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| 1 | Apoptosis and non-alcoholic fatty liver diseases显示文摘The number of patients with nonalcoholic fatty liver diseases(NAFLD) including nonalcoholic steatohepatitis(NASH), has been increasing. NASH causes cirrhosis and hepatocellular carcinoma(HCC) and is one of the most serious health problems in the world. The mechanism through which NASH progresses is still largely unknown. Activation of caspases, Bcl-2 family proteins, and c-Jun N-terminal kinase-induced hepatocyte apoptosis plays a role in the activation of NAFLD/NASH. Apoptotic hepatocytes stimulate immune cells and hepatic stellate cells toward the progression of fibrosis in the liver through the production of inflammasomes and cytokines. Abnormalities in glucose and lipid metabolism as well as microbiota accelerate these processes. The production of reactive oxygen species, oxidative stress, and endoplasmic reticulum stress is also involved. Cell death, including apoptosis, seems very important in the progression of NAFLD and NASH. Recently, inhibitors of apoptosis have been developed as drugs for the treatment of NASH and may prevent cirrhosis and HCC. Increased hepatocyte apoptosis may distinguish NASH from NAFLD, and the improvement of apoptosis could play a role in controlling the development of NASH. In this review, the association between apoptosis and NAFLD/NASH are discussed. This review could provide their knowledge, which plays a role in seeing the patients with NAFLD/NASH in daily clinical practice. | Tatsuo Kanda Shunichi Matsuoka Motomi Yamazaki Toshikatsu Shibata Kazushige Nirei Hiroshi Takahashi Tomohiro Kaneko Mariko Fujisawa Teruhisa Higuchi Hitomi Nakamura Naoki Matsumoto Hiroaki Yamagami Masahiro Ogawa Hiroo Imazu Kazumichi Kuroda Mitsuhiko Moriyama | 2018 | World Journal of Gastroenterology2018，24，25： | 32 |
| 2 | Genetic and epigenetic aspects of initiation and progression of hepatocellular carcinoma显示文摘Hepatocellular carcinoma(HCC) is a primary cancer of the liver that is predominant in developing countries and is responsible for nearly 600000 deaths each year worldwide. Similar to many other tumors, the development of HCC must be understood as a multistep process involving the accumulation of genetic and epigenetic alterations in regulatory genes, leading to the activation of oncogenes and the inactivation or loss of tumor suppressor genes. Extensive research over the past decade has identified a number of molecular biomarkers, including aberrant expression of HCCrelated genes and microRNAs. The challenge facing HCC research and clinical care at this time is to address the heterogeneity and complexity of these genetic and epigenetic alterations and to use this information to direct rational diagnosis and treatment strategies. The multikinase inhibitor sorafenib was the first molecularly targeted drug for HCC to show some extent of survival benefits in patients with advanced tumors. Although the results obtained using sorafenib support the importance of molecular therapies in the treatment of HCC, there is still room for improvement. In addition,no molecular markers for drug sensitivity, recurrence and prognosis are currently clinically available. In this review, we provide an overview of recently published articles addressing HCC-related genes and microRNAs to update what is currently known regarding genetic and epigenetic aspects of the pathogenesis of HCC and propose novel promising candidates for use as diagnostic and therapeutic targets in HCC. | Mitsuro Kanda Hiroyuki Sugimoto Yasuhiro Kodera | 2015 | World Journal of Gastroenterology2015，21，37： | 22 |
| 3 | Nonalcoholic fatty liver disease and hepatic cirrhosis: comparison with viral hepatitis-associated steatosis显示文摘Nonalcoholic fatty liver disease(NAFLD) including nonalcoholic steatohepatitis(NASH) is globally increasing and has become a world-wide health problem. Chronic infection with hepatitis B virus or hepatitis C virus(HCV) is associated with hepatic steatosis. Viral hepatitis-associated hepatic steatosis is often caused by metabolic syndrome including obesity,type 2 diabetes mellitus and/or dyslipidemia. It has been reported that HCV genotype 3 exerts direct metabolic effects that lead to hepatic steatosis. In this review,the differences between NAFLD/NASH and viral hepatitis-associated steatosis are discussed. | Yuki Haga Tatsuo Kanda Reina Sasaki Masato Nakamura Shingo Nakamoto Osamu Yokosuka | 2015 | World Journal of Gastroenterology2015，21，46： | 20 |
