The Role of Emphysema on Postoperative Prognosis in Early-Stage Nonsmall Cell Lung Cancer.

BACKGROUND: Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. METHODS: A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. RESULTS: The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age > 70 years (vs. < 70 years, hazard ratio 4.03, P < 0.001), and SUVmax > 1.8 (vs. ≤ 1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. CONCLUSIONS: Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.

Postoperative pulmonary function of patients with lung cancer and interstitial lung abnormalities.

OBJECTIVE: We investigated the impact of radiological interstitial lung abnormalities on the postoperative pulmonary functions of patients with non-small cell lung cancer. METHODS: A total of 1191 patients with clinical stage IA non-small cell lung cancer who underwent lung resections and pulmonary function tests ≥ 6 months postoperatively were retrospectively reviewed. Postoperative pulmonary function reduction rates were compared between patients with and without interstitial lung abnormalities and according to the radiological interstitial lung abnormality classifications. Surgical procedures were divided into wedge resection, 1-2 segment resection, and 3-5 segment resection groups. RESULTS: No significant differences in postoperative pulmonary function reduction rates 6 months after wedge resection were observed between the interstitial lung abnormality [n = 202] and non-interstitial lung abnormality groups [n = 989] [vital capacity [VC]: 6.82% vs. 5.00%; forced expiratory volume in 1 s [FEV1]: 7.05% vs. 7.14%]. After anatomical resection, these values were significantly lower in the interstitial lung abnormality group than in the non-interstitial lung abnormality group [VC: 1-2 segments, 12.50% vs. 9.93%; 3-5 segments, 17.42% vs. 14.23%; FEV1: 1-2 segments: 13.36% vs. 10.27%; 3-5 segments: 17.36% vs. 14.39%]. No significant differences in postoperative pulmonary function reduction rates according to the radiological interstitial lung abnormality classifications were observed. CONCLUSIONS: The presence of interstitial lung abnormalities had a minimal effect on postoperative pulmonary functions after wedge resections; however, pulmonary functions significantly worsened after segmentectomy or lobectomy, regardless of the radiological interstitial lung abnormality classification in early-stage non-small cell lung cancer.

Omitting Lymph Node Dissection for Small Ground-Glass Opacity-Dominant Tumors.

BACKGROUND: The purpose of this study was to determine the optimal extent of lymph node dissection required in patients with small (≤3 cm) radiologically ground-glass opacity-dominant, peripheral, non-small cell lung cancer tumors. METHODS: The study analyzed the clinicopathologic findings and surgical outcomes of 988 patients with radiologic, ground-glass opacity-dominant non-small cell lung cancer without lymph node involvement who underwent complete resection of the primary tumor between 2010 and 2020. Patients were followed up for 54.5 months (median). Kaplan-Meier curves and the log-rank test were used in statistical analyses of the prognosis. RESULTS: Median age, whole tumor size, solid tumor size, and maximum standardized uptake values were 68 years, 1.7 cm, 0.4 cm, and 0.9, respectively. Sixty percent of the cohort was female (n = 590). Wedge resection, segmentectomy, and lobectomy were performed in 206, 372, and 410 patients, respectively. A total of 982 of 988 (99%) tumors were adenocarcinomas. One patient had hilar lymph node involvement; however, no mediastinal lymph node metastasis or hilar or mediastinal lymph node recurrence was detected. The 5-year overall survival rate was 96.5% (95% CI, 94.8%-97.7%). Excellent survival outcomes were achieved regardless of procedure (wedge resection, 94.7% [95% CI, 89.1%-97.5%]; segmentectomy, 96.9% [95% CI, 93.7%-98.5%]; and lobectomy, 97.1% [95% CI, 94.4%-98.5%]). CONCLUSIONS: Omitting lymph node dissection may be acceptable with curative intent for small tumors with radiologic ground-glass opacity dominance. Appropriate surgical procedures such as wedge resection, segmentectomy, or lobectomy can provide satisfactory outcomes in patients with indolent tumors if surgical margins are secured.

Clinical Significance of Preserving Pulmonary Function After Lung Resection in Early-Stage Non-Small-Cell Lung Cancer.

