BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis i...BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the tumour.AIM To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)data.METHODS Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program database.The major observational endpoint was OS;hence,patients were se-parated into training and validation groups.Correlation analysis determined va-rious connections.Univariate and multivariate Cox analyses validated the independent predictive factors.Nomogram distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration curves.To evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was performed.The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.RESULTS For the purpose of creating the OS nomogram,a CIP plot based on CSS was generated.Cox multivariate regression analysis identified eleven significant prognostic factors(P<0.05)related to liver metastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to treatment.It was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/validation set AUC>0.7),and calibration curve(reliability slope closer to 45 degrees)results that the OS nomogram demonstrated a high level of predictive efficiency.The OS prediction model(New Model AUC=0.83)also performed much better than the old Cox-AJCC model(AUC difference between the new model and the old model greater than 0)in terms of risk stratification(P<0.0001)and verification using the IDI and NRI.CONCLUSION The OS nomogram for GCLM successfully predicts 1-and 3-year OS.Moreover,this approach can help to ap-propriately classify patients into high-risk and low-risk groups,thereby guiding treatment.展开更多
Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients w...Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.展开更多
Objective：To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer（NSCLC）.Methods：The expression of osteopontin mRNA were detected with R...Objective：To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer（NSCLC）.Methods：The expression of osteopontin mRNA were detected with RT-PCR technique.The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling.The tissues from fifteen patients with benign pulmonary diseases were studied as control group.Results：The overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues（P0.001）.Over-expression of osteopontin mRNA was significantly associated with clinical stage（P=0.009）.Advanced disease states had higher circulating level of osteopontin（stage I＋II versus stage III＋VI）.In multivariate analysis,stage was the only independent factor influencing circulating levels of osteopontin.All patients were followed up for 12 months,2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis.There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group.Conclusion：Preoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.展开更多
AIM:To investigate the clinicopathological characteristics of late-stage lung cancer patients with gastrointestinal(GI)-tract metastases,focusing on therapeutic options and outcomes.METHODS:Our institution(the Nationa...AIM:To investigate the clinicopathological characteristics of late-stage lung cancer patients with gastrointestinal(GI)-tract metastases,focusing on therapeutic options and outcomes.METHODS:Our institution(the National Taiwan University Hospital) diagnosed 8159 patients with lung cancer between 1987 and 2008,of which 21 developed symptomatic GI metastases.This study reviewed all of the patients' information,including survival data,pathological reports,and surgical notes.RESULTS:The most common histological type of lung cancer was adenocarcinoma,and 0.26% of patients with lung cancer developed GI metastases.The median duration from lung cancer diagnosis to GI metastases was three months(range,0-108 mo),and the average time from diagnosis of GI metastasis to death was 2.8 mo.Most patients with symptomatic gastric and/or duodenal metastases exhibited GI bleeding and were diagnosed by panendoscopy.In contrast,small bowel metastases typically presented as an acute abdomen and were not diagnosed until laparotomy.All patients with small bowel or colonic metastases underwent surgical intervention,and their perioperative mortality was 22%.Our data revealed a therapeutic effect in patients with solitary GI metastasis and a favorable palliative effect on survival when metastases were diagnosed preoperatively.In patients with multiple GI metastases,the presentation varied according to the locations of the metastases.CONCLUSION:Surgical treatment is worthwhile in a select group of patients with bowel perforation or obstruction.Physicians should be more alert to symptoms or signs indicating GI metastases.展开更多
