Preoperatively Predicting Survival Outcome for Clinical Stage IA Pure-Solid Non-Small Cell Lung Cancer by Radiomics-based Machine Learning.

OBJECTIVE: Clinical stage IA non-small cell lung cancer (NSCLC) showing a pure-solid appearance on computed tomography (CT) is associated with a worse prognosis. This study aimed to develop and validate machine learning models using preoperative clinical and radiomic features to predict overall survival (OS) in clinical stage IA pure-solid NSCLC. METHODS: Patients who underwent lung resection for NSCLC between January 2012 and December 2020 were reviewed. The radiomic features were extracted from the intratumoral and peritumoral regions on CT. The machine learning models were developed using random survival forests (RSF) and XGBoost algorithms, while the Cox regression model was set as a benchmark. Model performance was assessed using the integrated time-dependent area under the curve (iAUC) and validated by 5-fold cross-validation. RESULTS: In total, 642 clinical stage IA pure-solid NSCLC patients were included. Among 3748 radiomic and 34 preoperative clinical features, 42 features were selected. Both machine learning models outperformed the Cox regression model (iAUC, 0.753 [95% CI: 0.629, 0.829]). The XGBoost model showed a better performance (iAUC, 0.832 [95% CI: 0.779, 0.880]) than the RSF model (iAUC, 0.795 [95% CI: 0.734, 0.856]). The XGBoost model showed an excellent survival stratification performance with a significant overall survival (OS) difference among the low-risk (5-year OS: 100.0%), moderate low-risk (5-year OS: 88.5%), moderate high-risk (5-year OS: 75.6%), and high-risk (5-year OS: 41.7%) groups (P < 0.0001). CONCLUSIONS: Radiomics-based machine learning model can preoperatively and accurately predict OS and improve survival stratification in clinical stage IA pure-solid NSCLC.

Usefulness of final transection of the proximal pulmonary artery in robotic left upper lobectomy.

OBJECTIVES: The pulmonary artery runs around the left upper bronchus, which poses the risk of blood vessel injury when cutting in the blind spot of the bronchus. During robotic surgery, the robotic arm holds the tissue under constant tension; therefore, even if the pulmonary artery is left for final transection, it is not injured by unexpected tension. In this study, we examined the usefulness of final transection of the proximal pulmonary artery in robotic left upper lobectomy. METHODS: This retrospective single-institution study evaluated patients who had undergone robotic lung resection. Of the 453 robotic lung resections performed at our institution between 2017 and 2022, 49 patients who had undergone left upper lobectomy were evaluated. Patients who had undergone bronchial transection followed by pulmonary artery transection were assigned to the group, bronchus prior transection (BT group, n = 38), and those who had undergone pulmonary artery transection followed by bronchial transection were assigned to the group, pulmonary artery prior transection (AT group, n = 11). Patient characteristics and perioperative outcomes were compared between the groups. RESULTS: The groups did not differ significantly in age, sex, smoking history, tumour size, complication rates or 30-day mortality. The BT group inclined to shorter operative times and lesser blood loss. No active intraoperative bleeding occurred in the BT group. However, the AT group had 2 cases of intraoperative pulmonary artery bleeding, one of which required urgent conversion to thoracotomy. CONCLUSIONS: Final transection of the proximal pulmonary artery is a novel and effective surgical technique for robotic left upper lobectomy.

Investigating the predictive factors of thoracic aortic invasion and surgical outcomes in patients with primary lung cancer: A retrospective study.

BACKGROUND: This study aimed to investigate predictors of thoracic aortic invasion in lung cancer patients using preoperative clinical and imaging characteristics and elucidate surgical outcomes in cases of aortic invasion. METHODS: Of the 4751 lung cancer patients who underwent surgery at our hospital, we included 126 (6.8%) who underwent left-sided surgery and in whom tumor appeared to be in contact with the thoracic aorta on preoperative imaging. The patients were divided into two groups: group A, 23 patients (18%) who underwent combined aortic resection (+); group B, 103 patients (82%) who did not undergo combined aortic resection (-). RESULTS: The percentage of aortic invasion for tumor diameter <3 cm, 3-4 cm, 4-5 cm, 5-7 cm, and >7 cm was 0%, 13%, 23%, 16%, and 35%, respectively. The percentages of aortic invasion were 27%, 16%, and 0% for tumor localization in the upper division, S6, and S10, respectively. Multivariate analysis revealed that aortic depression due to tumor or loss of fatty tissue between tumor and mediastinum in the chest CT significantly predicted aortic invasion (odds ratio = 23.83, 16.66). Group A demonstrated significantly more blood loss, longer operative time, prolonged hospital stay, and increased percentage of recurrent nerve palsy (13%) compared to group B. The 1-, 3-, and 5-year survival rates for patients in group A were 53.4%, 24.3%, and 24.3%, respectively. CONCLUSION: If the chest CT of a patient demonstrates aortic depression due to tumor or loss of fatty tissue between tumor and mediastinum, aortic complications should be considered when planning surgery.

