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Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

IL‐2 is a pleiotropic cytokine that regulates immune cell homeostasis. Its immunomodulatory function has been used clinically as an active immunotherapy agent for metastatic cancers. However, severe adverse effects, including the vascular leak syndrome and the preferential stimulation of anti‐immunogenic Treg rather than effector T cells, have been obstacles. We newly designed a mutein IL‐2, Mutakine‐6 (MK‐6), with reduced IL‐2Rα–binding capability. MK‐6 induced comparable cell growth potential toward IL‐2Rβγ–positive T cells but was far less efficient in in vitro Treg proliferation and STAT5 activation. Unlike IL‐2, in vivo administration of MK‐6 produced minimal adverse effects. Using CT26 and B16F10‐syngeneic tumor models, we found MK‐6 was highly efficacious on tumor regression. Serum albumin conjugation to MK‐6 prolonged in vivo half‐life and accumulated in CT26 tumors, showing enhanced antitumor effect. Tumor‐infiltrating leukocytes analysis revealed that albumin‐fused MK‐6 increased the ratio of effector CD8+ T cells to CD4+ Treg cells. These results demonstrated that MK‐6 is an efficient immunomodulator potentially used for improved immunotherapy with decreased adverse effects and attenuated Treg stimulation., Albumin‐conjugated IL‐2 mutein, MK‐6, exerts a potent antitumor effect in the CT26 tumor model.

Background Currently, no classification system using magnification endoscopy for the diagnosis of superficial Barrett’s esophagus (BE)-related neoplasia has been widely accepted. This nationwide multicenter study aimed to validate the diagnostic accuracy and reproducibility of the magnification endoscopy classification system, including the diagnostic flowchart developed by the Japan Esophageal Society—Barrett’s esophagus working group (JES-BE) for superficial Barrett’s esophagus-related neoplasms. Methods The JES-BE acquired high-definition magnification narrow-band imaging (HM-NBI) images of non-dysplastic and dysplastic BE from 10 domestic institutions. A total of 186 high-quality HM-NBI images were selected. Thirty images were used for the training phase and 156 for the validation (test) phase. We invited five non-experts and five expert reviewers. In the training phase, the reviewers discussed how to correctly predict the histology based on the JES-BE criteria. In the validation phase, they evaluated whether the criteria accurately predicted the histology results according to the diagnostic flowchart. The validation phase was performed immediately after the training phase and at 6 weeks thereafter. Results The sensitivity and specificity for all reviewers were 87% and 97%, respectively. Overall accuracy, positive predictive value, and negative predictive value were 91%, 98%, and 83%, respectively. The overall strength of inter-observer and intra-observer agreements for dysplastic histology prediction was κ = 0.77 and κ = 0.83, respectively. No significant difference in diagnostic accuracy and reproducibility between experts and non-experts was found. Conclusion The JES-BE classification system, including the diagnostic flowchart for predicting dysplastic BE, is acceptable and reliable, regardless of the clinician’s experience level.

INTRODUCTION: During the coronavirus disease 2019 pandemic, whether endoscopy generates aerosols needs to be determined. METHODS: In patients undergoing upper gastrointestinal endoscopy with an enclosure covering their heads, 0.3-10-µm aerosols were measured for 60 seconds before, during, and after endoscopy by an optical counter. Whether aerosols increased in the situation with and without endoscopy was examined. RESULTS: The analysis included 103 consecutive patients undergoing endoscopy and 90 control patients. Aerosols increased significantly during endoscopy compared with the control group. Body mass index and burping were significant factors related to increased aerosols during endoscopy. DISCUSSION: Upper gastrointestinal endoscopy was an aerosol-generating procedure.