Objective: To investigate the prognostic factors for stage IV non-small cell lung cancer (NSCLC) with distant metas- tasis and establish a reliable model of clinical prognostic index. Methods: From January 1990 to Apr...Objective: To investigate the prognostic factors for stage IV non-small cell lung cancer (NSCLC) with distant metas- tasis and establish a reliable model of clinical prognostic index. Methods: From January 1990 to April 2005, 313 primary NSCLC patients with metastasis, who had been treated in Shanghai Chest Hospital, were reviewed. Survival time was estimated accord- ing to the Kaplan-Meier method. Cox proportional hazard regression model was used for multivariate analysis. Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage IV, there were 218 and 95 patients with metastasis to single and different organs, respectively. The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00, 12.30) months and the overall 1-, 2-, 3-, 4- and 5-year survival rate was 45%, 18%, 12%, 4% and 0%. There were 63, 174, 127, 36, 18, 11 and 5 patients with metastasis to brain (20.13%), bone (55.59%), lung (40.58%), liver (11.50%), adrenal gland (5.75%), subcutaneous (3.51%) and others, respectively. The survival time was shortest in subcutaneous metastasis (4.6 months), and liver 7.0 months, brain 8.0 months, adrenal gland 8.6 months, bone 10.6 months, lung 11.8 months. Kaplan-Meier estimation showed that patients anatomic typing, KPS, numbers of organ with metastasis, appetite, liver, adrenal gland and subcutane- ous metastasis, body weight loss, smoking, index of smoking, chemotherapy, cycles of chemotherapy were the predictors of survival. Multivariate analysis showed survival statistically significant correlation with anatomic typing, KPS, appetite, liver and subcutaneous metastasis, body weight loss, cycles of chemotherapy. The relative risk (RR) was 1.51, 1.97, 1.55, 1.67, 2.56, and 2.56 respectively. Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P<0.01). Bone is the commonest organ for distant metastasis in lung cancer. The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis. Independent prognostic factors in patient with stage IV non-small cell lung cancer were liver and subcutaneous metastasis, anatomic typing, KPS, appetite, body weight loss, cycles of chemotherapy.展开更多
Objective： To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase （Smac） proteins in non-small cell lung cancer （NSCLC）, and analyze their effect on patients＇ progno...Objective： To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase （Smac） proteins in non-small cell lung cancer （NSCLC）, and analyze their effect on patients＇ prognosis. Methods： The expressions of Livin and Smac proteins were detected in 89 NSCLC tissue samples and 25 normal lung tissue samples by immunohistochemical technique. Results： The positive expression rates of Livin and Smac proteins in NSCLC tissues were 53.9%, and 58.4% respectively, higher than that in normal lung tissues（P〈0.01）. Livin protein expression correlated with Smac protein significantly（Χ^2=1 8.451, P=0.000, r=0.455）. The expression level of Livin protein was closely related to lymph node metastasis, TNM stage and histological type （P〈0.05）, but not to sex, age, differentiation grade （P〉0.05）. The expression level of Smac protein was closely related to lymph node metastasis, TNM stage （P〈0.01）, but not to sex, age, histological types （P〉0.05）. Kaplan-Meier analysis revealed a significant impact on survival by Livin protein in NSCLC （P〈0.01）, but not by Smac protein （P〉0.05）. Conclusion： Overexpression of Livin protein may play a promoting role in the occurrence and progression of NSCLC. Moreover, it may bring an adverse effect on patients＇ prognosis. Although overexpression of Smac protein affects the occurrence and progression of NSCLC, it has no relationship with the prognosis. Livin protein may be helpful to evaluate the progression of NSCLC, and to predict the prognosis.展开更多
The isolated laminin receptor （LN-R） labeled by <sup>125</sup>I was reconstituted into liposomes.<sup>125</sup>I-LN-R-liposomes and free <sup>125</sup>I-LN-R were separated by Sep...The isolated laminin receptor （LN-R） labeled by <sup>125</sup>I was reconstituted into liposomes.<sup>125</sup>I-LN-R-liposomes and free <sup>125</sup>I-LN-R were separated by Sepharose 4B column chromatogra-phy. The LN-R-liposomes showed affinity for laminin （LN） and were capable of binding toimmobilized LN substrate. In order to make transplantation of LN-R, LN-R-liposomes werefused with cultured murine Lewis lung carcinoma cells with the help of polyethylene glycol（PEG） induction. The radiation with the fused cells was not removed by salt sclution. Thebinding of the fused cells enriched in foreign LN-R to LN substrate increased by 87.5%.Furthermore, the murine Lewis lung carcinoma cells with and without transplanted LN-Rwere injected into C<sub>57</sub>BL/6J mice through tail veins （5×10<sup>5</sup> cells/each mouse）respectively.The mice in the test group died earlier than those in the control group. The total weight oflung tumor in the test group remarkably increased in comparison with those in the controlgroup. The results taken展开更多
基金Supported by Peng-Cheng Talent-Medical Young Reserve Talent Training Program,No.XWRCHT20220002Xuzhou City Health and Health Commission Technology Project Contract,No.XWKYHT20230081and Key Research and Development Plan Project of Xuzhou City,No.KC22179.
