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Wataru Izumo,1 Kei Hosoda,1 Hidekazu Kuramochi,2 Go Nakajima,2 Shinsuke Maeda,1 Shunichi Ito,1 Yoji Nagashima,3 Michio Itabashi1 1Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan; 2Department of Chemotherapy and Palliative Care, Tokyo Women’s Medical University, Tokyo, 162-8666, Japan; 3Department of Surgical Pathology, Tokyo Women’s Medical University Hospital, Tokyo, 162-8666, JapanCorrespondence: Wataru Izumo, Department of Surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan, Tel +81-3-3353-8111, Fax +81-3-5269-7507, Email izumo.wataru@twmu.ac.jpAbstract: Gastric cancer with Virchow’s lymph node metastasis (LNM) is not indicated for initial curative surgery. Although there have been some case reports of curative resections after pre-operative treatment, including immune checkpoint inhibitors (ICIs), there is no consensus regarding the optimal timing of surgery. We describe a rare case of initially unresectable gastric cancer treated preoperatively with nivolumab combined chemotherapy, which achieved a pathologically complete response. An 82-year-old man was referred for gastric cancer treatment. Contrast-enhanced computed tomography revealed stomach wall thickening and swollen left supraclavicular LN. This gastric cancer was assessed as unresectable due to the presence of Virchow’s LNM; therefore, chemotherapy and ICI using S-1 plus oxaliplatin plus nivolumab were administered. After three courses of treatment, the primary tumor and Virchow’s LN showed a marked reduction in size. The patient underwent Virchow’s LNM resection as a preliminary step to determine indications for curative surgery. A pathological examination revealed no viable cancer cells were found inside the resected LN. The patient underwent distal gastrectomy. Pathological examination revealed complete degeneration of the primary tumor and regional LN without residual carcinoma. The patient did not receive adjuvant chemotherapy and survived with no evidence of recurrence for one year after the initial treatment.Keywords: gastric cancer, Virchow’s lymph metastasis, complete response, pre-operative treatment, nivolumab

Yuri Iwata,1 Yumiko Iwata,2 Hiroshi Iida,1 Masahiko Inamori,1 Shin Maeda3 1Department of Medical Education, Yokohama City University, Yokohama, Japan; 2Department of English Language, Communication and Cultures, University of the Sacred Heart, Tokyo, Japan; 3Department of Gastroenterology, Yokohama City University, Yokohama, JapanCorrespondence: Yuri Iwata, Department of Medical Education, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan, Tel +81-45-787-2626, Fax +81-45-787-2620, Email yuri.sagamed@gmail.comAim: To report on the effects of a smartphone application, among the medical staff and medical students, for learning English as a foreign language.Methods: We conducted an exploratory quasi-experimental study among eight medical staff and 10 medical students in Japan. The participants used an application called ABC Talking (created by ABC Talking Laboratories Inc, currently unavailable due to application renewal), loaded onto their smartphones, to talk with native English speakers from overseas. The participants used the application for five minutes twice a day over five consecutive days as per their convenience. The study collected quantitative and qualitative data using assessments on the participants’ listening and speaking skills and questionnaire. The assessment scores of the first five sessions were compared to those of the last five. Average self-assessment scores and teacher assessment scores were compared using a t-test. A paired t-test was performed on quantitative data of the questionnaire, and content analysis was performed on qualitative data.Results: More than 80% of the calls were made from home and 70% occurred between 9PM and 1AM. The participants’ self-assessment scores on their listening and speaking skills increased significantly from the first five sessions to the last five sessions (14.8– 26.1%). However, there was no significant change in the assessments by the teachers (− 4.5– 2.1%). The self-assessment scores of those with low English proficiency were lower than the teachers’ assessment scores. Improvement of communicative self-confidence and communicative competence, two factors that affect willingness to communicate, were seen from the questionnaire.Conclusion: Using smartphone applications allows on-demand English training, which may be especially useful to medical staff and students who have unpredictable work schedules. Teachers should be aware that learners tend to assess themselves lower than their actual ability so that they can give appropriate feedback to the learners.Keywords: limited English proficiency, communication, medical training, professional competence, language barrier