INTRODUCTION: To determine the association between changes in pulmonary function before and after surgery, and the subsequent prognosis, of patients with early-stage non-small-cell lung cancer (NSCLC). METHODS: A total of 485 patients who underwent lobectomy or segmentectomy for NSCLC with whole tumor size ≤2 cm and clinical stage IA at 2 institutions were retrospectively reviewed. The relationship between the postoperative reduction rate in vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV1) and overall survival (OS) was investigated. OS determined the cut-off value of the reduction rate, according to the reduction rate of every 10% in pulmonary function. RESULTS: Multivariable Cox regression analysis showed that a reduction rate in VC at 12 months postoperatively was an independent prognostic factor for OS (hazard ratio, 1.05; 95% confidence interval [CI], 1.02-1.07; P < .001) but those in FVC and FEV1 were not. OS was classified into good and poor with 20% reduction rate in VC. OS and recurrence-free survival (RFS) in a higher than 20% reduction rate in VC were worse than those in ≤20% reduction rate in VC (5 year-OS; 82.0% vs. 93.4%; P = .0004. Five year-RFS; 80.3% vs. 89.8%; P = .0018, respectively). Multivariable logistic analysis showed that lobectomy was a risk factor for the higher than 20% reduction rate in VC (odds ratio, 1.61; 95% CI, 1.01-2.56; P = .045). CONCLUSIONS: Postoperative decrease in VC was significantly associated with the prognosis. Preserving pulmonary function is important for survival of patients with early-stage NSCLC.

Sublobar Resection in Early Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutant.

BACKGROUND: Lobectomy is a standard surgical procedure for peripherally located early-stage non-small cell lung cancers (NSCLCs) measuring 2 to 4 cm. However, it is unclear whether sublobar resections, such as wedge resection and segmentectomy, are effective in treating tumors with driver mutations in the epidermal growth factor receptor (EGFR). METHODS: We analyzed the clinicopathologic findings and surgical outcomes of 1395 patients with radiologically solid-dominant NSCLC measuring 2 to 4 cm, without clinical lymph node involvement, who underwent complete resection between 2010 and 2020. The patients, who underwent sublobar resections (n = 231) or lobectomy (n = 1164), were categorized by their EGFR mutation status and the surgical procedures performed. The follow-up was conducted for a median of 45.3 months. RESULTS: The 5-year overall survival (OS) rates after sublobar resections (n = 39) were comparable to those after lobectomy (n = 359) in patients with EGFR mutation-positive tumors (80.5% [95% CI, 51.3%-93.2%] vs 88.8% [95% CI, 84.1%-92.1%], respectively; P = .16). Multivariable Cox regression analysis of OS revealed that the surgical procedure was an independent prognostic predictor in the entire cohort (hazard ratio, 0.6; 95% CI, 0.4-1.0; P = .028), but it was not an independent prognostic predictor in patients with EGFR-mutated tumors (hazard ratio, 0.6; 95% CI, 0.2-1.7; P = .32). CONCLUSIONS: Sublobar resection with a secure surgical margin could be a viable option for appropriately selected patients with peripheral early-stage NSCLC tumors measuring 2 to 4 cm and harboring EGFR mutations, because it provides comparable OS to that of lobectomy.

Effectiveness of pleurodesis for postoperative air leaks after lung resection.

BACKGROUND: Pleurodesis is often performed for air leaks; however, the ideal materials and timing of the procedure remain controversial. We investigated the efficacy of pleurodesis using different materials and timing. METHODS: We retrospectively reviewed 913 consecutive patients who underwent segmentectomy or lobectomy for non-small cell lung cancer between 2014 and 2021. Pleurodesis efficacy was assessed on the day of chest tube removal. RESULTS: Eighty-six patients (9%) underwent pleurodesis for postoperative air leaks. Pleurodesis was performed on a median of postoperative day (POD) 5. Talc was the most frequently used material (n = 52, 60%), followed by autologous blood patches (n = 20, 23%), OK-432 (n = 12, 14%), and others (n = 2, 2%). No difference existed in the number of days from initial pleurodesis to chest tube removal among the three groups (talc, 3 days; autologous blood patch, 3 days; OK-432, 2 days; P = 0.55). No difference in patient background, except for sex, was observed between patients who underwent pleurodesis within 4 PODs and those who underwent pleurodesis on POD 5 or later. Drainage time was significantly shorter in patients who underwent pleurodesis within 4 PODs (median, 7 vs. 9 days; P = 0.004). CONCLUSIONS: The efficacies of autologous blood patch, talc, and OK-432 would be considered comparable and early postoperative pleurodesis could shorten drainage time. Prospective studies are required.

