Impact of Tumor Size and Differentiation Grade on Survival After Lobectomy and Segmentectomy for Patients with Early-Stage Lung Adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the effect of tumor size and differentiation grade on long term survival in patients with early-stage lung adenocarcinoma (LUAD) after lobectomy and segmentectomy. PATIENTS AND METHODS: Patients with stage T1-2N0M0 LUAD who underwent lobectomy and segmentectomy were identified from the Surveillance, Epidemiology, and End Results database. Patients were stratified as grade I (well differentiated), grade II (moderately differentiated), and grade III/IV (poorly differentiated/undifferentiated) carcinomas. The effect of tumor size on overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the multivariate Cox regression model, including the interaction between tumor size, type of surgery, and tumor differentiation grade. The inverse probability of treatment weighting method was used to adjust for bias between the groups. RESULTS: A total of 19,857 patients were identified, including 18,759 (94.4%) who underwent lobectomy and 1098 (5.5%) who underwent segmentectomy. A three-way interaction among tumor size, differentiation grade, and type of surgery was observed in the overall cohort. After stratifying by differentiation grade, plots of interaction revealed that lobectomy was associated with improved survival compared with segmentectomy when the tumor size exceeded 23 mm for grade I LUAD and 14 mm for grade II LUAD. No interaction was observed between the studied factors in grade III/IV carcinomas. CONCLUSIONS: This study interpreted the interaction between tumor size and type of surgery on long-term survival in patients with early stage LUAD and established a tumor size threshold beyond which lobectomy provided survival benefits compared with segmentectomy.

Preoperative risk factors of lymph node metastasis in clinical N0 lung adenocarcinoma of 3 cm or less in diameter.

BACKGROUND: Lung adenocarcinoma is the most common subtype of non-small cell lung cancer. The surgical strategy of lymph node dissection is controversial because many more patients are diagnosed at an early stage in clinical practice. METHODS: We retrospectively reviewed 622 clinical N0 lung adenocarcinoma patients with 3 cm or less in tumor size who underwent lobectomy or segmentectomy combined with lymph node dissection in our hospital from January 2017 to December 2019. We performed univariate and multivariate analyses to identify preoperative risk factors of lymph node metastasis. RESULTS: Lymph node metastasis was found in 60 out of 622 patients. On univariate analysis, lymph node metastasis was linked to smoking history, preoperative CEA level, tumor size, tumor location (peripheral or central), consolidation/tumor ratio, pleural invasion, and pathologic type. However, only the preoperative CEA level, tumor size, and consolidation/tumor ratio were independent risk factors in multivariate analysis. The ROC curve showed that the cutoff value of tumor size was 1.7 cm. There was no lymph node metastasis in patients without risk factors. CONCLUSIONS: The preoperative CEA level, tumor size, and consolidation/tumor ratio were independent risk factors of lymph node metastasis in clinical N0 lung adenocarcinoma with tumor size ≤ 3 cm. The lymph node metastasis rate was extremely low in clinical N0 lung adenocarcinoma patients without risk factors and lymph node dissection should be avoided in these patients to reduce surgical trauma.

[Establishment of a predicting model to evaluate the probability of malignancy or benign in patients with solid solitary pulmonary nodules].

