Association between recovery from desaturation after stair climbing and postoperative complications in lung resection.

OBJECTIVE: The stair-climbing test (SCT) is used as a surrogate for cardiopulmonary exercise testing, which measures maximal oxygen uptake, and considered a useful method for assessing exercise capacity in thoracic surgery. This study aims to investigate whether the recovery time of percutaneous oxygen saturation (SpO2) after stair climbing is a predictor of postoperative complications after lobectomy. METHODS: We retrospectively identified 54 patients who performed SCT and underwent lobectomy between January 2015 and February 2023 at Shizuoka Cancer Center. The SpO2 recovery time was defined as the time required to recover from the minimum to resting value after stair climbing. The association between SpO2 recovery time and early postoperative pulmonary complications within 30 days after surgery was analyzed. RESULTS: Eleven patients (20.4%) had postoperative pulmonary complications (≥ Clavien-Dindo Classification Grade 2). The cutoff value of SpO2 recovery time obtained from the receiver operating characteristic curve analysis was 90 s [sensitivity, 81.8%; specificity, 72.1%; AUC, 0.77 (95% confidence interval, 0.64-0.90)]. The occurrence of postoperative pulmonary complications was 42.9% in the delayed recovery time (DRT; SpO2 recovery time ≥ 90 s) group and 6.1% in the non-DRT (SpO2 recovery time < 90 s) group (p = 0.002). DRT was a predictor of postoperative pulmonary complications (odds ratio, 11.60; 95% CI 2.19-61.80). CONCLUSIONS: DRT of SpO2 after stair climbing is a predictor of postoperative pulmonary complications following lobectomy in borderline patients who require exercise capacity assessment. SpO2 monitoring after stair climbing may be useful as one of the preoperative assessments in patients undergoing lobectomy.

Prediction of Pleural Lavage Cytology According to Thin-Section Computed Tomography in Non-Small-Cell Lung Cancer.

BACKGROUND: Although the positive rate of preresection pleural lavage cytology (PLC) is low, it is an important indicator of poor prognosis for non-small-cell lung cancer patients with frequent pleural dissemination (PD) recurrence. Thin-section computed tomography (TSCT) can reveal relationships between a primary tumor and the pleura at 1 to 2 mm intervals, and this is associated with visceral pleural invasion (VPI). However, its association with PLC remains unclear. Therefore, we aimed to improve PLC efficiency and predict PD recurrence by understanding the relationship between PLC and preoperative TSCT findings. PATIENTS AND METHODS: Between January 2014 and December 2018, we reviewed 978 patients with non-small-cell lung cancer who underwent PLC tests during complete resection surgery. Preoperative TSCT findings were evaluated, and factors with the highest specificity (proportion of patients with radiologically to pathologically diagnosed positive PLC) were investigated. We also evaluated their relationships with VPI and PD recurrence. RESULTS: PLC positive was identified in 55 (5.6%) of the 978 patients. The two TSCT findings predicting PLC results, "the absence of pleural findings," ie, tumor not attached to pleura or without pleural tag, and "consolidation-to-tumor ratio ≤0.5", had a specificity of 100% (95% confidence interval: 90.4%-100%); additionally, all cases with these findings were VPI negative and had no PD recurrence. And 24% of the cohort had either of these findings. CONCLUSION: The absence of pleural findings and/or consolidation-to-tumor ratio ≤0.5 of primary tumor on preoperative TSCT can predict PLC negativity with very high probability; therefore, PLC can be omitted for such patients.

Brain Metastasis of Non-small Cell Lung Cancer After Disease-Free Survival of 5 years: Case Series and Comprehensive Literature Review.