文摘BACKGROUND Gastric cancer(GC)is prevalent and aggressive,especially when patients have distant lung metastases,which often places patients into advanced stages.By identifying prognostic variables for lung metastasis in GC patients,it may be po-ssible to construct a good prediction model for both overall survival(OS)and the cumulative incidence prediction(CIP)plot of the tumour.AIM To investigate the predictors of GC with lung metastasis(GCLM)to produce nomograms for OS and generate CIP by using cancer-specific survival(CSS)data.METHODS Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance,epidemiology,and end results program database.The major observational endpoint was OS;hence,patients were se-parated into training and validation groups.Correlation analysis determined va-rious connections.Univariate and multivariate Cox analyses validated the independent predictive factors.Nomogram distinction and calibration were performed with the time-dependent area under the curve(AUC)and calibration curves.To evaluate the accuracy and clinical usefulness of the nomograms,decision curve analysis(DCA)was performed.The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer(AJCC)staging system by utilizing Net Reclassification Improvement(NRI)and Integrated Discrimination Improvement(IDI).Finally,the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.RESULTS For the purpose of creating the OS nomogram,a CIP plot based on CSS was generated.Cox multivariate regression analysis identified eleven significant prognostic factors(P<0.05)related to liver metastasis,bone metastasis,primary site,surgery,regional surgery,treatment sequence,chemotherapy,radiotherapy,positive lymph node count,N staging,and time from diagnosis to treatment.It was clear from the DCA(net benefit>0),time-de-pendent ROC curve(training/validation set AUC>0.7),and calibration curve(reliability slope closer to 45 degrees)results that the OS nomogram demonstrated a high level of predictive efficiency.The OS prediction model(New Model AUC=0.83)also performed much better than the old Cox-AJCC model(AUC difference between the new model and the old model greater than 0)in terms of risk stratification(P<0.0001)and verification using the IDI and NRI.CONCLUSION The OS nomogram for GCLM successfully predicts 1-and 3-year OS.Moreover,this approach can help to ap-propriately classify patients into high-risk and low-risk groups,thereby guiding treatment.
文摘Objective：To assess prognostic factors and validate the effectiveness of recursive partitioning analysis （RPA） classes and graded prognostic assessment （GPA） in 290 non-small cell lung cancer （NSCLC） patients with brain metastasis （BM）.Methods：From Jan 2008 to Dec 2009,the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation,systemic chemotherapy and tyrosine kinase inhibitors （TKIs） in two institutes were analyzed.Survival was estimated by Kaplan-Meier method.The differences of survival rates in subgroups were assayed using log-rank test.Multivariate Cox＇s regression method was used to analyze the impact of prognostic factors on survival.Two prognostic indexes models （RPA and GPA） were validated respectively.Results：All patients were followed up for 1-44 months,the median survival time after brain irradiation and its corresponding 95% confidence interval （95% CI） was 14 （12.3-15.8） months.1-,2-and 3-year survival rates in the whole group were 56.0%,28.3%,and 12.0%,respectively.The survival curves of subgroups,stratified by both RPA and GPA,were significantly different （P0.001）.In the multivariate analysis as RPA and GPA entered Cox＇s regression model,Karnofsky performance status （KPS） ≥ 70,adenocarcinoma subtype,longer administration of TKIs remained their prognostic significance,RPA classes and GPA also appeared in the prognostic model.Conclusion：KPS ≥70,adenocarcinoma subtype,longer treatment of molecular targeted drug,and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.