Aki Kawakami,1,2 Makoto Tanaka,2 Lee Meng Choong,1 Reiko Kunisaki,3 Shin Maeda,4 Ingvar Bjarnason,1 Bu’Hussain Hayee1 1Department of Gastroenterology, King’s College Hospital, London, UK; 2Department of Critical and Invasive-Palliative Care Nursing, Graduate School of Health Care Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Japan; 3Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan; 4Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, JapanCorrespondence: Makoto Tanaka, Department of Critical and Invasive-Palliative Care Nursing, Graduate School of Health Care Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan, Tel +81-3-5803-4507, Fax +81-3-5803-4507, Email tanaka.cc@tmd.ac.jpPurpose: Non-adherence to medication was reported by 28% of Japanese patients with ulcerative colitis, but in the United Kingdom, patients with inflammatory bowel disease have lower medication adherence, which increases clinical relapse risk. The objective of this study was to compare medication adherence among patients with ulcerative colitis in Japan with previously reported results and patients in the United Kingdom.Patients and Methods: This cross-cultural comparison study investigated medication adherence among 100 ulcerative colitis patients in the United Kingdom and 432 ulcerative colitis patients in Japan. Adherence was assessed using The Morisky Medication Adherence Scale-8 questionnaire. Patient clinical features were collected from medical records and the questionnaire. Distribution of responses for each item, questionnaire total score, difference in ratio for each item between Japanese and UK patients, and difference in percentage of low/medium/high adherence between Japanese and UK patients were compared.Results: The proportion of low/medium or high adherence was significantly different between countries (42.6% and 7.4% [Japan] vs 24.0% and 76.0% [United Kingdom]; p< 0.01). Significantly more Japanese patients reported taking medication correctly the day before the questionnaire compared with UK patients.Conclusion: UK patients were more likely to not take medication when they felt their symptoms were under control compared with Japanese patients. UK patients perceived it was more difficult to remember to take the medication than Japanese patients. This study highlights culturally sensitive medication-taking behaviors in Japanese and UK patients with ulcerative colitis.Keywords: cross-cultural comparison, self-management, race, inflammatory bowel disease

One-third of type-2 diabetic patients respond poorly to metformin. Despite extensive research, the impact of genetic and nongenetic factors on long-term outcome is unknown. In this study we combine nonlinear mixed effect modeling with computational genetic methodologies to identify predictors of long-term response. In all, 1,056 patients contributed their genetic, demographic, and long-term HbA1c data. The top nine variants (of 12,000 variants in 267 candidate genes) accounted for approximately one-third of the variability in the disease progression parameter. Average serum creatinine level, age, and weight were determinants of symptomatic response; however, explaining negligible variability. Two single nucleotide polymorphisms (SNPs) in CSMD1 gene (rs2617102, rs2954625) and one SNP in a pharmacologically relevant SLC22A2 gene (rs316009) influenced disease progression, with minor alleles leading to less and more favorable outcomes, respectively. Overall, our study highlights the influence of genetic factors on long-term HbA1c response and provides a computational model, which when validated, may be used to individualize treatment.

Objective To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. Patients and methods We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. Results We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15–30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). Conclusions The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency. [ABSTRACT FROM AUTHOR]

Katsuaki Ogushi,1,* Makoto Chuma,1,* Haruki Uojima,2 Hisashi Hidaka,2 Kazushi Numata,1 Satoshi Kobayashi,3 Shunji Hirose,4 Nobuhiro Hattori,5 Tomoaki Fujikawa,6 Takahide Nakazawa,2 Naohisa Wada,2 Shuitirou Iwasaki,2 Taito Fukushima,3 Yusuke Sano,3 Makoto Ueno,3 Kuniyuki Kawano,3 Kota Tsuruya,4 Masako Shomura,4 Tsunamasa Watanabe,5 Kotaro Matsunaga,5 Yosuke Kunishi,7 Yusuke Saigusa,8 Kuniyasu Irie,9 Shogo Iwabuchi,6 Makoto Kako,10 Manabu Morimoto,3 Tatehiro Kagawa,4 Katsuaki Tanaka,11 Shin Maeda9 1Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan; 2Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan; 3Hepatobiliary and Pancreatic Medical Oncology, Kanagawa Cancer Center Hospital, Yokohama, Japan; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Japan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; 6Department of Gastroenterology, Shonan Fujisawa General Hospital, Fujisawa, Japan; 7Department of Gastroenterology, Kanagawa Prefectural Ashigarakami Hospital, Kanagawa, Japan; 8Department of Biostatistics, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 9Department of Gastroenterology, Yokohama City University Hospital, Yokohama, Japan; 10Department of Gastroenterology, Shonan Kamakura General Hospital, Kamakura, Japan; 11Gastroenterology Division, Hadano Red Cross Hospital, Hadano, Japan*These authors contributed equally to this workCorrespondence: Makoto Chuma Gastroenterological CenterYokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama, Kanagawa 2320024, JapanTel +81 45 261 5656Fax +81 45 253 9955Email chuma@yokohama-cu.ac.jpPurpose: To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC).Methods: Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines.Results: Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P < 0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥ 0.7 vs < 0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5– 7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment.Conclusion: Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.Keywords: lenvatinib, tyrosine kinase inhibitor, hepatocellular carcinoma, Child-Pugh, adverse events, overall survival

