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Biomarkers for the early diagnosis of hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第37期21卷 10573-10583页

作者： Nobuhiro Tsuchiya Yu Sawada itaru endo Keigo Saito Yasushi Uemura Tetsuya Nakatsura Department of Gastroenterological Surgery Graduate School of MedicineYokohama City University Division of Cancer Immunotherapy Exploratory Oncology Research and Clinical Trial Center National Cancer Center

Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.

关键词： α-fetoprotein α-fetoprotein-L3 Biomarker Des-γ-car

Two-stage treatment of an unusual haemobilia caused by intrahepatic pseudoaneurysm

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World Journal of Hepatology 2010年第1期2卷 52-54页

作者： Kazuhisa Takeda Kuniya Tanaka itaru endo Shinji Togo Hiroshi Shimada Department of Gastroenterological Surgery Yokohama City University Graduate School of Medicine

A 84-year-old man with a surgical history of subtotal gastrectomy for gastric cancer was transferred to our department because of a disorder of consciousness. Septic shock due to obstructive suppurative cholangitis secondary to choledocholithiasis was diagnosed. Anemia was also present,and upper gastrointestinal tract endoscopy revealed blood emerging from the Papilla of *** cause of the anemia was identified as *** showed a small aneurysm over the artery on segment 3(A3) .The cause of the haemobilia was suspected to be the bleeding into the biliary tree from this *** the patient's general condition was poor,minimally invasive therapy was *** arterial embolization(TAE) was selected ***,lateral sectionectomy was performed in order to remove the aneurysm on A3. No surgical complication occurred and,after surgery,no haemobilia was *** conclusion,a twostage treatment,namely,surgery following TAE,is recommended for patients in a physically poor condition who have haemobilia due to intrahepatic aneurysm.

关键词： Two-stage treatment Haemobilia Intrahepatic pseudoaneurysm

Efficacy of neoadjuvant chemotherapy for initially resectable colorectal liver metastases:A retrospective cohort study

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World Journal of Gastrointestinal Oncology 2022年第7期14卷 1281-1294页

作者： Kazuhisa Takeda Yu Sawada Yasuhiro Yabushita Yuki Honma Takafumi Kumamoto Jun Watanabe Ryusei Matsuyama Chikara Kunisaki Toshihiro Misumi itaru endo Gastroenterological Center Yokohama City University Medical CenterYokohama 232-0024Japan Department of Gastroenterological Surgery Yokohama City University Graduate School of MedicineYokohama 236-0004Jordan Department of Biostatistics Yokohama City University Graduate School of MedicineYokohama 236-0004Japan

BACKGROUND The liver is the most common metastatic site of colorectal *** is the mainstay of treatment for patients with colorectal liver metastases(CRLMs).However,there are cases of early recurrence after upfront hepatectomy *** selected high-risk patients,neoadjuvant chemotherapy(NAC)may improve longterm *** To determine the efficacy of NAC for initially resectable *** Among 644 patients who underwent their first hepatectomy for CRLMs at our institution,297 resectable cases were stratified into an upfront hepatectomy group(238 patients)and a NAC group(59 patients).Poor prognostic factors for upfront hepatectomy were identified using multivariate logistic regression *** score matching was used to compare clinical outcomes between the upfront hepatectomy and NAC groups,according to the number of poor prognostic *** curves were estimated using the Kaplan-Meier method and compared using the log-rank *** Preoperative carcinoembryonic antigen levels(≥10 ng/mL)(P=0.003),primary histological type(other than well/moderately differentiated)(P=0.04),and primary lymph node metastases(≥1)(P=0.04)were identified as independent poor prognostic factors for overall survival(OS)in the upfront hepatectomy ***-risk status was defined as the presence of two or more risk *** propensity score matching,50 patients were matched in each *** high-risk patients,the 5-year OS rate was significantly higher in the NAC group(13 patients)than in the upfront hepatectomy group(18 patients)(100%vs 34%;P=0.02).CONCLUSION NAC may improve the prognosis of high-risk patients with resectable CRLMs who have two or more risk factors.

