Accurate preoperative prediction of lymph node metastasis(LNM)in esophageal cancer(EC)patients is of crucial clinical significance for treatment planning and prognosis.AIM To develop a clinical radiomics nomogram that...Accurate preoperative prediction of lymph node metastasis(LNM)in esophageal cancer(EC)patients is of crucial clinical significance for treatment planning and prognosis.AIM To develop a clinical radiomics nomogram that can predict the preoperative lymph node(LN)status in EC patients.METHODS A total of 32 EC patients confirmed by clinical pathology(who underwent surgical treatment)were included.Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy,and its correlation with LNM was analyzed.Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python.Feature extraction,data dimensionality reduction,and feature selection were performed using XGBoost model and leave-one-out cross-validation.Multivariable logistic regression analysis was used to establish the prediction model,which included radiomics features,LN status from computed tomography(CT)reports,and B7-H3 mRNA expression,represented by a radiomics nomogram.Receiver operating characteristic area under the curve(AUC)and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical application value of the model.RESULTS The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis,and the difference was statistically significant(P<0.05).The AUC value in the receiver operating characteristic(ROC)curve was 0.718(95%CI:0.528-0.907),with a sensitivity of 0.733 and specificity of 0.706,indicating good diagnostic performance.The individualized clinical prediction nomogram included radiomics features,LN status from CT reports,and B7-H3 mRNA expression.The ROC curve demonstrated good diagnostic value,with an AUC value of 0.765(95%CI:0.598-0.931),sensitivity of 0.800,and specificity of 0.706.DCA indicated the practical value of the radiomics nomogram in clinical practice.CONCLUSION This study developed a radiomics nomogram that includes radiomics features,LN status from CT reports,and B7-H3 mRNA expression,enabling convenient preoperative individualized prediction of LNM in EC patients.展开更多
AIM: To determine the distance between the branching point of the left colic artery (LCA) and the inferior mesenteric artery (IMA) by computed tomography (CT) scanning, for preoperative evaluation before laparo...AIM: To determine the distance between the branching point of the left colic artery (LCA) and the inferior mesenteric artery (IMA) by computed tomography (CT) scanning, for preoperative evaluation before laparoscopic colorectal operation. METHODS: From February 2004 to May 2005, 100 patients (63 men, 37 women) underwent angiography performed with a 16-scanner multi-detector row CT unit (Toshiba, Aquilion 16). All images were analyzed on a workstation (AZE Ltd, Virtual Place Advance 300). The distance from the root of the IMA to the bifurcation of the LCA was measured by curved multi-planar reconstruction on a workstation. RESULTS: The IMA could be visualized in all the cases, but the LCA was missing in two patients. The mean distance from the root of the IMA to the root of the LCA was 42.0 mm (range, 23.2-75.0 mm). There were no differences in gender, arterial branching types, body weight, height, and body mass index. CONCLUSION: Volume-rendered 3D-CT is helpful to assess the vascular branching anatomy for laparoscopic surgery.展开更多
AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor ...AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.展开更多
AIM: To assess whether differential expression of caspase-3 in paired metastatic lymph nodes (LNs) is prognostic of survival in patients with resectable esophageal squamous cell carcinoma (ESCC).
Background Twist is a highly conserved epithelial-mesenchymal transcription factor that has been reported to be a key factor in tumor malignancy, including lymph node metastasis. It represents the major step of dissem...Background Twist is a highly conserved epithelial-mesenchymal transcription factor that has been reported to be a key factor in tumor malignancy, including lymph node metastasis. It represents the major step of dissemination and serves as a chief prognostic indicator of disease progression. However, the mechanism by which Twist regulates lymph node metastasis remains incompletely understood. Studies on the mechanism of metastasis are thus required for determining appropriate therapeutic strategies.Methods Immunohistochemistry for lymphatic vessel endothelial receptor 1 (LYVE-1), Ki-67, Twist, vascular endothelial growth factor C (VEGF-C), and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed to detect lymphatic vessel density (LVD), cell proliferation levels and the expressions of Twist, VEGF-C, and VEGFR-3 were determined from 66 primary supraglottic carcinoma tissue samples from 36 patients with lymph node metastasis (pathological N+, pN+) and 30 patients without metastasis (pathological NO, pNO). Western blotting analysis of the proteins in pN+ and pNO primary tumors was used to characterize the expressions of