Background/Aims: Endoscopic transpapillary gallbladder drainage (ETGBD) is useful for the treatment of acute cholecystitis; however, the technique is difficult to perform. When intraductal ultrasonography (IDUS) is combined with ETGBD, the orifice of the cystic duct in the common bile duct may be more easily detected in the cannulation procedure. The aim of this study was to evaluate the efficacy of ETGBD with IDUS compared with that of ETGBD alone. Methods: A total of 100 consecutive patients with acute cholecystitis requiring ETGBD were retrospectively recruited. The first 50 consecutive patients were treated using ETGBD without IDUS, and the next 50 patients were treated using ETGBD with IDUS. Through propensity score matching analysis, we compared the clinical outcomes between the groups. The primary outcome was the technical success rate. Results: The technical success rate of ETGBD with IDUS was significantly higher than that of ETGBD without IDUS (92.0% vs. 76.0%, p=0.044). There was no significant difference in procedure length between the two groups (74.0 min vs. 66.7 min, p=0.310). The complication rate of ETGBD with IDUS was significantly higher than that of ETGBD without IDUS (6.0% vs. 0%, p

The bleeding complication risk of surgery or percutaneous transhepatic gallbladder drainage (PTGBD) may increase in patients with acute cholecystitis receiving antithrombotic therapy (ATT). Endoscopic gallbladder drainage (EGBD) may be recommended for such patients. English articles published between 1991 and 2018 in peer-reviewed journals that discuss cholecystectomy, PTGBD, and EGBD in patients with ATT or coagulopathy were reviewed to assess the safety of the procedures, especially in terms of the bleeding complication. There were 8 studies on cholecystectomy, 3 on PTGBD, and 1 on endoscopic transpapillary gallbladder drainage (ETGBD) in patients receiving ATT. With respect to EGBD, 28 studies on ETGBD (including 1 study already mentioned above) and 26 studies on endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) were also analyzed. The overall bleeding complication rate in patients with ATT who underwent cholecystectomy was significantly higher than that in patients without ATT (6.5% [23/354] vs. 1.2% [26/2,224], p

Although pancreatic cancer (PC) has an extremely poor prognosis, the 5-year survival rate of patients with pancreatic high-grade precancerous lesion without invasive carcinoma (PHP) is favorable. PHP diagnosis and identification of patients requiring intervention are needed. We aimed to validate a modified PC detection scoring system regarding its detection ability for PHP and PC in the general population.We modified an existing PC detection scoring system that incorporates low-grade risk (LGR) factors (family history, presence of diabetes mellitus [DM] or worsening DM, heavy drinking, smoking, stomach symptoms, weight loss, and pancreatic enzyme) and high-grade risk (HGR) factors (new-onset DM, familial PC, jaundice, tumor biomarkers, chronic pancreatitis, intraductal papillary mucinous neoplasm, cysts, hereditary PC syndrome, and hereditary pancreatitis). Each factor was scored as one point; LGR score ≥3 points and/or HGR score ≥1 point (positive scores) were indicative of PC. The newly modified scoring system incorporated main pancreatic duct dilation as an HGR factor. The PHP diagnosis rate using this scoring system combined with EUS was prospectively analyzed.Among 544 patients with positive scores, 10 had PHP. The diagnosis rates were 1.8% for PHP and 4.2% for invasive PC. Although the number of LGR and HGR factors tended to increase with PC progression, none of the individual factors were significantly different between patients with PHP and those without lesions.The newly modified scoring system evaluating multiple factors associated with PC could potentially identify patients with higher risk of PHP or PC.

We recently reported that methylation of PCDH17 gene is found in 30% of children with B-cell precursor acute lymphoblastic leukemia (ALL), and is significantly correlated to event-free or overall survival. We here evaluated PCDH17 mRNA expression in pediatric acute myeloid leukemia (AML) and ALL. PCDH17 mRNA expression levels in children with ALL/AML were lower than those in healthy counterparts. We next elucidated the mechanism underlying down-regulation of PCDH17 mRNA, using myeloid and lymphoid leukemic cell lines. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) resulted in restoration of PCDH17 mRNA expression and growth inhibition in K562, HL60, REH, and RCH-ACV cell lines. Upregulation of PCDH17 mRNA expression resulted from histone H3 acetylation. Knockdown of the PCDH17 gene, caused by transduction of PCDH17-targeted shRNA, significantly enhanced the proliferation of KU812 cells. Meanwhile, overexpression of PCDH17 via retroviral-particle transfection substantially inhibited the growth of Kasumi1 cells. The fold-increase in PCDH17 mRNA expression mediated by 5-azacytidine, an inhibitor of DNA methyltransferase, was fundamentally lower than that produced by TSA. In conclusion, our results suggest that PCDH17 gene functions as a common tumor suppressor gene in leukemic cells, and that histone deacetylase inhibitors re-express PCDH17 mRNA to a greater extent than demethylation reagents.

