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Background: Surgical resection followed by adjuvant chemotherapy is currently the first choice for the treatment of clinical N1 (cN1) non-small cell lung cancer (NSCLC). However, diagnosing cN1 correctly can be difficult, even with current imaging diagnostic technologies. We aimed to analyze the diagnostic accuracy of preoperative nodal status and the predictive factors for nodal upstaging of cN1-NSCLC., Methods: Patients receiving surgery for cN1-NSCLC in 2010 (n = 1040) were enrolled in the Japanese Joint Committee of Lung Cancer Registry Database. We investigated the diagnostic accuracy of cN1, predictive factors for nodal upstaging, and prognostic factors for overall survival (OS) and recurrence-free survival (RFS)., Results: The 5-year OS and RFS for all patients were 58.2% and 42.7%, respectively. The postoperative pathological nodal status included N0 (36.6%), N1 (39.7%), N2 (23.6%), and N3 (0.1%). In multivariate analysis, younger age (P = .005), no history of smoking (P = .006), and adenocarcinoma (P < .001) were significant predictive factors for nodal upstaging. Older age (P < .001) and higher clinical T (cT) factor (P < .001) were significant indicators for worse OS, while older age (P = .02), higher cT factor (P = .019), high carcinoembryonic antigen value (P = .002), and adenocarcinoma (P = .008) were significant indicators for worse RFS., Conclusions: The diagnostic accuracy of cN1 in this study was ~40%. No history of smoking and adenocarcinoma were significant predictors for nodal upstaging. Although younger age was a significant predictor for nodal upstaging, it was a significant factor for better prognosis., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Radiologically invasive non-small-cell lung cancer, defined as consolidation size to maximum tumour diameter ratio of over 0.5, is associated with pathological invasiveness and worse prognosis. However, there are no real-world, nationwide database studies on limited resections that consider radiological invasiveness. This study aimed to investigate the prognostic validity of limited resection, such as segmentectomy and wedge resection, in cStage IA (TNM 8th edition) radiologically invasive lung cancer., Methods: We conducted a retrospective analysis of patients who underwent complete resection according to the Japanese Joint Committee of Lung Cancer Registry Database. The relationship between surgical procedures and prognosis was examined using stratification by cT factor and radiological invasiveness., Results: Among the 5,692 patients enrolled, lobectomy, segmentectomy and wedge resection were performed in 4,323 (80.0%), 657 (11.5%) and 712 (12.5%) patients, respectively. Multivariable analysis with or without propensity score matching indicated that older age, poor performance status and wedge resection were significantly associated with worse prognosis and that patients who underwent segmentectomy showed an equivalent prognosis to those who underwent lobectomy. Subset analyses revealed that segmentectomy showed an equivalent prognosis to lobectomy in patients with cT1b or less, but not in those with cT1c, especially for non-pure radiological invasive cT1c; 5-year overall survival rates were 91.4% vs 90.4% in cT1b with non-pure radiological invasiveness and 80.0% vs 83.8% in cT1b with pure radiological invasiveness, respectively., Conclusions: Segmentectomy can be an alternative to lobectomy in patients with radiologically invasive lung cancer with cT1b or less but not in those with cT1c., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Debulking surgery, also called cytoreductive surgery, is a resection of the tumor as much as possible and an intended incomplete resection for unresectable malignant tumors. Since the most important principle in surgical oncology is complete R0 resection, debulking surgery goes against the basic principle and obscures the concept of operability. However, debulking surgery has been advocated for various types of advanced malignant tumors, including gynecological cancers, urological cancers, gastrointestinal cancers, breast cancers and other malignancies, with or without adjuvant therapy. Positive data from randomized trials have been shown in subsets of ovarian cancer, renal cell carcinoma, colorectal cancer and breast cancer. However, recent trials for renal cell carcinoma, colorectal cancer and breast cancer have tended to show controversial results, mainly according to the survival improvement of nonsurgical systemic therapy alone. On the other hand, debulking surgery still has a therapeutic role for slow-growing and borderline malignant tumors, such as pseudomyxoma peritonei and thymomas. The recent understanding of tumor heterogeneity and clonal evolution responsible for malignancy and drug resistance indicates that select patients may obtain prolonged survival by the synergistic effect of debulking surgery and novel systemic therapy. This review aimed to describe the current status and evidence of debulking surgery in a cross-organ manner and to discuss future perspectives in the current era with advances in systemic therapy., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Standard resection for patients with thymoma is resection of thymoma with total thymectomy (TTx) via median sternotomy. Hence, limited resection for thymoma means a lesser extent of resection of normal thymus compared with a standard procedure, i.e. resection of thymoma with partial thymectomy (PTx). In contrast, minimally invasive resection has been defined as resection of thymoma with TTx via a less-invasive approach. However, to date, few studies have precisely evaluated the differences in surgical and oncological outcomes among these three procedures. This report summarizes the differences among these three procedures with a review of studies (January 2000 to December 2020) focusing on the difference in surgical and oncological outcomes and presents current issues in the surgical management of thymoma. In this report, 16 studies were identified; 5 compared standard resection to limited resection, 9 compared standard resection to minimally invasive resection and 2 compared limited resection to minimally invasive resection. Most studies reported that the surgical and oncological outcomes of limited resection or minimally invasive resection were similar to those of standard resection in patients with early-stage thymoma. However, they did not include a sufficient follow-up period. Both limited resection and minimally invasive resection for early-stage thymoma might be reasonable treatment options. However, they are still promising modes of resection. Further studies with a long follow-up period are needed., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The purpose of this study was to clarify the prevalence, clinical features and survival of patients with thymoma and non-myasthenia gravis autoimmune disease (NMAD) using a nationwide cohort., Methods: The Japanese Association for Research on the Thymus nationwide database, which includes data from 32 institutions, was examined to clarify the prevalence and characteristics of NMAD associated with thymomas and elucidate the prognostic impact of NMAD for thymoma patients., Results: Among the 2423 patients with thymomas who were surgically treated between 1991 and 2010, 114 (4.7%) were identified with NMAD. The most frequently observed NMAD was pure red cell aplasia (PRCA) in 44 (1.8%), followed by hypogammaglobulinaemia (0.5%) and rheumatic arthritis (0.5%). Twenty-eight percent of patients with NMAD had concomitant myasthenia gravis. The presence of NMAD was not an independent prognostic factor for overall survival (OS) irrespective of the type of NMAD [PRCA+: hazard ratio (HR) 1.99, 95% confidence interval 0.74-4.47; PRCA- NMAD: HR 1.28, 0.30-3.56]; however, there were more cases with advanced age and disease of the thymoma amongst PRCA+ patients and these showed a worse OS than patients with PRCA- NMAD (P < 0.001), who had an OS similar to those without NMAD (P = 0.489). The 10-year OS rates in PRCA+, PRCA- NMAD and NMAD- groups were 45.5%, 97.4% and 89.5%, respectively. The main causes of death in PRCA+ patients were the progression of thymoma and other diseases including pneumonia., Conclusions: Although the presence of NMAD itself did not significantly affect survival after surgery for thymoma, the type of NMAD was associated with different clinical features and prognosis. The NMAD+ thymomas should be separately categorized according to the presence or absence of PRCA., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The tumour, node and the metastasis (TNM) staging system for thymic epithelial tumours was adopted by the Union for International Cancer Control (UICC) in 2016. Although the T factor is defined by the invasive nature of a thymoma, tumour size is not considered. The aim of this study was to examine the clinical importance of tumour size using a nationwide retrospective database of cases treated from 1991 to 2010 compiled by the Japanese Association for Research of the Thymus., Methods: Tumour size was evaluated by the maximum diameter shown by computed tomography imaging prior to resection. Tumour size was available for 2083 thymoma patients undergoing upfront surgical treatment. The tumour size ranged from 0.6 to 19.4 cm (mean 5.1 cm, median 4.9 cm). Harrell's C-index was adopted to determine the cut-off value of the tumour size in 0.5-cm increments., Results: The highest C-index value (0.7760) was obtained in terms of recurrence-free survival after the complete resection when the cut-off value was set at 5.0 cm. The 10-year recurrence-free survival rate was 93.8% in patients with a tumour ≤5.0 cm and 84.3% in patients with a tumour >5.0 cm (P < 0.0001). The highest C-index value (0.8885) in terms of disease-specific survival was obtained when the cut-off value was set at 8.0 cm. The 10-year disease-specific survival rate was 98.8% in patients with a tumour <8.0 cm and 90.1% in those with a tumour ≥8.0 cm (P < 0.0001). The Cox's proportional hazard model analysis showed that the tumour size and the TNM-based pathological stage were independent factors to determine both recurrence-free survival and disease-specific survival., Conclusions: Tumour size is an important prognostic factor and should be considered when determining the treatment strategy for thymoma patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

