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| 1 | 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 |
| 2 | 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 |
| 3 | 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 |
| 4 | 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 |
| 5 | 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 |
| 6 | 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 |
| 7 | Emerging evidence of the molecular landscape specific for hematogenous metastasis from gastric cancer显示文摘Gastric cancer(GC) is one of the most frequentlydiagnosed cancers in the world. Most GC patients are diagnosed when the cancer is in an advanced stage, and consequently, some develop metastatic lesions that generally cause cancer-related death. Metastasis establishment is affected by various conditions, such as tumor location, hemodynamics and organotropism. While digestive cancers may share a primary site, certain cases develop hematogenous metastasis with the absence of peritoneal metastasis, and vice versa. Numerous studies have revealed the clinicopathological risk factors for hematogenous metastasis from GC, such as vascular invasion, advanced age, differentiation, Borrmann type 1 or 2 and expansive growth. Recently, molecular mechanisms that contribute to metastatic site determination have been elucidated by advanced molecular biological techniques. Investigating the molecules that specifically participate in metastasis establishment in distinct secondary organs will lead to the development of novel biomarkers for patient stratification according to their metastatic risk and strategies for preventing and treating distinct metastases. We reviewed articles related to the molecular landscape of hematogenous metastasis from GC. | Dai Shimizu Mitsuro Kanda Yasuhiro Kodera | 2018 | World Journal of Gastrointestinal Oncology2018，10，6： | 5 |
| 8 | Presence of Somatic Mutations in Most Early-Stage Pancreatic Intraepithelial Neoplasia显示文摘 | Mitsuro Kanda Hanno Matthaei Jian Wu Seung–Mo Hong Jun Yu Michael Borges Ralph H. Hruban Anirban Maitra Kenneth Kinzler Bert Vogelstein Michael Goggins | 2012 | Gastroenterology2012，，4： | 3 |
| 9 | B?cell translocation gene 1 serves as a novel prognostic indicator ofhepatocellular carcinoma显示文摘 | Mitsuro Kanda Hiroyuki Sugimoto Shuji Nomoto Hisaharu Oya Soki Hibino Dai Shimizu Hideki Takami Ryoji Hashimoto Yukiyasu Okamura Suguru Yamada Tsutomu Fujii Goro Nakayama Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2015 | International Journal of Oncology2015，，2： | 3 |
| 10 | Mutant TP53 in Duodenal Samples of Pancreatic Juice From Patients With Pancreatic Cancer or High-Grade Dysplasia显示文摘 | Mitsuro Kanda Yoshihiko Sadakari Michael Borges Mark Topazian James Farrell Sapna Syngal Jeffrey Lee Ihab Kamel Anne Marie Lennon Spencer Knight Sho Fujiwara Ralph H. Hruban Marcia Irene Canto Michael Goggins | 2013 | Clinical Gastroenterology and Hepatology2013，，6： | 2 |
| 11 | Is the measurement of drain amylase content useful for predicting pancreas-related complications after gastrectomy with systematic lymphadenectomy?显示文摘Many studies investigating postoperative pancreatic fistula(POPF)after gastrectomy,including studies measuring drain amylase content(D-AMY)as a predictive factor have been reported.This article reviews previous studies and looks to the future of measuring D-AMY in patients after gastrectomy.The causes of pancreatic fluid leakage are;the parenchymal and/or thermal injury to the pancreas,and blunt injury to the pancreas by compression and retraction.Measurement of D-AMY to predict POPF has become common in clinical practice after pancreatic surgery and was later extended to the gastric surgery.Several studies have reported associations between D-AMY and POPF after gastrectomy,and the high value of D-AMY on postoperative day(POD)1 was an independent risk factor.To improve both sensitivity and