Intrahepatic cholangiocarcinoma(ICC)is a highly aggressive liver malignancy characterized by a subtle onset and rapid progression.Most patients are diagnosed at advanced stages,making radical surgical resection impossible,and the overall prognosis is poor.The ability to convert initially unresectable ICC to resectable tumors through multimodal comprehensive treatment is significant for prolonging patient survival.In recent years,with the application of immunotherapy and targeted therapy in advanced ICC,as well as improvements in surgical techniques,radiation therapy,hepatic arterial infusion chemotherapy,and selective internal radiation therapy,along with updates in treatment strategies and concepts,some initially unresectable ICC tumors have become resectable following downstaging with various treatment modalities,which has brought new hope for improving conversion resection success rates and patient prognosis.However,conversion therapy for ICC still faces numerous challenges and controversies,including the lack of a recognized standard treatment regimen,limited overall conversion success rates,a lack of long-term follow-up data to demonstrate survival benefits after conversion resection,and unresolved issues such as whether patients who achieve clinical complete remission should undergo resection or be monitored.Given that most current studies on ICC conversion therapy are small-sample,retrospective studies or case reports,lacking high-level evidence from randomized controlled trials,and the majority of studies include various types of biliary tract cancers without considering the heterogeneity across different anatomical locations,the relevance of these findings for guiding ICC conversion treatment strategies is limited.There is an urgent need for high-quality,multi-center,large-sample,prospective clinical studies and basic research to explore optimal ICC translational therapy regimens with rapid efficacy,high objective response rates,and good safety profiles,identify patient populations with potential benefits from different treatments,and develop individualized treatment strategies to improve conversion success rates and ultimately enhance patient prognosis.This article reviews the progress in the conversion treatment of unresectable ICC,intending to provide a reference for clinical practice.

Intrahepatic cholangiocarcinoma(ICC)is a highly aggressive liver malignancy characterized by a subtle onset and rapid progression.Most patients are diagnosed at advanced stages,making radical surgical resection impossible,and the overall prognosis is poor.The ability to convert initially unresectable ICC to resectable tumors through multimodal comprehensive treatment is significant for prolonging patient survival.In recent years,with the application of immunotherapy and targeted therapy in advanced ICC,as well as improvements in surgical techniques,radiation therapy,hepatic arterial infusion chemotherapy,and selective internal radiation therapy,along with updates in treatment strategies and concepts,some initially unresectable ICC tumors have become resectable following downstaging with various treatment modalities,which has brought new hope for improving conversion resection success rates and patient prognosis.However,conversion therapy for ICC still faces numerous challenges and controversies,including the lack of a recognized standard treatment regimen,limited overall conversion success rates,a lack of long-term follow-up data to demonstrate survival benefits after conversion resection,and unresolved issues such as whether patients who achieve clinical complete remission should undergo resection or be monitored.Given that most current studies on ICC conversion therapy are small-sample,retrospective studies or case reports,lacking high-level evidence from randomized controlled trials,and the majority of studies include various types of biliary tract cancers without considering the heterogeneity across different anatomical locations,the relevance of these findings for guiding ICC conversion treatment strategies is limited.There is an urgent need for high-quality,multi-center,large-sample,prospective clinical studies and basic research to explore optimal ICC translational therapy regimens with rapid efficacy,high objective response rates,and good safety profiles,identify patient populations with potential benefits from different treatments,and develop individualized treatment strategies to improve conversion success rates and ultimately enhance patient prognosis.This article reviews the progress in the conversion treatment of unresectable ICC,intending to provide a reference for clinical practice.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.

Objective:To explore the clinical value of adjuvant therapy in patients with T3 gallbladder cancer (GBC) who have undergone R0 resection.Methods:Clinical and pathological data from 415 patients with T3 GBC who underwent surgical treatment in 7 tertiary centers in China from January 2013 to December 2018 were collected,including 251 males and 164 females,aged (61±11)years (range: 26 to 88 years). Depending on whether to receive adjuvant therapy after radical resection,the patients were divided into the radical resection group alone (group A, n=358) and the radical resection combined with the postoperative adjuvant therapy group (group B, n=57). The general data of the two groups were matched 1∶1 by propensity score matching method,and the caliper value was 0.02.Clinicopathological characteristics,overall survival and disease-free survival of the two groups were compared.The Cox regression model was used for multivariate analysis,and patients with at least one or more independent risk factors were classified as high-risk clinicopathological subtypes. Subgroup analysis was performed to assess the clinical value of adjuvant therapy after radical resection in patients with high-risk clinicopathological subtypes. Results:After the matching,there were 42 patients in each of the two groups. The incidence of gallbladder cancer and the number of dissected lymph nodes in group B after cholecystectomy were higher than those in group A ( χ 2=9.224,2.570,both P<0.05). There were no significant differences in overall survival rate and disease-free survival rate between the two groups before and after matching (all P>0.05). The results of the univariate and multivariate analysis showed that CA19-9>39 U/ml,nerve invasion,tumor location (liver side or bilateral),TNM stage ⅢB to ⅣB ,poorly differentiated tumor were independent prognostic factors of overall survival and disease-free survival of patients with T3 stage gallbladder cancer (all P<0.05).Three hundred and twenty-nine patients(79.3%) had high-risk clinicopathological subtypes,and the median survival time after curative resection with and without adjuvant therapy was 17 months and 34 months respectively,and the 3-year and 5-year overall survival rates were respectively 40.0%,21.3% and 46.0%,46.0% ( χ 2=4.042, P=0.044);the median disease-free survival time was 9 months and 13 months,and the 3-year and 5-year disease-free survival rates were 23.4%,13.6% and 30.2%,18.2% ( χ 2=0.992, P=0.319). Conclusions:Postoperative adjuvant therapy following radical surgery did not yield significant improvements in the overall survival and disease-free survival rates of patients diagnosed with T3 gallbladder cancer. However, it demonstrated a significant extension in the overall survival rate for patients presenting high-risk clinicopathological subtypes.