In January 2017, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group commenced a randomized Phase III trial to confirm the clinical benefit of lobe-specific nodal dissection for clinical Stage I-II non-small cell lung cancer. The primary endpoint is overall survival, and the main objective is to confirm the non-inferiority of lobe-specific in comparison to systematic nodal dissection with regard to lobectomy. The secondary endpoints are relapse-free survival, %local recurrence, %regional lymph node recurrence, operation time, blood loss, length of hospitalization, duration of chest tube placement and adverse events. A total of 1700 patients will be accrued from 44 Japanese institutions within 5 years. This study is the first and large prospective trial to evaluate whether the difference in the area of nodal dissection affects the overall survival of patients with relatively early-stage non-small cell lung cancer. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000025530., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy., Methods: This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta&#95;num) was also evaluated., Results: The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P  = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P  = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P  = 0.004). Before adjusting for the propensity score, the delta&#95;num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P  = 0.001); however, after adjustment, there was no difference in the delta&#95;num (thoracoscopy: 0.04, open: 0.19, P  = 0.114)., Conclusions: Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: New chemotherapeutic regimens (i.e. FOLFOX or FOLFIRI with molecular targeted drugs) have improved the prognosis of patients with unresectable or recurrent colorectal cancer. To estimate the prognostic impact of these chemotherapies, we examined the chronological change in survival rates of patients who underwent pulmonary metastasectomy for colorectal cancer metastasis., Methods: Using a large database, we conducted a retrospective, multi-institutional study to collect data of 1223 eligible patients from 26 institutions who had undergone pulmonary metastasectomy with curative intent. We divided those patients who underwent metastasectomy in different time periods according to the major trend of chemotherapy regimens for recurrent colorectal cancer: those who underwent metastasectomy between 1990 and 1999 ( N  = 451, Group A), between 2000 and 2004 ( N  = 433, Group B) or between 2005 and 2007 ( N  = 339, Group C)., Results: Five-year overall survival rates after metastasectomy were 45% in Group A, 56% in Group B and 66% in Group C ( P  < 0.0001) whereas rates after metastasectomy plus chemotherapy were 32% in Group A, 47% in Group B and 70% in Group C ( P  = 0.0059). The prognosis of patients who underwent both metastasectomy and chemotherapy in Group C was significantly better than that of the other two groups. Overall survival of patients who did not receive chemotherapy was not significantly different between the groups., Conclusion: Survival rates of patients after pulmonary metastasectomy for colorectal cancer metastasis who underwent chemotherapy have increased over the years. It implies that newer chemotherapy regimens might have had a positive impact on these patients., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group was organized in 1986. Initially, 26 collaborative institutions participated. In the early period, the Lung Cancer Surgical Study Group focused on combined modality therapies and conducted nine trials, including JCOG9101: adjuvant chemotherapy for resected small-cell lung cancer, and JCOG9806: induction chemoradiotherapy followed by surgery for superior sulcus tumor, which greatly impacted the treatment strategies for some special kinds of lung cancer. Since the 2000s, the Lung Cancer Surgical Study Group has defined radiologically noninvasive adenocarcinoma: JCOG0201 and investigated adequate modes of surgical resection for small-sized non-small cell lung cancer: JCOG0802, JCOG0804 and JCOG1211. The accrual of these trials is now complete and we are waiting for the maturation of follow-up data. In addition, two adjuvant trials have been conducted: JCOG0707; a Phase III study of adjuvant chemotherapy for resected pathological stage I (T1 > 2 cm) non-small cell lung cancer, and JCOG1205; a Phase III study of adjuvant chemotherapy for completely resected pulmonary high-grade neuroendocrine tumor. The accrual of JCOG0707 is complete and we are waiting for the maturation of follow-up data. At present, 44 institutions are active members of the Lung Cancer Surgical Study Group. In addition to thoracic surgeons, medical oncologists, pathologists and radiotherapists are participating in the Lung Cancer Surgical Study Group. The Lung Cancer Surgical Study Group continues to conduct various clinical trials in an effort to improve survival in patients with lung cancer. In this review, we provide an overview of the past 30 years, as well as the present status and future direction of the Lung Cancer Surgical Study Group., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established., (© The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Since 'radical lobectomy' was reported by Cahan in 1960, the standard surgical care for lung cancer has been lobectomy, in which units of the lobe are excised with their specific regional hilar and mediastinal lymphatics. However, pulmonary function-preserving limited resection for lung cancer has gradually become more prevalent in the late 20th century. In 1995, Ginsberg et al. conducted a randomized controlled trial in which limited resection (segmentectomy and wide-wedge resection) and lobectomy for stage I lung cancer were compared and reported that limited resection should not be applied to healthy patients with clinical stage IA lung cancer. The detection of small-sized and early-stage lung cancers has improved with advancement in diagnostic technology. Ground-glass opacity of lung nodules, as recognized on thin-slice computed tomography, has also been widely recognized as being correlated with less-invasive pathological findings of alveolar epithelial cell replacement of cancer cells. The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group conducted a cohort study of early peripheral lung cancer and investigated the validity thin-slice computed tomography criteria to diagnose non-invasive lung adenocarcinoma for the preoperative prediction of pathological non-invasive cancer. Following this observational study, the on-going JCOG0802/WJOG4607L, JCOG0804/WJOG4507L and JCOG1211 trials were initiated to confirm the validity of limited resection for stage I lung cancer patients stratified according to preoperative thin-slice computed tomography findings; these trials will clarify whether limited resection for lung cancer is not function-preserving but