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BACKGROUND/AIMS: Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people. METHODS: A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire. RESULTS: The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS (P for trend = 0.018). CONCLUSION: Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.

DOI： 10.5056/jnm23015

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Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens. C16 suppressed the proliferation of CRC cells. Gene Ontology (GO) analysis revealed that the cell cycle-related GO category was substantially enriched in CRC cells treated with C16. C16 treatment resulted in G1 arrest and increased p21 protein and mRNA expression. Moreover, p21 expression was associated with CRC development as observed using immunohistochemical analysis of human CRC tissues. C16 upregulates p21 expression in CRC cells to regulate cell cycle and suppress tumor growth. Thus, PKR inhibitors may serve as a new treatment option for patients with CRC.

DOI： 10.1038/s41598-024-59671-7

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The association between ulcerative colitis (UC) and erectile dysfunction (ED) has been previously reported. Numerous previous studies have also reported an association between gastrointestinal symptoms and ED. Constipation and diarrhea are common in patients with UC. However, the specific association between bowel movement frequency and ED remains unclear. The aim of this study is to investigate the association between bowel movement frequency and ED in 164 patients with UC. The definition of ED, moderate to severe ED, and severe ED was the Sexual Health Inventory for Men score <22, <12, and <8, respectively. Bowel movement frequency was divided into three categories: (1) high (More than once a day), (2) normal (once a day, reference), and low (less than one time/day). The definition of constipation was based on the Rome I criteria and/or medication for constipation. The prevalence of constipation and ED was 10.4% and 86.0%, respectively. The rate of high, normal, and low bowel movement frequency was 56.1%, 25.0%, and 18.9%, respectively. High bowel movement frequency was independently and positively associated with ED and moderate to severe ED (ED: adjusted odds ratio [OR] 4.42, 95% confidence interval [CI] 1.35-15.98; moderate to severe: adjusted OR 2.98, 95% CI 1.22-7.61). Low bowel movement frequency was independently and positively associated with moderate to severe ED and severe ED (moderate to severe: adjusted OR 3.96, 95% CI 1.27-13.08; severe: adjusted OR 3.20, 95% CI 1.08-9.86). No association between constipation and ED was found. In conclusion, in Japanese patients with UC, both high and low bowel movement frequency were independently and positively associated with ED.

DOI： 10.1038/s41443-024-00884-9

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BACKGROUND: Constipation is a common gastrointestinal symptom in patients with ulcerative colitis (UC). Several studies on the general population have demonstrated a link between allergic diseases and constipation. However, evidence regarding the association between allergic diseases and constipation in UC is limited. This study aims to evaluate this issue in Japanese patients with UC. METHODS: This cross-sectional study recruited consecutive 387 patients with UC. We used a self-administered questionnaire to estimate the prevalence of physician-diagnosed allergic diseases. The definition of constipation was based on Rome I criteria and/or medication for constipation. RESULTS: The prevalence of constipation was 12.5%. The prevalence rates of asthma, atopic dermatitis, pollen allergy, food allergy, and drug allergy were 11.8%, 9.0%, 36.3%, 6.2%, and 8.3%, respectively. Allergic diseases were not associated with constipation (adjusted odds ratio [OR] with asthma (adjusted OR 0.98 [95% confidence interval [CI] 0.27-2.80]), atopic dermatitis (adjusted OR 0.67 [95% CI 0.10-2.56]), pollen allergy (adjusted OR 0.92 [95% CI 0.41-1.97]), food allergy (adjusted OR 0.76 [95% CI 0.11-2.95]), and drug allergy (adjusted OR 1.06 [95% CI 0.28-3.24]). Additionally, the number of allergic diseases was not associated with the prevalence of constipation. CONCLUSIONS: In Japanese UC patients, no association between allergic diseases and constipation was found.

DOI： 10.7759/cureus.55912

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BACKGROUND: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. METHODS: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%. RESULTS: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. CONCLUSION: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

DOI： 10.4093/dmj.2023.0200

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Socioeconomic status is a risk factor for poor disease prognosis. No studies of patients with ulcerative colitis (UC) have investigated the association between socioeconomic status and erectile dysfunction (ED), although UC is independently positively associated with ED. Therefore, the purpose of this survey to evaluate this issue in Japanese patients with UC. The study enrolled 165 patients with UC. Education status (low, middle, high) and household income (low, middle, high) were classified in three groups using self-administered surveys. The information regarding the Sexual Health Inventory for Men (SHIM) was obtained using self-administered questionnaires. The definition of mild to moderate or severe ED and severe ED was SHIM score <17 and SHIM score <8, respectively. The prevalence of mild to moderate or severe ED and severe ED was 64.9% and 47.9%, respectively. In crude analysis, household income was inversely associated with mild to moderate or severe ED and severe ED. After adjustment for age, current drinking, current smoking, exercise habit, body mass index, mucosal healing, and duration of UC, high household income was independently and inversely associated with mild to moderate or severe ED (adjusted odds ratio [OR] 0.23, 95% confidence interval [CI] [0.05, 0.93], p for trend = .038) and severe ED (adjusted OR 0.26, 95% CI [0.07, 0.85], p for trend = .024). In contrast, no association between education status and ED was found. In conclusion, household income was independently and inversely associated with ED in Japanese UC patients.

DOI： 10.1177/15579883241256833

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INTRODUCTION: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese. METHODS: Overall, 4693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders. RESULTS: The prevalence of IBS was 6.1%. Moderate (adjusted odds ratio [OR]: 1.89 [95% confidence interval (CI): 1.27-2.91]) and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain was independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS. CONCLUSION: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS.

DOI： 10.1159/000533264

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OBJECTIVE: To investigate the association between nocturia and constipation in patients with ulcerative colitis (UC). Constipation has recently been recognized as an important symptom in patients with UC. Although nocturia has been associated with constipation in the general population, the association between nocturia and constipation in UC patients is uncertain. METHODS: Consecutive series of 290 Japanese patients with UC, Information on constipation, nocturia, and lifestyle habits was obtained using self-administered questionnaires. The definition of constipation was based on Rome I criteria and/or current medication for constipation. Patients were divided into three groups based on nighttime urination: 1) no nocturia, 2) mild nocturia (nocturnal urination - one), and 3) serious nocturia (nocturnal urination - two or more). Multivariate logistic regression was used to evaluate the association between nocturia and constipation. RESULTS: Among all of the UC patients, the prevalence of mild nocturia, serious nocturia, and constipation was 35.2%, 26.9%, and 12.4%, respectively. The prevalence of constipation in the none, mild, and serious nocturia groups was 8.2%, 10.8%, and 20.5%, respectively. After adjustment for confounders such as age, sex, current drinking, current smoking, body mass index, and steroid use, nocturia severity was independently and positively associated with constipation (adjusted odds ratio for mild nocturia: 1.55 [95% confidence interval: 0.57-4.28], serious nocturia: 3.19 [95% confidence interval: 1.09-9.81], p for trend = 0.035). CONCLUSIONS: The severity of nocturia is positively associated with constipation, and physicians should consider the interrelationships between nocturia and constipation in managing UC patients.

DOI： 10.1016/j.urology.2023.07.035

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OBJECTIVE: Evidence regarding the association between exercise habits and irritable bowel syndrome (IBS) remains scarce in a young population. It is also unknown whether the existence of an exercise partner affects this issue. The purpose of this study was to explore the association between exercise habits that include an exercise partner and IBS in a young Japanese population. METHODS: This study enrolled 8923 Japanese university students and examined exercise frequency and intensity, and exercise partners using self-administered questionnaires. IBS and functional dyspepsia were defined according to the Rome III criteria. RESULTS: The prevalence of IBS in this survey was 6.5%. Moderate frequency exercise was inversely related with IBS [adjusted odds ratio (aOR): 0.65 (95% confidence interval, CI: 0.51-0.83), P for trend = 0.005]. Moderate and high exercise intensities were independently and inversely related with IBS, respectively [aORs were moderate: 0.76 (95% CI: 0.61-0.95) and high: 0.62 (95% CI: 0.48-0.78), P for trend = 0.001]. Exercising with a group or with friends instead of alone was independently inversely related with IBS [aOR with groups: 0.53 (95% CI: 0.40-0.70) and with friends: aOR 0.71 (95% CI: 0.54-0.93)]. After excluding subjects with overlapping IBS and functional dyspepsia, an inverse association between high intensity of exercise or exercise in a group and IBS remained significant. CONCLUSION: The frequency and intensity of exercise may be independently inversely related with IBS in a young Japanese population. Also, exercise with others may be important for preventing IBS.

DOI： 10.1097/MEG.0000000000002561

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AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

DOI： 10.1111/hepr.13925

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BACKGROUND: The association between disease activity and erectile dysfunction (ED) in patients with inflammatory bowel disease (IBD) is inconsistent, although IBD, including ulcerative colitis (UC), is reported as a risk factor for ED. AIM: The purpose of this study was to explore this association in Japanese patients with UC. METHODS: In this study, we enrolled 165 Japanese male patients with UC. Information regarding the Sexual Health Inventory for Men (SHIM) score, medication, and severity of UC was obtained from medical records, self-administered questionnaires, and reports from physicians. The definition of ED and severe ED is a SHIM score <17 and <8, respectively. OUTCOMES: No association between severity of UC and ED was found in Japanese patients. Aging is independently positively associated with ED in patients with UC. RESULTS: The prevalence of severe ED and ED was 47.9% and 64.9%, respectively. In this study, mucosal healing, clinical remission, duration of UC, disease extent, and medication were not associated with the prevalence of ED. Older age (≥63 years of age) was independently positively associated with ED (adjusted odds ratio, 12.93; 95% CI: 4.51-43.00) and severe ED (adjusted odds ratio, 9.02; 95% CI: 3.66-23.91). CLINICAL IMPLICATIONS: Disease severity of UC might not be associated with the prevalence of ED in patients with UC. STRENGTHS AND LIMITATIONS: This is the first study to investigate the association between several factors regarding UC activity and ED. The limitation of this study is the definition of ED based on SHIM scores. CONCLUSION: No association between severity of UC and ED was found in Japanese patients. As expected, aging may be independently positively associated with ED in patients with UC.

DOI： 10.1093/sexmed/qfad024

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

【緒言】がん病態栄養専門管理栄養士の配置による、がん患者の入院中の栄養状態に及ぼす効果について明らかにすることを目的とした。【方法】2015年4月1日から2021年3月31日に当院に入院した胃がん患者858名を対象とし、がん病態栄養専門管理栄養士の配置体制がなかった配置前群376名と配置後群482名の食事摂取割合および体重変化率を後ろ向きに比較検討した。【結果】退院時食事摂取割合は、配置前群56.7±23.2%から配置後群62.2±25.0%と有意に増加した(p=0.001)。また、入院中の体重変化率は配置前群-3.1±4.6%から配置後群-2.3±4.6%と有意な体重減少の抑制を認めた(p=0.015)。【考察】がん病態栄養専門管理栄養士を配置することにより、胃がん患者の入院治療に伴う食事摂取量の低下ならびに体重減少を抑制し、がん患者の円滑な治療の推進に寄与できる可能性が示唆された。(著者抄録)

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DOI： 10.14309/ajg.0000000000001982

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Aim: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. Methods: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. Results: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. Conclusions: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

DOI： 10.1111/hepr.13925

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INTRODUCTION: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC. METHODS: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0-1, respectively. RESULTS: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04-6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22-11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia. CONCLUSIONS: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C.

DOI： 10.1159/000527353

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Restless legs syndrome (RLS) is a common sleep disorder in the Western population. The prevalence of restless legs syndrome in the Japanese population is 4.6%. Inflammatory and/or immune alteration might be associated with the development of restless legs syndrome. Ulcerative colitis is a chronic inflammatory bowel disease. Evidence regarding the association between ulcerative colitis and the prevalence of restless legs syndrome is limited. Herein, we investigated the association between clinical outcomes and the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis. This was a cross-sectional study using baseline data from a prospective cohort study. Subjects in this study were 273 patients with ulcerative colitis. The definition of restless legs syndrome was achieved using a self-administered questionnaire based on the diagnostic criteria for restless legs syndrome in an epidemiological study approved by the Executive Committee of the International Restless Leg Syndrome Study Group in 2002. Clinical outcomes were clinical remission and mucosal healing. The association between clinical remission and mucosal healing and the prevalence of restless legs syndrome was assessed by multivariate logistic regression analyses. The percentage of clinical remission and mucosal healing was 58.4% and 63.1%, respectively. The prevalence of restless legs syndrome in this cohort was 4.7%. Clinical remission (adjusted odds ratio 0.23, 95% confidence interval 0.05-0.93) and mucosal healing (adjusted odds ratio 0.23, 95% confidence interval 0.05-0.90) were independently inversely associated with restless legs syndrome. No association between serum haemoglobin and restless legs syndrome was found. In conclusion, clinical remission and mucosal healing were independently and inversely associated with the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis.

DOI： 10.1111/jsr.13691

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PURPOSE: The association between body mass index (BMI) and irritable bowel syndrome (IBS) has been inconsistent in the Asian population. Also, no evidence regarding this issue in the young population exists. The aim of the present study is to investigate the association between BMI and IBS based on the Rome III criteria in young Japanese people. METHODS: This study was a cross-sectional study consisted of 8923 Japanese university students. The definition of IBS was based on the Rome III criteria. BMI was divided into four categories (quartiles) on the basis of the study subjects' distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, and overweight was BMI < 18.5 kg/m2, 18.5 ≤ BMI < 25 kg/m2 (reference), and 25 ≤ BMI kg/m2, respectively. Age, sex, drinking, smoking, exercise habit, anemia, and sports injury were selected a priori as potential confounding factors. RESULTS: The prevalence of IBS was 6.5%, with females having a significantly higher prevalence than males (6.0% vs. 7.2%, p = 0.029). In females, being overweight was independently positively associated with IBS after adjustment (adjusted odds ratio [OR]: 1.81 [95% confidence interval (CI): 1.13-2.79]). In contrast, in males, no association between being lean or overweight and IBS was found. CONCLUSIONS: Among the young Japanese population, being overweight might be independently positively associated with prevalence of IBS in females but not in males.

DOI： 10.1007/s00384-022-04267-8

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The incidence of inflammatory bowel disease (IBD) is increasing; hence, effective treatments are warranted. The therapeutic effect of human carbonic anhydrase I (hCA I) in IBD remains unknown. Therefore, we investigated whether oral tolerization to hCA I would induce antigen-specific protection from intestinal inflammation in vivo. Severe combined immunodeficient mice received hCA I, keyhole limpet hemocyanin (KLH), or phosphate-buffered saline (PBS) orally for 7 days. Colons and mesenteric lymph nodes (MLNs) were collected 4 weeks after cell transfer. Additionally, the mechanisms underlying the therapeutic effects were investigated. The comparison between the effects of well-established drugs and hCA I oral administration was investigated. Oral administration of hCA I ameliorated colitis remarkably. hCA I reached the cecum and ameliorated colitis more effectively than mesalazine and similarly to prednisolone. Compared with PBS treatment, hCA I treatment reduced interleukin (IL)-17a, IL-6, and retinoic acid-related orphan receptor gamma t (RORγt) expression in the colon or MLNs; moreover, hCA I markedly reduced IL-6, IL-17, and interferon-gamma (IFN-γ) levels in the MLN. Oral administration of hCA I induced immune tolerance and suppressed colitis in vivo. Thus, hCA I administration could be proposed as a new treatment option for IBD.

DOI： 10.1038/s41598-022-22455-y

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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OBJECTIVE: Socioeconomic status is a risk factor for worse outcomes in many diseases. However, evidence on the association between socioeconomic status and clinical outcome in patients with ulcerative colitis (UC) is limited. In the clinical setting, the therapeutic goal for UC is to achieve mucosal healing (MH). Thus, the aim of this study is to examine the association between socioeconomic status and MH in patients with UC. METHODS: The study population consisted of 298 patients with UC. Education status and household income were divided into three groups based on a self-administered questionnaire. MH and complete MH were defined as a Mayo endoscopic subscore of 0-1 and 0, respectively. The association of socioeconomic status with MH and complete MH was assessed by multivariate logistic regression analysis. Patients with UC were divided into a younger group (<51 years old) and an older group (≥51 years old) based on median age. RESULTS: The percentage of MH and complete MH was 62.4% and 25.2%, respectively. In all patients, socioeconomic status was not associated with MH and complete MH, respectively. In the older group, education but not household income was independently positively associated with MH and complete MH. In contrast, in the younger group, no association between socioeconomic status and MH and complete MH was found. CONCLUSION: In older Japanese patients with UC, education status but not household income was independently positively associated with MH and complete MH.

DOI： 10.1136/bmjgast-2022-001000

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Background/Aims: Functional dyspepsia (FD) may be a common digestive disease worldwide and reduces the quality of life of patients. However, only a few studies have investigated the association between eating behavior and FD. The purpose of this cross-sectional study is to examine the association between eating behavior and prevalence of FD in a young Japanese cohort. Methods: In this study, we enrolled 8923 Japanese university students. FD is diagnosed based on the Rome III criteria. Eating habits and frequency of meals were investigated using a self-administered questionnaire. Results: The FD subjects had a younger mean age, a lower body mass index, and a lower proportion of men compared to the non-FD subjects. An independent positive association between skipping breakfast and/or lunch and FD was found (adjusted ORs were 1.60 [95% CI, 1.10-2.32] for breakfast and 2.52 [95% CI, 1.04-5.18] for lunch). Skipping dinner, extra meals (snacks) or midnight snacks was not associated with FD. The prevalence of FD in subjects eating 1, 2, and 3 meals per day was 4.8%, 2.2%, and 1.7%, respectively. The frequency of meals was independently inversely associated with prevalence of FD (adjusted ORs were 1 per day: 2.72 [95% CI, 1.19-5.42], and 2 per day: 1.69 [95% CI, 1.16-2.43], P for trend = 0.001). Conclusions: In the young Japanese people, the frequency of meals may be independently inversely associated with prevalence of FD. In particular, skipping breakfast and/or lunch was associated with the prevalence of FD.

DOI： 10.5056/jnm21146

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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BACKGROUND: The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk. METHODS: There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008). CONCLUSIONS: IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

DOI： 10.1016/j.cyto.2022.155901

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DOI： 10.1055/a-1858-4826

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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The potential health benefits of laughter are recognized in relation to several chronic diseases. However, no study has yet investigated the association between laughter and functional dyspepsia (FD). The purpose of this study was to investigate this issue in a young Japanese population. METHODS: This study was conducted on 8923 Japanese university students. Information on the frequency of laughter and types of laughter-inducing situations, digestive symptoms (Rome III criteria) were obtained through a self-administered, web-based questionnaire. RESULTS: The percentage of respondents who laughed out loud almost every day was 64.3%. On the other hand, 1.8% of the subjects reported that they rarely laughed. No association was found between the total frequency of laughter and FD. Laughing while talking with family and friends almost every day was significantly inversely associated with FD (adjusted odds ratio (OR): 0.47 (95% confidence interval (CI): 0.28-0.81); p for trend was 0.003). On the other hand, laughing while watching TV or videos and laughing while looking at comics or magazines independently showed a positive correlation with FD (TV or videos: adjusted OR, 1-5 times a week: 1.74 (95% CI: 1.16-2.60); comics or magazines: adjusted OR, 1-5 times a week: 1.78 (95% CI: 1.08-2.81)). CONCLUSION: In this young Japanese population, no association between laughter frequency and FD was observed although laughing while talking with friends and family was independently and inversely associated with FD.

