Annual Report 2022

Department of Thoracic Surgery

Shun-ichi Watanabe, Kazuo Nakagawa, Yukihiro Yoshida, Masaya Yotsukura, Yuma Fukumoto

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 patients with lung cancer.

The Team and What We Do

 Our department has 4 attending surgeons and resident surgeons who perform all the inpatient care, surgeries, examinations, and outpatient care. In 2022, we performed a total of 738 operations, including lung cancer in 643, metastatic tumors in 12, mediastinal tumors in 49 and other tumors in 34 patients (Tables 1 and 2).

 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. Surgical resection is usually indicated for clinical stages I, II and some III with non-small cell lung cancer [NSCLC] and clinical stage I with small cell lung cancer [SCLC] in patients with lung cancer. Whereas, 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. In addition, adjuvant therapy has often been given to patients with advanced lung cancer, even after complete resection.

 For metastatic lung tumors, resection has been attempted based on Thomford’s criteria. For mediastinal tumors, thymic epithelial tumors are most commonly encountered for resection. Meanwhile, treatment must be carefully determined by cytologic/histologic diagnosis preoperatively in the mediastinum, where various tumor histologies can arise.

 As for meetings, there are two department meetings. One is for the preoperative evaluation and postoperative inpatient review on Fridays and the other is for the journal club on Wednesdays.

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 primary tumor location by the lobe. Minimally invasive open surgery (MIOS) is also an important challenge in our department. Recently, the role of segmentectomy has become more important because of the increasing detection rate for early-stage NSCLC. We have actively performed segmentectomy in recent years. In 2022, we performed the largest number of segmentectomies as well as lung cancer surgeries in Japan.

Clinical Trials

 Our department has played an important role as a leading hospital in the Japan Clinical Oncology Group (JCOG) - Lung Cancer Surgical Study Group (LCSSG). To date, the LCSSG has conducted a lot of clinical trials for lung cancer surgery.

 With the increased frequency of the early detection rate of small-sized or ground-glass opacity (GGO) lung tumors, the optimal mode of resection: limited resection (segmentectomy and wedge resection) or standard resection (lobectomy) remains controversial. In addition, GGO tumors are well known to have an indolent behavior, thus some cases might be followed up with careful monitoring by CT. Accordingly, the best management of such patients not only with resection but also with observation needs to be explored. Three clinical trials to determine the appropriateness of limited resection for early-stage NSCLC (JCOG0802, JCOG0804, and JCOG1211) have been conducted since the end of 2009. The results of these 3 trials were published, and the role of limited resection has been established. These 3 trials from the LCSSG could lead to major shifts in clinical practice towards limited resection for early-stage NSCLC. For GGO tumors, JCOG1906: a prospective evaluation of watchful waiting for early-stage lung cancer with GGO opened to accrual in June 2020.

 Investigating the appropriate resection mode for compromised patients is also crucial. Three clinical trials are ongoing: JCOG1708, sublobar resection versus lobectomy for patients with resectable stage I NSCLC with idiopathic pulmonary fibrosis (opened to accrual in May 2018); JCOG1909, anatomical segmentectomy versus wedge resection in high-risk operable patients with clinical stage IA NSCLC (opened to accrual in April 2020); and JCOG2109, anatomical segmentectomy versus wedge resection for small (≤2 cm) peripheral NSCLC in 80 or more aged elderly patients (opened to accrual in October 2022). In addition, JCOG1710A, daily living activities in elderly patients who have undergone lung cancer surgery, completed the full accrual of 986 patients.

 As for lymph node dissection, JCOG1413: lobe-specific versus systematic nodal dissection for c-stage I/II NSCLC, completed the full accrual of 1507 patients. We await the maturation of follow-up data.

 Regarding adjuvant or neoadjuvant therapy, JCOG1916: postoperative radiotherapy for pathological N2 NSCLC with adjuvant chemotherapy opened to accrual in January 2021. Furthermore, JCOG1807C: efficacy and safety of durvalumab before and after operation or durvalumab as maintenance therapy after chemoradiotherapy against superior sulcus NSCLC opened to accrual in September 2020.

