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Background: An increased focus on quality and patient safety led to the evolution of the hospitalist specialty. The number of hospitalists, who cover ward and outpatient care, is on the rise in Japan. However, it is unclear what roles hospitalists themselves consider important in their practice. Therefore, this study aimed to investigate what hospitalists and non-hospitalist generalists in Japan consider important for the practice of their specialty. Methods:This was an observational study that included Japanese hospitalists (1) currently working in a general medicine (GM) or general internal medicine department and (2) working at a hospital. Using originally developed questionnaire items, we surveyed what they think are important to hospitalists and what are important compared to that for non-hospitalist generalists. Results: There were 971 participants (733 hospitalist, 238 non-hospitalist) in the study. The response rate was 26.1％. Both hospitalists and non-hospitalists ranked evidence-based medicine as most important for their practice. Hospitalists ranked diagnosis and patient management as the second and third most important roles for their practice while non-hospitalists ranked patient management and elderly care as second and third. Conclusions: This is the first study investigating what roles Japanese hospitalists consider important and compare those to that of non-hospitalist generalists. Many of the items that hospitalists responded to that they actually consider important were those that hospitalists in Japan are actually working on within and outside of academic societies. We found that diagnostic medicine, and quality and safety are likely to be evolved by hospitalists because they specifically emphasized them, while the care of the elderly is an issue that hospitalists should be more concerned about. Future expected research includes proposals on how to further enhance items that hospitalists emphasize and should focus on, as well as international comparisons regarding the items.

Background: When monitoring patients with an intraductal mucinous neoplasm (IPMN), it is important to consider both IPMN-derived carcinoma and concomitant ductal adenocarcinoma (PDAC). The latter is thought to have a poorer prognosis. We retrospectively analyzed risk factors for concomitant PDAC in IPMN.Methods: In total, 547 patients with pancreatic cysts, including IPMN inappropriate for surgery on initial diagnosis, encountered from April 2005 to June 2019, were reviewed. We performed surveillance via imaging examination once or twice a year. Results: There were five intraductal papillary mucinous adenocarcinoma encountered. In comparison, there were 14 concomitant PDAC encountered. The prognosis was very poor in concomitant PDAC. All 14 PDAC patients had IPMN. In patients with IPMN, long-standing diabetes mellitus was the only significant risk factor for concomitant PDAC in both univariate and multivariate analysis ( P < 0.001 and P < 0.01, respectively). Further, patients with IPMN and diabetes mellitus had high frequency of concomitant PDAC (9.5%, 9/95) in a median 48-month surveillance period.Conclusions: When monitoring IPMN, concomitant PDAC should be considered, rather than IPMN-derived carcinoma. During this period, it may be prudent to concentrate on patients with other risk factors for PDAC, such as long-standing diabetes mellitus.

The present study investigated the possible risk factors, including relationship/HLA matching between donor and recipient, and immunosuppressive therapies on the recurrence of primary sclerosing cholangitis (PSC) after liver transplantation (LT). Subjects were 197 recipients of LT for PSC, among whom 180 surviving more than 1 year after LT were further analyzed for risk factors of recurrence. The 5- and 10-year patient- and graft survival rates were 83% and 68%, and 71% and 62%, respectively. The overall PSC recurrence rate was 25% with a 5- and 10-year graft survival rate of 34% and 18%, which was significantly lower than the survival rate of those without recurrence (P 0.001). Univariate analysis identified the following as risk factors for recurrence: donor age (P 0.001), cyclosporine use (P = 0.012), mono or no immunosuppressive agent (P 0.001), postoperative biliary complication (P 0.001), and active intestinal bowel disease after LT (P 0.001). Among these factors, donor age ≥45 years [hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.21-2.69; P = 0.003] and mono or no immunosuppressive agent 1-year after LT (HR, 2.38; 95% CI, 1.23-3.45; P = 0.011) were identified as independent risk factors in the final multivariate Cox regression model. The results were similar in sub-analysis for ABO-identical/compatible adult living donor LT cases.