Twist, VEGF-C, and VEGFR-3further.Results The LVD was 22.4±10.3 in pN+ patients and 6.8±4.1 in pNO ones. For Ki-67, the number of proliferous cells in pN+ patients was greater than that in pNO ones. Both, however, were associated with their clinical nodal stages. In pN+patients, Twist, VEGF-C, and VEGFR-3 expressions were 86.11% (31/36), 80.56% (29/36), and 58.33% (21/36),respectively. These values were higher than those found for pNO patients (i.e., 13/30, 11/30, and 7/30, respectively) (P 〈0.05). Among the samples with Twist expression, 88.64% were VEGF-C-positive and 59.09% were VEGFR-3-positive.The pNO counterparts were 4.55% and 9.09%, respectively (P〈0.05). The expressions of Twist, VEGF-C, and VEGFR-3in pN+ patients obtained through Western blotting analysis were significantly higher than those in pNO patients, and the levels of VEGF-C and VEGFR-3 were positively correlated with that of Twist.Conclusions Twist expression correlates with lymph node metastasis. The mechanism involved in such a correlation may be related to lymphangiogenesis.展开更多
Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapie...Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)展开更多
AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal ...AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.展开更多
基金The Yancheng Key Research and Development Program(Social Development),No.YCBE202324。
文摘Accurate preoperative prediction of lymph node metastasis(LNM)in esophageal cancer(EC)patients is of crucial clinical significance for treatment planning and prognosis.AIM To develop a clinical radiomics nomogram that can predict the preoperative lymph node(LN)status in EC patients.METHODS A total of 32 EC patients confirmed by clinical pathology(who underwent surgical treatment)were included.Real-time fluorescent quantitative reverse transcription-polymerase chain reaction was used to detect the expression of B7-H3 mRNA in EC tissue obtained during preoperative gastroscopy,and its correlation with LNM was analyzed.Radiomics features were extracted from multi-modal magnetic resonance imaging of EC using Pyradiomics in Python.Feature extraction,data dimensionality reduction,and feature selection were performed using XGBoost model and leave-one-out cross-validation.Multivariable logistic regression analysis was used to establish the prediction model,which included radiomics features,LN status from computed tomography(CT)reports,and B7-H3 mRNA expression,represented by a radiomics nomogram.Receiver operating characteristic area under the curve(AUC)and decision curve analysis(DCA)were used to evaluate the predictive performance and clinical application value of the model.RESULTS The relative expression of B7-H3 mRNA in EC patients with LNM was higher than in those without metastasis,and the difference was statistically significant(P<0.05).The AUC value in the receiver operating characteristic(ROC)curve was 0.718(95%CI:0.528-0.907),with a sensitivity of 0.733 and specificity of 0.706,indicating good diagnostic performance.The individualized clinical prediction nomogram included radiomics features,LN status from CT reports,and B7-H3 mRNA expression.The ROC curve demonstrated good diagnostic value,with an AUC value of 0.765(95%CI:0.598-0.931),sensitivity of 0.800,and specificity of 0.706.DCA indicated the practical value of the radiomics nomogram in clinical practice.CONCLUSION This study developed a radiomics nomogram that includes radiomics features,LN status from CT reports,and B7-H3 mRNA expression,enabling convenient preoperative individualized prediction of LNM in EC patients.
基金Supported by Kobayashi Magobe Memorial Medical Foundation
文摘AIM: To determine the distance between the branching point of the left colic artery (LCA) and the inferior mesenteric artery (IMA) by computed tomography (CT) scanning, for preoperative evaluation before laparoscopic colorectal operation. METHODS: From February 2004 to May 2005, 100 patients (63 men, 37 women) underwent angiography performed with a 16-scanner multi-detector row CT unit (Toshiba, Aquilion 16). All images were analyzed on a workstation (AZE Ltd, Virtual Place Advance 300). The distance from the root of the IMA to the bifurcation of the LCA was measured by curved multi-planar reconstruction on a workstation. RESULTS: The IMA could be visualized in all the cases, but the LCA was missing in two patients. The mean distance from the root of the IMA to the root of the LCA was 42.0 mm (range, 23.2-75.0 mm). There were no differences in gender, arterial branching types, body weight, height, and body mass index. CONCLUSION: Volume-rendered 3D-CT is helpful to assess the vascular branching anatomy for laparoscopic surgery.
基金Supported by National Basic Research Program of China(973 Program),No.2010CB529301Tianjin Health Bureau Research Foundation,No.09KC74
文摘AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.
文摘AIM: To assess whether differential expression of caspase-3 in paired metastatic lymph nodes (LNs) is prognostic of survival in patients with resectable esophageal squamous cell carcinoma (ESCC).
