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Objective:To investigate the influence of lymphadenectomy on efficacy of patients with intrahepatic cholangiocarcinoma (ICC) at different locations.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 123 patients with ICC who were admitted to the Affiliated Hospital of North Sichuan Medical College from January 2015 to January 2022 were collected. There were 78 males and 45 females, aged 55(rage, 50?60)years. All patients underwent radical resection. Observation indicators: (1) clinical characteristics of patients with ICC; (2) follow-up; (3) surgical situations in ICC patients with different number of lymph nodes dissected. Measurement data with normal distribution were represented as Mean± SD, and compari-son between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to draw survival curve and Log-Rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with ICC. Of the 123 patients, 81 cases had peripheral ICC and 42 cases had central ICC. The albumin-bilirubin grade (grade 1, grade 2?3), preoperative lymph node metastasis risk assessment (low risk, high risk), the number of lymph nodes dissected (<6, ≥6), lymph node metastasis (positive, negative) were 57, 24, 51, 30, 49, 32, 15, 66 in patients with peripheral ICC, versus 19, 23, 17, 25, 14, 28, 16, 26 in patients with central ICC, showing significant differences in the above indicators between them ( χ2=7.40, 5.66, 8.17, 5.62, P<0.05). (2) Follow-up. All the 123 patients were followed up for 28(range, 21?38)months. The 3-year overall survival rate was 57.8% in the 81 patients with peripheral ICC, versus 32.3% in the 42 patients with central ICC, showing a significant difference between them ( χ2=5.98, P<0.05). Of the 42 patients with central ICC, there were 25 cases with high risk of lymph node metastasis before surgery and 17 cases with low risk of lymph node metastasis before surgery. Of the 25 central ICC patients with high risk of lymph node metastasis before surgery, the 3-year overall survival rate was 28.9% in the 18 cases with the number of lymph nodes dissected ≥6, versus 14.3% in the 7 cases with the number of lymph nodes dissected <6, showing a significant difference between them ( χ2=8.90, P<0.05). (3) Surgical situa-tions in patients with the different number of lymph nodes dissected. Of the 123 patients, cases with the number of lymph nodes dissected <6 and ≥6 were 63 and 60, and there was no significant difference in the operation time, intraoperative blood transfusion, postoperative complications, bile leakage, liver insufficiency, pulmonary infection, pleural effusion, abdominal effusion, or lymphatic leakage between them ( P>0.05). One patient might have multiple complications. Conclusions:The prognosis of patients with peripheral ICC is better than that of patients with central ICC. For patients with central ICC who are at high risk of lymph node metastasis before surgery, adequate lymph node dissection may result in a better prognosis.
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The incidence of intrahepatic cholangiocarcinoma has been increasing worldwide in recent years. Hepatectomy is the first choice for surgical treatment of intrahepatic cholangiocarcinoma. However, due to high tumor invasion, early lymph node metastasis and other factors, only less than 30% of cases are resectable, and the overall prognosis of patients is very poor. Theoretically, liver transplantation can not only remove the tumor, but also replace the damaged liver. Therefore, many scholars have proposed liver transplantation for the treatment of intrahepatic cholangiocarcinoma in order to obtain better results. Intrahepatic cholangiocarcinoma was once listed as a contraindication of liver transplantation due to limited cases, tumor recurrence, and shortage of donors. However, with the optimization of recipient screening criteria and the development of neoadjuvant therapy, part of patients can also benefit from it, making liver transplantation a potential therapeutic strategy. Based on the literature review and the author′s experience, this article introduced the current situation of surgical treatment of intrahepatic cholangiocarcinoma, the comparison between hepatectomy and liver transplantation, the latest progress of liver transplantation treatment and the future challenges and solutions.