BACKGROUND: In the treatment of nonsmall cell lung cancer (NSCLC), a disease-free survival of 5 years is a criterion for cure. This study aimed to evaluate the characteristics and outcomes of patients with brain metastases of NSCLC after a disease-free survival of 5 years (late recurrent brain metastasis [LRBM]). METHODS: We reviewed 1281 consecutive patients with brain metastasis of lung cancer at a single institute between November 2014 and December 2022. Relevant articles were retrieved from PubMed. Only peer-reviewed journals published in English were included. RESULTS: Six patients (0.47%) showed LRBM. Three were male. The median age at lung cancer diagnosis was 45 years. The histological diagnosis of all patients was adenocarcinoma. Driver gene mutations were observed in five patients. The median latency period from lung cancer treatment to the development of brain metastasis was 13 years. All patients had no metastasis to any other organs and underwent craniotomies. The median follow-up duration after craniotomy was 3.5 years. No local intracranial recurrences were observed. Three patients had distant intracranial recurrences at 7, 2, and 0.6 years after craniotomy. Five patients survived for 8, 4, 3, 2, and 0.3 years after craniotomy. One patient experienced re-recurrence in the lung 4 years after craniotomy and died 3.7 years later. In our systematic review, only six studies described LRBM of NSCLC. CONCLUSIONS: LRBM is rare in patients with NSCLC. In our institution, many of these patients harbored driver gene mutations, and achieved long-term survival with aggressive local therapy. Multicenter analysis is mandatory.

Intraoperative rapid diagnosis of pleural lavage cytology in non-small cell lung cancer.

OBJECTIVE: Positive pleural lavage cytology (PLC +) is a poor prognostic factor for non-small cell lung cancer (NSCLC). However, data on the impact of intraoperative rapid diagnosis of PLC (rPLC) are lacking. Therefore, we evaluated the efficacy of rPLC before resection during surgery. METHODS: A total of 1,838 patients who underwent rPLC for NSCLC between September 2002 and December 2014 were studied retrospectively. We assessed the clinicopathological factors between rPLC findings and the impact on survival of patients with curative resection. RESULTS: The rPLC + status was observed in 96 (5.3%) among 1,838 patients. The rPLC + group had more unsuspected N2 (30%) than the rPLC- group (p < 0.001). The 5-year overall survival (OS) of patients who underwent lobectomy or more extensive resection with rPLC + , negative rPLC (rPLC-), and microscopic pleural dissemination (PD) and/or malignant pleural effusion (PE) were 67.3, 81.3, and 11.0%, respectively. In the rPLC + group, the prognosis of patients with pN2 was equal to that of pN0-1 (5-year OS: 77.9% vs. 63.4%, p = 0.263). Undetectable dissemination in the first evaluation immediately after starting surgery was found in 9% of rPLC + patients by additional evaluation of the thoracic cavity. CONCLUSIONS: Patients with rPLC + have more favorable survival than those with microscopic PD/PE after surgery. Curative resection should be performed in patients with rPLC + , even if N2 is detected during surgery. However, the rPLC + group often has N2 upstaging; therefore, systematic nodal dissection should be performed in rPLC + patients for exact staging. rPLC may contribute to preventing oversight PD by re-evaluation during surgery.

Long term outcomes beyond 5 years after pulmonary resection for non-small-cell lung cancer.

OBJECTIVES: We investigated the incidence of late recurrence beyond 5 years after pulmonary resection and aimed to identify candidates for long-term surveillance. METHODS: We retrospectively reviewed the medical records of 978 non-small-cell lung cancer patients who underwent pulmonary resection between 2002 and 2015 and survived without recurrence for 5 years. Clinicopathological factors associated with recurrence-free survival beyond 5 years after surgery were investigated using univariate and multivariate analyses. The development of late metachronous malignancies was also investigated. RESULTS: The median follow-up period from 5 years post-surgery was 27 months in the whole cohort. Late recurrence occurred in 37 (3.8%) patients. Late metachronous malignancies were diagnosed in 116 patients (11.9%), including 57 (5.8%) with lung cancer. One-, three-, and five-year recurrence-free survival rates beyond 5 years after surgery were 97.6%, 94.7%, and 94.7%, respectively. The recurrence-free survival of patients with pN1-2 was significantly poorer than that of patients with pN0 disease. Multivariate analysis revealed that adenocarcinoma and pN1-2 status were significantly associated with poor recurrence-free survival beyond 5 years post-surgery (P = 0.009 and 0.007, respectively). CONCLUSIONS: Non-adenocarcinoma histology and pN0 status were significant favorable factors for recurrence-free survival beyond 5 years post-surgery. The efficacies of long-term surveillance for the detection of late recurrence were considered limited for these populations. Twelve percent of the patients experienced late metachronous malignancies after pulmonary resection.