Significance of preoperative exercise oxygen desaturation in lung cancer with interstitial lung disease.

OBJECTIVES: Evaluating the diffusing capacity for carbon monoxide (DLco) is crucial for patients with lung cancer and interstitial lung disease. However, the clinical significance of assessing exercise oxygen desaturation (EOD) remains unclear. METHODS: We retrospectively analysed 186 consecutive patients with interstitial lung disease who underwent lobectomy for non-small-cell lung cancer. EOD was assessed using the two-flight test (TFT), with TFT positivity defined as ≥5% SpO2 reduction. We investigated the impact of EOD and predicted postoperative (ppo)%DLco on postoperative complications and prognosis. RESULTS: A total of 106 (57%) patients were identified as TFT-positive, and 58 (31%) patients had ppo% DLco < 30%. Pulmonary complications were significantly more prevalent in TFT-positive patients than in TFT-negative patients (52% vs 19%, P < 0.001), and multivariable analysis revealed that TFT-positivity was an independent risk factor (odds ratio 3.46, 95% confidence interval 1.70-7.07, P < 0.001), whereas ppo%DLco was not (P = 0.09). In terms of long-term outcomes, both TFT positivity and ppo%DLco < 30% independently predicted overall survival. We divided the patients into 4 groups based on TFT positivity and ppo%DLco status. TFT-positive patients with ppo%DLco < 30% exhibited the significantly lowest 5-year overall survival among the 4 groups: ppo%DLco ≥ 30% and TFT-negative, 54.2%; ppo%DLco < 30% and TFT-negative, 68.8%; ppo%DLco ≥ 30% and TFT-positive, 38.1%; and ppo%DLco < 30% and TFT-positive, 16.7% (P = 0.001). CONCLUSIONS: Incorporating EOD evaluation was useful for predicting postoperative complications and survival outcomes in patients with lung cancer and interstitial lung disease.

Hyperprogressive disease under anti-PD-1 rechallenge after initial response to anti-PD-1 treatment for non-small cell lung cancer: a case report.

Background: Hyperprogressive disease is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis. The rechallenge of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors can be a treatment option in non-small cell lung cancer (NSCLC) patients who once responded to them. Here, we reported the hyperprogressive phenomenon after PD-1/PD-L1 rechallenge in a patient with NSCLC. Case Description: This case report described a patient with recurrent large cell lung cancer undergoing hyperprogressive disease with pleural and pericardial dissemination shortly after the pembrolizumab rechallenge, although he had a favorable response to the initial pembrolizumab treatment. A lower ratio of CD8+ T cells to Foxp3+ regulatory T cells was distributed in the cell blocks of pleural and pericardial effusion which were taken after hyperprogressive disease, compared to the resected tumor microenvironment. Neutrophil-to-lymphocyte ratio (NLR) was lower in peripheral blood when the disease was controlled and it rose when the disease progressed. Notably, NLR increased dramatically when hyperprogression occurred. Conclusions: For the first time, we reported that a patient who showed a favorable response to initial anti-PD-1 treatment underwent hyperprogressive disease when rechallenging the same immunotherapy. The increased Foxp3+ regulatory T cells in the tumor microenvironment and the longitudinal change of NLRs in peripheral blood were suggested to be associated with hyperprogressive disease.

Salvage extended surgery after immune-checkpoint inhibitor treatment for advanced non-small cell lung cancer.

