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Understanding the impacts of high‐resolution ocean model provides valuable insights for future research. However, the outcomes of sea surface state changes in both the tropics and mid‐latitudes remain unclear, and initialized seasonal forecasts have not been studied extensively. This study investigates the impact of ocean model resolution with the first long‐term hindcast experiment of an eddy‐resolving (0.1°) ocean model used for global seasonal forecasting. We show that using the high‐resolution ocean model significantly changes boreal winter jet streams in the atmosphere, based on the comparison of 30‐year hindcasts with ocean resolutions ranging from 1° to 0.1° for the Japan Meteorological Agency/Meteorological Research Institute Coupled Prediction System version 3. In boreal winters, the cold sea surface bias in the equatorial Pacific is significantly reduced, leading to an equatorward shift in the intertropical convergence zone (ITCZ) and enhanced convective activity in the western equatorial Pacific. The subtropical jet shifts equatorward due to the ITCZ shift and the weakening of equatorward propagation of mid‐latitude atmospheric eddies. The enhanced convective activity in the tropics has a remote influence in the mid‐latitudes, significantly reducing the upward eddy propagation of zonal wavenumber 1. Sea surface warm‐up in the mid‐latitudes partially cancels the reduction impact by enhancing the zonal wavenumber 2. Overall, the polar night jet accelerates due to the reduced supply of eddy forcing. Plain Language Summary: Atmospheric and oceanic eddies play an important role in shaping the climate. In numerical climate simulations, the Earth is divided into a grid of discrete boxes, and the exchange of energy and mass between the boxes is computed step‐by‐step. Coarse grids are often used to reduce the computational cost, but recent studies have suggested that resolving fine ocean phenomena can make a significant difference. In this study, numerical seasonal forecasting experiments with ocean resolutions of 100 km, 25 km, and 10 km are compared to investigate the high‐resolution effects on the atmospheric flow for boreal winter. This is the first 30‐year‐long, retrospective seasonal forecast experiment for the past winters using a global eddy‐resolving (10 km) ocean model. The high‐resolution ocean model greatly warms the surface seawater in the tropical Pacific and in the mid‐latitude oceans. These changes in the sea surface influence atmospheric convection and eddies, with far‐reaching effects on distant regions and altitudes. Such effects on the westerly jet streams, which flow several kilometers to tens of kilometers above the sea surface, are observed in the southward shift of the subtropical jet and the strengthening of the polar night jet. Key Points: Altering the ocean model resolution from 1° to 0.1° in a seasonal forecast model shifts and enhances the subtropical and polar night jetsAtmospheric responses to both tropical and mid‐latitude oceans are observedWave‐mean flow diagnostics indicates that the jet stream responses are more strongly influenced by the tropics [ABSTRACT FROM AUTHOR]

Quasi‐biennial oscillations (QBOs) in thirteen atmospheric general circulation models forced with both observed and annually repeating sea surface temperatures (SSTs) are evaluated. In most models the QBO period is close to, but shorter than, the observed period of 28 months. Amplitudes are within ±20% of the observed QBO amplitude at 10 hPa, but typically about half of that observed at lower altitudes (50 and 70 hPa). For almost all models, the oscillation's amplitude profile shows an overall upward shift compared to reanalysis and its meridional extent is too narrow. Asymmetry in the duration of eastward and westward phases is reasonably well captured, though not all models replicate the observed slowing of the descending westward shear. Westward phases are generally too weak, and most models have an eastward time mean wind bias throughout the depth of the QBO. The intercycle period variability is realistic and in some models is enhanced in the experiment with observed SSTs compared to the experiment with repeated annual cycle SSTs. Mean periods are also sensitive to this difference between SSTs, but only when parametrized non‐orographic gravity wave (NOGW) sources are coupled to tropospheric parameters and not prescribed with a fixed value. Overall, however, modelled QBOs are very similar whether or not the prescribed SSTs vary interannually. A portrait of the overall ensemble performance is provided by a normalized grading of QBO metrics. To simulate a QBO, all but one model used parametrized NOGWs, which provided the majority of the total wave forcing at altitudes above 70 hPa in most models. Hence the representation of NOGWs either explicitly or through parametrization is still a major uncertainty underlying QBO simulation in these present‐day experiments. [ABSTRACT FROM AUTHOR]

