The Incidence and Effect of Different Organ Metastasis on the Prognosis of NSCLC.

OBJECTIVE: The aim of this study was to explore the effect of different organ metastasis on the prognosis of non-small cell lung cancer (NSCLC). METHODS: Patients with distant metastatic NSCLC were selected from Surveillance, Epidemiology, and End Results database during 2016 to 2019. The incidence of different organ metastasis and their association with clinicopathological factors were explored. Overall survival (OS) and lung cancer-specific survival (LCSS) for metastatic NSCLC were calculated, and multivariate Cox regression analysis was performed with a nomogram for OS being constructed based on Cox regression. RESULTS: Total 26,210 patients with distant metastatic NSCLC were included in this study. Around 48.9% of the metastatic NSCLC were multiple-organ metastasis and bone was the most commonly involved organ (44.4%). For patients with single-organ metastasis, the prognosis for lung or distant lymph nodes (LNs) metastasis was better than others (with median OS of 15 and 16 months for lung and distant LNs metastasis, respectively), and liver metastasis resulted in the worst prognosis with median OS of 8 months. A nomogram was constructed to visualize Cox regression model, along with the receiver operating characteristic (ROC) curve demonstrated good discrimination for the predictive model with 1- and 2-year area under the curve of ROC of 0.687 and 0.702, respectively. CONCLUSION: The prognosis of NSCLC patients with distant metastasis was poor. Liver metastasis results in the worst prognosis among the single-organ metastasis. The nomogram developed based on the Cox regression model has provided a useful tool to estimate the probability of OS of the metastatic NSCLC.

Influence of adverse effects of neoadjuvant chemoradiotherapy on the prognosis of patients with early-stage esophageal cancer (cT1b-cT2N0M0) based on the SEER database.

Objective: To analyze the prognostic impact of neoadjuvant chemoradiotherapy (NCRT) on early-stage (cT1b-cT2N0M0) esophageal cancer (ESCA) and construct a prognostic nomogram for these patients. Methods: We extracted the clinical data about patients diagnosed with early-stage esophageal cancer from the 2004-2015 period of the Surveillance, Epidemiology, and End Results (SEER) database. We applied the independent risk factors affecting the prognosis of patients with early-stage esophageal cancer obtained after screening by univariate and multifactorial COX regression analyses to establish the nomogram and performed model calibration using bootstrapping resamples. The optimal cut-off point for continuous variables is determined by applying X-tile software. After balancing the confounding factors by propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) method, Kaplan-Meier(K-M) curve, and log-rank test were applied to evaluate the prognostic impact of NCRT on early-stage ESCA patients. Results: Among patients who met the inclusion criteria, patients in the NCRT plus esophagectomy (ES) group had a poorer prognosis for overall survival (OS) and esophageal cancer-specific survival (ECSS) than patients in the ES alone group (p < 0.05), especially in patients who survived longer than 1 year. After PSM, patients in the NCRT + ES group had poorer ECSS than patients in the ES alone group, especially after 6 months, while OS was not significantly different between the two groups. IPTW analysis showed that, prior to 6 months patients in the NCRT + ES group had a better prognosis than patients in the ES group, regardless of OS or ECSS, whereas after 6 months, patients in the NCRT + ES group had a poorer prognosis. Based on multivariate COX analysis, we established a prognostic nomogram which showed areas under the ROC curve (AUC) for 3-, 5-, and 10-year OS 0.707, 0.712, and 0.706, respectively, with the calibration curves showing that the nomogram was well calibrated. Conclusions: Patients with early-stage ESCA (cT1b-cT2) did not benefit from NCRT, and we established a prognostic nomogram to provide clinical decision aid for the treatment of patients with early-stage ESCA.

APOC1 predicts a worse prognosis for esophageal squamous cell carcinoma and is associated with tumor immune infiltration during tumorigenesis.