also only curative surgery., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: No randomized controlled trials comparing stereotactic body radiotherapy and lobectomy for operable early-stage non-small-cell lung cancer have been successfully conducted. This study compared survival outcomes in two multi-institutional clinical trials for stereotactic body radiotherapy (Japan Clinical Oncology Group JCOG0403) and lobectomy (Japan Clinical Oncology Group JCOG0201) with propensity score analysis., Methods: Inclusion criteria were operable, cT1N0M0 and adenocarcinoma diagnosed prior to registration of each trial. Forty of 169 patients from JCOG0403 and 219 of 811 patients from JCOG0201 were included. The primary endpoint was overall survival adjusted with propensity score analysis. The patient selection factors included in the logistic model to estimate the propensity score were age, sex, tumor diameter and consolidation/tumor ratio., Results: Among patient selection factors, age distribution was quite different with little overlap: the median was 79 (interquartile range: 74.5-83.5) in stereotactic body radiotherapy and 62 (interquartile range: 55-68) in lobectomy. In propensity score analysis, 21 patients from each group were matched and the hazard ratio for stereotactic body radiotherapy over lobectomy was 9.00 (95% confidence interval: 1.14-71.04). In the post hoc subgroup analysis with propensity score analysis of inverse probability of treatment weighting, patients were limited to be aged 75 or younger because JCOG0201 only included them when aged 75 or younger. Thirteen patients for stereotactic body radiotherapy and 219 for lobectomy were compared, and the hazard ratio for stereotactic body radiotherapy over lobectomy was 1.19 (95% confidence interval: 0.38-3.73)., Conclusions: The point estimates of hazard ratio favored lobectomy over stereotactic body radiotherapy in the limited number of patients. A randomized controlled study is needed for valid comparison., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Thymic carcinoma is a rare thymic malignancy. The purpose of this study was to evaluate the prognostic impact of clinicopathological variables and perioperative therapy for surgically treated thymic carcinoma using a nationwide database., Methods: Of 2835 patients with surgically treated thymic epithelial tumours collected from 32 Japanese institutions, a total of 306 patients with thymic carcinomas, excluding neuroendocrine tumours, were enrolled in this retrospective study. Multivariable Cox regression analyses were performed for overall (OS) and recurrence-free survival (RFS) after R0 resection., Results: Of 306 patients, 228 (75%) patients presented with Masaoka stage III-IV. Squamous cell carcinoma was the most common histological type (n = 216, 71%). R0 resection was performed in 181 (61%) patients, R1 in 46 (16%), R2 sub-total (≥80% tumour resection) in 43 (14%) and R2 non-resection in 27 (9%). The 5-year OS rate was 61%. Prognostic factors for OS were Masaoka stage and resection status. R0 resection was associated with most improved OS; however, both R1 and R2 sub-total resection resulted in superior OS compared with R2 non-resection [hazard ratio (95% confidence interval) for R0, R1 and R2 sub-total, 0.27 (0.15-0.48), 0.40 (0.22-0.74) and 0.38 (0.20-0.72), respectively]. Histological type and perioperative therapy did not affect OS, whereas tumour size and postoperative radiotherapy were associated with improved RFS after R0 resection., Conclusions: R0 resection is essential for prolonged OS for surgically treated thymic carcinoma, but maximal debulking surgery might be beneficial and worth evaluating for advanced disease deemed difficult for R0 resection. The benefit of postoperative radiotherapy after R0 resection should also be evaluated prospectively., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Peripheral small lung tumours (LTs) showing ground-glass opacity (GGO) tend to be treated without preoperative histological diagnosis due to difficulty in obtaining tissue samples. Exclusion of non-neoplastic lesions (NNLs) is essential when considering non-surgical treatment such as stereotactic radiotherapy. Here, we sought to determine preoperative factors associated with NNLs in peripheral LTs using data from a prospective study that investigated the efficacy of lesser pulmonary resection (JCOG0804/WJOG4507L)., Methods: The key eligibility criteria of the study were as follows: (i) peripherally located definitive or suspected LC with maximum diameter ≤2 cm and (ii) radiological non-invasive tumour with consolidation/tumour ratio (CTR) of ≤0.25 based on thin-section computed tomography (CT). Among all the resected LTs, incidences of NNL and precancerous lesions were examined. Also, logistic regression analysis was conducted to investigate the predictors of NNL using maximum tumour dimension (≤1 cm/>1 cm) and CTR (0/>0) as an explanatory variable., Results: Between May 2009 and April 2011, 333 patients were prospectively enrolled from 51 institutions into the study. Among 333 patients, 345 LTs were included in the analysis. There were 314 (91.0%) LCs, 17 (4.9%) precancerous lesions and 14 (4.1%) non-cancerous lesions. Maximum tumour dimension ≤1 cm was identified as a significant predictor of NNLs with logistic regression analysis. There were 10 (8.6%) NNLs in 116 LT ≤1 cm, but 4 (1.7%) NNLs in 229 LTs >1 cm., Conclusions: NNLs were found in only 4.1% of peripheral LTs with GGO. However, when the tumour diameter was ≤1 cm, ∼10% were NNLs, necessitating a histological diagnosis when non-surgical treatment was considered., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Several clinical studies have demonstrated the efficacy and safety of adjuvant chemotherapy in patients with completely resected small cell lung cancer for a selected limited stage. However, it is unclear whether adjuvant chemotherapy is feasible in clinical practice. The objective of this study was to analyze the efficacy and safety of adjuvant chemotherapy for small cell lung cancer patients retrospectively in clinical practice., Methods: From January 2002 to March 2012, 56 small cell lung cancer patients underwent surgery as initial therapy in our institute. Of these, 26 patients received adjuvant chemotherapy. The clinical data of patients who received adjuvant chemotherapy were retrospectively analyzed., Results: The chemotherapy regimens were cisplatin and irinotecan in 16 patients, cisplatin and etoposide in 1 and carboplatin and etoposide in 9. Median follow-up time was 44.8 months. Nineteen (73%) patients received the full course of chemotherapy. Median recurrence-free survival was 21.4 months. Median survival time was not reached. There was no treatment-related death., Conclusion: Adjuvant chemotherapy may be generally safe and efficacious in selected small cell lung cancer patients., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