The Quasi‐Biennial Oscillation initiative (QBOi) is a model intercomparison programme that specifically targets simulation of the QBO in current global climate models. Eleven of the models or model versions that participated in a QBOi intercomparison study have upper boundaries in or above the mesosphere and therefore simulate the region where the stratopause semiannual oscillation (SAO) is the dominant mode of variability of zonal winds in the tropical upper stratosphere. Comparisons of the SAO simulations in these models are presented here. These show that the model simulations of the amplitudes and phases of the SAO in zonal‐mean zonal wind near the stratopause agree well with the information derived from available observations. However, most of the models simulate time‐average zonal winds that are more westward than determined from observations, in some cases by several tens of m·s–1. Validation of wave activity in the models is hampered by the limited observations of tropical waves in the upper stratosphere but suggests a deficit of eastward forcing either by large‐scale waves, such as Kelvin waves, or by gravity waves. [ABSTRACT FROM AUTHOR]

Background/aim: The long-term use of proton pump inhibitors (PPIs) has been reported to be strongly associated with the development of fundic gland polyps (FGPs). Conversely, a few cases of gastric hyperplastic polyps (GHPs) associated with PPI use have been reported. We experienced a case of PPI-associated multiple GHPs with uncontrollable bleeding., Case Report: A 64 year old man with a history of rheumatoid arthritis presented to the hospital with complaints of vertigo and black stools. Blood tests revealed anemia and hypoproteinemia. Esophagogastroduodenoscopy (EGD) showed blood and black residue accumulated in the stomach. The source of the bleeding was multiple hyperplastic polyps. Bleeding could be stopped even with fasting, and total blood transfusions amounted to 28 units of RBCs were required in 18 days. After the cessation of PPI, EGD showed that the polyps had almost disappeared. Pathological diagnosis of resected polyp was hyperplastic polyp, which was characterized by capillary hyperplasia and edema. Gastrin receptors were over-expressed in the foveolar epithelium and not in the capillaries. Methotrexate (MTX)-induced portal hypertensive gastroenteropathy was revealed during follow-up. We consider that the effect of portal hypertension may have caused the capillary hyperplasia., Conclusion: Although PPI-related polyps are usually fundic gland polyps and do not cause life-threatening adverse events, we experienced PPI-related GHPs in which hemostasis was difficult to control., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Chronic intestinal pseudo-obstruction (CIPO) is a rare intestinal disorder characterized by impaired propulsion of the digestive tract and associated with symptoms of intestinal obstruction, despite the absence of obstructive lesions. CIPO includes several diseases. However, definitive diagnosis of its etiology is difficult only with symptoms or imaging findings., Case Presentation: A 56-year-old man was referred to our hospital due to a 3-year history of continuous abdominal distention. Imaging, including computed tomography of the abdomen, and endoscopy revealed marked dilatation of the entire small intestine without any obstruction point. Therefore, he was diagnosed with CIPO. Since medical therapy didn't improve his symptoms, enterostomy and percutaneous endoscopic gastro-jejunostomy were performed. These procedures improved abdominal symptoms. However, he required home central venous nutrition due to dehydration. The pathological findings of full-thickness biopsies of the small intestine taken during surgery revealed decreased number and degeneration of ganglion cells in the normal plexus. These findings led to a final diagnosis of CIPO due to acquired isolated hypoganglionosis (AIHG)., Conclusions: Here, we report the case of a patient with CIPO secondary to adult-onset AIHG of the small intestine. Since AIHG cannot be solely diagnosed using clinical findings, biopsy is important for its diagnosis., (© 2023. Japanese Society of Gastroenterology.)

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

Background: Endoscopic biliary stenting is a standard treatment for biliary strictures after liver transplantation. Plastic stents are often replaced before stent dysfunction to prevent the development of cholangitis and jaundice. Therefore, the precise duration of stent patency is unclear., Methods: We compared retrospectively the stent patency period and stent dysfunction rate between inside stents (IS) and conventional plastic stents (PS) in 48 patients with post-transplant strictures, distinguishing endoscopic biliary stenting with and without stent dysfunction at stent replacement., Results: In observations focused on the first treatment, the median patency periods were 369 days for IS ( n = 18) and 154 days for PS ( n = 30; p = 0.01), significantly longer for IS. The 1-year cholangitis incidence rate was lower for IS (20% vs. 43%, p = 0.04). Additionally, no stent dislocation was observed for IS, but this occurred for 33.3% of PS ( p = 0.004). Comparing all endoscopic biliary stenting, including second and subsequent procedures, IS again had a longer patency period than PS (356 days, n = 89, vs. 196 days, n = 127, p = 0.009)., Conclusions: IS had a significantly longer patency period than PS, suggesting that IS replacement could be reduced to once per year for patients who prefer less frequent stent replacement., Competing Interests: None., (© 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Mediterranean fever ( MEFV ) gene mutations are responsible for familial Mediterranean fever (FMF) and associated with other inflammatory diseases. However, the effects of MEFV gene mutations on intestinal Behçet's disease (BD) are unknown. In this study, we investigated these mutations and clinical features in patients with intestinal BD., Methods: MEFV gene analysis was performed in 16 patients with intestinal BD, 10 with BD without intestinal lesions, and 50 healthy controls. Clinical features of patients with intestinal BD were retrospectively assessed., Results: The rates of MEFV gene mutations in patients with intestinal BD, BD without intestinal lesions, and healthy controls were 75%, 50%, and 38%, respectively. Only 2 of 12 patients with intestinal BD harboring MEFV gene mutations (17%) were controlled without immunosuppressive treatment, while 8 patients (67%) required therapy with tumor necrosis factor (TNF) inhibitors. Among patients with intestinal BD without MEFV gene mutations (four patients), three (75%) were controlled by the administration of 5-aminosalicylic acid with or without colchicine, and one (25%) required TNF inhibitors. All patients who underwent intestinal resection had MEFV gene mutations. Immunohistochemical analysis and in situ hybridization with interleukin-1β (IL-1β) showed a high expression of IL-1β only in injured areas, suggesting that IL-1β may be involved in the formation of ulcers in patients with intestinal BD carrying MEFV gene mutations., Conclusion: Mutations in the MEFV gene may be associated with intestinal lesions of BD and refractoriness to treatment.