 The relevance of postoperative follow-up and surveillance modalities remains debated after the NSCLC resection. JCOG2012: postoperative surveillance for pathological stage II-IIIA NSCLC opened to accrual in October 2022.

 The LCSSG in the JCOG continues to establish ideal surgical treatment strategies for lung cancer.

List of papers published in 2022

Journal

1. Aokage K, Suzuki K, Saji H, Wakabayashi M, Kataoka T, Sekino Y, Fukuda H, Endo M, Hattori A, Mimae T, Miyoshi T, Isaka M, Yoshioka H, Nakajima R, Nakagawa K, Okami J, Ito H, Kuroda H, Tsuboi M, Okumura N, Takahama M, Ohde Y, Aoki T, Tsutani Y, Okada M, Watanabe SI. Segmentectomy for ground-glass-dominant lung cancer with a tumour diameter of 3 cm or less including ground-glass opacity (JCOG1211): a multicentre, single-arm, confirmatory, phase 3 trial. The Lancet. Respiratory medicine, 11:540-549, 2023

2. Yotsukura M, Muraoka Y, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma. Annals of surgical oncology, 30:851-858, 2023

3. Matsuzaki J, Kato K, Oono K, Tsuchiya N, Sudo K, Shimomura A, Tamura K, Shiino S, Kinoshita T, Daiko H, Wada T, Katai H, Ochiai H, Kanemitsu Y, Takamaru H, Abe S, Saito Y, Boku N, Kondo S, Ueno H, Okusaka T, Shimada K, Ohe Y, Asakura K, Yoshida Y, Watanabe SI, Asano N, Kawai A, Ohno M, Narita Y, Ishikawa M, Kato T, Fujimoto H, Niida S, Sakamoto H, Takizawa S, Akiba T, Okanohara D, Shiraishi K, Kohno T, Takeshita F, Nakagama H, Ota N, Ochiya T. Prediction of tissue-of-origin of early stage cancers using serum miRNomes. JNCI cancer spectrum, 7:pkac080, 2023

4. Yotsukura M, Muraoka Y, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. ASO Visual Abstract: Long-Term Prognosis and Prognostic Indicators of Stage IA Lung Adenocarcinoma. Annals of surgical oncology, 30:859-860, 2023

5. Sugawara H, Yatabe Y, Watanabe H, Akai H, Abe O, Watanabe SI, Kusumoto M. Radiological precursor lesions of lung squamous cell carcinoma: Early progression patterns and divergent volume doubling time between hilar and peripheral zones. Lung cancer (Amsterdam, Netherlands), 176:31-37, 2023

6. Ohishi T, Kaneko MK, Yoshida Y, Takashima A, Kato Y, Kawada M. Current Targeted Therapy for Metastatic Colorectal Cancer. International journal of molecular sciences, 24:1702, 2023

7. Akamine T, Yotsukura M, Yoshida Y, Nakagawa K, Yatabe Y, Watanabe SI. Feasibility and effectiveness of segmentectomy versus wedge resection for clinical stage I non-small-cell lung cancer. European journal of cardio-thoracic surgery, 63:ezad018, 2023

8. Asamura H, Nishimura KK, Giroux DJ, Chansky K, Hoering A, Rusch V, Rami-Porta R. IASLC Lung Cancer Staging Project: The New Database to Inform Revisions in the Ninth Edition of the TNM Classification of Lung Cancer. Journal of thoracic oncology, 18:564-575, 2023

9. Takemura C, Imabayashi T, Furuse H, Uchimura K, Matsumoto Y, Tsuchida T, Watanabe SI. Thoracic SMARCA4-deficient undifferentiated tumor diagnosed by transbronchial mediastinal cryobiopsy: A case report. Thoracic cancer, 14:953-957, 2023

