Annual Report 2019
Department of Thoracic Surgery
Masahiro Tsuboi, Keiju Aokage, Tomohiro Miyoshi, Kenta Tane, Shoko Nakasone, Shinya Katsumata
Introduction
The Department of Thoracic Surgery has three missions: surgical treatment, surgical resident training, and clinical research. Thoracic surgeries involve the treatment of thoracic neoplasms and primary and metastatic lung tumors, as well as mediastinal, pleural, and chest wall tumors. Our department specializes in the surgical treatment of pulmonary carcinomas. Routine surgical treatment modalities for carcinomas include limited resection (wedge or segmental resection) and simple resection (lobectomy or pneumonectomy) with or without systematic lymph node dissection. Thoracoscopic assistance is almost always used. Non-routine surgical procedures involve complex approaches such as broncho-/angioplasty, combined resection with adjacent structures, and perioperative adjuvant treatment. Since its establishment in 1992, our department has been one of the most active leaders in the field of lung cancer in Japan. Moreover, it has been an active participant in international and national scientific venues. This year, in addition to 16 scientific papers published in English, our department made 30 presentations: four international, 23 national, and four regional.
The Team and What We Do
The Department of Thoracic Surgery is presently composed of four consultant surgeons including a chief and eight or nine residents. Our department has adopted a team approach in patient treatment and resident training. Potential surgical intervention candidate cases are presented every Tuesday evening at a multidisciplinary team conference of thoracic surgeons, oncology physicians, radiologists, and residents.
Each case is thoroughly and vigorously reviewed and discussed. To improve the English fluency of staff members and residents in preparation for international presentations, and to better involve visiting physicians from other countries, treatment modality discussions are conducted in English. Moreover, selected patients’ records are radiologically and cytopathologically reviewed every Friday morning. These reviews aim to improve the interpretation of radiologic indications for pathology findings, accurately evaluate surgical indications, and upgrade knowledge on rare histologies. We believe that these activities improve the knowledge base, treatment indications, and surgical treatment. For non-small cell histology, primary pulmonary carcinomas in clinical stages I/II and IIIA without bulky or multistation-involved mediastinal nodes, and primary pulmonary small cell carcinomas in clinical stage I, surgical resection is indicated as a cure. Optimum treatment modalities are being sought via clinical trials with the aim of improving the poor prognosis of patients with bulky or clinically and histologically proven multistation mediastinal lymph node metastases, with disease invading the neighboring vital structures, or with small cell cancers in clinical stage II and later. Resection of metastatic lung tumor is attempted based on modified Thomfold’s criteria after consultation with the patient. The majority of these cases are metastases from colorectal carcinomas, while most of the mediastinal tumors are thymic epithelial tumors. The surgical procedures of the Department of Thoracic Surgery have generally remained similar for the past decade, but we have employed port-access thoracoscopic surgery more often for the last several years. Approximately 20% of the surgeries are completed via a 3-port access, and 70% of the surgeries are video-thoracoscopically assisted. To date, the average postoperative hospital stay of patients in our department has been improved and become shorter, three days being the shortest with a median of seven days for cases of primary lung cancer. These shorter hospital stays are achieved with a slightly better complication rate than the normal rate. This year, 30-day operative mortality occurred in two patients undergoing surgery for primary lung cancer.
Research activities
Research in the area of combined treatment, especially immunotherapy, has now advanced to clinical trials. It is the goal for researchers in our department to acquire a basic understanding of the cellular and molecular mechanisms leading to the development and progression of lung cancer and apply these findings to further the development of immunotherapy-based prevention and treatment strategies.
Clinical trials
There are the following prospective trials in this department.
1. Primary investigator and a member of an organized trial of TS-1 vs. UFT adjuvant chemotherapy for completely resected pathologic stage I (> 2 cm) non-small cell lung cancer [JCOG 0707, phase III, patient accrual completed. The primary endpoint: DFS was reported in the WCLC2019 meeting.].
2. Primary investigator and a member of an organized trial of sublobar resection for peripheral GGO dominant cT1aN0M0 lung adenocarcinomas [JCOG 0804, phase II, patient accrual completed. The primary endpoint was presented in the AATS2019 meeting.].
3. Study coordinator and a member of an organized trial of segmental resection vs. lobectomy for peripheral T1aN0M0 non-small cell lung cancers [JCOG 0802, phase III, patient accrual completed. The safety data were published in “J Thorac Cardiovasc Surg”.].
