BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.展开更多
Biomarker identification is crucial for the selection of patients who might benefit from radiotherapy.To explore potential markers for response and prognosis in patients with locally advanced esophageal carcinoma trea...Biomarker identification is crucial for the selection of patients who might benefit from radiotherapy.To explore potential markers for response and prognosis in patients with locally advanced esophageal carcinoma treated with radiotherapy followed by surgery,we evaluated the expression of cell cycle checkpoint-related proteins Chk2,Cdc25C,and Cyclin D1.A total of 56 patients with locally advanced esophageal squamous cell carcinoma were treated with radiotherapy followed by surgery.Pretreatment tumor biopsy specimens were analyzed for Chk2,Cdc25C,and Cyclin D1 expression by immunohistochemistry.High expression of Chk2,Cyclin D1,and Cdc25C was observed in 44(78.6%),15(26.8%),and 27(48.2%) patients,respectively.The median survival was 16 months(range,3-154 months),with a 5-year overall survival rate of 19.6%.Overexpression of Chk2 was associated with smoking(P = 0.021),overexpression of Cdc25C was associated with patient age(P = 0.033) and tumor length(P = 0.001),and overexpression of Cdc25C was associated with pathologic complete response(P = 0.038).Univariate analysis demonstrated that overexpression of Cdc25C and pathologic complete response was associated with better survival.In multivariate analysis,Cdc25C was the most significant independent predictor of better survival(P = 0.014) for patients treated with radiotherapy followed by surgery.Overexpression of Cdc25C was significantly associated with pathologic complete response and better survival of patients with locally advanced esophageal cancer treated with radiotherapy followed by surgery.These results suggest that Cdc25C may be a biomarker of treatment response and good prognosis for esophageal carcinoma patients.Thus,immunohistochemical staining of Cdc25C in a pretreatment specimen may be a useful method of identifying optimal treatment for patients with esophageal carcinoma.展开更多
Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of...Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin were determined using immunohistochemistry. Correlations between NFAT and calcineurin expression and clinicopathologic characteristics were analyzed. We found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159), NFAT3 (28.3%, 45/ 159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159) expression were significantly higher in tumor tissues than in adjacent normal lung tissues (P < 0.001), respectively. The positive rate of NFAT1 expression was significantly higher in patients with adenocarcinoma (63.5% , 47/74) than in those with squamous cell carcinoma (43.5%, 37/85) (χ2 = 6.340, P = 0.012); with lymph node metastasis (61.6%, 53/ 86) than without lymph node metastasis (42.5%, 31/73) (χ2 = 5.818, P = 0.016); and with stage-II and -III diseases (61.8%, 55/89) than with stage-I disease (41.4%, 29/70) (χ2 = 6.524, P = 0.011). Moreover, the overexpression of NFAT1 was associated with poor survival of NSCLC patients (χ2 = 5.006, P = 0.025). The positive rate of NFAT4 was significantly higher in patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma (35.1%, 26/74) (χ2 = 8.045, P = 0.005) and with high and moderate differentiation (54.9% , 61/111) than with low differentiation (29.2% , 14/48) (χ2 = 8.943, P = 0.003). Calcineurin overexpression was significantly associated with histologic type (higher in squamous carcinoma than in adenocarcinoma, χ2 = 8.897, P = 0.003), differentiation grade (higher in high-moderation grade than in low grade, χ2 = 9.566, P = 0.002) and gender (higher in male than in female, χ2 = 5.766, P = 0.016). Furthermore, calcineurin expression was significantly correlated with NFAT4 level (r = 0.429, P < 0.001). These results suggest that NFAT1 expression is associated with lung adenocarcinoma progression, and NFAT4 expression, which was higher in squamous lung cancer, is associated with calcineurin expression and differentiation grade.展开更多
Spontaneous esophageal rupture,or Boerhaave syndrome,is a rare but potentially fatal condition with a mortality rate ranging from 20%to 30%in the literature.[1]In some European countries,the incidence is below 3 to 6/...Spontaneous esophageal rupture,or Boerhaave syndrome,is a rare but potentially fatal condition with a mortality rate ranging from 20%to 30%in the literature.[1]In some European countries,the incidence is below 3 to 6/1,000,000 persons.[2]Nowadays,the treatment of this disease remains a challenge to physicians due to the variable clinical manifestations and lack of consensus or guidelines.[3]To better understand this disease and summarize our experience in this field,we searched the medical files at our hospital using both electronic and manual methods.Herein,we report a series of 73 patients with spontaneous esophageal rupture in a single center over two decades.Between April 1983 and June 2013,a total of 73 consecutive patients were diagnosed with spontaneous esophageal rupture at the Fourth Hospital of Hebei Medical University.The clinical data were collected retrospectively with all of the patients’informed consent and the study was conducted in accordance with the Declaration of Helsinki.展开更多
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.