10. Higashiyama M, Motoi N, Yotsukura M, Yoshida Y, Nakagawa K, Yagishita S, Shirasawa M, Yoshida T, Shiraishi K, Kohno T, Ohe Y, Watanabe SI. Clinicopathological characteristics and molecular analysis of lung cancer associated with ciliated muconodular papillary tumor/bronchiolar adenoma. Pathology international, 73:188-197, 2023

11. Nakagawa K. Minimally invasive sleeve lobectomy: it is important to pass excellent techniques to the next generation. Journal of thoracic disease, 15:946-949, 2023

12. Saji H, Okada M, Tsuboi M, Nakajima R, Suzuki K, Aokage K, Aoki T, Okami J, Yoshino I, Ito H, Okumura N, Yamaguchi M, Ikeda N, Wakabayashi M, Nakamura K, Fukuda H, Nakamura S, Mitsudomi T, Watanabe SI, Asamura H. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet (London, England), 399:1607-1617, 2022

13. Muraoka Y, Yoshida Y, Nakagawa K, Ito K, Watanabe H, Narita T, Watanabe SI, Yotsukura M, Motoi N, Yatabe Y. Maximum standardized uptake value of the primary tumor does not improve candidate selection for sublobar resection. The Journal of thoracic and cardiovascular surgery, 163:1656-1665.e3, 2022

14. Saito T, Murakawa T, Shintani Y, Okami J, Miyaoka E, Yoshino I, Date H. Preoperative renal dysfunction and long-term survival after surgery for non-small cell lung cancer. The Journal of thoracic and cardiovascular surgery, 164:227-239.e6, 2022

15. Takemura C, Kashima J, Hashimoto T, Ichikawa H, Honma Y, Goto Y, Watanabe SI, Yatabe Y. A mimic of lung adenocarcinoma: a case report of histological conversion of metastatic thyroid papillary carcinoma. Histopathology, 80:1004-1007, 2022

16. Kobayashi AK, Nakagawa K, Nakayama Y, Ohe Y, Yotsukura M, Uchida S, Asakura K, Yoshida Y, Watanabe SI. Salvage Surgery Compared to Surgery After Induction Chemoradiation Therapy for Advanced Lung Cancer. The Annals of thoracic surgery, 114:2087-2092, 2022

17. Kawakubo N, Okubo Y, Yotsukura M, Yoshida Y, Nakagawa K, Yonemori K, Watanabe H, Yatabe Y, Watanabe SI. Assessment of Resectability of Mediastinal Germ Cell Tumor Using Preoperative Computed Tomography. The Journal of surgical research, 272:61-68, 2022

18. Aokage K, Tsuboi M, Zenke Y, Horinouchi H, Nakamura N, Ishikura S, Nishikawa H, Kumagai S, Koyama S, Kanato K, Kataoka T, Wakabayashi M, Fukutani M, Fukuda H, Ohe Y, Watanabe SI. Study protocol for JCOG1807C (DEEP OCEAN): a interventional prospective trial to evaluate the efficacy and safety of durvalumab before and after operation or durvalumab as maintenance therapy after chemoradiotherapy against superior sulcus non-small cell lung cancer. Japanese journal of clinical oncology, 52:383-387, 2022

19. Kawakubo N, Hishiki T, Arakawa A, Nakajima M, Kumamoto T, Nakagawa K, Kawai A, Ogawa C. Surgical Treatment for Pneumothorax and Tumor-bronchial Fistula Secondary to Pulmonary Metastasis of Osteosarcoma in Pediatric and Adolescent Patients. Journal of pediatric hematology/oncology, 44:393-397, 2022

20. Fujikawa R, Muraoka Y, Kashima J, Yoshida Y, Ito K, Watanabe H, Kusumoto M, Watanabe SI, Yatabe Y. Clinicopathologic and Genotypic Features of Lung Adenocarcinoma Characterized by the International Association for the Study of Lung Cancer Grading System. Journal of thoracic oncology, 17:700-707, 2022