关键词： Colorectal neoplasms Neoadjuvant therapy Neoplasm metastasis Prognosis Risk factors Survival

Long-term outcomes and prognostic factors of patients with obstructive colorectal cancer: A multicenter retrospective cohort study

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World Journal of Gastroenterology 2016年第22期22卷 5237-5245页

作者： Ishibe Atsushi Ota Mitsuyoshi Yamaguchi Kazuya Kaida Syuhei Kamiya Noriyuki Momiyama Masashi Watanabe Akira Sekizawa Kentaro Kamimukai Nobuyuki Sugimasa Natsuko Watanabe Jun Ichikawa Yasushi Kunisaki Chikara endo itaru Department of Gastroenterological Surgery Graduate School of Medicine Yokohama City University Fukuura Kanazawa-ku Yokohama 236-0004 Japan Department of Surgery Gastroenterological Center Yokohama City University Urafune Minami-ku Yokohama 232-0024 Japan Department of Surgery Yokohama City Hospital Okazawa Hodogaya-ku Yokohama 240-8555 Japan Department of Surgery Yokosuka Kyosai Hospital Maigahamadori Yokosuka 238-8558 Japan Department of Surgery Ito Municipal Hospital Ito 414-0055 Japan Department of Surgery Fujisawa City Hospital Fujisawa 251-8550 Japan Department of Surgery Yokosuka City Hospital Nagasaka Yokosuka 240-0195 Japan Department of Surgery Yokohama Hodogaya Central Hospital Kamadai Hodogaya-ku Yokohama 240-8585 Japan Department of Surgery Saiseikai Yokohamashi Nanbu Hospital Kounandai Kounan-ku Yokohama 234-0054 Japan Department of Oncology Graduate School of Medicine Yokohama City University Yokohama 236-0004 Japan

AIM: To investigate the long-term oncologic outcomes and prognostic factors in patients with obstructive colorectal cancer(CRC) at multiple Japanese ***: We identified 362 patients diagnosed with obstructive colorectal cancer from January 1, 2002 to December 31, 2012 in Yokohama Clinical Oncology Group's department of gastroenterological surgery. Among them, 234 patients with stage Ⅱ/Ⅲ disease who had undergone surgical resection of their primary lesions were analyzed, retrospectively. We report the long-term outcomes, the risk factors for recurrence, and the prognostic ***: The five-year disease free survival and cancer-specific survival were 50.6% and 80.3%, respectively. A multivariate analysis showed the ASAPS(HR = 2.23, P = 0.026), serum Albumin ≤ 4.0 g/d L(HR = 2.96, P = 0.007), T4 tumor(HR = 2.73, P = 0.002) and R1 resection(HR = 6.56, P = 0.02) to be independent risk factors for recurrence. Furthermore, poorly differentiated cancers(HR = 6.28, P = 0.009), a T4 tumor(HR = 3.46, P = 0.011) and R1 resection(HR = 6.16, P = 0.006) were independent prognostic factors in patients with obstructive ***: The outcomes of patients with obstructive CRC was poor. T4 tumor and R1 resection were found to be independent prognostic factors for both recurrence and survival in patients with obstructive CRC.