Background: Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. Methods: We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. We also conducted bioinformatics studies on the diagnostic value, prognostic value, and correlation between APOC1 and immune infiltrating cells in ESCA through STRING (https://cn.string-db.org/), the TISIDB (http://cis.hku.hk/TISIDB/) website, and various other analysis tools. Results: In patients with ESCA, APOC1 was significantly more highly expressed in tumor tissues than in normal tissues (p < 0.001). APOC1 could diagnose ESCA more accurately and determine the TNM stage and disease classification with high accuracy (area under the curve, AUC≥0.807). The results of the Kaplan-Meier curve analysis showed that APOC1 has prognostic value for esophageal squamous carcinoma (ESCC) (p = 0.043). Univariate analysis showed that high APOC1 expression in ESCC was significantly associated with worse overall survival (OS) (p = 0.043), and multivariate analysis shows that high APOC1 expression was an independent risk factor for the OS of patients with ESCC (p = 0.030). In addition, the GO (gene ontology)/KEGG (Kyoto encyclopedia of genes and genomes) analysis showed a concentration of gene enrichment in the regulation of T-cell activation, cornification, cytolysis, external side of the plasma membrane, MHC protein complex, MHC class II protein complex, serine-type peptidase activity, serine-type endopeptidase activity, Staphylococcus aureus infection, antigen processing and presentation, and graft-versus-host disease (all p < 0.001). GSEA (gene set enrichment analysis) showed that enrichment pathways such as immunoregulatory-interactions between a lymphoid and non-lymphoid cell (NES = 1.493, p. adj = 0.023, FDR = 0.017) and FCERI-mediated NF-KB activation (NES = 1.437, p. adj = 0.023, FDR = 0.017) were significantly enriched in APOC1-related phenotypes. In addition, APOC1 was significantly associated with tumor immune infiltrating cells and immune chemokines. Conclusion: APOC1 can be used as a prognostic biomarker for esophageal cancer. Furthermore, as a novel prognostic marker for patients with ESCC, it may have potential value for further investigation regarding the diagnosis and treatment of this group of patients.

Reconstruction of the Esophagus with Sternohyoid Flap after Resection of a Large Cervical Esophageal Leiomyosarcoma.

PURPOSE: Reconstruction of the esophagus with sternohyoid muscle after enucleation of the cervical esophageal leiomyosarcoma (ELS) was rarely reported. METHODS: A case of 55-year-old female with a large leiomyosarcoma in the cervical esophagus was reported. The tumor was enucleated, and the defect of the esophagus was patched with left sternohyoid muscle flap. RESULTS: The patient recovered uneventfully after surgery. She has not had any discomfort with swallowing since surgery, and nowadays, there is not any recurrence and metastasis being detected. CONCLUSION: It is minimal invasive and simple to enucleate the cervical ELS and patch the defect of esophagus with sternohyoid muscle flap. For some selected patients, this method may be a promising surgical procedure to achieve both good swallowing function and satisfying prognosis.

Propensity Score Matching Analysis for the Role of Surgery in Small Cell Lung Cancer.

BACKGROUND: The role of surgery for small cell lung cancer (SCLC) is not clear. We aimed to evaluate this issue using a population-based database. METHODS: Patients diagnosed between 2004 and 2014 with SCLC staged T1-4 N0-2 M0 disease were retrieved from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was used to reduce bias between the surgical and nonsurgical patient groups. The Kaplan-Meier method and Cox regression analysis were used to compare overall survival (OS) for the matched patients. RESULTS: A total of 8,811 patients were retrieved, including 863 patients who underwent surgical resection. After 1:1 PSM, a matched cohort with 1,562 patients was generated. In the matched cohort, surgery was associated with 5-year OS improvement (from 16.8 to 36.7%, p < 0.001) and lung cancer-specific survival improvement (from 21.6 to 43.2%, p < 0.001). Survival benefits of surgery were significant in all subgroups, including N1-2 disease, except for patients with a tumor size >5.0 cm or T3 disease. CONCLUSIONS: Patients with SCLC of limited stage can benefit from surgery, including N1-2 disease. However, patients with a tumor size >5.0 cm or advanced T stage may be unable to benefit from surgery.

Comparison of treatment strategies for patients with limited-stage small cell lung cancer who received chemotherapy.

BACKGROUND: The standard care for limited-stage small cell lung cancer (SCLC) is unclear. The purpose of this study is to compare the outcome for patients receiving chemotherapy alone, chemotherapy plus surgery (CS), chemotherapy plus radiation (CR), or chemotherapy plus surgery and radiation (CSR) for limited-stage SCLC. METHODS: Patients with T1-4N0-2M0 SCLC who received chemotherapy from 2004 to 2014 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) of these patients, stratified by different stage, was compared in accordance to the method of receiving different treatments using Kaplan-Meier method and Cox regression analysis. RESULTS: A total of 7,204 patients were included, where 1,347 (18.7%) patients received chemotherapy alone, 296 (4.1%) undergone CS, 5,296 (73.5%) patients were subjected to CR and 267 (3.7%) patients were managed by the three combination of CSR. Chemotherapy alone was associated with the worst survival in comparison to the other two method of combination i.e., chemotherapy with radiation or surgery. When compared with CR, CS had no survival benefit in patients with stage in excess of T1-2N0 disease, but was associated with improved 5-year OS in patients with T1-2N0 disease, which ranged from 29.1% to 54.3% (P<0.001). For patients with T1-2N2 disease who received CSR demonstrated superior OS over those who received CR (P=0.004) or CS (P=0.036). Cox regression analysis showed CS was associated with improved OS when compared with CR in patients with N0 disease (HR, 0.54; 95% CI, 0.43-0.68; P=0.000) and CSR was associated with better OS in comparison with CR in patients with N2 disease (HR, 0.71; 95% CI, 0.55-0.93; P=0.013). CONCLUSIONS: Patients with limited-stage SCLC can benefit from local treatment such as surgery, radiation, and surgery plus radiation. For patients with N0 disease, CS was associated with improved survival in comparison to CR. If N2 was identified after surgery, radiation may be added to improve OS.

