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Annual Report 2021

Department of Gastric Surgery

Takahiro Kinoshita, Masahiro Yura, Eigo Akimoto, Junichiro Harada, Mitsumasa Yoshida, Takafumi Okayama, Yuya Tanaka, Yuya Takabe, Takumi Habu, Yoshiaki Tomi, Hiromi Nagata, Masaru Komatsu, Tamae Takeuchi

Introduction

 Our department consists of three staff surgeons and nine junior surgeons. Our managing of tumors includes common gastric adenocarcinoma, adenocarcinoma of the esophagogastric junction (AEG: Siewert type 2/3), and gastric submucosal tumors (GIST, etc.). In 2021, 262 patients underwent a gastrectomy either by means of open, laparoscopic or robotic surgery (Table 1). Laparoscopic gastrectomy was introduced in 2010, and robot-assisted gastrectomy was implemented in 2014. This year, more than 80% of gastrectomies were performed by laparoscopy or robot-assisted (Table 2). The basis of our surgery is radical extirpation of cancer lesions with nodal dissection, but at the same time, organ functions and better quality of life (QOL) should be maintained. In addition, we strive to obtain better clinical outcomes for patients with diseases with dismal prognoses (type 4 gastric cancer or with progressive metastasis) through surgery combined with modern perioperative chemotherapy in cooperation with medical oncologists.

Table 1. Number of patients
Table 1. Number of patients

Table 1. Number of patients
Table 1. Number of patients

Table 2. Type of procedure
Table 2. Type of procedure

Table 2. Type of procedure
Table 2. Type of procedure

The Team and What We Do

 Usually, 10-14 patients are hospitalized and six to eight patients undergo operations per week. A clinical conference for our division is held once a week to decide our treatment strategies. Further, a conference with internal medicine is held every week with doctors from Medical Oncology and Gastrointestinal Endoscopy, to discuss accurate diagnosis of the patients to decide the optimal treatment method. Laparoscopic (robot) surgery covers distal, proximal, pylorus-preserving, and total gastrectomy. D2 dissection can also be done, and its indication is expanding to locally advanced cancer or cancer after NAC. Currently, due to the progress of chemotherapy regimens, down-staging from cStageIV is sometimes seen. For such patients, we selectively perform conversion surgery to achieve favorable outcomes. For AEGs, the transhiatal approach or thoraco-laparoscopic Ivor-Lewis surgery can be done by minimally invasive means.

Research activities

 We actively publish our clinical research data in domestic and international journals. In addition, we participate in multi-institutional clinical trials conducted by the Japan Clinical Oncology Group (JCOG) - Gastric Surgery Study Group and other international and domestic organizations, and work as PI for some clinical trials (JCOG1809) (COSMOS-GC regarding liquid biopsy). We have started conducting research into auto intelligence technology relevant to laparoscopic and robot-assisted surgery.

Clinical trials

 A list of multi-institutional clinical trials we participated in is shown below.

1)  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 (Trastuzumab in Gastric or Esophagogastric Junction Adenocarcinoma)

2)  JCOG1509 - Phase III trial to evaluate the efficacy of neoadjuvant chemotherapy with S-1 plus oxaliplatin followed by D2 gastrectomy with adjuvant S-1 in locally advanced gastric cancer (NAGISA trial)

3)  JCOG1809 - Single-arm phase II trial to evaluate safety of Laparoscopic Total Gastrectomy with Spleen-PReservING splenic hilar dissection for proximal gastric cancer invading the greater curvature (LTG-SPRING-PII)

4)  JCOG1907 - Randomized controlled phase III trial to investigate superiority of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-2N0-2 gastric cancer patients (MONA-LISA Study)

5)  A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects with Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma (KEYNOTE-585)

6)  An open label phase 2 study to evaluate the safety and efficacy of lenvatinib with pembrolizumab in the neoadjuvant / adjuvant treatment for patients with gastric cancer (EPOC2001)

7)  An open label phase 2 study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in the neoadjuvant treatment for patients with HER2 positive gastric and gastroesophageal junction adenocarcinoma (EPOC2003)

8)  Multiomics data cancer diagnostics therapies (TITANIA Study)

9)  Conquer Solid Malignancies by Blood Screening - Gastric Cancer - 01 (COSMOS-GC)

10)  Development of a Clinical Decision Support System (CDSS) with Artificial Intelligence for Gastric and Esophageal Adenocarcinomas (Ask Bob Study)

11)  The HOLD Study- StomacH Cancer Elective Surgery MOrbidity and Mortality at 90-Day / The OUTLIVE Study - Oesophageal and JUncTional Cancer ELectIVE Surgery Morbidity and Mortality at 90-Day: A TUGS Multinational Audit

12)  The UGIRA International Registry for Robot-Assisted Minimally Invasive Gastrectomy (RAMIG) for gastric cancer

13)  The UGIRA International Registry for Robot-Assisted Minimally Invasive Esophagectomy (RAMIE)

Education

 Resident doctors are trained to be specialized surgical oncologists with sufficient skills and knowledge. Nowadays, they are simultaneously given opportunities to perform laparoscopic, open, and robotic surgery. We also place importance on the education of surgeons at other institutions. In 2021, we could not accept foreign doctors due to the COVID-19 pandemic, but many candidates hope to visit our department. We are endorsed as an official certified institution for observation of robotic gastrectomy surgery.