DOI： 10.3390/ijerph19095686

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Background/Aims: Evidence regarding the association between body mass index (BMI) and functional dyspepsia (FD) in the Asian population is limited. Further, no study has evaluated this issue in young people in Asian and Western populations. Thus, we aim to investigate this issue among young Japanese people. Methods: The study subjects comprised of 8923 Japanese university students. BMI was divided into 4 categories (quartiles) on the basis of the study subjects' distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, overweight, and obese was BMI < 18.5 kg/m2, 18.5 ≤ BMI < 25 kg/m2 (reference), 25 kg/m2 ≤ BMI < 30 kg/m2, and 30 kg/m2 ≤ BMI, respectively. The definition of FD was based on the Rome III criteria. Results: The prevalence of FD was 1.9% in this cohort. The lowest BMI was independently associated with FD after adjustment (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.46-3.67); P for trend = 0.001). The lowest BMI was independently associated with FD in women but not in men (OR, 2.94; 95% CI, 1.59-5.77; P for trend = 0.001). Leanness was independently associated with FD in total and in women but not in men (total: adjusted OR, 2.01; 95% CI, 1.40-2.86) and women (OR, 2.19; 95% CI, 1.35-3.45). However, interaction analysis showed no significant difference for sex. Conclusions: Among young Japanese people, BMI may be independently inversely associated with FD. Leanness may be an independent associated factor for FD in the young Japanese women.

DOI： 10.5056/jnm21076

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AIMS: To investigate whether fibrosis-4 index can help stratify the risk of diabetes mellitus in subjects with fatty liver disease. METHODS: Based on fatty liver disease and fibrosis-4 index (cutoff value, 1.3), we retrospectively divided 9,449 subjects, who underwent at least two annual health checkups, into four groups stratified by gender: normal, high fibrosis-4 indexwithout fatty liver disease, low fibrosis-4 index with fatty liver disease, and high fibrosis-4 index with fatty liver disease groups. RESULTS: Onset rates for diabetes mellitus in the normal, high fibrosis-4 index without fatty liver disease, low fibrosis-4 index with fatty liver disease, and high fibrosis-4 index with fatty liver disease groups were 1.6%, 4.3%, 6.8%, and 10.2%, respectively, in men, and 0.6%, 0.9%, 5.3%, and 7.0%, respectively, in women. Compared with the normal group, the high fibrosis-4 index without fatty liver disease, low fibrosis-4 index with fatty liver disease, and high fibrosis-4 index with fatty liver disease groups were at a significant risk for diabetes mellitus onset in both male and female subjects. Moreover, in both genders, high fibrosis-4 index with fatty liver disease remained a significant risk factor on multivariate analysis (high fibrosis-4 index with fatty liver disease group: adjusted harzard ratio, 95% confidence interval: 4.03, 2.19-7.42 [men] and 6.40, 1.77-23.14 [women]). CONCLUSIONS: Subjects with fatty liver disease and high fibrosis-4 index had a higher risk of diabetes mellitus onset. Therefore, fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease and identify patients requiring intervention.

DOI： 10.1111/jdi.13812

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Language：Japanese   Publisher：(有)科学評論社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Purpose: The albumin-to-globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC. Methods: The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52-14.18 and adjusted OR, 4.97; 95% CI, 2.14-12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56-11.51 and adjusted OR, 5.22; 95% CI, 1.97-14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06-21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found. Conclusion: Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.

DOI： 10.3393/ac.2021.01032.0147

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction-associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM. MATERIALS AND METHODS: We retrospectively assessed 9,459 participants who underwent two or more annual health check-ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non-overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants). RESULTS: The DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre-diabetes (P < 0.01). CONCLUSIONS: Fatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.

DOI： 10.1111/jdi.13772

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

【目的】高齢早期胃癌・内視鏡的非治癒切除例において、追加手術と低骨格筋量の予後への影響を明らかにする。【方法】内視鏡的根治度C-2と判定された75歳以上の早期胃癌患者55例を、追加手術の有無で検討した。また、サルコペニア関連因子としてCTで測定したPsoas muscle mass index(PMI)を用い、予後との関連を評価した。【結果】再発率は、両群間で差がなかった。腸腰筋体積は、追加手術群で経年的減少が見られた。予後は、追加手術の有無で差はなく、ESD3年後の低PMI群において予後不良傾向を認めた(P=0.068)。【結論】高齢早期胃癌において、予後は術後低栄養との関連が示唆された。(著者抄録)

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BACKGROUND: A simple serum biomarker for clinical outcome in patients with ulcerative colitis (UC) remains an unmet need. Some studies have shown an association between C-reactive protein (CRP)-albumin ratio (CAR) and prognosis in patients with inflammatory bowel disease (IBD), but evidence regarding the association between CAR and UC remains limited. We evaluated the association between CAR and clinical outcome in Japanese patients with UC. METHODS: Subjects were 273 Japanese patients with UC. Clinical remission was defined as absence of both abnormally high stool frequency (< 3 per day) and rectal bleeding. Mucosal healing (MH) was defined as Mayo endoscopic subscore (MES) 0. Moderate to severe endoscopic activity was defined as MES 2-3. Subjects were divided according to CAR into tertiles (low, moderate, and high). RESULTS: The proportions of patients with clinical remission, MH, and moderate to severe endoscopic activity were 57.9%, 26.0%, and 37.0%, respectively. High CAR was significantly positively associated with moderate to severe endoscopic activity but not MH or clinical remission after adjustment (adjusted odds ratio [OR] 2.18 [95% confidence interval (CI) (1.11-4.35)], p for trend 0.023), but only in patients with long disease duration (> 7 years) (adjusted OR 2.95 [95% CI (1.06-8.79)], p for trend 0.023). CAR was not associated with clinical remission or MH. CONCLUSIONS: CAR may be significantly positively associated with moderate to severe endoscopic activity but not clinical remission or MH in Japanese patients with UC. In patients with long UC duration, CAR might be a useful serum marker for disease activity.

DOI： 10.1186/s12876-022-02113-3

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BACKGROUND: Functional dyspepsia (FD) is a very common disease worldwide. Dysmenorrhea impairs quality of life among females of reproductive age. Although dysmenorrhea is associated with irritable bowel syndrome (IBS), no study has yet evaluated the association between dysmenorrhea and FD. METHODS: This study's subjects consisted of 4693 female Japanese university students. We defined FD according to the Rome III criteria. Subjects completed a self-reported questionnaire regarding menstrual irregularity, menstrual pain, and medication for menstrual pain. Age, body mass index, drinking, smoking, exercise habit, anemia, and first-year student status were selected as potential confounding factors. RESULTS: The prevalence of FD, epigastric pain syndrome (EPS), and postprandial distress syndrome (PDS) was 2.5%, 0.6%, and 2.1%, respectively. Heavy menstrual pain was independently positively associated with FD and PDS but not EPS (adjusted ORs: FD, 3.18 [95% CI: 1.60-6.89] and PDS, 2.93 [95% CI: 1.56-7.93] for heavy menstrual pain, p for trend = 0.001 and 0.004, respectively). Using medication for menstrual pain often was independently positively associated with FD, EPS, and PDS, respectively, (adjusted ORs: FD, 2.41 [95% CI: 1.50-3.83], EPS, 2.93 [95% CI: 1.04-7.93], PDS, 2.44 [95% CI: 1.46-4.01]). Irregular menstrual cycle was not associated with FD or with subtype of FD. CONCLUSION: Among the young female Japanese population, menstrual pain might be independently positively associated with FD and PDS but not EPS. The use of medication for menstrual pain might be independently positively associated with FD including subtype of FD.

DOI： 10.1111/nmo.14324

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

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BACKGROUND AND AIM: Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. METHODS: A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past 4 years and 665 controls. RESULTS: Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). CONCLUSIONS: We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

DOI： 10.1111/jgh.15745

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INTRODUCTION: Monocytes play an important role in innate immunity. Some epidemiological evidence indicates an association between peripheral blood monocytes and ulcerative colitis (UC). The association between peripheral blood monocytes and mucosal healing (MH), however, remains unclear. We evaluated this issue in patients with UC. METHODS: Study subjects consisted of 272 Japanese patients with UC. Monocyte counts were taken in the morning after overnight fasting. Monocyte count was divided into tertiles based on the distribution of values among all study subjects. Information on clinical remission was obtained from medical records. MH was assessed using the Mayo endoscopic subscore. RESULTS: The mean monocyte count was 360.1 ± 155.3/mm3. Rates of clinical remission, MH, and complete MH were 61.0%, 66.2%, and 27.9%, respectively. High monocyte count was significantly inversely associated with clinical remission, MH, and complete MH (adjusted odds ratio [OR] 0.45 [95% confidence interval [CI]: 0.23-0.89], OR 0.45 [95% CI: 0.23-0.89], and OR 0.48 [95% CI: 0.23-0.97], respectively). Patients were also classified according to C-reactive protein (CRP) levels; in the low CRP group (<0.1 mg/dL), high monocyte count was independently inversely associated with complete MH but not with clinical remission or MH (OR 0.33 [95% CI: 0.10-0.92], P for trend = 0.027). In the high CRP group, there was no association between monocyte count and clinical outcomes. DISCUSSION: Our findings suggest that peripheral blood monocyte count can be used as a serum supplemental marker for MH in UC patients with low CRP levels.

DOI： 10.14309/ctg.0000000000000429

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OBJECTIVES: Oxidative stress is considered one of the etiologic factors involved in ulcerative colitis (UC), yet there is limited epidemiologic information regarding the relationship between antioxidant intake and the risk of UC. The aim of the present case-control study in Japan was to examine the association between intake of green and yellow vegetables, other vegetables, fruit, vitamin C, vitamin E, retinol, alpha-carotene, beta-carotene, and cryptoxanthin and UC risk. METHODS: A total of 384 cases within 4 y of diagnosis with UC and 665 controls were included in the study. Data on dietary intake and confounders were obtained using a self-reported questionnaire. Information on dietary factors was collected using a 169-item semiquantitative food-frequency questionnaire. Adjustment was made for sex, age, pack-y of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index. RESULTS: Higher intake levels of other vegetables, vitamin C, and retinol were independently associated with a reduced risk of UC. The adjusted odds ratio between extreme quartiles was 0.51 (95% confidence interval [CI], 0.34-0.76; P for trend ≤ 0.001) for other vegetables, 0.45 (95% CI, 0.30-0.69, P for trend ≤ 0.001) for vitamin C, and 0.64 (95% CI, 0.43-0.95, P for trend = 0.04) for retinol. There were no associations between intake of green and yellow vegetables, fruit, vitamin E, alpha-carotene, beta-carotene, or cryptoxanthin and UC risk (P for trend = 0.29, 0.56, 0.89, 0.20, 0.69, and 0.22, respectively). CONCLUSIONS: Intake of other vegetables, vitamin C, and retinol was inversely associated with UC risk.

DOI： 10.1016/j.nut.2021.111378

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BACKGROUND: Evidence regarding the association between sleep disturbance and functional dyspepsia (FD) remains limited in the young population. AIMS: This study aimed to investigate the association between sleep disturbance and FD including subgroups among Japanese young people. METHODS: Study subjects were 8923 university students. FD was defined according to the Rome III criteria. Subjects with FD were further categorized as having postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS). Subjects completed a self-reported questionnaire assessing self-reported sleep duration, sleep disturbance, difficulty falling asleep, deep sleep disorder, nocturnal awakening, early awakening, and daytime sleepiness. RESULTS: The prevalence of FD was 1.9%. After adjustment, all types of sleep disturbances were independently positively associated with FD (total sleep disturbance: OR 4.11 [95% CI: 2.89-5.78], difficulty falling asleep: OR 3.97 [95% CI: 2.53-6.01], deep sleep disorder: OR 4.85 [95% CI: 3.06-7.40], nocturnal awakening: OR 4.35 [95% CI: 1.90-8.67], early awakening: OR 4.50 [95% CI: 1.97-8.97], and daytime sleepiness: OR 2.83 [95% CI: 1.25-5.56]). While nocturnal awakening and daytime sleepiness were not associated with EPS, the other types of sleep disturbance were independently positively associated with EPS and PDS. No association between self-reported sleep duration and FD was found. CONCLUSIONS: Sleep disturbance may be independently positively associated with the prevalence of FD among Japanese young people. Nocturnal awakening and daytime sleepiness were not associated with EPS; the other types of sleep disturbance were independently positively associated with EPS and PDS.

DOI： 10.1007/s10620-021-07260-3

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)医事出版社  

便通異常を有する糖尿病患者の便通異常に対する意識などを明らかにすることを目的に、民間の疾患パネルデータベースを用いて抽出した過去1年以内に入通院歴のある2型糖尿病患者を対象にWebアンケート調査を行い、GSRSスコアを用いたスクリーニング調査で得られた過去1週間に便通異常のあった856名(男性739名、女性117名、平均年齢62.9±10.1歳)の回答を検討した。その結果、56.5%が便通異常により日常生活に何らかの影響があると回答し、食事療法を行っている患者の17.7%、運動療法を行っている患者の16.9%が、便通異常による治療の妨げを感じていることが分かった。

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：English   Publishing type：Research paper (scientific journal)  

Dietary palmitic acid (PA) promotes liver fibrosis in patients with nonalcoholic steatohepatitis (NASH). Herein, we clarified the intestinal absorption kinetics of dietary PA and effect of trans-portal PA on the activation of hepatic stellate cells (HSCs) involved in liver fibrosis in NASH. Blood PA levels after meals were significantly increased in patients with NASH compared to those in the control. Expression of genes associated with fat absorption and chylomicron formation, such as CD36 and MTP, was significantly increased in the intestine of NASH model rats compared with that in the controls. Plasma levels of glucagon-like peptide-2, involved in the upregulation of CD36 expression, were elevated in NASH rats compared with those in the controls. Furthermore, portal PA levels after meals in NASH rats were significantly higher than those in control and nonalcoholic fatty liver rats. Moreover, PA injection into the portal vein to the liver in control rats increased the mRNA levels associated with the activation of HSCs. Increased intestinal absorption of diet-derived PA was observed in NASH. Thus, the rapid increase in PA levels via the portal vein to the liver may activate HSCs and affect the development of liver fibrosis in NASH.

DOI： 10.1038/s41598-021-92790-z

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Publisher：Research Square Platform LLC  

<title>Abstract</title>
Background

The gut microbiota has potential implications in the pathogenesis of primary biliary cholangitis (PBC). However, little is known about the significance of small intestinal mucosa-associated microbiota (MAM) in PBC. We aimed to investigate the ileal MAM profile and identify its association with liver pathology in patients with PBC.
Methods

Forty-three patients with PBC and 24 healthy controls who underwent colonoscopy at our hospital between March 2018 and January 2020 were enrolled in a cross-sectional study. We performed 16S ribosomal RNA gene sequencing of MAM samples obtained from the mucosa of the terminal ileum of all subjects. We also examined the relationship between the abundance of ileal MAM and chronic nonsuppurative destructive cholangitis using liver specimens from patients with PBC.
Results

Dysbiosis of ileal MAM was observed in patients with PBC, with a characteristic overgrowth of <italic>Sphingomonadaceae</italic> and <italic>Pseudomonas</italic>. Multivariate analysis showed that the overgrowth of <italic>Sphingomonadaceae</italic> and <italic>Pseudomonas</italic> is an independent association factor for PBC. Moreover, the abundance of <italic>Sphingomonadaceae</italic> was associated with chronic nonsuppurative destructive cholangitis in PBC.
Conclusions

Overgrowth of <italic>Sphingomonadaceae</italic> and <italic>Pseudomonas</italic> in ileal MAM is an independent association factor for diagnosing PBC. <italic>Sphingomonadaceae</italic> may be particularly associated with the pathological development of PBC.

DOI： 10.21203/rs.3.rs-645870/v1

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Other Link： https://www.researchsquare.com/article/rs-645870/v1.html

Language：Japanese   Publisher：日本消化器病学会-四国支部  

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OBJECTIVE: Serum albumin is used as a marker of acute inflammation. Several studies have addressed the association between serum albumin and clinical outcome in patients with ulcerative colitis (UC). While mucosal healing (MH) has been indicated as the therapeutic goal for UC, the association between serum albumin and MH remains unclear. We evaluated this issue in patients with UC overall and explored whether duration of UC affected this association. DESIGN: This cross-sectional study recruited consecutive patients with UC. Study subjects consisted of 273 Japanese patients with UC. Serum albumin was divided into tertiles based on its distribution in all study subjects. One endoscopy specialist was responsible for measuring partial MH and MH, which were defined as a Mayo endoscopic subscore of 0-1 and 0, respectively. The association between serum albumin and clinical outcomes was assessed by multivariate logistic regression. RESULTS: Rates of clinical remission, partial MH and MH were 57.9%, 63% and 26%, respectively. Only high serum albumin (>4.4 mg/dL) was significantly positively associated with MH (OR 2.29 (95% CI: 1.03 to 5.29), p for trend=0.043). In patients with short UC duration (<7 years) only, high serum albumin was significantly positively associated with MH and clinical remission. In patients with long UC duration (≥7 years), in contrast, no association between serum albumin and clinical outcomes was found. CONCLUSION: In Japanese patients with UC, serum albumin was significantly positively associated with MH. In patients with short UC duration, serum albumin might be a useful complementary marker for MH.

DOI： 10.1136/bmjgast-2021-000662

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BACKGROUND: Functional dyspepsia (FD) has a high prevalence worldwide and reduces patients' quality of life. The etiology of FD is likely multifactorial. Although two studies showed an inverse association between exercise habits and FD, evidence regarding the association between exercise habits and FD remains scarce. AIMS: This study aimed to investigate the association between exercise habits and FD among the young Japanese population, taking the presence or absence of an exercise partner as an additional variable. METHODS: The study subjects consisted of 8923 Japanese university students. The definition of FD was based on the Rome III criteria. Information on exercise frequency, exercise intensity, and exercise partners was obtained from a self-administered questionnaire. RESULTS: The prevalence of FD was 1.9% in this cohort. Low, moderate, and high frequency of exercise was independently inversely associated with FD (adjusted odds ratio [OR] was low: OR 0.69 [95% confidence interval (CI) 0.47-0.997], moderate: OR 0.53 [95% CI 0.34-0.81] and high: OR 0.53 [95% CI 0.30-0.88], p for trend p = 0.002). Moderate and high intensity of exercise was independently inversely associated with FD (moderate: OR 0.56 [95% CI 0.36-0.84] and high: OR 0.49 [95% CI 0.30-0.76], p for trend p = 0.001). Exercise with groups and with friends was independently inversely associated with FD whereas the association between exercising alone and FD was not significant (groups: OR 0.28 [95% CI 0.14-0.50] and friends: OR 0.44 [95% CI 0.24-0.74]). CONCLUSION: Among the young Japanese population, frequency and intensity of exercise may be independently inversely associated with FD. Additionally, exercise with groups and with friends but not by oneself was inversely associated with exercise and FD, respectively.

DOI： 10.1007/s10620-021-07017-y

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BACKGROUND: Causes of non-alcoholic fatty liver disease and its progression include visceral fat accumulation and loss of muscle mass; however, which of the two phenomena is more critical is unclear. Therefore, we intended to examine the relationship between body composition and non-alcoholic fatty liver disease progression as indicated by fibrosis and the non-alcoholic fatty liver disease activity score. METHODS: This cross-sectional study comprised 149 patients (55 men; age, 20-76 years) treated for non-alcoholic fatty liver disease between December 2010 and January 2020. Body composition measurements, histological examinations of liver samples, and comprehensive blood chemistry tests were performed. The relationship between body composition and non-alcoholic fatty liver disease histology findings was analyzed using the logistic regression model. RESULTS: Fibrosis was significantly and inversely correlated with muscle mass and appendicular skeletal muscle mass and significantly and positively correlated with fat mass, fat mass/height squared, visceral fat area, and waist-hip ratio (P < 0.05). After adjustment for sex, blood chemistry measurements, and body composition indices, fibrosis remained associated with appendicular skeletal muscle mass, fat mass, fat mass/height squared, and visceral fat area (P < 0.05). Non-alcoholic fatty liver disease activity score ≥ 5 significantly correlated with fat mass and fat mass/height squared in a univariate but not multivariate analysis. CONCLUSIONS: Fibrosis in non-alcoholic fatty liver disease, an indicator of unfavorable long-term outcomes, is associated with more indices of fat mass than of those of muscle mass. Hence, fat mass should be controlled to prevent non-alcoholic fatty liver disease progression.

