Network-based analysis identifies potential therapeutic ingredients of Chinese medicines and their mechanisms toward lung cancer.

Lung cancer is one of the most common malignant tumors around the world, which has the highest mortality rate among all cancers. Traditional Chinese medicine (TCM) has attracted increased attention in the field of lung cancer treatment. However, the abundance of ingredients in Chinese medicines presents a challenge in identifying promising ingredient candidates and exploring their mechanisms for lung cancer treatment. In this work, two network-based algorithms were combined to calculate the network relationships between ingredient targets and lung cancer targets in the human interactome. Based on the enrichment analysis of the constructed disease module, key targets of lung cancer were identified. In addition, molecular docking and enrichment analysis of the overlapping targets between lung cancer and ingredients were performed to investigate the potential mechanisms of ingredient candidates against lung cancer. Ten potential ingredients against lung cancer were identified and they may have similar effect on the development of lung cancer. The results obtained from this study offered valuable insights and provided potential avenues for the development of novel drugs aimed at treating lung cancer.

Unveiling the mechanisms of nephrotoxicity caused by nephrotoxic compounds using toxicological network analysis.

Billions of people worldwide have experienced irreversible kidney injuries, which is mainly attributed to the complexity of drug-induced nephrotoxicity. Consequently, there is an urgent need for uncovering the mechanisms of nephrotoxicity caused by compounds. In the present study, a network-based methodology was applied to explore the mechanisms of nephrotoxicity induced by specific compounds. Initially, a total of 42 nephrotoxic compounds and 60 kinds of syndromes associated with nephrotoxicity were collected from public resources. Afterward, network localization and separation algorithms were used to map the targets of compounds and diseases into the human interactome. By doing so, 199 statistically significant nephrotoxic networks displaying the interaction between compound targets and disease genes were obtained, which played pivotal roles in compounds-induced nephrotoxicity. Subsequently, enrichment analysis pinpointed core Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways that highlight commonalities in nephrotoxicity induced by nephrotoxic compounds. It was found that nephrotoxic compounds primarily induce nephrotoxicity by mediating the advanced glycosylation end products-receptor for advanced glycosylation end products signaling pathway in diabetic complications, human cytomegalovirus infection, lipid and atherosclerosis, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and the phosphatidylinositol 3-kinase-Akt pathways. These results provide valuable insights for preventing drug-induced nephrotoxicity. Furthermore, the approaches we used are also helpful in conducting research on other kinds of toxicities.

Case report: A rare case of desmoid-type fibromatosis originating in the small intestine.

Background: Desmoid-type fibromatosis (DF) is characterized by a rare monoclonal fibroblast proliferation that exhibits variable and unpredictable clinical presentation. DF can be classified into sporadic and hereditary types. Despite extensive research efforts, the exact etiology of DF remains elusive. Case description: A 31-year-old male patient presented to the hospital with a progressively growing mass in the right lower abdomen, accompanied by abdominal discomfort. Symptoms are discovered 1 week before admission. Enteroscopy revealed no evidence of colonic abnormalities, and blood tests did not indicate any abnormalities. Due to the indeterminate nature of the mass during surgery, a partial resection of the ileum and cecum was performed, followed by ileocolonic end-to-end anastomosis, with no postoperative complications. The final pathological diagnosis confirmed primary desmoid-type fibromatosis of the distal ileum (invasive fibromatosis). To effectively manage DF, we recommend a follow-up schedule for patients. This includes appointments every 3 months in the first year following surgery, followed by appointments every 6 months up to the fifth year, and then once a year thereafter. The follow-up examinations should include collection of the patient's medical history, physical examination, blood tests, ultrasounds, CT scans, and other relevant assessments. During the first year of the follow-up period, no further treatment was administered, and the patient remained disease-free. Conclusion: Desmoid-type fibromatosis (DF) originating from the small intestine is an extremely rare condition that exhibits local invasiveness and can be life-threatening. Despite its benign histology, DF has a high local recurrence rate and lacks metastatic potential. Diagnosis of DF remains challenging, especially in cases where surgical intervention is not feasible due to asymptomatic patients or partial organ impairment. In such cases, a "watchful waiting" approach is recommended as the initial treatment strategy. However, when preoperative diagnosis is difficult, surgery is typically considered the best option. Given the potential for local recurrence and the uncertain long-term prognosis, regular follow-up is necessary.

