Annual Report 2017
Department of Thoracic Surgery
Masahiro Tsuboi, Keiju Aokage, Tomohiro Miyoshi, Kenta Tane, Takashi Sakai, Satoshi Okada, Shoko Nakasone
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, 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-/ angio-plasty, 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 28 scientific papers published in English, our department made 33 presentations: six international, 21 national, and six regional.
Our 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 to 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 for 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, an 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 the further 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 [JCOG0707, phase III, patient accrual completed]
2) Primary investigator and a member of an organized trial of sublobar resection for peripheral GGO dominant cT1aN0M0 lung adenocarcinomas [JCOG0804, phase II, patient accrual completed]
3) Study coordinator and a member of an organized trial of segmental resection vs. lobectomy for peripheral T1aN0M0 non-small cell lung cancers [JCOG0802, phase III, patient accrual completed]
4) Study coordinator and a member of an organized trial of sublobar resection for peripheral GGO dominant cT1bN0M0 lung adenocarcinomas [JCOG1211, 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 ongoing]
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 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]
Education
Our training program is 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, open communication between all health care providers, while maintaining a respectful and professional demeanor (Tables 1 and 2).
Table 1. Number of surgically resected patients
Future prospects
Treatment advances in thoracic cancers including lung, mesothelioma, thymic malignancies and lung metastases have been slow to develop, even though these cancers are among the most common clinical problems. This clinical and laboratory research is vital to making progress.
List of papers published in January 2017 - March 2018
Journal
1. Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Makinoshima H, Ishii G, Udagawa H, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Aokage K, Hishida T, Yoshida J, Nagai K, Goto K, Tsuboi M, Tsuchihara K. Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung. Clin Cancer Res, 23:757-765, 2017
2. Aokage K, Miyoshi T, Ishii G, Kusumoto M, Nomura S, Katsumata S, Sekihara K, Hishida T, Tsuboi M. Clinical and Pathological Staging Validation in the Eighth Edition of the TNM Classification for Lung Cancer: Correlation between Solid Size on Thin-Section Computed Tomography and Invasive Size in Pathological Findings in the New T Classification. J Thorac Oncol, 12:1403-1412, 2017
3. Adachi H, Sakamaki K, Nishii T, Yamamoto T, Nagashima T, Ishikawa Y, Ando K, Yamanaka K, Watanabe K, Kumakiri Y, Tsuboi M, Maehara T, Nakayama H, Masuda M. Lobe-Specific Lymph Node Dissection as a Standard Procedure in Surgery for Non-Small Cell Lung Cancer: A Propensity Score Matching Study. J Thorac Oncol, 12:85-93, 2017
4. Ichikawa T, Saruwatari K, Mimaki S, Sugano M, Aokage K, Kojima M, Hishida T, Fujii S, Yoshida J, Kuwata T, Ochiai A, Suzuki K, Tsuboi M, Goto K, Tsuchihara K, Ishii G. Immunohistochemical and genetic characteristics of lung cancer mimicking organizing pneumonia. Lung Cancer, 113:134-139, 2017