关键词： Obstructive colorectal cancer Prognostic factor Survival

Machine learning predicts unpredicted deaths with high accuracy following hepatopancreatic surgery

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Hepatobiliary Surgery and Nutrition 2021年第1期10卷 20-30,I0001,I0002页

作者： Kota Sahara Anghela Z.Paredes Diamantis I.Tsilimigras Kazunari Sasaki Amika Moro JMadison Hyer Rittal Mehta Syeda A.Farooq Lu Wu itaru endo Timothy M.Pawlik Division of Surgical Oncology The Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOHUSA Gastroenterological Surgery Division Yokohama City University School of MedicineYokohamaJapan Department of General Surgery Digestive Disease and Surgery InstituteCleveland ClinicClevelandOHUSA

Background:Machine learning to predict morbidity and mortality-especially in a population traditionally considered low risk-has not been previously *** sought to characterize the incidence of death among patients with a low estimated morbidity and mortality risk based on the National Surgical Quality Improvement Program(NSQIP)estimated probability(EP),as well as develop a machine learning model to identify individuals at risk for“unpredicted death”(UD)among patients undergoing hepatopancreatic(HP)***:The NSQIP database was used to identify patients who underwent elective HP surgery between *** risk of morbidity and mortality was stratified into three tiers(low,intermediate,or high estimated)using a k-means clustering method with bin sorting.A machine learning classification tree and multivariable regression analyses were used to predict 30-day mortality with a 10-fold cross validation.C statistics were used to compare model ***:Among 63,507 patients who underwent an HP procedure,median patient age was 63(IQR:54-71)*** underwent either pancreatectomy(n=38,209,60.2%)or hepatic resection(n=25,298,39.8%).Patients were stratified into three tiers of predicted morbidity and mortality risk based on the NSQIP EP:low(n=36,923,58.1%),intermediate(n=23,609,37.2%)and high risk(n=2,975,4.7%).Among 36,923 patients with low estimated risk of morbidity and mortality,237 patients(0.6%)experienced a *** to the classification tree analysis,age was the most important factor to predict UD(importance 16.9)followed by preoperative albumin level(importance:10.8),disseminated cancer(importance:6.5),preoperative platelet count(importance:6.5),and sex(importance 5.9).Among patients deemed to be low risk,the c-statistic for the machine learning derived prediction model was 0.807 compared with an AUC of only 0.662 for the NSQIP ***:A prognostic model derived using machine learning methodology performed better than t

关键词： Mortality unpredicted machine learning National Surgical Quality Improvement Program(NSQIP)

lmmunotherapy utilization for hepatobiliary cancer in the United States: disparities among patients with different socioeconomic status

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Hepatobiliary Surgery and Nutrition 2020年第1期9卷 13-24,中插2页

作者： Kota Sahara S.Ayesha Farooq Diamantis I.Tsilimigras Katiuscha Merath Anghela Z.Paredes Lu Wu Rittal Mehta J.Madison Hyer itaru endo Timothy M.Pawlik Department of Surgery Division of Surgical OncologyThe Ohio State University Wexner Medical Center and James Comprehensive Cancer CenterColumbusOHUSA Gastroenterological Surgery Division Yokohama City University School of MedicineYokohamaJapan

Background: Patients with advanced hepatobiliary cancer (HBC) have a dismal prognosis and limited treatment options. Immunotherapy has been considered as a promising treatment, especially for cancers not amenable to surgery. Methods: Between 2004, and 2015, patients diagnosed with hepatocellular carcinoma (HCC), intra- and extrahepatic cholangiocarcinoma and gallbladder cancer (GBC) were identified in the National Cancer Database. Results: Among 249,913 patients with HBC, only 585 (0.2%) patients received immunotherapy. Among patients who received immunotherapy, most patients were diagnosed between 2012 and 2015, had private insurance, as well as an income ≥$46,000 and were treated at an academic facility. The use of immunotherapy among HBC patients varied by diagnosis (HCC, 67.7%;bile duct cancer, 14%). On multivariable analysis, a more recent period of diagnosis (OR 1.80, 95% CI: 1.44-2.25), median income >$46,000 (OR 1.43, 95% CI: 1.11-1.87), and higher tumor stage (stage III, OR 2.22, 95% CI: 1.65-3.01;stage IV, OR 3.24, 95% CI:2.41-4.34) were associated with greater odds of receiving immunotherapy. Conclusions: Overall utilization of immunotherapy in the US among patients with HBC was very low, yet has increased over time. Certain socioeconomic factors were associated with an increased likely of receiving immunotherapy, suggesting disparities in access of patients with lower socioeconomic status.