OBJECTIVE: To develop a predicting model for evaluating the probability of malignancy or benign in patients with solid solitary pulmonary nodules through analyzing the clinical, radiologic, laboratory examination and radionuclide (18)F-Fluorodeoxyglucose examinations data. METHODS: The data of the 203 patients(110 males and 93 females) with solid SPN who underwent surgical resection with definite postoperative pathological diagnosis from January 2012 to December 2014 in Shanghai Chest Hospital (group A)were retrospectively analyzed. The clinical data included age, gender, history of smoking, history of tumor; radiologic data included diameter in lung window, location, shape, clear border, lobulation, spiculation, vascular convergence, tumor cycle blood vessel, density, calcification, pleura indentation; laboratory examination included five serum tumor markers consisting of CA125, CEA, CYFRAL21-1, NSE, SCC. (18)F-Fluorodeoxyglucose examinations included (18)F-FDG PET-CT or SPECT. The independent predictors of malignancy were estimated through univariate and multivariate analysis, then the predicting model was built. Another 110 patients with solid SPN(group B)from January 2015 to December 2015 with definite pathological diagnosis were used to validate the predictive value of the model. RESULTS: There were 159(78.3%) cases of malignancy and 44(21.7%) cases of benign in group A. Logistic regression analysis showed age, clear border, spiculation, calcification and (18)F-FDG examination were independent predictors of malignancy in patients with solid SPN(P<0.05). A predicting nomogram was built according to the result of the multivariate logistic regression analysis. The area under the ROC curve was 0.890±0.038 for group B. The cut off value was 0.708. The sensitivity in group B was 86%, specificity 80%, accuracy 84.5%. CONCLUSION: Age of patients, clear border, spiculation, calcification and (18)F-FDG examination were independent predictors of malignancy in patients with solid SPN. The model showed good diagnosis efficiency in external validation, and could be applied to make decision for patients with solid SPN.

Occurrence, formation, and proteins perturbation of disinfection byproducts in indoor air resulting from chlorine disinfection.

Increased amounts of chlorine disinfectant have been sprayed to inactivate viruses in the environment since the COVID-19 pandemic, and the health risk from chemicals, especially disinfection byproducts (DBPs), has unintentionally increased. In this study, we characterized the occurrence of haloacetic acids (HAAs) and trihalomethanes (THMs) in indoor air and evaluated their formation potential from typical indoor ingredients. Subsequently, the adverse effect of chloroacetic acid on A549 cells was depicted at the proteomic, transcriptional and silico levels. The results revealed that the total concentrations of HAAs and THMs ranged from 1.46 to 4.20 µg/m3 in ten indoor environments. Both classes of DBPs could be generated during the chlorination of prevalent terpenes by competing reactions, which are associated with the volatile state of indoor ingredients after disinfection. The C-type lectin receptor signaling pathway and cellular senescence were significantly perturbed pathways, which interfered with the development of lung fibrosis. The negative effect was further investigated by molecular docking and transcription, which showed that HAAs can interact with four C-type lectin receptor proteins by hydrogen bonds and inhibit the mRNA expression of related proteins. This study highlights the potential secondary biological risk caused by intensive DBPs generated from chlorination and draws our attention to the potential environmental factors leading to chronic respiratory disease.

Establishment and validation a prediction model for discrimination of invasive adenocarcinomas for patients with peripheral pulmonary subsolid nodules.

Background: The optimal management of patients with subsolid pulmonary nodules is of growing clinical concern. This study sought to develop and validate a more precise predictive model to evaluate the pathological invasiveness of patients with lung peripheral subsolid nodules (SSNs). Methods: The data of 1,140 patients with peripheral SSNs who underwent surgical resection at Shanghai Renji Hospital from January 2014 to December 2018 were retrospectively analyzed. The patients were randomly assigned to a training and validation cohort (at a ratio of 2 to 1). Clinical parameters and imaging features were collected to estimate the independent predictors of pathological invasiveness of SSNs. A nomogram model was developed and applied to the validation cohort. The predictive performance of the nomogram model was evaluated by a calibration curve analysis, an area under the receiver operating characteristic curve (AUC) analysis, and a decision curve analysis (DCA), which was also compared with other diagnostic models. Results: In the multivariate analysis, the nodule diameter (P<0.001), solid component size (P<0.001), mean CT attenuation (P=0.001), spiculation (P<0.001), and pleura indentation (P=0.011) were identified as independent predictors of the pathological invasiveness of SSNs. A nomogram model based on the results of the multivariate analysis was developed and showed a robust discrimination in the validation cohort, with an AUC of [0.890; 95% confidence interval (CI), 0873-0.907], which was higher than another two reported models. The calibration curve showed optimal agreement between the pathological invasive probability as predicted by the nomogram and the actual probability. Conclusions: We developed and validated a nomogram model to evaluate the risk of the pathological invasiveness for patients with lung SSNs. The AUC of this nomogram model was higher than another two reported models. Our nomogram model may help clinicians to make individualized treatment more precisely.