PURPOSE: We evaluated the surgical outcomes of salvage extended surgery after definitive medical treatment with an immune-checkpoint inhibitor (ICI) for locally advanced or unresectable non-small-cell lung cancer (NSCLC). METHODS: The subjects of this single-center retrospective analysis were 14 patients who underwent salvage surgery after ICI treatment between May, 2017 and April, 2023 at our institute. We reviewed the comprehensive surgical outcomes, including operative procedures, intraoperative findings, and postoperative morbidities. Overall survival (OS) was calculated using a Kaplan-Meier estimation. RESULTS: The initial clinical stage before medical treatment (c-stage) was stage III in eight patients, stage IV in five patients, and one patient had postoperative lung cancer recurrence. The indications for surgery were as follows: local control for relapse or residual tumor in ten patients and discontinuation of systemic therapy because of treatment-related complications in four patients. The surgical modes were segmentectomy (n = 1), lobectomy (n = 4), bilobectomy (n = 3), pneumonectomy (n = 6), and bronchoplasty (n = 7). Grade 3 or higher postoperative morbidities were observed in six patients, including only one case of 90-day mortality. CONCLUSIONS: Our series demonstrated that the surgical outcome of salvage extended surgery after ICI therapy may be positive with careful selection of the procedure and indication.

Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer with radiologically pure-solid appearance in Japan (JCOG0802/WJOG4607L): a post-hoc supplemental analysis of a multicentre, open-label, phase 3 trial.

BACKGROUND: Although segmentectomy was better than lobectomy in terms of overall survival for patients with non-small-cell lung cancer (NSCLC) with a pure-solid tumour appearance on thin-section CT in the open-label, multicentre, randomised, controlled, phase 3 JCOG0802/WJOG4607L trial, the reasons why segmentectomy was associated with better overall survival were unclear. We aimed to compare the survival, cause of death, and recurrence patterns after segmentectomy versus lobectomy in trial participants with NSCLC with a pure-solid appearance METHODS: We conducted a post-hoc supplemental analysis of the JCO0802/WJOG4607L randomised, controlled, non-inferiority trial for the patients (aged 20-85 years) with small-sized NSCLC with radiologically pure-solid appearance on thin-section CT (≤2 cm, consolidation tumour ratio 1·0). The primary aim was to compare the overall and relapse-free survival, cause of death, and recurrence patterns associated with segmentectomy and lobectomy for patients with radiologically pure-solid NSCLC to determine why the overall survival of segmentectomy was superior to that of lobectomy, even for oncologically invasive lung cancers. JCO0802/WJOG4607L is registered with the UMIN Clinical Trials Registry, UMIN000002317, and is complete. FINDINGS: Between Aug 10, 2009, and Oct 21, 2014, 1106 patients were randomly assigned to undergo either lobectomy or segmentectomy. Of these participants, 553 (50%) had radiologically pure-solid NSCLC and were eligible for this post-hoc supplemental analysis. Of these 553 participants, 274 (50%) patients underwent lobectomy and 279 (50%) underwent segmentectomy. Median patient age was 67 years (IQR 61-73), 347 (63%) of 553 patients were male and 206 (37%) were female, and data on race and ethnicity were not collected. As of data cutoff (June 13, 2020), after a median follow-up of 7·3 years (IQR 6·0-8·5), the 5-year overall survival rate was significantly higher after segmentectomy than after lobectomy (86·1% [95% CI 81·4-89·7] in the lobectomy group, with 55 deaths vs 92·4% [88·6-95·0] in the segmentectomy group, with 38 deaths; hazard ratio (HR) 0·64 [95% CI 0·41-0·97]; log-rank test p=0·033), whereas the 5-year relapse-free survival was similar between the groups (81·7% [95% CI 76·5-85·8], with 34 events vs 82·0% [76·9-86·0], with 52 events; HR 1·01 [95% CI 0·72-1·42]; p=0·94). Deaths after a median follow-up of 7·3 years due to lung cancer occurred in 20 (7%) of 274 patients after lobectomy and 19 (7%) of 279 after segmentectomy, and deaths due to other causes occurred in 35 (13%) patients after lobectomy compared with 19 (7%) after segmentectomy (lung cancer death vs other cause of death, p=0·19). The locoregional recurrence was higher after segmentectomy (21 [8%] vs 45 [16%]; p=0·0021). In subgroup analyses, better 5-year overall survival after segmentectomy than after lobectomy was observed in the subgroup of patients aged 70 years or older (77·1% [95% CI 68·2-83·8] with lobectomy vs 85·6% [77·5-90·9] with segmentectomy; p=0·013) and in male patients (80·5% [73·7-85·7] vs 92·1% [87·0-95·2]; p=0·0085). By contrast, better 5-year relapse-free survival after lobectomy than after segmentectomy was observed in the subgroup younger than 70 years (87·4% [95% CI 81·2-91·7] with lobectomy vs 84·4% [77·9-89·1] with segmentectomy; p=0·049) and in female patients (94·2% [87·6-97·4] vs 82·2% [73·2-88·4]; p=0·047). INTERPRETATION: This post-hoc analysis showed improved overall survival after segmentectomy in patients with pure-solid NSCLC compared with lobectomy. However, survival outcomes of segmentectomy depend on the patient's age and sex. Given the results of this exploratory analysis, further research is necessary to determine clinically relevant indications for segmentectomy in radiologically pure-solid NSCLC. FUNDING: Japanese National Cancer Center Research and Development Fund and Practical Research for Innovative Cancer Control Fund, and a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan.