Background: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for pharyngeal cancers. However, pharyngeal ESD is sometimes technically challenging because of the narrow and complex space in which to work. Traction is important to complete the procedure efficiently. Here, we report the technical details and efficacy of a new traction method for pharyngeal ESD using ring-shaped thread and grasping forceps., Methods: We analyzed pharyngeal ESD performed between January 2016 and March 2021 at our Institute. We designated cases resected using ring-shaped threads "Group R" and those resected without ring-shaped threads as conventional "Group C", and compared the technical outcomes between them. Multivariate analysis and the inverse probability treatment weighting (IPTW) method using propensity scores were adjusted by confounding variables., Results: We analyzed 89 lesions from 68 patients, of which 46 were in Group R and 43 in Group C. Median procedure time and median dissection speed were significantly shorter in Group R than C (37 min vs. 55 min, and 16.0 mm 2 /min vs. 7.0 mm 2 /min, respectively, both P < 0.05). These results were confirmed by both multivariate analysis and after IPTW adjustment. All lesions were resected en bloc, and the complete resection rate was not significantly different between Group R and C (91.3% vs. 79.1%, P = 0.14). There were no treatment-related adverse events in either group., Conclusions: The traction method using ring-shaped thread increases the efficiency of pharyngeal ESD. This simple new traction method should be a useful option for pharyngeal ESD., (© 2022. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Objectives: Endoscopic submucosal resection with band ligation (ESMR-L) and endoscopic submucosal dissection (ESD) are both standard endoscopic resection methods for rectal neuroendocrine tumors (NETs) <10 mm in size. However, there is no definitive consensus on which is better. Here, we compared the efficacy of ESMR-L and ESD for small rectal NETs., Methods: This was a multicenter retrospective cohort study including 205 patients with rectal NETs who underwent ESMR-L or ESD. Treatment outcomes were compared by univariate analysis, multivariate analysis, and inverse probability treatment weighting (IPTW) using propensity scores. Subgroup analysis evaluated the impact of the endoscopist's experience on the technical outcome., Results: Eighty-nine patients were treated by ESMR-L and 116 by ESD. The R0 resection rate was not significantly different between the two (90% vs. 92%, p = 0.73). The procedure time of ESMR-L was significantly shorter than for ESD (17 min vs. 52 min, p < 0.01) and the hospitalization period was also significantly shorter (3 days vs. 5 days, p < 0.01). These results were confirmed by multivariate analysis and also after IPTW adjustment. The procedure time of ESD was significantly prolonged by a less-experienced endoscopist (49 min vs. 70 min, p = 0.02), but that of ESMR-L was not affected (17 min vs. 17 min, p = 0.27)., Conclusions: For small rectal NETs, both ESMR-L and ESD showed similar high complete resection rates. However, considering the shorter procedure time and shorter hospitalization period, ESMR-L is the more efficient treatment method, especially for less-experienced endoscopists., Competing Interests: None., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Advanced hepatocellular carcinoma (HCC) remains a highly lethal malignancy, although several systemic therapeutic options are available, including sorafenib (SFN), which has been one of the standard treatment agents for almost a decade. As early prediction of response to SFN remains challenging, biomarkers that enable early prediction using a clinically feasible method are needed. Here, we report that the serum secretory form of clusterin (sCLU) protein and its related predictive index are potential beneficial biomarkers for early prediction of SFN response. Using high-throughput screening and subsequent multivariate analysis in the derivation cohort, we found that changes in the concentrations of CLU, vascular cell adhesion molecule-1 (VCAM1), and α-fetoprotein were significantly associated with response to SFN. Furthermore, we confirmed that an increase in CLU serum level 1 month after treatment initiation was significantly associated with shorter progression-free survival. In addition, "NR-index," which comprises these proteins, was evaluated as a tool for accurately predicting the efficacy of SFN and confirmed in the validation cohort. We also established SFN-resistant HepG2 cells (HepG2-SR) and found that sCLU significantly increased in HepG2-SR cells compared with normal HepG2 cells, and confirmed that HepG2-SR cells treated with SFN were resistant to apoptosis. The mechanism underlying activation of sCLU expression in acquired SFN resistance involves aberrant signaling and expression of Akt, mammalian target of rapamycin (mTOR), and a nutrient-related transcription factor, sterol regulatory element binding protein 1c (SREBP-1c). Furthermore, the PI3K and mTOR inhibitor BEZ235 markedly decreased sCLU expression in HepG2-SR cells. Conclusion: These results suggest that measurement of sCLU serum levels and the sCLU-related NR-index are promising clinical tools for the early prediction of SFN response in HCC. Additionally, sCLU-overexpressing HCC might be susceptible to mTOR inhibition., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: In recent years, with the growing availability of image-enhanced gastrointestinal endoscopy, gastroenterologists have contributed to the early detection of pharyngeal squamous cell carcinomas (SCC)., Aim: To clarify the clinical characteristics of pharyngeal SCCs detected by gastrointestinal endoscopy., Methods: This is a retrospective cohort study conducted in a single-center, a university hospital in Japan. We retrospectively assessed the clinical records of 522 consecutive patients with oropharyngeal or hypopharyngeal SCC who were examined in our hospital between 2011 and 2018. The lesions were classified into two groups: Group GE (detected by gastrointestinal endoscopy) and Group non-GE (detected by means other than gastrointestinal endoscopy). The clinical characteristics were compared between the two groups. Continuous data were compared using the Mann-Whitney U test. Pearson's χ 2 test or Fisher's exact test was used to analyze the categorical data and compare proportions. The Kaplan-Meier method was used to estimate the cumulative patient survival rates., Results: In our study group, the median age was 65 years and 474 patients (90.8%) were male. One hundred and ninety-six cases (37.5%) involved the oropharynx and 326 cases (62.5%) involved the hypopharynx. Three hundred and ninety-five cases (75.7%) had some symptoms at the time of diagnosis. One hundred and forty-five (27.8%) cases had concurrent ESCC or a history of ESCC. One hundred and sixty-four (31.4%) cases were detected by gastrointestinal endoscopy and classified as Group GE. The proportions of asymptomatic cases, cTis-1 cases and cases with no lymph node metastasis were significantly higher in Group GE than Group non-GE (61.6% vs 7.3%, P < 0.001, 32.9% vs 12.0%, P < 0.001 and 69.5% vs 19.0%, P < 0.001). Endoscopic laryngo-pharyngeal surgery or endoscopic submucosal dissection were performed in only 0.6% of the lesions in Group non-GE but in 21.3% of the lesions in Group GE ( P < 0.001). Overall survival was significantly longer in Group GE than in Group non-GE ( P = 0.018). The 2-year and 4-year survival rates were 82.5% and 70.7% in Group GE, and 71.5% and 59.0% in Group non-GE, respectively., Conclusion: Gastrointestinal endoscopy plays an important role in the early detection and improving the prognosis of pharyngeal SCCs., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest associated with this manuscript., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Our aim is to evaluate the utility of liver function measured by modified albumin-bilirubin (mALBI) grade to predict eligibility for second-line therapies, including regorafenib and ramucirumab therapy, at initiation of sorafenib therapy for patients with hepatocellular carcinoma (HCC)., Methods: Participants in this retrospective, single-center study comprised 197 patients with sorafenib-treated HCC, Child-Pugh scores (CPs) 5-7 and performance status 0-1 treated between October 2009 and June 2019. The factors at initiation of sorafenib therapy, including mALBI grade and CPs, were analyzed with regard to second-line eligibility, regorafenib eligibility and ramucirumab eligibility, respectively., Results: Proportions of eligibility for second-line therapies, regorafenib therapy and ramucirumab therapy were 48.7%, 35.5% and 18.3%. Modified ALBI grades 1 and 2a were contributing factors for second-line eligibility (odd ratios [OR] 16.7 and 5.6; 95% CI 6.5-43.3 and 2.6-12.2), regorafenib therapy (OR 13.9 and 6.9; 95% CI 5.6-34.4 and 2.9-16.2), and ramucirumab therapy (OR 9.5 and 4.8; 95% CI 2.9-30.8 and 1.6-14.4), with grade 2b defined as reference. Patients with mALBI grade 1 and CPs 5 exhibited especially high proportion of eligibility for regorafenib therapy (70.5%). In patients with mALBI grade 2b, those with CPs 5 displayed higher proportion of eligibility for second-line therapy and ramucirumab therapy (100% and 50%) than those with CPs 6 (31.8% and 11.4%)., Conclusions: Modified ALBI grade in combination with CPs at the initiation of sorafenib therapy would be useful to predict eligibility for second-line therapies.