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ObjectiveTo investigate the effect and mechanism of osthole on the proliferation and apoptosis in human intrahepatic cholangiocarcinoma HuCCT1 cells. MethodThe effect of 10， 20， 40， 80， and 120 μmol·L-1 osthole on the proliferation of HuCCT1 cells was detected by the cell counting kit-8 （CCK-8）. A blank group， and low-， medium-， and high-dose osthole groups （16， 32， and 64 μmol·L-1） were set up. The effect of osthole on cell clone formation rate was detected by colony formation assay. The effect of osthole on cell cycle and apoptosis was detected by flow cytometry. The effect of osthole on cell apoptotic morphology was detected by Hoechst 33342 fluorescent staining. The effect of osthole on cell cycle protein cyclin B1， proliferating cell nuclear antigen （PCNA）， cysteine-aspartic acid protease （Caspase）-9， Caspase-3， cleaved Caspase-9， cleaved Caspase-3， cleaved poly（ADP-ribose） polymerase （cleaved PARP）， B-cell lymphoma-2 （Bcl-2）， phosphorylated protein kinase B （p-Akt）， phosphorylated mammalian target of rapamycin （p-mTOR）， and phosphorylated ribosomal protein S6 （p-RPS6） was detected by Western blot. ResultThe cell viability in the osthole group（40，80，120 μmol·L-1） decreased （P<0.05，P<0.01）， with the half maximal inhibitory concentration （IC50） of 63.8 μmol·L-1 as compared with that in the blank group. Compared with the blank group， the osthole groups（32，64 μmol·L-1）showed reduced clone formation rate （P<0.01）， increased number of cells in the G2 phase （P<0.05，P<0.01）， decreased number of cells， increased pyknosis and fragmentation， increased apoptosis rate （P<0.05，P<0.01）， down-regulated expression of cyclin B1， PCNA， Bcl-2， Caspase-3， Caspase-9， p-Akt， p-mTOR， and p-RPS6 （P<0.05，P<0.01）， and up-regulated expression of cleaved Caspase-3， cleaved Caspase-9， and cleaved PARP （P<0.05，P<0.01）. ConclusionOsthole can inhibit the proliferation and promote the apoptosis of HuCCT1 cells， and its mechanism may be related to the Akt/mTOR signaling pathway.
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Malignant liver tumors have a high incidence and mortality rate. Therefore, it is of great significance to promptly learn about tumor advancement status through relevant examinations for patients' follow-up, diagnosis, and therapy as well as the improvement of the five-year survival rate. The primary lesions and intrahepatic metastases of malignant liver tumors have been better demonstrated in the clinical study with the use of various isotope-labeled fibroblast activating protein inhibitors because of their low uptake in liver tissues and high tumor/background ratio, which provides a new method for early diagnosis, precise staging, and radionuclide therapy. In light of this context, a review of the research progress of fibroblast-activating protein inhibitors for the diagnosis of liver malignant tumors is presented.
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Humans , Positron Emission Tomography Computed Tomography , Carcinoma, Hepatocellular , Liver NeoplasmsABSTRACT
ObjectiveTo investigate the prognostic value of the enhancement pattern in arterial phase of preoperative Gd-EOB-DTPA enhanced magnetic resonance imaging （MRI） in evaluating the disease-free survival （DFS） and overall survival （OS） in patients undergoing curative resection for intrahepatic cholangiocarcinoma （ICC）. MethodsA retrospective analysis was done on the clinical， preoperative MRI findings and postoperative follow-up results of 93 pathologically confirmed ICC patients undergoing surgery in our hospital between January 2018 and December 2021. Kaplan-Meier survival curves and log-rank test were used to compare the DFS and OS of three groups with different arterial enhancement patterns. Cox regression analysis was used to identify the factors affecting DFS and OS. ResultsThere were significant differences in DFS and OS among the 3 groups （log-rank test， P < 0.05）. The arterial enhancement pattern was an independent predictive factor for DFS （using diffuse hyperenhancement as a reference， peripheral rim enhancement： HR = 3.550； 95%CI： 1.16 ~ 10.8； P = 0.026；diffuse hypoenhancement： HR = 3.430； 95%CI： 1.04 ~ 11.3； P = 0.042）. The arterial enhancement pattern and tumor location were predictive factors for OS （（using diffuse hyperenhancement as a reference， diffuse hypoenhancement， HR = 8.500； 95%CI： 1.09-66.3； P = 0.041； using tumor distal location as a reference， tumor perihilar location HR=2.583，95%CI： 1.14-5.83， P =0.022）. The AUC of arterial enhancement patterns in predicting 1-， 2-， and 3- year DFS were 0.722， 0.748， and 0.617， respectively； in OS， 0.720， 0.704， and 0.730， respectively， which showed better prognostic efficacy than AJCC-TNM staging system. ConclusionArterial-phase enhancement pattern of preoperative Gd-EOB-DTPA enhanced MRI is an independent predictive factor for DFS and OS of ICC patients， with a better prognostic value than AJCC-TNM staging system， and can be used for the clinical management of ICC patients.