A randomized Phase III trial commenced in Japan in March 2013. Post-operative adjuvant chemotherapy with etoposide plus cisplatin is the current standard treatment for resected pulmonary high-grade neuroendocrine carcinoma including small cell lung cancer and large cell neuroendocrine carcinoma. The purpose of this study is to confirm the superiority of irinotecan plus cisplatin in terms of overall survival over etoposide plus cisplatin as post-operative adjuvant chemotherapy for pathological Stage I-IIIA completely resected pulmonary high-grade neuroendocrine carcinoma patients. A total of 220 patients will be accrued from 54 Japanese institutions within 6 years. The primary endpoint is overall survival and the secondary endpoints are relapse-free survival, proportion of treatment completion, adverse events, serious adverse events and second malignancy. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000010298 [http://www.umin.ac.jp/ctr/index.htm].

Objectives: This study intended to assess the clinicopathological features of the histological subtypes of adenocarcinoma of the lung in a large registry population., Methods: The Japanese Joint Committee of Lung Cancer Registry performed a nationwide retrospective registry study on the prognosis and clinicopathological profiles of 11 663 patients who underwent resection for primary lung neoplasm in 2004. The registry data of 7921 (62.5%) patients with adenocarcinoma were analysed regarding the prognosis and clinicopathological features according to the histological subtype of adenocarcinoma. The histological subtypes were defined according to the 1999 World Health Organization classification (third edition), where bronchioloalveolar carcinoma (BAC) is defined as adenocarcinoma with a pure bronchioloalveolar growth pattern without invasion., Results: The distribution of the histological subtype was acinar in 471 patients (7.5%), papillary in 2004 (32.2%), BAC in 1385 (22.3%), solid adenocarcinoma with mucin in 103 (1.7%) and adenocarcinoma with mixed subtypes (AMS) in 2257 (36.3%). The 5-year overall survival rates according to histological subtype were 63.4% for acinar, 72.9% for papillary, 90.3% for BAC, 54.4% for solid adenocarcinoma with mucin and 73.7% for AMS. While the survival rate in patients with BAC was significantly better than those for the other histological subtypes, acinar and solid adenocarcinoma with mucin had significantly worse prognoses than the other histological subtypes. The histological subtype was an independent predictor of survival in a multivariate analysis (P < 0.001). Regarding BAC, the pathological stage included not only Stage IA/IB (n = 1275; 92.1%), but also Stage II-IV (n = 110; 7.9%). One hundred twenty-five patients (9.0%) with BAC had recurrence, including both local and distant recurrence., Conclusions: The histological subtype in adenocarcinoma significantly correlated with the prognosis. In BACs with recurrence or pathological stage II-IV, these tumours might have been classified as invasive adenocarcinoma rather than as BAC. The need for the rigorous pathological evaluation of adenocarcinomas that are considered to be a preinvasive or minimally invasive tumour should be addressed in the new lung adenocarcinoma classification to be proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society.