基金supported by grants from the National High Technology Research and Development Program of China(863 Program)(No.2006AA020707 and No.2006AA02A403)
文摘Biomarker identification is crucial for the selection of patients who might benefit from radiotherapy.To explore potential markers for response and prognosis in patients with locally advanced esophageal carcinoma treated with radiotherapy followed by surgery,we evaluated the expression of cell cycle checkpoint-related proteins Chk2,Cdc25C,and Cyclin D1.A total of 56 patients with locally advanced esophageal squamous cell carcinoma were treated with radiotherapy followed by surgery.Pretreatment tumor biopsy specimens were analyzed for Chk2,Cdc25C,and Cyclin D1 expression by immunohistochemistry.High expression of Chk2,Cyclin D1,and Cdc25C was observed in 44(78.6%),15(26.8%),and 27(48.2%) patients,respectively.The median survival was 16 months(range,3-154 months),with a 5-year overall survival rate of 19.6%.Overexpression of Chk2 was associated with smoking(P = 0.021),overexpression of Cdc25C was associated with patient age(P = 0.033) and tumor length(P = 0.001),and overexpression of Cdc25C was associated with pathologic complete response(P = 0.038).Univariate analysis demonstrated that overexpression of Cdc25C and pathologic complete response was associated with better survival.In multivariate analysis,Cdc25C was the most significant independent predictor of better survival(P = 0.014) for patients treated with radiotherapy followed by surgery.Overexpression of Cdc25C was significantly associated with pathologic complete response and better survival of patients with locally advanced esophageal cancer treated with radiotherapy followed by surgery.These results suggest that Cdc25C may be a biomarker of treatment response and good prognosis for esophageal carcinoma patients.Thus,immunohistochemical staining of Cdc25C in a pretreatment specimen may be a useful method of identifying optimal treatment for patients with esophageal carcinoma.
基金supported by Hi-Tech Research and Development Program of China(No.2006AA020707)
文摘Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin were determined using immunohistochemistry. Correlations between NFAT and calcineurin expression and clinicopathologic characteristics were analyzed. We found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159), NFAT3 (28.3%, 45/ 159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159) expression were significantly higher in tumor tissues than in adjacent normal lung tissues (P < 0.001), respectively. The positive rate of NFAT1 expression was significantly higher in patients with adenocarcinoma (63.5% , 47/74) than in those with squamous cell carcinoma (43.5%, 37/85) (χ2 = 6.340, P = 0.012); with lymph node metastasis (61.6%, 53/ 86) than without lymph node metastasis (42.5%, 31/73) (χ2 = 5.818, P = 0.016); and with stage-II and -III diseases (61.8%, 55/89) than with stage-I disease (41.4%, 29/70) (χ2 = 6.524, P = 0.011). Moreover, the overexpression of NFAT1 was associated with poor survival of NSCLC patients (χ2 = 5.006, P = 0.025). The positive rate of NFAT4 was significantly higher in patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma (35.1%, 26/74) (χ2 = 8.045, P = 0.005) and with high and moderate differentiation (54.9% , 61/111) than with low differentiation (29.2% , 14/48) (χ2 = 8.943, P = 0.003). Calcineurin overexpression was significantly associated with histologic type (higher in squamous carcinoma than in adenocarcinoma, χ2 = 8.897, P = 0.003), differentiation grade (higher in high-moderation grade than in low grade, χ2 = 9.566, P = 0.002) and gender (higher in male than in female, χ2 = 5.766, P = 0.016). Furthermore, calcineurin expression was significantly correlated with NFAT4 level (r = 0.429, P < 0.001). These results suggest that NFAT1 expression is associated with lung adenocarcinoma progression, and NFAT4 expression, which was higher in squamous lung cancer, is associated with calcineurin expression and differentiation grade.
文摘Spontaneous esophageal rupture,or Boerhaave syndrome,is a rare but potentially fatal condition with a mortality rate ranging from 20%to 30%in the literature.[1]In some European countries,the incidence is below 3 to 6/1,000,000 persons.[2]Nowadays,the treatment of this disease remains a challenge to physicians due to the variable clinical manifestations and lack of consensus or guidelines.[3]To better understand this disease and summarize our experience in this field,we searched the medical files at our hospital using both electronic and manual methods.Herein,we report a series of 73 patients with spontaneous esophageal rupture in a single center over two decades.Between April 1983 and June 2013,a total of 73 consecutive patients were diagnosed with spontaneous esophageal rupture at the Fourth Hospital of Hebei Medical University.The clinical data were collected retrospectively with all of the patients’informed consent and the study was conducted in accordance with the Declaration of Helsinki.