DOI： 10.1186/s12876-021-01748-y

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BACKGROUND: Although the association between eating habits which can be modified and digestive diseases has been reported, to date, no research has evaluated the association between eating habits and ulcerative colitis (UC). Thus, we investigate the association between eating behavior and clinical outcome in Japanese patients with UC. METHODS: Eating quickly, eating until full, and skipping breakfast data was obtained from a self-administered questionnaire. Information on clinical outcome was collected from medical records. Mucosal healing (MH) and partial MH was defined as a Mayo endoscopic subscore of 0 or 0-1, respectively. Age, sex, BMI, current smoking, current drinking, prednisolone use, and anti-TNFα monoclonal antibody use were selected a priori as potential confounding factors. RESULTS: Study subjects consisted of 294 Japanese patients with UC. Eating at speed moderate and eating quickly were independently inversely associated with MH: the adjusted odds ratios (ORs) were 0.38 (95% confidence interval [CI] 0.16-0.85) and 0.38 (95% CI 0.17-0.81) (p for trend = 0.033). Eating until full was independently inversely associated with MH: the adjusted OR was 0.38 (95% CI 0.27-0.86). MH in patients who skipped breakfast was marginally lower than that in patients who did not skip breakfast. No association between eating habits and clinical remission or partial MH was found. CONCLUSION: Among patients with UC, eating rate and eating until full may be independently inversely associated with MH but not clinical remission.

DOI： 10.1186/s12876-021-01724-6

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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INTRODUCTION: Fatty liver disease (FLD) is a surrogate condition for glucose intolerance development. FLD may involve normal or abnormal liver enzyme levels. Whether FLD is a risk factor for glucose intolerance, regardless of liver enzyme levels, remains unknown. We assessed relationships between the development of impaired fasting glucose (IFG) and FLD, liver enzyme abnormalities, and alcohol consumption. MATERIALS AND METHODS: We retrospectively evaluated 8,664 participants with more than two annual health check-ups. Participants were classified according to sex, alcohol consumption, alanine aminotransferase (ALT) levels, and fatty liver status. RESULTS: In univariate analyses, IFG onset among men was related to normal or high ALT levels with FLD in the nonalcoholic and alcoholic groups (P-trend < 0.01). In multivariate analyses, IFG onset among nonalcoholic men was associated with normal or high ALT levels with FLD, independent of potential confounding factors (P-trend < 0.01). However, IFG onset was non-independently associated with any condition among alcoholic men. In univariate analyses, IFG onset among women was related to normal or high ALT levels with FLD in the nonalcoholic group (P-trend < 0.01) and high ALT levels with FLD in the alcoholic group (P-trend < 0.05). In multivariate analyses, IFG onset was independently associated with only normal ALT levels in nonalcoholic FLD women. CONCLUSIONS: Among nonalcoholic men and women, FLD was a risk factor for IFG onset, including normal ALT concentrations. Care is needed for individuals with nonalcoholic FLD, regardless of liver injury, possibly helping reduce glucose intolerance risk.

DOI： 10.1111/jdi.13548

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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BACKGROUND: Serum globulin is an inflammation marker. To date, no evidence regarding the association between serum globulin and disease activity in patients with ulcerative colitis has been reported. AIMS: We evaluated the association between serum globulin and endoscopic activity in patients with ulcerative colitis. METHODS: Serum globulin was divided into tertiles based on the distribution of study subjects (low globulin, ≤ 2.7 g/dl (reference); moderate globulin, 2.7-3.1 g/dl; and high globulin, > 3.1 g/dl). A single endoscopic specialist evaluated the endoscopic findings, and mucosal healing was based on Mayo endoscopic subscore. RESULTS: A total of 277 patients with ulcerative colitis were included in the study. Serum globulin was independently positively associated with diminished or absent vascular markings [moderate: adjusted odds ratio (OR) 3.70 (95% confidence interval, CI: 1.82-7.88) and high: adjusted OR 2.40 (95%CI: 1.20-4.94), p for trend = 0.005]. A similar positive association between globulin and erosion was found [high: adjusted OR 2.00 (95%CI: 1.05-3.86)]. Serum globulin was independently inversely associated with mucosal healing [moderate: adjusted OR 0.37 (95%CI: 0.18-0.73) and high: adjusted OR 0.31 (95%CI: 0.14-0.64), p for trend = 0.001] and adjusted partial mucosal healing [moderate: OR 0.51 (95%CI: 0.26-0.98), p for trend = 0.048]. The inverse association between globulin and mucosal healing was significant in the low but not the high C-reactive protein group. CONCLUSIONS: In patients with ulcerative colitis, serum globulin was significantly positively associated with endoscopic activity, and was significantly inversely associated with mucosal healing, especially in the low C-reactive protein group.

DOI： 10.1007/s10620-021-06834-5

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Language：Japanese   Publisher：(一社)日本消化管学会  

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BACKGROUND: Epidemiological evidence on the association between physical activity (PA) and ulcerative colitis (UC) is limited, and the effect of PA on the prognosis of UC is currently unknown. We evaluated the association between PA and clinical outcomes, including clinical remission and mucosal healing (MH), in Japanese patients with UC. METHODS: The study subjects were 327 Japanese patients with UC. Subjects were asked about the average time spent per day on 4 types of PA (sedentary, standing, walking, and strenuous activity) and metabolic equivalents (METs) using a validated questionnaire. Clinical outcomes were complete MH, MH, and clinical remission. The association between PA, including hours spent on each type of PA and average daily METs, and clinical outcomes was assessed by multivariate logistic regression. RESULTS: Plentiful strenuous activity was significantly inversely associated with MH and complete MH after adjustment (MH: adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.23-0.89; complete MH: adjusted OR 0.24, 95%CI 0.07-0.62; P for trend=0.008). A very high daily MET total was significantly inversely associated with complete MH after adjustment (adjusted OR 0.37, 95%CI 0.16-0.80; P for trend=0.010). In contrast, no association between PA and clinical remission was found (plentiful strenuous activity: adjusted OR 1.10, 95%CI 0.55-2.23; very high daily total METs: adjusted OR 0.74, 95%CI 0.37-1.46). CONCLUSION: In Japanese patients with UC, time spent per day on strenuous activity and total PA per day may be significantly inversely associated with complete MH, but not with clinical remission.

DOI： 10.20524/aog.2021.0663

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BACKGROUND: Endoscopic submucosal dissection (ESD) is recognized as a minimally invasive and curative treatment for superficial gastrointestinal (GI) cancers. However, ESD is still challenging and time-consuming with a high risk of adverse events such as bleeding and perforation. Various traction methods have been explored for maintaining good visualization of the submucosal layer during ESD. We developed a novel traction device (the EndoTrac) which can easily tie the thread and has the ability to change the towing direction. The aim of this study is to evaluate safety and feasibility of ESD using the EndoTrac for GI neoplasms. PATIENTS AND METHODS: We retrospectively analyzed 44 patients (45 lesions) with esophageal, gastric, duodenal, and colorectal neoplasms who had undergone ESD using the EndoTrac device between June 2018 and May 2019. Primary outcome measures were preparation time, procedural success using the EndoTrac device, and ease of ability to change towing direction. RESULTS: Mean preparation time was 2 (2-5) min in esophagus, 3 (1-5) min in stomach, 6 (5-9) min in duodenum, and 4 (2-8) min in colorectum. The procedural success rate was 100% (8/8) in esophagus, 100% (21/21) in stomach, 100% (4/4) in duodenum, and 100% (12/12) in colorectum. The rate of successful towing to both proximal and distal sides was 100% (8/8) in esophagus, 100% (21/21) in stomach, 0% (0/4) in duodenum, and 100% (12/12) in colorectum. CONCLUSIONS: Use of the EndoTrac device appears to be a feasible approach to ESD for GI neoplasms.

DOI： 10.1159/000511731

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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BACKGROUND: Mucosal healing (MH) has been indicated as the therapeutic goal for ulcerative colitis (UC). Platelet count is known as an inflammation evaluation. However, the association between platelet count and MH among patients with UC is still scarce. We therefore assessed this issue among Japanese patients with UC. METHODS: The study subjects consisted of 345 Japanese patients with UC. Platelet count was divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH and partial MH, which was defined as a Mayo endoscopic subscore of 0 and 0-1, respectively. Estimations of crude odds ratios (ORs) and their 95% confidence intervals (CIs) for partial MH and MH in relation to platelet count were performed using logistic regression analysis. Age, sex, CRP, steroid use, and anti-Tumor necrosis factor α (TNFα) preparation were selected a priori as potential confounding factors. RESULTS: The percentage of partial MH and MH were 63.2 and 26.1%, respectively. Moderate and very high was independently inversely associated with partial MH (moderate: OR 0.40 [95%CI 0.19-0.810], very high: OR 0.37 [95%CI 0.17-0.77], p for trend = 0.034). Similarly, moderate, high, and very high were independently inversely associated with MH (moderate: OR 0.37 [95% CI 0.18-0.73], high: OR 0.41 [95% CI 0.19-0.83], and very high: OR 0.45 [95% CI 0.21-0.94], p for trend = 0.033) after adjustment for confounding factors. CONCLUSIONS: Among patients with UC, platelet count was independently inversely associated with MH.

DOI： 10.1186/s12876-020-01538-y

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

門亢症に伴う出血リスクとして門脈圧亢進症性胃症(PHG)、胃前庭部毛細血管拡張症(GAVE)は食道胃静脈瘤(EV)と同様に重要である。近年、門脈圧と肝・脾硬度の相関について報告されているが、本研究ではPHG、GAVEも含めた消化管出血リスクを評価し、肝・脾硬度との関連を調べた。対象は上部消化管内視鏡検査と肝・脾硬度を測定した92名。EV、PHG、GAVE、および治療歴から定義した門亢症関連消化管病変(PHRGL)と肝・脾硬度等の関連を解析した。EVは41.3%、PHG43.5%、GAVE9.8%に合併していた。PHRGL有無別での肝硬度は2.114 vs 1.802、脾硬度は2.621 vs 2.263と各々合併群が高かった(p<0.05)。PHRGL合併に寄与する因子は血小板数、脾硬度、アルブミンであった。PHRGLは肝・脾硬度と関連し、特に脾硬度がその囲い込みに有用であった。(著者抄録)

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門亢症に伴う出血リスクとして門脈圧亢進症性胃症(PHG)、胃前庭部毛細血管拡張症(GAVE)は食道胃静脈瘤(EV)と同様に重要である。近年、門脈圧と肝・脾硬度の相関について報告されているが、本研究ではPHG、GAVEも含めた消化管出血リスクを評価し、肝・脾硬度との関連を調べた。対象は上部消化管内視鏡検査と肝・脾硬度を測定した92名。EV、PHG、GAVE、および治療歴から定義した門亢症関連消化管病変(PHRGL)と肝・脾硬度等の関連を解析した。EVは41.3%、PHG43.5%、GAVE9.8%に合併していた。PHRGL有無別での肝硬度は2.114 vs 1.802、脾硬度は2.621 vs 2.263と各々合併群が高かった(p<0.05)。PHRGL合併に寄与する因子は血小板数、脾硬度、アルブミンであった。PHRGLは肝・脾硬度と関連し、特に脾硬度がその囲い込みに有用であった。(著者抄録)

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PURPOSE: Bilirubin is known to have antioxidant effects. Several pieces of evidence regarding association between serum bilirubin and UC exist. Three studies found that serum bilirubin was inversely associated with severity of ulcerative colitis (UC), but no evidence regarding an association between serum bilirubin and mucosal healing (MH) has yet been shown. Thus, we evaluated this issue among Japanese patients with UC. METHODS: The study subjects consisted of 304 Japanese patients with UC. Serum total bilirubin and indirect bilirubin were divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH, which was defined as a Mayo endoscopic subscore of 0. The information on clinical remission was collected using medical records. RESULTS: The mean age was 49.9 years, the percentage of male patients was 59.2%, and the percentage of MH was 29.3%. High serum total bilirubin was independently positively associated with MH (OR 2.26 [95%CI 1.13-4.61]. However, after adjustment for confounding factors, the association between total bilirubin and MH disappeared. Very high serum indirect bilirubin was independently positively associated with MH (OR 2.31 [95%CI 1.10-5.00], p for trend = 0.026). No association between bilirubin and clinical remission was found. CONCLUSIONS: Among Japanese patients with UC, serum indirect bilirubin, but not total bilirubin, was significantly positively associated with MH but not clinical remission.

DOI： 10.1007/s00384-020-03774-w

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) seems to be a reasonable option for gastrointestinal subepithelial lesions (SELs) localized within the submucosa. Indications for ESD include small neuroendocrine tumors (NETs) and indeterminate SELs. However, the prospective data regarding ESD and surveillance remain unclear. This study was performed to prospectively investigate the outcomes of ESD, including organ-specific outcomes and the mid-term prognosis. METHODS: This prospective multicenter study included 57 patients who underwent ESD for SELs localized within the submucosa [definite NETs (n = 42) and indeterminate SELs (n = 15)]. The efficacy and safety of ESD were evaluated in the whole cohort and in subgroups (NETs and indeterminate SELs). All patients were followed up. RESULTS: The rates of en bloc resection, curative resection, and complications were 98.2%, 66.7%, and 7.7% for the overall population (n=57); 100%, 61.9%, and 2.4% for NETs (n=42); and 93.3%, 80.0%, and 20.0% for indeterminate SELs (n=15), respectively. The rates of curative resection for NETs were poorer in the stomach (20%, n=5) and duodenum (33%, n=3) than in the rectum (71%, n=34). Including 11 of 16 patients with NETs who underwent a conservative approach resulting in non-curative resection, no patients developed tumor recurrence during the follow-up period (median, 24.5 months; range, 1-60 months). ESD followed by surveillance demonstrated acceptable mid-term outcomes for non-curative NETs. CONCLUSIONS: ESD can be an efficient therapy for SELs localized within the submucosa. However, gastric and duodenal ESD for NETs may be limited in terms of its curative and technical aspects. Clinicians should be aware of the potential complications of ESD for indeterminate SELs.

DOI： 10.15403/jgld-510

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DOI： 10.2169/internalmedicine.3886-19

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Schistosomiasis infection is a major cause of morbidity and mortality in endemic areas. Developed countries have declared that schistosomiasis has been eradicated; however, residents of these countries may travel and stay in endemic areas and the number of foreign travelers is increasing in the recent years. Thus, schistosomiasis is regarded as an imported infection. Ultrasonography and serum antibody titer tests are well established as diagnostic methods for schistosomiasis. However, a definitive diagnosis cannot be obtained using these tests in some cases. We herein report a case in which schistosomiasis was confirmed based on laparoscopic liver biopsy without a definitive diagnosis by blood test, fecal examination, or imaging.

DOI： 10.2169/internalmedicine.2776-19

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Gastrointestinal motility is regulated by neural factors and humoral factors. Both motilin and ghrelin improve gastrointestinal motility, but many issues remain unclear. We prepared human motilin receptor transgenic (Tg) mice and performed experiments evaluating the effects of motilin, erythromycin (EM), and ghrelin. EM and ghrelin promoted gastric emptying (GE) when administered either peripherally or centrally to Tg mice. Atropine (a muscarinic receptor antagonist) counteracted GE induced by centrally administered EM, but not that induced by peripherally administered EM. The administration of EM in this model promoted the effect of mosapride (a selective serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist), and improved loperamide (a μ-opioid receptor agonist)-induced gastroparesis. The level of acyl-ghrelin was significantly attenuated by EM administration. Thus, we have established an animal model appropriate for the evaluation of motilin receptor agonists. These data and the model are expected to facilitate the identification of novel compounds with clinical potential for relieving symptoms of dyspepsia and gastroparesis.

DOI： 10.3390/ijms20071521

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Hepatic stellate cells (HSCs) were reported to promote the progression of hepatocellular carcinoma (HCC), however its mechanism is uncertain. We previously reported that protein kinase R (PKR) in hepatocytes regulated HCC proliferation. In this study, we focused on the role of PKR in HSCs, and clarified the mechanism of its association with HCC progression. We confirmed the activation of PKR in a human HSC cell line (LX-2 cell). IL-1β is produced from HSCs stimulated by lipopolysaccharide (LPS) or palmitic acid which are likely activators of PKR in non-alcoholic steatohepatitis (NASH). Production was assessed by real-time PCR and ELISA. C16 and small interfering RNA (siRNA) were used to inhibit PKR in HSCs. The HCC cell line (HepG2 cell) was cultured with HSC conditioning medium to assess HCC progression, which was evaluated by proliferation and scratch assays. Expression of PKR was increased and activated in stimulated HSCs, and IL-1β production was also increased molecular. Key molecules of the mitogen-activated protein kinase pathway were also upregulated and activated by LPS. Otherwise, PKR inhibition by C16 and PKR siRNA decreased IL-1β production. HCC progression was promoted by HSC-stimulated conditioning medium although it was reduced by the conditioning medium from PKR-inhibited HSCs. Moreover, palmitic acid also upregulated IL-1β expression in HSCs, and conditioning medium from palmitic acid-stimulated HSCs promoted HCC proliferation. Stimulated HSCs by activators of PKR in NASH could play a role in promoting HCC progression through the production of IL-1β, via a mechanism that seems to be dependent on PKR activation.

DOI： 10.1371/journal.pone.0212589

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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OBJECTIVES: In the general population, late-night dinner is positively associated with gastroesophageal reflux disease (GERD). No evidence exists regarding the relationship between eating behaviours and GERD in patients with type 2 diabetes mellitus, though the prevalence of GERD in patients with type 2 diabetes is higher than in those without diabetes. We conducted this study to investigate the association between eating behaviours and GERD in Japanese patients with type 2 diabetes. METHODS: The study's subjects were 817 Japanese patients with type 2 diabetes. GERD was defined as being present when a subject had a Quality of Life and Utility Evaluation Survey Technology (QUEST) score of 4 or higher. The assessment of eating behaviour was performed by self-administered questionnaire. Subjects were considered positive for late-night dinner if they answered yes to the question "Do you eat dinner within 2 hours before bedtime at least 3 times per week? RESULTS: The prevalence values of GERD, skipping breakfast, bedtime snacking, late-night dinner and fast eating were 32.0%, 13.7%, 27.1%, 28.8%, and 44.4%, respectively. Late-night dinner was independently positively associated with GERD in patients with type 2 diabetes; the adjusted odds ratio was 1.46 (95% CI 1.03 to 2.05). No relationships were found between skipping breakfast, bedtime snacking or fast eating and GERD. CONCLUSIONS: Late-night dinner may be positively associated with GERD in Japanese patients with type 2 diabetes.

