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Annual Report 2019

Department of Thoracic Surgery

Shun-ichi Watanabe, Kazuo Nakagawa, Yukihiro Yoshida, Masaya Yotsukura, Yu Okubo

Introduction

 The Department of Thoracic Surgery deals with various kinds of neoplasms and allied diseases in the thorax, except the esophagus. These include both primary and metastatic lung tumors, mediastinal tumors, pleural tumors (mesotheliomas) and chest wall tumors. The main clinical activity of our department and the subject of most of its research activities has been the surgical management of lung cancer patients. As well as continuing to improve procedures, such as the combined resection of neighboring vital structures and minimally invasive techniques (video-assisted thoracic surgery, VATS), it has become increasingly important to define the role of surgery in multimodality treatment for patients with poor prognoses.

The Team and What We Do

 Our department has four attending surgeons and resident surgeons perform all of the inpatient care, operations, examinations and outpatient care. In 2019, we performed a total of 857 operations: for lung cancer in 681 patients, metastatic tumors in 81, mediastinal tumors in 41 and other tumors in 48 (Tables 1 and 2).

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 treatment strategy for patients with lung cancer is based on tumor histology (non-small cell vs. small cell), the extent of the disease (clinical stage) and the physical status of the patient. In lung cancer patients, surgical resection is usually indicated for clinical stages I, II and some IIIA with non-small cell histology and clinical stages I with small cell histology. However, to improve the poor prognosis of patients with clinically and histologically proven mediastinal lymph node metastasis or with invasion of vital neighboring structures, optimal treatment modalities are sought in a clinical trial setting. Recently, adjuvant chemotherapy has often been given to patients with advanced lung cancer, even after complete pulmonary resection.

 For metastatic lung tumors, resection has been attempted on the basis of Thomford’s criteria: eligible patients are those who are a good risk, with no extrathoracic disease, with the primary site under control and with completely resectable lung disease. Metastasis from colorectal carcinomas is the most common disease.

 For mediastinal tumors, thymic epithelial tumors are most commonly encountered for resection. In the mediastinum meanwhile, where various tumor histologies can arise, treatment must be carefully determined by cytologic/histologic diagnosis before surgery. For patients with thymoma, we have already adopted video-assisted resection (VATS) of the tumor. VATS resection of mediastinal tumor is indicated exclusively for small thymomas.

 As for meetings, there are two department meetings. One is for the preoperative evaluation and postoperative inpatient review on Friday and the other is for the journal club on Tuesday. In addition, on Thursday, the chest group holds a plenary meeting to share basic information about current issues for diagnosing and treating patients with lung malignancy.

Research activities

 Lymph node dissection for lung cancer has been a major issue in lung cancer treatment and has been extensively studied in our department. We continue to improve our surgical dissection technique taking oncological and surgical aspects into consideration: a more effective and less invasive lymph node dissection called “selective mediastinal/hilar dissection” according to the location of the primary tumor by the lobe.

 Minimally invasive open surgery (MIOS), with a thoracoscope for thoracic malignancies, is also an important challenge in our department. Indications and surgical techniques of video-assisted surgery for early lung cancer are of special interest given the increased incidence of such minute tumors due to improvements in CT devices and CT screening.

Clinical trials

 The advent of new technologies in CT scanning means more small-sized lung cancers are being found in screening settings and by chance. They are usually present as “ground-glass opacity (GGO)” on CT and considered as early adenocarcinoma in pathological terms. The surgical management of such GGO-type lung cancer remains undetermined in terms of the extent of pulmonary parenchymal resection and lymph node dissection. Some cases might be followed up with careful monitoring by CT, since indolent tumors are known to exist and we are seeking how best to manage such patients. A clinical trial to determine the appropriateness of limited resection for early adenocarcinoma had been planned in the Japan Clinical Oncology Group (JCOG) - Lung Cancer Surgical Study Group and two clinical trials (phase III, JCOG 0802 and phase II, JCOG 0804) have been conducted since the end of 2009. In addition, another phase II trial (JCOG 1211), a confirmatory trial of segmentectomy for clinical T1N0 lung cancer dominant with GGO, was started in 2013. The accrual of these three trials, having investigated the appropriateness of limited resection, is complete and has achieved the planned number of patients. We now await maturation of the follow-up data regarding recurrence and prognosis.