文摘Background Twist is a highly conserved epithelial-mesenchymal transcription factor that has been reported to be a key factor in tumor malignancy, including lymph node metastasis. It represents the major step of dissemination and serves as a chief prognostic indicator of disease progression. However, the mechanism by which Twist regulates lymph node metastasis remains incompletely understood. Studies on the mechanism of metastasis are thus required for determining appropriate therapeutic strategies.Methods Immunohistochemistry for lymphatic vessel endothelial receptor 1 (LYVE-1), Ki-67, Twist, vascular endothelial growth factor C (VEGF-C), and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed to detect lymphatic vessel density (LVD), cell proliferation levels and the expressions of Twist, VEGF-C, and VEGFR-3 were determined from 66 primary supraglottic carcinoma tissue samples from 36 patients with lymph node metastasis (pathological N+, pN+) and 30 patients without metastasis (pathological NO, pNO). Western blotting analysis of the proteins in pN+ and pNO primary tumors was used to characterize the expressions of Twist, VEGF-C, and VEGFR-3further.Results The LVD was 22.4±10.3 in pN+ patients and 6.8±4.1 in pNO ones. For Ki-67, the number of proliferous cells in pN+ patients was greater than that in pNO ones. Both, however, were associated with their clinical nodal stages. In pN+patients, Twist, VEGF-C, and VEGFR-3 expressions were 86.11% (31/36), 80.56% (29/36), and 58.33% (21/36),respectively. These values were higher than those found for pNO patients (i.e., 13/30, 11/30, and 7/30, respectively) (P 〈0.05). Among the samples with Twist expression, 88.64% were VEGF-C-positive and 59.09% were VEGFR-3-positive.The pNO counterparts were 4.55% and 9.09%, respectively (P〈0.05). The expressions of Twist, VEGF-C, and VEGFR-3in pN+ patients obtained through Western blotting analysis were significantly higher than those in pNO patients, and the levels of VEGF-C and VEGFR-3 were positively correlated with that of Twist.Conclusions Twist expression correlates with lymph node metastasis. The mechanism involved in such a correlation may be related to lymphangiogenesis.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.81802296)Natural Science Foundation of Tianjin(Grant No.18JCQNJC82500)Tianjin Municipality Science and Technology Commission Projects(Grant No.12ZCDZSY15600).
文摘Objective:Lymphatic metastasis is one of the leading causes of malignancy dispersion in various types of cancer.However,few anti-lymphangiogenic drugs have been approved for clinical use to date.Therefore,new therapies to block lymphangiogenesis are urgently required.Methods:Immunohistochemistry,immunofluorescence,Western blot,migration assays,and lymphangiogenesis and lymphatic metastasis assays were used.Results:Anlotinib,a receptor tyrosine kinase inhibitor,suppressed the rate of new metastatic lesions(31.82%in the placebo arm and 18.18%in the anlotinib arm)in patients with advanced lung adenocarcinoma who were enrolled in our ALTER-0303 study.D2-40+-lymphatic vessel density was strongly correlated with disease stage,metastasis,and poor prognosis in 144 Chinese patients with lung adenocarcinoma.In mice bearing A549EGFP tumors,tumor lymphatic vessel density,tumor cell migration to lymph nodes,and the number of distant metastatic lesions were lower in the anlotinib group than in the controls.Anlotinib inhibited the growth and migration of human lymphatic endothelial cells(hLECs)and lymphangiogenesisin vitro andin vivo.Treatment of hLECs with anlotinib downregulated phosphorylated vascular endothelial growth factor receptor 3(VEGFR-3).Conclusions:Anlotinib inhibits lymphangiogenesis and lymphatic metastasis,probably through inactivating VEGFR-3 phosphorylation.The results indicate that anlotinib may be beneficial for treatment in avoiding lymphangiogenesis and distant lymphatic metastasis in lung adenocarcinoma.(Trial registration:ALTER0303;NCT02388919;March 17,2015.)
基金Supported by Gazi UniversityScientific Research Projects DivisionNo.01/2007-62
文摘AIM: To evaluate whether serum and tumor indoleamine 2,3-dioxygenase activities can predict lymphatic invasion (LI) or lymph node metastasis in colorectal carcinoma.METHODS: The study group consisted of 44 colorectal carcinoma patients. The patients were re-grouped according to the presence or absence of LI and lymph node metastasis. Forty-three cancer-free subjects without any metabolic disturbances were included into the control group. Serum neopterin was measured by enzyme linked immunosorbent assay. Urinary neopterin and biopterin, serum tryptophan (Trp) and kynurenine (Kyn) concentrations of all patients were determined by high performance liquid chromatography. Kyn/Trp was calculated and its correlation with serum neopterin was determined to estimate the serum indoleamine 2,3-dioxygenase activity. Tissue sections from the studied tumors were re-examined histopathologically and were stained by immunohistochemistry with indoleamine-2,3-dioxygenase antibodies.RESULTS: Neither serum nor urinary neopterin was significantly different between the patient and control groups (both P > 0.05). However, colorectal carcinoma patients showed a significant positive correlation between the serum neopterin levels and Kyn/Trp (r = 0.450, P < 0.01). Urinary biopterin was significantly higher in cancer cases (P < 0.05). Serum Kyn/Trp was significantly higher in colorectal carcinoma patients (P < 0.01). Lymphatic invasion was present in 23 of 44 patients, of which only 12 patients had lymph node metastasis. Eleven patients with LI had no lymph node metastasis. Indoleamine-2,3-dioxygenase intensity score was significantly higher in LI positive cancer group (44.56% ± 6.11%) than negative colorectal cancer patients (24.04% ± 6.90%), (P < 0.05). Indoleamine 2,3-dioxygenase expression correlated both with the presence of LI and lymph node metastasis (P < 0.01 and P < 0.05, respectively). A significant difference between the accuracy of diagnosis by using either total indoleamine-2,3-dioxygenase immunostaining score or of lymph node metastasis was found during the evaluation of cancer patients.CONCLUSION: Indoleamine-2,3-dioxygenase expression may predict the presence of unrecognized LI and lymph node metastasis and may be included in the histopathological evaluation of colorectal carcinoma cases.