DOI： 10.1016/j.jcjd.2017.07.007

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BACKGROUND: Atrophic gastritis can be classified according to characteristic mucosal patterns observed by Blue LASER Imaging (BLI) in a medium-range to distant view. AIMS: To facilitate the endoscopic diagnosis of Helicobacter pylori (HP)-related gastritis, we investigated whether atrophic mucosal patterns correlated with HP infection based on the image interpretations of three endoscopists blinded to clinical features. METHODS: This study included 441 patients diagnosed as having atrophic gastritis by upper gastrointestinal endoscopy at Nishikawa Gastrointestinal Clinic between April 1, 2015 and March 31, 2016. The presence/absence of HP infection was not taken into consideration. Endoscopy was performed using a Fujifilm EG-L580NW scope. Atrophic mucosal patterns observed by BLI were classified into Spotty, Cracked and Mottled. Image interpretation results were that 89, 122 and 228 patients had the Spotty, Cracked and Mottled patterns, respectively, and 2 patients an undetermined pattern. Further analyses were performed on 439 patients, excluding the 2 with undetermined patterns. RESULTS: The numbers of patients testing negative/positive for HP infection in the Spotty, Cracked and Mottled pattern groups were 12/77, 105/17, and 138/90, respectively. The specificity, positive predictive value and positive likelihood ratio for endoscopic diagnosis with positive HP infection based on the Spotty pattern were 95.3%, 86.5% and 8.9, respectively. In all patients with the Spotty pattern before HP eradication, the Cracked pattern was observed on subsequent post-eradication endoscopy. CONCLUSIONS: The Spotty pattern may represent the presence of HP infection, the Cracked pattern, a post-inflammatory change as seen after HP eradication, and the Mottled pattern, intestinal metaplasia.

DOI： 10.1371/journal.pone.0193197

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BACKGROUND: Palmitic acid is an important risk factor for the pathogenesis of non-alcoholic steatohepatitis (NASH), but changes in palmitic acid intestinal absorption in NASH are unclear. The aim of this study was to clarify changes in palmitic acid intestinal absorption and their association with the pathogenesis of NASH. METHODS: A total of 106 participants were recruited to the study, of whom 33 were control subjects (control group), 32 were patients with NASH Brunt stage 1-2 [early NASH (e-NASH)], and 41 were patients with NASH Brunt stage 3-4 [advanced NASH (a-NASH)]. 13C-labeled palmitate was administered directly into the duodenum of all participants by gastrointestinal endoscopy. Breath 13CO2 levels were measured to quantify palmitic acid absorption, and serum Apolipoprotein B-48 (ApoB-48) concentrations were measured after a test meal to quantify absorbed chylomicrons. Expressions of fatty acid (FA) transporters were also examined. The associations of breath 13CO2 levels with hepatic steatosis, fibrosis and insulin resistance was evaluated using laboratory data, elastography results and liver histology findings. RESULTS: Overall, 13CO2 excretion was significantly higher in e-NASH patients than in the control subjects and a-NASH patients (P < 0.01). e-NASH patients had higher serum ApoB-48 levels, indicating increased palmitic acid transport via chylomicrons in these patients. Jejunal mRNA and protein expressions of microsomal triglyceride transfer protein and cluster of differentiation 36 were also increased in both NASH patient groups. The 13CO2 excretion of e-NASH patients was significantly correlated with the degree of hepatic steatosis, fibrosis and insulin resistance (P = 0.005, P < 0.001, P = 0.019, respectively). CONCLUSIONS: Significantly upregulated palmitic acid absorption by activation of its transporters was evident in patients with NASH, and clinical progression of NASH was related to palmitic acid absorption. These dietary changes are associated with the onset and progression of NASH.

DOI： 10.1007/s00535-016-1298-6

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BACKGROUND: Only limited epidemiological evidence exists regarding the relationship between age and gastroesophageal reflux disease (GERD) among Japanese patients with type 2 diabetes mellitus. AIM: The purpose of the present study is to investigate this issue among Japanese patients with type 2 diabetes mellitus. METHODS: A multicenter cross-sectional study was conducted in 847 Japanese patients with type 2 diabetes mellitus. Subjects were divided into quartiles according to age: (1) 19 ≤ age < 56, (2) 56 ≤ age < 64, (3) 64 ≤ age < 71, and (4) 71 ≤ age < 89. GERD was defined as present when a subject had a Carlsson-Dent self-administered questionnaire (QUEST) score ≥4. RESULTS: The prevalence of GERD was 31.5 %. Younger age was independently associated with a higher prevalence of GERD: the adjusted odds ratios (95 % confidence intervals) for GERD in relation to age < 56, 56 ≤ age < 64, 64 ≤ age < 71, and ≥71 were 3.73 (2.16-6.53), 1.98 (1.21-3.27), 1.66 (1.05-2.68), and 1.00 (reference), respectively (P for trend = 0.001). Among 201 patients with PPI or histamine H2-receptor antagonist (H2RA), less than 56 years of age was independently positively associated with GERD: the adjusted OR was 5.68 (95 % CI 1.55-22.18) (P for trend = 0.02). CONCLUSIONS: Younger age may be independently positively associated with GERD among Japanese type 2 diabetes mellitus patients, regardless of the use of PPI or H2RA.

DOI： 10.1007/s10620-016-4311-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

BACKGROUND: Carbonic anhydrase I (CA I), a major cecal bacterial antigen, improves inflammatory bowel disease (IBD) symptoms in a murine model. The aim of this study was to identify the responsible epitope region within the CA I protein and evaluate its effect on inflammation using a murine IBD model. METHODS: Candidate peptides within the CA I protein sequence that interact with major histocompatibility complex class II were chosen and their immune responses were evaluated using mesentery lymph nodes (MLNs) from a CD4CD25 T-cell transfer murine colitis model. Mice were treated with regulatory dendritic cells (Reg-DCs)-pulsed CA I peptide. We assessed their clinical signs, histopathology, induction of cytokines and transcription factors, and generation of CD103CD11c dendritic cells and regulatory T cells (Tregs). RESULTS: We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCsCA I 58-73) alone ameliorated colitis. Reg-DCsCA I 58-73-treated mice showed higher mRNA expression levels of forkhead box protein 3, aldehyde dehydrogenase family 1a2, transforming growth factor-β, and interleukin (Il)10, when compared with lower mRNA expression of retinoic acid-related orphan receptor gamma and Il17a in MLNs. Compared with control mice, these mice also showed higher numbers of Foxp3CD4CD25 Tregs and CD103CD11c dendritic cells in MLNs and colon. Administration of Reg-DCsCA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice. CONCLUSIONS: CA I 58-73 peptide induces antigen-specific therapeutic effect in a murine IBD model using Reg-DCs, indicating that CA I 58-73 is a candidate epitope for IBD immunotherapy.

DOI： 10.1097/MIB.0000000000000781

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：GEORG THIEME VERLAG KG  

Pancreatobiliary fistulas associated with intraductal papillary mucinous neoplasms (IPMN) often develop obstructive jaundice and cholangitis; thus, early diagnosis is important. However, computed tomography and cholangiography, the current methods for detecting pancreatobiliary fistulas, are not always effective. We previously reported a case of IPMN-associated pancreatobiliary fistula and proposed a potential new diagnostic marker: the pig-nose appearance of the duodenal papilla, which results from dilated pancreatic and bile ducts and can be visualized via endoscopy. In this study, we report another three cases of IPMN-associated pancreatobiliary fistulas detected by a different technology, intraductal ultrasonography (IDUS). As with our previously reported case, we confirmed the utility of the pig-nose appearance and IDUS in the diagnosis of IPMN-associated pancreatobiliary fistulas. In addition, we found it difficult to manage biliary obstruction that resulted from the flow of mucinous material through pancreatobiliary fistulas. The obstruction was treated with endoscopic nasal biliary drainage (ENBD), but this was not always successful. In two of our cases, additional treatment with a large diameter fully covered metal stent failed to improve jaundice. Therefore, we conclude that standard endoscopic stenting may not be effective, and that alternative endoscopic methods or surgery may be necessary.

DOI： 10.1055/s-0042-102956

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

BACKGROUND: Epidemiologic studies show an association between short sleep duration and the presence of nonalcoholic fatty liver disease (NAFLD). This study examined the association between short sleep duration and the onset of NAFLD. METHODS: This community-based, retrospective, longitudinal cohort study included 6,370 Japanese subjects who had undergone annual health check-ups more than twice at a single center between April 2003 and March 2010. After excluding 3,941 subjects, the records of 2,429 Japanese subjects were reviewed. RESULTS: Two groups comprised the study cohort: those with short (≤ 6 h) sleep durations (n = 1,543) and those with moderate (7-8 h) sleep durations (n = 886). During the observation period, 296 subjects developed NAFLD. Multivariate analysis identified an association between short sleep duration and the reduced onset of NAFLD in men (odds ratio: 0.551, 95% confidence interval 0.365-0.832, p = 0.005). There was no association between short sleep duration and NAFLD onset in women. The prevalence of NAFLD onset in men increased significantly as sleep duration increased, as follows: 12.5, 18.4, and 27.4% among subjects who had sleep durations of ≤ 4, 5-6, and 7-8 h, respectively (p = 0.02). CONCLUSIONS: This study demonstrates an association between sleep duration and NAFLD onset. Short sleep duration reduced the risk of NAFLD onset in men. Correct recognition is important to prevent disease progression and further complications.

DOI： 10.1007/s00535-014-0989-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

PURPOSE: This study aimed at prospectively evaluating bile duct anatomy on ultrasonography and evaluating the safety and utility of radiofrequency ablation (RFA) assisted by virtual ultrasonography from gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). METHODS: The institutional review board approved this study, and patients provided written informed consent prior to entry into the study. Bile duct anatomy was assessed in 201 patients who underwent Gd-EOB-DTPA-enhanced MRI for the evaluation of hepatic tumor. Eighty-one of these patients subsequently underwent RFA assisted by ultrasound imaging. In 23 patients, the tumor was located within 5 mm of the central bile duct, as demonstrated by MRI. RESULTS: Virtual ultrasonography constructed by Gd-EOB-enhanced MRI was able to visualize the common bile duct, left hepatic duct, and right hepatic duct in 96.5, 94.0, and 89.6 % of cases, respectively. The target hepatic tumor nodule and biliary duct could be detected with virtual ultrasonography in all patients, and no severe complications occurred. CONCLUSION: The running pattern of the bile ducts could be recognized on conventional ultrasound by referencing virtual ultrasonography constructed by Gd-EOB-DTPA-enhanced MRI. RFA assisted by this imaging strategy did not result in bile duct injury.

DOI： 10.1007/s10396-014-0598-9

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Nonalcoholic fatty liver disease (NAFLD) is a risk factor for diabetes and cardiovascular disease that could progress to nonalcoholic steatohepatitis, cirrhosis, and liver failure. We aimed to assess the relationship between NAFLD and lifestyle habits.
Using a community-based, cross-sectional design, the records of 11,094 Japanese subjects who had undergone at least 1 annual health checkup were reviewed.
Of the 6,370 subjects who qualified for enrolment, 1,346 met the diagnostic criteria for NAFLD. The prevalence rate (PR) of NAFLD increased significantly to 36.6, 41.5, and 41.1 % with no snacking, snacking less than once/day, and snacking a parts per thousand yen2 times/day, respectively, in men (P = 0.0495) and to 10.8, 11.7, and 15.3 %, respectively, in women (P = 0.002). In men, the NAFLD PR decreased significantly to 48.8, 36.9, and 29.9 % with no exercise, exercise consciousness, and periodical exercise, respectively (P &lt; 0.001). In women, the NAFLD PR decreased significantly to 19.3, 13.5, 11, and 8 % with sleep durations of a parts per thousand currency sign4, 5-6, 7-8, and a parts per thousand yen9 h, respectively (P = 0.003). Periodical exercise was identified as an independent factor associated with NAFLD in men (odds ratio 0.707, 95 % confidence interval 0.546-0.914; P = 0.008).
Performing regular exercise was associated with a reduced risk for NAFLD in men. Men with a high risk for NAFLD can be identified using questionnaires on exercise in an outpatient setting. Disease progression and further complications may be prevented by educating high-risk NAFLD patients about the importance of exercise.

DOI： 10.1007/s00535-014-0959-6

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A 36-year-old Japanese woman took over-the-counter (OTC) medication for headaches for 20 days. Subsequently, five days after discontinuing the medication, a skin rash developed over the patient's upper and lower limbs and face, in addition to a fever, brown urine and serious liver dysfunction. Drug lymphocyte stimulation tests implicated ibuprofen, a main component of the OTC drugs, which has the potential to induce this pathology, and a diagnosis of drug-induced liver injury with multiform exudative erythema was made. The patient's symptoms and liver function tests returned to normal following treatment with systemic steroids.

DOI： 10.2169/internalmedicine.54.3204

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

G-protein coupled receptors (GPCRs) share a common seven-transmembrane topology and mediate cellular responses to a variety of extracellular signals. However, structural and functional approaches to GPCRs have often been limited by the difficulty of producing a sufficient amount of receptor protein using conventional expression systems. We synthesized human dopamine D1 receptors using a wheat cell-free protein synthesis system with liposomes and then analyzed their receptor binding ability. We determined the specific binding of [(3)H]SCH23390 to the synthesized receptors generated from a cell-free protein synthesis system or rat striatal membranes. From Scatchard plot analysis, the dissociation constant (Kd) and the maximum density (Bmax) of the synthesized receptors were 6.61±0.06 nM and 1.85±0.05 pmol/mg protein, respectively. The same analysis for rat striatal membrane gave a Kd of 2.67±0.05 nM and Bmax of 0.70±0.10 pmol/mg protein. Using a competition binding assay, Ki values of antagonists, SCH23390, LE300 and SKF83566, for the synthetic receptors were the same as those for rat striatal membranes, but Ki values of agonists, A68930, SKF38393 and dopamine, were 5-17 fold higher than those for rat striatal membranes. These results suggest that the dopamine D1 receptors synthesized in liposomes have a functional binding capacity. The different patterns of binding of antagonists and agonists to the synthetic receptors and rat striatal membranes indicate that G proteins are involved in agonist binding to dopamine D1 receptors. The cell-free protein synthesis method with liposomes will be invaluable for the functional analysis of GPCRs.

DOI： 10.1016/j.ejphar.2014.10.011

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Positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxyglucose (FDG-PET/CT) has become established in cancer imaging, and derived maximum standardized uptake values (SUVmax) add functional information regarding cancer, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to determine the clinical significance and association of tumor progression using SUVmax derived from PET/CT images in patients with ESCC. In total, 101 patients with ESCC were assessed using FDG-PET/CT and the SUVmax was then compared with the clinical backgrounds and prognoses of the patients. Endoscopic ESCC biopsy specimens were obtained in order to analyze mRNA expression relative to tumor progression. The results showed that values for SUVmax were significantly higher in patients with tumor progression factors, particularly those with lymph node metastasis. Analysis of receiver operating characteristics curves revealed an optimum SUVmax cut-off value of 10.26 for node-positive disease. Patients with SUVmax ≥10.26 had gene alterations with epithelial-mesenchymal transition (EMT) and significantly worse overall survival (P=0.0012). A higher SUVmax in patients with ESCC was associated with lymph node metastasis and a poorer prognosis. Thus, the SUVmax may reflect the potential of EMT in patients with ESCC.

DOI： 10.3892/mco.2014.238

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Language：English   Publisher：WILEY-BLACKWELL  

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The present report describes a case of a patient with hepatitis B virus (HBV)-human immunodeficiency virus (HIV) co-infection who was treated with tenofovir disoproxil (TDF)-based highly active antiretroviral therapy (HAART) and who achieved HBs antigen (Ag)/antibody (Ab) seroconversion. An 18-year-old Japanese man with HIV and HBV co-infection presented to our hospital. His CD4 count was decreased, and TDF-based HARRT was started. At 30 months after initiation of therapy, HBsAg was not detected. At 36 months after initiation of therapy, HBsAb was detected. We conclude that TDF-based therapy is useful for the management of patients with HBV and HIV co-infection.

DOI： 10.2169/internalmedicine.53.2131

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Biliary drainage was performed in a 71-year-old man with obstructive jaundice of unknown origin; however, he died due to acute pulmonary failure. At autopsy, proliferation of adenocarcinoma cells was observed in the gallbladder mucosa transitioning from isolated signet-ring cell carcinoma (SRCC) to the subserosa and bile ducts without growth toward the gallbladder lumen. Furthermore, fibrocellular intimal proliferation, tumor emboli and organized thrombi were observed in the small pulmonary arteries. The final diagnosis was gallbladder carcinoma complicated by SRCC associated pulmonary tumor thrombotic microangiopathy (PTTM). PTTM may present as rapidly progressive dyspnea, and a high level of clinical suspicion is required to make the differential diagnosis.

DOI： 10.2169/internalmedicine.53.1939

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Language：English   Publisher：WILEY-BLACKWELL  

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Background and Aims Serum des--carboxy prothrombin (DCP) is an established tumor marker in patients with hepatocellular carcinoma (HCC), which can be identified by using MU-3 antibody. The MU-3 antibody mainly reacts with the 910 glutamic acid residues of DCP (conventional DCP). Since other variants of DCP with fewer glutamic acid residues can be detected using P-11 and P-16 antibodies (code name: NX-PVKA), we examined the clinical characteristics associated with NX-PVKA, and whether NX-PVKA is a useful measure in HCC patients. Methods Participants comprised 197 HCC patients admitted to our hospital between 2001 and 2010. NX-PVKA, conventional DCP, alpha-fetoprotein, and L3 fraction of alpha-fetoprotein were measured prior to initiation of HCC treatment. Results Of the tumor markers assessed, NX-PVKA was the only significant predictor of prognosis (hazard ratio, 81.32; P&lt;0.0001). Patients with NX-PVKA level100mAU/mL showed significantly lower survival rates (P&lt;0.0001). NX-PVKA level was also significantly associated with platelet count, prothrombin time, C-reactive protein, sex, maximum tumor size, number of nodules, and portal venous invasion by HCC. Finally, using NX-PVKA level and other clinical parameters, we established a prognostic model to estimate patient survival time. Conclusions NX-PVKA offers the best marker of tumor prognosis among HCC patients, and is strongly associated with tumor factors and hepatic functional reserve. NX-PVKA could be useful for clinical evaluation of tumor severity, as well as the estimated duration of survival among patients with HCC.

DOI： 10.1111/jgh.12076

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Portal biliopathy is a morphological abnormality of the biliary ductal and gallbladder wall associated with portal hypertension. A patient with essential thrombocythemia was initially diagnosed with extrahepatic portal vein obstruction (EHPVO). The contrast-enhanced computed tomography (CT) findings were similar to those of cholangiocarcinoma or sclerosing cholangitis. However, color Doppler and contrast-enhanced ultrasound (US) were more specific. The paracholedocheal veins around the bile ducts appeared as beads soon after the injection of contrast medium, followed by linear enhancement of the epicholedochal veins and the gradual enhancement of the whole bile ducts. These findings led to a diagnosis of portal biliopathy, which prevented the patient from having to endure hazardous procedures such as bile duct biopsies. Color Doppler and contrast-enhanced US findings are useful for diagnosing or ruling out portal biliopathy in patients who present with EHPVO.

DOI： 10.2169/internalmedicine.52.8848

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Double-stranded RNA-activated protein kinase R (PKR) is known to be upregulated by hepatitis C virus (HCV) and overexpressed in hepatocellular carcinoma (HCC). However, the precise roles of PKR in HCC with HCV infection remain unclear. Two HCV replicating cell lines (JFH-1 and H77s), generated by transfection of Huh7.5.1 cells, were used for experiments reported here. PKR expression was modulated with siRNA and a PKR expression plasmid, and cancer-related genes were assessed by real-time PCR and Western blotting; cell lines were further analyzed using a proliferation assay. Modulation of genes by PKR was also assessed in 34 human HCC specimens. Parallel changes in c-Fos and c-Jun gene expression with PKR were observed. Levels of phosphorylated c-Fos and c-Jun were upregulated by an increase of PKR, and were related to levels of phosphorylated JNK1 and Erk1/2. DNA binding activities of c-Fos and c-Jun also correlated with PKR expression, and cell proliferation was dependent on PKR-modulated c-Fos and c-Jun expression. Coordinate expression of c-Jun and PKR was confirmed in human HCC specimens with HCV infection. PKR upregulated c-Fos and c-Jun activities through activation of Erk1/2 and JNK1, respectively. These modulations resulted in HCC cell proliferation with HCV infection. These findings suggest that PKR-related proliferation pathways could be an attractive therapeutic target.