 As for lymph node dissection, a randomized phase III trial of lobe-specific versus systematic nodal dissection for c-stage I/II non-small cell lung cancer (JCOG 1413) opened to accrual in January 2017, as did sublobar resection versus lobectomy for patients with resectable stage I non-small cell lung cancer with idiopathic pulmonary fibrosis in a phase III study evaluating survival (JCOG1708) in May 2018. More recently, a prospective observational study of daily living activities in elderly patients having undergone lung cancer surgery (JCOG1710A) opened to accrual.

 As for postoperative adjuvant therapy, a phase III clinical trial to compare the effectiveness of UFT with that of TS-1 for stage IA exceeding 2 cm and IB NSCLC planned in JCOG (JCOG 0707) has been conducted since 2008. This trial completed the full accrual of 960 patients in 2013. A phase III clinical trial (JCOG 1205) to compare Irinotecan/Cisplatin with Etoposide/Cisplatin for adjuvant chemotherapy of resected pulmonary high-grade neuroendocrine carcinoma was started in 2013. This trial also completed the full accrual of 221 patients in 2018. We are awaiting the maturation of follow-up data regarding recurrence and prognosis.

List of papers published in 2019

Journal

1. Yoshida A, Arai Y, Hama N, Chikuta H, Bando Y, Nakano S, Kobayashi E, Shibahara J, Fukuhara H, Komiyama M, Watanabe SI, Tamura K, Kawai A, Shibata T. Expanding the clinicopathologic and molecular spectrum of BCOR-associated sarcomas in adults. Histopathology, 76:509-520, 2020

2. 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

3. Kakinuma R, Muramatsu Y, Asamura H, Watanabe SI, Kusumoto M, Tsuchida T, Kaneko M, Tsuta K, Maeshima AM, Ishii G, Nagai K, Yamaji T, Matsuda T, Moriyama N. Low-dose CT lung cancer screening in never-smokers and smokers: results of an eight-year observational study. Transl Lung Cancer Res, 9:10-22, 2020

4. Edwards JG, Chansky K, Van Schil P, Nicholson AG, Boubia S, Brambilla E, Donington J, Galateau-Sallé F, Hoffmann H, Infante M, Marino M, Marom EM, Nakajima J, Ostrowski M, Travis WD, Tsao MS, Yatabe Y, Giroux DJ, Shemanski L, Crowley J, Krasnik M, Asamura H, Rami-Porta R. The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for Residual Tumor Descriptors for Non-Small Cell Lung Cancer. J Thorac Oncol, 15:344-359, 2020

5. Asakura K, Kadota T, Matsuzaki J, Yoshida Y, Yamamoto Y, Nakagawa K, Takizawa S, Aoki Y, Nakamura E, Miura J, Sakamoto H, Kato K, Watanabe SI, Ochiya T. A miRNA-based diagnostic model predicts resectable lung cancer in humans with high accuracy. Commun Biol, 3:134, 2020

6. Ito H, Suzuki K, Mizutani T, Aokage K, Wakabayashi M, Fukuda H, Watanabe SI. Long-term survival outcome after lobectomy in patients with clinical T1 N0 lung cancer. J Thorac Cardiovasc Surg, 2020

7. 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

8. 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

9. Sekimizu M, Yoshida A, Mitani S, Asano N, Hirata M, Kubo T, Yamazaki F, Sakamoto H, Kato M, Makise N, Mori T, Yamazaki N, Sekine S, Oda I, Watanabe SI, Hiraga H, Yonemoto T, Kawamoto T, Naka N, Funauchi Y, Nishida Y, Honoki K, Kawano H, Tsuchiya H, Kunisada T, Matsuda K, Inagaki K, Kawai A, Ichikawa H. Frequent mutations of genes encoding vacuolar H+ -ATPase components in granular cell tumors. Genes Chromosomes Cancer, 58:373-380, 2019

