Faculty Profiles - KANDA Mitsuro

Papers - KANDA Mitsuro

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Identification of a novel molecule target for the diagnosis, prediction, and treatment of hepatic metastasis of gastric cancer.

Kanda Mitsuro, Tanaka Haruyoshi, Miwa Takashi, Kobayashi Daisuke, Tanaka Chie, Takami Hideki, Hayashi Masamichi, Iwata Naoki, Niwa Yukiko, Yamada Suguru, Nakayama Goro, Sugimoto Hiroyuki, Koike Masahiko, Fujiwara Michitaka, Kodera Yasuhiro

JOURNAL OF CLINICAL ONCOLOGY Vol. 36 ( 4 ) page： . 2018.2

Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer.

Yamada Suguru, Fujii Tsutomu, Takano Nao, Takami Hideki, Suenaga Masaya, Niwa Yukiko, Hayashi Masamichi, Iwata Naoki, Kanda Mitsuro, Kobayashi Daisuke, Tanaka Chie, Nakayama Goro, Sugimoto Hiroyuki, Koike Masahiko, Fujiwara Michitaka, Kodera Yasuhiro

JOURNAL OF CLINICAL ONCOLOGY Vol. 36 ( 4 ) page： . 2018.2

Review of recent molecular landscape knowledge of gastric cancer Reviewed

Dai Shimizu, Mitsuro Kanda, Yasuhiro Kodera

HISTOLOGY AND HISTOPATHOLOGY Vol. 33 ( 1 ) page： 11 - 26 2018.1

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：F HERNANDEZ

Gastric cancer (GC) is one of the most frequently diagnosed cancers worldwide and its prognosis remains dismal. One reason for poor outcomes of GC patients is that most are diagnosed when the cancer has already advanced. Novel biomarkers with high sensitivity and specificity are needed to diagnose GC in the early stage. In addition, to improve the outcome of patients with GC, patient stratification according to prognostic factors and sensitivity to chemo(radio) therapy are necessary. Appropriate follow-up criteria and individualized treatment will contribute to improvement in prognosis. Over the past decades, development of microarray and sequencing technology have coalesced to increase reports regarding epigenetic alterations that affect the character of malignancies including GC. These advances help our understanding of gastric carcinogenesis and have the possibility of improving the prognosis of GC by contributing to the optimization of therapeutic strategies. Further development of biomarkers for diagnosis and prognosis are desperately needed. Here, we enumerate and describe some GC-related molecules reported over the past few years that may be useful biomarkers.

DOI： 10.14670/HH-11-898

Web of Science

PubMed

Effectiveness of plasma activated lactated Ringer's solution on pancreatic cancer cells in vitro and in vivo

Sato Yusuke, Yamada Suguru, Takeda Shigeomi, Kanda Mitsuo, Nakayama Goro, Koike Masahiko, Fujiwara Michitaka, Kodera Yasuhiro

CANCER SCIENCE Vol. 109 page： 707-707 2018.1

Oncogenic function of miR-23b-3p in hepatocellular carcinoma

Masamichi Hayashi, Yamada Suguru, Kanda Mitsuro, Tanaka Chie, Fujiwara Michitaka, Kodera Yasuhiro

CANCER SCIENCE Vol. 109 page： 1123-1123 2018.1

Nutritional Recovery after Open and Laparoscopic Distal Gastrectomy for Early Gastric Cancer: A Prospective Multicenter Comparative Trial (CCOG1204) Reviewed

Hidenobu Matsushita, Chie Tanaka, Kenta Murotani, Kazunari Misawa, Seiji Ito, Yuichi Ito, Mitsuro Kanda, Yoshinari Mochizuki, Kiyoshi Ishigure, Toyohisa Yaguchi, Jin Teramoto, Hiroshi Nakayama, Yoshihisa Kawase, Michitaka Fujiwara, Yasuhiro Kodera

DIGESTIVE SURGERY Vol. 35 ( 1 ) page： 11 - 18 2018

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：KARGER

Background: Little information from prospective clinical trials is available on the influences of surgical approaches on postoperative body compositions and nutritional status. We designed a prospective non-randomized trial to compare postoperative chronological changes in body composition and nutritional status between laparoscopic and open distal gastrectomy for stage I gastric cancer (GC). Methods: Body compositions and nutritional indicators in blood tests were measured at the baseline and at the 1st, 3rd, 6th, and 12th postoperative months (POM). The primary end point was the decrease relative to the baseline in the body muscle mass at POM 6. Results: Ninety-six patients for the laparoscopic group and 52 for the open group were eligible for data analysis. No significant differences were found in any baseline demographics, body compositions, and nutritional indicators between the groups. The changes of body muscle mass at POM 6 were similar in both groups. Overall, no significant differences between the groups were observed in any of the body composition and nutritional indicators during the first year after surgery. Conclusions: Postoperative body compositions and nutritional status were not affected by surgical approaches during the first 12 months after surgery in patients who underwent distal gastrectomy for stage I GC. (c) 2017 S. Karger AG, Basel