DOI： 10.1371/journal.pone.0067750

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC NUTRITION-ASN  

Background: Dietary long-chain fatty acid (LCFA) intake is an important risk factor for hepatic inflammation and hepatocarcinogenesis. An alternate route of dietary LCFA absorption has been suggested in patients with liver cirrhosis (LC).
Objective: We aimed to determine this alternate route and to identify its mechanism.
Design: Twenty healthy control subjects and 47 patients with LC-n = 23 with portal hypertension [PH(+)LC] and 24 without portal hypertension [PH(-)LC)]-were enrolled. [C-13]Palmitate (an LCFA) and octanoate (a medium-chain fatty acid [MCFA]) were administered by using gastrointestinal endoscopy. Breath (CO2)-C-13 was measured to quantify metabolized fatty acids. We also examined intestinal specimens of patients in these groups.
Results: A more rapid increase in metabolized palmitate, which showed a pattern similar to that of octanoate metabolism, was observed in patients with LC than in healthy control subjects. The increase in the PH(-)LC group was higher than that in the PH(+)LC group. However, the concentration of metabolized palmitate increased with treatment of the PH(+)LC group with a portal-systemic shunt. Morphologic changes such as expanded lymph and blood vessels were present, and glycosylated CD36 increased in the jejunum of the PH(+)LC group. This group had high serum concentrations of glucagon-like peptide-2. These data suggest that dietary LCFAs, similar to MCFAs, are absorbed via blood vessels in patients with LC.
Conclusions: Rapid absorption of LCFAs by an alternative method occurred in patients with LC. This altered LCFA processing is likely related to upregulation of intestinal glycosylated CD36 and could contribute to pathogenesis in patients with LC. This trial was registered at http://www.umin.ac.jp/ctr/index.htm as UMIN000006637 and UMIN000006638. Am J Clin Nutr 2012;96:90-101.

DOI： 10.3945/ajcn.111.033084

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

Untreated nonalcoholic fatty liver disease (NAFLD) may progress to liver cirrhosis or failure and is associated with the development of hepatocellular carcinoma, diabetes, and cardiovascular disease. It is therefore essential to diagnose and treat NAFLD at an early stage. To assist in this effort, this retrospective study explored the risk factors for NAFLD, and derived new surrogates, a revised alanine aminotransferase (ALT) cutoff level and a novel NAFLD index, to identify previously undiagnosed cases of NAFLD.
Using a community-based, cross-sectional design, the records of 6,370 Japanese subjects who had undergone at least 1 annual health check-up were reviewed for the identification of subjects meeting the diagnostic criteria for NAFLD and the variables associated with NAFLD for the estimation of ideal ALT cutoff levels.
The results of multivariate analysis of the 1,346 subjects who met the diagnostic criteria for NAFLD confirmed that metabolic disease markers and a novel NAFLD index, using the variables derived from multivariate analysis, were also markers of NAFLD. The ALT cutoff levels for NAFLD diagnosis were estimated at 25 U/L for males and 17 U/L for females.
ALT level and the novel NAFLD index were confirmed to be surrogate markers for NAFLD in addition to metabolic disease markers. The ALT cutoff level used in NAFLD diagnosis should be revised downward to identify subjects at risk of NAFLD to prevent NAFLD progression and the development of associated diseases.

DOI： 10.1007/s00535-012-0534-y

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS INC  

Background. The manner in which ribavirin (RBV) enhances the antiviral effects of interferon (IFN) against hepatitis C virus (HCV) remains unknown. We investigated whether RBV modifies IFN-stimulated genes (ISGs) in vivo and in vitro.
Methods. We measured the messenger RNA (mRNA) levels of ISGs in T lymphocytes from patients with HCV infection who were receiving IFN-alpha therapy with or without RBV. We added RBV and/or IFN-alpha to a plasmid-based HCV replication system containing a full-length HCV genotype la sequence in HepG2 and Huh7 cell lines and the JFH-1 HCV genotype 2a sequence in Huh7 cell lines and measured levels of ISGs and autocrine IFN-beta.
Results. The expression of protein kinase R and myxovirus resistance A mRNA was enhanced more with IFN-alpha and RBV than by IFN-alpha alone in assays in vivo and in vitro. Such enhancement depended on autocrine IFN-beta being enhanced by RBV. RBV upregulated interleukin 8 (IL-8) in the absence of IFN-alpha. The IL-8 upregulation induced by RBV was responsible for the activation of activator protein 1 (AP-1).
Conclusions. Ribavirin augments the anti-HCV effects of IFN-alpha induced by ISGs through enhancing autocrine IFN-beta. Moreover, RBV can enhance IL-8 through activating AP-1. Improved understanding of ISG modulation by RBV would help to establish a means of eliminating HCV.

DOI： 10.1093/infdis/jis025

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A 69-year-old man presented with multiple nodules on the spleen and liver that had been detected by computed tomography (CT). A liver tumor biopsy was performed, and the patient was diagnosed to have histiocytic sarcoma (HS). Splenectomy was performed, and the chemosensitivity of the spleen tumor was measured using the collagen gel droplet-embedded culture drug sensitivity test (CD-DST). Hepatic arterial infusion chemotherapy was administered, based on the results of the CD-DST. The patient achieved complete remission (CR) after this therapy and remained alive without recurrence at the final follow-up. This is the first known case of CR in response to chemotherapy for advanced splenic HS.

DOI： 10.2169/internalmedicine.51.8325

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：RADIOLOGICAL SOC NORTH AMERICA  

Purpose: To prospectively correlate spleen elasticity and degree of portal hypertension estimated with the hepatic venous pressure gradient (HVPG) and to evaluate splenic elasticity as a predictor of gastroesophageal varices.
Materials and Methods: The institutional review hoard approved this study, and patients provided written informed consent. In a pilot study or 60 patients with chronic liver damage, the authors measured liver and spleen elasticity with real-time tissue elastography (RTE), obtained serum markers related to fibrosis, examined hepatic and splenic blood flow with duplex Doppler ultrasonography, estimated HVPG, and performed upper gastrointestinal endoscopy. Then, with use of thresholds determined in the pilot study, the authors conducted a validation trial with another 210 patients, performing all studies except the measurement of HPVG. The relationship between HVPG and the other parameters was analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the diagnosis of gastroesophageal varices were calculated by using cutoff values obtained from receiver operating characteristic curves.
Results: Among the parameters associated with HVPG, correlation was closest with splenic elasticity (R = 0.854, P &lt; .0001). When 8.24 was selected as the cutoff of splenic elasticity for predicting HVPG of more than 10 mm Hg, the accuracy of diagnosing gastroesophageal varix was 90% (sensitivity, 96%; specificity, 85%; PPV, 83%; NPV, 97%). The results of the validation trial showed that the 8.24 cutoff for splenic elasticity was associated with a diagnostic accuracy of 94.8% (sensitivity, 98%; specificity, 93.8%; PPV, 82.1%; NPV, 99.4%) for gastroesophageal varices.
Conclusion: Splenic elasticity determined with RTE is the most closely associated parameter for evaluating HVPG and is useful as a clinical marker of portal hypertension and a predictive marker of gastroesophageal varices. (C) RSNA, 2011

DOI： 10.1148/radiol.11110156

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A 77-year-old man with hypertension, diabetes mellitus, ischemic heart disease and a smoking habit presented at our hospital with sudden abdominal pain. Computed tomography indicated edematous swelling and pneumatosis of the intestinal wall in a localized area of the ascending colon with inflamed adipose tissue. Acute mesenteric ischemia was diagnosed. Abdominal angiography showed stenosis of the mesenteric arteries. Virtual histology-intravascular ultrasound imaging indicated a fibrous change in the superior mesenteric artery with a necrotic core. Endovascular treatment with stent placement after percutaneous transluminal angioplasty was effective. Surgery would usually be considered as the first choice for treating patients with acute mesenteric ischemia; however, when this condition is complicated with metabolic diseases, stenotic changes in the mesenteric arteries that would normally be found in patients with chronic mesenteric ischemia need to be considered to ensure optimal treatment.

DOI： 10.1007/s12328-011-0236-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ROENTGEN RAY SOC  

OBJECTIVE. Transient elastography is a rapid, noninvasive, and reproducible approach to assessment of liver fibrosis by measurement of liver elasticity. However, transient elastographic measurements are of limited utility in patients with ascites or severe obesity. The aim of this study was to determine whether measurements of liver stiffness with real-time tissue elastography can be altered for patients with ascites.
SUBJECTS AND METHODS. The subjects were 54 patients being treated at a university hospital between January and December 2009. In 42 patients, real-time tissue elastography to evaluate liver stiffness was performed before and after injection to produce artificial ascites for radiofrequency ablation. The other 12 patients had ascites due to cirrhosis, and liver stiffness was measured with real-time tissue elastography before and after control of ascites.
RESULTS. Elastic ratios evaluated with real-time tissue elastography did not differ significantly before and after injection for artificial ascites or before and after control of ascites. This ratio was the same for patients with and those without cirrhosis and was unaffected by distance between the body surface and the targeted liver area. Stable values thus were measured with real-time tissue elastography.
CONCLUSION. Liver stiffness can be measured reproducibly with real-time tissue elastography even in patients with ascites. This method has the potential of being superior to transient elastography for assessment of liver stiffness, particularly in patients with decompensated cirrhosis.

DOI： 10.2214/AJR.10.4867

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We report a patient who developed ulcerative colitis during the course of primary biliary cirrhosis (PBC). PBC was diagnosed by liver histology when the patient was 31 years old, at which time no symptoms were observed. At 45 years of age, the patient complained of bloody diarrhea and abdominal pain, and she was diagnosed with ulcerative colitis by colonoscopy and histological examination. The patient had HLA-DRB1*1502 and *0802, which are associated with both diseases. Ulcerative colitis should be considered in the differential diagnosis of bowel disease in patients with PBC. The possible genetic associations between 2 diseases are also discussed.

DOI： 10.2169/internalmedicine.50.5919

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An epithelial cyst in an intrapancreatic accessory spleen (ECIAS) is a rare disease that is commonly misdiagnosed preoperatively. To identify the clinical and imaging features of ECIAS, we reviewed the relevant medical literature. Twenty-one cases of ECIAS were identified, including our own. The cases were mainly diagnosed as mucinous cystic neoplasm (MCN) preoperatively based on clinical and imaging features, such as, a woman in middle age; elevation of serum CA19-9 levels; location in the tail of the pancreas; and a solid component resembling a mural nodule. ECIAS is another lesion to be considered in the differential diagnosis of MCN.

DOI： 10.2169/internalmedicine.50.5340

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Early gastric cancer (EGC) has a favorable prognosis after surgical gastrectomy. For intramucosal EGC with little risk of lymph node metastasis, endoscopic mucosal resection (EMR) is an accepted treatment method. Herein we document a noteworthy case of small undifferentiated gastric cancer with nodal metastasis. A 60-year-old Japanese woman underwent gastrectomy with D2 lymph node dissection for the treatment of EGC in the lower gastric body. Histological examination revealed that signet-ring cell carcinoma was located in approximately one-third of the superficial portion of the mucosal layer, with a tumor size of 13 mm. No lymphatic invasion, venous invasion, or fibrosis was observed in the submucosal layer. This case had nodal metastasis and was finally diagnosed as stage IB (T1N1M0) according to the Japanese Classification of Gastric Carcinoma (JCGC). The patient is alive without recurrence 6 years after treatment.

DOI： 10.1007/s10120-010-0562-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: The therapeutic efficacy of lymphocytapheresis in autoimmune diseases is presumed to be caused by depletion of activated lymphocytes. However, nothing is known about the inducer of activated lymphocytes, the antigen-presenting dendritic cells, during lymphocytapheresis. Basic Procedures: Six sessions of lymphocytapheresis were done in five patients with ulcerative colitis. Dendritic cells were enriched from the buffy coat of depleted lymphocytes and also from the peripheral blood. The phenotype and function of dendritic cells were studied by dual-color flow cytometry and in allogenic mixed leukocyte reaction, respectively. The serum levels of inflammatory cytokines (interleukin-1alpha 6, 8, 10, and 12 and tumor necrosis factor-alpha and beta) were measured before and after lymphocytapheresis in all cases. Main Findings: Lymphocytapheresis was safe and caused clinical, endoscopic or histologic improvements in all patients with ulcerative colitis. Many CD83-positive mature dendritic cells were found in the buffy coats after each session of lymphocytapheresis. The function of dendritic cells, the frequencies of CD83-positive dendritic cells and the levels of interleukin-6 and interleukin-8 were down regulated in all patients with ulcerative colitis after lymphocytapheresis compared with their levels before lymphocytapheresis. Conclusions: Depletion and down regulation of the function of dendritic cells and diminished levels of inflammatory cytokines caused by lymphocytapheresis may contribute to the therapeutic efficacy of lymphocytapheresis.

DOI： 10.1097/01.DCR.0000054880.68257.B7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PROFESSOR D A SPANDIDOS  

To increase the sustained response (SR) rate in chronic hepatitis C (CHC), we tried a combination therapy with interferon (IFN) alpha and beta. Fifty patients were grouped into 4 groups: group 1H (n=9), HCV serotype 1 and high HCV-RNA titer (over 6 log copies/ml); group 1L (n = 11), HCV serotype 1 and low HCV-RNA titer (less than 6 log copies/ml); group 2H (n=23), HCV serotype 2 and high HCV-RNA titer; group 2L (n=7), HCV serotype 2 and low HCV-RNA titer. They were given a total dose of 768 MIU which included natural IFN 6 (6 MIU) once daily for 28 consecutive days and then natural IFN a (10 MIU) three times a week for 20 weeks. Forty-nine patients with CHC receiving IFN a at total dose of 480 MIU served as single therapy group. In combination group, SR rate was achieved in 62%,44% in 1H, 45% in 1L, 70% in 2H, and 86% in 2L, respectively. In single group, SR rate was achieved in 45, 14, 58, 60, and 82%, respectively. There was no significant difference for SR rate between combination group and single group. However, in patients with HCV-RNA titer between 6-7 log copies/ml of IH group, SR rate in combination group (67%, 4/6) was significantly higher than that of single group (18%, 3/17) (p&lt;0.05). These data suggest the usefulness of combination therapy with IFN a and 6 in CHC with serotype I having moderately high HCV-RNA titer.

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Background Antigen-presenting dendritic cells are the inducers and regulators of immune responses. Here, we have discussed the phenotype and function of dendritic cells in situ and their alteration during lymphocytapheresis in patients with ulcerative colitis. Methods. Dendritic cells were enriched from the peripheral blood mononuclear cells by culturing with granulocyte-macrophage colony-stimulating factors and interleukin 4 for 8 days. The function of dendritic cells was evaluated in an allogenic mixed leukocyte reaction. Flow cytometry was employed to study the phenotype of dendritic cells. Lymphocytapheresis was done by a continuous flow centrifugation technique using a CS-3000 separator. Immunohistochemical methodology was employed to detect dendritic cells at the colonic mucosa. Results. Peripheral blood dendritic cells had increased functional capacity, and these cells were matured and activated compared to dendritic cells from normal controls. CD83-positive activated and mature dendritic cells were found at the colonic mucosa from patients with ulcerative colitis. Lymphocytapheresis induced decreased function of peripheral blood dendritic cells in patients with ulcerative colitis. Also, the levels of inflammatory cytokines were reduced by lymphocytapheresis. Conclusions. Increased function of dendritic cells may be related to the inflammatory mucosal milieu found in patients with ulcerative colitis. Depletion of dendritic cells during lymphocytapheresis may downregulate the exacerbated immune response in patients with ulcerative colitis.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective Increased lymphocyte activation and production of inflammatory cytokines are implicated in the pathogenesis of ulcerative colitis, Because antigen-presenting dendritic cells play a cardinal role in the activation and survival of activated lymphocytes, the aim of the present study was to characterize dendritic cells in ulcerative colitis.
Design This study was designed to compare the phenotypes and functions of peripheral blood dendritic cells among healthy normal volunteers and patients with ulcerative colitis or Crohn's disease. Activated dendritic cells were also localized at the colonic mucosa,
Methods Peripheral blood dendritic cells were generated from 15 patients with ulcerative colitis, 10 patients with Crohn's disease and 15 healthy control volunteers. The stimulatory capacities of dendritic cells were analysed in an allogenic mixed lymphocyte reaction. Nitric oxide was detected by the Griess method. Single- and dual-colour flow cytometry was employed to study the levels of maturation of dendritic cells. Activated dendritic cells were localized immunohistochemically in the colonic mucosa,
Results In comparison to normal controls, peripheral blood dendritic cells from patients with ulcerative colitis showed significantly increased stimulatory capacities (P &lt;0.05) and produced significantly higher levels of nitric oxide (P &lt;0.05). The numbers of activated dendritic cells were also significantly higher in ulcerative colitis (P &lt;0.05). Mature and activated dendritic cells expressing the CD83 antigen were detected at the inflamed colonic mucosa in patients with ulcerative colitis and Crohn's disease.
Conclusions Activated and mature dendritic cells may have a role in the induction of an exacerbated immune response in ulcerative colitis, This study provides the scientific and logical basis for blocking the maturation and activation of dendritic cells in ulcerative colitis as a new therapeutic intervention. (C) 2001 Lippincott Williams & Wilkins.

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡技師会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

【背景・目的】原発性胆汁性胆管炎(PBC)における食道胃静脈瘤の評価は重要である。一方、門脈圧亢進症性胃症(PHG)も門脈圧亢進により発症し、無症候性PBCにも合併するが意義は不明で、それを明らかにするため検討を行った。【対象】PBCで食道胃静脈瘤、PHGを継続し評価しえた112例を調査した。【結果】PHG合併は、PBC診断時21例、観察期間中の出現例6例の計27例(21.9%)であった。PHG合併別では生命予後には有意な差異はなかったが、症候性への移行はPHG合併群が有意に早かった。症候性移行時点での食道胃静脈瘤合併はPHG合併群、非合併群でそれぞれ74%、40%であり、PHG合併群は門脈圧亢進症型への移行が多かった。また、PHG合併は症候性移行の独立した危険因子であった。【結語】PHGの合併は、症候性への進展、門脈圧亢進症型へ移行する可能性が高く、慎重な経過観察が必要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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J-GLOBAL

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Language：Japanese   Publisher：日本小腸学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡技師会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器病学会-四国支部  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡技師会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡技師会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化管学会  

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Language：English  

We herein report a 55-year-old woman who presented with erythema and bilateral hilar lymphadenopathy 4 months prior to the detection of pancreatic lesions on an ultrasound. A skin biopsy showed evidence of sarcoidosis. The largest lesion in the tail of the pancreas was hypoechoic on endoscopic ultrasonography (EUS). The lesion was initially iso-enhanced on contrast enhanced-EUS (CE-EUS) but subsequently became hypoenhanced. The lesion revealed heterogeneous components of both soft and hard tissue on EUS elastography. She was ultimately diagnosed with pancreatic sarcoidosis based on the presence of noncaseating granulomas seen on pancreatic tissue retrieved through an EUS-guided fine needle aspiration biopsy.