4. Study coordinator and a member of an organized trial of sublobar resection for peripheral GGO dominant cT1bN0M0 lung adenocarcinomas [JCOG 1211, phase III, patient accrual completed]
5. Primary investigator and a member of an organized trial of Cisplatin/Pemetrexed vs. Cisplatin/Vinorelbine adjuvant chemotherapy for completely resected pathologic stage II-IIIA non-small cell lung cancer [JIPANG, phase III, patient accrual completed. The primary endpoint: DFS was reported in the ASCO2019 meeting.].
6. A member of an organized trial of Human Atrial Natriuretic Peptide during perioperative period for completed resectable non-small cell lung cancer [JANP, randomized phase II, patient accrual completed. The follow-up phase is ongoing].
7. A member of an organized trial of postoperative maintenance adjuvant immunotherapy with S-588410 for completed resected stage II-IIIA non-small cell lung cancer [S-588410, phase II, patient accrual ongoing]
8. Study coordinator and a member of an organized trial of a randomized controlled trial of the therapeutic value of lobe-selective lymph node dissection for clinical stage I/II Non-Small Cell Lung Cancer. [L-SEPC trial, phase III, patient accrual ongoing]
In addition, we are conducting corporate trials for the development of perioperative treatment using a molecular targeted drug (osimertinib) and immune checkpoint inhibitors (nivolumab, pembrolizumab, atezolizumab), and a corporate trial for the development of sealants for intraoperative pulmonary fistulas.
Education
Our training program aims to educate residents by expanding their knowledge and technical skills in the treatment of lung cancer, other thoracic malignancies, and benign tumors, such as hamartoma and mediastinal cystic lesions. In addition, we seek to instill in the trainee a desire for continued introspection and self-education and open communication between all health care providers, while maintaining a respectful and professional demeanor. (Table 1, Table 2)
Future prospects
The treatment of thoracic cancers, including lung cancer, mesothelioma, thymic malignancies, and lung metastases, has made steady progress with the development of molecular targeted drugs and immune checkpoint inhibitors, but the situation in perioperative treatment remains exploratory. We are also continuing research and development on surgical techniques, taking into consideration both oncological aspects and invasiveness. Coordination of our laboratory's activities with such clinical research is essential for the advancement of treatment and improvement of cure rates after surgery. We will continue to focus on delivering effective treatments to patients with thoracic cancer as soon as possible, in cooperation with researchers and companies in Japan and around the world.
List of papers published in 2019
Journal
1. Sekihara K, Yoshida J, Oda M, Oki T, Ueda T, Ito T, Miyoshi T, Aokage K, Tane K, Tsuboi M. Delayed cut-end recurrence after wedge resection for pulmonary ground-glass opacity adenocarcinoma despite negative surgical margin. Gen Thorac Cardiovasc Surg, 68:644-648, 2020
2. Sugiyama E, Togashi Y, Takeuchi Y, Shinya S, Tada Y, Kataoka K, Tane K, Sato E, Ishii G, Goto K, Shintani Y, Okumura M, Tsuboi M, Nishikawa H. Blockade of EGFR improves responsiveness to PD-1 blockade in EGFR-mutated non-small cell lung cancer. Sci Immunol, 5:doi: 10.1126/sciimmunol.aav3937, 2020