specificity,attempts have been made to enhance the predictive accuracy of factors on POD 1 as well as on POD 3 as combined markers.Although several studies have shown a high predictive ability of POPF,it has not necessarily been exploited in clinical practice.Many problems remain unresolved;ideal timing for measurement,optimal cut-off value,and means of intervention after prediction.Prospective clinical trial could be imperative in order to develop D-AMY measurement in common clinical practice for gastric surgery. | Koki Nakanishi Mitsuro Kanda Junichi Sakamoto Yasuhiro Kodera | 2020 | World Journal of Gastroenterology2020，26，14： | 2 |
| 12 | Function and diagnostic value of Anosmin‐1 in gastric cancer progression显示文摘 | Mitsuro Kanda Dai Shimizu Tsutomu Fujii Satoshi Sueoka Yuri Tanaka Kazuhiro Ezaka Hideki Takami Haruyoshi Tanaka Ryoji Hashimoto Naoki Iwata Daisuke Kobayashi Chie Tanaka Suguru Yamada Goro Nakayama Hiroyuki Sugimoto Masahiko Koike Michitaka Fujiwara Yasu | 2016 | Int. J. Cancer2016，，3： | 1 |
| 13 | Postoperative adjuvant chemotherapy with S-1 alters recurrence patterns and prognostic factors among patients with stage II/III gastric cancer: A propensity score matching analysis显示文摘 | Mitsuro Kanda Kenta Murotani Daisuke Kobayashi Chie Tanaka Suguru Yamada Tsutomu Fujii Goro Nakayama Hiroyuki Sugimoto Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2015 | Surgery2015，，6： | 1 |
| 14 | Translational implication of Kallmann syndrome-1 gene expression inhepatocellular carcinoma显示文摘 | Yuri Tanaka Mitsuro Kanda Hiroyuki Sugimoto Dai Shimizu Satoshi Sueoka Hideki Takami Kazuhiro Ezaka Ryoji Hashimoto Yukiyasu Okamura Naoki Iwata Chie Tanaka Suguru Yamada Tsutomu Fujii Goro Nakayama Masahiko Koike Shuji Nomoto Michitaka Fujiwara Yasuhiro | 2015 | International Journal of Oncology2015，，6： | 1 |
| 15 | Clinical significance of expression and epigenetic profiling of TUSC1 in gastric cancer显示文摘 | Mitsuro Kanda Dai Shimizu Shuji Nomoto Soki Hibino Hisaharu Oya Hideki Takami Daisuke Kobayashi Suguru Yamada Yoshikuni Inokawa Chie Tanaka Tsutomu Fujii Hiroyuki Sugimoto Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2014 | J. Surg. Oncol2014，，2： | 1 |
| 16 | Clinical significance of expression and epigenetic profiling of TUSC1 in gastric cancer显示文摘 | Mitsuro Kanda Dai Shimizu Shuji Nomoto Soki Hibino Hisaharu Oya Hideki Takami Daisuke Kobayashi Suguru Yamada Yoshikuni Inokawa Chie Tanaka Tsutomu Fujii Hiroyuki Sugimoto Masahiko Koike Michitaka Fujiwara Yasuhiro Kodera | 2014 | Oncol2014，，2： | 1 |
| 17 | Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1, EFEMP1 , a Novel Tumor-Suppressor Gene Detected in Hepatocellular Carcinoma Using Double Combination Array Analysis显示文摘 | Shuji Nomoto Mitsuro Kanda Yukiyasu Okamura Yoko Nishikawa Li Qiyong Tsutomu Fujii Hiroyuki Sugimoto Shin Takeda Akimasa Nakao | 2010 | Annals of Surgical Oncology2010，，3： | 1 |
| 18 | Evaluation of MAGE‐D4 expression in hepatocellular carcinoma in Japanese patients显示文摘 | Hideki Takami Mitsuro Kanda Hisaharu Oya Soki Hibino Hiroyuki Sugimoto Masaya Suenaga Suguru Yamada Yoko Nishikawa Mikako Asai Tsutomu Fujii Shuji Nomoto Yasuhiro Kodera | 2013 | J Surg Oncol2013，，8： | 1 |
| 19 | Detection of metallothionein 1G as a methylated tumor suppressor genein human hepatocellular carcinoma using a novel method of double combination arrayanalysis显示文摘 | Mitsuro Kanda Shuji Nomoto Yukiyasu Okamura Yoko Nishikawa Hiroyuki Sugimoto Naohito Kanazumi Shin Takeda Akimasa Nakao | 2009 | International Journal of Oncology2009，，3： | 1 |
| 20 | Epithelial to mesenchymal transition correlates with tumor budding and predicts prognosis in esophageal squamous cell carcinoma显示文摘 | Yukiko Niwa Suguru Yamada Masahiko Koike Mitsuro Kanda Tsutomu Fujii Goro Nakayama Hiroyuki Sugimoto Shuji Nomoto Michitaka Fujiwara Yasuhiro Kodera | 2014 | Oncol2014，，6： | 1 |
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