DOI： 10.2169/internalmedicine.9084-17

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Language：English   Publisher：WILEY  

AimAssessing disease progression in patients with primary biliary cholangitis (PBC) is necessary in order to evaluate therapeutic effectiveness. Therefore, the aims of this study were to evaluate both the diagnostic accuracy of both real-time tissue elastography (RTE) and vibration-controlled transient elastography (VCTE), and the usefulness of hepatic and splenic elasticity as predictive markers for the progression of symptomatic PBC.
MethodsThe study participants were 44 patients with PBC. We assessed hepatic and splenic elasticity using RTE and VCTE and measured serum markers related to fibrosis and hepatic and splenic blood flow using Doppler ultrasonography. We then compared RTE and VCTE for diagnostic accuracy. Patients with asymptomatic PBC were followed every 1-3months.
ResultsBoth RTE and VCTE performed well and had superior diagnostic accuracy compared with biochemical markers. The areas under the receiver operating characteristic curve for RTE and VCTE were 0.92 and 0.92, 0.95 and 0.91, and 0.97 and 0.91 for F2, F3, and F=4, respectively. During follow-up, nine patients (25.0%) developed liver-related symptoms. Multivariate analysis revealed that splenic elasticity assessed using RTE was a significant independent factor for the development of liver-related symptoms (odds ratio, 2.19; P=0.024).
ConclusionsReal-time tissue elastography offered better diagnostic accuracy for severe fibrosis and cholangitis than VCTE. Splenic elasticity determined using RTE is a useful parameter for evaluating liver-related symptoms and an effective predictive marker of disease progression in patients with asymptomatic PBC.

DOI： 10.1111/hepr.12861

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Language：English   Publisher：GEORG THIEME VERLAG KG  

Background and study aim Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness.
Participants and methods This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored &lt; 80% accuracy on Test 1. The primary end point was the difference in accuracy between Test 1 and Test 2 for the two groups.
Results A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9% for the e-learning group and 61.7% for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively; P &lt; 0.001).
Conclusion This study clearly demonstrated the efficacy of the e-learning system in improving practitioners' capabilities to diagnose EGC using M-NBI.

DOI： 10.1055/s-0043-111888

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：MOSBY-ELSEVIER  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：The Japan Society of Ultrasonics in Medicine  

<B>Purpose</B>: This study aimed at prospectively evaluating bile duct anatomy on ultrasonography and evaluating the safety and utility of radiofrequency ablation (RFA) assisted by virtual ultrasonography from gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). <B>Methods</B>: The institutional review board approved this study, and patients provided written informed consent prior to entry into the study. Bile duct anatomy was assessed in 201 patients who underwent Gd-EOB-DTPA-enhanced MRI for the evaluation of hepatic tumor. Eighty-one of these patients subsequently underwent RFA assisted by ultrasound imaging. In 23 patients, the tumor was located within 5 mm of the central bile duct, as demonstrated by MRI. <B>Results</B>: Virtual ultrasonography constructed by Gd-EOBenhanced MRI was able to visualize the common bile duct, left hepatic duct, and right hepatic duct in 96.5, 94.0, and 89.6% of cases, respectively. The target hepatic tumor nodule and biliary duct could be detected with virtual ultrasonography in all patients, and no severe complications occurred. <B>Conclusion</B>: The running pattern of the bile ducts could be recognized on conventional ultrasound by referencing virtual ultrasonography constructed by Gd-EOB-DTPAenhanced MRI. RFA assisted by this imaging strategy did not result in bile duct injury.

DOI： 10.3179/jjmu.JJMU.K.14

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Language：Japanese   Publisher：(一社)日本病態栄養学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

Fontan術後の長期経過中に、Fontan循環に起因し肝線維化の進展と肝細胞癌の発症をきたすFontan術後肝合併症(Fontan-associated liver disease:FALD)が近年注目されている。FALD症例で肝線維化診断のため肝生検を施行した報告は少数ながらみられるが、腹腔鏡を施行し、肝の形態と組織評価の両方を行っている報告は無い。今回我々は腹腔鏡検査を施行しFALDを診断しえた3例を経験した。症例は34歳男性、33歳男性、25歳女性で、それぞれFontan術後から23年、17年、17年であった。腹腔鏡検査にて全例結節肝の所見であった。鬱血肝に対する肝生検では術後出血に注意する必要があるが、腹腔鏡では腹腔内出血の有無を詳細に観察可能であり、今回肝生検を施行した全例で出血が無く終了できた。肝組織所見は、中心静脈周囲を中心とした線維形成がみられ、鬱血による線維化進展に矛盾しない所見であった。Fontan術後症例では安全かつ確実な診断を行うためには従来の超音波ガイド下生検よりも腹腔鏡検査での施行が望ましい。FALDは術後経過により肝線維化が進展し肝発癌の高危険群になると考えられ、定期的な画像検査が必要である。(著者抄録)

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Language：English   Publisher：SPRINGER INTERNATIONAL PUBLISHING AG  

Introduction: Spontaneous esophageal rupture is a rare condition with a high mortality rate, and it is generally treated by surgery. In the present report, successful non-surgical closure of spontaneous esophageal rupture by endoscopic ligation with snare loops in a patient with pyopneumothorax and septicemia is presented.
Case description: The case of an 80-year-old man patient with spontaneous esophageal rupture who was cured by endoscopic ligation with snare loops is reported. The patient was admitted with severe chest pain. Chest CT scan revealed pneumomediastinum, and an upper gastrointestinal series using gastrografin showed leakage of contrast medium from the lower esophagus. Therefore, a diagnosis of spontaneous esophageal rupture to the thorax was made. Since the family refused surgery, the patient was treated conservatively. Since extensive blood in the stool was noted on day 5, an emergency endoscopic examination was performed. Clipping was performed around the perforation, and the clips were ligated with snare loops. The patient was discharged on day 83 without recurrence.
Discussion and evaluation: We suggest that endoscopic ligation with snare loops should be chosen for elderly people and high-risk cases.

DOI： 10.1186/s40064-016-2624-4

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：Japan Society of Hepatology  

Patients with Fontan circulation tend to develop liver fibrosis, liver cirrhosis, and even hepatocellular carcinoma. The present study describes two male patients and one female patient with congenital heart defects who were treated with the Fontan procedure and who subsequently developed cardiac cirrhosis. The Fontan procedure diverts blood from the inferior vena cava and superior vena cava to the pulmonary arteries, thereby increasing survival in infants born with a single effective ventricle. However, as such patients live longer, the high pulmonary and right-sided heart pressure causes chronic passive hepatic congestion and definitive cardiac cirrhosis. The three patients were asymptomatic, and their liver function tests were within normal limits. However, laparoscopy showed nodular cirrhosis, lymph vesicles, and white icing sugar-like (Zuckerguss) plaques on the surface of the liver in all three patients. Therefore, these patients were diagnosed with liver cirrhosis secondary to Fontan-associated liver disease.

DOI： 10.2957/kanzo.57.656

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：洛和会ヘルスケアシステム  

Klebsiella pneumoniaeは尿路感染症や肺炎の起因菌として日常診療でよく遭遇する細菌の1種であるが、同菌による侵襲性肝膿瘍症候群が1980年代より台湾を含む東アジアで報告されている。この症候群は免疫不全の無い健常者にも発症し、中枢神経感染症や眼内炎を伴い、しばしば神経障害や失明など重大な後遺症を残す。病原性の強さはムコイド産生型の過粘稠性K.pneumoniae株との関連が示唆されており、細菌検査室では平板培地上のコロニーで過粘稠性を確認するstring testが有用である。当院でも過粘稠性K.pneumoniaeによる侵襲性膿瘍症候群を2例経験したので報告する。(著者抄録)

CiNii Books

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Language：Japanese   Publisher：(一社)日本内科学会  

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Language：Japanese   Publisher：日本小児アレルギー学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：愛媛医学会  

症例は77歳女性で、呼吸困難、意識障害を主訴に救急搬送となった。来院時、敗血症性ショックを呈し、ICU入室にて集中治療を開始した。胸部CTでは誤嚥性肺炎を認め、腹部CTでは胆嚢気腫と十二指腸球部に存在する結石が確認され、Bouveret症候群の診断に至った。集学的治療により全身状態は改善し、経過中の腹部CTで胆石の空腸内への移動が確認された。入院後第25病日に胆石イレウスに対し開腹手術を施行し、空腸切除、結石採石、再縫合、胆嚢摘出を行った。切除標本は6×3×3cmの巨大な胆嚢結石で、術後経過良好にて、第72病日にリハビリ目的で転院となった。

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(株)医学書院  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(株)医薬ジャーナル社  

消化器領域は広く多様であり、いろいろな新薬の臨床試験が進んでいる。その中でも特に、C型肝炎の治療薬の開発進展が著しい。難治とされていたC型肝炎ウイルス(HCV)genotype 1型の治療薬も、2013年12月に第二世代のプロテアーゼインヒビターとしてシメプレビルが発売され、90%程度の高いウイルス排除率と副作用の軽減が見込まれている。B型肝炎もHBs抗原消失を目指した治療法が模索されている。また、消化管領域では機能性ディスペプシアに対するアコチアミド、慢性便秘症に対するルビプロストンが発売された。いずれの薬物も治療対象および正しい治療法の理解を必要とする。(著者抄録)

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Language：Japanese   Publisher：愛媛医学会  

72歳女。12年前に1型糖尿病と診断された。以来当院に通院し、最近は高血糖と低血糖を繰り返していた。4ヵ月ほど前から1日3回程度の下痢があり、近医で整腸剤を処方されたが改善せず、下部消化管内視鏡の所見から潰瘍性大腸炎(UC)を疑われ、血糖コントロールも不良であったため、精査目的で当院に入院となった。諸検査によりUCと診断し、下部消化管内視鏡所見から寛解期に入っていると考えられたため、それまで整腸剤で経過観察していたが、寛解維持のためにサラゾスルファピリジンを使用した。また、血清鉄とフェリチンの低値を認め、便潜血陽性であったため、潰瘍性大腸炎からの出血による貧血と考えてクエン酸第一鉄を投与した。本例では、糖尿病患者に多い便秘があったことに加え、高齢により腹部症状が軽微であったために、UCの診断に至るまで期間を要したと考えられた。

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Language：Japanese   Publisher：一般社団法人 日本消化器内視鏡学会  

Dietary saturated fatty acid (SFA) intake is an important risk factor for ischemic heart disease, non-alcoholic steatohepatitis and carcinogenesis. Dietary SFAs are absorbed by small intestinal villi after their hydrolysis from triacylglycerols by pancreatic lipase. &lt;SUP&gt;13&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt; breath tests, based on nondispersive infrared spectrometry, allow noninvasive quantitation of physiological processes. The breath &lt;SUP&gt;13&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt; assay after loading of &lt;SUP&gt;13&lt;/SUP&gt;C-labeled sodium palmitate, which is one of the most abundant dietary SFAs, is designed to assess the absorption of dietary SFAs from the small intestine. Traditionally, the breath &lt;SUP&gt;13&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt; assay after loading of &lt;SUP&gt;13&lt;/SUP&gt;C-labeled sodium palmitate requires its oral administration. Using gastrointestinal endoscopy, we administered &lt;SUP&gt;13&lt;/SUP&gt;C-labeled sodium palmitate directly into the duodenum to avoid the influence of gastric emptying. Palmitic acid is an SFA that is a solid at room temperature and is insoluble in water. However, &lt;SUP&gt;13&lt;/SUP&gt;C-labeled sodium palmitate can be maintained in a liquid state during administration by using the emulsifying effect of RACOL Liquid&lt;SUP&gt;&amp;reg;&lt;/SUP&gt; (Otsuka Pharmaceutical Factory, Inc.). Specifically, 200 mg of &lt;SUP&gt;13&lt;/SUP&gt;C sodium palmitate (Cambridge Isotope Laboratories, Inc.) is dissolved in 20 mL distilled water, heated to 70&amp;deg;C, and then blended with 20 mL warmed (50&amp;deg;C) RACOL Liquid&lt;SUP&gt;&amp;reg;&lt;/SUP&gt;, which is used to keep the fatty acid in a liquid state. After an overnight fast of 12 h, all subjects received &lt;SUP&gt;13&lt;/SUP&gt;C-labeled sodium palmitate in the horizontal portion of the duodenum using an upper gastrointestinal tract endoscope. Thereafter breath samples were collected every 30 min over a period of 6 h. Breath samples were also collected before loading. Samples were analyzed using nondispersive infrared spectrometry. Changes in the &lt;SUP&gt;13&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt;/&lt;SUP&gt;12&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt; ratio from baseline were expressed as &amp;Delta; (&amp;permil;). The time-dependent change in the &amp;Delta; (&amp;permil;) was used as a marker of the absorption of &lt;SUP&gt;13&lt;/SUP&gt;C-labeled SFAs from the small intestine. The use of this endoscopic approach for the breath &lt;SUP&gt;13&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt; assay after loading of &lt;SUP&gt;13&lt;/SUP&gt;CO&lt;SUB&gt;2&lt;/SUB&gt;-labeled sodium palmitate results in a more precise evaluation of the absorption of dietary SFAs from the small intestine than that obtained using the traditional method of administering it orally.

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

食事由来の脂質の中で、特に飽和脂肪酸は、動脈硬化性疾患、非アルコール性脂肪肝炎、種々の癌腫の発癌において重要な危険因子である。飽和脂肪酸は、食事中の中性脂肪が膵リパーゼなど消化酵素により脂肪酸の状態まで加水分解された後、主に上部空腸粘膜より吸収される。安定性・非放射性同位元素13C標識脂肪酸試薬を用いた13C呼気ガス診断は、小腸の脂肪酸吸収能を評価することができるが、従来からこの試験は経口投与で行われており、胃の排出時間の差がその結果の評価を困難にしていた。そこで、上部消化管内視鏡下に胃を介さず十二指腸に直接試薬を散布する方法を開発した。飽和脂肪酸は、常温で固形、水に不溶であるため、内視鏡投与のためには飽和脂肪酸を液状化する技術が必要だが、それは経腸栄養剤ラコールの乳化作用を利用することで可能である。この内視鏡アプローチ法によってより正確な小腸脂肪酸吸収能を評価することができる。(著者抄録)

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Language：Japanese   Publisher：(一社)日本病理学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(株)学研メディカル秀潤社  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

症例は66歳女性で、肝硬変で経過観察中にヘモグロビン低下を指摘され、上部消化管内視鏡で食道静脈瘤、前庭部び漫性毛細血管拡張(GAVE)、門脈圧亢進症性十二指腸症(PHD)が認められた。食道静脈瘤に対し内視鏡的硬化療法を、GAVEにはアルゴンプラズマ凝固止血法(APC)を施行し、肝生検で非アルコール性脂肪肝炎と診断した。しかしその後GAVEの再燃と持続するPHDにより消化管出血が生じ、APCを3回追加したが貧血進行を来たした。APCに加えてPHDに対する部分的脾動脈塞栓術を施行し、術前の圧測定では閉塞肝静脈圧17.4mmHg、開放肝静脈圧4.4mmHgと圧較差が認められた。脾動脈中極枝、下極枝を選択して2mmのジェルパートで塞栓を行い、75%の梗塞を得た。術後重篤な有害事象はなく、ドップラー超音波では右門脈一次分枝の血流が11.0cm/sから14.8cm/sと若干改善した。内視鏡での発赤所見や貧血は改善し、良好な状態が保たれている。

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

肝細胞癌に対しラジオ波焼灼術(RFA)を施行した症例で、術前血小板数が5万/μl未満であった77例(男47例、女30例、平均66歳)を対象に、術後の腹腔内出血について検討した。抜針直後にドップラーエコー信号が肝表面から腹腔内にみられた症例、またはペルフルブタン静脈注射後に腹腔内への造影剤漏出が認められた症例は76例(98.7%)で、高率に出血を疑う所見が認められた。抜針5分後に同所見が認められたのは7例(10.0%)で、持続的な腹腔内への出血が考えられた。これらの症例には再度穿刺を行い、ドップラー信号または造影剤漏出がなくなるまで焼灼を行った。治療終了3時間後にヘモグロビンが2.0g/dl以上低下した症例はなかった。なお同時期の術前血小板数5万/μl以上のRFA施行1298例では、治療翌日のCTで腹腔内出血が認められたのは2例のみであった。5万/μl未満群と以上群の患者背景では最大腫瘍径やChilde-Pugh gradeに有意差はなかった。

DOI： 10.11423/jsph.19.125

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Language：Japanese   Publisher：愛媛医学会  

症例1は59歳男性で、悪性リンパ腫再発に対しリツキシマブ+エトポシド療法を施行、6コース施行中の9月より肝機能増悪があった。HBs抗原陽性、HBV再活性化がみられ、HBs抗原陽転後ラミブジンを投与したが肝機能が増悪し、紹介入院となった。意識清明、皮膚黄染、眼球結膜に黄疸あり、総ビリルビン上昇、AST・ALT上昇著明で、PT35.8%と低下、肝予備能低下がみられた。ラミブジン投与を継続し、ステロイドパルス療法を開始し、HBV-DNA量は減少傾向であったが発熱、III度肝性脳症を合併し遅発性肝不全と診断した。治療を継続したが肝不全が進行し、47病日に死亡した。症例2は47歳男性で、悪性リンパ腫に対し、high dose CHOP療法を施行し、悪性リンパ腫再発に対し、リツキシマブ投与を開始した。HBs抗原陽性、HBVキャリアのためラミブジン投与を継続した。HBVによる肝障害と診断し、アデホビルを追加投与し、ステロイドパルス療法を開始したが肝機能が増悪し、入院後も治療を継続したが肝不全に肺炎を合併し16病日に死亡した。症例3は59歳男性で、悪性リンパ腫に対し、R-CHOP療法を開始した。HBs抗原陽転、HBV-DNAの増加し受診した。エンテカビル内服でHBV-DNA低下傾向であったが総ビリルビン上昇、PT低下傾向が持続し、ステロイドパルス療法を開始した。総ビリルビン値低下、PT改善がみられ53病日に退院した。

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Language：English   Publisher：FEDERATION AMER SOC EXP BIOL  

IBDs are thought to involve uncontrolled innate and adaptive immunity against intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD. We show here that oral tolerization to CA I induced antigen-specific protection from intestinal inflammation in a murine model. Oral administration of CA I but not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine colitis and DSS-induced murine colitis. Next, we investigated the mechanisms involved in the therapeutic effects of oral administration, such as induction of ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN and colon. When compared with PBS-treated mice, CA I-treated mice had higher Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon; had higher TGF-beta production in the MLN and colon; had lower ROR gamma t mRNA expression in the MLN and colon; and had lower IL-17 mRNA expression and production in the MLN. These results demonstrate that oral administration of CA I induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+) Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that oral tolerization with CA I is an effective therapeutic strategy for IBD regulation.

DOI： 10.1189/jlb.1212612

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Language：Japanese   Publisher：(NPO)日本食道学会  

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Language：Japanese   Publisher：(株)日本メディカルセンター  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：Japanese   Publisher：(株)医薬情報研究所  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：愛媛医学会  

膵癌ステージIVb死亡症例29例(男16名、女13名、43〜89歳)を対象に検討した。生存日数の中央値は171日で、生存日数170日以下の14例をA群、171日以上の15例をB群とした。平均年齢はA群が73歳と高い傾向がみられた。初発時の症状は両群間で有意差はみられなかった。診断時血液検査値は、A群において血清アルブミン値が有意に低く、ヘモグロビン(Hb)A1cが有意に高値であった。また、腫瘍マーカーのCEAがA群で高い傾向がみられた。A群では腹水を有する例が有意に多く、また体尾部癌が多い傾向がみられた。治療の有無については両群間で有意差はみられなかった。血清アルブミン、HbA1cが予後を予測する鋭敏なマーカーとなる可能性がある。

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publisher：ELSEVIER SCIENCE BV  

The motilin receptor belongs to a family of Class I G protein-coupled receptors, and is an important endogenous regulator of gastrointestinal motor function. Motilin and erythromycin, two chemically distinct full agonists of the motilin receptor, are known to bind to distinct regions of this receptor, based on previous systematic mutagenesis of extracellular regions that dissociated the effects on these two agents. The action of these different chemical classes of agonists likely yields a common activation state of the cytosolic face of this receptor that is responsible for interaction with its G protein. In the current work, we studied the predicted transmembrane (TM) domains of this receptor for functional responses to motilin and erythromycin. Motilin receptor constructs were prepared in which each residue in the TM domains was mutated to alanine or valine. Each construct was expressed in COS cells and characterized for motilin and erythromycin binding and intracellular calcium responses stimulated by both agonists. Constructs with mutations-of residues, Asp94, Leu95, Arg97 and Trp99 in TM2, Ser169 in TM4, and Tyr321 and Glu325 in TM6, were responsible for the negative impact on biological activity stimulated by erythromycin, but had no effect on motilin responses. On the other hand, constructs with mutations of residues, Leu113 in TM3, Pro172 in TM4,Trp250 and Tyr255 in TM5, and Gln334 in TM7, were negatively responsive to both erythromycin and motilin. These data support important roles of new regions in the TM domains of the motilin receptor for erythromycin action, suggesting differential mechanisms of actions by peptidyl and non-peptidyl ligands. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.regpep.2012.10.003

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：English   Publisher：SPANDIDOS PUBL LTD  

Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophagecolony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached a-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.

