Establishing a TNM-like risk classification for metachronous second pulmonary adenocarcinoma in patients with previously resected pulmonary adenocarcinoma.

Background: For metachronous second pulmonary adenocarcinoma (msPAD) in patients with resected PAD, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis. Methods: Patients received surgery for the primary and encountered msPAD were recruited into the Surveillance, Epidemiology, and End Results database. We extracted overall survival 1 (OS1) for the primary, overall survival 2 (OS2) for the msPAD, and defined interval survival as the interval time between the first and second PAD. Based on the nomogram and recursive partitioning analysis, a tumor, node, metastasis staging system (TNM)-like risk stratification system was established for OS2 on the premise of suspending the dispute of tumor clonality. Results: A total of 1,045 patients were identified. There is no significant association between interval survival and OS2. A TNM-like risk stratification system was established based on the independent pathological factors for prognosis, including tumor diameter (2nd), node metastasis (2nd), grade (2nd), and extrapulmonary metastasis (2nd). The proposed risk stratification system present well capacity in predicting and stratifying prognosis. Compared with the TNM stage system, the proposed risk stratification system presents a smaller Akaike information criterion (AIC) but larger c-index, and generates higher accuracy to predict prognosis at 160 months of follow-up according to the time-dependent receiver operating curve (ROC) curve. Conclusions: In conclusion, the TNM-like risk stratification appears to be suitable for prognostic prediction and risk stratification for msPAD patients with former PAD resection. This model validates and refines the known classification rules based on the easily collected variables, and highlights potentially clinical implications.

Establishing a prognostic model for metachronous second squamous cell lung cancer in patients with resected squamous cell lung cancer.

BACKGROUND: For metachronous second pulmonary squamous cell carcinoma (msPSC) in patients with resected PSC, the method to distinguish tumour clonality has not yet been well established, which makes it difficult to determine accurate staging and predict prognosis. METHODS: Patients who underwent surgery for first PSC and encountered msPSC were recruited from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted overall survival 1 (OS1) for the first PSC, overall survival 2 (OS2) for msPSC, and interval survival for the time interval between the first and second PSC. The nomogram was calibrated for OS2, and recursive partitioning analysis (RPA) was performed for risk stratification. RESULTS: A total of 617 patients were identified. Several independent prognostic factors were identified and integrated into the nomogram for OS2, including gender, age (2nd), nodal status (1st), node metastasis (2nd), and extrapulmonary metastasis (2nd). The calibration curves showed optimal agreement between the predictions and actual observations, and the c-index was 0.678. Surgery was associated with longer survival for msPSC patients. The prognosis of sublobectomy was comparable and inferior to that of lobectomy in the low- and moderate-risk groups, respectively. Radiotherapy was associated with better outcomes in patients who did not undergo surgery. CONCLUSIONS: The RPA-based clinical nomogram appears to be suitable for the prognostic prediction and risk stratification of OS2 in msPSC. This practical system may help clinicians make decisions and design clinical studies.

Impact of Examined Lymph Node Count for Esophageal Squamous Cell Carcinoma in Patients who Underwent Right Transthoracic Esophagectomy.

BACKGROUND: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who underwent right transthoracic esophagectomy is still unclear. METHODS: Patients with ESCC who underwent right transthoracic esophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem and ß-binomial distribution estimation, respectively. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression. RESULTS: Among the 875 included patients, greater ELNs were associated with a higher rate of nodal metastasis. Significant association between staging bias and the number of ELNs is only observed through the Bayes method. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted hazard ratio [aHR] 0.986), especially in those patients with node-negative disease (aHR 0.972). In patients with node-negative disease, cut-point analysis showed a threshold ELN count of 21. CONCLUSIONS: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 21 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease using the right thoracic approach.

Impact of treatment modality on long-term survival of stage IA small-cell lung cancer patients: a cohort study of the U.S. SEER database.

BACKGROUND: The optimal treatment modality for patients with stage IA (T1N0M0) small-cell lung cancer (SCLC) is still unclear. METHODS: Patients who received surgical resection or chemo-radiotherapy (CRT) between January 2004 and December 2014 were identified from The Surveillance, Epidemiology and End Results (SEER) database. Surgical resection included lobectomy, wedge resection, segmentectomy with lymphadenectomy [examined lymph node (ELN) ≥1]. Propensity score match analysis was utilized to balance the baseline characteristics. RESULTS: A total of 686 stage IA SCLC cases were included: 337 patients underwent surgery and 349 patients were treated by CRT alone. Surgery achieved a better outcome than CRT alone, with an adjusted hazard ratio (HR) of 0.495. Patients who underwent lobectomy demonstrated a longer overall survival (OS), compared to those who received sublobectomy (crude cohort, median OS, 69 vs. 38 months; match cohort, median OS, 67 vs. 38 months). Patients with ELN >7 presented with longer OS than those with ELN ≤7 (crude cohort, median OS, 91 vs. 49 months; matched cohort, median OS, 91 vs. 54 months). The additional efficacy of chemotherapy or radiotherapy in patients receiving lobectomy was observed. The best prognosis was achieved in the lobectomy plus CRT cohort, with a 5-year survival rate of 73.5%. CONCLUSIONS: The prolonged survival associated with lobectomy and chemotherapy or radiotherapy presents a viable treatment option in the management of patients with stage IA SCLC.