3. Kubota K, Kunitoh H, Seto T, Shimada N, Tsuboi M, Ohhira T, Okamoto H, Masuda N, Maruyama R, Shibuya M, Watanabe K. Randomized phase II trial of adjuvant chemotherapy with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: TORG 0503. Lung Cancer, 141:32-36, 2020
4. Sekihara K, Aokage K, Miyoshi T, Tane K, Ishii G, Tsuboi M. Perioperative pirfenidone treatment as prophylaxis against acute exacerbation of idiopathic pulmonary fibrosis: a single-center analysis. Surg Today, 50:905-911, 2020
5. Wong JYY, Zhang H, Hsiung CA, Shiraishi K, Yu K, Matsuo K, Wong MP, Hong YC, Wang J, Seow WJ, Wang Z, Song M, Kim HN, Chang IS, Chatterjee N, Hu W, Wu C, Mitsudomi T, Zheng W, Kim JH, Seow A, Caporaso NE, Shin MH, Chung LP, An SJ, Wang P, Yang Y, Zheng H, Yatabe Y, Zhang XC, Kim YT, Cai Q, Yin Z, Kim YC, Bassig BA, Chang J, Ho JCM, Ji BT, Daigo Y, Ito H, Momozawa Y, Ashikawa K, Kamatani Y, Honda T, Hosgood HD, Sakamoto H, Kunitoh H, Tsuta K, Watanabe SI, Kubo M, Miyagi Y, Nakayama H, Matsumoto S, Tsuboi M, Goto K, Shi J, Song L, Hua X, Takahashi A, Goto A, Minamiya Y, Shimizu K, Tanaka K, Wei F, Matsuda F, Su J, Kim YH, Oh IJ, Song F, Su WC, Chen YM, Chang GC, Chen KY, Huang MS, Chien LH, Xiang YB, Park JY, Kweon SS, Chen CJ, Lee KM, Blechter B, Li H, Gao YT, Qian B, Lu D, Liu J, Jeon HS, Hsiao CF, Sung JS, Tsai YH, Jung YJ, Guo H, Hu Z, Wang WC, Chung CC, Burdett L, Yeager M, Hutchinson A, Berndt SI, Wu W, Pang H, Li Y, Choi JE, Park KH, Sung SW, Liu L, Kang CH, Zhu M, Chen CH, Yang TY, Xu J, Guan P, Tan W, Wang CL, Hsin M, Sit KY, Ho J, Chen Y, Choi YY, Hung JY, Kim JS, Yoon HI, Lin CC, Park IK, Xu P, Wang Y, He Q, Perng RP, Chen CY, Vermeulen R, Wu J, Lim WY, Chen KC, Li YJ, Li J, Chen H, Yu CJ, Jin L, Chen TY, Jiang SS, Liu J, Yamaji T, Hicks B, Wyatt K, Li SA, Dai J, Ma H, Jin G, Song B, Wang Z, Cheng S, Li X, Ren Y, Cui P, Iwasaki M, Shimazu T, Tsugane S, Zhu J, Chen Y, Yang K, Jiang G, Fei K, Wu G, Lin HC, Chen HL, Fang YH, Tsai FY, Hsieh WS, Yu J, Stevens VL, Laird-Offringa IA, Marconett CN, Rieswijk L, Chao A, Yang PC, Shu XO, Wu T, Wu YL, Lin D, Chen K, Zhou B, Huang YC, Kohno T, Shen H, Chanock SJ, Rothman N, Lan Q. Tuberculosis infection and lung adenocarcinoma: Mendelian randomization and pathway analysis of genome-wide association study data from never-smoking Asian women. Genomics, 112:1223-1232, 2020
6. Suzuki J, Kojima M, Aokage K, Sakai T, Nakamura H, Ohara Y, Tane K, Miyoshi T, Sugano M, Fujii S, Kuwata T, Ochiai A, Ito M, Suzuki K, Tsuboi M, Ishii G. Clinicopathological characteristics associated with necrosis in pulmonary metastases from colorectal cancer. Virchows Arch, 474:569-575, 2019
7. Oki T, Hishida T, Yoshida J, Goto M, Sekihara K, Miyoshi T, Aokage K, Ishii G, Tsuboi M. Survival and prognostic factors after pulmonary metastasectomy of head and neck cancer: what are the clinically informative prognostic indicators? Eur J Cardiothorac Surg, 55:942-947, 2019
8. Naito T, Umemura S, Nakamura H, Zenke Y, Udagawa H, Kirita K, Matsumoto S, Yoh K, Niho S, Motoi N, Aokage K, Tsuboi M, Ishii G, Goto K. Successful treatment with nivolumab for SMARCA4-deficient non-small cell lung carcinoma with a high tumor mutation burden: A case report. Thorac Cancer, 10:1285-1288, 2019
9. Sakai T, Miyoshi T, Umemura S, Suzuki J, Nakasone S, Okada S, Tane K, Aokage K, Goto K, Motoi N, Ishii G, Tsuboi M. Large pulmonary sclerosing pneumocytoma with massive necrosis and vascular invasion: a case report. Oxf Med Case Reports, 2019:doi: 10.1093/omcr/omz066, 2019