Risk stratification by index colonoscopy is well established for first surveillance endoscopy, but whether the previous two colonoscopies affect the subsequent advanced neoplasias has not been established. Therefore, the subsequent risk based on the findings of the index and first surveillance colonoscopies were investigated. This retrospective, cohort study was conducted in two clinics and included participants who had undergone two or more colonoscopies after index colonoscopy. High-risk was defined as advanced adenoma (≥ 1 cm, or tubulovillous or villous histology, or high-grade dysplasia). Based on the findings of the index and first surveillance colonoscopies, patients were classified into four categories: category A (both colonoscopy findings were normal), category B (no high-risk findings both times), category C (one time high-risk finding), and category D (high-risk findings both times). The incidence of subsequent advanced neoplasia was examined in each category. A total of 13,426 subjects were included and surveyed during the study periods. The subjects in category D had the highest risk of advanced neoplasia (27.4%, n = 32/117). The subjects in category A had the lowest risk (4.0%, n = 225/5,583). The hazard ratio for advanced neoplasia of category D compared to category A was 9.90 (95% Confidence interval 6.82-14.35, P<0.001). Classification based on the findings of index and first surveillance colonoscopies more effectively stratifies the risk of subsequent advanced neoplasia, resulting in more proper allocation of colonoscopy resources after two consecutive colonoscopies., Competing Interests: The authors have declared that no competing interests exist.