| 4 | Importance of adequate immunosuppressive therapy for the recovery of patients with 'life-threatening' severe exacerbation of chronic hepatitis B显示文摘AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in 'clinically severe' exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as 'severe' exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ('early high-dose'group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ('non-early high-dose'group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the 'early high-dose' group survived, while only 2 of 11 patients of the 'non-early high-dose' group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the 'early high-dose'group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with 'clinically lifethreatening' severe exacerbation of chronic hepatitis B,when used in the early stage of illness. | Keiichi Fujiwara Osamu Yokosuka Hiroshige Kojima Tatsuo Kanda Hiromitsu Saisho Hiroyuki Hirasawa Hiroshi Suzuki | 2005 | World Journal of Gastroenterology2005，11，8： | 20 |
| 5 | Recent advances in the molecular diagnostics of gastric cancer显示文摘Gastric cancer(GC) is the third most common cause of cancer-related death in the world,representing a major global health issue. Although the incidence of GC is declining,the outcomes for GC patients remain dismal because of the lack of effective biomarkers to detect early GC and predict both recurrence and chemosensitivity. Current tumor markers for GC,including serum carcinoembryonic antigen and carbohydrate antigen 19-9,are not ideal due to their relatively low sensitivity and specificity. Recent improvements in molecular techniques are better able to identify aberrant expression of GC-related molecules,including oncogenes,tumor suppressor genes,micro RNAs and long non-coding RNAs,and DNA methylation,as novel molecular markers,although the molecular pathogenesis of GC is complicated by tumor heterogeneity. Detection of genetic and epigenetic alterations from gastric tissue or blood samples has diagnostic value in the management of GC. There are high expectations for molecular markers that can be used as new screening tools for early detection of GC as well as for patient stratification towards personalized treatment of GC through prediction of prognosis and drug-sensitivity. In this review,the studies of potential molecular biomarkers for GC that have been reported in the publicly available literature between 2012 and 2015 are reviewed and summarized,and certain highlighted papers are examined. | Mitsuro Kanda Yasuhiro Kodera | 2015 | World Journal of Gastroenterology2015，21，34： | 20 |
| 6 | Peroxisome proliferator-activated receptors for hypertension显示文摘Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be studied.This article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases. | Daisuke Usuda Tsugiyasu Kanda | 2014 | World Journal of Cardiology2014，6，8： | 19 |
| 7 | Antiviral therapies for chronic hepatitis C virus infection with cirrhosis显示文摘Patients who are infected with hepatitis C virus(HCV) and also have advanced fibrosis or cirrhosis have beenrecognized as 'difficult-to-treat' patients during an era when peginterferon and ribavirin combination therapy is the standard of care. Recent guidelines have clearly stated that treatment should be prioritized in this population to prevent complications such as decompensation and hepatocellular carcinoma. Recent advances in the treatment of chronic hepatitis C have been achieved through the development of direct-acting antiviral agents(DAAs). Boceprevir and telaprevir are first-generation DAAs that inhibit the HCV NS3/4A protease. Boceprevir or telaprevir, in combination with peginterferon and ribavirin, improved the sustained virological response rates