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Intrahepatic cholangiocarcinoma (ICC) is a primary malignant tumor of the liver, secondary to hepatocellular carcinoma, and its incidence tends to elevate worldwide. Hepatectomy is the optimal surgical regimen for ICC patients. ICC is considered as a contraindication for liver transplantation due to high tumor recurrence rate and poor survival outcome. At present, multiple significant progresses have been made in liver transplantation for ICC. For strictly-selected ICC patients, liver transplantation or liver transplantation after neoadjuvant therapy has achieved encouraging survival outcomes. Meantime, with the improvement of prognostic risk stratification of liver transplantation for ICC, the inclusion criteria of ICC candidates undergoing liver transplantation will be further optimized. In addition, the advancement of modern multi-mode comprehensive treatment of ICC will further guide the selection of neoadjuvant therapy before liver transplantation for ICC. The application of immune checkpoint inhibitors in ICC before liver transplantation is also an important research direction in the future. In this article, clinical prognosis of liver transplantation for ICC, prognostic risk factors and inclusion criteria of ICC candidates undergoing liver transplantation, and the ongoing trials and existing challenges were summarized, aiming to provide reference for liver transplantation for ICC and improve the quality of life for ICC patients.
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Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.
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Intrahepatic cholangiocarcinoma is a primary hepatic malignant tumor with high malignancy and poor prognosis. In addition to surgical resection, there are no clear studies showing that there are other effective treatments. In recent years, with the deepening of the research on the immune mechanism of various malignant tumors, immunotherapy has been gradually attached importance to various anti-solid tumor treatments, and has also become an important direction in the treatment of intrahepatic cholangiocarcinoma. The important role of tumor microenvironment in the immunotherapy of malignant tumors is gradually recognized. In this paper, the characteristics of immune microenvironment in intrahepatic cholangiocarcinoma has been summarized, and the application of immunotherapy in intrahepatic cholangiocarcinoma has been reviewed, with emphasis on the development of immune checkpoint inhibitors, cancer vaccines and adoptive cellular immunotherapy.
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Objective To evaluate the value of PLT and its parameters combined with AFP, CA199, CA125 and CEA on the preoperative differential diagnosis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods We analyzed retrospectively 274 patients with liver cancer who underwent surgery in the Second Hospital of Lanzhou University. They were divided into 229 cases in HCC group and 45 cases in ICC group according to postoperative pathological results. The differences of PLT, its parameters and tumor markers between the two groups were compared. ROC curve was used to evaluate the differential diagnosis effect on HCC and ICC by significantly different indicators in single and combined forms. The best scheme was verified in the patients with determined and undetermined preoperative diagnosis. Results Compared with HCC group, the levels of PLT, PCT, CA199 and CA125 in ICC group were higher (P < 0.05) and the level of AFP was lower (P < 0.05). The diagnostic analysis results of ROC curve showed that in single test, the AUC of AFP for HCC diagnosis was the largest (0.827). The AUC of the combined groups was higher than the single groups of tumor markers; the AUC of the PCT+AFP+CA199+CA125 group was the highest in all combination groups, and AUC was 0.891. The verification of the best combination group showed that the AUC was 0.924 in the preoperative determined diagnosis group and 0.854 in the undetermined diagnosis group. Conclusion Tumor markers in combination with PLT and PCT can increase the preoperative differential diagnosis efficacy of HCC and ICC. The combination of PCT, AFP, CA199 and CA125 before operation is helpful to further determine the diagnosis and plan the operation scheme.