Prognostic significance of preoperative exercise tolerance in patients with early-stage lung cancer.

OBJECTIVE: To investigate the influence of simple preoperative exercise tests as prognostic factors for early-stage lung cancer. METHODS: This single-institution retrospective study included consecutive patients who underwent pulmonary resection for stage 0 to I lung cancer between April 2017 and December 2019. Before surgery, 7 metabolic equivalents of task in the double Master 2-step test were loaded into the exercise echocardiogram. The relationship between prognosis and exercise stress test results in terms of availability, symptoms, and saturation of percutaneous oxygen was investigated. RESULTS: This study included 862 patients with pathological stage 0 to I lung cancer. Among the 862 patients, 673 patients (78.1%) who were able to complete 7 metabolic equivalents of task exercise for 3 minutes without assistance were classified into the complete group. The 5-year survival of the complete group was significantly better than that of the incomplete group. Multivariable analysis revealed that age (hazard ratio, 1.06; P = .008), male sex (hazard ratio, 2.23; P = .011), carcinoembryonic antigen level >5 ng/mL (hazard ratio, 2.33; P = .011), and inability to complete 7 metabolic equivalents of task exercise (hazard ratio, 3.90; P < .001) were the prognostic factors. Patients in the older group who had the ability to complete exercise had a better prognosis than those in the younger group without the ability (P = .003). CONCLUSIONS: Preoperative exercise ability is a prognostic factor for early-stage lung cancer. Patients who can tolerate an exercise load of 7 metabolic equivalents of task, even if they are aged 70 years or older, have a better prognosis than patients younger than age 70 years without exercise tolerance.

Postoperative management using a digital drainage system for massive air leakage after pulmonary resection.

PURPOSE: To elucidate clinical outcomes using a digital drainage system (DDS) for massive air leakage (MAL) after pulmonary resection. METHODS: A total of 135 consecutive patients with pulmonary resection air leakage of > 100 ml/min on the DDS were evaluated retrospectively. In this study, MAL was defined as ≥ 1000 ml/min on the DDS. We analyzed the clinical characteristics and surgical outcomes of patients with MAL compared with non-MAL (101-999 ml/min). Using the DDS data, the duration of the air leak was plotted with the Kaplan‒Meier method and compared using the log-rank test. RESULTS: MAL was detected in 19 (14%) patients. The proportions of heavy smokers (P = 0.04) and patients with emphysematous lung (P = 0.03) and interstitial lung disease (P < 0.01) were higher in the MAL group than in the non-MAL group. The MAL group had a higher persistence rate of air leakage at 120 h after surgery than the non-MAL group (P < 0.01) and required significantly more frequent pleurodesis (P < 0.01). Drainage failure occurred in 2 (11%) and 5 (4%) patients from the MAL and non-MAL groups, respectively. Neither reoperation nor 30-day surgical mortality was observed in patients with MAL. CONCLUSIONS: MAL was able to be treated conservatively without surgery using the DDS.

Rare but clinically important salivary gland-type tumor of the lung: A review.