Background and Aims Colorectal endoscopic submucosal dissection (ESD) is a time-consuming procedure because of the technical difficulty. The newly developed saline-pocket ESD (SP-ESD) provides a clearer view and better traction of the submucosal layer compared with the standard ESD with gas insufflation (S-ESD). This study aimed to prospectively compare the efficacy and safety between S-ESD and SP-ESD in patients with superficial colorectal neoplasms (SCNs). Methods From April 2017 to November 2018, 95 patients with SCNs ≥20 mm in diameter were prospectively and randomly enrolled. Four patients were excluded because of an incomplete ESD procedure. Patients were finally allocated to 2 groups, S-ESD with 45 patients and SP-ESD with 46 patients. The primary outcome was dissection speed. Secondary outcomes were ESD procedure time, en bloc and complete resection rates, perforation rate, and adverse effects. Results Median dissection speed was significantly faster in the SP-ESD than the S-ESD group (20.1 mm2/min [range, 17.3-28.1] vs 16.3 mm2/min [range, 11.4-19.8]; P Conclusions SP-ESD improved dissection speed and procedure time compared with S-ESD. SP-ESD may be an alternative method for resection of SCNs. (Clinical trial registration number: UMIN 000026317.)

Given that risk factors for Barrett’s carcinogenesis are predictive, appropriate management and surveillance of Barrett’s esophagus (BE) may be provided. The presence of colorectal neoplasms (CRNs) is a possible predictor of the development of BE and the progression to esophageal adenocarcinoma (EAC). We evaluated the relationship between BE or EAC and colonic diseases, including neoplasms and diverticulosis. Patients (N = 5606) who underwent both colonoscopy and esophagogastroduodenoscopy between January 2016 and December 2017 at three institutions were enrolled. The relationships between the presence of colonic diseases and BE or EAC and other clinical or endoscopic predictors of the presence of BE were investigated retrospectively. The prevalence of BE ≥ 1 cm and ≥ 3 cm in length was 13.0% and 0.52%, respectively. BE was closely related with the presence of colorectal adenoma (48.4% vs. 37.2% in non-BE; P

Background Endoscopic submucosal dissection (ESD) for gastric neoplasms during continuous low-dose aspirin (LDA) administration is generally acceptable according to recent guidelines. This retrospective study aimed to investigate the effect of continuous LDA on the postoperative bleeding after gastric ESD in patients receiving dual antiplatelet therapy (DAPT). Aim To investigate the feasibility of gastric ESD with continuous LDA in patients with DAPT. Methods A total of 597 patients with gastric neoplasms treated with ESD between January 2010 and June 2017 were enrolled. The patients were categorized according to type of antiplatelet therapy (APT). Results The postoperative bleeding rate was 6.9% (41/597) in all patients. Patients were divided into the following two groups: no APT (n = 443) and APT (n = 154). APT included single-LDA (n = 95) and DAPT (LDA plus clopidogrel, n = 59) subgroups. In the single-LDA and DAPT subgroups, 56 and 39 patients were received continuous LDA, respectively. The bleeding rate with continuous single-LDA (10.7%) was similar to that with discontinuous single-LDA (10.3%) (P > 0.99). Although the bleeding rate with continuous LDA in patients receiving DAPT (23.1%) was higher than that with discontinuous LDA in patients receiving DAPT (5.0%), no significant difference was observed (P = 0.141). Conclusion The bleeding rate with continuous LDA in patients receiving DAPT was not statistically different from that with discontinuous LDA in patients receiving DAPT. Therefore, continuous LDA administration may be acceptable for ESD in patients receiving DAPT, although patients should be carefully monitored for possible bleeding.