文摘Objective：To investigate the relationship between postoperative metastasis and circulating levels of osteopontin in non-small cell lung cancer（NSCLC）.Methods：The expression of osteopontin mRNA were detected with RT-PCR technique.The circulating levels of osteopontin were measured through ELASA in 46 NSCLC cases that had not been received any anti-cancer treatment at the time of sampling.The tissues from fifteen patients with benign pulmonary diseases were studied as control group.Results：The overall median mRNA expression level of osteopontin was approximately 70-fold higher in tumor tissues than in matched normal lung tissues（P0.001）.Over-expression of osteopontin mRNA was significantly associated with clinical stage（P=0.009）.Advanced disease states had higher circulating level of osteopontin（stage I＋II versus stage III＋VI）.In multivariate analysis,stage was the only independent factor influencing circulating levels of osteopontin.All patients were followed up for 12 months,2 of the 46 patients with both osteopontin mRNA expression and elevated plasma osteopontin levels had local recurrence and 10 had distant metastasis.There was a significant difference in the osteopontin levels between metastasis group and non-metastasis group.Conclusion：Preoperative plasma levels of osteopontin are significantly associated with post-operative metastasis in advanced NSCLC.
文摘AIM:To investigate the clinicopathological characteristics of late-stage lung cancer patients with gastrointestinal(GI)-tract metastases,focusing on therapeutic options and outcomes.METHODS:Our institution(the National Taiwan University Hospital) diagnosed 8159 patients with lung cancer between 1987 and 2008,of which 21 developed symptomatic GI metastases.This study reviewed all of the patients' information,including survival data,pathological reports,and surgical notes.RESULTS:The most common histological type of lung cancer was adenocarcinoma,and 0.26% of patients with lung cancer developed GI metastases.The median duration from lung cancer diagnosis to GI metastases was three months(range,0-108 mo),and the average time from diagnosis of GI metastasis to death was 2.8 mo.Most patients with symptomatic gastric and/or duodenal metastases exhibited GI bleeding and were diagnosed by panendoscopy.In contrast,small bowel metastases typically presented as an acute abdomen and were not diagnosed until laparotomy.All patients with small bowel or colonic metastases underwent surgical intervention,and their perioperative mortality was 22%.Our data revealed a therapeutic effect in patients with solitary GI metastasis and a favorable palliative effect on survival when metastases were diagnosed preoperatively.In patients with multiple GI metastases,the presentation varied according to the locations of the metastases.CONCLUSION:Surgical treatment is worthwhile in a select group of patients with bowel perforation or obstruction.Physicians should be more alert to symptoms or signs indicating GI metastases.
