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Clinical Significance of Circulating Tumor Cells and Lymph Node Micrometastases in Gastrointestinal cancer

Research Project

Project/Area Number 19390339
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKagoshima University

Principal Investigator

UENOSONO Yoshikazu  Kagoshima University, 医学部・歯学部・附属病院, 助教 (60398279)

Co-Investigator(Kenkyū-buntansha) AIKOU Takashi  鹿児島大学, 大学院・医歯学総合研究科, 教授 (60117471)
NATSUGOE Shoji  鹿児島大学, 大学院・医歯学総合研究科, 教授 (70237577)
ISHIGAMI Sumiya  鹿児島大学, 医学部・歯学部附属病院, 助教 (90325803)
KITAZONO Masaki  鹿児島大学, 医学部・歯学部附属病院, 助教 (30398276)
松本 正隆  鹿児島大学, 医学部・歯学部附属病院, 助教 (40398293)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2007: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Keywordsセンチネルリンパ節 / 微小転移 / 循環癌細胞 / 消化器癌 / 循環癌 / 胃癌 / 食道癌 / RT-PCR
Research Abstract

(1) Circulating tumor cells in blood detected by CellSearch System in gastric cancer The purposes of this study are to evaluate CTCs of peripheral blood (PB) and portal vein blood (PV) with gastric cancer patients using CellSearch System (CSS), and to investigate the relation of the recurrence. 【Methods】 In 50 patients with T1-3 gastric cancer, PB was collected 10ml before the gastrectomy, and PV was collected 10ml during operation. 【Results】CTCs were detected in 18% from PB, 24% from PV and 28% from PB and/or PV. CTCs were found in 8% with T1, 26% with T2, 44% with T3. Detection rate of CTCs were correlated with the results of Stage (p=0.007), vessel invasion (p=0.008), lymphatic invasion (p=0.007) and lymph node metastasis (p=0.01). The recurrences were detected in 11 patients (78.5%) with CTCs, and there was statistically significant difference in over all survival between patients with or without CTCs (p=0.0049). 【Conclusions】The identification of CTCs is very useful to follow up a … More fter operation and to perform the adjuvant chemotherapy in gastric cancer.
(2)-1 The utility of rapid diagnosis of lymph node metastasis in gastric cancer using a multiplex real-time RT-PCR assay
The purpose of this study was to evaluate the utility of a prototype RT-PCR assay run on the SmartCycler^[○!R] that enables the rapid diagnosis of lymph node metastasis in gastric cancer within 40 minutes. The purpose of this study was to verify the utility of the SmartCycler^[○!R] as compared to conventional RT-PCR using the LightCycler^[○!R]. 【Patients and methods】47 overt metastatic lymph nodes from 8 patients with advanced gastric cancer and 22 benign lymph nodes from patients without malignant tumor who received surgery were obtained with informed consent. We examined the metastatic lymph nodes by RT-PCR using multiple markers using CEA and CK19 by the LightCycler^[○!R] and SmartCycler^[○!R]. 【Results】 In the singlex assay, the sensitivity of CEA and CK19 was 91.5% and 70.2% in the LightCycler^[○!R], and 97.9% and 95.7% in the prototype assay system, respectively. In the multiplex assay, the sensitivity was 91.5% in the LightCycler^[○!R] system and 97.9% in the SmartCycler^[○!R], respectively. 【Conclusion】Rapid diagnosis for lymph node metastasis using RT-PCR by the SmartCycler^[○!R] has equally high precision for detecting lymph node metastasis as the conventional LightCycler^[○!R]. In this study the SmartCycler^[○!R] is advantageous for the diagnosis of lymph node metastasis in gastric cancer when run with the prototype assay.
(2)-2 Utility of the GeneSearch BLN Assay for Rapid Evaluation of Sentinel Lymph Nodes in Breast Cancer
Our goal was to evaluate the clinical application of the Breast Lymph Node (BLN) assay, a real-time RT-PCR assay for SLN metastases, by comparing this test with routine pathological examination. 【Methods】One hundred seventeen patients with breast cancer underwent breast surgery with SLN biopsy. Each SLN was cut in half along the plane of the longest dimension. Half of each node was examined by the BLN assay's 2 markers, mammaglobin (MG) and cytokeratin 19 (CK19), and the other half was examined by hematoxylin and eosin staining (HE) and immunohistochemical staining (IHC) for pancytokeratins. 【Results】A total of 204 SLNs were obtained from 117 patients. HE identified metastases in 31 SLNs (15.2%), and IHC detected metastases in 6 SLNs ; 40 SLNs from 32 patients were positive for metastasis by the BLN assay. The assay results correlated with the pathological diagnoses by HE and IHC (p<0.001). BLN Assay sensitivity compared with pathological findings classified according to TNM was 95.7% for macrometastases, 60.0% for micrometastases, and 55.6% for isolated tumor cells. 【Conclusion】The 2-marker BLN assay has performance comparable to, and analyzes more tissue than, routine pathological examination. Therefore, clinical intraoperative use of the BLN assay for SLNs may result in reduction of the second surgery for axillary lymph node dissections. Less

