Faculty Profiles - KANDA Mitsuro

Papers - KANDA Mitsuro

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腹腔鏡下胃切除術におけるIndocyanine Green蛍光法を用いた病変位置同定方法 Reviewed

田中千恵, 神田光郎, 林真路, 服部憲史, 小林大介, 山田豪, 中山吾郎, 小池聖彦, 藤原道隆, 小寺泰弘

日本臨床外科学会雑誌 Vol. 80 ( 増刊 ) page： 472 - 472 2019.10

胃癌根治切除術後S-1補助化学療法の忍容性予測因子の検討 Reviewed

三輪高嗣, 神田光郎, 田中千恵, 小林大介, 園原史訓, 高見秀樹, 服部憲史, 猪川祥邦, 林真路, 山田豪, 中山吾郎, 小池聖彦, 藤原道隆, 小寺泰弘

日本臨床外科学会雑誌 Vol. 80 ( 増刊 ) page： 570 - 570 2019.10

Incorporating molecular biomarkers into clinical practice for gastric cancer. Reviewed International journal

Shunsuke Nakamura, Mitsuro Kanda, Yasuhiro Kodera

Expert review of anticancer therapy Vol. 19 ( 9 ) page： 757 - 771 2019.9

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

Introduction: Gastric cancer is one of the most common causes of cancer-related mortality worldwide. To improve clinical outcomes, it is critical to develop appropriate approaches to diagnosis and treatment. Biomarkers have numerous potential clinical applications, including screening, assessing risk, determining prognosis, monitoring recurrence, and predicting response to treatment. Furthermore, biomarkers may contribute to the development of effective therapies. Areas covered: Here we review recent progress in exploiting GC-specific biomarkers such as protein-coding genes, microRNAs, long noncoding RNAs, and methylated gene promoters. Expert opinion: The development of biomarkers for diagnosing and monitoring gastric cancer and for individualizing therapeutic targets shows great promise for improving gastric cancer management.

DOI： 10.1080/14737140.2019.1659136

Web of Science

PubMed

Biological and conditional factors should be included when defining criteria for resectability for patients with pancreatic cancer. International journal

Kato Y, Yamada S, Tashiro M, Sonohara F, Takami H, Hayashi M, Kanda M, Kobayashi D, Tanaka C, Nakayama G, Koike M, Fujiwara M, Kodera Y

HPB : the official journal of the International Hepato Pancreato Biliary Association Vol. 21 ( 9 ) page： 1211 - 1218 2019.9

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

BACKGROUND: This study aimed to evaluate novel resectability criteria for pancreatic ductal adenocarcinoma (PDAC) proposed by the International Association of Pancreatology (IAP) by comparing them with the National Comprehensive Cancer Network (NCCN) guidelines. METHODS: 369 patients who underwent upfront surgery for PDAC were retrospectively analyzed. Overall survival (OS) of each group as defined by either of the guidelines were compared and preoperative prognostic factors for OS were identified. RESULTS: Based on the IAP-criteria, 157 patients were classified as resectable (R), 192 as borderline resectable (BR) and 20 as unresectable (UR), with the median survival time (MST) of 40 months, 17 and 11, respectively. In contrast to the NCCN-criteria, BR demonstrated significantly better OS than UR (P = 0.023) under the IAP-criteria. Performance status ≥2 (hazard ratio [HR]: 2.47, P = 0.014) and lymph node metastasis suspected by imaging (HR: 1.55, P = 0.003) were identified as independent prognostic factors by the multivariate analysis along with portal or arterial invasion, while carbohydrate antigen 19-9 ≥ 500 U/ml was not (HR: 1.23, P = 0.190). CONCLUSION: The IAP-criteria, which includes biological and conditional factors, resulted in superior separation of survival curves stratified by the resectablity when compared with the NCCN-criteria.