Risk Factors for Recurrence of Stage I Epidermal Growth Factor Receptor Mutated Lung Adenocarcinoma.

BACKGROUND: We aimed to clarify the risk factors for postoperative recurrence in patients with epidermal growth factor receptor (EGFR)-mutated stage I lung adenocarcinoma, using EGFR wild-type adenocarcinoma as a comparator, to select optimal candidates for adjuvant therapy with EGFR tyrosine kinase inhibitor (TKI). METHODS: Data of patients with pathologic stage I EGFR-mutated (n = 713) and wild-type (n = 673) adenocarcinoma who did not receive adjuvant therapy were retrospectively analyzed. The cumulative incidence of recurrence (CIR) was estimated using Gray's method, and multivariable Fine-Gray competing risk models identified independent risk factors associated with recurrence. RESULTS: The CIR did not differ significantly between patients with EGFR-mutated and wild-type adenocarcinoma (P = .32). Multivariable analysis revealed that greater size (cm) of invasive tumor (hazard ratio 1.539; 95% CI, 1.077-2.201), lymphovascular invasion (hazard ratio 5.180; 95% CI, 2.208-12.15), pleural invasion (hazard ratio 3.388; 95% CI, 1.524-7.533), and high-grade histologic subtype (hazard ratio 4.295; 95% CI, 1.539-11.99) were independent risk factors for recurrence in patients with EGFR-mutated adenocarcinoma. The 5-year CIR was significantly higher among patients with these factors (tumor size greater than 2 cm, 15.9%; lymphovascular invasion, 26.9%; pleural invasion, 39.3%; and high-grade subtype, 44.4%) than among patients without them (4.4%, 2.2%, 3.9%, and 5%, respectively; P < .001). For patients with EGFR wild-type adenocarcinoma, independent risk factors for recurrence were invasive tumor size, lymphovascular invasion, and pleural invasion, but not histologic subtypes. CONCLUSIONS: Even for patients with EGFR-mutated stage I lung adenocarcinoma, recurrence risk is stratified. Adjuvant therapy may be considered if they have high-risk factors for recurrence.

Tumor distance from the mediastinum predicts N2 upstaging in clinical stage I lower-lobe non-small cell lung cancer.

OBJECTIVE: Pulmonary lymphatic drainage of the lower lobe into the mediastinal lymph nodes includes not only the pathway via the hilar lymph nodes but also the pathway directly into the mediastinum via the pulmonary ligament. This study aimed to determine the association between the distance from the mediastinum to the tumor and the frequency of occult mediastinal nodal metastasis (OMNM) in patients with clinical stage I lower-lobe non-small cell lung cancer (NSCLC). METHODS: Between April 2007 and March 2022, data of patients who underwent anatomical pulmonary resection and mediastinal lymph node dissection for clinical stage I radiological pure-solid lower-lobe NSCLC were retrospectively reviewed. In computed tomography axial sections, the ratio of the distance from the inner edge of the lung to the inner margin of the tumor within the lung width of the affected lung was defined as the inner margin ratio. Patients were divided into 2 groups based on whether the inner margin ratio was ≤0.50 (inner-type) or >0.50 (outer-type), and the association between inner margin ratio status and clinicopathological findings was assessed. RESULTS: In total, 200 patients were enrolled in the study. OMNM frequency was 8.5%. More inner-type than outer-type patients had OMNM (13.2% vs 3.2%; P = .012) and skip N2 metastasis (7.5% vs 1.1%; P = .038). Multivariable analysis revealed that the inner margin ratio was the only independent preoperative predictor of OMNM (odds ratio, 4.72; 95% CI, 1.31-17.07; P = .018). CONCLUSIONS: Tumor distance from the mediastinum was the most important preoperative predictor of OMNM in patients with lower-lobe NSCLC.