Diagnostic sensitivity of solid volume measurement for pathological invasion in non-solid lung adenocarcinoma.

Background: In the current tumor-node-metastasis (TNM) classification, the clinical T descriptor is defined by solid size (SS) on a computed tomography (CT) slice and the pathological one is done by invasive size (IS) in microscopic evaluations. We sometimes experience discrepancies in diagnosis of both descriptors. A volume analyzing application enables semi-automatic measurement of three-dimensional (3D) parameters in cases where there are discrepancies in diagnosing tumors' solid size and IS. In this study, we aimed to evaluate the association between 3D parameters and pathological invasion in non-solid small-sized lung adenocarcinomas. Methods: We enrolled 246 consecutive patients who underwent pulmonary resection at Shizuoka Cancer Center. Patients with lung adenocarcinomas that were radiologically non-solid, node-negative and sized ≤3 cm were eligible. We used a volume analyzing application to retrospectively measure 3D parameters of max and mean Hounsfield units (HUs) and solid volume (SV). The cut-off value of these parameters for diagnosing invasive adenocarcinoma (IAD) was set by describing receiver operating characteristic (ROC) curves. The correlation of IAD with these parameters was compared to its correlation with the SS. This study was not registered. Results: Of 246 patients with adenocarcinoma, 183 (74.4%) had IADs. In multivariate analyses, the total size (TS) and SS were significantly associated with IAD (P=0.006, 0.001, respectively), whereas 3D parameters including SV were not (P=0.80). In radiological adenocarcinoma (2.1-3.0 cm), SV >300 mm3 diagnosed IAD with a higher sensitivity than that of the SS (0.93 and 0.83, respectively). Conclusions: TS >20 mm and SS >5 mm were well-correlated with IAD. SV measurement may complement the current computed tomographic diagnosis of IAD based on the SS (2.1-3.0 cm).

Pulmonary Vein Stump Thrombosis and Cerebral Infarction after Left Upper Lobectomy.

BACKGROUND: Pulmonary vein stump thrombosis may occur after left upper lobectomy (LUL) and is a potential risk factor for cerebral infarction. However, there are few reports on the role of pulmonary vein stump thrombosis in the development of cerebral infarction. We aimed to clarify the correlation between pulmonary vein stump thrombosis and cerebral infarction following LUL. METHODS: We evaluated 296 patients who underwent contrast-enhanced computed tomography (CT) after LUL for lung cancer at the Shizuoka Cancer Center Hospital in Shizuoka, Japan, between September 2002 and December 2015. The cerebral infarction in patients with pulmonary vein stump thrombosis was examined, and the risk factors for cerebral infarction were identified via a univariate analysis of the clinicopathological and surgical variables. RESULTS: Overall, 179 men and 117 women (median age: 68 years; range: 36-88 years) were included. The median observation period was 68 months. Pulmonary vein stump thrombosis occurred in 21 (7%) patients and cerebral infarction occurred in 15 (5%) patients. None of the 21 patients with pulmonary vein stump thrombosis developed cerebral infarction. Most cerebral infarctions (12/15) were diagnosed in the late phase (> 3 months). The pathological stage of cancer was found to be the only significant risk factor for cerebral infarction by the univariate analysis. CONCLUSION: Pulmonary vein stump thrombosis following LUL was not necessarily associated with cerebral infarction, including the late phase. A prospective observational study with contrast-enhanced chest CT would be required to investigate the risk factors for cerebral infarction in each phase of the postoperative period.

