive tumors. The cumulative 1-year recurrence rates in the 18F-FDG negative and positive groups were 30 and 64% (P = 0.017), respectively, and cumulative 1-year metastatic recurrence rates were 6 and 36% (P < 0.001), respectively. The cumulative 5-year survival rates were 88 and 22% (P < 0.001), respectively. Multivariate analysis revealed 18F-FDG-PET positivity and tumor size as independent factors related to metastatic recurrence and survival after RFA. Conclusions 18F-FDG-PET positivity was significantly associated with outcomes after RFA. RFA should not be readily selected as the first-line treatment for small HCC that includes a component of visually strong 18F-FDG uptake.

Characteristics of the chronotypes of patients with gastrointestinal disease are unknown. We evaluated chronotypes of patients with upper gastrointestinal diseases with the Munich ChronoType Questionnaire (MCTQ). A total of 2027 subjects from 29 institutions in Japan who had undergone esophagogastroduodenoscopy were asked to answer the MCTQ. The subjects' chronotypes were divided into three groups (early, intermediate, and late chronotype) using the sleep-corrected mid-point of sleep on free days (MSF

BACKGROUND AND AIM Although duodenal cancer is rare, no epidemiological research on this disease has been conducted in Asian countries. We aimed to elucidate the incidence and clinical features of duodenal cancer in Japan using a large-scale national database. METHODS Data of patients with primary duodenal cancer diagnosed from January 1, 2016, to December 31, 2016, were extracted from the Japanese national cancer registry. Excluding malignant neoplasm of the Vater's ampulla, we calculated the incidence among the population as a crude number of patients with duodenal cancer divided by the total Japanese population in 2016. We performed multivariate analyses using logistic regression models to identify risk factors for advanced cancer, defined as metastatic cancer or local invasion to adjacent organs. RESULTS Data on 3005 patients were included. The incidence of duodenal cancer was 23.7 per 1 000 000 person-years. In total, 56.4% of cases were detected at the localized stage. In the localized cancer group, endoscopic resection was more frequently performed (48.0%), whereas in the advanced cancer group, surgery and chemotherapy were the major treatment options (39.3% and 41.5%, respectively). Multivariate analyses identified age ≥80 years (odds ratio [OR], 1.489; 95% confidence interval [CI], 1.113-1.992; P = 0.007), incidental detection (OR, 2.325; CI, 1.623-3.331; P

Background Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. Methods We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. Discussion The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. Trial registration UMIN-CTR UMIN000023720. Registered on 22 August 2016

Delayed bleeding after gastric endoscopic submucosal dissection (ESD) in patients receiving anticoagulants remains an unpreventable adverse event. Although direct-acting oral anticoagulants (DOACs) have superior efficacy in preventing thromboembolism, their effects on the occurrence of delayed bleeding remain unclear. This study aimed to elucidate the clinical effect of DOACs on delayed bleeding after gastric ESD. We retrospectively examined 728 patients who received anticoagulants and were treated for gastric neoplasms with ESD in 25 institutions across Japan. Overall, 261 patients received DOACs, including dabigatran (92), rivaroxaban (103), apixaban (45) and edoxaban (21), whereas 467 patients were treated with warfarin. Delayed bleeding occurred in 14% of patients taking DOACs, which was not considerably different in patients receiving warfarin (18%). Delayed bleeding rate was significantly lower in patients receiving dabigatran than in those receiving warfarin and lower than that observed for other DOACs. Multivariate analysis showed that age ≥ 65, receiving multiple antithrombotic agents, resection of multiple lesions and lesion size ≥ 30 mm were independent risk factors, and that discontinuation of anticoagulants was associated with a decreased risk of bleeding. In multivariate analysis among patients taking DOACs, dabigatran therapy was associated with a significantly lower risk of delayed bleeding. The effects of DOACs on delayed bleeding varied between agents, but dabigatran therapy was associated with the lowest risk of delayed bleeding. Switching oral anticoagulants to dabigatran during the perioperative period could be a reasonable option to reduce the risk of delayed bleeding after gastric ESD.

Background and Aims Although various procedures have been used to prevent serious adverse events after endoscopic resection of the duodenum, their effectiveness has not been determined. In this study, we conducted a systematic review and meta-analysis to determine whether endoscopic preventive procedures reduce delayed adverse events. Methods Studies on endoscopic treatment for superficial nonampullary duodenal tumors were selected. We compared the following 2 groups: the closure group, which underwent mucosal sutures and coverage of mucosal defects after resection, and the unclosed group, which did not. The primary outcome was the rate of delayed adverse events, including perforation and bleeding. The pooled risk ratios (RRs) of all outcomes investigated, the 95% confidence intervals (CIs), and P values were calculated. Results A total of 438 patients from 4 studies were included in the meta-analysis. The pooled overall adverse event rates in the closure group and unclosed group were 3.6% and 21.1%, respectively. This rate was significantly lower in the closure group (RR, 0.19; 95% CI, 0.10-0.38; P Conclusions Preventive procedures significantly reduced the risk of delayed adverse events by more than 80%. After endoscopic resection of the duodenum, the implementation of preventive procedures, including mucosal sutures and coverage of mucosal defects, to delay adverse events is strongly recommended.