Background/Aims: Residual common bile duct (CBD) stones occasionally become symptomatic after stone removal with endoscopic retrograde cholangiopancreatography (ERCP) upon removal of the endoscopic biliary stent (EBS). An accurate evaluation of residual stones before stent removal is necessary. This study evaluated a new two-step check method using endoscopic ultrasound (EUS) for the detection of residual stones after ERCP stone removal. Methods: Fifty-six patients who underwent CBD stone removal and EBS placement were prospectively enrolled. Residual stones were evaluated by the check method. EBS was removed at the time of the check method or at a later time of residual stone removal. The primary outcome was to evaluate the efficacy of this check method. Results: Residual CBD stone/sludge was detected in 20 of 56 patients (35.7%; stones: 28.6%, sludge: 7.1%) by the check method and removed by the ERCP procedure at a later time. After stent and final stone removal, patients were followed for an average of 211 days; cholangitis recurred in only 1.8% of patients. There were no adverse events associated with the check method. Temporary EBS prevented the recurrence of cholangitis by residual stone and caused no adverse events in the pancreatobiliary tract until the two-step check method (median, 113 days; range, 17–232 days). Conclusion: The new check method may be ideal and feasible for EBS removal because recurrences are very rare when a clear CBD has been verified, and an additional ERCP procedure is also possibly avoided.

Simple Summary Pancreatic ductal adenocarcinoma (PDAC) is typically associated with an extremely poor prognosis; however, small PDAC tumors show good prognosis. High-grade pancreatic intra-epithelial neoplasia (PanIN), which precedes invasive PDAC, is a primary target for improving the prognosis of PDAC. However, detection of high-grade PanIN without invasive carcinoma by existing imaging modalities is difficult because the lesions are only microscopically detectable. Recent studies have reported the characteristics of imaging findings associated with localized high-grade PanIN and the usefulness of serial pancreatic-juice aspiration cytologic examination as a method to confirm the pre-operative histopathology. In this review, we aimed to clarify recent clinical findings regarding detection of localized high-grade PanIN, which may contribute to improvement of the prognosis of patients with PDAC. Abstract Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions, such as pancreatic intra-epithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN). The prognosis of high-grade precancerous lesions, including high-grade PanIN and high-grade IPMN, without invasive carcinoma is good, despite the overall poor prognosis of PDAC. High-grade PanIN, as a lesion preceding invasive PDAC, is therefore a primary target for intervention. However, detection of localized high-grade PanIN is difficult when using standard radiological approaches. Therefore, most studies of high-grade PanIN have been conducted using specimens that harbor invasive PDAC. Recently, imaging characteristics of high-grade PanIN have been revealed. Obstruction of the pancreatic duct due to high-grade PanIN may induce a loss of acinar cells replaced by fibrosis and lobular parenchymal atrophy. These changes and additional inflammation around the branch pancreatic ducts (BPDs) result in main pancreatic duct (MPD) stenosis, dilation, retention cysts (BPD dilation), focal pancreatic parenchymal atrophy, and/or hypoechoic changes around the MPD. These indirect imaging findings have become important clues for localized, high-grade PanIN detection. To obtain pre-operative histopathological confirmation of suspected cases, serial pancreatic-juice aspiration cytologic examination is effective. In this review, we outline current knowledge on imaging characteristics of high-grade PanIN.

Given that endoscopic findings can be used to predict the potential of neoplastic progression in Barrett’s esophagus (BE) cases, the detection rate of dysplastic Barrett’s lesions may become higher even in laborious endoscopic surveillance because a special attention is consequently paid. However, endoscopic findings for effective detection of the risk of neoplastic progression to esophageal adenocarcinoma (EAC) have not been confirmed, though some typical appearances are suggestive. In the present review, endoscopic findings that can be used predict malignant potential to EAC in BE cases are discussed. Conventional results obtained with white light endoscopy, such as length of BE, presence of esophagitis, ulceration, hiatal hernia, and nodularity, are used as indicators of a higher risk of neoplastic progression. However, there are controversies in some of those findings. Absence of palisade vessels may be also a new candidate predictor, as that reveals degree of intense inflammation and of cyclooxygenase-2 protein expression with accelerated cellular proliferation. Furthermore, an open type of mucosal pattern and enriched stromal blood vessels, which can be observed by image-enhanced endoscopy, including narrow band imaging, have been confirmed as factors useful for prediction of neoplastic progression of BE because they indicate more frequent cyclooxygenase-2 protein expression along with accelerated cellular proliferation. Should the malignant potential of BE be shown predictable by these endoscopic findings, that would simplify methods used for an effective surveillance, because patients requiring careful monitoring would be more easily identified. Development in the near future of a comprehensive scoring system for BE based on clinical factors, biomarkers and endoscopic predictors is required.