Single-cell profiling of the copy-number heterogeneity in colorectal cancer.

BACKGROUND: With functionally heterogeneous cells, tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment. Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth, invasion, and immune evasion. However, no reliable method to classify tumor cell subtypes is yet available. In this study, we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable (MSS) colorectal cancer (CRC). METHODS: To characterize the somatic copy number alteration (SCNA) of MSS CRC in a single cell profile, we analyzed 26 tissue samples from 19 Korean patients (GSE132465, the Samsung Medical Center [SMC] dataset) and then verified our findings with 15 tissue samples from five Belgian patients (GSE144735, the Katholieke Universiteit Leuven 3 [KUL3] dataset). The Cancer Genome Atlas (TCGA) cohort, GSE39582 cohort, and National Cancer Center (NCC) cohort (24 MSS CRC patients were enrolled in this study between March 2017 and October 2017) were used to validate the clinical features of prognostic signatures. RESULTS: We employed single cell RNA-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics. Among these three types of tumor cells, C1 and C3 had a higher SCNA burden; C1 had significant chromosome 13 and 20 amplification, whereas C3 was the polar opposite of C1, which exhibited deletion in chromosome 13 and 20. The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations. C1 and C2 were linked to the immune response and hypoxia, respectively, while C3 was critical for cell adhesion activity and tumor angiogenesis. Additionally, one gene ( OLFM4 ) was identified as epithelium-specific biomarker of better prognosis of CRC (TCGA cohort: P  = 0.0110; GSE39582 cohort: P  = 0.0098; NCC cohort: P  = 0.0360). CONCLUSIONS: On the basis of copy number characteristics, we illustrated tumor heterogeneity in MSS CRC and identified three types of tumor cells with distinct roles in tumor microenvironment. By understanding heterogeneity in the intricate tumor microenvironment, we gained an insight into the mechanisms of tumor evolution, which may support the development of therapeutic strategies.

The value of a risk model combining specific risk factors for predicting postoperative severe morbidity in biliary tract cancer.

Purpose: Several surgical risk models are widely utilized in general surgery to predict postoperative morbidity. However, no studies have been undertaken to examine the predictive efficacy of these models in biliary tract cancer patients, and other perioperative variables can also influence morbidity. As a result, the study's goal was to examine these models alone, as well as risk models combined with disease-specific factors, in predicting severe complications. Methods: A retrospective study of 129 patients was carried out. Data on demographics, surgery, and outcomes were gathered. These model equations were used to determine the morbidity risks. Severe morbidity was defined as the complication comprehensive index ≥ 40. Results: Severe morbidity was observed in 25% (32/129) patients. Multivariate analysis demonstrated that four parameters [comprehensive risk score ≥1, T stage, albumin decrease value, and international normalized ratio (INR)] had a significant influence on the probability of major complications. The area under the curve (AUC) of combining the four parameters was assessed as having strong predictive value and was superior to the Estimation of Physiologic Ability and Surgical Stress System (E-PASS) alone (the AUC value was 0.858 vs. 0.724, p = 0.0375). The AUC for the modified E-PASS (mE-PASS) and Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) in patients over the age of 70 was classified as no predictive value (p = 0.217 and p = 0.063, respectively). Conclusion: The mE-PASS and POSSUM models are ineffective in predicting postoperative morbidity in patients above the age of 70. In biliary tract cancer (BTC) patients undergoing radical operation, a combination of E-PASS and perioperative parameters generates a reasonable prediction value for severe complications.

The Independent Prognostic Effect of Lymph Node Dissection on Patients With Stage IA NSCLC With Different T Stages.