Background Pancreaticobiliary maljunction and intrahepatic gallstones are at a high risk for biliary malignancy. Lysophosphatidylcholine (LPC) is increased in the bile of these patients, and we have previously reported that LPC-induced cytotoxicity causes senescence-associated secretory phenotype (SASP) in cholangiocytes. We aimed to determine the protective effect of phosphatidylcholine (PC) on LPC-induced cholangiocyte cytotoxicity. Methods MMNK-1, a human immortalized cholangiocyte cell line was treated with LPC with or without PC. To assess the biological effects of SASP components on cholangiocarcinoma, HuH28 and HuCCT1 (human cholangiocarcinoma cell lines) were cultured in the conditioned media where MMNK-1 cells treated with LPC. Results The presence of PC reduced reactive oxygen species generation and oxidative DNA damage in MMNK-1 treated with LPC. Moreover, SA-β-gal activity was markedly downregulated by PC. The secretion of SASP components, including interleukin (IL)-8, IL-6, and C-C motif chemokine ligand 2 was also substantially reduced in the presence of PC. Cellular proliferation and migration were enhanced in HuCCT1 and HuH28 cells when cultured in the conditioned media, and these observations were suppressed by simultaneous addition of PC. Conclusion PC protects cholangiocytes against LPC-induced cytotoxicity and cellular senescence, suggesting its potential as a target for inhibiting LPC-related carcinogenesis and its promotion.

Here, we describe a case of giant cell arteritis (GCA) simultaneously diagnosed with chronic subdural hematoma. In this case, head to chest computed tomography angiography was useful for the diagnosis and treatment of GCA.

A 78-year-old woman with fever of unknown origin that had persisted for 3 months, systemic edema, and cervical lymphadenopathy was admitted to our hospital. Skin purpura and jaw claudication were subsequently observed. Histopathological examinations of the lymph nodes, skin, and temporal artery revealed findings characteristic of eosinophilic granulomatosis with polyangiitis (EGPA). However, she had no past medical history of asthma with modest eosinophilia. Although EGPA is a systemic vasculitis characterized by asthma and eosinophilia, various limited forms have been described. This was therefore considered to be an atypical form of non-asthmatic EGPA complicating with temporal arteritis (TA) diagnosed by tissue biopsy.

Background and aim Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, inflammation, and hepatocellular injury with varying degrees of fibrosis. There are currently no established treatment approaches for NASH other than lifestyle interventions. Periostin, a matricellular protein required for tissue remodeling and fibrosis, plays an important role in hepatic steatosis and fibrosis and could be a potential target for NASH treatment. Advances in molecular biology and biochemical engineering have led to the development of antisense oligonucleotides (ASOs) that can inhibit target genes with no significant toxic effects. Herein, we investigated the therapeutic effects of periostin-targeting ASO (PNASO) in NASH. Methods C57BL/6J mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) to induce NASH with or without intraperitoneal injection of mouse PNASO. To explore the role of periostin in hepatocellular steatosis, Hc3716 cells, an immortalized human hepatocyte line, were treated with recombinant periostin in vitro. Results The induced periostin expression in the liver of CDAHFD-fed mice was significantly suppressed by PNASO. The deletion of hepatic periostin by PNASO significantly ameliorated hepatic steatosis while restoring the expression levels of peroxisome proliferator-activated receptor-alpha (PPAR-α) and its target genes. PNASO also inhibited hepatic fibrosis, reflected by the reduction of alpha-smooth muscle actin, collagen type I, and other fibrotic markers. In vitro experiments demonstrated that treatment with recombinant periostin increased cellular lipid accumulation in Hc3716 cells accompanied with the downregulation of PPAR-α. Conclusions Periostin-targeting ASO is a potential therapeutic approach for the efficient treatment of hepatic steatosis and fibrosis in NASH.

Familial Mediterranean fever (FMF) is the most common genetic autoinflammatory disease, but it has been considered a rare disease in Japan. We herein describe five patients with FMF who were diagnosed both clinically and genetically at a single Japanese institute. A genetic investigation of Mediterranean fever (MEFV) detected heterozygosity for the compound mutations L110P/E148Q (n=2) and L110P/148Q/P369S/R406Q (n=1), and heterozygosity for M694I (n=1) and S503C (n=1). Colchicine prevented febrile attacks and accompanying symptoms in four patients. One patient with an S503C mutation showed resistance. Physicians should be aware of the characteristic symptoms, as well as the more unusual symptoms such as headache, when diagnosing FMF.

Background Fever of unknown origin (FUO) has many possible causes, so detailed history taking and physical examination are required. We identified key diagnostic features of medical history and physical findings for an efficient diagnosis of FUO. Methods A total of 42 consecutive patients (mean age: 50.6±20.3 years) with classic FUO were retrospectively recruited from January 2010 to March 2012. Key diagnostic features were identified from among diagnostic criteria for underlying diseases, indicators for diagnostic tests, and more useful factors for differential diagnosis. Results The mean number of abnormal findings per patient was 5.8 from taking the history and 2.0 from performing physical examination. In addition, the mean number of key diagnostic features identified was 0.7 (14.0%) from history taking and 0.6 (35.0%) from physical examination. The most relevant key diagnostic feature was arthritis, followed by cervical lymphadenopathy, dyspnea (with hypoxia), and ocular symptoms. Conclusion The usefulness of certain features of medical history and physical findings for diagnosing FUO was determined. Focusing on arthritis, cervical lymphadenopathy, dyspnea with hypoxia, and ocular symptoms might improve diagnostic efficiency in patients with FUO.

