Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women.Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development.Stress leads to dysfunctions of cells,molecules and neural circuits,thus promoting depression.Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

Objective:To examine the value of number of metastatic lymph nodes(NMLN), lymph node ratio(LNR) and log odds of metastatic lymph nodes(LODDS) in assessing the prognosis of patients with intrahepatic cholangiocarcinoma(ICC).Methods:The clinical and pathological data of 440 ICC patients who underwent curative-intent resection in 10 of Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected, and the deadline of follow-up was April 30th, 2019. Among them, 205 were males and 235 were females, with age of (57.0±9.9) years (range:23-83 years).Eighty-five cases (19.3%) had intrahepatic bile duct stones, and 98 cases (22.3%) had chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis. The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:A total of 440 patients underwent curative-intent resection and lymphadenectomy.R0 resection were achieved in 424 cases (96.4%) and R1 resection were in 16 cases (3.6%). The results of postoperative pathological examination showed that high, moderate and poor differentiation was 4.2%(18/426), 60.6%(258/426) and 35.2%(150/426), respectively.Adenocarcinoma was seen in 90.2%(397/440) and non-adenocarcinoma was seen in 9.8%(43/440), respectively. T stage: 2 cases (0.5%) with Tis, 83 cases(18.9%) with T1a, 97 cases(22.0%) with T1b, 95 cases(21.6%) with T2, 122 cases (27.7%) with T3 and 41 cases(9.3%) with T4.The overall median survival time was 24.0 months, and the 1-,3-, and 5-year survival rate was 74.3%, 37.7% and 18.3%, respectively. Lymphatic metastasis occurred in 175 patients(39.8%), the median total number of TNLE( M( Q R)) was 6(5), the median number of NMLN was 0(1), the median number of LNR was 0 (0.33) and the median number of LODDS was -0.70(-0.92). Rerults of univariate analysis showed that combined stones, pathological differentiation, vascular invasion, LODDS, margin and T staging affected the prognosis (all P<0.05). Rerults of multivariate analysis showed that pathological differentiation, LODDS, margin, and T staging were independent risk factors affecting the prognosis of ICC patients (all P<0.05). Conclusion:LODDS could be used as an optimal prognostic lymph node staging index for ICC, and it is also an independent risk factor for survival after curative intent resection.

ABSTRACT:Objective To study the effects of propofol on the metastasis of tumor cells related PI3K/Akt signaling pathway.Methods The breast cancer model was established by transplanting human derived breast cancer cell lines into immunodeficient mice with naked gene.The mice,inoculated successfully,were randomly divided into 4 groups:control group (C group,n =6),propofol group (P group,n =6),propofol+PI3K inhibitor (BYL71 9)group (P+B group,n =6),and PI3K inhibitor group (BYL71 9)(B group,n =6).The expressions of PI3K,p-Akt and Akt were examined by Western blot at week 4 after administration;the gene levels of PI3KR1, Akt1 and Akt2 were detected by RT-PCR at week 4 after administration;the number of metastatic lung nodules from both lungs was also observed at week 4 after administration.Results Compared with those in C group,the expressions of PI3K and p-Akt were significantly higher in P group (P <0.05),the level of PI3KR1 mRNA but not Akt1 and Akt2 mRNA was significantly increased(P < 0.05 ),and metastatic lung nodules significantly decreased (P <0.05).In B group,the expressions of PI3K and p-Akt were significantly decreased (P <0.05 ),the levels of PI3KR1,Akt1 and Akt2 mRNA were not significantly increased (P >0.05),but metastatic lung nodules significantly increased (P < 0.05 ).Compared with those in B group,in P+ B group the expressions of PI3K and p-Akt were markedly higher (P <0.05),the level of PI3KR1 mRNA but not Akt1 and Akt2 mRNA was significantly increased (P <0.05),and metastatic lung nodules significantly decreased (P <0.05).Conclusion Propofol can inhibit the metastasis of tumor cells through the upregulated and activated PI3K/Akt signaling pathway.