Oncologic outcomes of lobectomy vs. segmentectomy in non-small cell lung cancer with clinical T1N0M0 stage: a literature review and meta-analysis.

BACKGROUND: Lobectomy has long been regarded as the standard treatment for operable non-small cell lung cancer (NSCLC). Recent studies suggested that segmentectomy could achieve a good prognosis for early-stage NSCLC and might be an alternative to lobectomy in this cohort. Until now, on the issue of comparison between lobectomy and segmentectomy, there remains no published randomized controlled trial (RCT), and all existing evidence is low. Recently, a categorization of lower-level evidence has been proposed, namely, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The aim of this meta-analysis is to compare the oncologic outcome between lobectomy and segmentectomy in NSCLC with the clinical T1N0M0 stage according to the GRADE system. METHODS: PubMed, the PMC database, EMBASE, Web of Science, and the Cochrane library were searched prior to May 2019 to identify studies that compared the prognosis between lobectomy and segmentectomy for clinical T1N0M0 NSCLC. The evidence level of the included studies was assessed according to the GRADE system, including level IIA, probably not confounded nonrandomized comparison; level IIB, possibly confounded nonrandomized comparison; and level IIC, probably confounded nonrandomized comparison. The predefined outcomes included overall survival (OS) and disease-free survival (DFS). Univariable and multivariable hazard ratios (HRs) with 95% confidence intervals (95% CI) were pooled using a random-effects model. RESULTS: Twelve nonrandomized studies involving 8,072 participants were included. Of these studies, two were classified as IIA level (16.7%), six as IIB level (50.0%), and four as IIC level (33.3%). When crude HRs were included, compared with lobectomy, segmentectomy was associated with shorter OS but comparable DFS in the entire cohort (OS, pooled HR =1.45, 95% CI, 1.23 to 1.67; DFS, pooled HR =1.03, 95% CI, 0.65 to 1.82) and in patients with nodules ≤2 cm (OS, pooled HR =1.55, 95% CI, 1.33 to 1.80; DFS, pooled HR =0.98, 95% CI, 0.55 to 1.77). When adjusted HRs were included, the impact of segmentectomy on OS and DFS was comparable to that of lobectomy in the entire cohort (OS, pooled HR =1.39, 95% CI, 0.92 to 2.10; DFS, pooled HR =0.83, 95% CI, 0.66 to 1.03) and in patients with nodules ≤2 cm (OS, pooled HR =1.61, 95% CI, 0.87 to 3.00; DFS, pooled HR =0.90, 95% CI, 0.63 to 1.27). CONCLUSIONS: Based on our results, although shorter OS is observed in patients received segmentectomy, it is necessary to wait for more results from RCT to draw a valid conclusion.

Impact of examined lymph node count for oesophageal squamous cell carcinoma in patients who underwent left transthoracic oesophagectomy.

BACKGROUND: The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with oesophageal squamous cell carcinoma (ESCC) who underwent left transthoracic oesophagectomy is still unclear. METHODS: Patients with ESCC who underwent left transthoracic oesophagectomy at Sun Yat-sen University Cancer Center between January 1997 and December 2013 were retrospectively enrolled. The Cox proportional hazards regression model was used to determine the effect of ELN count on overall survival (OS). The association between ELN count and nodal status was investigated through scatter plot and binary logistic regression analyses. The impact of ELN count on stage correction was evaluated using the hypergeometric distribution and Bayes theorem. The threshold of ELNs was determined using the LOWESS smoother and piecewise linear regression. RESULTS: Among the 1826 included patients, greater ELNs were associated with a higher rate of nodal metastasis (adjusted OR = 1.018). When the ELN count increased, the omission rate of positive lymph nodes (LNs) decreased. The ELN count did not impact 90-day mortality but significantly impacted long-term survival (adjusted HR = 0.983), especially in those with node-negative disease (adjust HR = 0.972). In patients with node-negative disease, cut point analysis showed a threshold ELN count of 18. CONCLUSIONS: A greater number of ELNs is associated with more accurate node staging and better long-term survival in resected ESCC patients. We recommended harvesting at least 18 LNs to acquire accurate staging and long-term survival information for patients with declared node-negative disease in the left thoracic approach.