ObjectiveTo identify the key diagnostic features and causes of fever of unknown origin (FUO) in Japanese patients.DesignMulticentre prospective study.SettingSixteen hospitals affiliated with the Japanese Society of Hospital General Medicine, covering the East and West regions of Japan.ParticipantsPatient aged ≥20 years diagnosed with classic FUO (axillary temperature≥38.0°C at least twice within a 3-week period, cause unknown after three outpatient visits or 3 days of hospitalisation). A total of 141 cases met the criteria and were recruited from January 2016 to December 2017.InterventionJapanese standard diagnostic examinations.Outcome measuresData collected include usual biochemical blood tests, inflammatory markers (erythrocyte sedimentation rate (ESR), C reactive (CRP) protein level, procalcitonin level), imaging results, autopsy findings (if performed) and final diagnosis.ResultsThe most frequent age group was 65–79 years old (mean: 58.6±9.1 years). The most frequent cause of FUO was non-infectious inflammatory disease. After a 6-month follow-up period, 21.3% of cases remained undiagnosed. The types of diseases causing FUO were significantly correlated with age and prognosis. Between patients with and without a final diagnosis, there was no difference in CRP level between patients with and without a final diagnosis (p=0.121). A significant difference in diagnosis of a causative disease was found between patients who did or did not receive an ESR test (p=0.041). Of the 35 patients with an abnormal ESR value, 28 (80%) had causative disease identified.ConclusionsAge may be a key factor in the differential diagnosis of FUO; the ESR test may be of value in the FUO evaluation process. These results may provide clinicians with insight into the management of FUO to allow adequate treatment according to the cause of the disease.

Background Geographical maldistribution of physicians, and their subsequent shortage in rural areas, has been a serious problem in Japan and in other countries. Family Medicine, a new board-certified specialty started 10 years ago in Japan by Japan Primary Care Association (JPCA), may be a solution to this problem. Methods We obtained the workplace information of 527 (78.4%) of the 672 JPCA-certified family physicians from an online database. From the national census data, we also obtained the workplace information of board-certified general internists, surgeons, obstetricians/gynaecologists and paediatricians and of all physicians as the same-generation comparison group (ages 30 to 49). Chi-squared test and residual analysis were conducted to compare the distribution between family physicians and other specialists. Results Five hundred nineteen JPCA-certified family physicians and 137,587 same-generation physicians were analysed. The distribution of family physicians was skewed to municipalities with a lower population density, which shows a sharp contrast to the urban-biased distribution of other specialists. The proportion of family physicians in non-metropolitan municipalities was significantly higher than that expected based on the distribution of all same-generation physicians (p Conclusions Family physicians distributed in favour of rural areas much more than any other specialists in Japan. The better balance of family physician distribution reported from countries with a strong primary care orientation seems to hold even in a country where primary care orientation is weak, physician distribution is not regulated, and patients have free access to healthcare. Family physicians comprise only 0.2% of all Japanese physicians. However, if their population grows, they can potentially rectify the imbalance of physician distribution. Government support is mandatory to promote family medicine in Japan.

BACKGROUND Previous findings on hepatic bile acid compositions in nonalcoholic fatty liver disease (NAFLD) have been inconsistent and complicated. The aim of this study was to investigate the effects of steatosis on hepatic bile acid composition in a hypertensive NAFLD model without obesity and diabetes mellitus and compare hepatic bile acid composition between hypertensive rats with and without steatosis. METHODS Two groups of hypertensive rats were studied: spontaneously hypertensive rats (SHR) fed with a normal diet (SHR-N) or a choline-deficient diet (SHR-CD). Two groups of normotensive rats were studied: Wistar Kyoto rats (WKY) fed a normal diet (WKY-N) or a choline-deficient diet (WKY-CD). Hepatic bile acid analysis was performed using liquid chromatography-electrospray ionization-tandem mass spectrometry. RESULTS Regarding bile acid composition, the hyodeoxycholic acid (HDCA) species in the SHR-CD group showed the largest change in bile acid composition, significantly decreasing to 21.9% of that found in the SHR-N group. In the WKY-CD group, no reduction of HDCA species was observed. CONCLUSIONS We demonstrated that the decrease in HDCA species was the main alteration in a hypertensive NAFLD model. It was suggested that the decrease in HDCA species in the SHR-CD group was caused by dysbiosis.