An asymptomatic 38-year-old man was endoscopically followed because of a gastric submucosal tumor (SMT) showing a positive cushion sign in the greater curvature of the gastric antrum. The mucosal surface of SMT dramatically changed from normal to red color, whereas with a normal micro-surface pattern (figures 1 and 2). The lesion was harder with poorer mobility. The biopsy samples revealed hyperplastic and hyperemic changes without malignant findings. He had no subjective symptoms or abnormal blood test. Contrast-enhanced computed tomography revealed the SMT with a cystic degenerative lesion …

BACKGROUND: Allergic transfusion reactions (ATR) and febrile non-haemolytic transfusion reactions (FNHTR) are common transfusion-related adverse reactions; however, their pathogenesis remains unclear and it is difficult to predict their occurrence. Single-nucleotide polymorphisms (SNP) are related to the onset of various diseases and therapy-related adverse events; therefore, identification of SNP related to transfusion-related adverse reactions may help to elucidate the underlying mechanism and predict the onset of these reactions. MATERIALS AND METHODS: We retrospectively analysed the association between the onset of ATR or FNHTR and 22 allergic sensitisation-related SNP in 219 children (aged ≤20 years) who had haematological and oncological diseases and who had received transfusions of platelets and/or red blood cell concentrates. RESULTS: Among the 219 children, 105 had developed an ATR and/or FNHTR at least once. The patients who developed ATR frequently had a risk allele in rs6473223, while the patients who developed FNHTR frequently had a risk allele in rs10893845. Furthermore, patients who developed ATR accompanied by febrile symptoms also frequently had a risk allele in rs10893845, similar to patients who developed FNHTR. DISCUSSION: The results suggested that allergic sensitisation is associated with the onset of ATR and/or FNHTR in some patients. Although further prospective evaluation is necessary, analysis of these SNP might help to provide safer transfusion therapy by predicting patients at higher risk of transfusion-related adverse reactions and further clarifying the pathogenic mechanism underlying such reactions.

Postpolypectomy bleeding (PPB) is the most common adverse event after colorectal polypectomy. Use of anticoagulants is an important risk factor for PPB. This study aimed to evaluate PPB in patients receiving treatment with warfarin and direct oral anticoagulants (DOACs).Between August 2017 and July 2019, 5449 patients with 12,601 polyps who underwent endoscopic snare resection of colorectal polyps were enrolled. Endoscopic snare resection was performed in patients receiving continuous warfarin (C-warfarin) and in patients who experienced 1 day cessation of (O-) of DOACs in accordance with the Japanese Gastroenterological Endoscopy Society guidelines.The PPB rate in the group receiving anticoagulants was statistically higher than that in the group without anticoagulants (8.5% [33/387] vs 1.2% [63/5,062], respectively; P .001). By multivariate logistic regression analysis, male gender (odds ratio [OR], 2.17; P = .007), warfarin (OR, 4.64; P .001), DOACs (OR, 6.59; P .001), and multipolyp removal (OR, 1.77; P = .007) were significant risk factors for PPB. PPB was observed in 9 and 21 patients in the C-warfarin and O-DOACs groups, respectively: C-warfarin (8.0% [9/113]), O-dabigatran (6.1% [2/33]), O-rivaroxaban (14.8% [9/61]), O-apixaban (9.8% [9/92]), and O-edoxaban (1.8% [1/56]). The PPB rate with the O-edoxaban group was significantly lower than that with the O-rivaroxaban group (P .05).Use of anticoagulant therapy was an independent risk factor for PPB. The rates of PPB in patients receiving C-warfarin and O-DOACs were also higher than those in patients not receiving anticoagulants. Edoxaban may be safe through short-term withdrawal in patients undergoing endoscopic snare resection of colorectal polyps.