Background: Currently, the extent of lymph node evaluation necessary for patients with early-stage non-small-cell lung cancer (NSCLC) remains controversial according to the latest ESMO and NCCN guidelines. In this study, we aimed to evaluate the survival effect of different numbers of lymph nodes examined (LNE) and regions of lymph nodes removed (LNR) in patients with stage IA NSCLC. Method: All patients with stage IA NSCLC undergoing lobectomy or bilobectomy were selected from the surveillance, epidemiology, and end results (SEER) database. The number of LNE and LNR were stratified into 4 groups (0, 1-2, 3-8, and ≥9 lymph nodes) and 3 groups (0, 1-3, and ≥4 regions) respectively. Additionally, the survival curves of overall survival (OS) and cancer-specific survival (CSS) were plotted and compared with the Kaplan-Meier method and log-rank test. Independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression and subgroup analysis. Results: Totally, 12,490 patients with stage IA NSCLC were enrolled in our study. Patients with ≥9 LNE and ≥4 LNR in both the T1b and T1c stages consistently demonstrated the significantly best OS and CSS outcomes. In the multivariate analysis, patients with ≥9 LNE consistently had a significantly better CSS [hazards ration (HR) (95% CI):0.539 (0.438-0.663)], and those with ≥4 LNR consistently had a significantly better OS [HR (95% CI):0.678 (0.476-0.966)]. Furthermore, ≥9 LNE and ≥4 LNR were associated with better survival in most subgroups. Conclusion: This study demonstrated that ≥9 LNE and ≥4 LNR are highly recommended for stage IA2 and stage IA3 patients but optional for stage IA1 patients.

The Prognostic Value of Log Odds of Positive Lymph Nodes in Early-Stage Esophageal Cancer Patients: A Study Based on the SEER Database and a Chinese Cohort.

OBJECTIVE: Early detection and timely treatment are important for improving the prognosis of esophageal cancer (EC). Identification of the prognostic risk factors could help us to discern the high-risk population. This study was aimed at exploring the prognostic significance of log odds of positive lymph nodes (LODDS) in early-stage EC patients. METHODS: Patients who underwent esophagectomy and diagnosed as pathologic T1-2 N0 EC were reviewed between January 2005 and December 2015 from the Surveillance, Epidemiology, and End Results (SEER) database (the development cohort, n = 1004). The X-tile software was used to determine the optimal cutoff values of LODDS. A separate Chinese cohort including 245 patients (the validation cohort) was used to externally validate the results of the SEER database. RESULT: Patients were divided into two groups based on the cutoff points of LODDS: <-1.40 (LODDS1) and ≥-1.40 (LODDS2). In the development cohort, the 5-year overall survival (OS) rate was 75.3% for patients in the LODDS1 group, compared with 67.5% for those in the LODDS2 group (P=0.002). In multivariate Cox analysis, LODDS was associated with OS significantly (hazard ratio (HR), 1.48; 95% confidence intervals (CI), 1.19-1.85). In the validation cohort, the 5-year OS rate was 76.6% for patients in the LODDS1 group, compared with 64.4% for those in the LODDS2 group (P=0.006). The HR value in multivariate Cox analysis for OS was 2.00 (95% CI, 1.26-3.18). CONCLUSION: LODDS was an important independent factor for survival in early-stage EC patients.

Proposed Modification of the pN2 Classification of the 8th Edition AJCC Staging System for Esophageal Squamous Cell Carcinoma: A Preliminary Study Based on the Chinese Population.

OBJECTIVE: To evaluate the efficacy of the nodal staging of the 8th edition AJCC staging system for esophageal squamous cell carcinoma (ESCC) and propose a modification of the current pN2 classification. METHODS: 1188 patients who underwent esophagectomy for ESCC at Sun Yat-sen University Cancer Center in Guangzhou (Guangdong, China) between January 2005 and June 2010 were reviewed. We used the X-tile software to determine the optimal cutoff points. Kaplan-Meier method and log-rank test were used to compare the differences of survival. Multivariate Cox regression analysis was performed for the factors that were statistically significant in univariate analysis. RESULT: In multivariate Cox regression analysis, alcohol consumption, pT status, and pN status were independent prognostic factors for overall survival (OS) according to the current pN classifications. And the observed 5-year OS rates for groups pN0, pN1, pN2, pN3 were 66.7%, 45.0%, 31.5%, and 21.5%, respectively (P<0.001). Based on the above results, the current pN2 classification was further subdivided as pN2a [3 metastatic lymph nodes (LNs)] and pN2b (4-6 metastatic LNs) groups. The 5-year OS rates for groups pN0, pN1, pN2a, pN2b, and pN3 were 66.7%, 45.0%, 37.7%, 26.3% and 21.5%, respectively (P<0.001). The rate of 5-year disease-free survival (DFS) was 60.0% for patients with pN0, compared with 36.8%, 29.3%, 20.8%, and 14.3% for those with pN1, pN2a, pN2b, and pN3, respectively (P<0.001).The current pN2 classification should be subdivided as pN2a (3 metastatic LNs) and pN2b (4-6 metastatic LNs) groups. The modified pN2 classification could better discriminate the survival differences between patients with 3-6 metastatic LNs for ESCC in the Chinese population.