DOI： 10.3892/ijo.2012.1626

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Language：Japanese   Publisher：(一社)日本消化器内視鏡技師会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本門脈圧亢進症学会  

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Language：English   Publisher：ELSEVIER MASSON  

A lesion was discovered in the tail of the pancreas by ultrasonography performed during a health checkup for a 59-year-old Japanese man. Abdominal contrast-enhanced computed tomography (CE-CT) revealed strong enhancement in a 4-cm tumor in the pancreatic tail and in a 1-cm tumor in the pancreatic body. Serum glucagon levels were elevated to 54,405 pg/mL and a preoperative diagnosis of glucagonoma was made. The pancreatic tail and spleen were resected en bloc, along with a protruding tumor in the pancreatic body. However, histopathological evaluation revealed diffuse glucagonoma throughout the pancreas. When we retrospectively reviewed abdominal CE-CT after the operation, the entire pancreas was seen to be enlarged and diffusely enhanced by strong spots. Immunohistochemical examination using anti-CD31 demonstrated rich microvessels in two solid glucagonomas as well as microglucagonoma throughout the entire pancreas, indicating hypervascularity. Enlarged pancreas and diffuse enhancement of the pancreas by strong spots may be characteristic features of diffuse glucagonoma on abdominal CE-CT. (C) 2011 Elsevier Masson SAS. All rights reserved.

DOI： 10.1016/j.clinre.2011.12.003

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Language：Japanese   Publisher：愛媛医学会  

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Language：English   Publisher：ELSEVIER SCIENCE BV  

The motilin receptor (MR) belongs to a family of Class I G protein-coupled receptors that also includes growth hormone secretagogue receptor (GHSR). Their potentially unique structure and the molecular basis of their binding and activation are not yet clear. We previously reported that the perimembranous residues in the predicted extracellular loops and amino-terminal tail of the MR were important for responses to the natural peptide ligand, motilin, and the transmembrane domains of the MR were important for a non-peptidyl ligand, erythromycin. We also reported that the perimembranous residues in the second extracellular loop of the GHSR were critical for natural ligand ghrelin binding and activity. The MR is 52% identical to GHSR, with 86% sequence identity in the transmembrane domains. In the current work, to gain insight into a relationship between MR and GHSR, we studied functional responses to motilin, erythromycin and ghrelin of expression cells of chimeric constructs of MR and GHSR and co-expression cells of both MR and GHSR We also generated human MR transgenic mice, and clarified a relationship between motilin and ghrelin. MR(1-62)/GHSR(68-366) construct responded only to ghrelin, MR(1-102)/GHSR(108-366) responded to ghrelin and erythromycin, and MR(1-129)/GHSR(135-366) and MR(1-178)/GHSR(184-366) responded to erythromycin, while GHSR(1-183)/MR(179-412) responded to neither motilin, erythromycin nor ghrelin. MR and GHSR co-expression cells have no additional responses to these ligands. Motilin or erythromycin administration to human MR transgenic mice resulted in a decrease of serum acyl-ghrelin levels, while MR and GHSR mRNA expression in the gastrointestinal tracts were not changed. These data suggested that in species expressing both motilin-MR and ghrelin-GHSR, there is a compensatory relationship in vivo. (C) 2012 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.regpep.2012.03.001

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER SCIENCE BV  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：日本消化器免疫学会  

免疫寛容を誘導する樹状細胞、いわゆる制御性樹状細胞が自己免疫性疾患の病態を改善させることが報告されている。盲腸細菌抗原をパルスした制御性樹状細胞(Reg-DCCBA)が炎症性腸疾患モデルマウスの腸炎を抑制できるか否かを明らかにすることを目的とした。Reg-DCCBAは体重減少、腸管長の短縮を抑制し、組織学的にも腸炎の進展を抑制した。その機序としては腸間膜リンパ節における制御性T細胞の誘導が考えられた。Reg-DCを用いた細胞療法が炎症性腸疾患に対する新しい治療法となる可能性が示唆された。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器内視鏡技師会  

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Language：English   Publisher：AMER ASSOC IMMUNOLOGISTS  

Inflammatory bowel disease (IBD), which is characterized by a dysregulated intestinal immune response, is postulated to be controlled by intestinal self-antigens and bacterial Ags. Fecal extracts called cecal bacterial Ag (CBA) have been implicated in the pathogenesis of IBD. In this study, we identified a major protein of CBA related to the pathogenesis of IBD and established a therapeutic approach using Ag-pulsed regulatory dendritic cells (Reg-DCs). Using two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry, carbonic anhydrase I (CA I) was identified as a major protein of CBA. Next, we induced colitis by transfer of CD4(+)CD25(-) T cells obtained from BALB/c mice into SCID mice. Mice were treated with CBA- or CA I-pulsed Reg-DCs (Reg-DCsCBA or Reg-DCsCA1), which expressed CD200 receptor 3 and produced high levels of IL-10. Treatment with Reg-DCsCBA and Reg-DCsCA1 ameliorated colitis. This effect was shown to be Ag-specific based on no clinical response of irrelevant Ag (keyhole limpet hemocyanin)-pulsed Reg-DCs. Foxp3 mRNA expression was higher but ROR gamma t mRNA expression was lower in the mesenteric lymph nodes (MLNs) of the Reg-DCsCA1-treated mice compared with those in the MLNs of control mice. In the MLNs, Reg-DCsCA1-treated mice had higher mRNA expression of IL-10 and TGF-beta 1 and lower IL-17 mRNA expression and protein production compared with those of control mice. In addition, Reg-DCsCBA-treated mice had higher Foxp3(+)CD4(+)CD25(+) and IL-10-producing regulatory T cell frequencies in MLNs. In conclusion, Reg-DCsCA1 protected progression of colitis induced by CD4(+)CD25(-) T cell transfer in an Ag-specific manner by inducing the differentiation of regulatory T cells. The Journal of Immunology, 2012, 188: 2164-2172.

DOI： 10.4049/jimmunol.1100559

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：(公社)日本超音波医学会  

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Language：Japanese   Publisher：The Japanese Society of Gastroenterology  

Pancreatic cancer shows the worst prognosis among the solid tumors, and survival for patients with high-grade liver metastasis is estimated at around a few months. We reported the effects of combination therapy with gemcitabine and S-1 (GS therapy) on pancreatic cancer patients with high-grade hepatic metastasis. Patients with severe metastatic pancreatic cancer received chemotherapy comprising S-1 (30mg/m 2 p.o. bid., days 1-14) and gemcitabine (1000mg/m 2 on days 1 and 8), repeated every 3 weeks. Fourteen patients (7 men, 7 women) received treatment at a mean age of 56.5 years (range, 39-76 years), achieving complete response in 1 patient, partial response in 5 patients, and stable disease in 3 patients and progressive disease in 5 patients. The response rate was thus 43%. Median progression-free survival was 186 days (95% confidence interval, 40-247 days). Median overall survival was 261 days (95% confidence interval, 162-358 days). GS therapy appears to be well-tolerated and effective in patients with high-grade hepatic metastasis.

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Language：Japanese   Publisher：(公社)日本超音波医学会  

胃重積は,胃腫瘍などによる胃-十二指腸重積,胃切除後などに発生する胃-空腸重積が一般的に知られているが,胃-胃重積はきわめて稀である.今回我々は,超音波検査にて胃にmultiple concentric ring signを呈した胃巨大ポリープによる胃-胃重積を経験したので報告する.症例は54歳,女性.子宮頸癌の経過観察中に施行された造影CT検査にて胃内に巨大腫瘤を指摘され,超音波検査を行った.心窩部縦走査にて,胃体部より幽門側にかけてmultiple concentric ring sign及びHay-Fork signを認め,その肛門側に直径40mm程度で境界は明瞭,内部不均一な腫瘤が見られた.上部消化管内視鏡検査で,胃体下部前壁大彎よりに約50mmの有茎性の腫瘤が見られ,病理検査結果は,過形成性ポリープ(GroupI)であった.内視鏡的粘膜下層剥離術(ESD)により胃ポリープは切除された.胃-胃重積は非常に稀な病態で,特徴的な超音波画像を呈した.超音波検査は診断に有用であった.(著者抄録)

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：愛媛医学会  

24歳男。横紋筋肉腫の既往があった。腹部超音波で肝左葉に境界明瞭な径50mmの高エコー結節を認め、また両葉にも高エコー結節が多数あり、造影超音波および腹部MRI所見と合わせて血管筋脂肪腫を疑った。しかし、転移性肝腫瘍と肝血管筋脂肪腫の鑑別、悪性の有無の鑑別を要したため超音波誘導下肝腫瘍生検を施行したところ、病理所見で腫瘍は脂肪細胞と血管成分、平滑筋成分から構成され、免疫染色でHMB-45陽性、SMA陽性、腫瘍内血管にCD34陽性を示し、肝血管筋脂肪腫と診断した。外来で経過観察とし、1年5ヵ月経過現在も腫瘍径の増大、腫瘍個数の増加は認めていない。

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Language：English   Publisher：SPRINGER  

Background A few reports suggest that the emergence of double balloon endoscopy (DBE) has likely changed the clinical picture of small bowel tumors (SBTs).
Aim To further clarify the characteristics of SBTs detected by DBE.
Methods A retrospective chart review was conducted in 227 patients who had undergone DBE.
Results The SBT group contained more symptomatic patients than the non-SBT group (90% vs. 49%, P &lt; 0.0005) with a significantly higher rate of gastrointestinal symptoms at presentation (72% vs. 33%, P &lt; 0.005). Twenty patients (8.8%) were eventually diagnosed with SBT, and their indications for DBE were obscure gastrointestinal bleeding (n = 5), abdominal pain (n = 5), abdominal fullness (n = 5), vomiting (n = 2), and diarrhea (n = 1). Tumors were located in the jejunum in 14 patients (70%) and in the ileum in 6 (30%). A final histological diagnosis was assigned to all 20 patients: primary adenocarcinoma (n = 8, 40%), malignant lymphoma (n = 5, 25%), metastatic cancer (n = 4, 20%), gastrointestinal stromal tumor (n = 1, 5%), carcinoid tumor (n = 1, 5%) and inflammatory fibroid polyp (n = 1, 5%). Stenosis or ulceration were the most frequently observed endoscopic findings (n = 13, 65%). All primary adenocarcinomas and three of four (75%) metastatic cancers showed stenosis or ulceration. Three of five (60%) malignant lymphomas showed multiple lymphomatous polyps. All patients but one underwent surgical resection or chemotherapy or both.
Conclusions DBE is a safe and useful procedure that enables a precise diagnosis of SBTs.

DOI： 10.1007/s10620-011-1741-8

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Two patients who had gastrointestinal hemorrhage due to Sorafenib are presented. In case 1, bloody stools occurred within 1 week after the Sorafenib treatment. The endoscopic findings revealed edematous and reddish changes in the duodenal mucosa. In case 2, bloody stools occurred 1 month after the Sorafenib treatment. Colonoscopic findings indicated similar mucosal change in the colon. The hemorrhagic points were difficult to detect in both cases. However, a quick improvement in the bloody stools after stopping Sorafenib intake suggested that the gastrointestinal hemorrhage was associated with Sorafenib treatment. The endoscopic mucosal findings in both cases would probably be characteristic of patients with gastrointestinal hemorrhage due to Sorafenib.

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

症例1は62歳男で、肝細胞癌(病期IVb)の診断でソラフェニブ800mg/日内服を開始したところ、意識消失と下血が出現し、十二指腸下行脚の発赤からの出血が疑われた。症例2は81歳女で、肝細胞癌に対してソラフェニブ800mg/日を開始したところ、血便と貧血が出現し、大腸回盲部からの出血が疑われた。2症例ともソラフェニブ投与開始後、比較的早期に出血が出現したが、内服中止により速やかに出血は改善し、再出血は認めていない。また、2症例の内視鏡所見より、門脈圧亢進症粘膜病変のような血管拡張や発赤、または明らかな出血部位の同定が困難な粘膜病変がソラフェニブによる粘膜出血病変の特徴である可能性が示唆された。ソラフェニブを投与する際には、消化管出血の副作用を念頭に置いて経過観察を行い、出血出現後は速やかに服用を中止することが必要と考えられた。

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Language：Japanese   Publisher：耳鼻咽喉科展望会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：W B SAUNDERS CO-ELSEVIER INC  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一社)日本胃癌学会  

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Language：Japanese   Publisher：日本消化器免疫学会  

関節リウマチ、全身性エリテマトーデスなどの自己免疫性疾患の病態形成にBAFF(B cell activating factor)が関与していることが報告されている。BAFFが自己免疫性膵炎(AIP)の病態に関与しているか否かを検討した。AIP患者の血清BAFF濃度は、慢性膵炎、膵癌および健常人と比較して有意に高く、血清IgGおよびIgG4との間に相関がみられた。AIP患者ではステロイド投与により血清中BAFF濃度は治療前と比較して有意に低下した。BAFFがAIPの病態に関与していることが示唆された。(著者抄録)

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English  

Intussusception of the stomach can result from a tumor or from surgery. Although both gastroduodenal and gastrojejunal intussusception are known, gastrogastric intussusception is rare. We encountered a case of gastrogastric intussusception resulting from an unusually large hyperplastic polyp in a 54-year old woman. The characteristic multiple concentric ring sign was observed on ultrasonography. Computed tomography revealed an unusually large gastric polyp. The ultrasound longitudinal scan showed the typical multiple concentric ring and Hay-Fork signs indicative of a gastrogastric intussusception produced by a 40-mm polypoidal mass in the gastric antrum. With this diagnosis, endoscopic submucosal dissection was carried out and the histologic examination identifi ed an unusually large hyperplastic polyp. These ultrasonographic signs are characteristic in gastrogastric intussusception, and ultrasonography proved useful in reaching this diagnosis. © 2011, The Japan Society of Ultrasonics in Medicine. All rights reserved.

DOI： 10.3179/jjmu.38.651

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

69歳男。排便時出血を主訴に近医を受診し、大腸内視鏡検査で異常を指摘された。直腸のMALTリンパ腫と診断し、H.pylori除菌療法を施行した。上部消化管内視鏡では胃体部大彎の襞皺の軽度の肥厚と軽度のびらんを認めた。除菌は成功したが、直腸病変は変化がなかったため、精査加療目的で紹介となった。免疫組織染色を用いた病理組織学的検査の結果、節性マントル細胞リンパ腫と診断した。確定診断後、Rituximab併用Hyper CVAD/MTx-Ara-C療法を施行した。上部消化管内視鏡検査では、胃体部大彎の襞皺の肥厚、潰瘍、びらん、直腸の病変も消失した。化学療法が奏効したと考えた。化学療法は4コースを予定していたが、骨髄抑制が遷延したため、3コースで治療を終了した。治療終了から20ヵ月後の現在、無再発で経過観察中である。

DOI： 10.11280/gee.52.3099

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Language：Japanese   Publisher：(一社)日本臨床栄養学会  

化学療法(抗がん剤)における食欲不振対策の実際について調査した。自己記入方式による食事アンケート調査で食事実態調査を行い、食事提供システムや献立内容、食事基準を改善した。改善した後の翌年度(次年度記)に再調査し、がん治療における副作用対策食が有効であるか検討した。初年度の調査では「食事がおいしくない」と訴えた患者は191例中39例で、理由は「味付けが薄い(20.9%)」「がん治療の副作用に食事対応できていない(19.6%)」であった。「がん治療中に食事で困った経験があるか」の問いに対して71例(37.2%)が困った経験を持ち、喫食患者3人に1人はがん治療中に食事で困った経験を訴えた。次年度に調査を行ったところ、がん治療中に苦しんだ症状、食事で困った内容については同傾向を示したが、「がん治療の副作用に食事対応できていない」という苦情は減少し、「食事がおいしくない」という訴えも減少した。

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(株)東京医学社  

感染管理の基本は、標準予防策(standard precaution:汗を除くすべての血液、体液、分泌物には感染性があるとして扱うという概念)と感染経路の遮断である。個人用防護具の着用、血液飛散防止への対策、汚染部位の清掃、清拭、内視鏡および処置具の適切な洗浄・消毒が重要である。救命救急内視鏡、特に出血例の緊急内視鏡においては、血液に曝露される機会が多い。術者、介助者、処置後に内視鏡を受ける患者を守るために、平素からの十分な感染対策が必要である。当院では、平成14年から順次、スコープカートの開発、透明キャビネットの設置、清潔区域・非清潔区域の動線分離、内視鏡保管前のエアダスターガンでのスコープ水分除去、洗浄履歴管理の低底を行い、全国で5番目に消化器内視鏡室感染対策認定を受けた。これらの感染管理においては、看護師、内視鏡技師、洗浄員のほか、医師、病院全体の感染管理に対する関心と協力が重要である。(著者抄録)

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publisher：IOS PRESS  

Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology, characterized by injury of the intrahepatic bile ducts that may eventually lead to cirrhosis and liver failure. Evidence suggests cardinal roles for both environmental factors and genetic susceptibility. Nevertheless, the absolute etiology of PBC is unclear, despite recent well-designed case-control studies that reported environmental risk factors, including infectious agents, for PBC. Of the reported infectious agents, some of them are not reproducible and remain controversial. However, infection is no doubt one of the major risks among the environmental factors. This is supported by the fact that infectious agents in autoimmune diseases express antigens resulting in molecular mimicry and xenobiotics that play a role in breaking tolerance. Taken together, recent findings from genome wide assays as well as novel animal models may enable us to better understand the mechanism of pathogenesis responsible for this disease.

DOI： 10.3233/DMA-2010-0747

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：(一社)日本肝臓学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一社)日本癌治療学会  

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Language：Japanese   Publisher：耳鼻咽喉科展望会  

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Language：Japanese   Publisher：(公社)日本医学放射線学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(株)医学書院  

門脈圧亢進症は食道胃静脈瘤,門脈圧亢進症性胃症,門脈圧亢進症性腸症を合併する.これらは消化管出血や貧血の原因となり,臨床上重要である.本稿では,門脈圧亢進症性小腸症について,今までの報告とダブルバルーン内視鏡を中心とした当科での知見を概説した.門脈圧亢進症における小腸病変として,発赤,びらん,毛細血管拡張様所見,静脈瘤が今までにも報告があったが,今回,数の子様粘膜を新たな特徴的所見として加えた.小腸の数の子様粘膜は,絨毛の浮腫,毛細血管の拡張像を表したものであり,脾容積増加,門脈圧亢進症性胃症,門脈圧亢進症性腸症の存在,血小板減少などの門脈圧亢進を示す症候に多かった.(著者抄録)

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：English   Publisher：SPRINGER JAPAN KK  

Background Double-balloon endoscopy (DBE) and capsule endoscopy have opened up a new field of investigation regarding the small intestine. Although DBE has been widely used for diagnosis and treatment of different lesions in the small intestine, there is a paucity of information regarding endoscopic features of the small intestine in patients with liver cirrhosis (LC). Methods. Endoscopic images of the small intestine were taken in 21 patients with LC by DBE (EN-450P5/20 or EN-450T5/W). Biopsy specimens were taken from various parts of the small intestine and examined microscopically. Different endoscopic features of the small intestine were compared in relation to the clinical parameters of these patients. Results. Erythema and telangiectasia were observed in five patients (24%) and one patient (5%), respectively. In eight patients (38%), the small intestinal mucosa was edematous, and the intestinal villi of these patients were swollen and rounded, resembling herring roe. The patients with a herring roe appearance in the small intestine had advanced LC (Child's classification B and Q, and all of them also had portal hypertensive gastropathy and portal hypertensive colopathy. In comparison with patients without a herring roe appearance in the small intestine, patients with a herring roe appearance had a significantly increased spleen volume (P &lt; 0.05) and decreased platelet counts (P &lt; 0.05). Conclusions. Although preliminary, this study indicated that DBE may be useful for detecting different types of endoscopic lesions in patients with LC. A herring roe appearance seems to be one of the characteristic features of portal hypertensive enteropathy. However, further study will be required to develop insights about its pathogenesis.