21. Ruffini E, Rami-Porta R, Huang J, Ahmad U, Appel S, Bille A, Boubia S, Brambilla C, Cangir AK, Cilento V, Detterbeck F, Falkson C, Fang W, Filosso PL, Giaccone G, Girard N, Guerrera F, Infante M, Kim DK, Lucchi M, Marino M, Marom EM, Nicholson AG, Okumura M, Rimner A, Simone CB 2nd, Asamura H. The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: Unresolved Issues to be Addressed for the Next Ninth Edition of the TNM Classification of Malignant Tumors. Journal of thoracic oncology, 17:838-851, 2022

22. Kojima N, Komiyama M, Shinoda Y, Watanabe SI, Yatabe Y, Kawai A, Yoshida A. Liposarcoma With Hibernoma-like Histology: A Clinicopathologic Study of 16 Cases. The American journal of surgical pathology, 46:1319-1328, 2022

23. Inoue M, Yotsukura M, Yoshida Y, Nakagawa K, Watanabe SI. A case of cardiac herniation after right pneumonectomy. Asian cardiovascular & thoracic annals, 30:737-740, 2022

24. Soh J, Toyooka S, Shintani Y, Okami J, Ito H, Ohtsuka T, Mori T, Watanabe SI, Asamura H, Chida M, Endo S, Nakanishi R, Kadokura M, Suzuki H, Miyaoka E, Yoshino I, Date H. Limited resection for stage IA radiologically invasive lung cancer: a real-world nationwide database study. European journal of cardio-thoracic surgery, 62:ezac342, 2022

25. Nakayama S, Kobayashi E, Nishio J, Toda Y, Yotsukura M, Watanabe SI, Yamamoto T, Kawai A. Prognostic Factors of Pulmonary Metastasectomy for Soft Tissue Sarcomas Arising in the Trunk Wall and Extremities. Cancers, 14:3329, 2022

26. Higashiyama M, Kobayashi Y, Kashima J, Muraoka Y, Watanabe H, Kusumoto M, Watanabe SI, Yatabe Y. Invasive Mucinous Adenocarcinoma of the Lung With a Mural Nodule-like Lesion. The American journal of surgical pathology, 46:1524-1532, 2022

27. Yotsukura M, Nakagawa K, Takemura C, Yoshida Y, Ito K, Watanabe H, Kusumoto M, Yatabe Y, Watanabe SI. Aggressive histological component in subsolid lung adenocarcinoma: priority for resection without delay. Japanese journal of clinical oncology, 52:1321-1326, 2022

28. Ishiguro Y, Uchimura K, Furuse H, Imabayashi T, Matsumoto Y, Watanabe SI, Tsuchida T. Esophageal submucosal tumor diagnosed with EBUS-guided transbronchial mediastinal cryobiopsy: A case report. Thoracic cancer, 13:3068-3072, 2022

29. Kajiyama A, Ito K, Watanabe H, Mizumura S, Watanabe SI, Yatabe Y, Gomi T, Kusumoto M. Consistency and prognostic value of preoperative staging and postoperative pathological staging using (18)F-FDG PET/MRI in patients with non-small cell lung cancer. Annals of nuclear medicine, 36:1059-1072, 2022

30. Yamauchi Y, Kawamura M, Okami J, Shintani Y, Ito H, Ohtsuka T, Toyooka S, Mori T, Watanabe SI, Asamura H, Chida M, Endo S, Kadokura M, Nakanishi R, Miyaoka E, Suzuki H, Yoshino I, Date H. Hazard Function Analysis of Recurrence in Patients with Curatively Resected Lung Cancer: Results from the Japanese Lung Cancer Registry in 2010. Cancers, 14:5119, 2022

31. Kashima J, Hashimoto T, Yoshida A, Goto Y, Ushiku T, Ohe Y, Watanabe SI, Yatabe Y. Insulinoma-associated-1 (INSM1) expression in thymic squamous cell carcinoma. Virchows Archiv, 481:893-901, 2022

32. Yoshida Y, Saeki N, Yotsukura M, Nakagawa K, Watanabe H, Yatabe Y, Watanabe SI. Visualization of patterns of lymph node metastases in non-small cell lung cancer using network analysis. JTCVS open, 12:410-425, 2022