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Objective:To study the risk factors of lymph node metastases in patients with intrahepatic cholangiocarcinoma (ICC) and to establish a risk prediction model of lymph node metastases in ICC.Methods:The clinicopathological data of 587 ICC patients who underwent radical hepatectomy and lymph node dissection at Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) from January 2007 to December 2011 were retrospectively analyzed. There were 395 males and 192 females with ages which ranged from 20 to 82 (54.7±10.8) years. Independent risk factors of lymph node metastases were studied using univariate and multivariate logistic regression analysis, and a risk prediction model was established. Receiver operating characteristic (ROC) curve was used to evaluate the accuracy of this model.Results:Of 587 patients, 158 (26.9%) had lymph node metastases. Multivariate logistic regression analysis showed that platelet count >300×10 9/L ( OR=1.985, 95% CI: 1.030-3.824, P=0.041), carbohydrate antigen 19-9 >37 U/ml ( OR=2.978, 95% CI: 1.994-4.448, P<0.001), tumor situated in left hemiliver ( OR=1.579, 95% CI: 1.065-2.341, P=0.023), multiple tumors ( OR=1.846, 95% CI: 1.225-2.783, P=0.003), and absence of cirrhosis ( OR=2.125, 95% CI: 1.192-3.783, P=0.011) were independent risk factors for lymph node metastases in ICC. The area under the ROC curve was 0.714, with a cutoff value of 0.215, and the sensitivity and specificity being 75.9% and 58.3%, respectively. Conclusions:The risk prediction model of ICC lymph node metastases was established using readily available clinical data obtained before operation. This model has good predictive values and can provide a reference for treatment decision on patients with ICC.
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Objective To investigate the efficacy and safety of lenvatinib combined with sintilimab as the second-line therapy for advanced intrahepatic cholangiocarcinoma (ICC). Methods A retrospective analysis was performed for the clinical data of the patients with advanced ICC who were admitted to Beijing Ditan Hospital from October 31, 2019 to October 31, 2021 and could not undergo surgery or experienced metastasis after surgery. All patients were treated with lenvatinib combined with sintilimab as the second-line therapy. The patients were followed up, and the RECIST1.1 criteria were used to assess treatment outcome. The primary endpoint was time to progression (TTP), and the secondary endpoints were tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS) time, and safety. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison between groups. Results A total of 27 patients were enrolled, among whom there were15 male patients (55.6%) and 12 female patients (44.4%), with a median age of 58 years (range 33-73 years). The median TTP for these patients was 5.5 (95% confidence interval [ CI ]: 1.7-9.3) months, and 13 patients (48.1%) died of disease progression, with a median OS time of 11.2 (95% CI : 5.0-17.4) months. The overall ORR and DCR were 40.7% and 70.3%, respectively. Of all patients, 66.7% experienced varying degrees of adverse events, and among these patients, 44.4% had an increase in alanine aminotransferase, 44.4% had an increase in aspartate aminotransferase, 37.0% had hypertension, 29.6% had an increase in bilirubin, 29.6% experienced diarrhea, and 25.9% each experienced proteinuria, anorexia, and weakness. No treatment-related death was observed, and only 1 patient developed grade Ⅳ immune-related hepatotoxicity and was relieved without sequelae after corticosteroid therapy, resulting in permanent withdrawal of sintilimab. The patients with lymph node metastasis had a significantly shorter median TTP than those without lymph node metastasis (4.5 months vs 18.8 months, P =0.035), and the patients who achieved disease remission had a significantly longer median TTP [11.6 months (95% CI : 5.6-17.6) vs 2.8 months (95% CI : 1.8-3.8), P < 0.001]; the patients with lymph node metastasis had a shorter median OS time [9.6 months (95% CI: 7.9-11.3) vs 21.9 months (95% CI : 0-44.9), P =0.053], and the patients who achieved disease remission had a significantly longer median OS time [16.6 months (95% CI : 9.0-24.2) vs 6.9 months (95% CI : 3.6-10.2), P =0.011]. Conclusion Lenvatinib combined with sintilimab has a marked clinical effect and a low incidence rate of serious adverse events as the second-line therapy for advanced ICC, and therefore, it is a safe and effective treatment regimen.
