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Recent advances in mouse models of obesity-and nonalcoholic steatohepatitis-associated hepatocarcinogenesis

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世界肝病学杂志：英文版（电子版） 2015年第17期7卷 2110-2118页

作者： Hayato Nakagawa Department of Gastroenterology the University of Tokyo

Hepatocellular carcinoma(HCC) is the fifth most common cancer, and obesity has been established as a risk factor for HCC development. Nonalcoholic steatohepatitis(NASH) is apparently the key link between obesity and hepatocarcinogenesis, and obesity also accelerates HCC development synergistically with other risk factors, such as hepatitis virus infection and alcohol consumption. As an explanation for the pathogenesis of NASH, the so-called "two-hit" theory has been widely accepted, but recently, a better model, the so-called "multiple-hits hypothesis" was proposed, which states that many disease-promoting factors may occur in parallel, rather than consecutively. However, the overall mechanism remains largely unknown. Various cell-cell and organ-organ interactions are involved in the pathogenesis of NASH, and thus appropriate in vivo disease models are essential for a deeper understanding. However, replicating the full spectrum of human NASH has been difficult, as NASH involves obesity, insulin resistance, steatohepatitis, fibrosis, and ultimately HCC, and the lack of an appropriate mouse model has been a considerable barrier to determining the missing links among obesity, NASH, and HCC. In recent years, several innovative mouse models presenting obesity- and NASHassociated HCC have been established by modified diets, chemotoxic agents, genetic manipulation, or a combination of these factors, shedding some light on this complex network and providing new therapeutic strategies. Thus, in this paper, I review the mouse models of obesity- and NASH-associated HCC, especially focusing on recent advances and their clinical relevance.

关键词： Obesity Metabolic syndrome Nonalcoholicsteatohepatitis Hepatocellular carcinoma Mouse model

Assessment of disease progression in patients with transfusion-associated chronic hepatitis C using transient elastography

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World Journal of Gastroenterology 2012年第12期18卷 1385-1390页

作者： Ryota Masuzaki Ryosuke Tateishi Haruhiko Yoshida Toru Arano Koji Uchino Kenichiro Enooku Eriko Goto Hayato Nakagawa Yoshinari Asaoka Yuji Kondo Tadashi Goto Hitoshi Ikeda Shuichiro Shiina Masao Omata Kazuhiko Koike Department of Gastroenterology Graduate School of MedicineThe University of Tokyo Department of Clinical Laboratory The University of Tokyo Hospital Yamanashi Prefectural Hospital Organization

AIM:To evaluate the relationship between liver stiffness and duration of infection in blood transfusion-associated hepatitis C virus (HCV) patients with or without hepatocellular carcinoma (HCC).METHODS:Between December 2006 and June 2008,a total of 524 transfusion-associated HCV-RNA positive patients with or without HCC were enrolled.Liver stiffness was obtained noninvasively by using Fibroscan (Echosens,Paris,France).The date of blood transfusion was obtained by interview.Duration of infection was derived from the interval between the date of bloodtransfusion and the date of liver stiffness measurement (LSM).Patients were stratified into four groups based on the duration of infection (17-29 years;30-39 years;40-49 years;and 50-70 years).The difference in liver stiffness between patients with and without HCC was assessed in each group.Multiple linear regression analysis was used to determine the factors associated with liver stiffness.RESULTS:A total of 524 patients underwent LSM.Eight patients were excluded because of unsuccessful measurements.Thus 516 patients were included in the current analysis (225 with HCC and 291 without).The patients were 244 men and 272 women,with a mean age of 67.8 ± 9.5 years.The median liver stiffness was 14.3 kPa (25.8 in HCC group and 7.6 in nonHCC group).The patients who developed HCC in short duration of infection were male dominant,having lower platelet count,with a history of heavier alcohol consumption,showing higher liver stiffness,and receiving blood transfusion at an old age.Liver stiffness was positively correlated with duration of infection in patients without HCC (r=0.132,P=0.024) but not in patients with HCC (r=-0.103,P=0.123).Liver stiffness was significantly higher in patients with HCC than in those without in each duration group (P < 0.0001).The factors significantly associated with high liver stiffness in multiple regression were age at blood transfusion (P < 0.0001),duration of infection (P=0.0015),and heavy alcohol consumption (P=0.043) CONCLUSION:Although liver

关键词：丙型肝炎评估患者病情慢性血相弹性瞬时

Enlarged folds on endoscopic gastritis as a predictor for submucosal invasion of gastric cancers

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World Journal of Gastrointestinal Endoscopy 2021年第9期13卷 426-436页

作者： Osamu Toyoshima Shuntaro Yoshida Toshihiro Nishizawa Akira Toyoshima Kosuke Sakitani Tatsuya Matsuno Tomoharu Yamada Takashi Matsuo Hayato Nakagawa Kazuhiko Koike Department of Gastroenterology Toyoshima Endoscopy ClinicSetagayaku 157-0066TokyoJapan Department of Gastroenterology and Hepatology International University of Health and WelfareNarita HospitalNarita 286-8520ChibaJapan Department of Colorectal Surgery Japanese Red Cross Medical CenterShibuya-ku 150-8935TokyoJapan Department of Gastroenterology Sakitani Endoscopy ClinicNarashino 275-0026ChibaJapan Department of Gastroenterology Graduate School of MedicineThe University of TokyoBunkyo-ku 113-8655TokyoJapan Department of Internal Medicine Sakura Internal Medicine ClinicSetagayaku 157-0071TokyoJapan