Objective: This study aimed to verify the prognostic impact of pleural invasion according to the revised TNM classification, seventh edition., Methods: The study consisted of 1488 patients with surgically resected non-small cell carcinoma. The degree (pl0-3) and location of pleural invasion were examined using hematoxylin and eosin- and elastica van Gieson-stained slides, and outcome was compared with stratification by several clinicopathological factors., Results: The 5-year overall survival rates of 1008, 260, 85 and 135 patients with pl0, pl1, pl2 and pl3 tumours were 80, 60, 55 and 52%, respectively. Overall survival differed significantly between patients with pl0 tumours and those with pl1 tumours (P < 0.0001). The difference was significant for patients with 1<≤ 2 cm (P = 0.004), 2<≤ 3 cm (P = 0.003) and 3<≤ 5 cm (P = 0.02) tumours. The overall survival of pl0 patients was also significantly better in patients with adenocarcinoma (P < 0.0001) than squamous cell carcinoma (P = 0.043). The overall survival of pl0 patients was significantly better in patients without lymph node metastasis (P < 0.0001) than in those with lymph node metastasis. The 5-year overall survival rates of patients with interlobar, lateral, mediastinal and diaphragmatic pl3 tumours were 65, 51, 51 and 40%, respectively. Overall survival did not differ significantly among these four groups., Conclusions: Outcome differs between patients with pl0 tumours and those with pl1-3 tumours, particularly among patients with 1<≤ 2 cm, 2 <≤ 3 cm and 3<≤ 5 cm tumours, adenocarcinoma histology and no lymph node metastasis. The location of pl3 pleural invasion did not affect outcome significantly.

A Phase III study was started in Japan to evaluate the non-inferiority in overall survival of segmentectomy compared with lobectomy in patients with small-sized (diameter

Background: Costal coaptation pins made of hydroxyapatite and poly-l-lactide (HA/PLLA) composite are used to prevent slippage of the connected ribs in posterolateral thoracotomy. The objective of this study was to evaluate rib fixation achieved by HA/PLLA costal coaptation pins., Methods: Between September 2005 and January 2006, HA/PLLA costal coaptation pins were used in 106 consecutive patients who underwent posterolateral thoracotomy at the National Cancer Center Hospital, Tokyo, Japan. Among these, 96 patients who were followed for one year were analyzed. Fixation was assessed on chest X-ray at one week, two months, and one year after surgery, and classified into four types: no displacement, vertical displacement, lateral displacement, and combined vertical with lateral displacement., Results: The incidence of displacement at one week, two months, and one year after surgery was 22%, 19%, and 31%, respectively. No severe adverse events leading to the removal of HA/PLLA pins occurred. At one year, the most frequent type of displacement was vertical displacement (15%), which reflected a delay in bone formation. The use of analgesics among patients with different types of displacement was not significantly different (p=0.97)., Conclusions: Based on the results of this study, the fixation of cut ribs with HA/PLLA costal coaptation pins may be less advantageous in posterolateral thoracotomy, as displacement and delay of bone formation appear to occur frequently.