Survival outcome of upfront surgery for clinical single-station N2 non-small cell lung cancer.

BACKGROUND: Pathological N2 (pN2) non-small cell lung cancer (NSCLC) is diverse; its treatment depends on the clinical N (cN) status. We aimed to determine the efficacy of upfront surgery for cN2pN2 NSCLC. METHODS: The study included 43 cN2pN2 NSCLC patients who underwent upfront surgery at the Shizuoka Cancer Center between 2002 and 2017. Survival outcome, focusing on cN2 status, was retrospectively investigated. Mediastinal lymph nodes were pre-operatively evaluated using computed tomography and positron emission tomography. Surgical eligibility criteria included single-station cN2. N2 with N1 and skip N2 were defined as N2 with and without ipsilateral hilar lymph node metastasis, respectively. A platinum-doublet regimen was used for adjuvant chemotherapy. Survival curves were analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model. RESULTS: Clinical-skip N2 and cN2 with N1 cases included 22 and 21 patients, respectively. Twenty-three patients received adjuvant chemotherapy. The median follow-up duration was 73 months. Clinical-skip N2 had a significantly better 5-year recurrence-free survival (RFS) than cN2 with N1 (58.3 vs 28.6%, P = 0.038) and was an independent favorable RFS predictor. Recurrence within 18 months occurred in 71% of cN2 with N1 cases. Five-year overall survival and RFS rates in patients receiving adjuvant chemotherapy vs those without adjuvant chemotherapy were 82.2 vs 41.9% (P = 0.019) and 56.5 vs 28.0% (P = 0.049), respectively. CONCLUSIONS: Clinical-skip N2 had an excellent prognosis, and upfront surgery was acceptable. Conversely, upfront surgery followed by chemotherapy is not recommended for cN2 with N1 patients because of early recurrence.

The efficacy of a machine learning algorithm for assessing tumour components as a prognostic marker of surgically resected stage IA lung adenocarcinoma.

BACKGROUND: The importance of the stromal components in tumour progression has been discussed widely, but their prognostic role in small size tumours with lepidic components is not fully understood. Applying digital tissue image analysis to whole-slide imaging may enhance the accuracy and reproducibility of pathological assessment. This study aimed to evaluate the prognostic value of tumour components of lung adenocarcinoma by measuring the dimensions of the tumour consisting elements separately, using a machine learning algorithm. METHODS: Between September 2002 and December 2016, 317 patients with surgically resected, pathological stage IA adenocarcinoma with lepidic components were analysed. We assessed the whole tumour area, including the lepidic components, and measured the epithelium, collagen, elastin areas and alveolar air space. We analysed the prognostic impact of each tumour component. RESULTS: The dimensions of the epithelium and collagen areas were independent significant risk factors for recurrence-free survival (hazard ratio, 8.38; 95% confidence interval, 1.14-61.88; P = 0.037, and hazard ratio, 2.58; 95% confidence interval, 1.14-5.83; P = 0.022, respectively). According to the subgroup analysis when combining the epithelium and collagen areas as risk factors, patients with tumours consisting of both large epithelium and collagen areas showed significantly poor prognoses (P = 0.002). CONCLUSIONS: We assessed tumour components using a machine learning algorithm to stratify the post-operative prognosis of surgically resected stage IA adenocarcinomas. This method might guide the selection of patients with a high risk of recurrence.

Lobe-specific nodal dissection with intraoperative frozen section analysis for clinical stage-I non-small cell lung cancer: a validation study by propensity score matching.

