Suitable Patient Selection and Optimal Timing of Treatment for Persistent Air Leak after Lung Resection.

OBJECTIVES: The choice of therapeutic intervention for postoperative air leak varies between institutions. We aimed to identify the optimal timing and patient criteria for therapeutic intervention in cases of postoperative air leaks after lung resection. METHODS: This study utilized data from a prospective multicenter observational study conducted in 2019. Among the 2187 cases in the database, 420 cases with air leaks on postoperative day 1 were identified. The intervention group underwent therapeutic interventions, such as pleurodesis or surgery, while the observation group was monitored without intervention. A comparison between the intervention group and the observation group were analyzed using the cumulative distribution and hazard functions. RESULTS: Forty-six patients (11.0%) were included in the intervention group. The multivariate analysis revealed that low body mass index (p = 0.019), partial resection (p = 0.010), intraoperative use of fibrin glue (p = 0.008), severe air leak on postoperative day 1 (p < 0.001), and high forced expiratory volume in 1 s (p = 0.021) were significant predictors of the requirement for intervention. The proportion of patients with persistent air leak in the observation group was 20% on postoperative day 5 and 94% on postoperative day 7. The hazard of air leak cessation peaked from postoperative day 3 to postoperative day 7. CONCLUSIONS: This research contributes valuable insights into predicting therapeutic interventions for postoperative air leaks and identifies scenarios where spontaneous cessation is probable. A validation through prospective studies is warranted to affirm these findings.

Favourable surgical outcomes for either second primary lung cancer or intrapulmonary metastasis after resection of non-small-cell lung cancer.

OBJECTIVES: Metachronous lung cancer arising after resection of non-small-cell lung cancer is either a second primary lung cancer (SPLC) or intrapulmonary metastasis (IPM) of the initial lung cancer; however, differential diagnosis is difficult. We evaluated the surgical outcomes of metachronous lung cancer in a combined population of patients with SPLC and IPM. METHODS: A retrospective study of 3534 consecutive patients with resected non-small-cell lung cancer between 1992 and 2016 was conducted at 4 institutions. RESULTS: A total of 105 patients (66 males; median age, 70 years) who underwent a second pulmonary resection for metachronous lung cancer were included. Most patients (81%) underwent sublobar resection, and there was no 30-day mortality. All metachronous lung cancers were cN0, 5 were pN1-2. The postoperative comprehensive histologic assessment revealed SPLC (n = 77) and IPM (n = 28). The 5-year overall survival rate after the second resection was 70.6% (median follow-up: 69.7 months). A multivariable analysis showed that age >70 years at the second resection (P = 0.013), male sex (P = 0.003), lymph node involvement in metachronous cancer (P < 0.001), pathological invasive size of metachronous cancer >15 mm (P < 0.001) and overlapping squamous cell carcinoma histology of the initial and metachronous cancers (P = 0.003) were significant prognostic factors for poor survival after the second resection, whereas histological IPM was not (P = 0.065). CONCLUSIONS: Surgery for cN0 metachronous lung cancer is safe and shows good outcomes. There were no statistically significant differences in the SPLC and IPM results. Caution should be exercised when operating on patients with overlapping squamous cell carcinoma.

Benefit of Adjuvant Chemotherapy for Patients Older Than 75 Years With Completely Resected p-Stage II-IIIA Non-Small-Cell Lung Cancer: A Retrospective Cohort Study Using Japanese Nationwide Real-World Data.

BACKGROUND: The efficacy of adjuvant chemotherapy (ACT) in elderly patients with completely resected p-stage II-IIIA non-small-cell lung cancer (NSCLC) remains unclear because all previous randomized controlled trials on ACT have been conducted among patients aged <75 years. Thus, this study aimed to evaluate the effectiveness of ACT in elderly patients with completely resected NSCLC. PATIENTS: We extracted the nationwide data of 812 patients aged ≥75 years who underwent lobectomy with mediastinal nodal dissection in 2010 and were diagnosed with p-stage II-IIIA NSCLC, from nationwide registry data accumulated in 2016. METHODS: We classified the 812 patients into 2 groups based on the ACT administration status and analyzed the differences in their postoperative overall survival (OS). RESULTS: Overall, 295 patients received ACT (36.3%; group A), whereas 517 patients did not (63.70%; group N). Group A showed significantly better OS as a whole (hazard ratio [HR]: 0.650 [95% confidence interval {CI}: 0.526-0.804]), in the p-stage II subset (HR: 0.688 [95% CI: 0.513-0.925]), and p-stage IIIA subset (HR: 0.547 [95% CI: 0.402-0.743]) than group N. Even after propensity score matching, group A showed significantly better OS as a whole (HR: 0.626 [95% CI: 0.495-0.792]), in the p-stage II subset (HR: 0.690 [95% CI: 0.493-0.964]), and p-stage IIIA subset (HR: 0.554 [95% CI: 0.398-0.772]) than group N. CONCLUSION: ACT is recommended even in elderly patients with completely resected p-stage II-IIIA NSCLC. Hence, physicians should not avoid ACT in patients with completely resected NSCLC based solely on age.