Purpose To show the practice location of graduates from two Japanese programs recruiting physicians to rural areas: a regional quota program of medical schools and a prefecture scholarship program (a prefecture is an administrative geographic division). Graduates of each program must work in a designated rural prefecture for a fixed period. Method A nationwide cohort study was conducted for three groups of participants graduating between 2014 and 2016: quota graduates without scholarship (quota alone), nonquota graduates with scholarship (scholarship alone), and quota graduates with scholarship. A questionnaire was sent via medical school or prefecture office to each potential subject to collect baseline individual data, including home prefecture and graduation year. Data were connected through physician identification number to the Physician Census 2016 of the Ministry of Health, Labour and Welfare to identify the subjects’ practice location and compared with data for other physicians in the census. Comparisons were conducted with Mann-Whitney and chi-square tests. Results The proportion of physicians working in nonmetropolitan municipalities for quota alone (185/244; 75.8%), scholarship alone (305/363; 84.0%), and quota with scholarship (341/384; 88.8%) was significantly higher than for other physicians (13,299/22,906; 58.1%). Median population density of the municipalities where subjects worked for quota alone (1,042.4 persons per square kilometer), scholarship alone (613.5), and quota with scholarship (547.4) was significantly lower than that for other physicians (3,214.0). These disparities increased with number of years since graduation. Conclusions The regional quota and prefecture scholarship programs succeeded in producing physicians who practiced in rural areas of Japan., This study was funded by the Japanese Ministry of Education, Culture, Sports, Science and Technology KAKENHI Grant-in-Aid for Scientific Research (C), Grant Number (25460803) and (18K10084).

A 37-year-old woman presented to our hospital with mild abdominal pain experienced for 2 months and hepatic nodules in segments 3 and 8. Peripheral blood eosinophilia was observed, and toxocariasis was serologically diagnosed. Seventeen days after the first imaging evaluation, a new lesion was found in segment 9 of the right lung, which was contiguous through the diaphragm to the hepatic nodule in segment 8. After treatment with albendazole, the liver and lung nodules disappeared. We suspect that larvae had directly invaded the lung from the liver, through the diaphragm.

Background Wisteria floribunda agglutinin (WFA)-sialylated mucin core polypeptide 1 (MUC1) was investigated as a new glycoprotein marker for cholangiocarcinoma (CC) using glycoproteomics technologies. In this multicenter study, WFA-sialylated MUC1 levels in serum and bile samples were measured to determine their diagnostic capability in biliary tract carcinoma (BTC) and intrahepatic (Ih) CC. Methods The study included 244 patients with BTC, 59 patients with IhCC, 287 patients with benign biliary tract diseases, and 44 control subjects. Results Serum WFA-sialylated MUC1 levels were significantly higher in patients with either BTC or IhCC than in control subjects and those with benign biliary tract diseases. Patients with IhCC showed higher WFA-sialylated MUC1 levels than patients with tumors at other sites. No significant differences in WFA-sialylated MUC1 levels were found with regard to cancer stage or tissue type. Receiver operating characteristic curve analysis showed that WFA-sialylated MUC1 was superior to carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for the diagnosis of benign biliary tract diseases, BTC, and IhCC, as well as for stage I and II carcinomas. Significantly higher levels of biliary WFA-sialylated MUC1 were observed in BTC/IhCC than in benign biliary tract diseases. The diagnostic capability of biliary WFA-sialylated MUC1 was also superior to that of CA19-9, and diagnostic sensitivity was higher than that of biliary cytology for BTC/IhCC. Conclusions WFA-sialylated MUC1 is a useful novel biomarker for BTC/IhCC. In the future, this measurement should be applied in the clinical setting.