Yu Monden, Chikako Nagashima, Noriko Yokote, Fumi Hotokezaka, Satoshi Maeda, Kensuke Sasaki, Ryoji Yamakawa, Shigeo Yoshida Department of Ophthalmology, Kurume University School of Medicine, Fukuoka, JapanCorrespondence: Yu MondenDepartment of Ophthalmology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830 0011, JapanTel +81-942-317574Fax +81-942-370324Email you@med.kurume-u.ac.jpPurpose: The aim of this study was to evaluate the clinical outcomes of management of recurrent pterygium with severe symblepharon using mitomycin C, double amniotic membrane transplantation, cryopreserved limbal allograft, and a conjunctival flap.Patients and Methods: This retrospective case series included 10 eyes of 10 patients with recurrent pterygium with severe symblepharon. Eight patients have diplopia in primary gaze. All patients underwent pterygium excision, application of mitomycin C (MMC), double amniotic membrane transplantation (AMT), cryopreserved limbal allograft (CLA) transplantation, and placement of a conjunctival flap. Outcome measures were visual acuity, astigmatism, and recurrence. Recurrence was defined as the presence of fibrovascular proliferative tissue crossing the limbus.Results: The patients’ mean age was 73.8 years. The mean follow-up period was 3.0 years. The mean preoperative and postoperative best-corrected visual acuities (logMAR conversion) were 0.43 and 0.30, respectively. The mean preoperative and postoperative astigmatism were – 3.89 diopters and – 1.54 diopters, respectively, and there was a significant difference. No recurrence occurred in any of the eyes. Symblepharon was released in all eyes. Diplopia in primary gaze was resolved in all eyes.Conclusion: Management of recurrent pterygium with severe symblepharon using MMC, double AMT, CLA, and a conjunctival flap was an effective treatment.Keywords: pterygium, symblepharon, limbal allograft, amnion, mitomycin C

One-third of type 2 diabetes patients do not respond to metformin. Genetic variants in metformin transporters have been extensively studied as a likely contributor to this high failure rate. Here, we investigate, for the first time, the effect of genetic variants in transcription factors on metformin pharmacokinetics (PK) and response. Overall, 546 patients and healthy volunteers contributed their genome-wide, pharmacokinetic (235 subjects), and HbA1c data (440 patients) for this analysis. Five variants in specificity protein 1 (SP1), a transcription factor that modulates the expression of metformin transporters, were associated with changes in treatment HbA1c (P < 0.01) and metformin secretory clearance (P < 0.05). Population pharmacokinetic modeling further confirmed a 24% reduction in apparent clearance in homozygous carriers of one such variant, rs784888. Genetic variants in other transcription factors, peroxisome proliferator-activated receptor-α and hepatocyte nuclear factor 4-α, were significantly associated with HbA1c change only. Overall, our study highlights the importance of genetic variants in transcription factors as modulators of metformin PK and response.

Accumulation of hyperphosphorylated tau in the entorhinal cortex (EC) is one of the earliest pathological hallmarks in patients with Alzheimer's disease (AD). It can occur before significant Aβ deposition and appears to "spread" into anatomically connected

Aki Kawakami,1,2 Makoto Tanaka,3 Makoto Naganuma,4 Shin Maeda,5 Reiko Kunisaki,1 Noriko Yamamoto-Mitani2 1Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Minami-ku, Yokohama, Japan; 2Department of Gerontological Home Care and Long-term Care Nursing, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan; 3Ramathibodi School of Nursing, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok, Thailand; 4Division of Gastroenterology and Hepatology, Keio University, Shinjuku-ku, Tokyo, Japan; 5Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan Background: Overall, 30%–45% of patients with ulcerative colitis (UC) are non-adherent and have difficulties taking their medications; this non-adherence increases the risk of clinical relapse 1.4- to 5.5-fold. This study aimed to clarify the strategies patients employ to facilitate adherence and determine whether the strategies had an impact on good adherence.Methods: This was a cross-sectional survey using a self-administered questionnaire and review of medical records. Patients diagnosed as having UC and attending one of the outpatient clinics of four urban hospitals from June 2009 to December 2012 were enrolled. A questionnaire was developed to identify the strategies patients employ to facilitate adherence and then administered to patients with UC. Adherence to 5-aminosalicylic acid was calculated, and univariate and multiple logistic regression analyses were performed to determine the strategies that were associated with good adherence.Results: The final analyses included 671 participants (mean age 40.2 years; 54.3% males). The valid response rate was 96.9%; 186 (27.7%) participants were classified as non-adherent, the mean adherence rate being 86.1% (standard deviation [SD] 17.9). Seven strategies that patients employ to facilitate adherence were identified, the following two being significantly associated with good adherence: “I keep my medicines where I eat meals” and “I keep each day’s medicine in a pill case or something similar to make sure I have taken them”.Conclusion: The identified strategies might be used to develop a program to improve medication adherence in patients with UC. Keywords: medication adherence, self-management, ulcerative colitis, 5-aminosalicylic acid