Background: Sarcopenia is a syndrome characterized by progressive and systemic decreases in skeletal muscle mass and muscle strength. The influence or prognosis of various liver diseases in this condition have been widely investigated, but little is known about whether sarcopenia and/or muscle mass loss are related to minimal hepatic encephalopathy (MHE)., Methods: To clarify the relationship between MHE and sarcopenia and/or muscle mass loss in patients with liver cirrhosis., Methods: Ninety-nine patients with liver cirrhosis were enrolled. MHE was diagnosed by a neuropsychiatric test. Skeletal mass index (SMI) and Psoas muscle index (PMI) were calculated by dividing skeletal muscle area and psoas muscle area at the third lumbar vertebra by the square of height in meters, respectively, to evaluate muscle volume., Results: This study enrolled 99 patients (61 males, 38 females). MHE was detected in 48 cases (48.5%) and sarcopenia in 6 cases (6.1%). Patients were divided into two groups, with or without MHE. Comparing groups, no significant differences were seen in serum ammonia concentration or rate of sarcopenia. SMI was smaller in patients with MHE (46.4 cm 2 /m 2 ) than in those without (51.2 cm 2 /m 2 , P = 0.027). Similarly, PMI was smaller in patients with MHE (4.24 cm 2 /m 2 ) than in those without (5.53 cm 2 /m 2 , P = 0.003). Skeletal muscle volume, which is represented by SMI or PMI was a predictive factor related to MHE (SMI ≥ 50 cm 2 /m 2 ; odds ratio 0.300, P = 0.002, PMI ≥ 4.3 cm 2 /m 2 ; odds ratio 0.192, P = 0.001)., Conclusions: Muscle mass loss was related to minimal hepatic encephalopathy, although sarcopenia was not. Measurement of muscle mass loss might be useful to predict MHE.

Immune checkpoint inhibitors can affect any organ, including the salivary glands. A case of Sjögren's syndrome (SjS) induced by nivolumab for the treatment of gastric cancer is herein presented. Nivolumab treatment caused marked tumor shrinkage, but xerostomia developed after two cycles. It took 3 months after symptom onset to confirm the diagnosis of SjS. Prednisolone and pilocarpine hydrochloride did not relieve the symptoms. SjS is a relatively rare immune-related adverse event that might sometimes be overlooked. Since SjS can severely impair a patient's quality of life, oncologists should not miss any signs of salivary gland hypofunction and cooperate with specialists for SjS.