compared with peginterferon and ribavirin alone and were tolerated in patients with HCV genotype 1 infection without cirrhosis or compensated cirrhosis. However, the efficacy is lower especially in prior non-responders with or without cirrhosis. Furthermore, a high incidence of adverse events was observed in patients with advanced liver disease, including cirrhosis, in real-life settings. Current guidelines in the United States and in some European countries no longer recommend these regimens for the treatment of HCV. Next-generation DAAs include second-generation HCV NS3/4A protease inhibitors, HCV NS5 A inhibitors and HCV NS5 B inhibitors, which have a high efficacy and a lower toxicity. These drugs are used in interferon-free or in interferon-based regimens with or without ribavirin in combination with different classes of DAAs. Interferon-based regimens, such as simeprevir in combination with peginterferon and ribavirin, are well tolerated and are highly effective especially in treatmentnave patients and in patients who received treatment but who relapsed. The efficacy is less pronounced in nullresponders and in patients with cirrhosis. Interferonfree regimens in combination with ribavirin and/or two or more DAAs could be used for treatment-nave, treatment-experienced and even for interferon-ineligible or interferon-intolerant patients. Some clinical trials have demonstrated promising results, and have shown that the efficacy and safety were not different between patients with and without cirrhosis. There are also promising regimens for genotypes other than genotype 1. Interferonis contraindicated in patients with decompensated cirrhosis, and further studies are needed to establish the optimal treatment regimen for this population. In the future, interferon-free and ribavirin-free regimens with high efficacy and improved safety are expected for HCVinfected patients with advanced liver diseases. | Shingo Nakamoto Tatsuo Kanda Hiroshi Shirasawa Osamu Yokosuka | 2015 | World Journal of Hepatology2015，7，8： | 17 |
| 8 | Current and future directions for treating hepatitis B virus infection显示文摘Hepatitis B virus(HBV) persistently infects approximately 350 million people, and approximately 600000 liverrelated deaths are observed per year worldwide. HBV infection is also one of the major risk factors for hepatocellular carcinoma(HCC). The persistence of serum hepatitis B e antigen(HBe Ag) and high level of serum HBV DNA are thought to reflect a high HBV replication status in hepatocytes, causing cirrhosis, HCC and liver-related deaths. It has been reported that antiviral therapy, such as peginterferon and nucleos(t)ide analogues(NUCs), could suppress liver-related death by inhibiting the HBV DNA levels and inducing seroconversion from HBe Ag to antibody to HBe antigen. Currently, peginterferon is widely used, but there are also several disadvantages in the use of peginterferon, such as various adverse events, the administration route and duration. It is difficult to predict the effects of treatment and interferon is contraindicated for the patients with advanced fibrosis of the liver and cirrhosis. With respect to NUCs, entecavir and tenofovir disoproxil fumarate are current the first-choice drugs. NUCs can be administered orally, and their anti-viral effects are stronger than that of peginterferon. However, because cessation of NUC administration leads to high levels of viral replication and causes severe hepatitis, they must be administered for a long time. On the other hand, the use of both interferon and NUCs cannot eliminate covalently closed circular DNA of HBV. In this review, we evaluate the natural course of chronic HBV infection and then provide an outline of these representative drugs, such as peginterferon, entecavir and tenofovir disoproxil fumarate. | Akinobu Tawada Tatsuo Kanda Osamu Yokosuka | 2015 | World Journal of Hepatology2015，7，11： | 16 |