关键词： Immunotherapy hepatobiliary cancer (HBC) trends socioeconomic status

Patient-derived orthotopic xenograft models for cancer of unknown primary precisely distinguish chemotherapy,and tumor-targeting *** A1-R is superior to first-line chemotherapy

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Signal Transduction and Targeted Therapy 2018年第1期3卷 220-225页

作者： Kentaro Miyake Tasuku Kiyuna Masuyo Miyake Kei Kawaguchi Sang Nam Yoon Zhiying Zhang Kentaro Igarashi Sahar Razmjooei Sintawat Wangsiricharoen Takashi Murakami Yunfeng Li Scott D.Nelson Tara A.Russell Arun S.Singh Yukihiko Hiroshima Masashi Momiyama Ryusei Matsuyama Takashi Chishima Shree Ram Singh itaru endo Fritz C.Eilber Robert M.Hoffman AntiCancer Inc.San DiegoCAUSA Department of Surgery University of CaliforniaSan DiegoCAUSA Department of Gastroenterological Surgery Yokohama City University Graduate School of MedicineYokohamaJapan Department of Pathology University of CaliforniaLos AngelesCAUSA Division of Surgical Oncology University of CaliforniaLos AngelesCAUSA Division of Hematology-Oncology University of CaliforniaLos AngelesCAUSA Basic Research Laboratory National Cancer InstituteFrederickMDUSA

Cancer of unknown primary(CUP)is a recalcitrant disease with poor prognosis because it lacks standard first-line *** consists of diverse malignancy groups,making personalized precision therapy *** present study aimed to identify an effective therapy for a CUP patient using a patient-derived orthotopic xenograft(PDOX)*** paper reports the usefulness of the PDOX model to precisely identify effective and ineffective chemotherapy and to compare the efficacy of *** A1-R with first-line chemotherapy using the CUP PDOX *** present study is the first to use a CUP PDOX model,which was able to precisely distinguish the chemotherapeutic *** found that a carboplatinum(CAR)-based regimen was effective for this CUP *** also demonstrated that *** A1-R was more effective against the CUP tumor than first-line *** results indicate that *** A1-R has clinical potential for CUP,a resistant disease that requires effective therapy.

关键词： chemotherapy precisely therapy

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胆道肿瘤临床实践指南(英文第三版)

中华消化外科杂志 2021年第4期20卷 359-375页

作者： Masato Nagino Satoshi Hirano Hideyuki Yoshitomi Taku Aoki Katsuhiko Uesaka Michiaki Unno Tomoki Ebata Masaru Konishi Keiji Sano Kazuaki Shimada Hiroaki Shimizu Ryota Higuchi Toshifumi Wakai Hiroyuki Isayama Takuji Okusaka Toshio Tsuyuguchi Yoshiki Hirooka Junji Furuse Hiroyuki Maguchi Kojiro Suzuki Hideya Yamazaki Hiroshi Kijima Akio Yanagisawa Masahiro Yoshida Yukihiro Yokoyama Takashi Mizuno itaru endo 杨翼飞(译) 仇毓东(译) 赵梦珂(译) 伏旭(译) 蔡正华(译) 毛凉(审校) 爱知癌症中心日本名古屋北海道大学医学院胃肠外二科日本札幌独协医科大学琦玉医学中心普通外科日本越谷独协医科大学普通外二科日本米布静冈癌症中心肝胆胰外科日本长崎东北大学医学院外科系日本仙台名古屋大学医学院外科系日本名古屋国立癌症中心医院东院区肝胆胰外科日本柏市京都大学医学院外科系日本东京国立癌症中心医院日本东京帝京大学千叶医学中心外科系日本市原东京女子医科大学胃肠病研究所普通外科日本东京新泻大学医学与牙科研究生院消化与普通外科日本新泻均天道大学医学研究生院消化内科日本东京国立癌症中心医院肝胆胰肿瘤科日本东京千叶县锯原医院消化内科日本锯原藤田医科大学消化内科及消化肿瘤科日本丰明杏林大学医学院肿瘤内科日本三鹰泰恩金凯医院教育研究中心日本札幌爱知医科大学放射科日本长谷京都府立医科大学医学研究生院放射科日本京都广崎大学医学研究部病理学与生物科学系日本广崎日本红十字会京都第二医院病理科日本京都国际医疗福利大学肝胆胰胃肠外科日本一川横滨市立大学医学研究生院消化外科日本横滨南京大学医学院附属鼓楼医院肝胆胰中心