Salivary gland-type tumor (SGT) of the lung, which arises from the bronchial glands of the tracheobronchial tree, was first recognized in the 1950s. SGT represents less than 1% of all lung tumors and is generally reported to have a good prognosis. Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are the two most common subtypes, comprising more than 90% of all SGTs. The reported 5-year survival rate of patients with SGT is 63.4%. Because this type of tumor develops in major bronchi, patients with SGT commonly present with symptoms of bronchial obstruction, including dyspnea, shortness of breath, wheezing, and coughing; thus, the tumor is usually identified at an early stage. Most patients are treated by lobectomy and pneumonectomy, but bronchoplasty or tracheoplasty is often needed to preserve respiratory function. Lymphadenectomy in the surgical resection of SGT is recommended, given that clinical benefit from lymphadenectomy has been reported in patients with MEC. For advanced tumors, appropriate therapy should be considered according to the subtype because of the varying clinicopathologic features. MEC, but not ACC, is less likely to be treated with radiation therapy because of its low response rate. Although previous researchers have learned much from studying SGT over the years, the diagnosis and treatment of SGT remains a complex and challenging problem for thoracic surgeons. In this article, we review the diagnosis, prognosis, and treatment (surgery, chemotherapy, and radiotherapy) of SGT, mainly focusing on MEC and ACC. We also summarize reports of adjuvant and definitive radiation therapy for ACC in the literature.

Sublobar resection is not always superior for early-stage lung cancer in high-risk patients.

OBJECTIVES: The phase III trial, Japan Clinical Oncology Group 0802, illustrated the superiority of sublobar resection for early-stage lung cancer in terms of overall survival, with more non-lung cancer-related deaths after a lobectomy. The advantages of sublobar resection may be more pronounced in high-risk patients. The goal of this study was to elucidate the prognoses of high-risk patients. METHODS: Patients with a risk of being ineligible for Japan Clinical Oncology Group 0802 for general conditions were classified as the high-risk group, and those who were not at risk of being ineligible were classified as the normal-risk group. Overall survival and prognostic factors were analysed in the high-risk group. RESULTS: There were 254 (19.4%) and 1054 patients in the high- and normal-risk groups, respectively. Five-year survival rates were 94.5% and 79.1% in the normal-risk and high-risk groups, respectively (P < 0.001). More patients in the high-risk group died of lung cancer (P < 0.001) and non-lung cancer deaths (P < 0.001) than patients in the normal-risk group.In the high-risk group, 151 lobectomies and 103 sublobar resections were performed. There was no significant difference in the numbers of lung cancer deaths and of non-lung cancer deaths between the procedures. Stratified survival analyses showed that the diffusing capacity of the lungs for carbon monoxide < 40% tended to favour sublobar resection; being female and having a high carcinoembryonic antigen level tended to favour a lobectomy. CONCLUSIONS: Sublobar resection is not always superior for early-stage lung cancer. Even in such cases, the surgical method should be determined by taking into consideration the patient's background and lung cancer surveillance.

Oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA lung adenocarcinoma with radiologically pure-solid appearance.

OBJECTIVES: We evaluated the clinicopathological and oncological characteristics of epidermal growth factor receptor-mutated clinical stage IA radiological pure-solid lung adenocarcinoma and compared them with those of a ground-glass opacity component. METHODS: Between 2008 and 2020, data from 1014 surgically resected clinical stage 0-IA epidermal growth factor receptor-mutated lung adenocarcinomas were evaluated. Oncological outcomes were assessed using multivariable analysis. Overall survival was estimated using Kaplan-Meier analysis and the log-rank test. The cumulative incidence of recurrence was estimated using the Gray's test. RESULTS: Of these, 233 (23%) were radiologically pure-solid tumors, which demonstrated a higher proportion of nodal metastasis, micropapillary component, spread through alveolar space, and Ex19 subtype compared with those of tumors with ground-glass opacity (P < .001). Multivariable analysis revealed that the presence of ground-glass opacity was an independently significant factor for overall survival (P = .037) and cumulative incidence of recurrence (P < .001). In cases where the oncological outcomes were stratified by the presence of ground-glass opacity component, the 5-year overall survival was excellent at more than 90% in tumors with ground-glass opacity despite clinical-T categories (P = .2044); however, tumor size significantly affected survival only in pure-solid tumors (T1a, 100%; T1b, 77.7%; T1c, 68.5%; P = .0056). Furthermore, the cumulative incidence of recurrence was low in tumors with ground-glass opacity despite the clinical-T categories, whereas tumor size significantly affected the cumulative incidence of recurrence only in pure-solid tumors (5-year cumulative incidence of recurrence: T1a-b, 18.9%; T1c, 41.3%; P < .001). CONCLUSIONS: Oncologic behavior and prognosis of radiologically pure-solid tumors were significantly poorer than those of tumors with ground-glass opacity among patients with epidermal growth factor receptor-mutated early-stage lung adenocarcinoma. These findings imply distinct tumorigenesis based on the presence of ground-glass opacity, even in tumors with epidermal growth factor receptor mutations.