Background and Aim: In Japan, risk stratification after baseline colonoscopy is not widely accepted. We investigated the findings of baseline colonoscopies at 17 community practices and evaluated the risk of the incidence of advanced neoplasia over a 5-year period., Methods: This retrospective cohort study enrolled 3115 subjects over 40 years of age who underwent baseline colonoscopies and had at least one repeated colonoscopy within 5 years. Each group was classified based on the endoscopic findings of the baseline colonoscopy: no neoplasia/diminutive polyp <5 mm (N/D); small adenoma <10 mm; advanced adenoma; invasive cancer, respectively. We examined the incidence of advanced neoplasia during these 5 years and investigated the relationship between the surveillance colonoscopy and newly detected advanced neoplasia., Results: The small adenoma group did not show any significant increased risk as compared to the N/D group (hazard ratio [HR]: 0.799. 95% CI 0.442-1.443). There was a significantly increased risk in the advanced adenoma and invasive cancer groups (HR: 4.996, 95% CI 2.940-8.491, HR: 3.737, 95% CI 1.309-10.666). Cancer incidences during the study period were 0.18% in the N/D group, and 1.9% in the invasive cancer group, respectively. Undergoing surveillance colonoscopies twice within 5 years decreased the risk of advanced neoplasia., Conclusions: There was a close relationship between the endoscopic findings of baseline colonoscopies and subsequent advanced neoplasia development. Risk stratification for advanced neoplasia based on the baseline findings can serve as a useful index for determining the optimal interval and frequency of colonoscopies over a 5-year period., (© 2019 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

The adenoma-carcinoma sequence, the sequential mutation and deletion of various genes by which colorectal cancer progresses, is a well-established and accepted concept of colorectal cancer carcinogenesis. Proteins of the polycomb repressive complex 2 (PRC2) function as transcriptional repressors by trimethylating histone H3 at lysine 27; the activity of this complex is essential for cell proliferation and differentiation. The histone methyltransferase enhancer of zeste homolog 2 (EZH2), an essential component of PRC2, is associated with the transcriptional repression of tumor suppressor genes. EZH2 expression has previously been reported to increase with the progression of pancreatic intraductal papillary mucinous neoplasm. Thus, we hypothesized that EZH2 expression also increases during the adenoma-carcinoma sequence of colorectal cancer. The present study investigated changes in EZH2 expression during the colorectal adenoma-carcinoma sequence. A total of 47 patients with colorectal adenoma, 20 patients with carcinoma in adenoma and 43 patients with colorectal carcinoma who underwent surgical or endoscopic resection were enrolled in this study. Non-cancerous tissue from the clinical specimens was also examined. The association between EZH2 expression, pathology and expression of tumor suppressor genes during colorectal carcinogenesis were analyzed. Each specimen was immunohistochemically stained for EZH2, proliferation marker protein Ki-67 (Ki-67), cyclin-dependent kinase inhibitor (CDKN) 1A (p21), CDKN1B (p27) and CDKN2A (p16). Total RNA was extracted from formalin-fixed paraffin-embedded blocks and reverse transcription-quantitative polymerase chain reaction analysis of these genes was performed. Ki-67 and EZH2 expression scores increased significantly during the progression of normal mucosa to adenoma and carcinoma (P=0.009), and EZH2 expression score was positively associated with Ki-67 expression score (P=0.02). Conversely, p21 mRNA and protein expression decreased significantly, whereas expression of p27 and p16 did not change significantly. During the carcinogenesis sequence from normal mucosa to adenoma and carcinoma, EZH2 expression increased and p21 expression decreased significantly. EZH2 may therefore contribute to the development of colorectal cancer from adenoma via suppression of p21.

Background and Aim: Right colon polyps can especially be overlooked when they are located on the backs of haustral folds. Previous studies have reported that repeated forward-view examinations in the right colon were effective in reducing adenoma miss rates. The aim of this study was to clarify the impact of retroflexion in the right colon after repeated forward-view examinations., Methods: This multicenter, prospective, observational study was conducted at three institutions in Kumamoto, Japan, between February 2014 and December 2015. Subjects who were over 40 years old and scheduled for colonoscopy were recruited. For the forward view, after cecal intubation, the colonoscope was withdrawn to the hepatic flexure. The colonoscope was sequentially reinserted to the cecum and then withdrawn to the hepatic flexure. For the retroflexion view (RV), the colonoscope was reinserted to the cecum, retroflexed, and then withdrawn to the hepatic flexure. All polyps were resected at the time of detection. The primary outcome of this study was the adenoma miss rate for the repeated forward-view examinations., Results: Of the 777 enrolled participants, retroflexion was successful in 730 (94.0%). The repeated forward-view withdrawal technique detected 291 adenomas, while the third withdrawal in the RV detected 53. The adenoma miss rate for the repeated forward-view withdrawal was 15.4%. No severe adverse events occurred during retroflexion., Conclusion: Because adenomas located on potential blind spots can be missed when only using forward-view examinations, retroflexion in the right colon after repeated forward-view examinations might improve colonoscopy detection rates.