Incidence of venous thromboembolism and hemorrhage in Chinese patients after pulmonary lobectomy: mechanical prophylaxis or mechanical prophylaxis combined with pharmacological prophylaxis: a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) and postoperative bleeding are important complications of lung resection surgery. We investigated the preventive effect of mechanical prophylaxis versus pharmacological prophylaxis after lobectomy, and evaluated the effect of both on the incidence of hemorrhagic events. METHODS: A prospective study of 424 lobectomies with moderate to high risk of VTE (Caprini risk score <5) in a single center was performed from April 2020 to March 2021. Patients were 1:1 randomly allocated to mechanical prophylaxis or to the low-molecular-weight heparin (LMWH)-combination-prophylaxis. The incidence of postoperative thrombotic and bleeding events and relevant factors of the two groups were analyzed. RESULTS: A total of 410 participants, with 202 and 208 in the mechanical prophylaxis and LMWH-combination-prophylaxis groups respectively, were selected for analysis. Both groups had similar baseline and clinical characteristics. There were no cases of VTE or major bleeding during the study, but the incidence rate of minor bleeding in the LMWH-combination-prophylaxis group was significantly higher than mechanical prophylaxis group [odds ratio (OR) 0.035, 95% confidence interval (CI): 0.011-0.113]. CONCLUSIONS: A case-by-case risk assessment of VTE and hemorrhage remains necessary to determine the most appropriate method of thrombosis prophylaxis for patients undergoing pulmonary surgery. Mechanical prophylaxis may be preferable for lung cancer patients with moderate to high risk of VTE (Caprini risk score <5) undergoing lobectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051073.

A Recurrence Predictive Model for Thymic Tumors and Its Implication for Postoperative Management: a Chinese Alliance for Research in Thymomas Database Study.

OBJECTIVE: Our aim was to investigate appropriate postoperative management based on the risk of disease recurrence in thymic epithelial tumors after complete resection. METHODS: The Chinese Alliance for Research in Thymomas retrospective database was reviewed. Patients having stage I to IIIa tumors without pretreatment and with complete resection were included. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram for building a recurrence predictive model. RESULTS: A total of 907 cases, including 802 thymomas, 88 thymic carcinomas, and 17 neuroendocrine tumors, were retrieved between 1994 and 2012. With a median follow-up of 52 months, the 10-year overall survival rate was 89.5%. Distant and/or locoregional recurrences were noted in 53 patients (5.8%). The nomogram model revealed histologic type and T stage as independent predictive factors for recurrence, with a bootstrap-corrected C-index of 0.86. On the basis of this model, patients with T1 thymomas or T2 or T3 type A, AB, or B1 thymomas had a significantly lower incidence of recurrence (low-risk group) than those with T2 or T3 type B2 or B3 thymomas and all thymic carcinomas and neuroendocrine tumors (high-risk group) (2.7% versus 20.1% [p < 0.001]). In the high-risk group, more than half of the recurrences (55.2% [16 of 29]) were seen within the first 3 postoperative years, whereas all recurrences but one were recorded within 6 years after surgery. Recurrence occurred quite evenly over 10 postoperative years in the low-risk group. CONCLUSIONS: A 6-year active surveillance should be considered in high-risk patients regardless of adjuvant therapy. For low-risk patients, annual follow-up may be sufficient. Studies examining postoperative adjuvant therapies would be plausible in high-risk patients.

Development and validation of a predictive model for the diagnosis of solid solitary pulmonary nodules using data mining methods.

BACKGROUND: The purpose of this study is to develop a predictive model to accurately predict the malignancy of solid solitary pulmonary nodule (SPN) by data mining methods. METHODS: A training cohort of 388 consecutive patients with solid SPNs was used to develop a predictive model to evaluate the malignancy of solid SPNs. By using SPSS Modeler, we utilized logistic regression (LR), artificial neural network (ANN), k-nearest neighbor (KNN), random forest (RF), and support vector machines (SVM) classifiers to build predictive models. Another cohort of 200 consecutive patients with solid SPNs was used to verify the accuracy of the predictive model. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: There was no significant difference in patients' characteristics between the training cohort and the validation cohort. The AUCs of LR, ANN, KNN, RF, and SVM models for the validation cohort were 0.874±0.0280 (P=0.605), 0.833±0.0351 (P=0.104), 0.792±0.0418 (P=0.014), 0.775±0.0400 (P=0.013), and 0.890±0.0323 (reference), respectively. The SVM algorithm had the highest AUC, and the best sensitivity (90.3%), specificity (80.4%), positive predictive value (93.9%), negative predictive value (71.2%) and accuracy (88.0%) for the validation cohort among the five models. CONCLUSIONS: Data mining by SVM might be a useful auxiliary algorithm in predicting malignancy of solid SPNs.