日本肝胆胰外科学会(JSHBPS)于2007年出版第一版胆道肿瘤(胆管癌、胆囊癌及壶腹癌)临床实践指南,于2014年更新第二版,2021年英文第三版胆道肿瘤临床实践指南围绕6个主题提出若干临床问题,基于相关循证医学证据并组织专家讨论后,最终确... 详细信息

日本肝胆胰外科学会(JSHBPS)于2007年出版第一版胆道肿瘤(胆管癌、胆囊癌及壶腹癌)临床实践指南,于2014年更新第二版,2021年英文第三版胆道肿瘤临床实践指南围绕6个主题提出若干临床问题,基于相关循证医学证据并组织专家讨论后,最终确定推荐意见、推荐强度以及推荐说明。根据证据推荐分级的评估、制订与评价(GRADE)系统,推荐强度被分为1级(强)或者2级(弱)。英文第三版胆道肿瘤临床实践指南中提出的31个临床问题涵盖:(1)预防性治疗;(2)诊断;(3)胆道引流;(4)外科治疗;(5)化疗;(6)放疗。31个临床问题中,14个问题给予推荐强度为强的推荐意见,14个问题给予推荐强度为弱的推荐意见,剩余的3个问题未给予推荐意见。每条推荐意见都进行推荐强度说明。最新版指南基于循证医学证据,为临床提供了重要建议。未来与癌症登记数据库协作将是评估指南和建立新证据的关键。

关键词：胆道肿瘤临床实践指南预防性治疗循证医学证据肝胆胰外科胆道引流推荐意见壶腹癌

Seismic assessment of two multi-tiered pagodas damaged by the 2015 Nepal earthquake

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Earthquake Engineering and Engineering Vibration 2021年第2期20卷 453-469页

作者： Yohei endo Toshikazu Hanazato Department of Architecture Shinshu University4-17-1 WakasatoNagano 380-8553Japan Department of Architecture Mie University1577 Kurimamachiya-chōTsuMie 514-8507MieJapan

A seismic assessment of two multi-tier pagodas by numerical analysis is presented *** Changu Narayan temple and the Kumbeshwar temple in Nepal are used as the case *** pagodas are built of brick masonry in earthen mortar,with timber columns and *** Changu Narayan temple is a two-tier pagoda,and was seriously damaged during the 2015 Gorkha *** Kumbeshwar temple is a five-tier pagoda,and its top-tier collapsed due to the Gorkha earthquake.A seismic assessment was carried out using finite element(FE)*** FE models were prepared,and dynamic identification tests and penetrometer tests were *** analysis and nonlinear dynamic analysis were performed as part of the seismic *** main shock of the 2015 Gorkha earthquake was considered as the input *** behavior between the two pagodas was compared with the collapse mechanisms and damage patterns observed in the actual *** comparison suggested common structural features of multi-tier *** study is dedicated to providing a better understanding of the seismic behavior of multi-tier pagoda-type structures and provides suggestions for their effective analysis.

关键词： masonry multi-tier pagoda seismic assessment nonlinear dynamic analysis FEM analysis