OBJECTIVE: Lobe-specific nodal dissection (LND) is increasingly used for non-small cell lung cancer (NSCLC) in Japan; however, its treatment validity remains unclarified. Since 2013, LND has been used as a standard procedure for clinical stage-I (c-stage-I) NSCLC at our institution. We aimed to evaluate its validity using intraoperative frozen section analysis (FSA) for c-stage-I NSCLC. METHODS: The participants comprised patients with NSCLC who underwent LND between 2013 and 2016 (n = 307) or systematic nodal dissection (SND) between 2002 and 2013 (n = 367) for c-stage-I disease. FSA was routinely performed in LND to examine at least three stations. Outcomes were compared between the LND and SND groups. Patients in whom LND was converted to SND due to metastasis on FSA of the sampled lymph node were still categorized into the LND group, i.e., intention-to-treat analysis. The prognostic impact was compared using propensity score matching. RESULTS: The rate of conversion from LND to SND was 10.4%. Of the patients converted to SND, 12.5% had metastases outside the LND area. False-negative N2 results were detected in only 0.7% of the LND group patients after FSA. After matching, each group had 220 patients. There were no significant between-group differences in the lymph-node recurrence rate (7% vs. 6%), 5-year recurrence-free survival (80.1% vs. 79.0%), and overall survival (90.4% vs. 90.3%). CONCLUSIONS: LND with intraoperative FSA is a valid modality that could serve as a standard surgical procedure for c-stage-I NSCLC. Intraoperative FSA may lower the residual lymph-node metastasis risk in LND.

Chylothorax after pulmonary resection and lymph node dissection for primary lung cancer; retrospective observational study.

BACKGROUND: Pulmonary resection with mediastinal lymph node dissection for treating primary lung cancer could sometimes causes chylothorax as a postoperative complication. This study examined the validity of treatments for chylothorax in our hospital. METHODS: We evaluated 2019 patients who underwent lobectomy, bilobectomy, or pneumonectomy with mediastinal lymph node dissection for primary lung cancer at Shizuoka Cancer Center Hospital, Shizuoka, Japan, between September 2002 and March 2018. The diagnostic criteria for postoperative chylothorax were that the drainage from the pleural drain was evidently white and turbid, or the pleural effusion contained a triglyceride level of > 110 mg/dL. The clinical courses and treatments were retrospectively reviewed. RESULTS: Postoperative chylothorax occurred in 37 patients (1.8%), 20 men and 17 women, with a median age of 70 years (33-80). A low-fat diet was instituted to all patients; 35 cases improved with conservative treatment, and 2 cases required reoperation. Nine cases had a drainage volume ≥ 500 mL one day following the low-fat diet commencement, which was resolved with conservative treatment and decreased drainage was observed on the third day of treatment in seven of those cases. Two cases with excessive drainage of ≥ 1000 mL in one day and systemic symptoms associated with chyle loss needed surgery. CONCLUSIONS: Even when the daily drainage volume exceeds 500 mL following a low-fat diet, there were many cases that could be cured conservatively. The indication for surgery needs to be carefully considered.

Validity of surgical decision based on intraoperative frozen section diagnosis for unconfirmed pulmonary nodules with previous malignancy.

OBJECTIVES: The lung is a major target organ of metastasis in several cancers. To distinguish primary lung cancer from pulmonary metastases is a clinical challenge. Small pulmonary nodules (PNs) are frequently diagnosed by frozen section diagnosis (FSD) intraoperatively after resection. Intraoperative FSD is very important to determine the extent of subsequent surgical procedures. This study aimed to know the validity of surgical decision based on FSD for preoperatively unconfirmed PN with previous malignancy. METHODS: We retrospectively evaluated 96 patients with suspected malignant PN who underwent intraoperative FSD between 2018 and 2020. Intraoperative FSD, final diagnosis, and surgical procedure data were examined. RESULTS: Surgical procedure adequacy, based on FSD for preoperatively unconfirmed PN with previous malignancy, was 91% (88/96). The overall diagnostic accuracy of FSD was 83.3% (80/96). Discrepancy was noted in two cases (2.1%), and conclusive diagnosis could not be reached intraoperatively in 14 cases (14.6%). A second surgery was required in three patients and no additional excision for primary lung cancer was performed in three patients. Conversely, there were three cases of over-surgery, namely, lobectomy for pulmonary metastasis. CONCLUSIONS: Surgical decision-making based on FSD for preoperatively unconfirmed PN in patients with previous malignancy was generally adequate. However, there were inadequate or excessive surgical procedures due to limitations in the accuracy of intraoperative FSD. Improving the accuracy of intraoperative FSD is a necessary step for obtaining adequate surgical decision-making and precision medicine.