Background: High-resolution computed tomography (HRCT) of lung adenocarcinoma at early stage shows pure ground-glass opacity (GGO) and most cases of pure GGO remain stable during follow-up. There is no consensus on the strategy for follow-up. Identification of the molecular mechanisms that are associated with the natural history of lung adenocarcinoma should provide useful information., Methods: Twenty-three lung adenocarcinomas that were followed-up for more than 6 months pre-operatively by HRCT were included in this study. Patterns of radiological changes during the follow-up period were classified into three groups; type 1, pure GGO without consolidation; type 2, appearance or increase in consolidation within pure GGO; type 3, consolidation without pure GGO. Mutational analysis of the epidermal growth factor receptor (EGFR) and K-ras genes and immunohistochemical staining of p53 protein were performed., Results: EGFR mutations were found in 17 cases (74%), and there was no K-ras mutation. Positive staining of p53 was found in 8 cases (35%). As for radiological findings during the follow-up period, the frequencies of EGFR mutations and positive p53 staining were 67 and 0% in type 1 (n = 9), 89 and 44% in type 2 (n = 9) and 60 and 80% in type 3 (n = 5)., Conclusions: EGFR mutations were frequently found in lung adenocarcinoma with GGO on HRCT in this study. Inactivation of p53 may be associated with the appearance of central consolidation within pure GGO on HRCT which reflects invasive features and may be useful as a molecular marker during the follow-up of pure GGO.

A new strategy for selective nodal dissection in non-small cell lung cancer (NSCLC) patients according to the segment of primary tumor was explored. Data on 504 patients with NSCLC of less than 5 cm, histologically revealed to be N2 disease after thoracotomy, were analyzed. In right upper lobe (RUL) tumor, when the pretracheal node was negative, the incidence of subcarinal involvement was 3.8%. In lower lobe tumor, superior segment (RLL-Superior and LLL-Superior) tumor showed a significantly higher incidence of superior mediastinal involvement than basal segment (RLL-Basal and LLL-Basal) tumor (right, P=0.0036; left, P=0.0499). When the subcarinal node was negative, the incidence of superior mediastinal metastasis in RLL-basal and LLL-Basal tumor was 11% and 8%, respectively. In left upper lobe tumor, superior segment (LUL-Superior) tumor showed a significantly lower incidence of subcarinal involvement than lingular segment (LUL-Lingular) tumor (P=0.0381). When aortic nodes were negative in LUL-Superior tumor, the incidence of subcarinal metastasis was 6%. Collectively, in RUL and LUL-Superior tumors, subcarinal dissection may be unnecessary if superior mediastinal node is negative. In RLL-Superior and LLL-Superior tumors, extensive dissection is required. In RLL-Basal and LLL-Basal tumors, superior mediastinal dissection may be unnecessary if subcarinal node is negative.

Background: Primary mediastinal malignant germ cell tumors (GCTs) are rare and have a worse prognosis than their gonadal counterparts. Although multimodality treatment is a standard therapeutic strategy in mediastinal GCTs, the clinical implications of surgical intervention remain unclear., Methods: Forty-eight patients with primary mediastinal malignant GCT who were treated at the National Cancer Center Hospital, Tokyo, from 1962 to 2002 were studied retrospectively with regard to their histology and clinical profile., Results: Mediastinal GCT occurred predominantly in young males, with a mean age of 28.8 years at the time of diagnosis. There were 46 males (96%) and two females (4%). Histologically, seven patients (15%) were diagnosed as having pure seminoma and 41 (85%) had non-seminomatous GCT. Treatment consisted of surgery alone in nine patients, surgery followed by chemotherapy in two, and chemotherapy followed by surgery in 20. The other 17 patients received chemotherapy and/or radiotherapy without surgery. Of these latter 17 patients, 14 developed progressive disease and three were followed up with a sustained partial response. Among the 31 patients who underwent surgery, complete resection was performed in 27 (87%) and incomplete resection was performed in four (13%). Twelve (41%) patients had elevated serum tumor marker levels preoperatively. Among the 20 patients who received preoperative chemotherapy, viable cells were found in the resected specimen in six (30%). With regard to tumor recurrence in patients with surgical intervention, the preoperative serum tumor marker levels and the presence of viable cells in the resected specimen were significantly associated with recurrence. There was no significant association between surgical curability and recurrence. The 5-year overall survival rate in all 48 patients was 45.5%., Conclusions: Surgical intervention for mediastinal GCT may be needed to remove a chemotherapy-refractory tumor or to assess the pathological response to chemotherapy to determine the indications for further chemotherapy.

Despite the wide use of the Masaoka staging system for thymoma, the distribution of survival by stage group is not well balanced. The new staging systems for testing were defined as follows: stage I was created by merging Masaoka's stages I and II, and stage IV remained unchanged. Stages II and III were defined as thymomas with invasive growth and the following combinations of tumor diameter and number of involved structures/organs. Scheme 1: stage II included tumors less than 10 cm in diameter and involving one neighboring structure/organ. Stage III included tumors with all combinations of diameter and number of involved structures/organs other than those in stage II. Scheme 2: stage II included tumors of all combinations other than those in stage III. Stage III included tumors 10 cm or more in diameter and involving two or more structures/organs. The survival curves were assessed for 138 patients treated at the National Cancer Center, Tokyo. The 10-year survival rates for each stage according to the Masaoka, Scheme 1, and Scheme 2 systems were as follows: stage I (100%, 100%, 100%), stage II (100%, 86%, 83%), stage III (70%, 64%, 34%), and stage IV (34%, 34%, 34%), respectively. The survival curves for Scheme 1 gave the most balanced distribution of survival in each staging group. By considering both tumor diameter and number of involved structures/organs, Masaoka's stages I-III could be rearranged with more balanced distribution of survival.