A retrospective study on the impact of the number of resected lymph nodes on the survival outcome of stage IV rectal cancer patients after preoperative therapy.

BACKGROUND: There is no consensus on the optimal number of examined LNs for stage IV rectal cancer patients after preoperative therapy. We aimed to explore the impact of the number of resected lymph nodes (LNs) on the survival outcomes of stage IV rectal cancer patients after preoperative therapy. METHODS: Clinicopathologic data of 556 patients diagnosed with stage IV rectal cancer between 1st January, 2010 and 31st December, 2015 from the Surveillance, Epidemiology, and End Results (SEER) database after preoperative therapy were reviewed. The patients were further divided into two groups: the ≥15 resected LNs group and <15 resected LNs group based on the X-tile software analysis results of the number of resected LNs. RESULTS: Both univariate and multivariate regression analyses revealed that the number of resected LNs and N status were significantly positively correlated with the survival outcome of the patients. Patients in the ≥15 resected LNs group had a significant better cancer-specific survival (CSS) (P=0.003) than those in the <15 resected LNs group. The 3-year CSS rate was 63.2% for patients with ≥15 resected LNs compared with 55.7% for those with <15 resected LNs. The 5-year CSS rate was 50.2% and 30.5% for patients in the ≥15 resected LNs group and those in the <15 resected LNs group, respectively. CONCLUSIONS: The number of resected LNs is an important independent prognostic factor that influences the survival outcome of stage IV rectal cancer patients after receiving preoperative therapy.

Development and validation of a preoperative noninvasive predictive model based on circular tumor DNA for lymph node metastasis in resectable non-small cell lung cancer.

BACKGROUND: Clinical lymph node staging in resectable non-small cell lung cancer (NSCLC) patients not only indicates prognosis, but also determines primary treatment strategy. The demand of noninvasive tool for preoperative lymph node metastasis prediction remains significant. This study aimed to develop and externally validate a preoperative noninvasive predictive model based on circular tumor DNA (ctDNA) for the lymph node metastasis in resectable NSCLC patients. METHODS: Resectable NSCLC patients in TRACERx cohort were included as training group. Potential preoperative noninvasively accessible predictors were incorporated into the development of a nomogram via multivariate logistic regression. The predictive model was externally validated by a similar cohort from our hospital. RESULTS: Overall, 58 patients from TRACERx cohort were included as training group and 37 patients from our hospital were included as external validation group. Variant allele frequency (VAF) level of ctDNA was significantly associated with lymph node metastasis (OR: 4.89, 95% CI: 1.22-19.54, P=0.03). The predictive model incorporating age, tumor size and VAF demonstrated satisfactory discrimination and calibration in both training group (AUC =0.77, 95% CI: 0.65-0.90, P=0.001) and external validation group (AUC =0.84, 95% CI: 0.70-0.99, P=0.005). CONCLUSIONS: High VAF level in preoperative ctDNA may indicate lymph node metastasis of resectable NSCLC. And a preoperative noninvasive predictive model based on ctDNA for the lymph node metastasis in resectable NSCLC patients was developed and externally validated with satisfactory discrimination and calibration.

Early Detection of Non-Small Cell Lung Cancer by Using a 12-microRNA Panel and a Nomogram for Assistant Diagnosis.