| 9 | Current management of patients with hepatocellular carcinoma显示文摘The current management therapies for hepatocellular carcinoma(HCC) patients are discussed in this review. Despite the development of new therapies, HCC remains a 'difficult to treat' cancer because HCC typically occurs in advanced liver disease or hepatic cirrhosis. The progression of multistep and multicentric HCC hampers the prevention of the recurrence of HCC. Many HCC patients are treated with surgical resection and radiofrequency ablation(RFA), although these modalities should be considered in only selected cases with a certain HCC number and size. Although there is a shortage of grafts, liver transplantation has the highest survival rates for HCC. Several modalities are salvage treatments; however, intensive care in combination with other modalities or in combination with surgical resection or RFA might offer a better prognosis. Sorafenib is useful for patients with advanced HCC. In the near future, HCC treatment will include stronger molecular targeted drugs, which will have greater potency and fewer adverse events. Further studies will be ongoing. | Tatsuo Kanda Sadahisa Ogasawara Tetsuhiro Chiba Yuki Haga Masao Omata Osamu Yokosuka | 2015 | World Journal of Hepatology2015，7，15： | 15 |
| 10 | Molecular mechanisms of peritoneal dissemination in gastric cancer显示文摘Peritoneal dissemination represents a devastating form of gastric cancer(GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets. | Mitsuro Kanda Yasuhiro Kodera | 2016 | World Journal of Gastroenterology2016，22，30： | 15 |
| 11 | Clinical utility of the platelet-lymphocyte ratio as a predictor of postoperative complications after radical gastrectomy for clinical T2-4 gastric cancer显示文摘AIM To identify simple and sensitive markers for postoperative complications after gastrectomy, the predictive values were compared among candidate preoperative factors. METHODS Three-hundred and twelve patients with previously untreated clinical T2-4 gastric cancer who underwent a D2 standard gastrectomy(distal gastrectomy or total gastrectomy) were included in the analysis.Correlations between 21 parameters that can be determined by preoperative routine blood tests and clinically relevant postoperative complications(grade Ⅱ or higher according to the Clavien-Dindo classification) were evaluated. The optimal cutoff values and clinical significance of the selected markers were further evaluated by subgroup analyses according to age, body mass index, operative procedure and clinical disease stage.RESULTS Sixty-six patients(21.1%) experienced grade Ⅱ or higher postoperative complications. The plateletlymphocyte ratio(PLR, total lymphocyte count/platelet count × 100) exhibited the highest area under the curve value(0.639) for predicting postoperative complications among the 21 parameters, and the optimal cutoff value was determined to be 0.71(sensitivity = 70%, specificity = 56%). In the univariate analysis, the odds ratio of a low PLR for the occurrence of postoperative complications was 2.94(95%CI: 1.66-5.35, P < 0.001), and a multivariate binomial logistic analysis involving other potential risk factors identified a low PLR as an independent risk factor for postoperative complications(OR = 3.32, 95%CI: 1.82-6.25, P < 0.001). In subgroups classified according to age, body mass index, operative procedure and clinical disease stage, the low PLR group exhibited an increased incidence of postoperative complications. CONCLUSION The preoperative PLR is a simple and useful predictor of complications after curative gastrectomy in patients with clinical T2-4 gastric cancer. | Kenichi Inaoka Mitsuro Kanda Hiroaki Uda Yuri Tanaka Chie Tanaka Daisuke Kobayashi Hideki Takami Naoki Iwata Masamichi Hayashi Yukiko Niwa Suguru Yamada Tsutomu Fujii Hiroyuki Sugimoto Kenta Murotani Michitaka Fujiwara Yasuhiro Kodera | 2017 | World Journal of Gastroenterology2017，23，14： | 13 |