Objective: Inflammatory myofibroblastic tumor (IMT) is a rare disease that usually occurs in the lung. Recently, several reports have suggested that IMT is a true neoplasm rather than a reactive lesion. In this retrospective study, we reviewed clinicopathological characteristics and prognoses for all patients with surgically resected IMT of the lung at our institute., Methods: From January 1985 to December 2002, nine patients had surgical intervention for IMT of the lung at the National Cancer Center Hospital, Tokyo. The resected lesions were studied histologically, immunohistochemically, and ultrastructurally. Follow-up was complete in all patients and varied from 3 months to 16 years 2 months (median, 6 years 2 months)., Results: These nine patients included five men and four women. They ranged in age from 25 to 66 years. Seven patients were asymptomatic. The two symptomatic patients had problems including cough, hemoptysis, and dyspnea. For all these patients, the diagnostic procedure was surgical excision. The resected tumor size ranged from 1.0 to 4.0 cm in diameter. Histologically, a variety of inflammatory and spindle cells were observed. The spindle cells corresponded ultrastructurally to myofibroblasts or fibroblasts. With the exception of one patient who had spontaneous resolution of a recurrent tumor, there was no recurrence in these patients, and all of them are in good health., Conclusions: Histopathologically, IMT is characterized by myofibroblasts that are mixed with chronic inflammatory cells, including plasma cells, lymphocytes, and histiocytes. Surgical resection, when possible, can be chosen as the treatment. Complete resection leads to excellent survival.

Background: There is little information available regarding the relative advantage of stapling over ligation for major pulmonary vessels in lung resection. The thin and fragile structure of pulmonary vascular walls for their large luminal size might have made surgeons reluctant to use staplers. This study was intended to demonstrate the feasibility of pulmonary vascular division by staplers., Methods: A total of 842 mechanical vascular divisions were performed for pulmonary artery (PA, n=376), pulmonary vein (PV, n=462), and azygos vein (AV, n=4) in 603 consecutive pulmonary resections from 1997 to 1999 at the National Cancer Center Hospital, Tokyo. In this series, 99.8% of mechanical vascular divisions were performed with endostaplers (840 vessels), and only 0.2% was performed with conventional TA-type staplers (two vessels). The prevalence of problems related to mechanical stapling (stapling failure) and postoperative bleeding was studied retrospectively., Results: There was only one incidence of stapling failure, in which the superior pulmonary vein was divided without the formation of staples (overall stapling failure rate, 0.1%). The bleeding was controlled by ligation of each divided stump during thoracotomy. There was no stapling failure for PAs or AVs. In no case did postoperative bleeding require rethoracotomy at the stapled line of the vessels., Conclusions: Although temporary oozing was sometimes seen along the staple line, vascular division with endostaplers was highly reliable with only a 0.1% incidence of stapling failure for all kinds of vascular structures in the thorax.

Invasion into the lumen of the main pulmonary artery is an uncommon mode of extension in lung carcinoma and its prognostic significance remains unclear. We describe here two resected cases of lung carcinoma that showed such a rare tumor spread. Although a preoperative evaluation, such as angiography or perfusion scan of the lung, had shown a significant decrease in circulation, we could not diagnose the intraluminal tumor growth preoperatively. Pneumonectomy was finally needed to perform a curative operation. The tumors were centrally located and showed polypoid growth in the main pulmonary artery. Postoperative pathological examination revealed the tumors to be adenosquamous carcinoma of the lung in both cases. No intrapulmonary metastases were detected. One patient is doing well with no signs of recurrence after a follow-up period of 10 years. Although intra-arterial polypoid growth of lung carcinoma is extremely rare, such tumor extension should be considered preoperatively to perform a curative surgical resection, especially when the tumor is centrally located. While arterial invasion is generally an ominous prognostic factor, curative surgical resection would offer a good prognosis, even for lung carcinoma invading the main pulmonary arterial trunk.

A case of hemangioma of the left seventh rib is presented. In January 1999, a 59-year-old woman presented with an enlarged costal mass which had been followed up for 4 years. Preoperative examination suggested chondrosarcoma because of tumor growth beyond the disrupted bony cortex. She underwent resection of the left seventh rib along with the sixth and seventh intercostal muscles and reconstruction of the chest wall defect. The pathological diagnosis of the lesion was hemangioma. She was discharged after an uneventful postoperative course. There has been no evidence of recurrence after a 14-month follow-up. Tumor growth beyond the disrupted bony cortex was a characteristic feature by both imagery and pathological examination in this case. This case represents a difficulty of a preoperative definite diagnosis of the chest wall tumors by imagery alone.