Risk factors for loss of pulmonary function after wedge resection for peripheral ground-glass opacity dominant lung cancer.

OBJECTIVES: This study aimed to identify the risk factors for pulmonary functional deterioration after wedge resection for early-stage lung cancer with ground-glass opacity, which remain unclear, particularly in low-risk patients. METHODS: We analysed 237 patients who underwent wedge resection for peripheral early-stage lung cancer in JCOG0804/WJOG4507L, a phase III, single-arm confirmatory trial. The changes in forced expiratory volume in 1 s were calculated pre- and postoperatively, and a cutoff value of -10%, the previously reported reduction rate after lobectomy, was used to divide the patients into 2 groups: the severely reduced group (≤-10%) and normal group (>-10%). These groups were compared to identify predictors for severe reduction. RESULTS: Thirty-seven (16%) patients experienced severe reduction. Lesions with a total tumour size ≥1 cm were significantly more frequent in the severely reduced group than in the normal group (89.2% vs 71.5%; P = 0.024). A total tumour size of ≥1 cm [odds ratio (OR), 3.287; 95% confidence interval (CI), 1.114-9.699: P = 0.031] and pleural indentation (OR, 2.474; 95% CI, 1.039-5.890: P = 0.041) were significant predictive factors in the univariable analysis. In the multivariable analysis, pleural indentation (OR, 2.667; 95% CI, 1.082-6.574; P = 0.033) was an independent predictive factor, whereas smoking status and total tumour size were marginally significant. CONCLUSIONS: Of the low-risk patients who underwent pulmonary wedge resection for early-stage lung cancer, 16% experienced severe reduction in pulmonary function. Pleural indentation may be a risk factor for severely reduced pulmonary function in pulmonary wedge resection.

Lymph node dissection in small peripheral lung cancer: Supplemental analysis of JCOG0802/WJOG4607L.

OBJECTIVE: The optimal region of lymph node dissection (LND) during segmentectomy in patients with small peripheral non-small cell lung cancer requires clarification. Through a supplemental analysis of the Japan Clinical Oncology Group (JCOG) 0802/West Japan Oncology Group (WJOG) 4607L, we investigated the associated factors, distribution, and recurrence pattern of lymph node metastases (LNMs) and proposed the optimal LND region. METHODS: Of the 1106 patients included in the JCOG0802/WJOG4607L, 1056 patients with LNDs were included in this supplemental analysis. We investigated the distribution and recurrence pattern of LNMs along with the radiologic findings (with ground-glass opacity, part-solid tumor; without ground-grass opacity component, pure-solid tumor). RESULTS: The radiologic findings were the only significant factor for LNMs. Of 533 patients with part-solid tumors, 8 (1.5%) had LNMs. Further, only 3 (0.5%) patients had pN2 disease, and no patients had interlobar LNMs from nonadjacent segments. Of the 523 patients with pure-solid tumors, 55 (10.5%) had LNMs, and 28 (5.4%) had pN2 disease. Five patients had metastases to nonadjacent interlobar lymph nodes (LNs). Two (2.0%) patients with S6 tumors had upper mediastinal LNMs. In addition, the incidence of mediastinal LN recurrence in patients with S6 lung cancer was greater in those who underwent selective LND than those who underwent systematic LND (P = .0455). CONCLUSIONS: Nonadjacent interlobar and mediastinal LND have little impact on pathologic nodal staging in patients with part-solid tumors. In contrast, selective LND is recommended at least for patients with pure-solid tumors.

Risk factors for bronchopleural fistula based on surgical procedure and sex in 4794 consecutive patients undergoing anatomical pulmonary resection.

PURPOSE: Bronchopleural fistula (BPF) is a lethal complication, even in the modern era. Therefore, we investigated the details of patients with BPF to select an appropriate surgical strategy. METHODS: This retrospective study included 4794 consecutive patients who underwent anatomical pulmonary resection between 2008 and 2022. We evaluated the predictors of BPF using a multivariable analysis and investigated the mortality and clinical course after BPF in detail. RESULTS: BPF was observed in 32 patients (0.67%). In the multivariable analysis, the predictors for BPF were male sex (odds ratio [OR], 6.91), the body mass index (OR, 2.40), the vital capacity (%VC) (OR, 2.93), surgery performed (right lower lobectomy [OR, 10.92], right middle and lower lobectomy [OR, 6.97], and right pneumonectomy [OR, 16.68]), and additional resection of surrounding organs (OR, 3.47). Among the risk factors, surgery performed and male sex were very strong risk factors, with the frequency itself very low in females (0.1%). The 90-day mortality was 15.6%, and the 5-year overall survival in patients with BPF was 28.1%. CONCLUSION: Our study revealed that independent risk factors and consideration of the surgical methods and sex might help determine whether or not special attention should be given to the bronchial stump, which will be of great help in surgical strategies.