Background and aim Colonic diverticulosis (CD) has been reported to be associated with presence of colon neoplasms (CNs) in Western patients, since most of the associated risk factors are common between them. However, such correlation has not been fully investigated in Asian patients. In this study, the association of CNs with CD was evaluated in a multicenter investigation. Methods We enrolled 5633 patients who underwent both colonoscopy and esophagogastroduodenoscopy due to annual follow-up, screening for positive occult blood testing and abdominal symptoms between January 2016 and December 2017 at three institutions. The relationship between the presence of CNs and CD was investigated, and predictors for presence of CNs were determined by multivariate logistic analysis. Results The enrolled patients consisted of 1799 (31.9%) with CD (average age 70.0 years, male 64.0%) and 3834 without CD (66.0 years, male 52.9%), with the prevalence of CNs in those groups 46.6% and 44.2%, respectively (P = 0.090). Predictors for early colon cancer were shown to be age (OR 1.02, 95% CI 1.01-1.04, P = 0.010), laxatives use (OR 1.76, 95% CI 1.17-2.64, P = 0.007), gastric neoplasms (OR 2.16, 95% CI 1.23-3.81, P = 0.008), and CD (OR 1.64, 95% CI 1.16-2.31, P = 0.005). Early colon cancer in the distal colon was most frequently detected in patients with right-sided CD (RR 2.50, P = 0.001). Conclusion In Japanese patients, early colon cancer was more frequently found in those with as compared to those without CD. The presence of CD may be an important indicator for an index colonoscopy examination to detect colon cancer. (Clinical-trial-registry: UMIN000038985).

Background Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) as a treatment for patients with acute cholecystitis has been shown to obtain high technical and clinical success rates and a low recurrence rate. However, the safety of EUS-GBD for patients receiving antithrombotic therapy (ATT) has not been proven. The aim was to evaluate the safety and efficacy of EUS-GBD in patients receiving ATT. Methods Twelve patients with acute cholecystitis associated with gallstones who were receiving antithrombotic therapy and underwent EUS-GBD were enrolled in this retrospective study. Patients with grade II or III cholecystitis who had failed endoscopic transpapillary GBD (ETGBD) or developed recurrence after multiple ETGBD procedures underwent urgent drainage by EUS-GBD. The primary outcome was the rate of bleeding complications after the procedure and the secondary outcomes were the technical and clinical success rates, complications, and recurrence. Results Eleven (91.6%) patients underwent EUS-GBD with continuation of ATT (at least 1 agent). Five of 12 patients (41.7%) were receiving more than 1 agent for ATT. The rate of bleeding complications was 0% and the technical success rate was 100%, even though some patients had high-grade (severe) cholecystitis and/or several underlying diseases. Early complications were found in 2 (16.7%) patients. The clinical success rate was 91.7% (11/12). There were no recurrences of cholecystitis during the follow-up period (mean 261 [range 5-650] days). Conclusions EUS-GBD yielded high technical and clinical success rates and a low recurrence rate. No patients receiving ATT developed bleeding complications. EUS-GBD might be a good option for patients on ATT.

Aim and methods The Japan Esophageal Society created a working committee group consisting of 11 expert endoscopists and 2 pathologists with expertise in Barrett’s esophagus (BE) and esophageal adenocarcinoma. The group developed a consensus-based classification for the diagnosis of superficial BE-related neoplasms using magnifying endoscopy. Results The classification has three characteristics: simplified, an easily understood classification by incorporating the diagnostic criteria for the early gastric cancer, including the white zone and demarcation line, and the presence of a modified flat pattern corresponding to non-dysplastic histology by adding novel diagnostic criteria. Magnifying endoscopic findings are composed of mucosal and vascular patterns, and are initially classified as “visible” or “invisible.” Morphologic features were evaluated for “visible” patterns, and were subsequently rated as “regular” or “irregular,” and the histology, non-dysplastic or dysplastic, was predicted. Conclusion We introduce the process and outline of the magnifying endoscopic classification.