Successful conservative treatment for massive tracheal necrosis after lung segmentectomy.

BACKGROUND: Tracheal necrosis, which is rare because the trachea has rich in blood supply, can be a serious condition. Herein, we report the case of extensive tracheal necrosis that developed after right apical segmentectomy for a metastatic lung tumor of esophageal cancer. CASE PRESENTATION: A 74-year-old man who had undergone thoracoscopic subtotal esophagectomy and gastric tube reconstruction via the posterior sternal route for esophageal adenocarcinoma 2 years previously was referred to our department with an enlarging nodal lesion in the right upper lung lobe. Computed tomography revealed a 30-mm tumor in the right apical segment with no lymph node enhancement, suggesting primary lung cancer or a metastatic lung tumor. The patient underwent right apical segmentectomy. The upper lobe was adherent to the chest wall and mediastinal fat from the apex of the lung to the dorsal side, with particularly strong adhesion at the esophagectomy site. After dissecting the adhesions, right apical segmentectomy was performed via complete video-assisted thoracic surgery. The patient was discharged on the 9th day after surgery without any complications. Pathologic findings revealed a metastatic lung tumor originating from the patient's esophageal cancer. On the 26th day after surgery, the patient returned with dyspnea and increased sputum. Computed tomography images revealed that the posterior wall of the trachea was missing an area of 16 × 42 mm and was connected to the dead space after the right apical segmentectomy, with no effusion. We diagnosed extensive tracheal necrosis. Considering that the patient's status was very well despite the extensive tracheal necrosis, we chose conservative treatment. After receiving 12 days of intravenous antibiotic treatment, his symptoms improved, and he was discharged on day 26 after admission. CONCLUSIONS: Right upper lung lobe resection after esophagectomy has a risk of tracheal necrosis. Conservative treatment is one approach to manage massive tracheal necrosis in patients with stable respiratory conditions.

Segmentectomy for cancer control in radiologically pure-solid clinical stage IA3 lung cancer.

OBJECTIVES: This study aimed to compare cancer control after segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 non-small-cell lung cancer (NSCLC). METHODS: Patients with radiologically pure-solid clinical stage IA3 NSCLC who underwent lobectomy or segmentectomy at 3 institutions between 2010 and 2019 were identified. We estimated propensity scores to adjust for confounding variables regarding tumour malignancy, including age, sex, smoking history, tumour size, maximum standardized uptake value on 18F-fluorodeoxyglucose positron emission tomography, lymph node dissection, histological type and lymphatic, vascular and pleural invasion. Cumulative incidence of recurrence (CIR) was evaluated as a primary end point. RESULTS: Among 412 patients, postoperative recurrence occurred in 7 of 44 patients (15.9%) undergoing segmentectomy, and 71 of 368 patients (19.3%) undergoing lobectomy. CIR was comparable between patients undergoing segmentectomy (5-year rate, 21.9%) and those undergoing lobectomy (5-year rate, 20.8%; P = 0.88). Locoregional recurrence did not differ between patients undergoing segmentectomy (6.8%) and those undergoing lobectomy (9.0%). In multivariable analysis, segmentectomy (versus lobectomy) was not identified as an independent prognostic factor for CIR (hazard ratio, 1.045; 95% confidence interval, 0.475-2.298; P = 0.91). In propensity score matching of 40 pairs, CIR was not significantly different between patients undergoing segmentectomy (5-year rate, 20.7%) and those undergoing lobectomy (5-year rate, 18.4%; P = 0.81). CONCLUSIONS: Cancer control may be comparable between segmentectomy and lobectomy in patients with radiologically pure-solid clinical stage IA3 NSCLC. Further studies are warranted to clarify the survival benefits of segmentectomy in these patients.