Pulmonary function changes after different extent of pulmonary resection under video-assisted thoracic surgery.

BACKGROUND: Limited resections for early stage lung cancer have been of increasing interests recently. However, it is still unclear to what extent a limited resection could preserve pulmonary function comparing to standard lobectomy, especially in the context of minimally invasive surgery. The purpose of this study was to evaluate postoperative changes of spirometry in patients undergoing video-assisted thoracic surgery (VATS) lobectomy or limited resections. METHODS: Spirometry tests were obtained prospectively before and 6 months after 75 VATS lobectomy, 34 VATS segmentectomy, 15 VATS wedge resection. Eleven VATS mediastinal procedures without lung resection were taken as a control group. Results were compared between groups of different resection extent. RESULTS: Demographic characteristics and preoperative pulmonary function showed no differences among the four groups. Forced vital capacity (FVC) loss after lobectomy was significantly greater than after segmentectomy (P=0.048), and much significantly greater than after wedge resection (P<0.001). Forced expiratory volume in 1 second (FEV1) loss after lobectomy was similar to segmentectomy (P=0.273), both significantly greater than after wedge resection (P<0.01). Diffusing capacity of the lungs for carbon monoxide (DLCO) loss was similar among these three groups (P=0.293). There was no significant difference in any spirometry index between wedge resection and mediastinal procedures (FVC: P=0.856; FEV1: P=0.671; DLCO: P=0.057). When compared by average value per segment resected, pulmonary function loss was significantly less after lobectomy than after segmentectomy in all spirometry indexes (P<0.001). On average, pulmonary function loss was around 5% per segment for VATS lobectomy and 10% per segment for VATS segmentectomy. CONCLUSIONS: In minimal invasive surgery, wedge resection best preserves pulmonary function with similar spirometry change with VATS mediastinal procedures without lung resection. Compared with VATS lobectomy, VATS segmentectomy may help minimize loss of FVC but not FEV1 or DLCO. Pulmonary function loss per segment resected is doubled after VATS segmentectomy than after lobectomy. These results should be taken into account when deciding the extent of resection for patients with early stage lung cancer.