DOI： 10.1159/000458714

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Perioperative Serum Carcinoembryonic Antigen Levels Predict Recurrence and Survival of Patients with Pathological T2-4 Gastric Cancer Treated with Curative Gastrectomy Reviewed

Hiroaki Uda, Mitsuro Kanda, Chie Tanaka, Daisuke Kobayashi, Kenichi Inaoka, Yuri Tanaka, Masamichi Hayashi, Naoki Iwata, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Kenta Murotani, Michitaka Fujiwara, Yasuhiro Kodera

DIGESTIVE SURGERY Vol. 35 ( 1 ) page： 55 - 63 2018

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：KARGER

Background/Aims: Do serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 levels serve as prognostic indicators in patients with gastric cancer (GC)? This is a question that has long been disputed. The aim of this study was to evaluate the significance of perioperative serum levels of CEA and CA19-9 for predicting the recurrence and long-term survival after patients with pT2-4 GC undergo curative gastrectomy. Methods: This study included 251 patients with radically resected pT2-4 GC without preoperative treatment. Associations between the preoperative and postoperative serum levels of CEA or CA19-9 and postoperative long-term outcomes and recurrence patterns were evaluated. Results: Preoperative CEA > 5.0 ng/mL was an independent prognostic factor of overall survival. Elevation of both preoperative CEA and CA19-9 levels showed no synergistic adverse effects on prognosis. Preoperative levels of these markers achieved superior predictive performance compared with the postoperative values. Adverse prognosis is significantly associated with persistent elevation of CEA levels before and after gastrectomy. Elevation of CEA levels, particularly at postoperative measurement, was significantly associated with hematogenous recurrence. Conclusion: Determination of perioperative CEA levels facilitated predictions of recurrence patterns and prognosis among patients with pT2-4 GC who underwent curative gastrectomy. (c) 2017 S. Karger AG, Basel

DOI： 10.1159/000471931

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PubMed

Review of recent efforts to discover biomarkers for early detection, monitoring, prognosis, and prediction of treatment responses of patients with gastric cancer Reviewed

Sawaki Koichi, Kanda Mitsuro, Kodera Yasuhiro

EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY Vol. 12 ( 7 ) page： 657 - 670 2018

Prognostic Impact of Portal System Invasion in Pancreatic Cancer Based on Image Classification

Morimoto Daishi, Yamada Suguru, Murotani Kenta, Sonohara Fuminori, Takami Hideki, Suenaga Masaya, Hayashi Masamichi, Niwa Yukiko, Tashiro Mitsuru, Hattori Norifumi, Iwata Naoki, Kanda Mitsuro, Tanaka Chie, Kobayashi Daisuke, Nakayama Goro, Koike Masahiko, Fujiwara Michitaka, Fujii Tsutomu, Kodera Yasuhiro

PANCREAS Vol. 47 ( 10 ) page： 1350 - 1356 2018

Randomized phase II study of daily and alternate-day administration of S-1 for advanced gastric cancer (JFMC43-1003) Reviewed

Hiroaki Tanaka, Mitsuro Kanda, Satoshi Morita, Masataka Taguri, Kazuhiro Nishikawa, Mitsuo Shimada, Kazuya Muguruma, Keisuke Koeda, Masazumi Takahashi, Mikihito Nakamori, Hiroyuki Konno, Akihito Tsuji, Yoshinori Hosoya, Tetsuhiko Shirasaka, Susumu Yamamitsu, Michio Sowa, Masaki Kitajima, Masazumi Okajima, Michiya Kobayashi, Junichi Sakamoto, Shigetoyo Saji, Kosei Hirakawa

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY Vol. 22 ( 6 ) page： 1052 - 1059 2017.12

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

Purpose Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer.
Methods 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m(2)/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate.
Results The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15-2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97-2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007).
Conclusion The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.