10. Omori T, Aokage K, Nakamura H, Katsumata S, Miyoshi T, Sugano M, Kojima M, Fujii S, Kuwata T, Ochiai A, Ikeda N, Tsuboi M, Ishii G. Growth patterns of small peripheral squamous cell carcinoma of the lung and their impacts on pathological and biological characteristics of tumor cells. J Cancer Res Clin Oncol, 145:1773-1783, 2019
11. Okumura M, Yoshino I, Yano M, Watanabe SI, Tsuboi M, Yoshida K, Date H, Yokoi K, Nakajima J, Toyooka SI, Asamura H, Miyaoka E. Tumour size determines both recurrence-free survival and disease-specific survival after surgical treatment for thymoma. Eur J Cardiothorac Surg, 56:174-181, 2019
12. Miyoshi T, Aokage K, Katsumata S, Tane K, Ishii G, Tsuboi M. Ground-Glass Opacity Is a Strong Prognosticator for Pathologic Stage IA Lung Adenocarcinoma. Ann Thorac Surg, 108:249-255, 2019
13. Nakamura H, Sugano M, Miyashita T, Hashimoto H, Ochiai A, Suzuki K, Tsuboi M, Ishii G. Organoid culture containing cancer cells and stromal cells reveals that podoplanin-positive cancer-associated fibroblasts enhance proliferation of lung cancer cells. Lung Cancer, 134:100-107, 2019
14. Goto M, Aokage K, Sekihara K, Miyoshi T, Tane K, Yokoi K, Tsuboi M. Prediction of prolonged air leak after lung resection using continuous log data of flow by digital drainage system. Gen Thorac Cardiovasc Surg, 67:684-689, 2019
15. Katsumata S, Aokage K, Ishii G, Nakasone S, Sakai T, Okada S, Miyoshi T, Tane K, Tsuboi M. Prognostic Impact of the Number of Metastatic Lymph Nodes on the Eighth Edition of the TNM Classification of NSCLC. J Thorac Oncol, 14:1408-1418, 2019
16. Suzuki E, Yamazaki S, Naito T, Hashimoto H, Okubo S, Udagawa H, Goto K, Tsuboi M, Ochiai A, Ishii G. Secretion of high amounts of hepatocyte growth factor is a characteristic feature of cancer-associated fibroblasts with EGFR-TKI resistance-promoting phenotype: A study of 18 cases of cancer-associated fibroblasts. Pathol Int, 69:472-480, 2019
17. Ota T, Niho S, Kirita K, Ishii G, Tsuboi M, Goto K. Impressive response to nivolumab of non-small-cell lung cancer containing sarcomatoid components. Respirol Case Rep, 7:e00477, 2019
18. Suzuki K, Saji H, Aokage K, Watanabe SI, Okada M, Mizusawa J, Nakajima R, Tsuboi M, Nakamura S, Nakamura K, Mitsudomi T, Asamura H. Comparison of pulmonary segmentectomy and lobectomy: Safety results of a randomized trial. J Thorac Cardiovasc Surg, 158:895-907, 2019
19. Oki T, Aokage K, Ueda T, Sugano M, Tane K, Miyoshi T, Kojima M, Fujii S, Kuwata T, Ochiai A, Funai K, Tsuboi M, Ishii G. Proportion of goblet cell is associated with malignant potential in invasive mucinous adenocarcinoma of the lung. Pathol Int, 69:526-535, 2019
20. Ichikawa T, Aokage K, Miyoshi T, Tane K, Suzuki K, Makinoshima H, Tsuboi M, Ishii G. Correlation between maximum standardized uptake values on FDG-PET and microenvironmental factors in patients with clinical stage IA radiologic pure-solid lung adenocarcinoma. Lung Cancer, 136:57-64, 2019
21. Hisamitsu S, Miyashita T, Hashimoto H, Neri S, Sugano M, Nakamura H, Yamazaki S, Ochiai A, Goto K, Tsuboi M, Ishii G. Interaction between cancer cells and cancer-associated fibroblasts after cisplatin treatment promotes cancer cell regrowth. Hum Cell, 32:453-464, 2019
22. Naito T, Udagawa H, Umemura S, Sakai T, Zenke Y, Kirita K, Matsumoto S, Yoh K, Niho S, Tsuboi M, Ishii G, Goto K. Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden. Lung Cancer, 138:35-42, 2019