Osteogenic and brain metastases after non-small cell lung cancer resection.

BACKGROUND: A significant number of non-small cell lung cancer (NSCLC) patients develop osteogenic metastases (OMs) and/or brain metastases (BMs) after surgery, however, routine chest computed tomography (CT) sometimes fails to diagnose these recurrences. We investigated the incidence of BMs and OMs after pulmonary resection and aimed to identify candidates who can benefit from brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in addition to CT. METHODS: We retrospectively reviewed medical records of 1099 NSCLC patients who underwent pulmonary resection between 2002 and 2013. Clinicopathological factors associated with OM and/or BM were investigated using univariate and multivariate analyses. RESULTS: Postoperative recurrence occurred in 344 patients (32.6%). OMs were diagnosed in 56 patients (5.6%) with 93% within 3 years. BMs were identified in 72 patients (6.6%) with 91.1% within 3 years. Multivariate analysis revealed that poorly differentiated tumor and the presence of pathological nodal metastases were significantly associated with postoperative BM (p = 0.037, < 0.001), preoperative serum carcinoembryonic antigen (CEA) level of 5 ng/mL or higher and the presence of pathological nodal metastases were significantly associated with OM (p = 0.034, < 0.001). The prevalence of OM and/or BM in 5 years was as high as 25.9% in patients with pathological nodal metastases. CONCLUSIONS: We identified significant predictive factors of postoperative BM and OM. Under patient selection, the effectiveness of intensive surveillance for the modes of recurrence should be investigated with respect to earlier detection, maintenance of quality of life, and survival outcomes.

Impact of Positive Pleural Lavage Cytology for Each Stage of Non-Small Cell Lung Cancer Patients.

BACKGROUND: Positive preresection pleural lavage cytology (PLC+) is a poor prognostic factor in non-small cell lung cancer (NSCLC). This study evaluated the prognostic value of PLC+ for the different pathologic stages (p-stages) of NSCLC. METHODS: A retrospective analysis was conducted of all 1293 staged patients who underwent curative resection in the Shizuoka Cancer Center Hospital, Shizuoka, Japan, for NSCLC to evaluate the impact of PLC+ on survival, specifically in patients with p-stage I NSCLC. The survival rate between patients with and without PLC+ was compared using the Kaplan-Meier method with the log-rank test for comparison. RESULTS: PLC+ was identified in 50 of the 1293 patients (3.9%) and was correlated with lymph node metastasis (P < .001), a pathologic tumor size larger than 3 cm (P = .033), the presence of pleural invasion (P < .001), and adenocarcinoma (P = .038). In patients with PLC+, the 5-year disease-free survival (DFS) was 31.1%, compared with 75.7% for patients with a negative PLC (PLC-) (P < .001). On multivariate analysis, the PLC+ status was an independent prognostic factor of DFS (hazard ratio 1.70; P = .013). Among the 818 patients with p-stage I NSCLC, PLC+ was identified in 22, with a 5-year DFS of 40.4%. The prognosis in patients with p-stage I NSCLC with PLC+ was equal to that in patients with p-stage IIIA NSCLC with PLC- (5-year DFS, 40.4% and 39.0%). CONCLUSIONS: PLC is an independent prognostic factor in early-stage NSCLC. Therefore, it may be appropriate to up-stage an NSCLC diagnosis in the presence of PLC+, especially for patients with p stage I.