Periostin is a matricellular protein that serves as a ligand for integrins and is required for tissue remodeling and fibrosis. We investigated the role of periostin in hepatic fibrosis and the mechanisms involved. Primary hepatic stellate cells (HSCs) and the HSC-immortalized cell line LX2 were used to study the profibrotic property of periostin and the interaction of periostin with integrins. Wild-type and periostin-deficient (periostin−/−) mice were subjected to two distinct models of liver fibrosis induced by hepatotoxic (carbon tetrachloride or thioacetamide) or cholestatic (3.5-diethoxycarbonyl-1.4-dihydrocollidine) injury. Periostin expression in HSCs and LX2 cells increased in association with their activation. Gene silencing of periostin resulted in a significant reduction in the levels of profibrotic markers. In addition to enhanced cell migration in response to periostin, LX2 cells incubated on periostin showed significant induction of α-smooth muscle actin and collagen, indicating a profibrotic property. An antibody targeting αvβ5 and αvβ3 integrins suppressed cell attachment to periostin by 60 and 30 % respectively, whereas anti-α5β1 antibody had no effect. Consistently, αv integrin-silenced LX2 cells exhibited decreased attachment to periostin, with a significant reduction in the levels of profibrotic markers. Moreover, these profibrotic effects of periostin were observed in the mouse models. In contrast to extensive collagen deposition in wild-type mice, periostin−/− mice developed less noticeable hepatic fibrosis induced by hepatotoxic and cholestatic liver injury. Accordingly, the profibrotic markers were significantly reduced in periostin−/− mice. Periostin exerts potent profibrotic activity mediated by αv integrin, suggesting the periostin–αv integrin axis as a novel therapeutic target for hepatic fibrosis.

BACKGROUND Certain lipid-lowering drugs increase bile lithogenicity. Here we investigated whether long-term administration of ezetimibe, a new class of hypocholesterolemic agents designed to inhibit intestinal cholesterol absorption by inhibiting Niemann-Pick C1-like 1, alters bile lithogenicity in patients with hepatobiliary diseases. METHODS Eleven dyslipidemic patients with gallstones and/or fatty liver diseases were treated with ezetimibe (10 mg/day) for 12 months. Bile samples were collected by nasal endoscopy before and after 3 and 12 months of treatment. Serum and bile lipids and serum metabolic parameters were analyzed. RESULTS Serum levels of campesterol, total cholesterol, and low-density lipoprotein cholesterol were significantly decreased after 3 and 12 months of treatment. In contrast, serum lathosterol levels increased gradually. The lithogenic index of bile was unsaturated and unchanged in patients who were previously and concomitantly receiving ursodeoxycholic acid (UDCA). In patients who were not receiving UDCA, bile was initially supersaturated, but eventually was unsaturated. However, ezetimibe tended to elevate bile lithogenicity in cholecystectomy patients. CONCLUSIONS Long-term treatment with ezetimibe improves lipid metabolism without significantly altering the bile lithogenicity. Therefore, inhibiting intestinal cholesterol absorption in dyslipidemic patients with hepatobiliary diseases is a safe therapeutic strategy without worsening biliary physiology.

Jugular paraganlioma is a benign, slow-growing tumor originating from the paraganglion cells and it is associated with catecholamine secretion. Paragangliomas can secrete Interleukin-6 (IL-6) and present as a systemic inflammatory syndrome; these characteristics have not been previously associated with jugular paragangliomas. A 63-year-old man with a jugular tumor in the skull base was referred to our hospital for an evaluation of pyrexia, back pain, and acute inflammation. His serum IL-6 level was elevated on admission and it decreased after radiotherapy. This is the first known case of a jugular paraganglioma exhibiting systemic inflammatory syndrome.

Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine, in collaboration with four other medical societies, launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines (all clinical questions and recommendations were shown in supplementary information). A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. A total of 108 questions based on nine subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

Background: Since acute abdomen requires accurate diagnosis and treatment within a particular time limit to prevent mortality, the Japanese Society for Abdominal Emergency Medicine in collaboration with four other medical societies launched the Practice Guidelines for Primary Care of Acute Abdomen that were the first English guidelines in the world for the management of acute abdomen. Here we provide the highlights of these guidelines (all CQ and recommendations were shown in supplementary information). Methods: A systematic and comprehensive evaluation of the evidence for epidemiology, diagnosis, differential diagnosis, and primary treatment for acute abdomen was performed to develop the Practice Guidelines for Primary Care of Acute Abdomen 2015. Because many types of pathophysiological events underlie acute abdomen, these guidelines cover the primary care of adult patients with nontraumatic acute abdomen. Results: A total of 108 questions based on 9 subject areas were used to compile 113 recommendations. The subject areas included definition, epidemiology, history taking, physical examination, laboratory test, imaging studies, differential diagnosis, initial treatment, and education. Japanese medical circumstances were considered for grading the recommendations to assure useful information. The two-step methods for the initial management of acute abdomen were proposed. Early use of transfusion and analgesia, particularly intravenous acetaminophen, were recommended. Conclusions: The Practice Guidelines for Primary Care of Acute Abdomen 2015 have been prepared as the first evidence-based guidelines for the management of acute abdomen. We hope that these guidelines contribute to clinical practice and improve the primary care and prognosis of patients with acute abdomen.