Wedge resection is an acceptable treatment option for radiologically low-grade lung cancer with solid predominance.

OBJECTIVES: This study aimed to determine the clinical characteristics for predicting low-grade cancer in radiologically solid predominant non-small-cell lung cancer (NSCLC) and compare the survival outcomes of wedge resection with those of anatomical resection for patients with and without these characteristics. METHODS: Consecutive patients with clinical stages IA1-IA2 NSCLC showing radiologically solid predominance ≤2 cm at 3 institutions were retrospectively evaluated. Low-grade cancer was defined as the absence of nodal involvement and blood vessel, lymphatic and pleural invasion. The predictive criteria for low-grade cancer were established by multivariable analysis. The prognosis of wedge resection was compared with that of anatomical resection for patients who met the criteria, using the propensity score-matched analysis. RESULTS: Among 669 patients, multivariable analysis showed that ground-glass opacity (GGO) (P < 0.001) on thin-section computed tomography and an increased maximum standardized uptake value on 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (P < 0.001) were independent predictors of low-grade cancer. The predictive criteria were defined as GGO presence and maximum standardized uptake value ≤1.1 (specificity: 97.8%, sensitivity: 21.4%). In the propensity score-matched pairs (n = 189), overall survival (P = 0.41) and relapse-free survival (P = 0.18) were not significantly different between patients who underwent wedge resection and anatomical resection among those who fulfilled the criteria. CONCLUSIONS: The radiologic criteria for GGO and a low maximum standardized uptake value could predict low-grade cancer, even in solid-dominant NSCLC sized ≤2 cm. Wedge resection could be an acceptable surgical option for patients with radiologically predicted indolent NSCLC showing a solid-dominant appearance.

Segmentectomy preserves better immune-nutritional status than lobectomy in patients with early-stage lung cancer.

OBJECTIVES: This study aimed to compare the postoperative immune-nutritional status of patients undergoing segmentectomy and lobectomy for early-stage non-small-cell lung cancer. METHODS: Patients with clinical stage 0-IA non-small-cell lung cancer who underwent lobectomy or segmentectomy were retrospectively analysed. Postoperative immune-nutritional indices (prognostic nutritional index, serum albumin levels and total lymphocyte count) at 1 month, 6 months, 1 year, 2 years and 3 years after surgery were compared using mixed effects linear models and mixed effects logistic regression models. RESULTS: There were 164 and 210 patients in the lobectomy and segmentectomy groups, respectively. Postoperative prognostic nutritional index and albumin levels were significantly higher in the segmentectomy group than those in the lobectomy group (P < 0.001 and P < 0.001, respectively), despite the nonsignificant difference in the total lymphocyte count (P = 0.563). In 126 propensity score-matched pairs adjusted for confounding variables affecting postoperative nutritional status, postoperative prognostic nutritional index and albumin levels were significantly higher in the segmentectomy group than in the lobectomy group (P = 0.009 and P = 0.007, respectively). At each time point after surgery, these indices were higher in the segmentectomy group than in the lobectomy group at 1 month, 2 years and 3 years postoperatively. There were significantly more patients with lower immune-nutritional indices (prognostic nutritional index <45, albumin <4.0 g/dl) in the lobectomy group than in the segmentectomy group at 3 years postoperatively (P = 0.026 and P = 0.029, respectively), despite nonsignificant statistical differences throughout the study period (P = 0.219 and P = 0.113, respectively). CONCLUSIONS: Patients who underwent segmentectomy showed better postoperative immune-nutritional status than those who underwent lobectomy.

Risk factors for long-term decline in post-operative pulmonary function after lung resection.