Background: We previously identified a 12-microRNA (miRNA) panel (miRNA-17, miRNA-146a, miRNA-200b, miRNA-182, miRNA-155, miRNA-221, miRNA-205, miRNA-126, miRNA-7, miRNA-21, miRNA-145, and miRNA-210) that aided in the early diagnosis of non-small cell lung cancer (NSCLC). We validated the diagnostic value of this miRNA panel and compared it with that of traditional tumor markers and radiological diagnosis. We constructed a nomogram based on the miRNA panel's results to predict the risk of NSCLC. Methods: Eighty-two participants with pulmonary nodules on a CT scan and who underwent a pathological examination and surgical treatment were enrolled in our study. Patients were randomly divided into a training group or a validation group. The miRNA concentrations were quantified by RT-PCR and log-transformed for analysis. The cutoff value was determined in the training group and then applied in the validation group. A comparison between the miRNAs and traditional tumor markers [CEA, NSE, and cytokeratin 19 fragment 21-1 (Cyfra21-1)] and radiological diagnosis was performed. A nomogram based on the miRNA panel's results to predict the risk of NSCLC was constructed. Results: The expression level of these 12 miRNAs was significantly higher in NSCLC patients than in benign patients. In the validation group, the specificity and positive predictive value were 96.4 and 95.8%, respectively, which were significantly higher than those using traditional tumor markers or radiological diagnosis. The sensitivity was 42.6%, which was also higher than that using tumor markers. Moreover, the sensitivity increased to 63.6% when the nodule diameters were larger than 2 cm. The miRNAs and seven clinical factors were integrated into the nomogram, and the calibration curves showed optimal agreement between the predicted and actual probabilities. Conclusions: Our miRNA panel has clinical value for the early detection of NSCLC. A nomogram was constructed and internally validated, and the results indicate that it can assist clinicians in making treatment recommendations in the clinic.

Extent of resection and lymph node evaluation in early stage metachronous second primary lung cancer: a population-based study.

BACKGROUND: Evidence of the optimal surgery strategy for early stage metachronous second primary lung cancer (SPLC) has been limited and controversial. This study aims to compare the survival outcomes of different extents of resection and lymph node evaluation in these patients. METHODS: Early stage metachronous SPLC patients, who had received lobectomy for initial primary lung cancer (IPLC) and developed SPLC more than 3 months later, were selected from the Surveillance, Epidemiology, and End Results (SEER) database according to the American College of Chest Physicians (ACCP) guideline. Overall survival (OS) and lung cancer-specific survival (CSS) of different extents of resection and lymph node evaluation were analyzed using Kaplan-Meier method and multivariate Cox regression model. RESULTS: Overall, 1,784 SPLC patients without nodal or distant metastasis were identified. Lobectomy was associated with significantly longer OS (HR: 0.83, 95% CI: 0.71-0.97, 5-year survival: 59.2% vs. 53.3%, P=0.02) and CSS (HR: 0.72, 95% CI: 0.60-0.88, 5-year survival: 71.5% vs. 63.2%, P=0.001) compared with sublobar resection. In addition, examined lymph node number ≥10 demonstrated longer OS (HR: 0.63, 95% CI: 0.50-0.81, 5-year survival: 66.6% vs. 53.9%, P<0.001) and CSS (HR: 0.54, 95% CI: 0.40-0.74, 5-year survival: 77.4% vs. 64.7%, P<0.001) compared with an examined lymph node number <10. The survival benefits of lobectomy and examined lymph node number ≥10 were further validated in multivariate Cox regression and subgroup analysis stratified by tumor size. CONCLUSIONS: Lobectomy and thorough lymph node evaluation provided significantly longer survival, and thus should be considered for early stage metachronous SPLC whenever possible.

A Comparison of the Current N2 Classification and a Modified N2 Categorization in TNM Staging of Esophageal Cancer Patients.

OBJECTIVE: To compare the effectiveness of the current N classification and a modified N2 categorization in TNM staging of esophageal cancer (EC) patients. METHODOLOGY: A total of 2753 EC patients were enrolled in the study: 2283 EC patients from the Surveillance, Epidemiology, and End Results (SEER) database and 470 separate Chinese patients were used to verify the results of the SEER database. X-tile software was employed to determine the optimal cutoff points of the number of metastatic lymph nodes (LNs) in the N2 category. Univariate and multivariate Cox regression analyses were performed to identify the survival risk factors. RESULT: Patients in the N2 category were divided into two groups based on the number of metastatic LNs. Patients with three and four metastatic LNs were categorized as N2a, while those with five and six metastatic LNs were categorized as N2b. The 3-year overall survival (OS) rate in the SEER database was 71.5%, 42.3%, 23.6%, 17.2%, and 10.7% for patients with N0, N1, N2a, N2b, and N3, respectively (P<0.001). Furthermore, a separate Chinese cohort was enrolled to validate the revised N2 category. Additionally, the 3-year OS rate was 71.5%, 42.3%, 23.6%, 17.2%, and 10.7% for patients with N0, N1, N2a, N2b, and N3, respectively (P<0.001). CONCLUSION: The current N2 category should be further divided into two groups (N2a and N2b) to provide more accurate prognosis information that could further help in developing personalized therapeutic strategies.