DOI： 10.1016/j.hpb.2019.01.012

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PubMed

Multi-institutional analysis of the prognostic significance of postoperative complications after curative resection for gastric cancer. Reviewed International journal

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

Cancer medicine Vol. 8 ( 11 ) page： 5194 - 5201 2019.9

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

BACKGROUND: Insufficient data are available on the prognostic significance of complications after resection of gastric cancer. Therefore, we aimed to assess this gap in our knowledge by studying patients with resectable gastric cancer. METHODS: A multi-institutional retrospective database comprising clinical information of 3575 patients who received resection of gastric cancer from 2010 to 2014 at nine institutions. Grades 2 or greater complications of the Clavien-Dindo classification were judged as clinically relevant postoperative complications, and their associations with postoperative survival were assessed. We assessed the effect of complications on times of initiation and continuation of postoperative adjuvant chemotherapy by S-1. RESULTS: A total of 2954 patients were included in the analysis. Clinically relevant postoperative complications occurred in 664 (23%) patients. Patients' recurrence-free survival rate incrementally decreased as the grade of complications became greater. Patients with abdominal complications (eg, leakage of pancreatic fluids, intra-abdominal abscess, and anastomotic leakage) and those with nonabdominal complications (eg, pneumonia) experienced worse recurrence-free survival compared to those without complications. Patients who had complications were generally at greater risk of disease recurrence, except for those who underwent laparoscopic surgery and those with pathological stage I. Delayed initiation and shorter continuation of adjuvant S-1 chemotherapy was experienced by patients with postoperative complications. CONCLUSIONS: Postoperative complications adversely affected the prognosis in patients with resectable gastric cancer.

DOI： 10.1002/cam4.2439

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PubMed

Recent advances in molecular biomarkers for patients with hepatocellular carcinoma. Reviewed International journal

Shinichi Umeda, Mitsuro Kanda, Yasuhiro Kodera

Expert review of molecular diagnostics Vol. 19 ( 8 ) page： 725 - 738 2019.8

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

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide and recurrence rate after curative resection remains high. To improve HCC prognosis, novel sensitive biomarkers and targeted molecular therapies are needed. Accumulation of multiple genetic aberrations caused by pathologically derived liver damage results in HCC carcinogenesis. Elucidating the genes associated with tumorigenesis and progression of HCC may lead to the development of early detection and prognosis markers and to the identification of therapeutic targets. Areas covered: We review recently reported (January 2017-March 2019) HCC-associated molecules, including protein-coding genes, microRNAs, long non-coding RNAs, and methylated gene promoters. Expert opinion: The molecules reviewed have the potential to be clinical biomarkers and therapeutic targets for HCC. The accumulation and understanding of genetic and epigenetic data are essential to improve the management of HCC patients.

DOI： 10.1080/14737159.2019.1638254

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PubMed

Proposal of a Scoring Scale to Estimate Risk of the Discontinuation of S-1 Adjuvant Monotherapy in Patients with Stage II to III Gastric Cancer: A Multi-Institutional Dataset Analysis. International journal

Iizuka A, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y

World journal of surgery Vol. 43 ( 8 ) page： 2016 - 2024 2019.8

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

BACKGROUND: Discontinuation of postoperative S-1 adjuvant monotherapy is a frequent problem in the management of patients with gastric cancer. METHODS: A total of 355 stage II/III gastric cancer patients who underwent gastrectomy and adjuvant S-1 were retrospectively analyzed using a multicenter dataset. We randomly assigned patients into either discovery or validation cohort in a 2:1 ratio. In the discovery cohort, 29 parameters were assessed as candidate factors to predict discontinuation of S-1 adjuvant within 6 months. A scoring system was designed using independent risk factors identified by the multivariate analysis. Reproducibility was tested in the validation cohort. RESULTS: Overall, 92 patients (25.9%) discontinued the treatment within 6 months because of adverse effects. Age, preoperative urea nitrogen (UN) and the preoperative albumin-to-bilirubin index (ALBI) showed the highest area under the curve (AUC) for the discontinuation of S-1 adjuvant within 6 months in each category: body status, blood tests and indices. In the multivariate analysis, age ≥ 64 years, preoperative UN ≥ 15.2 mg/dl and preoperative ALBI ≥ -0.265 were identified as independent risk factors. A scoring scale consisting of these three factors was developed for the prediction of drug discontinuation and demonstrated a greater AUC (0.728) than that of each of the three constituents. The time to treatment discontinuation decreased incrementally as the risk score increased. The reproducible findings were confirmed in the validation cohort. CONCLUSIONS: We identified risk factors and developed a scoring scale to predict S-1 adjuvant monotherapy discontinuation in patients with stage II/III gastric cancer.