OBJECTIVES: The study aimed to examine the risk factors for long-term decline in pulmonary function after anatomical resection for lung cancer and the effects of the decrease on survival. METHODS: We retrospectively examined 489 patients who underwent anatomical resection for lung cancer between 2010 and 2020. Pulmonary function tests were performed preoperatively and at 1, 3, 6 and 12 months after surgery. The lower interquartile medians of the reduction rates of forced expiratory volume in 1 s and vital capacity at 12 months after surgery were taken as the cut-off values of risk factors for the decrease in post-operative pulmonary function. RESULTS: Forced expiratory volume in 1 s and vital capacity decreased the most in the first month after surgery and then gradually recovered. Vital capacity continued to increase even after 6 months post-surgery, whereas forced expiratory volume in 1 s stabilized. Multivariable logistic analysis showed that the number of resected segments (odds ratio, 2.09; 95% confidence interval, 1.12-3.89; P = 0.019) was a risk factor for the decrease in forced expiratory volume in 1 s at 12 months, and the numbers of resected segments (odds ratio, 1.36; 95% confidence interval, 1.13-1.63; P < 0.001) and post-operative complications (odds ratio, 2.32; 95% confidence interval, 1.01-5.35; P = 0.047) were independent risk factors for decrease in vital capacity. Multivariate cox regression analysis showed that the decrease in vital capacity at 12 months was significantly associated with overall survival (hazard ratio, 2.02; 95% confidence interval, 1.24-3.67; P = 0.004). CONCLUSIONS: Long-term decrease in vital capacity, which was influenced by the number of resected segments and post-operative complications, adversely affected survival.

Impact of the amount of preoperative erector spinae muscle in stage I non-small-cell lung cancer.

OBJECTIVES: Erector spinae muscle (ESM) is an antigravity muscle group that can be evaluated as an index of muscle loss on chest computed tomography. The amount of ESM has been reported to be related to the prognosis of several respiratory diseases. However, few studies clarify the impact on postoperative non-small-cell lung cancer (NSCLC). We investigated the relationship between ESM and postoperative prognosis in patients with early-stage NSCLC. METHODS: We reviewed the medical records of 534 patients with stage I NSCLC who underwent lobectomy or segmentectomy. The ESM was identified by preoperative computed tomography, and the amount was normalized according to height and sex. Overall survival, lung cancer-related deaths and non-lung cancer-related deaths (NLCRD) were analysed using log-rank and Gray's tests. Multivariable analyses were conducted to identify factors that influenced overall survival (OS) and NLCRD. RESULTS: The amount of ESM normalized according to height and sex was significantly associated with age and body mass index. When the amount was low, OS (5-year OS, 79.6 vs 89.5%; P< 0.001) and NLCRD (5-year cumulative mortality rate, 14.7 vs 6.8%; P< 0.001) were significantly worse, although no difference was found in lung cancer-related deaths. CONCLUSIONS: The amount of preoperative ESM was strongly related to non-lung cancer-related death and was a significant prognostic factor for stage I NSCLC. Patients with a low amount of the muscle should be treated based on proper risk assessment.

Histopathology and Cytology of Pulmonary Myoepithelial Neoplasms: 2 Cases.

Myoepithelial neoplasms (MNs) of the lung are extremely rare tumors. Approximately 40 cases of pulmonary MNs have been reported to date. Herein, we report extremely rare cases of different types of pulmonary MN, including cytological features. Case 1 is an 18-year-old female, and case 2 is a 73-year-old female patient. They presented to our hospital with nodules of the lung. Histological examination revealed tumor cells with round to oval nuclei and acidophilic cytoplasm that formed nests or fascicles with mild hyalinized stroma in case 1 and tumors containing the bi-phasic components of a nest-like and fascicle pattern with pleomorphism in case 2. Immunohistochemically, these tumors were positive for cytokeratin (CK) AE1/AE3, CK5/6, vimentin, calponin, and EMA, and focal positive for S-100a protein and alpha smooth muscle actin. The pathological diagnoses in cases 1 and 2 were myoepithelioma and myoepithelial carcinoma, respectively. In conclusion, we encountered two cases of extremely rare MNs that occurred in the lung. This disease can be diagnosed by collecting appropriate cytological and histological findings and should be listed as a differential diagnosis.

Classification based on skeletal muscle mass and the severity of lung emphysema impacts on clinical outcomes after anatomical resection for lung cancer.