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ObjectiveTo explore the mechanism of cucurbitacin B （CuB） in inhibiting cell proliferation and glycolysis. MethodCell counting kit-8 （CCK-8） was applied to investigate the effect of different concentrations of CuB （0， 40， 80， 120， 160， 200， 400， and 800 nmol·L-1） on the proliferation of HuCCT1 cells. The effect of different concentrations of CuB （50， 100， and 200 nmol·L-1） on the colony formation ability of HuCCT1 cells was detected by plate cloning assay. The effect of different concentrations of CuB （50， 100， 200 nmol·L-1） on the HuCCT1 cell cycle was analyzed by flow cytometry. Visible spectrophotometry was employed to detect the activity of key glycolytic enzymes hexokinase （HK） and pyruvate kinase （PK）） and changes in glucose consumption， lactate production， and adenosine triphosphate （ATP） production in HuCCT1 cells after administration of different concentrations of CuB （50， 100， 200 nmol·L-1）. Western blotting was used to assay the effect of CuB on the expression of cell cycle-related proteins， proliferation-related proteins， key glycolytic proteins， and Akt/mammalian target of rapamycin （mTOR） pathway-related proteins. ResultAs compared with the blank group， CuB at dose of 160-800 nmol·L-1 after 24 h administration and CuB at dose of 80-800 nmol·L-1 after 48 h administration inhibited the proliferation of HuCCT1 cells in a time- and dose-dependent manner （P<0.05， P<0.01）， and the median inhibitory concentration was 200 nmol·L-1 48 h after administration. CuB can restrain the colony formation ability of HuCCT1 cells in a dose-dependent manner （P<0.01）， and block HuCCT1 cell cycle in G2 phase （P<0.05， P<0.01）. CuB （100 and 200 nmol·L-1） can suppress the activities of HK and PK and reduce cell glucose consumption and production of lactate and ATP （P<0.05， P<0.01）. Western blot results showed that CuB （100 and 200 nmol·L-1） can inhibit the protein levels of cycle-related protein Cyclin B1， proliferating cell nuclear antigen （PCNA）， HK1， HK2， PKM1， PKM2， phosphorylated Akt （p-Akt）， phosphorylated mTOR （p-mTOR）， and phosphorylated ribosomal protein S6 （p-RPS6） （P<0.05， P<0.01）. ConclusionCuB can inhibit aerobic glycolysis in HuCCT1 cells via the Akt/mTOR pathway， thereby affecting cell proliferation.