Combining Plasma miRNAs and Computed Tomography Features to Differentiate the Nature of Pulmonary Nodules.

Objective: The purpose of this study was to evaluate the diagnostic efficiency of combining plasma microRNAs (miRNAs) and computed tomography (CT) features in the diagnosis of pulmonary nodules. Methods: Ninety-two pulmonary nodule patients who had undergone surgery were enrolled in our study from July 2016 to March 2018 at the Sun Yat-sen University Cancer Center. A prediction model was established by combining 3 miRNAs (miRNA-146a, -200b, and -7) and CT features to identify the pulmonary nodules of these patients. We evaluated the diagnostic performance of this prediction model for pulmonary nodules using the Receiver Operating Characteristic (ROC) curve. Results: The expression levels of miRNA-146a, -200b, and -7 in early-stage non-small cell lung cancer (NSCLC) patients are significantly higher than those in benign nodule patients. We used these three miRNAs and CT features (pleural indentation and speculation) to establish a prediction model for early-stage NSCLC, with a sensitivity and specificity of 92.9%, 83.3% in the training set, respectively. For the validation process, with the sensitivity of 71.8% and the specificity of 69.2%. For ROC curve analyses, area under the curve (AUC) for tumor identification in the training stage and validation stage were 0.929 and 0.781, respectively. Conclusion: Plasma miRNA-146a, miRNA-200b, and miRNA-7 may be potential biomarkers for the early diagnosis of lung cancer. Our prediction model can help to identify the nature of pulmonary nodules with a relatively high diagnostic efficiency.

Alpha-l-fucosidase: a novel serum biomarker to predict prognosis in early stage esophageal squamous cell carcinoma.

BACKGROUND: Alpha-l-fucosidase (AFU) not only detects hepatocellular carcinoma (HCC) early but also is used as a clinical prognostic indicator of several malignant tumors. However, no study has investigated the prognostic significance of AFU in a cohort of patients with esophageal squamous cell carcinomas (ESCCs). METHODS: A retrospective dataset that included 160 consecutive patients with early stage (pT1N0) ESCC who received surgery between January 2005 and December 2012 was analyzed to identify the prognostic value of serum AFU for overall survival (OS) by using Kaplan-Meier analysis and Cox multivariate regression modeling. RESULTS: The level of serum AFU ranged from 6.2 to 77.0 U/L with a median of 19.9 U/L, and the best cutoff point for OS was 17.95 U/L. Analysis by Pearson's correlation showed that the levels of serum ALT and GGT were both positively correlated with the level of serum AFU (r=0.403, P<0.001 and r=0.264, P=0.001, respectively). After adjusting for significant factors identified by univariate analysis, the Cox multivariate regression model indicated that a young age (<65 years), no history of alcohol consumption, and a low AFU level (≤17.95 U/L) were still significantly associated with longer OS (P=0.008, 0.004 and 0.017, respectively). The 5-year and 10-year OS rates for patients with high AFU levels vs. low AFU levels were 76.2% vs. 86.0%, and, 46.7% vs. 83.4%, respectively. CONCLUSIONS: Compared with other serum biomarkers, AFU showed a better prognostic value for long-term survival in patients with early stage ESCC.

Impact of Different Types of Lymphadenectomy Combined With Different Extents of Tumor Resection on Survival Outcomes of Stage I Non-small-cell Lung Cancer: A Large-Cohort Real-World Study.