5. Kanamori J, Aokage K, Hishida T, Yoshida J, Tsuboi M, Fujita T, Nagino M, Daiko H. The role of pulmonary resection in tumors metastatic from esophageal carcinoma. Jpn J Clin Oncol, 47:25-31, 2017
6. Suzuki S, Aokage K, Yoshida J, Ishii G, Matsumura Y, Haruki T, Hishida T, Nagai K. Thin-section computed tomography findings of lung adenocarcinoma with inherent metastatic potential. Surg Today, 47:619-626, 2017
7. Neri S, Miyashita T, Hashimoto H, Suda Y, Ishibashi M, Kii H, Watanabe H, Kuwata T, Tsuboi M, Goto K, Menju T, Sonobe M, Date H, Ochiai A, Ishii G. Fibroblast-led cancer cell invasion is activated by epithelial-mesenchymal transition through platelet-derived growth factor BB secretion of lung adenocarcinoma. Cancer Lett, 395:20-30, 2017
8. Kameda Y, Nishii T, Tsuboi M, Arai H, Inui K, Kaneko T, Kimura N, Naruse M, Masuda M. Alveolar soft-part sarcoma of the mediastinum: A case report. SAGE open medical case reports, 5:2050313X17695473, 2017
9. Ikemura S, Aramaki N, Fujii S, Kirita K, Umemura S, Matsumoto S, Yoh K, Niho S, Ohmatsu H, Kuwata T, Kojima M, Ochiai A, Betsuyaku T, Tsuboi M, Goto K, Ishii G. Changes in the tumor microenvironment during lymphatic metastasis of lung squamous cell carcinoma. Cancer Sci, 108:136-142, 2017
10. Aokage K, Yoshida J, Hishida T, Tsuboi M, Saji H, Okada M, Suzuki K, Watanabe S, Asamura H. Limited resection for early-stage non-small cell lung cancer as function-preserving radical surgery: a review. Jpn J Clin Oncol, 47:7-11, 2017
11. Shimizu K, Kirita K, Aokage K, Kojima M, Hishida T, Kuwata T, Fujii S, Ochiai A, Funai K, Yoshida J, Tsuboi M, Ishii G. Clinicopathological significance of caveolin-1 expression by cancer-associated fibroblasts in lung adenocarcinoma. J Cancer Res Clin Oncol, 143:321-328, 2017
12. Hashimoto H, Suda Y, Miyashita T, Ochiai A, Tsuboi M, Masutomi K, Kiyono T, Ishii G. A novel method to generate single-cell-derived cancer-associated fibroblast clones. J Cancer Res Clin Oncol, 143:1409-1419, 2017
13. Ohtaki Y, Shimizu K, Aokage K, Nakao M, Yoshida J, Kamiyoshihara M, Sugano M, Takahashi Y, Nakazawa S, Nagashima T, Obayashi K, Hishida T, Tsuboi M, Mori S, Mun M, Okumura S, Igai H, Matsutani N, Mogi A, Kuwano H. Histology is a Prognostic Indicator After Pulmonary Metastasectomy from Renal Cell Carcinoma. World J Surg, 41:771-779, 2017
14. Hishida T, Tsuboi M, Okumura T, Boku N, Ohde Y, Sakao Y, Yoshiya K, Hyodo I, Mori K, Kondo H. Does Repeated Lung Resection Provide Long-Term Survival for Recurrent Pulmonary Metastases of Colorectal Cancer? Results of a Retrospective Japanese Multicenter Study. Ann Thorac Surg, 103:399-405, 2017
15. Tsuboi M, Hamada C, Kato H, Ohta M. The Effect of Tegafur-Uracil on Survival in T Categories as Defined in the Eighth Edition of the TNM Classification: An Exploratory Analysis of Postoperative Adjuvant Tegafur-Uracil on Survival in Patients with Adenocarcinoma of the Lung. Chemotherapy, 62:357-360, 2017
16. Nojiri T, Yamamoto H, Hamasaki T, Onda K, Ohshima K, Shintani Y, Okumura M, Kangawa K. A multicenter randomized controlled trial of surgery alone or surgery with atrial natriuretic peptide in lung cancer surgery: study protocol for a randomized controlled trial. Trials, 18:183, 2017