OBJECTIVES: Both sarcopenia and lung emphysema are prognostic factors in lung cancer and can be easily assessed using the psoas muscle index and Goddard score, respectively. We investigated the clinical significance of the classification based on psoas muscle index and Goddard score in non-small cell lung cancer. METHODS: A total of 303 consecutive patients who underwent anatomical resection for non-small cell lung cancer were retrospectively analyzed. The psoas muscle at the level of the third lumbar vertebrae and Goddard score were measured on preoperative computed tomography. The psoas muscle was adjusted by height as the psoas muscle index (cm2/m2). We divided patients into three groups: low-, middle- and high-risk, using cut-off values of psoas muscle index < 6.36 cm2/m2 for males and 3.92 cm2/m2 for females and Goddard score higher than 7. The predictors of postoperative complications and prognosis were examined. RESULTS: High-, middle- and low-risk were present in 30 (10%), 164 (54%) and 109 (36%) patients, respectively. High risk was significantly associated with male sex, low pulmonary function, more comorbidities and increased postoperative complications. High-risk patients showed poorer overall survival than middle- and low-risk patients (P < 0.001). Multivariable analysis revealed that high risk was an independent risk factor for postoperative complications and unfavorable prognostic factors (P = 0.011, P = 0.014, respectively). CONCLUSIONS: Classification based on psoas muscle index and Goddard score is significantly associated with short- and long-term outcomes in patients with lung cancer. This method can be easily assessed for patients and may help select patients for nutritional support and rehabilitation before surgery.

Rb and p53-Deficient Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma Require Skp2 for Survival.

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are highly genetically complex soft tissue sarcomas. Up to 50% of patients develop distant metastases, but current systemic therapies have limited efficacy. MFS and UPS have recently been shown to commonly harbor copy number alterations or mutations in the tumor suppressor genes RB1 and TP53. As these alterations have been shown to engender dependence on the oncogenic protein Skp2 for survival of transformed cells in mouse models, we sought to examine its function and potential as a therapeutic target in MFS/UPS. Comparative genomic hybridization and next-generation sequencing confirmed that a significant fraction of MFS and UPS patient samples (n = 94) harbor chromosomal deletions and/or loss-of-function mutations in RB1 and TP53 (88% carry alterations in at least one gene; 60% carry alterations in both). Tissue microarray analysis identified a correlation between absent Rb and p53 expression and positive expression of Skp2. Downregulation of Skp2 or treatment with the Skp2-specific inhibitor C1 revealed that Skp2 drives proliferation of patient-derived MFS/UPS cell lines deficient in both Rb and p53 by degrading p21 and p27. Inhibition of Skp2 using the neddylation-activating enzyme inhibitor pevonedistat decreased growth of Rb/p53-negative patient-derived cell lines and mouse xenografts. These results demonstrate that loss of both Rb and p53 renders MFS and UPS dependent on Skp2, which can be therapeutically exploited and could provide the basis for promising novel systemic therapies for MFS and UPS. SIGNIFICANCE: Loss of both Rb and p53 renders myxofibrosarcoma and undifferentiated pleomorphic sarcoma dependent on Skp2, which could provide the basis for promising novel systemic therapies.See related commentary by Lambert and Jones, p. 2437.

Prolonged post-recurrence survival following pleurectomy/decortication for malignant pleural mesothelioma.

The present study analyzed surgical results in patients with malignant pleural mesothelioma (MPM) who underwent extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). Data for 44 patients who achieved macroscopic complete resection following neoadjuvant chemotherapy followed by EPP (n=29) or P/D (n=15) were reviewed. Patient demographics and oncological outcomes were compared between the EPP and P/D groups. The median overall (OS) and progression-free survival (PFS) times were 22 and 14 months, respectively. OS was significantly different between the EPP and P/D groups (median OS, 17 vs. 34 months; 5-year OS, 11 vs. 44%; P=0.019); no difference was noted in PFS (median PFS, 13 vs. 21 months; 5-year PFS, 11 vs. 17%; P=0.373). Univariate analysis demonstrated that epithelial histology (P=0.0003) and P/D (P=0.018) were significant favorable prognostic factors for OS. Using multivariate analysis, epithelial histology (P=0.001) remained the only significant factor. Post-recurrence survival (PRS) among all patients was significantly longer in the P/D group (median PRS, 3 vs. 20 months; 1.5-year PRS, 5 vs. 54%; P=0.003), even among patients with epithelial-type MPM (median PRS, 6 s vs. 20 months; 1.5-year PRS, 8 vs. 61%; P=0.012). Chemotherapy following recurrence (P=0.033) was significantly associated with superior PRS in multivariate analysis. Postoperative pulmonary function was significantly improved in the P/D group. In summary, P/D may be an alternative procedure to EPP for resectable MPM providing similar PFS and improved PRS.