Prognostic impact of the number of involved lymph node stations in patients with completely resected non-small cell lung cancer: a proposal for future revisions of the N classification.

OBJECTIVE: The current nodal staging for lung cancer is defined only by the anatomical site of metastasis. However, the International Association for the Study of Lung Cancer (IASLC) proposed further subdivisions of the N descriptor that considers the locations and numbers of involved lymph node stations. This study aimed to test the new IASLC categories and compare their prognostic abilities to those of our proposed model that considers only the number of involved lymph node stations instead of the sites of metastasis. METHODS: Between September 2002 and December 2016, 1581 patients who underwent complete resection for pathologically diagnosed Tis-4N0-2M0 non-small cell lung cancer were retrospectively analyzed. We evaluated the survival rates according to the patients' N classification as recently proposed by the IASLC and by the number of involved lymph node stations, and determined the optimal N classification. RESULTS: The 5-year survival rates for patients with IASLC stages N1a, N1b, N2a1, N2a2, and N2b were 71.5%, 49.9%, 73.7%, 62.1%, and 46.9%, respectively. These results showed relatively good categorizations; however, some prognostic overlaps existed and not all differences were significant. After redefining the number of involved stations as Nα for 1, Nß for 2-3, and Nγ for ≥ 4 without considering the metastasis sites, the 5-year survival rates for patients in these categories were 72.1%, 58.3%, and 29.6%, respectively; the differences between them were significant. CONCLUSION: The number of involved lymph node stations is a more accurate prognostic indicator in patients with completely resected non-small cell lung cancer.

Conversion surgery for locally advanced malignant pleural mesothelioma.

Two women in their sixties were diagnosed with inoperable locally advanced epithelioid malignant pleural mesothelioma, c-stage IIIB. Post-chemotherapy, the tumors down-staged to yc-stage IA, and pleurectomy/decortication were performed. The pathological diagnoses were p-stages II and IA. One patient had tumor recurrence 6 months after surgery; she is currently undergoing fourth-line chemotherapy and is alive 30 months postoperatively. The second patient had tumor recurrence 4 months after surgery and died 2 months later. Conversion surgery for advanced malignant mesothelioma does not improve progression-free survival but might have a chance to extend overall survival in selected patients without deteriorating performance status.

Radiotherapy for local recurrence of non-small-cell lung cancer after lobectomy and lymph node dissection-can local recurrence be radically cured by radiation?

BACKGROUND: There is no standard therapeutic approach for local recurrence of non-small cell lung cancer (NSCLC) after complete resection. We investigated the outcomes of radiotherapy (RT) for patients with local recurrence. METHODS: We reviewed 46 patients who underwent curative-intent RT for local recurrence after lobectomy or pneumonectomy accompanied with mediastinal lymph node dissection between 2002 and 2014. We analyzed overall survival (OS), progression-free survival (PFS), local control, tumour response and the re-recurrence pattern. RESULTS: Among the 46 patients, 16 received concurrent chemotherapy. The median follow-up period was 48 months. The response rate was 91%. The 5-year OS and local control rates were 47.9 and 65.3%, respectively, and the 5-year PFS rate was 22.8%. Female sex and complete response to radiation were favourable prognostic factors. Of the 33 patients with recurrence after radiation, 32 (97%) had distant metastasis. CONCLUSIONS: Although RT for local recurrence has high efficacy, distant relapse after radiation remains a major issue. Therefore, combination systemic therapy for local recurrence at any site should be further investigated. Since it is difficult to achieve a radical cure for local recurrence using RT, further study, for the administration of post-operative adjuvant therapy, is recommended.

Characterization of tumour mutation burden in patients with non-small cell lung cancer and interstitial lung disease.