Background and study aims A 72-year-old man with complete situs inversus presented with early gastric cancer on the lesser curvature wall of the antrum of the stomach. Endoscopic submucosal dissection (ESD) was selected as a treatment. When the patient was positioned in the left decubitus position, the lesion was hidden by blood and gastric fluid because it was located on the gravitational side. Therefore, we decided to perform ESD with the patient in the right lateral decubitus position and use an inverted overtube, which provided a good endoscopic view without the need to rearrange the endoscopist, assistants, or endoscopic system. ESD was safe and feasible using the inverted overtube.

Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients., Article, PEDIATRIC RHEUMATOLOGY.17:34(2019)

Background and study aims: We present a case of invasive micropapillary carcinoma (IMPC) of the colon treated by endoscopic resection following magnifying endoscopy. A 47-year-old woman visited our hospital for follow-up of a positive fecal occult blood test. Colonoscopy revealed a semi-pedunculated reddish polyp, the surface of which showed gentle irregularity, and mild tension in the sigmoid colon. Magnifying colonoscopy with narrow band imaging revealed an irregular surface pattern with heterogeneity in vascular diameter and distribution. Magnifying endoscopic findings using crystal violet staining showed an irregular pit pattern with an expansion of stromal areas. Endoscopic resection of the sigmoid colon tumor was performed, and the histology of the resected specimen primarily revealed a micropapillary component with a small moderately differentiated adenocarcinoma component that massively invaded into the submucosal layer, accompanied by lymphatic invasion, although the tumor was very small (7 mm in diameter, smaller than any in previous reports). Laparoscopy-assisted sigmoidectomy and regional lymph node resection were performed; neither cancer nor lymph node metastases were present. This is the first report of a case with early-stage colonic IMPC observed with magnifying colonoscopy.

We read with interest the article by van der Sommen et al ,1 and assert some important and relevant points of adopting artificial intelligence (AI)-assisted endoscopy in clinical practice. Computer-aided diagnosis systems have successfully applied to all segments of the GI tract, even the diagnosis of dysplasia in Barrett’s oesophagus which is the bane of expert endoscopists.2 Recently, colonoscopy with real-time computer-aided detection (CADe) systems achieved higher polyp detection as compared with the performance of expert endoscopists.3 However, in adopting CADe to conventional oesophagogastroduodenoscopy (OGD), related discussions for improving the detection of hard-to-find gastric cancers (GC) are inevitable. The stomach has a wider, bent lumen, implicating more laborious gastric observations without a blind spot, compared with other GI tract anatomical features such as the oesophagus and colon. In routine OGD, the endoscopists have to distinguish gastric neoplasms from surrounding gastritis mucosa at more distant view, as opposed to detection of colorectal neoplasms and Barrett-related dysplasia by near-view images. In addition, early GCs usually show subtle elevation or depression and their irregular appearances easily hide in the coarse background gastritis caused by Helicobacter pylori infection. Therefore, it is sometimes difficult even for experts to discover early GCs, particularly smaller sizes. …

The withdrawal of antithrombotic therapy from patients at high risk of thromboembolism is controversial. Previously, treatment with anticoagulants, such as warfarin and dabigatran, was recommended for heparin bridge therapy (HBT) during endoscopic submucosal dissection (ESD). However, HBT is associated with a high risk of bleeding during and after ESD. This study aimed to investigate the clinical outcomes of colorectal ESD in patients treated with warfarin and direct oral anticoagulants (DOAC). This study included 412 patients with superficial colorectal neoplasms that were resected by ESD between June 2010 and June 2018. The patients were classified into two groups: without antithrombotics (n = 286) and with anticoagulants (n = 51). The anticoagulants group was further divided into two groups: warfarin (n = 26) and DOAC (n = 25). Among all patients, delayed bleeding occurred in 35 (8.5% [35/412]) patients. The bleeding rate in the anticoagulants group (11.8% [6/51]) was higher than that in the group without antithrombotics (6.6% [19/286]), but the difference was not statistically significant (P = 0.240). The bleeding rate in the DOAC group (16.0% [4/25]) was higher than that in the warfarin group (7.7% [2/26]), but the difference was not statistically significant (P = 0.419). All delayed bleeding was successfully managed with endoscopic hemostasis. Thromboembolic events were not observed in any patients. The bleeding rate with anticoagulants was relatively high. However, all bleeding events with anticoagulants were minor and clinically controllable. Colorectal ESD with DOAC and warfarin may be feasible and acceptable.