Future Prospects

 We will keep striving to obtain better survival outcomes for patients with far-advanced diseases; for multidisciplinary therapy (chemotherapy, molecular-target agents or immune oncology agents), collaborating with medical oncologists is essential. Additionally, we will continue to develop less-invasive surgical methods (laparoscopic or robotic surgery), to improve patients’ QOL and achieve complete cures. It is also our obligation to expand our knowledge and experience globally as one of the main countries in terms of incidence of gastric cancer.

List of papers published in 2021

Journal

1. Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, Ito D, Fujii R, Watanabe S, Sai A, Fukuoka S, Sugiyama E, Watanabe G, Owari T, Nishinakamura H, Sugiyama D, Maeda Y, Kawazoe A, Yukami H, Chida K, Ohara Y, Yoshida T, Shinno Y, Takeyasu Y, Shirasawa M, Nakama K, Aokage K, Suzuki J, Ishii G, Kuwata T, Sakamoto N, Kawazu M, Ueno T, Mori T, Yamazaki N, Tsuboi M, Yatabe Y, Kinoshita T, Doi T, Shitara K, Mano H, Nishikawa H. Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer cell, 40:201-218.e9, 2022

2. Tokunaga M, Yoshikawa T, Boku N, Nishida Y, Tanahashi T, Yamada T, Haruta S, Etoh T, Hirahara N, Kawachi Y, Tsuji K, Kinoshita T, Kanazawa T, Tokumoto N, Fujita J, Terashima M. Impact of COVID-19 on gastric cancer treatment in Japanese high-volume centers: a JCOG stomach cancer study group survey. Surgery today, 52:231-238, 2022

3. Ikematsu H, Ishihara M, Okawa S, Minamide T, Mitsui T, Kuwata T, Ito M, Kinoshita T, Fujita T, Yano T, Omori T, Ozawa S, Murakoshi D, Irisawa K, Ochiai A. Photoacoustic imaging of fresh human surgically and endoscopically resected gastrointestinal specimens. DEN open, 2:e28, 2022

4. Kinoshita T, Sato R, Akimoto E, Tanaka Y, Okayama T, Habu T. Reduction in postoperative complications by robotic surgery: a case-control study of robotic versus conventional laparoscopic surgery for gastric cancer. Surgical endoscopy, 36:1989-1998, 2022

5. Tanaka Y, Kinoshita T, Akimoto E, Sato R, Yura M, Harada J, Yoshida M, Tomi Y. The impact of hiatal hernia on survival outcomes in patients with gastroesophageal junction adenocarcinoma. Annals of gastroenterological surgery, 6:366-374, 2022

6. Hasegawa H, Shitara K, Takiguchi S, Takiguchi N, Ito S, Kochi M, Horinouchi H, Kinoshita T, Yoshikawa T, Muro K, Nishikawa H, Suna H, Kodera Y. A multicenter, open-label, single-arm phase I trial of neoadjuvant nivolumab monotherapy for resectable gastric cancer. Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 25:619-628, 2022

7. Akimoto E, Tokunaga M, Sato R, Yoshida A, Naito Y, Yamashita R, Kinoshita T, Kuwata T. Gastric mesenchymal tumor with smooth muscle differentiation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion. Pathology international, 71:707-711, 2021

8. Ishii T, Suzuki A, Kuwata T, Hisamitsu S, Hashimoto H, Ohara Y, Yanagihara K, Mitsunaga S, Yoshino T, Kinoshita T, Ochiai A, Shitara K, Ishii G. Drug-exposed cancer-associated fibroblasts facilitate gastric cancer cell progression following chemotherapy. Gastric cancer: official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 24:810-822, 2021

9. Sasaki K, Kobayashi S, Kudo M, Sugimoto M, Takahashi S, Nakamura Y, Kawazoe A, Shitara K, Kinoshita T, Gotohda N. Hypothyroidism and hypopituitarism as immune-related adverse events due to lenvatinib plus pembrolizumab therapy in the immediate postoperative period after laparoscopic hepatectomy for liver metastases from gastric cancer: a case report. Surgical case reports, 7:267, 2021