Background Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC. Methods We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA. Results We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart. Conclusions We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.

Familial Mediterranean fever (FMF) is the most common genetic autoinflammatory disease, but it has been considered a rare disease in Japan. We herein describe five patients with FMF who were diagnosed both clinically and genetically at a single Japanese institute. A genetic investigation of Mediterranean fever (MEFV) detected heterozygosity for the compound mutations L110P/E148Q (n=2) and L110P/148Q/P369S/R406Q (n=1), and heterozygosity for M694I (n=1) and S503C (n=1). Colchicine prevented febrile attacks and accompanying symptoms in four patients. One patient with an S503C mutation showed resistance. Physicians should be aware of the characteristic symptoms, as well as the more unusual symptoms such as headache, when diagnosing FMF.

A 46-year-old man with severe back pain visited our hospital. Magnetic resonance imaging revealed extensive bone metastasis and rectal wall thickness. Colonoscopy revealed circumferential stenosis with edematous mucosa, suggesting colon cancer. However, histological findings of biopsy specimens revealed inflammatory cells but no malignant cells. The patient underwent endoscopic ultrasound, which demonstrated edematous wall thickness without destruction of the normal layer structure. After unsuccessful detection of neoplastic cells by boring biopsies, we performed endoscopic mucosal resection followed by boring biopsies that finally revealed signet ring cell carcinoma. Herein, we present a case and provide a review of the literature.

Background The disparity in the number of urban and rural physicians is a social problem in Japan. There may also be a disparity in the age of physicians. This study longitudinally examines both geographic and age distributions of physicians. Methods Individual data from the Survey of Physicians, Dentists and Pharmacists in 1994, 2004 and 2014 and municipality data from the National Population Census were used. The 2015 municipality border was applied to all years, and all municipalities were classified into equalsize quintiles based on population density. Both municipalities and physicians were longitudinally observed. Results Between 1994 and 2014, the number of physicians per 100,000 population increased by 31.8% in the most urban group of municipalities and 17.4% in the most rural group. The average age of physicians was highest in the most rural and lowest in the most urban group. The difference in average age between the urban and rural physicians widened from 2.1 years in 1994 to 6.0 years in 2014. This disparity is particularly pronounced among hospital physicians (from 1.5 years in 1994 to 7.6 years in 2014). In the most rural group, the number of hospital physicians younger than 40 years old has decreased by 59.4%, while the number of those 55±70 has grown by 153% and the number older than 70 years old by 41.0%. Between 1994 and 2004, only 23.0% of hospital physicians younger than 40 years old were retained in the most rural group; the retention rate fell to 19.3% between 2004 and 2014, while the rates increased in older physicians. Conclusions The uneven distribution of physicians is increasing in Japan, as is the aging of rural hospital physicians. Shortage of physicians in rural areas may be more serious than that shown as their headcount., This research was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 16K09145 (http://www.jsps.go.jp/english/e-grants/index.html) (KI).

The 3(rd) English edition of the Japanese classification of biliary tract cancers was released approximately 10 years after the 5(th) Japanese edition and the 2(nd) English edition. Since the first Japanese edition was published in 1981, the Japanese classification has been in extensive use, particularly among Japanese surgeons and pathologists, because the cancer status and clinical outcomes in surgically resected cases have been the main objects of interest. However, recent advances in the diagnosis, management and research of the disease prompted the revision of the classification that can be used by not only surgeons and pathologists but also by all clinicians and researchers, for the evaluation of current disease status, the determination of current appropriate treatment, and the future development of medical practice for biliary tract cancers. Furthermore, during the past 10 years, globalization has advanced rapidly, and therefore, internationalization of the classification was an important issue to revise the Japanese original staging system, which would facilitate to compare the disease information among institutions worldwide. In order to achieve these objectives, the new Japanese classification of the biliary tract cancers principally adopted the 7(th) edition of staging system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). However, because there are some points pending in these systems, several distinctive points were also included for the purpose of collection of information for the future optimization of the staging system. Free mobile application of the new Japanese classification of the biliary tract cancers is available via http://www.jshbps.jp/en/classification/cbt15.html.