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Objective To investigate the effect of 6-paradol on the proliferation, migration, and invasion of human intrahepatic cholangiocarcinoma cells and its mechanism. Methods Human intrahepatic cholangiocarcinoma cell lines HCCC 9810 and HUCCT1 were treated with different concentrations of 6-paradol or an equal volume of DMSO (control group), and then CCK-8 assay, plate colony formation assay, wound healing assay, and Transwell assay were used to measure cell proliferation, migration, and invasion. The bioinformatics software Swiss Target Prediction was used to predict the protein targets of 6-paradol, and Western blot was used to measure the protein expression levels of STAT3, p-STAT3, SRC, p-mTOR, p21, Bcl-2, and p53; Drug Affinity Responsive Target Stability (DARTS) assay was used to investigate the interaction between 6-paradol and STAT3. After cholangiocarcinoma HCCC 9810 and HUCCT1 cells were transfected with STAT3 overexpression plasmid or sh-p21 plasmid, quantitative real-time PCR was used to measure the mRNA expression levels of STAT3 and p21, and Western blot was used to measure the protein expression levels of STAT3 and p21; CCK-8 assay, wound healing assay, and Transwell assay were used to measure cell proliferation, migration, and invasion. The t -test was used for comparison of data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, the 6-paradol treatment groups had significant reductions in cell proliferation, migration, and invasion ( P 0.05). In the 6-paradol treatment groups, the proportion of STAT3 hydrolyzed by protease was reduced by 48.66% and 45.33%, respectively ( t =16.64 and 8.76, both P < 0.05); after transfection with STAT3 overexpression plasmid or p21-silencing plasmid in cholangiocarcinoma cells, there was a significant increase in the mRNA expression level of STAT3 ( t HCCC 9810 =2.82, t HUCCT1 =5.60, both P < 0.05) and a significant reduction in the mRNA expression level of p21 ( t HCCC 9810 =6.84, t HUCCT1 =3.91, both P < 0.05). CCK-8 assay showed that for HCCC 9810 and HUCCT1 cells treated with 6-paradol for 48 and 72 hours, the STAT3 overexpression group had a significantly higher proliferation rate than the single administration group, and the p21 silencing group also had a significantly higher proliferation rate than the single administration group ( P < 0.05). The wound healing assay showed that the HCCC 9810 and HUCCT1 cells with STAT3 overexpression or p21 silencing had a significantly higher wound healing rate than the single administration group (all P < 0.05). Transwell assay showed that the HCCC 9810 and HUCCT1 cells with STAT3 overexpression or p21 silencing had significant increases in migration rate and invasion rate compared with the single administration group (all P < 0.05). Conclusion 6-Paradol inhibits the proliferation, migration, and invasion of cholangiocarcinoma cells by targeting the STAT3-p21 pathway.
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Intrahepatic cholangiocarcinoma (ICC) is highly invasive and has poor prognosis. At present, there is no effective adjuvant treatment. With the indepth researches on ICC-related tumor microenvironment, gene, protein, epigenetic modification and signaling pathway, the potential therapeutic targets have been found. This article will review the novel potential therapeutic targets of ICC.
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Liver transplantation is an effective approach to treat intrahepatic cholangiocarcinoma (ICC). It is necessary to strictly control surgical indications of ICC because of its high invasiveness, lymph node metastasis and recurrence rate after liver transplantation. Liver transplantation yields high efficacy for single ICC with a diameterof ≤2 cm. For advanced ICC, neoadjuvant therapies including locoregional treatment and systemic chemotherapy should be initially delivered. According to the response of these neoadjuvant therapies, whether liver transplantation should be performed can be determined, and individualized adjuvant therapy should be delivered after operation. At present, multiple gene mutation targets and targeted therapeutic drugs for cholangiocarcinoma have been identified. Comprehensive treatment before and after liver transplantation may expand surgical indications of liver transplantation for ICC and improve clinical prognosis of the recipients. In this article, liver transplantation for ICC, neoadjuvant therapy before liver transplantation, postoperative adjuvant therapy and targeted therapy for ICC were reviewed.
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Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy that originates from epithelial cells of bile duct. Lack of diagnostic measures and therapies leads to an increasing number of deaths from ICC worldwide. Here we described a case of 61-year-old Chinese female, who initially presented with right upper quadrant pain, combined with the results that a low density mass accompanied by multiple nodules occupied the right liver lobe by CT-scan, which also showed an aberrant right hepatic artery that participated in the right liver lobe and origining from the superior mesenteric artery, this patient was clinically considered as hepatic abscess (HA). The patient’s right upper quadrant pain was alleviated after been treated with the infusion chemotherapy of the aberrant right hepatic artery (ARHA) via percutaneous femoral arterial catheterization by Seldinger technique (Meropenem 7 days) following the failure of the liver-puncture drainage. However, the right upper quadrant pain occurred again 6 days later, serum CA19-9>1000.0 U/ml, which indicated the possibility of hepatic malignancy, so we performed laparotomy. The histopathological result of intraoperative frozen section demonstrated cholangiocarcinoma, unfortunately, it was unresectable. Finally, right lower lung pneumonia and pleural empyema happened to her and she succumbed to respiratory failure 22 days following surgery. In this report, we will discuss the case with reference to the literature.