DOI： 10.1007/s00268-019-04942-y

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PubMed

Risk factors for paraaortic lymph-node recurrence in colorectal cancer

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

Annals of Cancer Research and Therapy Vol. 27 ( 2 ) page： 52 - 56 2019.7

Language：English Publishing type：Research paper (scientific journal) Publisher：The Japanese Society of Strategies for Cancer Research and Therapy

Background: The paraaortic lymph-node (PALN) is a relatively uncommon metastasis as a first site of recurrence following colorectal cancer (CRC) surgery. Localized and resectable PALN recurrence has the potential of long-term survival by curative resection. We evaluated the risk factors for the recurrence of PALN following curative surgery in patients with CRC in a pooled analysis of two large randomised control studies.

Patients and Methods: Individual patient data from the Japanese Foundation for Multidisciplinary Treatment of Cancer clinical Trials 7 and 15 were pooled for this analysis. We included total 4459 patients who had stage I-III colorectal cancer and underwent curative resection with over D2 lymph node dissection.

Results: Recurrent PALN occurred in 0.7% of all patients (30/4459). Of the 30 patients with recurrent PALN, 19 had PALN alone, whereas 11 had a recurrence in at least one other organ in addition to PALN. PALN recurrence occurred after the 3-year postoperative period in 10 patients (33%). In multivariate analysis, lymph node involvement was the only independent predictor of recurrent PALN (hazard ratio, 2.670; p = 0.0106).

Conclusions: Our findings clarify the risk factors for PALN recurrence in stage I–III CRC who undergo curative resection. These results will be useful to identify optimal subgroups for high risk of PLAN recurrence.

DOI： 10.4993/acrt.27.52

Other Link： https://search.jamas.or.jp/link/ui/2020287179

Number of retrieved lymph nodes is an independent prognostic factor after total gastrectomy for patients with stage III gastric cancer: propensity score matching analysis of a multi-institution dataset.

Hayashi S, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 22 ( 4 ) page： 853 - 863 2019.7

Functions of FRAS1 as a driver gene of liver metastasis from gastric cancer analyzed by the genome editing technology Reviewed

Umeda Shinichi, Kanda Mitsuro, Tanaka Haruyoshi, Sonohara Fuminori, Takami Hideki, Hattori Norifumi, Hayashi Masamichi, Tanaka Chie, Kobayashi Daisuke, Yamada Suguru, Nakayama Goro, Koike Masahiko, Fujiwara Michitaka, Kodera Yasuhiro

CANCER RESEARCH Vol. 79 ( 13 ) 2019.7

Genomewide expression profiling identifies a novel miRNA-based signature for the detection of peritoneal metastasis in gastric cancer Reviewed

Shimura Tadanobu, Toden Shusuke, Kandimalla Raju, Toiyama Yuji, Okugawa Yoshinaga, Kanda Mitsuro, Baba Hideo, Kodera Yasuhiro, Kusunoki Masato, Hori Hiroki, Goel Ajay

CANCER RESEARCH Vol. 79 ( 13 ) 2019.7

切除不能胃癌に対するConversion Surgeryの適応と予後因子の検討 Reviewed

小林大介, 神田光郎, 田中千恵, 服部憲史, 林真路, 山田豪, 中山吾郎, 小池聖彦, 藤原道隆, 小寺泰弘

日本消化器外科学会総会 Vol. 74回 page： P33 - 1 2019.7

胃癌に対するS-1術後補助化学療法の開始時期と予後に関する検討 Reviewed

中西香企, 神田光郎, 伊藤誠二, 望月能成, 寺本仁, 石榑清, 村井俊文, 浅田崇洋, 石山聡治, 小寺泰弘

日本消化器外科学会総会 Vol. 74回 page： P75 - 3 2019.7

Long-lasting discussion: Adverse effects of intraoperative blood loss and allogeneic transfusion on prognosis of patients with gastric cancer. Reviewed International journal

Nakanishi K, Kanda M, Kodera Y

World journal of gastroenterology Vol. 25 ( 22 ) page： 2743 - 2751 2019.6

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

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.