10. Tsutani Y, Suzuki K, Koike T, Wakabayashi M, Mizutani T, Aokage K, Saji H, Nakagawa K, Zenke Y, Takamochi K, Ito H, Aoki T, Okami J, Yoshioka H, Okada M, Watanabe SI. High-Risk Factors for Recurrence of Stage I Lung Adenocarcinoma: Follow-up Data From JCOG0201. Ann Thorac Surg, 108:1484-1490, 2019

11. Nakanishi K, Nakagawa K, Asakura K, Yoshida Y, Watanabe H, Watanabe SI. Is Calcification in the Regional Lymph Nodes a Benign Feature in Patients with Lung Cancer? World J Surg, 43:1850-1856, 2019

12. Yoshida A, Wakai S, Ryo E, Miyata K, Miyazawa M, Yoshida KI, Motoi T, Ogawa C, Iwata S, Kobayashi E, Watanabe SI, Kawai A, Mori T. Expanding the Phenotypic Spectrum of Mesenchymal Tumors Harboring the EWSR1-CREM Fusion. Am J Surg Pathol, 43:1622-1630, 2019

13. Asakura K, Yoshida Y, Sakurai H, Nakagawa K, Motoi N, Watanabe SI. Prognostic Impact of Tumor Doubling Time in Patients with Metachronous Lung Cancer. World J Surg, 43:3259-3266, 2019

14. Hamaji M, Sozu T, Machida R, Watanabe SI, Yoshida K, Toyooka S, Tanahashi M, Kondo K, Horio H, Okumura M, Date H. Mortality from extrathymic malignancy after thymic tumour resections: incidences and risk factors. Interact Cardiovasc Thorac Surg, 29:729-736, 2019

15. Nakamura A, Esaki M, Nakagawa K, Asakura K, Kishi Y, Nara S, Shimada K, Watanabe SI. Three risk factors for pulmonary metastasectomy in patients with hepatocellular carcinoma. Gen Thorac Cardiovasc Surg, 67:782-787, 2019

16. Uchida S, Yoshida Y, Ohe Y, Nakayama Y, Motoi N, Kobayashi A, Asakura K, Nakagawa K, Watanabe SI. Trimodality therapy for superior sulcus tumour: experience of a single institution over 19 years. Eur J Cardiothorac Surg, 56:167-173, 2019

17. Ohashi-Nakatani K, Shibuki Y, Fujima M, Watanabe R, Yoshida A, Yoshida H, Matsumoto Y, Tsuchida T, Watanabe SI, Motoi N. Primary pulmonary meningioma: A rare case report of aspiration cytological features and immunohistochemical assessment. Diagn Cytopathol, 47:330-333, 2019

18. Hino H, Karasaki T, Yoshida Y, Fukami T, Sano A, Tanaka M, Furuhata Y, Kashiwabara K, Ichinose J, Kawashima M, Nakajima J. Competing Risk Analysis in Lung Cancer Patients Over 80 Years Old Undergoing Surgery. World J Surg, 43:1857-1866, 2019

19. Yoshida Y, Sakane T, Isogai J, Suzuki Y, Miki S, Nomura Y, Nakajima J. Computer-assisted detection of metastatic lung tumors on computed tomography. Asian Cardiovasc Thorac Ann, 27:199-207, 2019

20. Yoshida Y, Manaka T, Nitadori JI, Shinozaki-Ushiku A, Doke Ts, Saito T, Sato J, Miyaji T, Yamaguchi T, Oyama H, Fukayama M, Nakajima Y, Nakajima J. A comparison between 2- and 3-dimensional approaches to solid component measurement as radiological criteria for sublobar resection in lung adenocarcinoma ≦ 2 cm in size. Surg Today, 49:828-835, 2019

21. Nakagawa K. Induction chemotherapy for locally advanced thymic epithelial tumors: consideration from the RYTHMIC prospective cohort. Mediastinum, 3:13, 2019