[Associated factors of postoperative relapse and metastasis in pT1bN0M0-pT4aN0M0 thoracic esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the associated high risk factors of postoperative relapse and metastasis for patients with confined tumors (grade pT1b-4a) without lymph-node metastases (pN0) in thoracic esophageal squamous cell carcinoma (ESCC). METHODS: Clinicopathological and follow up data of ESCC patients undergoing radical surgical resection as primary treatment in the Department of Thoracic Surgery, Shanghai Chest Hospital between January 2004 and December 2012 from Hospital Database were retrospectively collected. The inclusion criteria were as follows: (1) the first development of ESCC confirmed by histopathology without lymphatic and distant metastasis; (2) pathological stage of pT1bN0M0 to pT4aN0M0 according to the Union for International Cancer Control (UICC) in 2009; (3) curative trans-thoracic esophagectomy with R0 (tumor-free surgical margin) resection, using the Ivor-Lewis or McKeown procedure; two-field lymphadenectomy or three-field lymph node dissection based on the positive results of preoperative cervical ultrasonography examination or CT scan; (4) without adjuvant chemotherapy and/or radiotherapy before and after operation; (5) complete follow-up data. Logistic regression analysis was employed to identify the clinicopathological factors affecting the postoperative relapse and metastasis. RESULTS: A total of 112 patients were eligible, including 94 male cases and 18 female cases; age of (58.6±7.7) years; squamous carcinoma of upper thorax in 25 cases, of middle thorax in 67 cases and of lower thorax segment in 20 cases; 12 cases of high-differentiated ESCC, 49 cases of moderate-differentiated ESCC, poorly-differentiated ESCC in 48 cases; 4 cases of I(a stage, 9 cases of I(b, 24 cases of II(a, 62 cases of II(b, 13 cases of III(a; the tumor length >4 cm in 43 cases, ≤4 cm in 69 cases. Forty-three (38.4%) patients presented relapse or metastasis during the follow-up, including 24 (21.4%) of loco-regional relapse, 13 (11.6%) of distant metastasis, and 6(5.4%) of both above. Multivariate regression analysis revealed that poorly-differentiated tumor (OR=1.899, 95%CI:1.233-2.925, P=0.004), upper-middle location (OR=2.351, 95%CI:1.188-4.653, P=0.014), and tumor length >4 cm (OR=2.381, 95%CI:1.009-5.618, P=0.048) were independent risk factors of overall postoperative relapse and metastasis for thoracic ESCC with stage pT1b N0M0-T4aN0M0. Further stratified analysis identified that only poorly-differentiated tumor (OR=1.730, 95%CI:1.121-2.671, P=0.013) was an independent risk factor of loco-regional relapse, whereas pathological stage II(b-III(a (OR=3.372, 95%CI:1.206-9.428, P=0.021) was an independent risk factor of distant metastasis. CONCLUSIONS: Poorly-differentiated tumor, tumor length >4 cm, and upper-middle location may be regarded as high risk factors for predicting overall relapse and metastasis of pN0 thoracic ESCC patients after esophagectomy. Moreover, poorly-differentiated tumor is the only independent risk factor of postoperative loco-regional relapse, meanwhile it should be noted that pathological stage II(b-III(a is closely related to postoperative distant metastasis.

A multi-center retrospective study of single-port versus multi-port video-assisted thoracoscopic lobectomy and anatomic segmentectomy.

BACKGROUND: To assess the feasibility and perioperative outcomes of single-port (SP) and multi-port (MP) approaches for video-assisted thoracoscopic surgery (VATS) lobectomy and anatomical segmentectomy. METHODS: Retrospective data from 458 patients who received VATS lobectomy or anatomical segmentectomy at Shanghai Chest Hospital, Korea University Guro Hospital, Affiliated Hospital of National Taiwan University, University of Hong Kong Queen Mary Hospital and Shenzhen Hospital were collected. Patients were divided into SP group and MP group according to the surgical approach. Perioperative factors such as operation time, blood loss during surgery, conversion rate, the number and stations of lymph nodes harvested, postoperative chest tube drainage time, postoperative hospitalization time, perioperative morbidity and mortality, and pain scores during the first 3 days after surgery were compared between the two groups. RESULTS: There were no differences in the number (P=0.278) and stations (P=0.564) of lymph nodes harvested, postoperative morbidity (P=0.414) or mortality(P=0.246), and pain score on the third day (P=0.630) after surgery between the two groups. The SP group had a longer operation time (P=0.042) and greater intraoperative blood loss (P<0.001), but the conversion rate was even higher in the MP group (P=0.018). Patients in the SP group had shorter chest tube removal time (P=0.012) and postoperative hospitalization time (P=0.005). Pain scores were lower on the first (P=0.014) and second (P=0.006) day after surgery in the SP group. CONCLUSIONS: SP VATS lobectomy and anatomical segmentectomy is technologically more demanding than MP VATS. It can be safe and feasible in the hands of experienced surgeons, with comparable preoperative outcomes to MP VATS, but less pain in the early postoperative period.

Minimally invasive thymectomy for locally advanced recurrent thymoma.