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (29 results)

All 2010 2009 2008 2007

All Journal Article (18 results) (of which Peer Reviewed: 11 results) Presentation (11 results)

  • [Journal Article] Utility of the GeneSearch BLN Assay for Rapid Evaluation of Sentinel Lymph Nodes in Breast Cancer2010

    • Author(s)
      Funasako Y, Uenosono Y, Hirata M, Arigami T, Yanagita S, Arima H, Ehi K, Kijima Y, Yoshinaka H, Natsugoe S, Cancer
    • Journal Title

      (in press)

    • Related Report
      2009 Final Research Report
  • [Journal Article] Sentinel node navigation surgery in esophageal cancer2009

    • Author(s)
      Uenosono Y, Arigami T, Arima H, Yanagita S, Okumura H, Matsumoto M, Ohwaki T, Ishigami S, Natsugoe S. Nippon Geka Gakkai Zasshi
    • Journal Title

      110(2)

      Pages: 63-7

    • NAID

      110007133436

    • Related Report
      2009 Final Research Report
  • [Journal Article] The utility of rapid diagnosis of lymph node metastasis in gastric cancer using a multiplex real-time reverse transcription polymerase chain reaction assay.2009

    • Author(s)
      Yanagita S, Natsugoe S, Uenosono Y, Arigami T, Funasako Y, Hirata M, Kozono T, Ehi K, Arima H, Green G, Wang Y, Aikou T. Oncology
    • Journal Title

      77(3-4)

      Pages: 205-11

    • Related Report
      2009 Final Research Report
  • [Journal Article] CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer.2009

    • Author(s)
      Arigami T, Natsugoe S, Uenosono Y, Yanagita S, Arima H, Hirata M, Ishigami S, Aikou T
    • Journal Title

      Int J Oncol 35(1)

      Pages: 19-24

    • Related Report
      2009 Final Research Report
  • [Journal Article] The utility of rapid diagnosis of lymph node metastasis in gastric cancer using a multiplex real-time reverse transcription polymerase chain reaction assay2009

    • Author(s)
      Yanagita S, Natsugoe S, Uenosono Y, et al.
    • Journal Title

      Oncology 77

      Pages: 205-211

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer2009

    • Author(s)
      Arigami T, Natsugoe S, Uenosono Y, et al.
    • Journal Title

      Int J Oncology 35

      Pages: 19-24

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pN0 early gastric cancer2009

    • Author(s)
      Arigami T, Natsugoe S, Uenosono Y, et al.
    • Journal Title

      J Surg Oncol. 99

      Pages: 148-153

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 胃癌における抹消循環腫瘍細胞(CTC)の実態とその臨床的意義2009

    • Author(s)
      上之園芳一
    • Journal Title

      医学のあゆみCTC(抹消循環腫瘍細胞) 228(11)

      Pages: 1089-1093

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sentinel node navigation surgery in esophageal cancer.2009

    • Author(s)
      Uenosono Y
    • Journal Title

      Nippon Geka Gakkai Zasshi 110(2)

      Pages: 63-67

    • NAID

      40020027007

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Vascular endothelial growth factor-C and -D expression correlates with lymph node micrometastasis in pNO early gastrie cancer.2009

    • Author(s)
      Arigami T
    • Journal Title

      J Surg Oncol 99(3)

      Pages: 148-153

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological distribution of metastatic foci in sentinel lymph nodes with gastric cancer.2008

    • Author(s)
      Yanagita S, Natsugoe S, Uenosono Y, Arima H, Kozono T, Ehi K, Arigami T, Higashi H, Aikou T
    • Journal Title

      Ann Surg Oncol 15(3)

      Pages: 770-6

    • Related Report
      2009 Final Research Report
  • [Journal Article] A case of advanced gastrie cancer with multiple liver metastases completely responding to combination of paclitaxel and S-1.2008

    • Author(s)
      Ishigami S
    • Journal Title

      Gan to kagaku Ryoho 35(7)

      Pages: 1197-1199

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of micrometastases in sentinel node navigation surgery for gastrie cancer.2008

    • Author(s)
      Yanagita S
    • Journal Title

      Surg Oncol. 17(3)

      Pages: 203-210

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Salvage gastrectomy following a combination of biweekly paditaxel and S-1 for stage IV gastrie cancer.2008

    • Author(s)
      Ishigami S
    • Journal Title

      J Gastrointest Surg. 12(8)

      Pages: 1370-75

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intramammary sentinel lymph node in patients with breast cancer : report of four cases.2008

    • Author(s)
      Kijima Y
    • Journal Title

      Surg Today 38(6)

      Pages: 536-540

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of T-helper type 1 and 2 cells and T-cytotoxic type l and 2 cells of sentinel lymph nodes in breast cancer2008

    • Author(s)
      Ehi K
    • Journal Title

      Oncol Rep 19(3)