BACKGROUND Accurate diagnosis of the depth of gastric cancer invasion is crucial in clinical practice.The diagnosis of gastric cancer depth is often made using endoscopic characteristics of the tumor and its margins;however,evaluating invasion depth based on endoscopic background gastritis remains unclear.AIM To investigate predicting submucosal invasion using the endoscopy-based Kyoto classification of gastritis.METHODS Patients with gastric cancer detected on esophagogastroduodenoscopy at Toyoshima Endoscopy Clinic were enrolled.We analyzed the effects of patient and tumor characteristics,including age,sex,body mass index,surveillance endoscopy within 2 years,current Helicobacter pylori infection,the Kyoto classification,and Lauren’s tumor type,on submucosal tumor invasion and curative endoscopic resection.The Kyoto classification included atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness.Atrophy was characterized by non-reddish and low mucosa.Intestinal metaplasia was detected as patchy whitish or grayish-white flat elevations,forming an irregular uneven surface.An enlarged fold referred to a fold width≥5 mm in the greater curvature of the corpus.Nodularity was characterized by goosebump-like multiple nodules in the antrum.Diffuse redness was characterized by uniform reddish nonatrophic mucosa in the greater curvature of the corpus.RESULTS A total of 266 gastric cancer patients(mean age,66.7 years;male sex,58.6%;mean body mass index,22.8 kg/m2)were enrolled.Ninety-three patients underwent esophagogastroduodenoscopy for surveillance within 2 years,and 140 had current Helicobacter pylori infection.The mean Kyoto score was 4.54.Fifty-eight cancers were diffuse-type,and 87 cancers had invaded the submucosa.Multivariate analysis revealed that low body mass index(odds ratio 0.88,P=0.02),no surveillance esophagogastroduodenoscopy within 2 years(odds ratio 0.15,P<0.001),endoscopic enlarged folds of gastritis(odds ratio 3.39,P=0.001),and Lauren’s diffuse-type(odds ratio 5.09,P<0.001)were indep

关键词： Gastric cancer Gastritis Enlarged fold Endoscopy Kyoto classification

Comparison of endoscopic gastritis based on Kyoto classification between diffuse and intestinal gastric cancer

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World Journal of Gastrointestinal Endoscopy 2021年第5期13卷 125-136页

作者： Osamu Toyoshima Toshihiro Nishizawa Shuntaro Yoshida Tomonori Aoki Fumiko Nagura Kosuke Sakitani Yosuke Tsuji Hayato Nakagawa Hidekazu Suzuki Kazuhiko Koike Department of Gastroenterology Toyoshima Endoscopy ClinicTokyo 157-0066Japan Department of Gastroenterology and Hepatology International University of Health and WelfareNarita HospitalNarita 286-8520Japan Department of Gastroenterology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Internal Medicine Chitosefunabashi Ekimae ClinicTokyo 157-0054Japan Department of Gastroenterology Sakiatani Endoscopy ClinicNarashino 275-0026Japan Department of Gastroenterology and Hepatology Tokai University School of MedicineIsehara 259-1193Japan

BACKGROUND Gastric cancers can be categorized into diffuse-and intestinal-type cancers based on the Lauren histopathological classification.These two subtypes show distinct differences in metastasis frequency,treatment application,and prognosis.Therefore,accurately assessing the Lauren classification before treatment is crucial.However,studies on the gastritis endoscopy-based Kyoto classification have recently shown that endoscopic diagnosis has improved.AIM To investigate patient characteristics including endoscopic gastritis associated with diffuse-and intestinal-type gastric cancers in Helicobacter pylori(H.pylori)-infected patients.METHODS Patients who underwent esophagogastroduodenoscopy at the Toyoshima Endoscopy Clinic were enrolled.The Kyoto classification included atrophy,intestinal metaplasia,enlarged folds,nodularity,and diffuse redness.The effects of age,sex,and Kyoto classification score on gastric cancer according to the Lauren classification were analyzed.We developed the Lauren predictive background score based on the coefficients of a logistic regression model using variables independently associated with the Lauren classification.Area under the receiver operative characteristic curve and diagnostic accuracy of this score were examined.RESULTS A total of 499 H.pylori-infected patients(49.6%males;average age:54.9 years)were enrolled;132 patients with gastric cancer(39 diffuse-and 93 intestinal-type cancers)and 367 cancer-free controls were eligible.Gastric cancer was independently associated with age≥65 years,high atrophy score,high intestinal metaplasia score,and low nodularity score when compared to the control.Factors independently associated with intestinal-type cancer were age≥65 years(coefficient:1.98),male sex(coefficient:1.02),high intestinal metaplasia score(coefficient:0.68),and low enlarged folds score(coefficient:-1.31)when compared to diffuse-type cancer.The Lauren predictive background score was defined as the sum of+2(age≥65 years),+1(male sex),+1(endoscopic intestinal metaplasia),a

关键词： Gastric cancer Lauren classification Endoscopy Pathology Gastritis Kyoto classification