Background In the reform of specialist training by Japanese Medical Specialty Board, general practice is expected to be one of 19 core specialties. University departments of general practice can play a central role in training board‐certified generalists, but whether they are actually preparing to do so is unknown. Method We sent a questionnaire to 79 universities and requested to forward it to the general practice department. Fifty‐six departments of general practice (37 public and 19 private universities) completed the questionnaire (response rate 71%). Results Fifty‐one (91.9%) universities planned to be the base institutes of certified programs. The annual seats per program ranged from 2 to 20 (median 5). In these 51 university‐based programs, 33 (64.7%) departments provide the general practice II element. Twenty‐eight (54.9%) require the program trainees to belong to the departments (do nyukyoku) and 11 (21.6%) recommend that they do so. Forty‐seven (92.2%) programs had affiliated institutions in rural areas. Thirty‐nine (76.5%) were willing to accept graduates of regional quota (chiikiwaku). Twenty‐nine (56.9%) program directors took into account the obligatory service of regional quota when making the programs. Programs that accept regional quota graduates were more likely to be affiliated with rural institutions (P=.002) and conscious of the obligatory service in making the program than other programs (P

Key Clinical Message Salicylate‐induced acute respiratory syndrome (ARDS) is a well‐known entity occurring in 35% of salicylate‐intoxicated patient. Careful history taking, physical examination, arterial blood gas analysis, and measurement of serum salicylate concentration will lead to early recognition to initiate appropriate treatment.

ObjectivesThis study examined the retention of regional quota graduates of Japanese medical schools and prefecture scholarship recipients within their designated prefectures where they are obliged or expected to work and revealed the personal and regional characteristics associated with their emigration to non-designated prefectures. Regional quota and prefecture scholarship are two of the most ambitious policies ever conducted in Japan for recruiting physicians to practice in rural areas.DesignProspective cohort study.SettingNationwide.ParticipantsRegional quota graduates with prefecture scholarship, quota graduates without scholarship and non-quota graduates with scholarship of Japanese medical schools who obtained their physician license between 2014 and 2016.Primary outcomeThe emigration in 2016 of the participants from the designated prefectures.ResultsTotal participants were 991 physicians, three of whom were excluded due to the missing values of crucial items, leaving 988 participants for analysis (quota with scholarship 387, quota alone 358 and scholarship alone 243). The percentage of those who emigrated was 11.9% (118/988). The mean (±SD) proportion of subjects who emigrated was 11.7% (±10.3) among all prefectures and the proportion varies widely among prefectures (0%–44.4%). Multilevel logistic regression analysis showed those who received prefecture scholarship (OR 0.23; 95% CI 0.08 to 0.67) and whose designated prefecture has an ordinance-designated city (ie, large city) were less likely to emigrate (OR 0.47; 95% CI 0.24 to 0.90). In contrast, graduates from a medical school outside the designated prefecture (OR 4.20; 95% CI 2.20 to 7.67) and who have a right to postpone their obligatory service (OR 3.42; 95% CI 1.52 to 7.67) were more likely to emigrate.ConclusionsA substantial proportion of regional quota graduates and prefecture scholarship recipients emigrated to non-designated prefectures. Emigrations should be reduced by improving the potential facilitators for emigration such as discordance in location between medical school and designated prefecture.

Background We previously conducted nationwide surveys for primary sclerosing cholangitis (PSC) in Japan, and demonstrated several characteristic features of Japanese PSC patients, yet patients with IgG4-related sclerosing cholangitis (IgG4-SC) might be misdiagnosed as PSC. Since the clinical diagnostic criteria of IgG4-SC were established in 2012, we again conducted a nationwide survey to investigate the characteristics of PSC and IgG4-SC lacking pancreatic involvement. Methods The design was a questionnaire-based, multi-center retrospective study. The enrolled subjects were patients with PSC and IgG4-SC without pancreatic involvement diagnosed after 2005. Results We enrolled 197 PSC and 43 IgG4-SC patients without pancreatic lesions. The male dominance was significantly evident in IgG4-SC (P = 0.006). In patients with PSC, two peaks in age distribution were clearly observed. IgG4-SC was not detected in any patient younger than 45 years of age. At presentation, serum albumin and IgM were significantly higher in PSC, while serum IgG and IgG4 were significantly elevated in IgG4-SC. Inflammatory bowel disease (IBD) was detected in only 68/197 PSC patients (34%). The prognosis of IgG4-SC was considerably better than that of PSC. Conclusion We confirmed several interesting clinical details of PSC in Japanese patients: two peaks in the age distribution and lower prevalence of IBD.