Effect of second primary cancer on the prognosis of patients with non-small cell lung cancer.

BACKGROUND: Second primary cancer (SPC) is not a rare event for patients with non-small cell lung cancer (NSCLC), especially for those who survive for a longer period of time. This study was aimed to explore the effects of SPC on the survival of NSLCL patients. METHODS: A total of 241,805 patients with primary NSCLC were identified between 2004 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence of SPC and its effect on the overall survival (OS) and lung cancer-specific survival (LCSS) was explored and analyzed using Cox regression model with SPC being treated as a time-dependent covariate. RESULTS: The incidence of SPCs after the diagnosis of NSCLC was 6.4%, with the second primary lung cancer being the most common one (45.1%). About half of the SPCs (50.7%) occurred during the first year after the diagnosis of NSCLC. It seemed that patients who developed SPC late in the follow-up period tended to have poor prognosis. Multivariable analysis with Cox regression showed that the occurrence of SPC was a poor prognostic factor for patients with NSCLC [hazard ratio (HR), 1.298; 95% confidence interval (CI), 1.270-1.326; P=0.000], and it increased the risk of LCSS (versus no SPC, HR, 1.094; 95% CI, 1.066-1.123; P=0.000). CONCLUSIONS: The occurrence of SPC after the diagnosis of NSCLC was not a rare event, and it indicated a poorer prognosis compared with patients without it. During the follow-up, attention should be paid to the screening of SPC especially the second primary lung cancer, and a rational surveillance policy should be formed and implemented.

[Comparison of the Survival Time in the Non-small Cell Lung Cancer Patients with Different Organ Metastasis].

BACKGROUND: The purpose of this study is to compare the survival time of non-small cell lung cancer (NSCLC) patients with different organ metastasis. Among all cancers, the morbidity and mortality of lung cancer is the highest worldwide, which may caused by local recurrence and distant metastasis, and the location of metastasis may predict the prognosis of patients. METHODS: A total of 117,542 patients with NSCLC diagnosed between 2010 and 2014 were enrolled from Surveillance, Epidemiology, and End Result (SEER) databases, and the relationship between distant metastasis and survival time was retrospectively analyzed. RESULTS: Of all the 117,542 patients diagnosed with non-small cell lung cancer, 42,071 (35.8%) patients had different degrees of distant metastasis during their medical history, including 26,932 single organ metastases and 15,139 multiple organ metastases, accounting for 64.0% and 36.0% of the metastatic patients respectively. Compared with patients with no metastasis, whose median survival time was 21 months, the median survival time of patients with metastases was 7 months (lung), 6 months (brain), 5 months (bone), 4 months (liver), and 3 months (multiple organ) respectively, and the difference was significant (P<0.001, except liver vs multiple organ P=0.650); Most patients with NSCLC (88.4%) eventually died of lung cancer. CONCLUSIONS: Distant metastasis of NSCLC patients indicates poor prognosis. In NSCLC patients with single organ metastasis, the prognosis of lung metastasis is the best, and liver metastasis is the worst, and multiple organ metastasis is worse than single organ metastasis.

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

PURPOSE: To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. METHODS: A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. RESULTS: The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. CONCLUSIONS: Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Propensity score-matching analysis of postoperative radiotherapy for stage IIIA-N2 non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

BACKGROUND: To investigate the effects of postoperative radiotherapy (PORT) on the survival of patients with resected stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A total of 3,334 patients with resected stage IIIA-N2 NSCLC in 2004 to 2013 were identified in the Surveillance, Epidemiology, and End Results database and stratified according to use of PORT. Propensity score-matching (PSM) methods were used to balance the baseline characteristics of patients who did (n = 744) or did not (n = 744) undergo PORT. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared between these two patient groups. RESULTS: After PSM, PORT increased OS (hazard ratio, 0.793; p = 0.001) and LCSS (hazard ratio, 0.837; p = 0.022) compared with no PORT. The OS benefit for PORT was mainly seen in patients aged <60 years (5-year OS, 35.4% versus 28.9% for PORT versus no PORT, respectively; p = 0.026) and in those who underwent lobectomy (5-year OS, 43.5% versus 34.5% for PORT versus no PORT, respectively; p = 0.001). The LCSS benefit for PORT was significant in patients undergoing lobectomy (5-year LCSS, 48.3% versus 42.3% for PORT versus no PORT, respectively; p = 0.036). CONCLUSIONS: The survival benefits of PORT were primarily observed in patients with resected stage IIIA-N2 NSCLC who were <60 years of age or had undergone lobectomy.