| 12 | Hepatitis C virus NS5A inhibitors and drug resistance mutations显示文摘Some direct-acting antiviral agents for hepatitis C virus(HCV),such as telaprevir and boceprevir have been available since 2011.It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis.HCV NS5A inhibitors efficiently inhibited HCV replication in vitro.Human studies showed that dual,triple and quad regimens with HCV NS5A inhibitors,such as daclatasvir and ledipasvir,in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin,could efficiently inhibit HCV replication according to HCV genotypes.These combinations might be a powerful tool for'difficult-to-treat'HCV-infected patients.'First generation'HCV NS5A inhibitors such as daclatasvir,ledipasvir and ABT-267,which are now in phaseⅢclinical trials,could result in resistance mutations.'Second generation'NS5A inhibitors such as GS-5816,ACH-3102,and MK-8742,have displayed improvements in the genetic barrier while maintaining potency.HCV NS5A inhibitors are safe at low concentrations,which make them attractive for use despite low genetic barriers,although,in fact,HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors,HCV NS5B inhibitors or peginterferon plus ribavirin.This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants. | Shingo Nakamoto Tatsuo Kanda Shuang Wu Hiroshi Shirasawa Osamu Yokosuka | 2014 | World Journal of Gastroenterology2014，20，11： | 12 |
| 13 | Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer显示文摘Gastrectomy with radical lymph node dissection is the most promising treatment avenue for patients with gastric cancer. However, this procedure sometimes induces excessive intraoperative blood loss and requires perioperative allogeneic blood transfusion. There are lasting discussions and controversies about whether intraoperative blood loss or perioperative blood transfusion has adverse effects on the prognosis in patients with gastric cancer. We reviewed laboratory and clinical evidence of these associations in patients with gastric cancer. A large amount of clinical evidence supports the correlation between excessive intraoperative blood loss and adverse effects on the prognosis. The laboratory evidence revealed three possible causes of such adverse effects: anti-tumor immunosuppression, unfavorable postoperative conditions, and peritoneal recurrence by spillage of cancer cells into the pelvis. Several systematic reviews and meta-analyses have suggested the adverse effects of perioperative blood transfusions on prognostic parameters such as all-cause mortality, recurrence, and postoperative complications. There are two possible causes of adverse effects of blood transfusions on the prognosis: Anti-tumor immunosuppression and patient-related confounding factors (e.g., preoperative anemia). These factors are associated with a worse prognosis and higher requirement for perioperative blood transfusions. Surgeons should make efforts to minimize intraoperative blood loss and transfusions during gastric cancer surgery to improve patients’ prognosis. | Koki Nakanishi Mitsuro Kanda Yasuhiro Kodera | 2019 | World Journal of Gastroenterology2019，25，22： | 11 |
| 14 | Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer显示文摘 | Yuji Maehata Shotaro Nakamura Kiyoshi Fujisawa Motohiro Esaki Tomohiko Moriyama Kouichi Asano Yuta Fuyuno Kan Yamaguchi Issei Egashira Hyonji Kim Motonobu Kanda Minako Hirahashi Takayuki Matsumoto | 2012 | Gastrointestinal Endoscopy2012，，1： | 10 |
| 15 | Androgen receptor signaling in hepatocellular carcinoma and pancreatic cancers显示文摘Hepatocellular carcinoma(HCC)and pancreatic cancer remain difficult to treat,and despite the ongoing development of new treatments,the overall survival rate has only modestly improved over the past decade.Liver and pancreatic progenitors commonly develop from endoderm cells in the embryonic foregut.A previous study showed that HCC and pancreatic cancer cell lines variably express androgen receptor(AR),and these cancers and the surrounding tissues also express AR.AR is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily.Androgen response element is present in regulatory elements on the AR-responsive target genes,such as transforming growth factor beta-1(TGF beta-1)and vascular endothelial growth factor(VEGF).It is well known that the activation of AR is associated with human carcinogenesis in prostate cancer as well as HCC and pancreatic cancer and that GRP78,TGF beta,and VEGF all play important roles in carcinogenesis and cancer development in these cancers.HCC is a male-dominant cancer irrespective