The differences in histological changes among pulmonary vessels divided with an energy device.

OBJECTIVES: Histological changes after division of the pulmonary artery (PA) and the pulmonary vein (PV) using a vessel-sealing device are not fully understood. The goal of the present study was to clarify histologically and immunohistochemically how division with the device affects the wall layers of the pulmonary vasculature. METHODS: This prospective cohort study analysed outcomes of 20 patients who underwent anatomical lung resection. After a single proximal ligation, the PA and the PV (diameter 2-7 mm) were divided using a LigaSure Blunt Tip (LSB). Histological findings and thermal damage were evaluated in vascular specimens from resected lungs. RESULTS: The PA has a well-developed media with rich elastic fibres and a thin adventitia, whereas the PV has a thinner media and a thicker adventitia with abundant collagen fibres. Vascular division of the PAs and PVs appeared complete to the naked eye. However, in all divided PAs, the area adjacent to the sealed zone comprised only adventitia and thin disrupted media. Additionally, thermal energy generated by the LSB resulted in a wide area of thermal necrosis over the histologically fragile region in all cases. Conversely, the wall layers of all divided PVs were completely fused without disruption. Thermal spread and disruption did not significantly differ between small (2-4 mm) and large (5-7 mm) PAs [187 (150-253) vs 236 (190-275) µm, P = 0.22; 180 (138-200) vs 210 (161-305) µm, P = 0.22]. Histological changes differed significantly between the pulmonary vessels after division using the LSB. CONCLUSIONS: Surgeons should consider that dividing the pulmonary vessels with a vessel-sealing device might have more histological impact on the layers of the wall of the PA than on those of the PV, although it remains unclear whether these findings constitute a clinical risk.

Segmentectomy Versus Lobectomy for Radiologically Pure Solid Clinical T1a-bN0M0 Lung Cancer.

BACKGROUND: Segmentectomy for radiologically pure solid tumors is still controversial because these tumors are more aggressive in malignancy than those with ground-glass opacity. This study aimed to determine the feasibility of intentional segmentectomy for pure solid small-sized lung cancer. METHODS: We retrospectively analyzed 96 radiologically pure solid tumors in clinical T1a-bN0M0 lung cancer. Patients whose tumor was located at a central region or right middle lobe were excluded. Forty-four patients who underwent lobectomy were compared with 52 those who underwent segmentectomy. Segmentectomy got converted to lobectomy if lymph node metastases or inadequate surgical margin was confirmed. Factors affecting survival were assessed using Cox regression. Propensity score stratification analysis was also performed. RESULTS: Eight patients (8%) were identified as a histological type other than adenocarcinoma or squamous cell carcinoma. Moreover, 14 patients (14%) displayed lymph node metastasis. Among those who underwent segmentectomy, nine patients (16%) were converted to lobectomy due to lymph node metastasis or inadequate surgical margin. The 3-year recurrence-free survival rates were 84.1 and 82.2% in patients who underwent segmentectomy and lobectomy, respectively (P = 0.745). In addition, the recurrence-free survival was not statistically significant between segmentectomy and lobectomy, as determined via multivariable Cox regression analysis (hazard ratio 1.11; 95% confidence interval 0.40-3.06), even after propensity score stratification (hazard ratio 1.17; 95% confidence interval 0.38-3.65). CONCLUSIONS: Segmentectomy with intraoperative assessment of lymph node metastasis and adequate surgical margin may be a feasible surgical procedure for pure solid tumors in clinical T1a-bN0M0 lung cancer.