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国立がん研究センター 中央病院

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Department of Gastric Surgery

Hitoshi Katai, Takeo Fukagawa, Shinji Morita, Hisataka Fujiwara, Takeyuki Wada, Hiroshi Moro

Introduction

This department treats not only gastric adenocarcinoma but also sarcomas of gastric origin, such as malignant lymphomas or gastrointestinal stromal tumors (GISTs). Principally, we treat tumors of the esophagogastric junction.

Routine activities

The Department includes five staff surgeons, one chief resident and three or four rotating residents at any given time. Nine to eleven patients are operated upon every week. The Department shares a ward with the Departments of Hepatobiliary and Pancreatic Surgery and Oncology. Patients with stage I disease are followed-up without adjuvant chemotherapy. Adjuvant S-1 chemotherapy is used for patients with stage II and III disease. Adjuvant XELOX chemotherapy is applied for stage IIIC disease. Neoadjuvant chemotherapy is frequently used for patients with locally advanced tumors.

Patients with a superficial well-differentiated adenocarcinoma lesion are treated with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Some undergo subsequent surgery based on the histological findings of the resected specimen. Every Tuesday from 6:15 to 7:00 P.M., a clinical conference is held for surgeons, a medical oncologist and endoscopists. All patients with gastric malignancies in the ward or on the waiting list for admission are briefly reviewed and those whose treatment is controversial are discussed in detail. Every Friday between 7:15 and 8:30 A.M., another clinical conference is held, in which endoscopists, radiologists, and pathologists present all candidates for surgical and endoscopic treatment for the following week, and the treatment strategy for each case is discussed in detail. These conferences are held in English whenever a foreign guest doctor is present.

We consider the education of foreign surgeons to be an important function. In 2015, more than 20 surgeons from various countries visited this division for 1 week to 6 months to learn about the management of gastric cancer patients, especially surgical techniques for lymph node dissection and postoperative care. All staff surgeons have sufficient experience in teaching in English.

Research activities

Several translational studies are being carried out in cooperation with the National Cancer Center Research Institute. Genomic scanning in gastric cancer is being carried out. DNA methylation as a gastric cancer metastasis risk factor has been investigated. A mini-chip assay of peritoneal washings for prediction of gastric cancer recurrence is being developed. Research on the detection of small amounts of cancer cells in peripheral blood and bone marrow of gastric cancer patients is being carried out.

Clinical trials

Our Department has been playing a central role in conducting multi-institutional clinical trials. H. Katai is a representative of the Gastric Cancer Surgical Study Group of the Japan Clinical Oncology Group (JCOG). Patients with gastric cancer are, when eligible, invited to participate in one of the ongoing clinical trials mentioned below. The JCOG 0501 phase III trial to evaluate the effect of neo-adjuvant (S-1 and CDDP) and adjuvant chemotherapy (S-1) for large type III and type IV tumors has been completed for accrual. JCOG 1001, which is designed to evaluate the significance of bursectomy for advanced cancer, has been completed for accrual. This trial includes the evaluation of long-term survival, postoperative morbidity, and mortality. The JCOG 0912 phase III trial to prove the non-inferiority of laparoscopic gastrectomy over its open counterpart for patients with clinical stage IA and IB gastric cancer has also been completed for accrual. The JCOG 1104 phase III trial to evaluate the optimal period of adjuvant S-1 chemotherapy for pathological stage II gastric cancer patients who underwent D2 gastrectomy is ongoing. The JCOG1301C, a randomized phase II study of systemic chemotherapy with and without trastuzumab followed by surgery in HER2 positive advanced gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis, just started. JCOG1302-A is a study to evaluate the accuracy of pre-operative staging for advanced tumors and has been completed for accrual and the results were reported. A phase II study to check the feasibility of Oxaliplatin, and S-1 neoadjuvant chemotherapy for stage III disease was carried out and the results were reported. We started a new phase II trial to prove the feasibility of laparoscopic total and proximal gastrectomy for stage IA and IB gastric cancer (JCOG 1401).

Education

Education of surgical operations has been introduced for chief and rotating residents throughout the perioperative management of more than 500 gastric cancer patients.