17. Ishibashi M, Neri S, Hashimoto H, Miyashita T, Yoshida T, Nakamura Y, Udagawa H, Kirita K, Matsumoto S, Umemura S, Yoh K, Niho S, Tsuboi M, Masutomi K, Goto K, Ochiai A, Ishii G. CD200-positive cancer associated fibroblasts augment the sensitivity of Epidermal Growth Factor Receptor mutation-positive lung adenocarcinomas to EGFR Tyrosine kinase inhibitors. Sci Rep, 7:46662, 2017
18. Sekihara K, Hishida T, Yoshida J, Oki T, Omori T, Katsumata S, Ueda T, Miyoshi T, Goto M, Nakasone S, Ichikawa T, Matsuzawa R, Aokage K, Goto K, Tsuboi M. Long-term survival outcome after postoperative recurrence of non-small-cell lung cancer: who is 'cured' from postoperative recurrence? Eur J Cardiothorac Surg, 52:522-528, 2017
19. Miyoshi T, Yoshida J, Aramaki N, Matsumura Y, Aokage K, Hishida T, Kobayashi T, Tsubura S, Katsuhara S, Kasai S, Sasano Y, Nagai K, Tsuboi M. Effectiveness of Bone Suppression Imaging in the Detection of Lung Nodules on Chest Radiographs: Relevance to Anatomic Location and Observer's Experience. J Thorac Imaging, 32:398-405, 2017
20. Hishida T, Tsuboi M, Okumura T, Boku N, Hyodo I, Mori K, Kondo H. Reply. Ann Thorac Surg, 104:1435-1436, 2017
21. Asamura H, Aokage K, Yotsukura M. Wedge Resection Versus Anatomic Resection: Extent of Surgical Resection for Stage I and II Lung Cancer. Am Soc Clin Oncol Educ Book, 37:426-433, 2017
22. Sakuraba M, Umezawa H, Miyamoto S, Fujiki M, Higashino T, Oshima A, Tsuboi M. Reconstructive Surgery for Bronchopleural Fistula and Empyema: New Application of Free Fascial Patch Graft Combined with Free Flap. Plastic and reconstructive surgery. Global open, 5:e1199, 2017
23. Goto M, Naito M, Saruwatari K, Hisakane K, Kojima M, Fujii S, Kuwata T, Ochiai A, Nomura S, Aokage K, Hishida T, Yoshida J, Yokoi K, Tsuboi M, Ishii G. The ratio of cancer cells to stroma after induction therapy in the treatment of non-small cell lung cancer. J Cancer Res Clin Oncol, 143:215-223, 2017
24. Aokage K, Okada M, Suzuki K, Nomura S, Suzuki S, Tsubokawa N, Mimae T, Hattori A, Hishida T, Yoshida J, Tsuboi M. Is cancer history really an exclusion criterion for clinical trial of lung cancer? Influence of gastrointestinal tract cancer history on the outcomes of lung cancer surgery. Jpn J Clin Oncol, 47:145-156, 190, 2017
25. Yamamoto N, Kenmotsu H, Yamanaka T, Nakamura S, Tsuboi M. Randomized Phase III Study of Cisplatin With Pemetrexed and Cisplatin With Vinorelbine for Completely Resected Nonsquamous Non-Small-Cell Lung Cancer: The JIPANG Study Protocol. Clin Lung Cancer, 19:e1-e3, 2018
26. Aokage K, Miyoshi T, Ishii G, Kusumoto M, Nomura S, Katsumata S, Sekihara K, Tane K, Tsuboi M. Influence of Ground Glass Opacity and the Corresponding Pathological Findings on Survival in Patients with Clinical Stage I Non-Small Cell Lung Cancer. J Thorac Oncol, 13:533-542, 2018
27. Sekihara K, Aokage K, Oki T, Omori T, Katsumata S, Ueda T, Miyoshi T, Goto M, Nakasone S, Ichikawa T, Hishida T, Yoshida J, Hisakane K, Goto K, Tsuboi M. Long-term survival after complete resection of non-small-cell lung cancer in patients with interstitial lung disease. Interact Cardiovasc Thorac Surg, 26:638-643, 2018
28. Nakamura H, Ichikawa T, Nakasone S, Miyoshi T, Sugano M, Kojima M, Fujii S, Ochiai A, Kuwata T, Aokage K, Suzuki K, Tsuboi M, Ishii G. Abundant tumor promoting stromal cells in lung adenocarcinoma with hypoxic regions. Lung Cancer, 115:56-63, 2018