Expression of cyclooxygenase-2, vascular endothelial growth factor, and epidermal growth factor receptor in Chinese patients with esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a frequently occurring cancer with poor prognosis despite combined therapeutic strategies. The aim of the current study was to elucidate a further finding on the clinicopathologic significance of immunohistochemical expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor receptor (EGFR) in Chinese patients with ESCC. METHODS: Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained from 140 randomly selected Chinese patients with ESCC. Sections were immunohistochemically stained for COX-2, VEGF, and EGFR. The correlations between clinicopathological features and the high expression of COX-2, VEGF, and EGFR were analyzed using the Statistical Package for the Social Sciences 19.0 software (IBM Inc., Chicago, IL, USA). RESULTS: In the present study, high expression of COX-2, EGFR, and VEGF was found in 64.3%, 62.1%, and 65.0%, respectively. Results showed that COX-2 overexpression was significantly correlated with degree of differentiation (P = 0.000), and lymph node metastasis (negative/positive, P = 0.002). EGFR and VEGF overexpression was significantly correlated with a differentiated degree, T stage, N stage, and tumor, node, metastases stage. CONCLUSION: High expression of COX-2, EGFR, and VEGF is an unfavorable prognostic factor in ESCC, and could be used as a poor prognosis indicator for the ESCC patients. Targeting therapy to these three targets should be considered to the combined treatment in ESCC.

[Variations in Serum CEA and CYFRA21-1 Levels Before and After Surgery Facilitate Prognosis of Non-small Cell Lung Cancer Patients].

BACKGROUND AND OBJECTIVE: Serum carcinoembryonic antigen (CEA) and the soluble fragment of cytokeratin 19 (CYFRA21-1) are important tumor markers (TMs) in the preoperative examination of patients with non-small cell lung cancer (NSCLC). However, the prognostic role of these markers in NSCLC patients remains controversial. The aim of the study was to investigate the clinical significance of serum CEA variances and CYFRA21-1 levels for the prognosis of NSCLC patients following surgery. METHODS: This retrospective study investigated the clinical records and follow-up sessions of 175 patients with NSCLC who accepted surgery and adjuvant chemotherapy. Patients were subdivided into groups based on serum CEA and CYFRA21-1 levels. Survival analysis was conducted using Kaplan-Meier method for each group. The prognostic factor was evaluated using Cox proportional hazards model. RESULTS: The overall survival (OS) of patients with high preoperative CEA or CYFRA21-1 levels was lower than that of patients with normal preoperative CEA or CYFRA21-1 levels. The OS displayed a significant difference (P=0.001) between groups with high and normal preoperative CYFRA21-1. Compared with groups exhibiting normal preoperative and postoperative levels of CEA or CYFRA21-1, the OS was shorter for groups with high preoperative and postoperative levels of CEA or CYFRA21-1. The difference of the paired groups was significant (P<0.05). Compared with the groups with normal preoperative and postoperative levels of CEA and CYFRA21-1, the OS was lower for the groups with high preoperative and postoperative levels of CEA and CYFRA21-1, which indicated a significant difference (P<0.001). The CEACYFRA211 (HHHH), CEACYFRA211 (NNHH), CYFRA21-1 (HH), CEA (HH), and male gender were identified as independent prognostic factors (P<0.05). CONCLUSIONS: This study suggested that the prognosis of NSCLC patients was not significantly satisfactory if preoperative and postoperative level of serum CEA or CYFRA21-1 was higher than standard value, especially if the preoperative and postoperative levels of CYFRA21-1 and CEA were higher than the standard values. The measurement of preoperative and postoperative levels of CYFRA21-1 and CEA proved helpful for the prognosis of patients with NSCLC.
.

Surgical treatment of chylothorax caused by lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare progressive disease caused by infiltration of smooth muscle-like cells in lymph vessels as well as the lung. We report a case of pulmonary LAM in a 22-year-old female with shortness of breath, recurrent pneumothorax and chylous pleural effusions. Multiple ligation of thoracic in lower part of thoracic duct was performed and biopsy of thoracic duct confirmed the diagnosis of LAM. The operation was successful and the patient was discharged. Although the thoracic duct involvement is extensive, multiple ligation in lower part of thoracic duct may be a good choice.