Future prospects

D2 gastrectomy is considered the standard surgical treatment for advanced gastric cancer but multi-modality treatments combined with surgery will further improve survival rates. There are several surgical options for early gastric cancer depending on the risk of nodal metastasis. The efficacy of laparoscopic surgery for early gastric cancer is being assessed. Moreover, robotic surgery is introduced as advanced medical care services and the safety and effectiveness has currently been evaluated. These procedures will require good quality control achieved through supervision and training by experienced surgeons in high volume centers.


Table 1. Number of Patients Table 2. Operative morbidity and mortality after gastrectomy


Table 3. Operative Procedures Table 4. Overall Survival Rates

List of papers published in 2015

Journal

  1. Sekiguchi M, Kushima R, Oda I, Suzuki H, Taniguchi H, Sekine S, Fukagawa T, Katai H. Clinical significance of a papillary adenocarcinoma component in early gastric cancer: a single-center retrospective analysis of 628 surgically resected early gastric cancers. J Gastroenterol, 50:424-434, 2015
  2. Abe S, Oda I, Suzuki H, Nonaka S, Yoshinaga S, Nakajima T, Sekiguchi M, Mori G, Taniguchi H, Sekine S, Katai H, Saito Y. Long-term surveillance and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection. Endoscopy, 47:1113-1118, 2015
  3. Yoda Y, Takeshima H, Niwa T, Kim JG, Ando T, Kushima R, Sugiyama T, Katai H, Noshiro H, Ushijima T. Integrated analysis of cancer-related pathways affected by genetic and epigenetic alterations in gastric cancer. Gastric Cancer, 18:65-76, 2015
  4. Takeshima H, Niwa T, Takahashi T, Wakabayashi M, Yamashita S, Ando T, Inagawa Y, Taniguchi H, Katai H, Sugiyama T, Kiyono T, Ushijima T. Frequent involvement of chromatin remodeler alterations in gastric field cancerization. Cancer Lett, 357:328-338, 2015
  5. Shirahige A, Suzuki H, Oda I, Sekiguchi M, Mori G, Abe S, Nonaka S, Yoshinaga S, Sekine S, Kushima R, Saito Y, Fukagawa T, Katai H. Fatal submucosal invasive gastric adenosquamous carcinoma detected at surveillance after gastric endoscopic submucosal dissection. World J Gastroenterol, 21:4385-4390, 2015
  6. Hosoda F, Arai Y, Okada N, Shimizu H, Miyamoto M, Kitagawa N, Katai H, Taniguchi H, Yanagihara K, Imoto I, Inazawa J, Ohki M, Shibata T. Integrated genomic and functional analyses reveal glyoxalase I as a novel metabolic oncogene in human gastric cancer. Oncogene, 34:1196-1206, 2015
  7. Ohashi M, Saka M, Katayama H, Okinaka K, Morita S, Fukagawa T, Katai H. A Prospective Cohort Study To Evaluate the Feasibility of Intraoperative Antimicrobial Prophylaxis in Open Gastrectomy for Gastric Cancer. Surg Infect (Larchmt), 16:833-839, 2015
  8. Ohashi M, Morita S, Fukagawa T, Oda I, Kushima R, Katai H. Functional Advantages of Proximal Gastrectomy with Jejunal Interposition Over Total Gastrectomy with Roux-en-Y Esophagojejunostomy for Early Gastric Cancer. World J Surg, 39:2726-2733, 2015
  9. Inada R, Sekine S, Taniguchi H, Tsuda H, Katai H, Fujiwara T, Kushima R. ARID1A expression in gastric adenocarcinoma: clinicopathological significance and correlation with DNA mismatch repair status. World J Gastroenterol, 21:2159-2168, 2015
  10. Seishima R, Wada T, Tsuchihashi K, Okazaki S, Yoshikawa M, Oshima H, Oshima M, Sato T, Hasegawa H, Kitagawa Y, Goldenring JR, Saya H, Nagano O. Ink4a/Arf-Dependent Loss of Parietal Cells Induced by Oxidative Stress Promotes CD44-Dependent Gastric Tumorigenesis. Cancer Prev Res (Phila), 8:492-501, 2015