BACKGROUND: Minimally invasive thymectomy for early stage thymoma patients has been shown to yield similar oncological results while being helpful in reducing surgical trauma, improving postoperative recovery, and diminishing incisional pain. However, patients with locally advanced tumors, preoperative induction therapies, or prior history of mediastinal surgery have been considered as not suitable for video-assisted thoracoscopic surgery (VATS). This video aims to show that VATS thymectomy may also be feasible in reoperation for recurrent invasive thymoma in selected cases. METHODS: A 45-year-old female patient had recurrent type B2 thymoma in the anterior mediastinum 10 years after tumor resection through left thoracotomy. The lesion was in rcStage III. Reoperation was carried out via left approach VATS. The tumor was resected completely together with remnant thymus, pericardium, the left phrenic nerve, and the left innominate vein. RESULTS: The patient recovered uneventfully and was discharged on postoperative day 4. Pathologic study revealed an rpStage III type B tumor, invading the left phrenic nerve and the left innominate vein. CONCLUSIONS: VATS thymectomy may also be feasible in locally advanced thymic tumors or recurrent diseases. In selected cases, VATS should at least be tried so that this subgroup of patients may also benefit from minimally invasive surgery.

The correlation between high body mass index and survival in patients with esophageal cancer after curative esophagectomy: evidence from retrospective studies.

OBJECTIVE: To investigate the predictive value of high body mass index (H-BMI) on the survival of patients with esophageal cancer (EC) after curative esophagectomy. METHODS: Studies were systematically identified to investigate the relationship between overweight and obese (H-BMI) and clinical outcomes in EC patients treated with curative esophagectomy. Measured clinical outcomes were disease-free survival (DFS) and overall survival (OS). The pooled hazard ratio (HR) with 95% confidence interval (CI) was estimated. Subgroup analyses were performed according to tumour type and body mass index (BMI). RESULTS: Fourteen studies with 4823 cases were included in the final pooled quantitative analysis. In EC patients overall, H-BMI was associated with improved DFS (HR, 0.83; 95% CI: 0.75-0.90) and OS (HR, 0.79; 95 % CI: 0.73-0.85), as compared with normal BMI. The results were consistent with those who were overweight. Among patients with esophageal adenocarcinoma (EAC), a better prognosis, as reflected by OS, was observed with H-BMI (HR, 0.81; 95% CI: 0.73-0.89). The same results were also observed in EAC patients who were obese and overweight. In contrast, among patients with esophageal squamous cell carcinoma (ESCC), H-BMI was associated with a worse prognosis, as reflected by DFS (HR, 2.26; 95% CI: 1.29-3.24). CONCLUSIONS: H-BMI has distinctly different impacts on the postoperative survival of EAC and ESCC patients. H-BMI is a potential predictor for better prognosis in EC patients overall, and particularly in EAC patients, treated with curative esophagectomy. However, in ESCC patients, H-BMI is a potential predictor for a worse prognosis of postoperative survival.

The IASLC/ATS/ERS classification of lung adenocarcinoma-a surgical point of view.

Adenocarcinoma has become the most common histologic type of lung cancers. Ground glass nodules (GGN), most of them early stage noninvasive or minimally invasive adenocarcinomas (MIA), have been encountered more frequently with the application of computed tomography (CT) screening. The International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic lung adenocarcinoma classification combines radiologic, histologic, clinic, and molecular features to form a diagnostic approach for different subgroups of diseases. One of the major focuses of this new classification is the introduction of adenocarcinoma in situ (AIS) and MIA, to replace the old term of bronchioloalveolar carcinoma (BAC). Not all GGNs are malignant lesions that should be surgically resected upon first presentation. A management approach different to solid nodules has been suggested based on the understanding that these lesions tend to have a more indolent nature. Hasty intervention should be avoided and potential surgical risks, radiation exposure, patient psychology, and socio-economical burden must be balanced comprehensively before surgery is decided upon. In the mean time, surgical issues concerning extent of resection and lymphadenectomy should also be carefully contemplated once intervention is deemed necessary. Extremely good prognosis with a near 100% disease-free survival could be expected when a pure GGN is completely resected. This has led to re-evaluation of sublobar resections, including both segmentectomy and big wedge resection, for small (≤2 cm) less invasive histology (AIS or MIA) appearing as GGN on CT scan. Evidences are accumulating that these limited resections are oncologically equivalent to standard lobectomy. And extensive lymph node dissection may not have additional staging or prognostic benefit. These would add new meaning to the contemporary definition of minimally invasive surgery for lung cancers. Overall, joint effort from a multiple disciplinary team is imperative, and decision making should be based on both anatomical and biological nature of the disease.