We examined whether synbiotics enhance improvement by probiotics.Probiotics, which are beneficial microbacteria, are a nutritional intervention for treatment of functional constipation or its tendency. Prebiotics, meanwhile, can promote the proliferation of probiotics in the gastrointestinal tract and enhance their beneficial effects. Synbiotics, a combination of probiotics and prebiotics, may be superior to probiotics in the treatment of defecation-related symptoms, but this requires elucidation.This randomized, double-blind, placebo-controlled study enrolled 69 healthy adults with constipation tendency. Participants were allocated to either control, probiotics, or synbiotics groups and they recorded details of their defecations and their condition. The first 2 weeks were the observation period and the latter 2 weeks were the intervention period, in which participants took test foods. Probiotic foods included Bifidobacterium longum NT strain (1010 CFU/day), synbiotic foods included the NT strain (1010 CFU/day) and galactooligosaccharide (1 g/day). Placebo foods contained the vehicle only. Participants answered questionnaires (Patient Assessment on Constipation Symptoms [PAC-SYM], and one on dietary history) on the last day of each period.Nine participants withdrew consent, and 2 of the remaining 60 had missing data. Age, body mass index, and sex were not significantly different between the 3 groups. Frequency of bowel movements in the fourth week, the primary endpoint, was not increased in the probiotics or synbiotics groups compared with the control group, and the frequency of bowel movements and days with defecation were not changed by probiotics or synbiotics during the intervention period. Probiotics and synbiotics did not improve stool conditions, although incomplete defecation was improved by probiotics but not by synbiotics compared with placebo. PAC-SYM indicated that stool condition and total scores were improved by probiotics but not by synbiotics during the intervention compared with placebo.The probiotic strain Bifidobacterium longum NT can improve constipation symptoms, especially stool condition, but it does not increase bowel movement frequency in healthy adults with constipation tendency. Synbiotics treatment seemed to diminish this improvement of constipation induced by probiotics. This study indicates the possibility of attenuation of beneficial effects from probiotics by the use of synbiotics, contrary to synbiotics theory.

ObjectivesWe previously demonstrated that lansoprazole provided hepatoprotection in a drug-induced hepatitis animal model partially through the Nrf2/HO-1 pathway. Here, we examined whether lansoprazole could also provide hepatoprotection in a rat model of non-alcoholic steatohepatitis (NASH).MethodsSix-week-old rats were fed a normal chow or a choline-deficient amino acid-defined (CDAA) diet to establish a rat model of NASH. The groups fed a CDAA diet for 5 weeks were subcutaneously administered either a vehicle or a lansoprazole suspension for 4 weeks beginning the second week of the experiment.Key findingsBridging fibrosis was observed in the livers of almost all the NASH model rats (six of seven), but it was not always observed in NASH model rats (one of seven) continuously administered lansoprazole. The serum aspartate aminotransferase level elevated by the CDAA diet was significantly decreased following lansoprazole administration. Lansoprazole also increased the expression of Nrf2, but not HO-1, in the liver of NASH model rats. Lansoprazole decreased the level of activated TGF-β protein. Furthermore, interleukin-6 gene and protein expression were decreased.ConclusionsLansoprazole inhibits hepatic fibrogenesis, at least during the early stages, in CDAA diet-induced NASH model rats. The mechanisms might be associated with cytokine suppression but not the inhibition of reactive oxygen species.

Background and study aims Re-commencement of bleeding (rebleeding) of colonic diverticula after endoscopic hemostasis is a clinical problem. This study aimed to examine whether endoscopic visibility of colonic diverticular bleeding affects the risk of rebleeding after endoscopic hemostasis. Patients and methods We performed a retrospective review of endoscopic images and medical charts of patients with colonic diverticular bleeding who underwent endoscopic hemostasis. Endoscopic visibility was classified into two types according to visibility of the source of bleeding; source invisibility due to bleeding or attached hematin (type 1), or endoscopically visible responsive vessels (type 2). Rebleeding rates within one year after initial hemostasis were examined. Results Of 93 patients with successful endoscopic hemostasis, 38 (41 %) showed type 1 visibility, while the remaining presented type 2. All patients received hemostasis with clipping, rebleeding developed in 20 patients (22 %). Type 1 visibility was more likely to be observed in patients with rebleeding (65 % vs. 34 %, P = 0.013). Multivariate analysis revealed that after endoscopic hemostasis, type 1 visibility (invisible source) was the only independent risk factor for colonic diverticular rebleeding (odds ratio, 3.05; 95 % confidence interval, 1.03 – 9.59, P = 0.044). Kaplan-Meier curve showed the cumulative incidence of rebleeding was significantly higher in patients with type 1 visibility than those with type 2 visibility (P = 0.0033, log-rank test) Conclusion Hemostasis by clipping for colonic diverticular bleeding without definite observation of the source of bleeding may not be sufficiently effective. Other hemostatic methods, including band ligation, should be considered when the source of bleeding is unclear.