DOI： 10.3748/wjg.v25.i22.2743

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PubMed

Albumin-Bilirubin Score Predicts Tolerability to Adjuvant S-1 Monotherapy after Curative Gastrectomy. Reviewed International journal

Miwa T, Kanda M, Tanaka C, Kobayashi D, Hayashi M, Yamada S, Nakayama G, Koike M, Kodera Y

Journal of gastric cancer Vol. 19 ( 2 ) page： 183 - 192 2019.6

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

PURPOSE: Due to adverse events, dose reduction or withdrawal of adjuvant chemotherapy is required for some patients. To identify the predictive factors for tolerability to postoperative adjuvant S-1 monotherapy in gastric cancer (GC) patients, we evaluated the predictive values of blood indicators. MATERIALS AND METHODS: We analyzed 98 patients with pStage II/III GC who underwent postoperative adjuvant S-1 monotherapy. We retrospectively analyzed correlations between 14 parameters obtained from perioperative routine blood tests to assess their influence on the withdrawal of postoperative adjuvant S-1 monotherapy, within 6 months after discontinuation. RESULTS: Postoperative adjuvant chemotherapy was discontinued in 21 patients (21.4%) within 6 months. Univariable analysis revealed that high preoperative albumin-bilirubin (ALBI) scores had the highest odds ratio (OR) for predicting the failure of adjuvant S-1 chemotherapy (OR, 6.47; 95% confidence interval [CI], 2.08-20.1; cutoff value, -2.696). The high ALBI group had a significantly shorter time to failure of postoperative adjuvant S-1monotherapy (hazard ratio, 3.48; 95% CI, 1.69-7.25; P=0.001). Multivariable analysis identified high preoperative ALBI score as an independent prognostic factor for tolerability (OR, 10.3; 95% CI, 2.33-45.8; P=0.002). CONCLUSIONS: Preoperative ALBI shows promise as an indicator associated with the tolerability of adjuvant S-1 monotherapy in patients with pStage II/III GC.

DOI： 10.5230/jgc.2019.19.e15

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Genome-wide Discovery of a Novel Gene-expression Signature for the Identification of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma. Reviewed International journal

Fuminori Sonohara, Feng Gao, Naoki Iwata, Mitsuro Kanda, Masahiko Koike, Naoki Takahashi, Yasuhide Yamada, Yasuhiro Kodera, Xin Wang, Ajay Goel

Annals of surgery Vol. 269 ( 5 ) page： 879 - 886 2019.5

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

OBJECTIVE: This study aimed to develop a gene-expression signature for identification of lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA: LN metastasis is recognized as the most important independent risk factor for therapeutic decision-making of ESCC patients. METHODS: A bioinformatic approach was used to analyze RNA sequencing profiles of ESCC patients, and to develop a gene-expression signature for identifying LN metastasis. The robustness of this panel was assessed in 2 independent patient cohorts (n = 56 and 224). RESULTS: We initially prioritized a 16-gene signature out of the total 20,531 mRNAs. The model estimated by these 16 genes discriminated LN status with an area under the curve (AUC) of 0.77 [95% confidence interval (95% CI), 0.68-0.87, 5-fold cross-validation]. Subsequently, a reduced and optimized 5-gene panel was trained in a clinical cohort, which effectively distinguished ESCC patients with LN metastasis (cohort-1: AUC, 0.74; 95% CI, 0.58-0.89; cohort-2, T1-T2: AUC, 0.74; 95% CI, 0.63-0.86), and was significantly superior to preoperative computed tomography (AUC, 0.61; 95% CI, 0.50-0.72). Furthermore, a combination signature comprising of the 5-gene panel together with the lymphatic vessel invasion (LVI) and venous invasion (VI) demonstrated a significantly improved diagnostic performance compared with individual clinical variables, in both cohorts (cohort-1: AUC, 0.87; 95% CI, 0.78-0.96; cohort-2: AUC, 0.76; 95% CI, 0.65-0.88). CONCLUSION: Our novel 5-gene panel is a robust diagnostic tool for LN metastasis, especially in early-T stage ESCC patients, with a promising clinical potential.

DOI： 10.1097/SLA.0000000000002622

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PubMed

Homeobox C10 Influences on the Malignant Phenotype of Gastric Cancer Cell Lines and its Elevated Expression Positively Correlates with Recurrence and Poor Survival. International journal

Miwa T, Kanda M, Umeda S, Tanaka H, Tanaka C, Kobayashi D, Suenaga M, Hayashi M, Yamada S, Nakayama G, Koike M, Kodera Y