OBJECTIVES A Japanese multicenter study of pancreatolithiasis was performed to investigate its clinical features and determine treatment strategies for pancreatolithiasis. METHODS A retrospective study was performed on 916 patients managed in 34 institutions for a period of more than 5 years. RESULTS The treatment methods were extracorporeal shock wave lithotripsy (ESWL) in 479 patients, surgery in 133, and endoscopy alone in 68. Fragmentation of stones after ESWL was achieved in 92.4% of the patients. However, complete stone clearance was achieved in 49.4% of the patients after ESWL alone. The complete stone clearance rate was lower after ESWL than after endoscopy (87.9%). The incidence of early complications was significantly higher after surgery (13.3%) than after ESWL (6.1%). The frequencies of total stone recurrence after ESWL (22.5%) and endoscopy (12.0%) were significantly higher than that after surgery (1.5%). After ESWL (17.6%), abdominal pain recurred significantly more frequently than after surgery (2.2%). Stones and abdominal pain most often recurred within 3 years after ESWL and endoscopy. CONCLUSIONS First-line treatment of pancreatic stones should be ESWL alone or with endoscopy because of its minimal invasiveness and low incidence of early complications. Surgery should be performed on patients in whom ESWL and endoscopy failed.

Cholelithiasis is one of the commonest diseases in gastroenterology. Remarkable improvements in therapeutic modalities for cholelithiasis and its complications are evident. The Japanese Society of Gastroenterology has revised the evidence-based clinical practice guidelines for cholelithiasis. Forty-three clinical questions, for four categories—epidemiology and pathogenesis, diagnosis, treatments, and prognosis and complications—were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases for the period between 1983 and June 2012. The guidelines were developed with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. This article preferentially describes the clinical management of cholelithiasis and its complications. Following description of the diagnosis performed stepwise through imaging modalities, treatments of cholecystolithiasis, choledocholithiasis, and hepatolithiasis are introduced along with a flowchart. Since there have been remarkable improvements in endoscopic treatments and surgical techniques, the guidelines ensure flexibility in choices according to the actual clinical environment. The revised clinical practice guidelines are appropriate for use by clinicians in their daily practice.

Background & Aims Immunoglobulin G4 sclerosing cholangitis (IgG4-SC) is a biliary tract manifestation of IgG4-related systemic disease. We investigated the demographics, clinical features at presentation, treatment response, and outcomes of IgG4-SC using data from a large-scale survey in Japan. Methods We performed a retrospective cohort study of 527 patients with IgG4-SC (436 female; median age, 66.2 years; range, 23–89 years) in Japan from 2000 to 2015. Data on patient demographics, presentation, treatment response, and outcomes were collected from questionnaires given to patients at 211 referral centers in Japan in 2015. Patients were diagnosed with IgG4-SC based on the clinical diagnostic criteria established by the Japanese Biliary Association in 2012. Patients were followed for a median of 4.1 ± 3.1 years. Survival was assessed using the Kaplan-Meier curve and log-rank test. Results Symptoms at presentation included jaundice (35% of patients) and pruritus (13% of patients); 28% of patients were asymptomatic. It was extremely rare for patients with IgG4-SC to present with symptoms of decompensated cirrhosis. At presentation, serum levels of IgG4 were increased (>135 mg/dL) in 84% of patients. Response to prednisolone was excellent in 90% of patients. No patients received liver transplants, and cholangiocarcinoma was found in only 4 patients (0.7%). Restenosis of bile ducts was observed in 19% of patients but did not affect overall survival. Conclusions In a retrospective cohort study of 527 patients with IgG4-SC in Japan, we found the disease to be benign. Most patients (90%) respond to treatment with prednisolone and few develop decompensated cirrhosis or cholangiocarcinoma.

Aim The present study examined whether social support, informal socializing and social participation are associated with glycemic control in older people. Methods Data for this population-based cross-sectional study was obtained from the Japan Gerontological Evaluation Study (JAGES) 2010 linked to the annual health check-up data in Japan. We analyzed 9,554 individuals aged ≥65 years without the certification of needed long-term care. Multivariate logistic regression models were used to assess the effect of social support, informal socializing and social participations on glycemic control. The outcome measure was HbA1c ≥8.4%. Results 1.3% of the participants had a level of HbA1c over 8.4%. Better glycemic control was significantly associated with meeting with friends one to four times per month (odds ratio [OR] 0.51, 95% confidence interval [CI]0.30-0.89, compared to meeting with friends a few times per year or less) and participation in sports groups (OR 0.50, 95% CI 0.26-0.97) even after adjusting for other variables. Meeting with friends more than twice per week, receiving social support, and being married were not associated with better control of diabetes. Conclusions Meeting with friends occasionally is associated with better glycemic control among older people.