DOI： 10.1007/s10147-017-1157-3

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PubMed

Prevalence of Helicobacter pylori infection in dyspeptic patients in Andkhoy Afghanistan Reviewed

Mohammad Hussain Hamrah, Mohammad Shoaib Hamrah, Mohammad Hassan Hamrah, Mitsuro Kanda, Ahmad Edris Hamrah, Ahmad Elias Dahi, Farhat Homayoun, Mohammad Hashem Hamrah, Akbar Fotouhi, Junichi Sakamoto

Asian Pacific Journal of Cancer Prevention Vol. 18 ( 11 ) page： 3123 - 3127 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Asian Pacific Organization for Cancer Prevention

Background: The prevalence of Helicobacter pylori (H. pylori) infection is reported to be more than 50% worldwide. It has been associated with peptic ulcer disease, gastric carcinoma, and mucosal-associated lymphoid tissue lymphoma. The seroprevalence of H. pylori varies greatly among societies and geographical locations. The objective of this study was to determine the seroprevalence and factors associated with H. pylori infection among dyspeptic patients in Afghanistan. Materials and Methods: This cross-sectional study was designed to determine the seroprevalence of H. pylori among dyspeptic patients in an outpatient clinic in Andkhoy, Afghanistan from January 2017 to April 2017. Data were obtained from patients using a questionnaire, including socio-demographic data and history of smoking and dyspeptic symptoms. Serum samples were also collected from the patients and tested for H. pylori antibodies using the enzyme-linked immunosorbent assay. Results: A total of 152 patients with dyspepsia were included in the analysis
59 were men (40.0%), and 93 were women (60.0%). The overall seroprevalence of H. pylori was 75.6%. The predictor of seroprevalence of H. pylori was found to be illiteracy (odds ratio [OR] 4.99, 95% confidence interval [CI] 1.03-24.17), epigastric pain (OR 12.01, 95% CI 3.56- 40.52), and rural population (OR 9.66, 95% CI 3.36- 27.82). There was an inverse association between employed status and seroprevalence of H. pylori (OR 0.08, 95% CI 0.01- 0.52). Conclusions: The seroprevalence of H. pylori was high among patient with dyspepsia in an outpatient clinic in Afghanistan. Illiteracy, unemployment and rural populations, and epigastric pain were significantly associated with H. pylori infection.

DOI： 10.22034/APJCP.2017.18.11.3123

Scopus

PubMed

Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials. Reviewed International journal

Michitaka Honda, Koji Oba, Takashi Akiyoshi, Hiromichi Maeda, Kosuke Kashiwabara, Mitsuro Kanda, Shuhei Mayanagi, Toru Aoyama, Chikuma Hamada, Sotaro Sadahiro, Yosuke Fukunaga, Masashi Ueno, Junichi Sakamoto, Shigetoyo Saji, Takaki Yoshikawa

Oncotarget Vol. 8 ( 58 ) page： 99150 - 99160 2017.11

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

Background: Few prediction models have so far been developed and assessed for the prognosis of patients who undergo curative resection for colorectal cancer (CRC). Materials and Methods: We prepared a clinical dataset including 5,530 patients who participated in three major randomized controlled trials as a training dataset and 2,263 consecutive patients who were treated at a cancer-specialized hospital as a validation dataset. All subjects underwent radical resection for CRC which was histologically diagnosed to be adenocarcinoma. The main outcomes that were predicted were the overall survival (OS) and disease free survival (DFS). The identification of the variables in this nomogram was based on a Cox regression analysis and the model performance was evaluated by Harrell's c-index. The calibration plot and its slope were also studied. For the external validation assessment, risk group stratification was employed. Results: The multivariate Cox model identified variables; sex, age, pathological T and N factor, tumor location, size, lymphnode dissection, postoperative complications and adjuvant chemotherapy. The c-index was 0.72 (95% confidence interval [CI] 0.66-0.77) for the OS and 0.74 (95% CI 0.69-0.78) for the DFS. The proposed stratification in the risk groups demonstrated a significant distinction between the Kaplan-Meier curves for OS and DFS in the external validation dataset. Conclusions: We established a clinically reliable nomogram to predict the OS and DFS in patients with CRC using large scale and reliable independent patient data from phase III randomized controlled trials. The external validity was also confirmed on the practical dataset.