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Objective To investigate the clinical value of lymph node dissection (LND) in the radical resection of intrahepatic cholangiocarcinoma (ICC).Methods The propensity score matching and retrospective cohort study was conducted.The clinicopathological data of 448 patients with ICC who were admitted to 12 medical centers from December 2011 to December 2017 were collected,including 279 in the Eastern Hepatobiliary Surgery Hospital of Navy Medical University,32 in the Mengchao Hepatobiliary Hospital of Fujian Medical University,21 in the First Hospital Affiliated to Army Medical University,20 in the Cancer Hospital Chinese Academy of Medical Science and Peking Union Medical College,19 in the West China Hospital of Sichuan University,18 in the Second Hospital Affiliated to Zhejiang University School of Medicine,18 in the Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine,16 in the Beijing Friendship Hospital Affiliated to Capital Medical University,10 in the Xuanwu Hospital Affiliated to Capital Medical University,7 in the Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology,5 in the Beijing Tiantan Hospital Affiliated to Capital Medical University,and 3 in the Affiliated Hospital of North Sichuan Medical College.There were 281 males and 167 females,aged from 22 to 80 years,with a median age of 57 years.Of the 448 patients,143 with routinely intraoperative LND were divided into LND group and 305 without routinely intraoperative LND were divided into control group,respectively.Observation indicators:(1) the propensity score matching conditions and comparison of general data between the two groups after matching;(2) intraoperative and postoperative situations;(3) follow-up;(4) survival analysis.Patients were followed up by outpatient examinafion,telephone interview and email to detect survival of patients and tumor recurrence up to October 31,2018 or death.Follow-up was conducted once every 3 months within postoperative 1-2 years,once every 6 months within postoperative 2-5 years,and once a year after 5 years.The propensity score matching was realized using the nearest neighbor method with 1∶1 ratio.Measurement data with normal distribution were represented as Mean±SD,and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were represented as M (range),and comparison between groups was analyzed using the Mann-Whitney U test.Count data were described as absolute numbers,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Kaplan-Meier method was used to calculate survival rates and draw survival curve,and Log-rank test was used to perform survival analysis.Univariate analysis and multivaraiate analysis were conducted using the Log-rank test and COX regression model,respectively.Results (1) The propensity score matching conditions and comparison of general data between the two groups after matching:286 of 448 patients had successful matching,including 143 in each group.The number of males and females,cases with hepatitis,cases with grade A and B of Child-Pugh classification,cases with distance from margin to tumor ＜ 1 cm and ≥ 1 cm,cases with highly,moderately,and poorly differentiated tumor,cases with anatomical hepatectomy and nonanatomical hepatectomy before propensity score matching were 77,66,33,96,47,70,73,105,38,79,64 in the LND group,and 204,101,121,165,140,207,98,251,54,124,181 in the control group,respectively,showing significant differences in the above indices between the two groups (x2 =7.079,11.885,7.098,14.763,5.184,8.362,P＜0.05).After propensity score matching,the above indices were 77,66,33,96,47,70,73,105,38,79,64 in the LND group,and 79,64,29,88,55,71,72,112,31,74,69 in the control group,respectively,showing no significant difference in the above indices between the two groups (x2 =0.056,0.329,2.158,0.014,0.936,1.400,P＞0.05).