Serum Peroxisome Proliferator-activated Receptor Gamma Coactivator-1α Related to Myocardial Energy Expenditure in Patients With Chronic Heart Failure.

BACKGROUND: Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) plays key roles in controlling cardiac metabolism and function. Myocardial energy expenditure (MEE) can reflect myocardial energy metabolism and cardiac function. Whether the variation of PGC-1α can influence MEE levels in chronic heart failure (CHF) is unclear. Therefore, we investigated the relationship between PGC-1α and MEE. MATERIAL AND METHODS: We studied 219 patients with CHF and 66 healthy controls. MEE was measured according to echocardiographic parameters. Serum PGC-1α, N-terminal pro-B-type natriuretic peptide and other parameters were detected. Patients with CHF were divided into different groups according to the left ventricular ejection fraction (LVEF) and the tertile range of MEE. RESULTS: Serum PGC-1α was lower in the MEE 2 and 3 groups compared with controls (both P < 0.05). Patients in the MEE 2 (1.73 ± 0.83 versus 2.16 ± 0.82 ng/mL, P = 0.001) and 3 groups (1.65 ± 0.73 versus 2.16 ± 0.82 ng/mL, P < 0.001) possessed lower levels of PGC-1α than those in the MEE 1 group. Compared with high LVEF, patients with low LVEF had higher MEE (median, 167 versus 73 cal/minute, P < 0.05) and lower PGC-1α (1.71 ± 0.65 versus 1.95 ± 0.91 ng/mL, P = 0.032). Multivariate logistic regression analysis showed that MEE (OR = 0.517, 95% CI = 0.267-0.998, P = 0.049) and creatinine (OR = 2.704, 95% CI = 1.144-6.391, P = 0.023) were independently associated with increased PGC-1α. CONCLUSIONS: Serum PGC-1α was related to MEE and LVEF in patients with CHF and can reflect the degree of MEE and the systolic function of the left ventricle.

Predicting prognosis in resected esophageal squamous cell carcinoma using a clinical nomogram and recursive partitioning analysis.

BACKGROUND: Development demand of precise medicine in resectable esophageal squamous cell carcinoma (ESCC) require to recognize patients at high risk treated by surgery alone. Thus, our aim was to construct a clinical nomogram and recursive partitioning analysis (RPA) to predict long-term survival in ESCC treated by surgery alone. METHODS: Based on the patients with ESCC who treated by three-incisional esophagectomy and two-field lymphadenectomy alone, we identified and integrated significant prognostic factors for survival to build a nomogram. The nomogram was calibrated for overall survival (OS) and the predictive accuracy and discriminative ability was measured by concordance index (c-index) and Akaike information criterion (AIC). Based on the nomogram, the RPA was performed for risk stratification. RESULTS: A total of 747 patients were included for analysis. Five independent prognostic factors were identified and entered into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year OS showed optimal agreement between nomogram prediction and actual observation. The AIC value of the nomogram was lower than that of the 7th edition staging system, whereas the c-index of the nomogram was higher than that of the 7th edition staging system. The risk groups stratified by RPA allowed significant distinction between survival curves within respective TNM categories. CONCLUSION: The RPA based on a clinical nomogram appears to be suitable for risk stratification in OS for resected ESCC. This practical system may help clinicians in decision making and design of clinical studies.

Relationship between the maximum carotid plaque area and the severity of coronary atherosclerosis.

BACKGROUND: Carotid artery plaque is associated with coronary artery disease (CAD). Besides the presence of plaque, plaque characteristics is also related to the severity of CAD. So the characteristic difference of carotid plaque may affect this assessment role. However, it is unclear whether the maximum carotid plaque area can reflect the extents and severity of CAD. METHODS: We enrolled 388 consecutive CAD patients and 45 controls, and 204 patients were studied after excluding 184 patients without carotid plaque or coronary angiogram. Carotid intima media thickness and carotid plaque were measured by carotid ultrasound. Coronary angiography was applied and Gensini score was calculated. Blood lipid and other parameters were also detected. RESULTS: The total and right maximum carotid plaque area were greater in high Gensini Score group than those in low and moderate score groups (both P<0.05) and multivessel disease patients possessed the highest maximum plaque area. The total and right maximum carotid plaque area were also higher in collateral circulation group than those in non-collateral group (P=0.036 and 0.002 respectively). Multivariate logistic regression showed that Gensini score (OR=2.458, 95% CI=1.111 to 5.439, P=0.027) was associated with increased total maximum carotid plaque area. The optimal cut-off value for predicting the severity of CAD was 46.75 mm2 for total maximum plaque area. CONCLUSIONS: The maximum carotid plaque area can reflect the clinical severity of CAD, and it can be used as a simple noninvasive indicator of severity of coronary atherosclerosis.