Objective: The method used to achieve bronchial closure, especially the relative merits of sutured versus stapled closure, remains an important topic among thoracic surgeons who seek the best way to prevent postoperative bronchopleural fistula (BPF) formation., Methods: Bronchial closure in 533 consecutive stumps in pulmonary resection from 1995 to 1997 at the National Cancer Center Hospital, Tokyo, was reviewed in terms of the incidence of troubles related to mechanical stapling (stapling failure) and to BPF formation. Fifty stumps (9%) were closed by manual suturing and 483 (91%) by mechanical stapling. For stapling, endostaplers were used for 313 stumps (65%), and other types of conventional staplers for 170 stumps (35%)., Results: There were 18 stapling failures (a 3.7% overall incidence, 4.8% for endostaplers, 1.8% for other types of staplers). However, of these 18 patients only one developed BPF after surgery. Seven BPFs developed postoperatively among the 533 closures (overall incidence, 1.3%): two after manual suturing (4%) and five after stapling (1%), and this difference was not statistically significant. Of seven patients with BPF, four died of BPF-related complications., Conclusions: Although bronchial closure by stapling was accompanied by failure, its incidence was acceptable and was not directly associated with the development of BPF postoperatively, as long as properly repaired. Newly developed endostaplers had similar incidence of stapling failure and BPF formation compared with other types of conventional staplers. These results suggest endostaplers can be used safely for various types of bronchial closure. The advantage of such devices could be the least chance of pollution of the operative field, simultaneous performance of stapling and division by one motion, and subsequently great saving of time.

Objectives: Systematic lymph node dissection in radical operation for lung cancer is recognized as an operative procedure which is expected to improve local control. We investigate the most effective method of lymph node dissection or sampling., Methods: A retrospectrive study was carried out on 1815 patients who underwent systematic lymph node dissection and complete resection. The lymphatic route of metastatis from each lobe was investigated by examining which nodes had the most likelihood of metastasis, or to find out which is the sentinel lymph node in the case of small sized tumor, suitable for the video assisted thoracic surgery (VATS) approach., Results: At N2 level, distribution of major metastases from each lobe are as follows: right upper lobe tumor, #3 - 12.3% (80/648) and/or #4 - 8% (52/648); right middle lobe tumor, #3 and/or #7 - 16.4% (13/79); right lower lobe tumor, #7 - 13.7% (52/380); left upper lobe tumor, #5 - 12.3% (60/489) and/or #6 - 6.7% (33/489); and left lower lobe tumor, #7 - 11.9% (26/219). Small sized tumor requires lymph node sampling upon staging, and the lymph node most likely to become the first metastasis, i.e. sentinel node, are as follows: regardless of the location of tumor, #12, #11, and/or #10 in N1 level, which means dissection or sampling within these locations of lymph nodes are prerequisite. In N2 level, #3 and/or #4 in right upper lobe tumor, #3 and/or #7 in right middle lobe tumor, #7 in right lower lobe tumor, #5 and/or #6 in left upper lobe tumor, and, #7 in left lower lobe tumor., Conclusions: In clinical T1NO lung cancer, sentinel lymph node sampling should be done first, if the nodes are negative, complete mediastinal lymph node dissection might be omitted. On the other hand, if the sentinel nodes are positive for pathology, complete medistinal lymph node dissection is required for curative resection.

We report a case of primary lung cancer in a 16-year-old boy. A histologic diagnosis of squamous cell carcinoma was made by bronchoscopic biopsy before surgery. The serum alphafetoprotein (AFP) level was markedly elevated at 193 ng/dl. Preoperative and postoperative evaluation revealed no evidence of scrotal mass. We performed right pneumonectomy with combined resection of the invaded portion of the left atrium under extracorporeal circulation. Despite the rapid improvement in the patient's general condition after surgery, the AFP level continued to increase without a transient decrease and reached 3160 ng/ml on the 23rd postoperative day. When the patient was readmitted because of dyspnea and headache on the 36th postoperative day, hypercalcemia of 13.9 mg/dl was noted, and this was resistant to subsequent treatment. The patient died on the 46th postoperative day.

A case of ovarian carcinoma which has been followed up for more than 28 years after the initial ovarian resection is reported. A 50-year-old woman came forward with a metastatic esophageal tumor 16 years after a salpingo-oophorectomy for ovarian carcinoma. After irradiation with a dose of 3090 cGy, an esophagectomy and a partial resection of the directly invaded pericardium was successfully performed. Ten years later, progressive dyspnea due to a total collapse of the right lung developed. The right main stem bronchus was almost occluded by an endobronchial tumor, contiguous with the recurrent mass at the previous resectional margin. A right pneumonectomy and a combined resection of the pericardium and left atrium were performed. The patient has been followed up for further two years, and no signs of recurrence are evident. In spite of distant thoracic involvement and its local regrowth, the patient has survived for 28 years following her initial resection with surgical interventions.

A case of hepatocellular carcinoma (HCC) with tumor thrombi in the vein in the major omentum is reported. A 54-year-old man underwent a second operation for recurrent HCC. Intraoperative ultrasonography revealed a tumor thrombus in the vein of the adhering omentum. Part of the antero-inferior area of the liver adjacent to the tumor was resected with the major omentum. Since it is characteristic of HCC often to form tumor thrombi in the veins, it is not surprising that the tumor budded into the epiploic vein. This is apparently the first report of tumor thrombi of HCC in the epiploic vein.