DOI： 10.18632/oncotarget.21845

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PubMed

FBXO50 Enhances the Malignant Behavior of Gastric Cancer Cells Reviewed

Takashi Miwa, Mitsuro Kanda, Haruyoshi Tanaka, Chie Tanaka, Daisuke Kobayashi, Shinichi Umeda, Naoki Iwata, Masamichi Hayashi, Suguru Yamada, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera

ANNALS OF SURGICAL ONCOLOGY Vol. 24 ( 12 ) page： 3771 - 3779 2017.11

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

Challenges to our understanding the molecular mechanisms of the progression of gastric cancer (GC) must be overcome to facilitate the identification of novel biomarkers and therapeutic targets. In this article, we analyzed the expression of the gene encoding F-box-only 50 (FBXO50) and determined whether it contributes to the malignant phenotype of GC.
FBXO50 messenger RNA (mRNA) levels and copy numbers of the FBXO50 locus were determined in 10 GC cell lines and a nontumorigenic epithelial cell line. Polymerase chain reaction array analysis was performed to identify genes coordinately expressed with FBXO50. The effects of inhibiting FBXO50 on GC cell proliferation, adhesion, invasiveness, and migration were evaluated using a small interfering RNA targeted to FBXO50 mRNA. To evaluate the clinical significance of FBXO50 expression, we determined the levels of FBXO50 mRNA in tissues acquired from 200 patients with GC.
The levels of FBXO50 mRNA were increased in five GC cell lines and positively correlated with those of ITGA5, ITGB1, MMP2, MSN, COL5A2, GNG11, and WNT5A. Copy number gain of the FBXO50 locus was detected in four GC cell lines. Inhibition of FBXO50 expression significantly decreased the proliferation, adhesion, migration, and invasiveness of GC cell lines. In clinical samples, high FBXO50 expression correlated with increased pT4, invasive growth, lymph node metastasis, and positive peritoneal lavage cytology. Patients with high FBXO50 expression had a significantly higher prevalence of recurrence after curative gastrectomy and were more likely to experience shorter overall survival.
FBXO50 may represent a biomarker for GC phenotypes and as a target for therapy.

DOI： 10.1245/s10434-017-5882-7

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PubMed

Clinical impact of postoperative surgical complications on the colorectal cancer survival and recurrence: Analyses of pooled individual patients' data from three large phase III randomized trials

Aoyama T., Oba K., Honda M., Sadahiro S., Hamada C., Mayanagi S., Kanda M., Maeda H., Sakamoto J., Saji S., Yoshikawa T.

ANNALS OF ONCOLOGY Vol. 28 page： . 2017.11

Clinical impact of tumor location on the colon cancer survival and recurrence: analyses of pooled data from three large phase III randomized clinical trials. Reviewed International journal

Toru Aoyama, Kosuke Kashiwabara, Koji Oba, Michitaka Honda, Sotaro Sadahiro, Chikuma Hamada, Hiromichi Maeda, Shuhei Mayanagi, Mitsuro Kanda, Junichi Sakamoto, Shigetoyo Saji, Takaki Yoshikawa

Cancer medicine Vol. 6 ( 11 ) page： 2523 - 2530 2017.11

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

The aim of the present study was to determine whether or not the overall survival (OS) and disease-free survival (DFS) were affected by the tumor location in patients who underwent curative resection for colon cancer in a pooled analysis of three large phase III studies performed in Japan. In total, 4029 patients were included in the present study. Patients were classified as having right-side colon cancer (RC) if the primary tumor was located in the cecum, ascending colon, hepatic flexure or transverse colon, and left-side colon cancer (LCC) if the tumor site was within the splenic flexure, descending colon, sigmoid colon or recto sigmoid junction. The risk factors for the OS and DFS were analyzed. In the present study, 1449 patients were RC, and 2580 were LCC. The OS rates at 3 and 5 years after surgery were 87.6% and 81.6% in the RC group and 91.5% and 84.5% in the LCC group, respectively. Uni- and multivariate analyses showed that RRC increased the risk of death by 19.7% (adjusted hazard ratio = 1.197; 95% confidence interval, 1.020-1.408; P = 0.0272). In contrast, the DFS was similar between the two locations. The present study confirmed that the tumor location was a risk factor for the OS in patients who underwent curative treatment for colon cancer. Tumor location may, therefore, need to be considered a stratification factor in future phase III trials of colon cancer.