      Pages: 601-607

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sentinel node micrometastases have high proliferative potential in gastric cancer2008

    • Author(s)
      Shigehiro Yanagita
    • Journal Title

      Journal of Surgical Research 145(2)

      Pages: 238-243

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] センチネルリンパ節生検応用の拡大2007

    • Author(s)
      夏越祥次
    • Journal Title

      臨床消化器内科 22

      Pages: 1101-1106

    • Related Report
      2007 Annual Research Report
  • [Presentation] 胃癌におけるセンチネルリンパ節概念に基づく縮小手術2009

    • Author(s)
      上之園芳一, 有上貴明, 柳田茂寛, 平田宗嗣, 小園勉, 舩迫和, 衣裴勝彦, 石神純也, 愛甲孝, 夏越祥次
    • Organizer
      (シンポジウム)第33回日本リンパ学会総会
    • Place of Presentation
      高槻市
    • Year and Date
      2009-07-18
    • Related Report
      2009 Final Research Report
  • [Presentation] Circulating tumor cells in blood detected by the CellSearch system are a predictive factor of recurrence in gastric cancer (Symposium)2009

    • Author(s)
      Uenosono Y., Arigami T., Kozono T., Yanagita S., Hirata M., Arima H., Ishigami S., Aikou T., Natsugoe S.
    • Organizer
      8th International Gastric Cancer Congress
    • Place of Presentation
      Krakow Poland
    • Year and Date
      2009-06-12
    • Related Report
      2009 Final Research Report
  • [Presentation] Circulating tumor cells in blood detected by Cell Search System are the predictive factor of recurrences in gastric cancer2009

    • Author(s)
      Yoshikazu Uenosono
    • Organizer
      8th International Gastric Cancer Congress
    • Place of Presentation
      ポーランドクラクフ
    • Year and Date
      2009-06-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] 胃癌におけるmesothelin発現の臨床的意義2009

    • Author(s)
      馬場研二
    • Organizer
      Gastric Cancer第81回日本胃癌学会総会
    • Place of Presentation
      東京ファッションダウンビルTFTホール(東京都)
    • Year and Date
      2009-03-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] Sentinel node conceptを用いたESD適用拡大の可能性2009

    • Author(s)
      有上貴明
    • Organizer
      Gastrie Cancer第81回日本胃癌学会総会
    • Place of Presentation
      東京ファッションタウンビルTFTホール(東京都)
    • Year and Date
      2009-03-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] 胃癌センチネルリンパ節のRT-PCR術中迅速診断の検討2009

    • Author(s)
      平田宗嗣
    • Organizer
      Gastric Cancer第81回日本胃癌学会総会
    • Place of Presentation
      東京ファッションタウンビルTFTホール(東京都)
    • Year and Date
      2009-03-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] 肺癌術後5年に切除した転移性胃癌の1例2009

    • Author(s)
      平原徹志
    • Organizer
      Gastric Cancer第81回日本胃癌学会総会
    • Place of Presentation
      東京ファッションタウンビルTFTホール(東京都)
    • Year and Date
      2009-03-05
    • Related Report
      2008 Annual Research Report
  • [Presentation] 胃癌症例における血中遊離癌細胞の検出による再発予測の可能性2008

    • Author(s)
      上之園芳一, 夏越祥次, 小園勉, 柳田茂寛, 有上貴明, 舩迫和, 有馬豪男, 中条哲浩, 石神純也, 愛甲孝
    • Organizer
      第46回日本癌治療学会総会
    • Place of Presentation
      名古屋市
    • Year and Date
      2008-10-30
    • Related Report
      2009 Final Research Report
  • [Presentation] 胃癌におけるSentinel Node Navigationの現状と将来展望2008

    • Author(s)
      上之園芳一, 夏越祥次, 有上貴明, 柳田茂寛, 有馬豪男, 平田宗嗣, 舩迫和, 小園勉, 石神純也, 愛甲孝
    • Organizer
      (シンポジウム)第10回Sentinel Node Navigation Surgery研究会学術集会
    • Place of Presentation
      秋田市
    • Year and Date
      2008-09-20
    • Related Report
      2009 Final Research Report
  • [Presentation] 胃癌における血中遊離癌細胞検出による再発予測の可能性2008

    • Author(s)
      上之園芳一
    • Organizer
      日本胃癌学会
    • Place of Presentation
      横浜市
    • Year and Date
      2008-02-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] Investigation of false negative cases in SN mapping with cT1-2N0 gastric cancer2008

    • Author(s)
      Uenosono Y., Natsugoe S., Yanagita S., Funasako Y., Kozono T., Arigami T., Arima H., Ehi K., Ishigami S., Aikou T.
    • Organizer
      6th BIENNIAL INTERNATIONAL SENTINEL NODE SOCIETY MEETING
    • Place of Presentation
      SYDONEY AUSTRALIAN
    • Year and Date
      2008-02-19
    • Related Report
      2009 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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