(2) Intraoperative and postoperative situations:the operation time,volume of intraoperative blood loss,cases with intraoperative blood transfusion,cases with postoperative complications,and duration of postoperative hospital stay were 265 minutes (range,160-371 minutes),300 mL (range,200-500 mL),37,46,12 days (range,9-17 days) for the LND group,and 59 minutes (range,46-250 minutes),200 mL (range,100-400 mL),24,25,9 days (range,7-11 days) for the control group,respectively.There was no significant difference in the volume of intraoperative blood loss or cases with intraoperative blood transfusion between the two groups (Z =1.700,x2 =3.520,P ＞ 0.05).There were significant differences in the operation time,cases with postoperative complications,and duration of postoperative hospital stay (Z=6.520,x2=8.260,Z=4.270,P＜0.05).(3) Follow-up:143 patients in the LND group was followed up for 18-26 months.The 1-,3-,5-year survival rates were 66.9％,32.8％,25.0％,and the median survival time was 22.0 months (range,18.0-26.0 months).In the control group,143 patients were followed up for 11-32 months.The 1-,3-,5-year survival rates were 71.7％,38.0％,31.0％,and the median survival time was 22.0 months (range,11.0-32.0 months).There was no significant difference in the overall survival between the two groups (x2 =0.466,P＞0.05).(4) Survival analysis:results of univariate analysis showed that distance from margin to tumor,tumor diameter,the number of tumors,microvascular tumor thrombus,and lymph node metastasis by pathological examination were related factors for prognosis of patients undergoing radical resection of ICC (x2 =10.662,9.477,16.944,6.520,11.633,P＜0.05).Results of multivariate analysis showed that distance from margin to tumor＜ 1 cm,tumor diameter＞5 cm,multiple tumors,microvascular tumor thrombus,positive lymph node metastasis by pathological examination were independent risk factors for prognosis of patients undergoing radical resection of ICC (hazard ratio =0.600,1.571,1.601,1.750,1.723,95％ confidence interval:0.430-0.837,1.106-2.232,1.115-2.299,1.083-2.829,1.207-2.460,P＜0.05).Conclusion Lymph node metastasis is an independent risk factor affecting the prognosis of ICC patients,and it is necessary to perform LND in radical resection for patients with ICC and lymph node metastasis.
ABSTRACT
Intrahepatic cholangiocarcinoma (ICC) is a rare primary liver cancers.The pathogenesis is obscure and usually,it is asymptomatic in early stage,the diagnosis is made with difficulty.Most patients are in advanced stage upon diagnosis and have unresectable tumors.Strategies and indications for surgery are variable by different doctors.Standard,effective and individualized treatment strategies are lacking,with high malignancy,the tumor often shows unfavorable prognosis.In this review,we elucidate the cancer staging system,diagnostic algorithm,choice of surgical approaches and progress of nonsurgical treatment in conjunction with domestic and foreign literatures,so as to enhance the awareness of ICC and avoid misdiagnosis or underdiagnosis,eccessive or inadequate treatment in clinical work and confer benefit to patients.
ABSTRACT
Intrahepatic cholangiocellular carcinoma (ICC) has become the second common malignant tumors of the liver,with its incidence being next only to hepatocellular carcinoma (HCC).Due to the lack of targeted screening methods and specific clinical manifestations,most intrahepatic cholangiocarcinoma (ICC) is clearly diagnosed as advanced,which brings great difficulties to the treatment of ICC.At present,radical surgical resection is still the most effective method to ICC.However,for some patients who had a positive-margin (R1) resection or positive lymph node metastasis,multidisciplinary comprehensive treatment including transcatheter arterial chemoembolization (TACE),local ablation,systemic chemotherapy,targeted therapy and immunotherapy,etc.can effectively improve the prognosis of these patients.
ABSTRACT
Intrahepatic cholangiocarcinoma (ICC) is the second prevalent primary liver cancer,next to hepatocellular carcinoma.Epidemiologic studies suggest the morbidity of ICC is on the rise worldwide.Owing to the complex etiology,lack of effective screening methods,the concealment of early clinical symptoms and the limited treatment strategy,it is tough to diagnose to ICC and difficult for further treatment.In recent years,with the development of medical technology and the progress of medical treatment idea,active explorations have been made on the early diagnosis and treatment strategies of ICC.The aim of this narrative review is to summarize the research status relating to diagnostic methods and treatment strategies.