Background and Aims: The aim of this study was to evaluate structural and functional alterations of human serum albumin (HSA), with a special focus on the oxidized and reduced forms, in patients with chronic liver disease. We also investigated whether oral branched-chain amino acid (BCAA) supplementation could induce structural changes and improve the functions of HSA., Methods: The proportion of reduced and oxidized HSA was determined in 16 healthy controls and in 20 chronic hepatitis and 100 cirrhotic patients with stable conditions. To evaluate the functional properties of HSA, this study focused on the antioxidant and binding functions. The radical scavenging activity and binding ability of purified HSA were measured in 68 participants. After BCAA administration for 6 months, 29 patients were evaluated for HSA structural changes, with 19 out of the 29 patients also analyzed for HSA functional changes., Results: There was a significant decrease in the amounts of reduced HSA in conjunction with liver disease progression. Receiver operating characteristic curve analysis demonstrated that the levels of reduced HSA had high accuracy in determining disease progression. Functional alterations were strongly correlated to the levels of reduced HSA. BCAA supplementation led to substantial increases in the amount of reduced HSA. The altered HSA was able to scavenge significantly more radicals and restore the binding ability., Conclusion: This study describes structural alterations and functional disturbances of HSA in patients with chronic liver disease, and indicates that the levels of reduced HSA might reflect disease progression and the functional properties of HSA. Moreover, oral BCAA supplementation increases the amount of reduced HSA, thereby leading to the restoration of HSA function in cirrhotic patients.

Background: Adenocarcinoma with enteroblastic differentiation is a subtype of alpha-fetoprotein (AFP) producing adenocarcinoma. This type of tumor is associated with a poor prognosis and is prone to metastasize. Esophageal adenocarcinoma with enteroblastic differentiation is extremely rare., Case Presentation: The patient was a 65-year-old woman who was referred to our hospital with dysphagia. Endoscopic examination revealed an elevated lesion 20mm in diameter at 17cm from the upper incisors. Endoscopic submucosa dissection (ESD) was performed and histopathological examination revealed tubular adenocarcinoma composed of cuboidal cells with clear cell cytoplasm. Immunohistochemical stain was diffusely positive for Sall-like protein 4 (SALL4) and weakly positive for AFP and glypican 3. From this result, we diagnosed esophageal adenocarcinoma with enteroblastic differentiation. The patient is still alive without recurrence of cancer 40 months after ESD., Conclusion: To our knowledge, this is the first report to undergo ESD for esophageal adenocarcinoma with enteroblastic differentiation arising from ectopic gastric mucosa in the esophagus.