文摘Objective: To investigate the prognostic factors for stage IV non-small cell lung cancer (NSCLC) with distant metas- tasis and establish a reliable model of clinical prognostic index. Methods: From January 1990 to April 2005, 313 primary NSCLC patients with metastasis, who had been treated in Shanghai Chest Hospital, were reviewed. Survival time was estimated accord- ing to the Kaplan-Meier method. Cox proportional hazard regression model was used for multivariate analysis. Results: Among the 313 cases of non-small cell lung cancer (NSCLC) at stage IV, there were 218 and 95 patients with metastasis to single and different organs, respectively. The overall median survival time for all 313 cases of NSCLC patients was 10.8 (9.00, 12.30) months and the overall 1-, 2-, 3-, 4- and 5-year survival rate was 45%, 18%, 12%, 4% and 0%. There were 63, 174, 127, 36, 18, 11 and 5 patients with metastasis to brain (20.13%), bone (55.59%), lung (40.58%), liver (11.50%), adrenal gland (5.75%), subcutaneous (3.51%) and others, respectively. The survival time was shortest in subcutaneous metastasis (4.6 months), and liver 7.0 months, brain 8.0 months, adrenal gland 8.6 months, bone 10.6 months, lung 11.8 months. Kaplan-Meier estimation showed that patients anatomic typing, KPS, numbers of organ with metastasis, appetite, liver, adrenal gland and subcutane- ous metastasis, body weight loss, smoking, index of smoking, chemotherapy, cycles of chemotherapy were the predictors of survival. Multivariate analysis showed survival statistically significant correlation with anatomic typing, KPS, appetite, liver and subcutaneous metastasis, body weight loss, cycles of chemotherapy. The relative risk (RR) was 1.51, 1.97, 1.55, 1.67, 2.56, and 2.56 respectively. Conclusion: Survival time decreases distinctly in patients who had distant metastasis to more than two different organs (P<0.01). Bone is the commonest organ for distant metastasis in lung cancer. The prognosis is poor when lung cancer appears subcutaneous metastasis and liver metastasis. Independent prognostic factors in patient with stage IV non-small cell lung cancer were liver and subcutaneous metastasis, anatomic typing, KPS, appetite, body weight loss, cycles of chemotherapy.
文摘Objective： To investigate the expression characteristics of Livin and second mitochondrial activator of Caspase （Smac） proteins in non-small cell lung cancer （NSCLC）, and analyze their effect on patients＇ prognosis. Methods： The expressions of Livin and Smac proteins were detected in 89 NSCLC tissue samples and 25 normal lung tissue samples by immunohistochemical technique. Results： The positive expression rates of Livin and Smac proteins in NSCLC tissues were 53.9%, and 58.4% respectively, higher than that in normal lung tissues（P〈0.01）. Livin protein expression correlated with Smac protein significantly（Χ^2=1 8.451, P=0.000, r=0.455）. The expression level of Livin protein was closely related to lymph node metastasis, TNM stage and histological type （P〈0.05）, but not to sex, age, differentiation grade （P〉0.05）. The expression level of Smac protein was closely related to lymph node metastasis, TNM stage （P〈0.01）, but not to sex, age, histological types （P〉0.05）. Kaplan-Meier analysis revealed a significant impact on survival by Livin protein in NSCLC （P〈0.01）, but not by Smac protein （P〉0.05）. Conclusion： Overexpression of Livin protein may play a promoting role in the occurrence and progression of NSCLC. Moreover, it may bring an adverse effect on patients＇ prognosis. Although overexpression of Smac protein affects the occurrence and progression of NSCLC, it has no relationship with the prognosis. Livin protein may be helpful to evaluate the progression of NSCLC, and to predict the prognosis.
基金Project supported by the National Natural Science Foundation of China.
文摘The isolated laminin receptor （LN-R） labeled by <sup>125</sup>I was reconstituted into liposomes.<sup>125</sup>I-LN-R-liposomes and free <sup>125</sup>I-LN-R were separated by Sepharose 4B column chromatogra-phy. The LN-R-liposomes showed affinity for laminin （LN） and were capable of binding toimmobilized LN substrate. In order to make transplantation of LN-R, LN-R-liposomes werefused with cultured murine Lewis lung carcinoma cells with the help of polyethylene glycol（PEG） induction. The radiation with the fused cells was not removed by salt sclution. Thebinding of the fused cells enriched in foreign LN-R to LN substrate increased by 87.5%.Furthermore, the murine Lewis lung carcinoma cells with and without transplanted LN-Rwere injected into C<sub>57</sub>BL/6J mice through tail veins （5×10<sup>5</sup> cells/each mouse）respectively.The mice in the test group died earlier than those in the control group. The total weight oflung tumor in the test group remarkably increased in comparison with those in the controlgroup. The results taken