of its etiology.Previous work has reported that vertebrae forkhead box A 1/2 are involved in estrogen receptors and/or AR signaling pathways,which may contribute to the gender differences observed with HCC.Our recent work also showed that AR has a critical role in pancreatic cancer development,despite pancreatic cancer not being a male dominant cancer.Aryl hydrocarbon(or dioxin)receptor is also involved in both HCC and pancreatic cancer through the formation of complex with AR.It is possible that AR might be involved in their carcinogenesis through major histocompatibility complex classⅠchain-related gene A/B.This review article describes AR and its role in HCC and pancreatic cancer and suggests that more specific AR signaling-inhibitors may be useful in the treatment of these'difficult to treat'cancers. | Tatsuo Kanda Xia Jiang Osamu Yokosuka | 2014 | World Journal of Gastroenterology2014，20，28： | 9 |
| 16 | APASL consensus statements and management algorithms for hepatitis C virus infection显示文摘 | Masao Omata Tatsuo Kanda Ming-Lung Yu Osamu Yokosuka Seng-Gee Lim Wasim Jafri Ryosuke Tateishi Saeed S. Hamid Wan-Long Chuang Anuchit Chutaputti Lai Wei Jose Sollano Shiv Kumar Sarin Jia-Horng Kao Geoffrey W. McCaughan | 2012 | Hepatology International2012，，2： | 8 |
| 17 | Prognostic significance of perioperative tumor marker levels in stage Ⅱ/Ⅲ gastric cancer显示文摘AIM To evaluate the prognostic significance of perioperative carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9(CA19-9) levels in stage Ⅱ/Ⅲ gastric cancer.METHODS From a multi-institutional retrospective database compiled by integrating clinical data from nine institutions, data of 998 patients who underwent curative resection for stage Ⅱ/Ⅲ gastric cancer between 2010 and 2014 were retrieved and analyzed. The prognostic impact of the preoperative and postoperative levels and chronological changes in CEA, CA19-9 and their combination were evaluated. To test whether postoperative adjuvant chemotherapy alters the prognostic impact of perioperative CEA and CA19-9 levels, the hazard ratios for mortality were compared between patients who underwent surgery alone and patients who underwent surgery followed by adjuvant chemotherapy.RESULTS The prognostic impact of postoperative CEA and CA19-9 was superior to that of the preoperative levels. Multivariable analysis identified high postoperative CEA and CA19-9 levels as independent prognostic factors for overall survival.Disease-free survival rates clearly decreased in a stepwise manner in association with postoperative CEA and CA19-9 levels, and patients with high levels of both markers showed significantly poorer prognosis than other patient groups. When we analyzed perioperative changes in serum CEA and CA19-9 levels, patients with high levels before and after surgery had the worst disease-free survival rates among all patient groups. Patients with normalized CEA levels after surgery had a significantly lower disease-free survival rate than those with normal perioperative levels, whereas patients with normalized CA19-9 levels after surgery had equivalent survival to those with normal perioperative levels. The prognostic impact of high CEA levels was observably smaller in patients who underwent adjuvant chemotherapy than in patients who underwent surgery alone, whereas that of high CA19-9 was greater in patients who underwent adjuvant chemotherapy. High postoperative CEA levels were significantly associated with an increased prevalence of liver, lung and bone recurrences, and high postoperative CA19-9 levels were significantly associated with increased frequencies of lymph node and liver recurrences.CONCLUSION The evaluation of serum CEA and CA 19-9 levels both before and after surgery provides useful information for precise risk stratification after curative gastrectomy. | Yasuhito Suenaga Mitsuro Kanda Seiji Ito Yoshinari Mochizuki Hitoshi Teramoto Kiyoshi Ishigure Toshifumi Murai Takahiro Asada Akiharu Ishiyama Hidenobu Matsushita Chie Tanaka Daisuke Kobayashi Michitaka Fujiwara Kenta Murotani Yasuhiro Kodera | 2019 | World Journal of Gastrointestinal Oncology2019，11，1： | 7 |