DOI： 10.1002/cam4.1208

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PubMed

FAM46C Serves as a Predictor of Hepatic Recurrence in Patients with Resectable Gastric Cancer Reviewed

Haruyoshi Tanaka, Mitsuro Kanda, Dai Shimizu, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Naoki Iwata, Suguru Yamada, Tsutomu Fujii, Goro Nakayama, Hiroyuki Sugimoto, Michitaka Fujiwara, Yukiko Niwa, Yasuhiro Kodera

ANNALS OF SURGICAL ONCOLOGY Vol. 24 ( 11 ) page： 3438 - 3445 2017.10

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

Gastric cancer (GC) relapse can occur even if curative resection is achieved. Biomarkers predicting recurrence are needed to provide appropriate postoperative surveillance and perioperative therapeutic strategy.
A global expression profiling was performed using tissues from GC patients with synchronous liver-confined metastasis. Family with sequence similarity 46, member C (FAM46C), was identified as a candidate biomarker. mRNA expression analysis, direct nucleotide sequencing, bisulfite sequencing and copy number assays for FAM46C were performed with eleven GC cell lines. Expression levels of FAM46C in primary GC tissues from 129 patients who underwent curative GC resection were determined and correlated with clinicopathological factors, including postoperative outcome.
Levels of FAM46C mRNA differed among GC cell lines. Point mutations in FAM46C were detected in five GC cell lines accompanied with reduced FAM46C transcription. No hypermethylation was found in the promoter region of FAM46C. Copy number alterations were found in six GC cell lines with differing FAM46C transcription levels. Reduced FAM46C mRNA expression levels were detected in 117 (91 %) GC specimens compared with adjacent noncancerous tissues. Low FAM46C expression levels were significantly associated with larger macroscopic GC tumor sizes. The low FAM46C expression group was likely to have shorter disease-free survival than the high group and low FAM46C level was identified as an independent risk factor for recurrence after curative resection. FAM46C expression levels were low in all cases that were later found to have hepatic recurrence.
Reduced GC expression of FAM46C is a potential biomarker to predict hepatic recurrence after curative gastrectomy.

DOI： 10.1245/s10434-016-5636-y

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PubMed

Identification of NCCRP1 as an epigenetically regulated tumor suppressor and biomarker for malignant phenotypes of squamous cell carcinoma of the esophagus Reviewed

Takashi Miwa, Mitsuro Kanda, Masahiko Koike, Naoki Iwata, Haruyoshi Tanaka, Shinichi Umeda, Chie Tanaka, Daisuke Kobayashi, Masamichi Hayashi, Suguru Yamada, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera

ONCOLOGY LETTERS Vol. 14 ( 4 ) page： 4822 - 4828 2017.10

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

The poor prognosis and increasing incidence of esophageal squamous cell carcinoma (ESCC) highlight the need for identification of novel ESCC-associated molecular events to improve the diagnosis, and treatment of this disease. Non-specific cytotoxic cell receptor protein 1 (NCCRP1) was reported to be abundantly expressed in human squamous epithelium and to be involved in cell proliferation; however, the role of NCCRP1 in ESCC remains unclear. To elucidate the oncological roles of NCCRP1 in ESCC, NCCRP1 expression, DNA methylation, and copy numbers were analyzed in ESCC cell lines. Nine ESCC cell lines demonstrated different NCCRP1 mRNA expression levels and all exhibited hypermethylation of the NCCRP1 promoter, but no copy number loss. Additionally, NCCRP1 expression was determined in 213 surgically resected esophageal tissue samples. NCCRP1 mRNA expression levels were reduced in ESCC tissues compared with corresponding non-cancerous adjacent tissues in 204 (95.8%) patients. Patients in the low NCCRP1 expression group tended to have a higher recurrence rate and a shorter overall survival time compared with those in the high NCCRP1 expression group. Additionally, multivariate analysis revealed that low NCCRP1 expression was an independent prognostic factor (hazard ratio, 1.75; 95% confidence interval, 1.08-2.87; P=0.022). The findings of the current study indicate that NCCRP1 acts as a putative tumor suppressor that is inactivated through promoter hypermethylation, and serves as a promising biomarker to predict postoperative prognosis in ESCC.