Oncologic outcomes of segmentectomy versus lobectomy for clinical T1c radiological pure-solid non-small-cell lung cancer.

OBJECTIVES: We aimed to compare the outcomes of segmentectomy with those of lobectomy in T1c (>2-3 cm) radiological pure-solid non-small-cell lung cancer detected on thin-section computed tomography. METHODS: This retrospective review compared the survival outcomes, causes of death and recurrence patterns between the segmentectomy and lobectomy in patients with c-T1cN0M0 radiological pure-solid non-small-cell lung cancer. Multivariable analysis was performed to control for confounders of survival. The overall survival (OS) and recurrence-free survival were analysed using the Kaplan-Meier method. Differences in cumulative incidence of recurrence between groups were assessed using the methods of Gray. RESULTS: Of the 426 patients, lobectomy was performed in 381 patients and segmentectomy in 45 patients. Nodal metastasis was noted in 104 (24.4%) patients. Multivariable analysis revealed that lobectomy was an independent prognosticator of better OS (hazard ratio 0.596, 95% confidence interval 0.366-0.969; P = 0.037). Lobectomy arm showed favourable 5-year OS and recurrence-free survival (OS: 72.9% vs 59.7%, log-rank test P = 0.007; recurrence-free survival: 64.4% vs 48.7%, P = 0.034) (median follow-up: 53 months). Approximately 14% of the patients in the lobectomy group and 27% in the segmentectomy group died of lung cancer. Furthermore, 5-year cumulative incidence of loco-regional recurrence rate was significantly higher in the segmentectomy group (35.5% vs 15.8%, P < 0.001). CONCLUSIONS: In T1c radiological pure-solid non-small-cell lung cancer, segmentectomy was significantly associated with worse survival and insufficient loco-regional cancer control. Lobectomy remains the standard surgical treatment; meanwhile, segmentectomy should be applied with great caution.

Stepwise progression of invasive mucinous adenocarcinoma based on radiological and biological characteristics.

INTRODUCTION: Invasive mucinous lung adenocarcinoma (IMA) has unique radiological findings and pathological characteristics. IMA is classified into solitary and pneumonic types; however, it is unclear whether these are biologically identical. METHODS: A single-center retrospective analysis was performed for 70 IMA patients (solitary type [n = 38] and pneumonic type [n = 32]) who underwent pulmonary resection between January 2010 and December 2018. We compared clinical and biological characteristics between the two types. RESULTS: The frequencies of genetic alternations such as EGFR, KRAS, BRAF, GNAS, ERBB2, TP53, NRG1, and MET were not different. Immunohistochemically, expression of MUC1 was significantly more common in the pneumonic type (5.0% versus 20.0%, p = 0.01) and diffuse MUC6 positive in the solitary type (39.0% versus 13.0%, p = 0.02). We further classified solitary types into those with or without ground-glass opacity (GGO) and pneumonic types into those with or without crazy-paving appearance (CPA), and evaluated their surgical outcomes. Five-year overall survival and relapse free survival rates were 95.8%/86.6%, 64.3%/70.7%, 74.6%/68.9%, and 50.0%/28.6% in patients with solitary type with GGO, solitary type without GGO, pneumonic type without CPA, and pneumonic type with CPA, respectively. CONCLUSIONS: There were no differences in genetic alternations; however, mucin expression pattern was different. Surgical outcomes were different according to the presence of GGO in the solitary type and the presence of CPA in the pneumonic type. These findings suggested a stepwise progression from solitary to pneumonic IMA.

A problem with clinical T factor in the 8th TNM edition: Prognosis and EGFR mutation status of small sized lung cancers with difficulty to measure the diameter of solid component in part-solid tumor.