| 18 | Endobronchial metastasis from adenocarcinoma of gastric cardia 7 years after potentially curable resection显示文摘Endobronchial metastasis(EBM) is a rare form of metas-tasis from extrapulmonary malignant tumors,although there are few reports of EBM from gastric cancer specifically.We report the case of a 51-year-old woman who had undergone gastrectomy for advanced gastric cancer seven years previously but was diagnosed with a solitary lung tumor by follow-up computed tomography.On diagnosis of primary lung cancer,she underwent pulmonary lobectomy,but immunohistochemical examination confirmed the resected tumor to be an EBM from the gastric cancer.Six months later,she was diagnosed with peritoneal metastases and underwent chemotherapy with gastric cancer regimen.She is still alive at 33 mo after the lobectomy.Generally,the prognosis for EBM is poor although multidisciplinary treatment can lead to long-term survival.Precise diagnosis on the basis of detailed pathological and immunohistochemical evaluation can contribute to deciding the most effective treatment and improving prognosis. | Takaaki Hanyu Tatsuo Kanda Atsushi Matsuki Go Hasegawa Kazuhito Yajima Masanori Tsuchida Shin-ichi Kosugi Makoto Naito Katsuyoshi Hatakeyama | 2010 | World Journal of Gastrointestinal Surgery2010，2，8： | 7 |
| 19 | Hepatocellular carcinoma in extremely elderly patients:An analysis of clinical characteristics,prognosis and patient survival显示文摘瞄准:80 年或更多与肝细胞癌(HCC ) 识别病人的临床、预示的特征。方法:有 HCC 的 1310 个病人的一个总数在这研究被包括。80 年或更多的 91 个病人在 HCC 的诊断的时候被定义为极其老的组。>
或 = 的 234 个病人 50 年但是不到 60 年被认为是非老的组。结果:两性比率(到女性的男性) 比在非老的组在极其老的组(0.90:1 ) 是显著地更低的(3.9:1, P <
0.001 ) 。为 HBsAg 的积极的率在极其老的组和为显然在极其老的组增加的 HBsAg 和 HCVAb 否定的病人的比例是显著地更低的(P <
0.001 ) 。在下列参数没有有效差量:肿瘤,分级的孩子呸,肿瘤阶段,门静脉血栓形成或腹水的存在,和为 HCVAb 的积极的率的直径和数字。极其老的病人经常没收到外科疗法(P <
0.001 ) 并且他们是更可能的收到保守疗法(P <
0.01 ) 。基于与在二个组之间的全面病人比较的 Kaplan-Meier 方法在幸存曲线没有有效差量。然而,幸存曲线在有阶段 I/II 的极其老的病人是显著地更坏的,上演 I/II,孩子呸分级与非老的组比较的肝硬化。死亡的原因没在病人之中不同,并且大多数盒子甚至在极其老的病人死于肝相关的疾病。结论:在有好肝功能和好表演地位的病人,为 HCC 的好攻击的治疗可能改进幸存率,甚至在极其老的病人。 | Gengo Tsukioka Satoru Kakizaki Naondo Sohara Ken Sato Hitoshi Takagi Hirotaka Arai Takehiko Abe Mitsuo Toyoda Kenji Katakai Akira Kojima Yuichi Yamazaki Toshiyuki Otsuka Yutaka Matsuzaki Fujio Makita Daisuke Kanda Katsuhiko Horiuchi Tetsuya Hamada Mieko Kaneko Hideyuki Suzuki Masatomo Mori | 2006 | World Journal of Gastroenterology2006，12，1： | 7 |
| 20 | Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity显示文摘Hepatitis B virus(HBV)chronically infects more than350 million people worldwide.HBV causes acute and chronic hepatitis,and is one of the major causes of cirrhosis and hepatocellular carcinoma.There exist complex interactions between HBV and the immune system including adaptive and innate immunity.Tolllike receptors(TLRs)and TLR-signaling pathways are important parts of the innate immune response in HBV infections.It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense.Previous immunological studies demonstrated that HBV e antigen(HBeAg)is more efficient at eliciting T-cell tolerance,including production of specific cytokines IL-2 and interferon gamma,than HBV core antigen.HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase.MicroRNAs(miRNAs)are also able to regulate various biological processes such as the innate immune response.When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15,which could produce HBV virion that infects chimpanzees,using real-time RT-PCR,we observed several different expression levels in miRNAs related to TLRs.Although we and others have shown that HBV modulates the host immune response,several of the miRNAs seem to be involved in the TLR signaling pathways.The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered.This article is intended to comprehensively review the association between HBV and innate immunity,and to discuss the role of miRNAs in the innate immune response to HBV infection. | Xia Jiang Tatsuo Kanda Shuang Wu Masato Nakamura Tatsuo Miyamura Shingo Nakamoto Arup Banerjee Osamu Yokosuka | 2014 | World Journal of Gastroenterology2014，20，23： | 6 |
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