DOI： 10.3892/ol.2017.6753

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Evaluation and proposal of novel resectability criteria for pancreatic cancer established by the Japan Pancreas Society Reviewed

Suguru Yamada, Tsutomu Fujii, Hideki Takami, Masamichi Hayashi, Naoki Iwata, Mitsuro Kanda, Chie Tanaka, Hiroyuki Sugimoto, Goro Nakayama, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera

SURGERY Vol. 162 ( 4 ) page： 784 - 791 2017.10

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：MOSBY-ELSEVIER

Background. The guidelines for the classification of the resectability of pancreatic cancer established by the National Comprehensive Cancer Network can be difficult to utilize in clinical practice. We evaluated novel criteria proposed by the Japan Pancreas Society.
Methods. We analyzed 382 patients with pancreatic cancer between 2001 and 2015 for survival differences among subgroups classified according to the Japan Pancreas Society classification. Overall survival and disease-free survival were expressed as median values and compared with data based on the National Comprehensive Cancer Network classification, and differences in initial patterns of recurrence were analyzed.
Results. Overall survival times according to the Japan Pancreas Society criteria were 34.2, 29.7, 17.3, 14.3, and 15.8 months for the groups defined as resectable, resectable with portal vein invasion, borderline resectable with portal vein invasion, borderline resectable with arterial invasion, and unresectable by locally advanced disease respectively. The overall survival of the resectable group was better than those of the borderline resectable with portal vein invasion or borderline resectable with arterial invasion groups (P <.0001); however, the borderline resectable with portal vein invasion, borderline resectable with arterial invasion, and unresectable by locally advanced groups showed no differences in overall survival. The resectable group showed a tendency toward better survival than the resectable with portal vein invasion group (P=.058). The median overall survival times according to the classic 2012 National Comprehensive Cancer Network criteria were 30.5, 20.5, 15.8, and 13.8 months for the resectable, portal invasion, common hepatic artery and superior mesenteric artery invasion groups, respectively. Each survival curve was clearly separate. The borderline resectable with arterial invasion and unresectable by locally advanced groups exhibited high local recurrence rates (42.0% and 44. 8 %, respectively).
Conclusion. The Japan Pancreas Society criteria, which are simpler, predicted survival differences between the resectable group and the other subgroups. Our data suggest that cancer patients with borderline resectable pancreatic cancer (borderline resectable with portal vein invasion and borderline resectable with arterial invasion) can be managed as a single subset.

DOI： 10.1016/j.surg.2017.04.023

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PubMed

An integrated multigene expression panel to predict long-term survival after curative hepatectomy in patients with hepatocellular carcinoma Reviewed

Mitsuro Kanda, Kenta Murotani, Hiroyuki Sugimoto, Takashi Miwa, Shinichi Umeda, Masaya Suenaga, Masamichi Hayashi, Norifumi Hattori, Chie Tanaka, Daisuke Kobayashi, Suguru Yamada, Michitaka Fujiwara, Yasuhiro Kodera

ONCOTARGET Vol. 8 ( 41 ) page： 71070 - 71079 2017.9

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：IMPACT JOURNALS LLC

Hepatocellular carcinoma (HCC) frequently recurs even after curative hepatectomy. To develop an integrated multigene expression panel, 144 patients were randomly assigned to either discovery or validation set in a 1: 2 ratio. Using surgically resected HCC specimens, expression levels of 12 candidate molecular markers were determined using quantitative reverse-transcriptase PCR. In the discovery set, an expression panel was developed according to the concordance index (C-index) values for overall survival from all 4095 combinations of the 12 candidate molecular markers. Expression scores was determined with weighting according to the coefficient in a Cox regression, and patients were classified into grade 1, 2 and 3. Reproducibility was then tested in the validation set. A panel consisting of four markers, PRMT5, MAGED4, DPYSL3 and AJAP1 was selected as the optimal and most well-balanced set with a C-index value of 0.707. Patient prognosis was clearly stratified by the expression grade using this panel. In the validation set, both overall and disease-free survival rates decreased incrementally with as the grade increased. Higher grades were significantly associated with tumor multiplicity and vessel invasion. The prevalence of extrahepatic recurrences was increased in grade 3 patients. The integrated multigene expression panel clearly stratified HCC patients into low, intermediate and high risk.

DOI： 10.18632/oncotarget.20369

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PubMed

Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma Reviewed

Shinichi Umeda, Mitsuro Kanda, Hiroyuki Sugimoto, Haruyoshi Tanaka, Masamichi Hayashi, Suguru Yamada, Tsutomu Fujii, Hideki Takami, Yukiko Niwa, Naoki Iwata, Chie Tanaka, Daisuke Kobayashi, Michitaka Fujiwara, Yasuhiro Kodera

BMC CANCER Vol. 17 ( 1 ) page： 610 2017.9

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

Background: Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker.
Methods: We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection.
Results: GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative alpha-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences.
Conclusions: Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.

DOI： 10.1186/s12885-017-3629-2

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Papers - KANDA Mitsuro