Nationwide prospective registry database of patients with newly diagnosed untreated pleural mesothelioma in Japan.

Due to the scarcity of large-sized prospective databases, the Japanese Joint Committee for Lung Cancer Registry conducted a nationwide prospective registry for newly diagnosed and untreated pleural mesothelioma. All new cases diagnosed pathologically as any subtype of pleural mesothelioma in Japan during the period between April 1, 2017, to March 31, 2019, were included before treatment. Data on survival were collected in April 2021. The eligible 346 patients (285 men [82.3%]; 61 women [17.7%]; median age, 71.0 years [range, 44-88]) were included for analysis. Among these patients, 138 (39.9%) underwent surgery, 164 (47.4%) underwent non-surgical therapy, and the remaining 44 (12.7%) underwent best supportive care. The median overall survival for all 346 patients was 19.0 months. Survival rates at 1, 2, and 3 years for all patients were, 62.8%, 42.3%, and 26.5%, respectively. Median overall survival was significantly different among patients undergoing surgery, non-surgical treatment, and best supportive care (32.2 months vs. 14.0 months vs. 3.8 months, p < 0.001). The median overall survival of patients undergoing pleurectomy/decortication and extrapleural pneumonectomy was 41.8 months and 25.0 months, respectively. Macroscopic complete resection resulted in longer overall survival than R2 resection and partial pleurectomy/exploratory thoracotomy (41.8 months vs. 32.2 months vs. 16.8 months, p < 0.001). Tumor shape, maximum tumor thickness, and sum of three level thickness were significant prognostic factors. The data in the prospective database would serve as a valuable reference for clinical practice and further studies for pleural mesothelioma.

High density and proximity of CD8+ T cells to tumor cells are correlated with better response to nivolumab treatment in metastatic pleural mesothelioma.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. METHODS: A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD-L1 positive cells, cell density, and cell-to-cell distance were analyzed by multiplex immunofluorescence. RESULTS: PD-L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. CONCLUSIONS: High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.

Malignant pleural mesothelioma in situ.

Although the diagnosis of malignant pleural mesothelioma at an in situ stage was traditionally challenging, it is now possible owing to advances in molecular biological methods such as P16 fluorescence in situ hybridization or BRCA1-associated protein 1 immunohistochemistry. Here, we report the first case, to our knowledge, of total parietal pleurectomy for mesothelioma in situ. Future follow-up and accumulation of cases are necessary to determine whether total parietal pleurectomy could be applied as a treatment for mesothelioma in situ or not.

Impact of the first surge of the coronavirus disease pandemic on general thoracic surgery practices in Kanagawa: a questionnaire survey by the Kanagawa General Thoracic Surgical Study Group.

OBJECTIVES: The first surge in severe acute respiratory syndrome coronavirus 2 infection had a significant impact on health care institutions. Understanding how the pandemic affected general thoracic surgery would provide valuable data for establishing a health care protocol for upcoming surges. METHODS: A questionnaire survey on coronavirus disease-related patient statistics and health care was conducted between February 2020 and June 2020 across 14 facilities affiliated with the Kanagawa General Thoracic Surgery Study Group. RESULTS: The average number of newly referred patients from February to June 2020 was 65% of that during the same period in 2019. Six facilities placed restrictions on medical care services, among which four restricted surgeries. At all institutions and those placed on surgical restriction, the total number of surgeries under general anesthesia was 92% and 78%, the total number of primary lung cancers was 94% and 86%, and the total number of surgeries for pneumothorax was 71% and 77% of that in the preceding year, respectively. Infection control and insufficient resources of the medical material were the most influential factors impacting the medical institutions' decision to restrict the services provided. CONCLUSIONS: Restrictions on surgery had a significant impact on the care provided by general thoracic surgery departments. To avoid patient inconvenience, establishing a collaborative system that refers patients to operational medical institutions in case of medical treatment restrictions may be useful.

A prophylaxis study of acute exacerbation of interstitial pneumonia after lung cancer surgery.

INTRODUCTION: Acute exacerbation of interstitial pneumonia (AE-IP) is a lethal complication after lung surgery. We conducted a prospective, multi-institutional phase II trial to assess the efficacy and safety of prophylactic measures. METHOD: Patients with lung cancer with dorsal subpleural fibrotic changes occupying three or more segments of both lower lobes and planned anatomical lung resection were enrolled. Prior to surgery, patients received a 125-mg bolus injection of methylprednisolone and continuous intravenous infusion of sivelestat sodium hydrate (sivelestat) for 2 days. RESULTS: Sixty-nine patients were analysed. Preoperative high-resolution computed tomography (HRCT) showed 37 (53.6%) cases presented with usual interstitial pneumonia (UIP) and possible UIP pattern. There were 60 lobectomies and 9 segmentectomies. Thirty-eight cases were in clinical stage I. No adverse events associated with prophylaxis were observed. There were four cases of AE-IP (5.8%), higher than the expected 2.0%. Three of the four cases showed inconsistencies with the UIP pattern in preoperative HRCT and were pathologically diagnosed as UIP. All patients died of respiratory failure. Overall, 89.9% were diagnosed as idiopathic interstitial pneumonias; UIP was found in 48 patients (69.6%). Severe post-operative complications occurred in 11.6% of the cases. There were 35 deaths, 17 cases of lung cancer and 11 cases related to interstitial pneumonias. The overall survival rate at 3 years was 41.8% of the total and 47.2% of cases with clinical stage I. CONCLUSIONS: Perioperative use of sivelestat and low-dose methylprednisolone in patients with anatomical lung resection was safe but did not prove to be a prophylactic effect for AE-IP.