BACKGROUND AND OBJECTIVE: The efficacy expectation of immune checkpoint inhibitors against NSCLC in patients with ILD seems to be high because these populations are supposed to have high TMB. However, information about the characterization of TMB in patients with NSCLC and ILD is limited. Therefore, this study aimed to evaluate TMB in samples of NSCLC with ILD and clarify factors that influence TMB values. METHODS: The medical records of patients with NSCLC who underwent thoracic surgery at our institution between January 2014 and January 2017 were retrospectively reviewed. Whole-exome sequencing with an Ion Proton system and gene expression profiling of fresh surgical specimens were performed. RESULTS: Among 367 patients with NSCLC, 62 (16.9%) were diagnosed with ILD. All samples were collected from primary tumours with a median TMB of approximately 2.1 (range: 0.1-64.4) mutation/Mb. Among 81 squamous cell carcinomas, we compared 27 tumours with concomitant ILD and 54 tumours without ILD. Univariate analyses revealed that tumours with concomitant ILD showed lower TMB values than those without ILD. Multivariate analysis revealed that concomitant ILD was significantly associated with low TMB values. Conversely, no difference was noted in the TMB value of adenocarcinoma between patients with and without ILD. CONCLUSION: Squamous cell carcinoma and adenocarcinoma with ILD do not have high TMB values. Therefore, considering the risk of severe pneumonitis, immune checkpoint inhibitors should not be used routinely against patients with NSCLC and ILD based on the expectation of high TMB values.

[Current Status of Limited Resection for Lung Cancer as Minimally Invasive Surgery].

This review article describes limited resection for lung cancer based on previous reports and a retrospective examination of the operative results at our hospital.The importance of limited resection as a surgical treatment is becoming much greater than before. In minimally invasive surgery for lung cancer, ① limited resection for pulmonary functional preservation, ② limited resection of lymph node dissection, and ③ minimally invasive thoracic approach may be considered. Radical segmentectomy was limited to the cases registered in the clinical trials [the Japan Clinical Oncology Group (JCOG) study 0802/1211]to verify the validity of limited surgery. The patients who would not tolerate lobectomy underwent passive sublobar resection. Selective lymph node dissection(SLND) is commonly performed in daily clinical practice in Japan, although there is no scientific verification proven by prospective study clinical trials. Since 2013, the indication for selective lymph node dissection in our hospital has been a clinico-surgical N0 cases with a tumor diameter of 5 cm or less, excluding the right middle lobe, left lingular segment, and S6 primary tumor. Rapid intraoperative diagnosis of lymph node metastases is indispensable. Limited resection involves less surgical invasion in terms of operative duration and blood loss volume than a standard procedure, with fewer postoperative complications. In the future, the results of randomized controlled trials (RCTs) originated in Japan is expected to determine whether segmentectomy and SLND are valid and practical enough to become standard procedures of surgical treatment for early-staged patients. In limited resection for lung cancer, it is important to evaluate lymph node, not only preoperatively but also intraoperatively making appropriate diagnoses.

[Sentinel Lymph Node Diagnosis for Lung Cancer].

Many researchers have reported that the sentinel node (SN) theory has been established for lung cancer. However, sentinel node navigation surgery (SNNS) has not yet become a routine medical procedure in lung cancer surgery. SN identification is important for efficient retrieval of micrometastases. Methods for identifying SNs include the dye method and the radioisotope (RI) method, but methods such as the indocyanine green (ICG) method, computed tomographic lymphography (CTLG), and the magnetic method are also being studied. More careful surgical adaptation is required for reduction surgery for early lung cancer, and rapid intraoperative diagnosis is frequently used. SN lymph nodes may be used as an indicator for selecting lymph nodes to be diagnosed intraoperatively. SN identification is considered an important method for ensuring that reduction surgery is curative. Furthermore, if overlooking lymph node metastases can be avoided by using intraoperative rapid diagnosis of micrometastases, we believe that the safety of reduction surgery will be enhanced. In addition, SN identification provides a theoretical basis to support the omission of lymph node dissection. Future developments of SN research and technology are expected.