Background: To investigate the prognostic impact of different types of lymphadenectomy with different extents of tumor resection on the outcomes of stage I non-small-cell lung cancer (NSCLC). Methods: Patients were classified into lobectomy and sublobectomy groups, and then each group was subdivided according to the types of lymphadenectomy. The end points of the study were overall survival (OS) and disease-free survival (DFS). Propensity score matched (PSM) comparative analysis and univariate and multivariate Cox regression analyses were performed. Result: A total of 1,336 patients were included in the current study. Lobectomy was associated with better OS and DFS. In the lobectomy group, lobectomy with bilateral mediastinal lymphadenectomy (BML) was associated with better OS than lobectomy with systematic nodal dissection (SND) or lobe-specific systematic node dissection (L-SND). Lobectomy with SND or L-SND was associated with better OS than lobectomy with systematic nodal sampling (SNS) or selected lymph node biopsy (SLNB). Additionally, lobectomy with BML or SND was associated with better DFS than lobectomy with L-SND or SNS or SLNB. After PSM, compared with lobectomy with SNS or SLNB, lobectomy with SND resulted in more favorable OS and DFS. There was no survival difference between different types of lymphadenectomy for patients who underwent sublobectomy. A multivariable analysis revealed independent associations of lobectomy with BML or SND with better OS and DFS compared with those of lobectomy with SNS or SLNB. Conclusion: This study reveals an association of lobectomy with more systematic and complete lymph node dissection, such as BML or SND, with better prognosis in stage I NSCLC patients.

A Model Shows Utility in Predicting Postoperative Recurrence and Distant Metastasis in Curatively Resected Esophageal Squamous Cell Cancer.

After curative treatment of esophageal squamous cell cancer (ESCC), patients are at high risk for recurrence. The objective of this study was to develop an index with a high sensitivity and specificity to predict ESCC patients' recurrence and prognosis. A retrospective analysis was conducted on consecutive patients with EC who underwent esophagectomy. In total, 1417 patients were included in the current investigation. In total, 770 patients were included in the current study's exploratory group. Alcohol consumption, TNM classification, number of lymph node station metastases, and number of lymph node metastases were significantly correlated with recurrence. Multivariate logistical regression analysis resulted in the development of an equation for predicting recurrence and prognosis (REEC). When using the REEC value to predict recurrence, the cutoff value was 1.095, the area under the curve (AUC) values of the REEC were 0.68 ( p < 0.001) in the Exploratory Group and 0.65 ( p < 0.001) in the Validation Group, and the sensitivity and specificity were 76.68% and 51.18%, respectively. When using the REEC value to predict prognosis, the cutoff value was 1.215, the AUC values of the REEC were 0.65 ( p < 0.001) in the Exploratory Group and 0.64 ( p < 0.001) in the Validation Group, and the sensitivity and specificity were 73.12% and 50.67%, respectively. In the Exploratory Group, when the REEC value was >1.095, patients had a longer median overall survival (OS) and median disease-free survival (DFS) than those whose REEC value was < 1.095 (70.01±2.01 months versus 50.92±2.85 months and 75.66±1.35 months versus 53.68±2.81 months, respectively, p < 0.001). The differences were confirmed to still exist in the Validation Group (48.12±1.47 vs 32.68±2.53 months and 55.61±1.32 vs 35.68±2.73 months respectively, p < 0.001).This study reported an index that can predict esophageal cancer recurrence and prognosis, and its use can benefit patients.

Resection of Early-Stage Second Primary Non-small Cell Lung Cancer After Small Cell Lung Cancer: A Population-Based Study.

Introduction: A certain number of small cell lung cancer (SCLC) patients become long-term survivors after treatment, and they are at high risk to develop a second primary malignancy, including non-small cell lung cancer. However, the optimal management of early-stage second primary non-small cell lung cancer (SPLC) after SCLC remains unknown. This study aims to evaluate the survival benefits of surgery in these patients. Methods: Patients with early-stage SPLC after SCLC were identified from the Surveillance, Epidemiology, and End Results database. Patients were balanced with propensity score matching (PSM). Overall survival (OS) and lung cancer-specific survival (CSS) were compared between non-surgery group and surgery group with the Kaplan-Meier method and Cox multivariate regressions. Results: A total of 228 patients with early-stage SPLC after SCLC were identified. Surgery was associated with significantly improved OS and CSS in the multivariate Cox regression analysis (OS, 5-year survival: 41.2 vs. 11.6%, HR: 0.42, 95% CI: 0.31-0.59, P < 0.01; CSS, 5-year survival: 46.8 vs. 24.3%, HR: 0.53, 95% CI: 0.37-0.75, P < 0.01). However, no statistically significant survival difference was found between sublobar resection and lobectomy (OS, 5-year survival: 41.0 vs. 45.3%, P = 0.73; CSS, 5-year survival: 43.5 vs. 54.1%, P = 0.49). After 1:1 PSM, 162 patients were selected for further analysis, and surgery continued to demonstrate superior survival (OS, 5-year survival: 44.2 vs. 7.2%, HR: 0.48, 95% CI: 0.33-0.70, P < 0.01; CSS, 5-year survival: 48.0 vs. 20.6%, HR: 0.44, 95% CI: 0.42-0.97, P = 0.03). Conclusion: The resection of early-stage SPLC after SCLC led to significantly improved OS and CSS and therefore should be considered whenever possible. Nevertheless, further randomized controlled trials are warranted to investigate the safety and effect of surgery in these patients.