  11. Katai H. Current status of a randomized controlled trial examining laparoscopic gastrectomy for gastric cancer in Japan. Asian J Endosc Surg, 8:125-129, 2015
  12. Sasako M, Terashima M, Ichikawa W, Ochiai A, Kitada K, Kurahashi I, Sakuramoto S, Katai H, Sano T, Imamura H. Erratum to: Impact of the expression of thymidylate synthase and dihydropyrimidine dehydrogenase genes on survival in stage II/III gastric cancer. Gastric Cancer, 18:549, 2015
  13. Umemura A, Koeda K, Sasaki A, Fujiwara H, Kimura Y, Iwaya T, Akiyama Y, Wakabayashi G. Totally laparoscopic total gastrectomy for gastric cancer: literature review and comparison of the procedure of esophagojejunostomy. Asian J Surg, 38:102-112, 2015
  14. Ohashi M, Morita S, Fukagawa T, Kushima R, Katai H. Surgical treatment of non-early gastric remnant carcinoma developing after distal gastrectomy for gastric cancer. J Surg Oncol, 111:208-212, 2015
  15. Sasako M, Terashima M, Ichikawa W, Ochiai A, Kitada K, Kurahashi I, Sakuramoto S, Katai H, Sano T, Imamura H. Impact of the expression of thymidylate synthase and dihydropyrimidine dehydrogenase genes on survival in stage II/III gastric cancer. Gastric Cancer, 18:538-548, 2015
  16. Matsumoto T, Sasako M, Mizusawa J, Hirota S, Ochiai A, Kushima R, Katai H, Tanaka Y, Fukushima N, Nashimoto A, Tsuburaya A, Stomach Cancer Study Group of the Japan Clinical Oncology Group. HER2 expression in locally advanced gastric cancer with extensive lymph node (bulky N2 or paraaortic) metastasis (JCOG1005-A trial). Gastric Cancer, 18:467-475, 2015
  17. Yamashita H, Katai H. Should adenocarcinoma of the esophagogastric junction be classified as esophageal cancer? Limited to Siewert type II, yes. Ann Surg, 261:e67, 2015
  18. Abe S, Oda I, Nakajima T, Suzuki H, Nonaka S, Yoshinaga S, Sekine S, Taniguchi H, Kushima R, Iwasa S, Saito Y, Katai H. A case of local recurrence and distant metastasis following curative endoscopic submucosal dissection of early gastric cancer. Gastric Cancer, 18:188-192, 2015
  19. Ichikawa H, Yoshida A, Kanda T, Kosugi S, Ishikawa T, Hanyu T, Taguchi T, Sakumoto M, Katai H, Kawai A, Wakai T, Kondo T. Prognostic significance of promyelocytic leukemia expression in gastrointestinal stromal tumor; integrated proteomic and transcriptomic analysis. Cancer Sci, 106:115-124, 2015
  20. Fujita H, Yoshida A, Taniguchi H, Katai H, Sekine S. Adult-onset inflammatory myofibroblastic tumour of the stomach with a TFG-ROS1 fusion. Histopathology, 66:610-612, 2015
  21. Yamanoi K, Arai E, Tian Y, Takahashi Y, Miyata S, Sasaki H, Chiwaki F, Ichikawa H, Sakamoto H, Kushima R, Katai H, Yoshida T, Sakamoto M, Kanai Y. Epigenetic clustering of gastric carcinomas based on DNA methylation profiles at the precancerous stage: its correlation with tumor aggressiveness and patient outcome. Carcinogenesis, 36:509-520, 2015
  22. Suzuki M, Chiwaki F, Sawada Y, Ashikawa M, Aoyagi K, Fujita T, Yanagihara K, Komatsu M, Narita M, Suzuki T, Nagase H, Kushima R, Sakamoto H, Fukagawa T, Katai H, Nakagama H, Yoshida T, Uezono Y, Sasaki H. Peripheral opioid antagonist enhances the effect of anti-tumor drug by blocking a cell growth-suppressive pathway in vivo. PLoS One, 10:e0123407, 2015
  23. Fujita T, Chiwaki F, Takahashi RU, Aoyagi K, Yanagihara K, Nishimura T, Tamaoki M, Komatsu M, Komatsuzaki R, Matsusaki K, Ichikawa H, Sakamoto H, Yamada Y, Fukagawa T, Katai H, Konno H, Ochiya T, Yoshida T, Sasaki H. Identification and Characterization of CXCR4-Positive Gastric Cancer Stem Cells. PLoS One, 10:e0130808, 2015