Mucosa-associated lymphoid tissue (MALT) lymphoma is rarely observed in the gallbladder, and its diagnosis before surgery is difficult. This report describes a case of primary MALT lymphoma of the gallbladder in an 80-year-old man. Imaging studies revealed a protruding lesion on the inside of the gallbladder, which led us to diagnose gallbladder carcinoma prior to the patient undergoing extended cholecystectomy. Microscopic examination of the resected specimen of the gallbladder demonstrated lymphoid follicles with atypical lymphocytes and the formation of lymphoepithelial lesions. These findings led to a final pathological diagnosis of primary MALT lymphoma of the gallbladder. The patient has been free of recurrence for 39 months after the surgery. Although precise diagnosis before the surgery was difficult in this case, preoperative examinations revealed a submucosal tumour-like lesion. MALT lymphomas should be considered when imaging findings are atypical for gallbladder carcinoma., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The incidence rate of esophagogastric junction (EGJ) adenocarcinoma has been rapidly increasing worldwide. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are major serum tumor markers in gastrointestinal cancers. However, the role of these markers in EGJ adenocarcinoma has not been thoroughly investigated. A total of 211 patients with EGJ adenocarcinoma who underwent surgery or endoscopic submucosal dissection at two academic institutions, Kumamoto University Hospital or Kyushu University Hospital between January 1996 and March 2014, were eligible for this study. Serum CEA and CA19-9 were examined within 1 month before resection. The cut-off values for CEA and CA19-9 were set at 5.0 ng/mL and 37 U/mL, respectively. The clinicopathological features and prognostic roles of the markers were examined using univariate and multivariate analyses. The positive ratios for preoperative CEA (>5.0 ng/mL) and CA19-9 (>37 U/mL) were 20.3% and 12.9%, respectively. The positive ratio of CEA and CA19-9 was significantly higher in patients with tumors invading muscular or deeper layers (P = 0.002 and <0.001, respectively). Cox proportional hazards model revealed that CA19-9 positivity, but not CEA positivity, was an independent prognostic factor in patients with EGJ adenocarcinoma for cancer-specific survival (multivariate hazard ratio [HR] = 3.89, 95% confidence interval [CI] 1.41-10.33; P = 0.010) and overall survival (multivariate HR = 2.43, 95% CI 1.03-5.35; P = 0.043). Preoperative serum CA19-9 is a useful prognostic marker in patients with EGJ adenocarcinoma., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (< 3 cm) intrahepetic lesion, was positively associated with good prognosis and negatively associated with disease progression in the SFN group. Maximum tumor size (> 5 cm) and low albumin (≤ 3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS., (© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Unlabelled: Anti-tumor necrosis factor (TNF)-α therapy is established as a new standard for the treatment of various autoimmune inflammatory diseases. We report the first case showing subacute thyroiditis-like symptoms with an amyloid goiter after anti-TNF-α therapy. A 56-year-old man with Crohn's disease presented with fever and a diffuse, tender goiter. To control the diarrhea, anti-TNF therapy (infliximab) was administered 4 weeks before the thyroid symptoms emerged. The patient reported a swollen neck with tenderness on the right side and fever 4 days after the second infliximab injection. An elevated serum C-reactive protein (CRP) and serum thyroid hormone level with suppressed serum thyrotropin were observed. The thyroid-stimulating antibody was not elevated. An ultrasonograph of the thyroid revealed an enlarged goiter with posterior echogenicity attenuation and a low echoic region that was tender. The thyroid uptake value on technetium-99m scintigraphy was near the lower limit of the normal range. The patient was initially diagnosed with thyrotoxicosis resulting from subacute thyroiditis. Administration of oral prednisolone improved the fever, thyroid pain, and thyroid function, but his thyroid remained swollen. The patient developed diarrhea after prednisolone withdrawal; therefore, adalimumab, another TNF inhibitor, was administered. After three injections, his abdominal symptoms were alleviated, but the thyroid pain and fever recurred. Elevated serum CRP levels in the absence of thyroid dysfunction were observed. The patient's symptoms resolved after prednisolone retreatment, but an elastic, firm goiter persisted. A fine-needle biopsy revealed amyloid deposition in the thyroid., Learning Points: Many cases with thyroid dysfunction accompanied by amyloid goiter have been reported.There are cases that develop amyloid goiter with subacute thyroiditis-like symptoms after anti-TNF therapy.When the thyroid remains swollen after improvement of thyrotoxicosis following treatment with prednisolone, it should be assessed to differentiate between an amyloid goiter and common subacute thyroiditis.

Three new multiflorane-type triterpene esters, i.e. 7α-hydroxymultiflor-8-ene-3α,29-diol 3-acetate-29-benzoate (1), 7α-methoxymultiflor-8-ene-3α,29-diol 3,29-dibenzoate (2), and 7β-methoxymultiflor-8-ene-3α,29-diol 3,29-dibenzoate (3), were isolated from seeds of Cucurbita maxima, along with the known compound, multiflora-7,9(11)-diene-3α,29-diol 3,29-dibenzoate (4). Compound 1 exhibited melanogenesis inhibitory activities comparable with those of arbutin. In cytotoxicity assays, compounds 1 and 3 exhibited weak cytotoxicity, with IC50 values of 34.5-93.7 μM against HL-60 and P388 cells.

Differentiation of placental trophoblast stem (TS) cells to trophoblast giant (TG) cells is accompanied by transition from a mitotic cell cycle to an endocycle. Here, we report that Cdh1, a regulator of the anaphase-promoting complex/cyclosome (APC/C), negatively regulates mitotic entry upon the mitotic/endocycle transition. TS cells derived from homozygous Cdh1 gene-trapped (Cdh1(GT/GT)) murine embryos accumulated mitotic cyclins and precociously entered mitosis after induction of TS cell differentiation, indicating that Cdh1 is required for the switch from mitosis to the endocycle. Furthermore, the Cdh1(GT/GT) TS cells and placenta showed aberrant expression of placental differentiation markers. These data highlight an important role of Cdh1 in the G2/M transition during placental differentiation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

A 61-year-old female with refractory corrosive esophageal stenosis repeatedly underwent endoscopic balloon dilation at another hospital; however, no improvements were observed in the esophageal stenosis. Consequently, she had been on a liquid diet for the previous three years. She was admitted to our department for further treatment. A radial incision was made, by use of the SB knife Jr, for a pinhole-like stenosis in a short segment 39 cm from the incisor, and dilation was safely performed by use of a CRE balloon dilator. Subsequently, prednisolone was orally administered to prevent re-stenosis. This was followed by a favorable clinical course.