OBJECTIVE: Clinical T factors in the 8th TNM classification of lung cancer have a practical problem. In some cases, it is difficult to measure the size of the solid components in part-solid tumors, and the classification of these tumors is controversial. METHODS: We evaluated 590 resected cT1N0M0 stage IA non-small-cell lung cancers based on the 7th edition between 2009 and 2012. Tumor and solid component diameters were measured using thin-section computed tomography (CT). We defined tumors with difficulty in measuring the size of the solid components as lung cancers with scattered or mixed consolidation (LCSMCs). LCSMCs were observed in 79 (13.4%) patients. Other tumors were classified as cTis, cT1mi, cT1a, cT1b, and cT1c, according to the 8th edition. We compared prognosis and epidermal growth factor receptor mutations (EGFRm) status of LCSMCs with those of cT1a, cT1b, and cT1c. RESULTS: The difference in overall survival (OS) among cT1a, cT1b, and cT1c was significant (5-year-OS: 96.9% vs. 76.8% vs. 65.0%). There was no significant difference in prognosis between LCSCs and cT1a (5-year-OS: 92.4% vs. 96.9%). A significant difference was observed in the frequency of EGFRm between cT1a, cT1b, and cT1c (52.4%, 42.4%, and 29.8%). The incidence of EGFRm in LCSMCs was 54.8% and there was no significant difference between LCSMCs and cT1a. CONCLUSIONS: The prognosis and frequency of EGFRm in LCSMCs were close to those in cT1a. As we cannot measure the diameter of the solid component in subsolid lung cancers, it may be appropriate to classify these tumors as cT1a tumors.

Predictive factors inhibiting recovery of the respiratory function after anatomical pulmonary resection.

PURPOSE: Some patients have worse actual observed postoperative (apo) respiratory function values than predicted postoperative (ppo) values. The present study therefore clarified the predictive factors that hinder the recovery of the postoperative respiratory function. METHODS: This study enrolled 255 patients who underwent anatomical pulmonary resection for lung cancer. A pulmonary function test (PFT) was carried out before surgery and at one, three, and six months after surgery. In each surgical procedures, the forced expiratory volume in 1 s (FEV1) ratio was calculated as the apo value divided by the ppo value. In addition, we investigated the predictive factors that inhibited postoperative respiratory function improvement in patients with an FEV1 ratio < 1.0 at 6 months after surgery. RESULTS: The FEV1 ratio gradually improved over time in all surgical procedures. However, 49 of 196 patients who underwent a PFT at 6 months after surgery had an FEV1 ratio < 1.0. In a multivariate analysis, right side, upper lobe, segmentectomy and pleurodesis for prolonged air leakage were independent significant predictors of a decreased FEV1 ratio (p = 0.003, 0.006, 0.001, and 0.009, respectively). CONCLUSION: Pleurodesis was the only controllable factor that might help preserve the postoperative respiratory function. Thus, the intraoperative management of air leakage is important.

Problems and countermeasures for surgical resection of primary pulmonary artery intimal sarcoma.

Background: Pulmonary artery intimal sarcoma (PAIS) is a rare but aggressive malignancy. This study clarified the problems and countermeasures of surgical treatment by examining surgical cases of PAIS. Methods: Between January 2007 and October 2020, 10 patients with PAIS who underwent surgery at our hospital were retrospectively examined. Results: The surgical procedure that aimed at complete resection was pulmonary resection only (three cases), along with pulmonary artery vascular replacement (six cases) and pulmonary endarterectomy (PE) (one case). The positive rate of vascular stumps was 7/10. In all cases, chest computed tomography scan showed positive margins of ≤20 mm between the tumor and surgical dissection (6/6). In addition, the distance between the location of the tumor on computed tomography and the dissection line during surgery needed to be at least 20 mm (2/3). However, even at a distance of 25 mm, one case with a positive margin was observed. Postoperative recurrence was 8/9 cases, and the median recurrence period was as short as 10 months (range, 3-19 months). Postoperative treatment was required in 7/9 cases (operation/chemotherapy/radiotherapy/chemoradiotherapy/heavy ion radiotherapy =1/2/2/1/1). The median survival was 15 months (range, 0.5-36 months). Conclusions: Extended surgery should be performed as much as possible, with a distance of at least 20 mm between the location of the tumor on computed tomography scan and the incision line during surgery. The median postoperative recurrence period was as short as 10 months. Therefore, intensive care for intrathoracic recurrence follow-up is required for 1 year after surgery.