The number of resected lymph nodes is associated with the long-term survival outcome in patients with T2 N0 non-small cell lung cancer.

OBJECTIVE: For the patients with pathologic T2 N0 non-small cell lung cancer (NSCLC), the extent of lymph node (LN) removal required for survival is controversial. We aimed to explore the prognostic significance of examined LNs and to identify how many nodes should be examined. METHODS: We reviewed 549 patients who underwent pulmonary or pneumonectomy surgery or plus lymphadenectomy who were confirmed as T2 stage and LN negative by postoperative pathological diagnosis. According to Martingale residuals of the Cox model, the patients were classified into four groups by the number of examined LNs (1-2 LNs, 3-7 LNs, 8-11 LNs, and ≥12 LNs). Kaplan-Meier analysis and Cox regression analysis were used to evaluate the association between survival and the number of examined LNs. RESULT: Compared with the 1-2 LNs, 3-7 LNs, and 8-11 LNs groups, the survival was significantly better in the ≥12 LNs group. The 5-year cancer-specific survival rate was 60.5% for patients with 1-2 negative LNs, compared with 68.7%, 72.6%, and 78.4% for those with 3-7, 8-11, and >11 LNs examined, respectively. The 7-year cancer-specific survival rate was 52.9% for patients with 1-2 negative LNs, compared with 63.7%, 63.8%, and 70.8% for those with 3-7, 8-11, and >11 LNs examined, respectively (P=0.045). There was a significant drop in mortality risk with the examination of more LNs. The lowest mortality risk occurred in those with 32 or more LNs examined. Multivariate analysis showed that age and the number of examined LNs were strong independent predictors of survival. CONCLUSION: The number of examined LNs is a strong independent prognostic factor. Our study demonstrates that patients with T2 N0 NSCLC should have at least 12 LNs examined and that the results of this study may provide information for the optimal number of resected LNs in surgery.

Prognostic significance of combined preoperative platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio in patients undergoing surgery with stage IB non-small-cell lung cancer.

BACKGROUND: Research indicates that the presence of a systemic inflammatory response plays an important role in predicting survival in patients with cancer. The aim of this study was to investigate the prognostic value of preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), prognostic nutritional index, and the combination of preoperative LMR and PLR (LMR-PLR) in predicting the survival of patients with stage IB non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively analyzed clinical data of 577 patients with stage IB NSCLC who underwent pneumonectomy from January 1999 to December 2009. Univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including LMR-PLR. The cutoff values for LMR and PLR were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cutoff values of LMR and PLR were 3.16 and 81.07, respectively. We divided the patients into three groups according to their LMR and PLR status and defined them with different scores. Patients with both high LMR (>3.16) and low PLR (≤81.07) were given a score of 2, whereas those with one or neither were scored 1 or 0, respectively. Survival curves were plotted using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards analyses were used to identify the factors associated with overall survival (OS). RESULTS: The median follow-up time was 93.77 months. The allocation of the LMR-PLR score was as follows: LMR-PLR = 0, 193 (33.4%) patients; LMR-PLR = 1, 308 (53.4%) patients; and LMR-PLR = 2, 76 (13.2%) patients. After multivariate analysis, our results showed that LMR-PLR was an independent prognostic indicator for OS (P=0.001). The 10-year OS rates were 70.0%, 60.4%, and 49.5% for LMR-PLR =2, LMR-PLR =1, and LMR-PLR =0, respectively (P<0.001). CONCLUSION: This study demonstrated that preoperative LMR and PLR are simple, readily available, and low-cost biomarkers. Preoperative LMR-PLR score can be used as a valuable prognostic marker for long-term survival in stage IB NSCLC patients who underwent surgery.