During endoscopic submucosal dissection (ESD), a clear view is essential for precise dissection of the appropriate submucosal layer. Some advantages have been reported for underwater techniques of endoscopic resection in comparison with the gas insufflation method. We have developed a new ESD method with the creation of a local water pocket (WP) that provides a clear view in the dissection field. Therefore, we aimed to investigate the feasibility and safety of WP-ESD for superficial gastric neoplasms.We prospectively recruited 50 patients with gastric neoplasms (early gastric cancer or gastric adenomas) between April 2017 and December 2017. Among them, 48 patients were treated with the WP-ESD technique. The patients undergoing WP-ESD were compared with 48 patients treated with standard ESD (S-ESD) who were selected by propensity score matching. The primary outcome was the ESD procedure time.Total procedure time was significantly shorter in the WP-ESD group than in the S-ESD group (median [interquartile range], 27.5 [19-45] minutes vs 41 [29.8-69] minutes; P .001). Similarly, the dissection speed was significantly greater in the WP-ESD group than in the S-ESD group (median [interquartile range], 22.5 [16.8-35.3] mmWP-ESD was associated with a shorter procedure time than S-ESD. WP-ESD may provide an alternative method for resection of superficial gastric neoplasms. (Clinical trial registration number: UMIN 000030266.).

Magnification endoscopy with narrow-band imaging (NBIME) and NBIME with acetic acid enhancement (A-NBIME) visualize the capillary and microstructure patterns of the gastric mucosal surface, respectively. This study aimed to compare the diagnostic accuracy and interobserver agreement for white-light endoscopy (WLE), NBIME, and A-NBIME in the different histologic types of gastric mucosal neoplasm.Consecutive gastric neoplasms (n = 220; 49 adenomas, 144 differentiated adenocarcinomas, and 27 undifferentiated adenocarcinomas) were photographed with WLE, NBIME, and A-NBIME. Macroscopic patterns using WLE, capillary patterns using NBIME, and microstructure patterns using A-NBIME were respectively classified into type M1/M2/M3, type C1/C2/C3/C4, and type S1/S2/S3, as the indicators of adenoma, differentiated adenocarcinoma, and undifferentiated adenocarcinoma (Type C4, unevaluable because of capillary invisibility), according to the previously reported classifications. Endoscopic images were independently reviewed by three experts and three non-experts. Diagnostic accuracy and interobserver diagnostic agreement were compared among the modalities.Kappa values (95 % confidence interval [CI]) for WLE, NBIME, and A-NBIME diagnosis were 0.36 (0.33 - 0.39), 0.58 (0.54 - 0.61), and 0.62 (0.55 - 0.68) for experts and 0.31 (0.29 - 0.33), 0.36 (0.34 - 0.38), and 0.52 (0.48 - 0.56) for non-experts, showing good reproducibility of A-NBIME diagnosis regardless of proficiency. All experts and non-experts diagnosed the histologic types statistically more accurately with A-NBIME than with WLE and NBIME (P 0.05). Overall the "experts-agreed" diagnostic accuracy (95 %CI) was 75.5 % (70.0 - 81.0) for WLE vs. 74.1 % (67.6 - 80.6) for NBIME vs. 90.5 % (86.7 - 94.1) for A-NBIME (P 0.05). WLE and NBIME were insufficient to predict the diagnosis of adenomas and undifferentiated adenocarcinomas.A-NBIME showed statistically significantly higher diagnostic accuracy for gastric mucosal neoplasms, with good reproducibility, compared with WLE and NBIME, which provided similar lower accuracy.