Annals of surgical oncology Vol. 26 ( 5 ) page： 1535 - 1543 2019.5

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

BACKGROUND: The detection of molecules and mechanisms affecting the malignant phenotype of gastric cancer cells may contribute to the identification of biomarkers for metastasis and recurrence, and such molecules may serve as targets of therapy. For this purpose, in this study transcriptome analysis was performed using surgically resected specimens from patients with gastric cancer with synchronous metastasis. We identified homeobox C10 (HOXC10) as the most highly expressed gene in gastric cancer tissues compared with the adjacent noncancerous gastric mucosa. METHODS: Polymerase chain reaction (PCR) array analysis was performed to identify genes coordinately expressed with HOXC10. The effects of inhibiting HOXC10 on malignant phenotype was evaluated using HOXC10 knockout gastric cancer cell lines, and antibody array analysis was performed to assess the effect of HOXC10 knockout on intracellular signaling. We used a mouse subcutaneous xenograft model to evaluate the tumorigenicity. HOXC10 expression was determined in gastric cancer tissues acquired from 300 patients with gastric cancer. RESULTS: PCR array analysis revealed that the levels of HOXC10 messenger RNA positively correlated with those of FGFBP1 and SOX10. The phosphorylation of ERK1/2 was decreased in HOXC10 knockout cells. HOXC10 knockout significantly suppressed proliferation by increasing apoptosis and reducing the migration and invasiveness of gastric cancer cells. Mouse xenograft models revealed that the tumorigenicity of HOXC10 knockout cells was attenuated compared with the parental cells. The relatively high expression levels of HOXC10 in gastric cancer tissues were significantly associated with hepatic and peritoneal recurrence, as well as worse prognosis. CONCLUSIONS: Our results indicated that HOXC10 enhances the malignant phenotype of gastric cancer cells. The expression levels of HOXC10 may therefore serve as a prognostic biomarker and the products of HOXC10 may provide targets of therapy.

DOI： 10.1245/s10434-019-07166-5

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PubMed

Long-term quality of life and nutrition status of the aboral pouch reconstruction after total gastrectomy for gastric cancer: a prospective multicenter observational study (CCOG1505).

Tanaka C, Kanda M, Murotani K, Yoshikawa T, Cho H, Ito Y, Matsui T, Nakayama H, Yamada T, Kobayashi D, Fujiwara M, Kodera Y

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association Vol. 22 ( 3 ) page： 607 - 616 2019.5

Increased Expression of DNAJC12 is Associated with Aggressive Phenotype of Gastric Cancer. International journal

Uno Y, Kanda M, Miwa T, Umeda S, Tanaka H, Tanaka C, Kobayashi D, Suenaga M, Hattori N, Hayashi M, Yamada S, Nakayama G, Fujiwara M, Kodera Y

Annals of surgical oncology Vol. 26 ( 3 ) page： 836 - 844 2019.3

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

BACKGROUND: Identification of gastric cancer-related molecules is necessary to elucidate the pathological mechanisms of this heterogeneous disease. The purpose of this study was to identify novel genes associated with aggressive phenotypes of gastric cancer. METHODS: Global expression profiling was conducted using tissues from four patients with metastatic gastric cancer to identify genes overexpressed in gastric cancer. Fifteen gastric cell lines and 262 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. The contribution of the candidate gene on gastric cancer cell proliferation, invasion, adhesion, and migration were evaluated using small interfering RNA. RESULTS: DnaJ heat shock protein family (Hsp40) member C12 (DNAJC12) was identified as a candidate gene by transcriptome analysis. In clinical samples, DNAJC12 mRNA levels were higher in gastric cancer tissues compared with normal adjacent tissues. Patients with high DNAJC12 expression showed significantly shorter overall survival in our cohort and in the extra-validation cohort analyzed by a published microarray dataset. High DNAJC12 expression in gastric cancer tissues was significantly associated with lymphatic involvement, infiltrative growth type, lymph node metastasis, and advanced stage and was identified as an independent prognostic factor for overall survival in multivariable analysis. Increased expression of DNAJC12 was found in 12 of 14 examined gastric cancer cell lines. Knockdown of DNAJC12 expression significantly decreased the proliferation and invasion abilities of gastric cancer cells. CONCLUSIONS: Our findings support DNAJC12 as a candidate gene associated with aggressive phenotypes of gastric cancer.

DOI： 10.1245/s10434-018-07149-y

Web of Science

PubMed

Intraoperative Blood Loss is Associated with Shortened Postoperative Survival of Patients with Stage II/III Gastric Cancer: Analysis of a Multi-institutional Dataset.

Ito Y, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y

World journal of surgery Vol. 43 ( 3 ) page： 870 - 877 2019.3

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Papers - KANDA Mitsuro