DOI： 10.1007/s00535-008-2166-9

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Language：Japanese   Publisher：(有)科学評論社  

著者らはダブルバルーン内視鏡による検査において、補助具を使用しない一人挿入法のための手技を考案し、その有用性について検討した。考案した手技は、まず、術者が左手に内視鏡の操作部を保持して左右アングル操作、送気送水操作、吸引操作を行う。そして右手では母指、示指および中指にてオーバーチューブを固定するように保持し、環指、小指および手掌にてスコープのシャフトを挿入するように操作する。その際、透視モニター画面と内視鏡モニター画面は術者から同時に見えるように機器を配置する、であった。以上、このような本手技による内視鏡検査を11例に行ったところ、経口挿入7件および経肛門挿入7件のいずれにおいても一人でダブルバルーン内視鏡を挿入し、検査することが可能であった。

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：Japanese   Publisher：日本膵臓学会  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：MOSBY-ELSEVIER  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：愛媛医学会  

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Language：Japanese   Publisher：日本リンパ学会  

炎症性腸疾患患者の樹状細胞機能を検討した。通院中の潰瘍性大腸炎患者15例、クローン病患者10例、および健常者15例を対象とした。樹状細胞機能を治療前後で比較した。潰瘍性大腸炎患者、末梢血樹状細胞のCD83陽性率、CD86陽性率は健常者に比べて有意に上昇した。クローン病患者は健常者と差がなかった。また、潰瘍性大腸炎患者のT細胞幼若化補助能は、健常者に比べて有意に上昇し、反対に抗原取り込み能は低下した。炎症性腸疾患患者、とりわけ潰瘍性大腸炎患者においては、樹状細胞によってリンパ球が活性化されている機序が予想された。不適切に活性化した樹状細胞、T細胞をリンパ球除去療法で除去した後、強力に免疫寛容を誘導できる樹状細胞を投与すれば、炎症性腸疾患の新しい治療となる可能性が示唆された。

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

肝硬変における食道静脈瘤治療前後の栄養状態の変化を検討するため,当科で加療された内視鏡的食道静脈瘤初回治療例144例を対象に治療前後の血清アルブミン値,コリンエステラーゼ値,コレステロール値を比較した.治療前後でコリンエステラーゼ値が有意に低下していた.65歳以上の高齢者群では非高齢者群と比較してアルブミン値の低下が有意であった.分岐鎖アミノ酸高含有経腸栄養剤の内服を併用した高齢者群では,血清アルブミン値の低下が有意に抑えられていた.高齢者に内視鏡的食道静脈瘤治療を行う際には,分岐鎖アミノ酸高含有経腸栄養剤を併用した栄養管理を行うべきであると思われる(著者抄録)

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Language：Japanese  

We investigated the alteration of nutritional status in 144 patients who were treated for the first time with endoscopic sclerotherapy or endoscopie variceal ligation during their therapies. The serum levels of albumin, cholinesterase and total cholesterol were compared before and after treatment. The serum level of cholinesterase declined significantly. To investigate the impact of aging on the changes of nutritional status we divided all patients into two groups: 1) under 65 years, and 2) over 65 years. The decline of serum albumin of elderly patients (n = 65) was significantly greater than that of younger patients (n = 79). A branched-chain amino acid (BCAA)-enriched nutrient mixture for nutritional treatment significantly suppressed the decline of serum albumin in elderly patients. Nutritional treatment with a BCAA-enriched nutrient mixture should be considered during endoscopic therapy for esophageal varices, especially in elderly patients.

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：うず潮フォーラム事務局  

潰瘍性大腸炎患者7名に対するリンパ球除去療法について,その有効性をマクロファージ遊走阻止因子(MIF)から検討した.リンパ球除去療法施行後,臨床的重症度は全例軽症に改善した.内視鏡所見のMatts分類による重症度分類では4例に改善がみられたが,3例は不変であった.樹状細胞のCD83陽性細胞率,血中MIF濃度は低下した.樹状細胞の活性化抑制はMIF濃度を低下させ,リンパ球除去療法が炎症性腸疾患の治療として有効である可能性が示唆された

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：English   Publisher：SPRINGER TOKYO  

Background. Variceal bleeding is a common, life-threatening complication of primary biliary cirrhosis (PBC). Recently, several reports have suggested that the existence of esophageal varices in patients with PBC is a significant factor in the assessment of disease prognosis. However, there have been no reports on the recurrence of esophageal varices following treatment in patients with PBC. In this study, we investigated the recurrence of esophageal varices in PBC patients and attempted to identify predictive factors for the recurrence of esophageal varices. Methods. Between April 1993 and August 2003, 138 patients with esophageal varices who had been treated by endoscopic variceal ligation (EVL; 96 men and 42 women; age, 33-83 years; mean, 62.6 +/- 10.1 years), were enrolled in the present study. The diagnosis of esophageal varices was made by upper gastrointestinal endoscopy, and the varices were graded according to the criteria of the Japanese Research Society for Portal Hypertension. The relationship between the recurrence of esophageal varices and factors such as biochemical and hematological parameters, as well as the etiology of the liver disease, was analyzed using the Kaplan-Meier method and the multivariate Weibull regression model. Results. PBC patients had an earlier recurrence of esophageal varices compared to non-PBC patients, and two factors, prothrombin time and etiology (PBC/non-PBC), were indicative of significantly earlier recurrence of esophageal varices. Conclusions. We should be extra careful in the follow-up of patients with PBC after therapy for esophageal varices.

DOI： 10.1007/s00535-004-1447-1

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese  

A 20-years-old female was admitted to our hospital with a history of fever for four weeks. She also complained of upper abdominal pain. Laboratory tests suggested the existence of severe inflamation. Abdominal ultrasonography revealed only a hyper echoic shadow between the liver and the abdominal wall. The patient was diagnosed to have Fitz-Hugh-Curtis syndrome due to the presence of Anti-Chlamydia trachomatis anti-body, a hyperechoic shadow between the liver and the abdominal wall by abdominal ultrasonography and abdominal pain. Even, after conservative therapy, her abdominal pain was not disappeared, so we decided to perform laparoscopy for assessing both the existence and the severity of the adhesion. Laparoscopic examination revealed the existence of, so called, &quot;violin string adhesions&quot; between the anterior wall of the liver capsule and the abdominal wall, and Chlamydia trachomatis antigen in ascitic fluid was positive. The clearance of adhesion let to relieve her abdominal pain. In conclusion, a diagnosis of Fitz-Hugh-Curtis syndrome should be considered in femele patients presenting with upper abdominal pain without any apparent causes. Laparoscopy appears to be beneficial not only for the diagnosis but also therapy in patients with Fitz-Hugh-Curtis syndrome.

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

20歳女.主訴は右上腹部痛,発熱.血清クラミジア抗体はIgA型,IgG型共に陽性であった.腹部エコー所見で胆嚢は腫大なく,壁肥厚もなかった.胆管,膵臓にも異常なかった.肝と腹壁の間に層状の高エコー域があった.腹腔鏡検査所見で肝右葉前面と腹膜の間に&quot;violin string adhesion&quot;と呼ばれる線維性癒着があり,淡血性の腹水が少量あった.癒着部近傍の肝被膜と壁側腹膜は白濁していた.入院時の血清クラミジア抗体と腟分泌液のクラミジア抗原が陽性,問診で不特定多数のsexual partnerの存在が確認されたことより,クラミジア感染によるFitz-Hugh-Curtis症候群(FHCS)と確定診断した.癒着剥離術後腹腔鏡所見で持続する腹痛の原因はFHCSによる癒着と考え,同時に癒着剥離術を施行した.術後腹痛は消失し,第31病日には経過良好にて退院した.退院後1年経過した現在も腹痛の出現なく経過良好である

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Language：English  

A 21-year-old man with an 8-year history of acquired immunodeficiency syndrome (AIDS) presented with abdominal pain, jaundice and dark urine. Laboratory data on admission revealed cholestasis. The total bilirubin concentration was 10.0 mg/dL. Alanine transaminase and aspartate transaminase were 198 IU/L and 195 IU/L, respectively. The serum alkaline phosphatase level was 2724 IU/L. γ-Glutamyl transferase was 1770 IU/L. Abdominal ultrasonography and computed tomography revealed dilation of the common bile duct and intrahepatic ducts without gallstones. Endoscopic retrograde cholangiopancreatography showed dilation of the common bile duct up to the level of the ampulla of Vater with partial stenosis. Endoscopic sphincterotomy was performed. The abdominal pain and jaundice resolved immediately and the liver function tests were significantly improved. The patient developed a subarachnoid hemorrhage and died of respiratory arrest 2 months after the endoscopic sphincterotomy.

DOI： 10.1111/j.1443-1661.2004.00344.x

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：(株)自然科学社  

1977年4月から2002年10月までに加療歴のある原発性胆汁性肝硬変(PBC)115例において食道胃静脈瘤合併の有無別で臨床症候,臨床像,組織学的進行度臨床経過および予後を調べた.無症候性PBC(a-PBC),症候性PBC(S-PBC)でS1-PBC(掻痒感を伴う)およびS2-PBC(掻痒感および黄疸を伴う)は各々85例,14例および16例であった.S-PBCはa-PBCに比し食道胃静脈瘤合併率が有意に高かった.食道胃静脈瘤合併は,組織学的に進行するほど頻度は高くなった.生存の有無が確認し得た84例中死亡例は9例であった.累積生存率は,臨床症候が進行するにつれて予後は不良であった.a-PBCで3年間経過を追跡できた56例の3年後の症候,食道胃静脈瘤合併の有無を調べ,a-PBCのままであったのは45例で,S-PBCに移行したのは11例であった.診断時に食道胃静脈瘤を合併していた3例のうち1例がS-PBCへ移行し,a-PBCからS-PBCへ進行した11例のうち4例に食道胃静脈瘤合併がみられた

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Language：Japanese  

CiNii Books

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Language：Japanese   Publisher：The Japan Society of Hepatology  

症例は76歳, 女性. 非B非C型肝細胞癌にて通院中であった. 1997年右舌縁部に発赤, びらん, 疼痛が出現し, 舌生検にて上皮細胞索の鋸歯状増生, 炎症細胞浸潤がみられ, 舌扁平苔癬と診断した. 2001年5月肝性脳症にて入院した際, 舌病変の拡大, 疼痛の増強がみられ, 生検にて扁平上皮癌と診断した. 同月局所麻酔下に右舌部分切除術が施行された. その後徐々に肝不全の進行がみられ同年9月死亡した. HCV患者での肝外病変は高頻度であり口腔内病変, 特に扁平苔癬との関連の検討は散見される. しかし, 非B非C型肝疾患における肝外病変の合併の検討と口腔内病変の合併の報告は少ない. 本症例は非B非C型肝細胞癌に舌扁平苔癬, 舌癌を合併しており, 今後症例の蓄積による検討が必要と考えられた.

DOI： 10.2957/kanzo.44.528

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Language：Japanese   Publisher：The Japan Society of Hepatology  

症例は56歳, 男性. 兄弟に体質性黄疸あり. 20歳頃より黄疸が出現し, 37歳頃某大学病院で腹腔鏡下肝生検. 50歳時に近医でHCV-RNA陽性を指摘され, インターフェロン (IFN) 治療精査目的で当科紹介. D. Bil 優位な高度な黄疸があり, ICG負荷試験やBSP負荷試験では延長があり. 入院後腹腔鏡下肝生検を施行. 黒色肝はなく, 肝組織上黒色顆粒もなし. 以上より Rotor 症候群を合併したC型慢性肝炎と診断. IFN投与開始後, 黄疸は著明に低下し, 投与終了後も投与前と比較して改善した. 我々が調べる限り, 本邦で Rotor 症候群を合併したC型肝炎にIFN投与を行った初めての報告である. ビリルビン代謝および Rotor 症候群を考える上で興味深いと考えられたので, 文献的考察を加えて報告する.

DOI： 10.2957/kanzo.44.443

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Purpose: The therapeutic efficacy of lymphocytapheresis in autoimmune diseases is presumed to be caused by depletion of activated lymphocytes. However, nothing is known about the inducer of activated lymphocytes, the antigen-presenting dendritic cells, during lymphocytapheresis. Basic Procedures: Six sessions of lymphocytapheresis were done in five patients with ulcerative colitis. Dendritic cells were enriched from the buffy coat of depleted lymphocytes and also from the peripheral blood. The phenotype and function of dendritic cells were studied by dual-color flow cytometry and in allogenic mixed leukocyte reaction, respectively. The serum levels of inflammatory cytokines (interleukin-1alpha 6, 8, 10, and 12 and tumor necrosis factor-alpha and beta) were measured before and after lymphocytapheresis in all cases. Main Findings: Lymphocytapheresis was safe and caused clinical, endoscopic or histologic improvements in all patients with ulcerative colitis. Many CD83-positive mature dendritic cells were found in the buffy coats after each session of lymphocytapheresis. The function of dendritic cells, the frequencies of CD83-positive dendritic cells and the levels of interleukin-6 and interleukin-8 were down regulated in all patients with ulcerative colitis after lymphocytapheresis compared with their levels before lymphocytapheresis. Conclusions: Depletion and down regulation of the function of dendritic cells and diminished levels of inflammatory cytokines caused by lymphocytapheresis may contribute to the therapeutic efficacy of lymphocytapheresis.

DOI： 10.1097/01.DCR.0000054880.68257.B7

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

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Language：Japanese   Publisher：一般社団法人 日本消化器内視鏡学会  

A 75-year-old male was diagnosed to have a gastric polyp by routine uppergastrointestinalendoscopy in 1985. The lesion was located on the greater curvature of the antrum of thestomach. Histological examination of biopsy specimens showed hyperplastic polyp. In 1995, polypectomy was performed, because histological examination of biopsy specimensrevealed group IV prior to the treatment. Pathologically, the lesion was diagnosed as welldifferentiated adenecarcinoma. fn this study we report a case of early gastric cancer arisingfrom a hyperplastic polyp.

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

75歳男性.10年6ヵ月の経過観察中に過形成ポリープから発生した隆起型早期胃癌の1例を経験した.検診で胃前庭部に無茎性隆起病変を認め,生検でGroup Iの過形成性ポリープと診断した.以後,毎年内視鏡検査で経過観察をしていたが,10年6ヵ月での生検組織がGroup IVとなって入院となった.ポリープは3年後には亜有茎性に,4年後には有茎性で表面結節状に変化し増大傾向であった.9年後には表面に白色調変化を伴ったが,生検ではGroup Iであった造影検査では頭部は24×35mm,茎は径9mmで壁変形はなく,内視鏡的ポリテクトミーを施行した.組織所見では大部分が高分化型腺癌で,基部の一部に過形成性ポリープの成分が残存し,過形成性ポリープが癌化したと考えられた.術後6年11ヵ月経過で再発は認めていない

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Language：Japanese   Publisher：(一財)日本消化器病学会  

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Language：Japanese   Publisher：一般社団法人 日本消化器内視鏡学会  

Endoscopic injection selerotherapy (EIS) is a very potent therapy for esophageal varices, However, its effect can only be achieved if done by an experienced endoscopist. It is difficult to ensure the placement of needle at varices for sufficient duration using the present therapeutic regimen. This is mainly due to an involuntary movement of the esophagus. As it is difficult to fix the endoscope at a variceal point, the needle may be fallen off even after entering into the varices. The aims of the study was to develop a new device for EIS so that the following purposes can be achieved 1) proper maintenance of expanded visual field, 2) fixation of the endoscope at a vaiceal point. We modified a commercially-available&#039;straight type.. of transparent hood. We made a concave groove in this hood measuring 6.5 &amp;times; 5.0 mm. This groove was adjusted to the endoscope so that it remains at 80&#039;clock position. The groove of the hood remain. aligned to the variceal point perfectly after the entry of the endoscope, Then 5% ethanolamine oleate iopamidol(EOI) was injected into the varix. EIS using this new device showed better therapeutic effects. For example, it was possible to introduce EOI in 89% of the supplying vessels by this new device compared to 30% by the previous method(p&lt;0.05). This new device is cheap, easy to use, has no complication and ensures better EIS.

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Language：Japanese   Publisher：(NPO)日本高齢消化器病学会  

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Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

内視鏡装着用のフードに幅6.5mm,深さ5mmの窪みを設けた.食道静脈瘤硬化療法に際して,このフードを鉗子口から出た穿刺針の先端が窪みの中間地点に位置するように装着し,窪みと穿刺する静脈瘤の位置を合わせ,装着バルーンで静脈瘤の血流を遮断すると共に,フードで静脈瘤を圧迫しながら穿刺針を刺入し,Ethanolamine oleate iopamidol注入を行った.本法を14例(男10例,女4例,平均65歳)に適用し,F2以上の9例と従来法による10例と比較したところ,血管内注入率,注入量,治療時間に有意差はなかったが,供血路造影率は本法群89%,従来法群30%と有意に改善した.F1の3例中2例,F0の2例中1例でも供血路造影が可能であった.術中の視野は妨げられることがなく,常に穿刺部を確認でき,送気は必要なかった.穿刺後の出血に対して従来はバルーンで圧迫していたが,本法ではフード越しに穿刺孔を見ながら圧迫止血でき,バルーン止血の回数は減少した.治療に伴う合併症はなかった

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Language：English   Publisher：SPRINGER-VERLAG TOKYO  

Background Primary biliary cirrhosis (PBC) is usually classified as either asymptomatic PBC (a-PBC) or symptomatic PBC (s-PBC). Although the proportion of a-PBC versus s-PBC patients has been consistently increasing, it is not clear whether the present criteria for the staging of PBC are optimal or not. We investigated the clinical stage of PBC patients from the standpoint of esophagogastric varices (EGV). Methods. One hundred and nine PBC patients were enrolled in this retrospective study. We investigated the clinical features of PBC based on laboratory data, histological stage, symptoms, and existence of EGV. In addition, the clinical course and prognosis in patients who were periodically followed up were also studied. Results. (1) EGV was detected in a-PBC patients, and there was no difference in the grade of EGV between a-PBC and s-PBC patients. (2) a-PBC patients with EGV had more liver damage than those without EGV, and a-PBC patients with EGV had a poorer prognosis than those without EGV. (3) Three of 11 patients who progressed from a-PBC to s-PBC within 3 years had EGV. (4) One of 3 a-PBC patients with EGV had progressed to s-PBC at 3-year follow-up. Conclusions. These results indicate that EGV is one of the most important factors for evaluating PBC. Therefore, we would like to propose that a-PBC patients with EGV should either be included in the presently defined s-PBC class, or that new prognostic classes of PBC be created that include EGV as a prognostic factor.

DOI： 10.1007/s00535-003-1196-6

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Language：Japanese   Publisher：(株)北隆館  

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