Prospective registry database of patients with malignant mesothelioma: directions for a future Japanese registry-based lung cancer study.

BACKGROUND: The International Association for the Study of Lung Cancer, in collaboration with members of the International Mesothelioma Interest Group (IMIG), developed a large international database and TNM-based system to study malignant pleural mesothelioma (MPM). However, this database has some limitations since it was a retrospective study and it was based predominantly on surgical cases. The Japanese Joint Committee of Lung Cancer Registry (JJCLCR) employs a project of prospective registry database of patients in Japan with MPM in order to clarify MPM's epidemiology, current management practices, and prognosis and also to investigate the potential capabilities to target the best patients for therapy. METHODS: Tumor stage is described using the 7th and 8th versions of IMIG staging system. This prospective cohort study has been conducted from April 1, 2017 to March 31, 2019. DISCUSSION: We will analyze the data in this registry to determine the most recent outcomes and trends related to MPM treatment in Japan. The present prospective study is expected to validate the 8th version of IMIG staging system, and to investigate whether tumor thickness is a reliable T-descriptor. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: UMIN 000024664.

HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.

The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.

Thoracoscopic lobectomy for lung cancer in a patient with a partial anomalous pulmonary venous connection: a case report.

BACKGROUND: A partial anomalous pulmonary venous connection is a rare congenital defect in which blood from the pulmonary vein is returned to the right atrium. Asymptomatic patients with a partial anomalous pulmonary venous connection with a small left-to-right shunt do not require surgical treatment. If such patients require a major lung resection, the surgical procedure could precipitate fetal right heart failure if the anomalous venous connection remains uncorrected. CASE PRESENTATION: A 59-year-old man was found to have an abnormal shadow on chest roentgenogram. Chest computed tomography imaging showed a mass in the right upper lobe. At the same time, we incidentally found an anomalous vessel. We diagnosed the abnormality as a partial anomalous pulmonary venous connection. Because the mass may have been lung cancer, a right upper lobectomy was performed using video-assisted thoracoscopic surgery. The right upper lobe vein drained into the superior vena cava. The anomaly was not corrected and the surgery was successful. His postoperative course was uneventful without cardiac failure. CONCLUSIONS: Before performing a major lung resection, surgeons should be aware of this rare anomaly and carefully interpret clinical images of all pulmonary veins.

Influence of visceral pleural invasion on survival in completely resected non-small-cell lung cancer.

OBJECTIVES: Although the prognostic implications of visceral pleural invasion (VPI) are well established, it remains controversial whether the extent of VPI affects survival in patients with completely resected non-small-cell lung cancer (NSCLC). In addition, the impact of VPI according to nodal status is unclear. We evaluated the influence of the extent of pleural invasion on survival by analysing a multicentre retrospective database of patients who had undergone surgery for NSCLC. METHODS: We retrospectively reviewed the clinicopathological characteristics and outcomes of 639 patients with NSCLC who underwent anatomic complete resection from 2005 to 2007 at nine hospitals affiliated with the Yokohama Consortium of Thoracic Surgeons. RESULTS: The median follow-up was 65.0 months. The extent of pleural invasion was PL0 in 462 patients, PL1 in 135 and PL2 in 42. The 5-year overall survival rate was significantly higher in patients with PL0 tumours (75.9%) than in those with PL1 (63.6%) or PL2 tumours (54.1%). On subgroup analysis according to nodal status, PL0 was associated with a higher survival rate than that of PL1 or PL2 tumours in patients with N0 or N1 metastasis, but not in those with N2 metastasis. There was no difference between PL1 and PL2 in any subgroup. CONCLUSIONS: Our results suggest that the presence of VPI, rather than the extent, has an impact on postoperative survival in patients with NSCLC who have N0 or N1 metastasis. Because very few previous studies have addressed the effects of VPI in patients with N1 disease, further re-evaluation of the prognostic impact of VPI is necessary in this subgroup of patients.

[Three cases of pulmonary hamartoma appearing after radical nephrectomy for renal cell carcinoma].

We report 3 patients with pulmonary hamartoma, all of whom had undergone nephrectomy for renal cell carcinoma. A lung tumor was detected 2 to 9-months following nephrectomy. Preoperative diagnosis was pulmonary metastasis from renal cell carcinoma and pulmonary tumor resection was performed in each case. There was a 9- to 12-month interval between the detection and resection of the lung tumor. The histological diagnosis of the lung tumor in all three patient was pulmonary hamartoma. Following the resection of the lung tumor, recurrence was not noted in any of the patients.