Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma

Zhang, Xu Feng; Xue, Feng; He, Jin; Alexandrescu, Sorin; Aldrighetti, Luca; Maithel, Shishir K.; Pulitano, Carlo; Bauer, Todd W.; Shen, Feng; Poultsides, George A.; Soubrane, O.; Martel, Guillaume; Koerkamp, B. Groot; Endo, Itaru; Lv, Yi; Pawlik, Timothy M.

doi:10.1016/j.hpb.2021.02.009

Cited by 13 publications

(4 citation statements)

References 26 publications

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“…This was because patients with stage IIIA tumor for instance had T3N0M0 which is defined as tumor progression to the visceral peritoneum, but studies have shown that these patients actually had a better outcome despite involvement of the visceral peritoneum. A modification to the AJCC eighth edition for CCA has therefore been proposed, specifically to T and M (21). Our novel staging system incorporated imaging findings of patients but unlike the AJCC, histologic samples of patients were not used and it was solely based on clinical parameters known to have a mortality impact.…”

Section: Discussionmentioning

confidence: 99%

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation

et al. 2023

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INTRODUCTION: Intrahepatic cholangiocarcinoma (iCCA) is a primary liver malignancy with poor prognosis. Current prognostic methods are most accurate for patients with surgically resectable disease. However, a significant proportion of patients with iCCA are not surgical candidates. We aimed to develop a generalizable staging system based on clinical variables to determine prognosis of all patients with iCCA. METHODS:The derivation cohort included 436 patients with iCCA seen between 2000 and 2011. For external validation, 249 patients with iCCA seen from 2000 to 2014 were enrolled. Survival analysis was performed to identify prognostic predictors. All-cause mortality was the primary end point. RESULTS:Eastern Cooperative Oncology Group status, tumor number, tumor size, metastasis, albumin, and carbohydrate antigen 19-9 were incorporated into a 4-stage algorithm. Kaplan-Meier estimates for 1-year survival were 87.1% (95% confidence interval [CI] 76.1-99.7), 72.7% (95% CI 63.4-83.4), 48.0% (95% CI 41.2-56.0), and 16% (95% CI 11-23.5), respectively, for stages I, II, III, and IV. Univariate analysis yielded significant differences in risk of death for stages II (hazard ratio [HR] 1.71; 95% CI 1.0-2.8), III (HR 3.32; 95% CI 2.07-5.31), and IV (HR 7.44; 95% CI 4.61-12.01) compared with stage I (reference). Concordance indices showed the new staging system was superior to the TNM staging for predicting mortality in the derivation cohort, P < 0.0001. In the validation cohort, however, the difference between the 2 staging systems was not significant.

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Section: Discussionmentioning

confidence: 99%

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation

et al. 2023

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“…The prognostic factors of ICC include tumor size, multifocality, microvascular invasion (MVI), nerve invasion, and lymph node metastasis [9][10][11][12]. Studies have indicated that even in the early stages of ICC without MVI and lymph node metastasis, the recurrence rate in patients after resection may still be as high as 60-80% [13][14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line, ICC-X2

Xu,

Chai,

Tang

et al. 2024

World J Oncol

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Background Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignant tumor of the biliary tract that is prone to recurrence and metastasis and is characterized by poor sensitivity to chemotherapy and overall prognosis. For these reasons, there is an urgent need to understand its pathological mechanisms and develop effective treatments. To address this challenge, the establishment of suitable preclinical models is critical. Methods Fresh ICC tissue samples were used for primary culture and subculture. The cell line was evaluated by cell proliferation assays, clonal formation assays, karyotype analysis, and short tandem repeat (STR) analysis. Drug resistances against oxaliplatin, paclitaxel, gemcitabine and 5-fluorouracil (5-FU) were evaluated by CCK-8 assay. Subcutaneous injection of 1 × 10 6 cells to three BALB/c nude mice was conducted for xenograft studies. The hematoxylin and eosin (H&E) staining was used to detect the pathological status of the cell line. The expression of biomarkers CK7, CK19, Ki-67, E-cadherin and vimentin was determined by immunocytochemistry assay. Results A new ICC cell line named ICC-X2 was successfully established. Like ICC-X3 established using the same patient’s metastatic tumor, the cell line has been continuously cultured in vitro for more than a year and has been passaged more than 100 times. ICC-X2 retained the typical biliary epithelial morphology. The population doubling time of ICC-X2 is 48 h. The cells demonstrated an abnormal nearly tetraploid karyotype. The STR analysis confirmed that ICC-X2 was highly consistent with the primary tumor tissue and not cross-contaminated by existing cell lines. ICC-X2 cells positively expressed CK7, CK19, E-cadherin, and vimentin, and the positive expression of Ki-67 in ICC-X2 cells was 40%. The ICC-X2 cells exhibited a strong clonogenic ability. The drug sensitivity test indicated that ICC-X2 was sensitive to oxaliplatin and paclitaxel, but naturally resistant to gemcitabine and 5-FU. ICC-X2 was rapidly able to form transplanted tumors in vivo after subcutaneous inoculation in nude mice. Conclusions ICC-X2 is an excellent experimental model that can be used for studying the occurrence, development, and metastasis of ICC and investigating the mechanism of tumor drug resistance.

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“…Intrahepatic cholangiocarcinoma (ICC) is a well-characterized hepatobiliary cancer, and its incidence and mortality are increasing worldwide. [1][2][3][4] ICC shows high frequencies of vascular invasion, lymph node metastasis, and distant metastasis due to accelerated epithelialmesenchymal transition (EMT) and cancer stem cell (CSC)-like properties. 5 As such, the 5-year survival rate for advanced ICC is only 20% after curative resection.…”

Section: Introductionmentioning

confidence: 99%

Tspan15‐ADAM10 signalling enhances cancer stem cell‐like properties and induces chemoresistance via Notch1 activation in ICC

Yoshizumi,

Kuboki,

Takayashiki

et al. 2023

Liver International

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Background & AimsNotch1 activation promotes ICC progression and is associated with chemoresistance; however, therapies directly targeting Notch1 showed severe adverse effects. Notch1 activation is mediated by ADAM10, a molecular scissor that separates the target protein from its substrates in the cell membrane. Tspan15 regulates ADAM10 function, but the role of Tspan15 in ICC progression is unclear.MethodsTspan15, ADAM10, and Notch1 expression and activation in fresh surgical specimens from 80 ICC patients and ICC cells were evaluated by immunohistochemistry, RT‐PCR, western blotting, and flow cytometry.ResultsTspan15 expression was increased in ICC compared with adjacent liver tissue, and high Tspan15 expression was an independent factor for poor prognosis. In ICC with high Tspan15 expression, vascular invasion, lymph node metastasis, and haematogenous recurrence were increased. Tspan15 was co‐expressed with ADAM10 in ICC, and associated with the expression of stemness and EMT markers. In ICC cells, Tspan15 induced ADAM10 activation by mediating the translocation of activated m‐ADAM10 from the cytoplasm to the surface of the cell membrane, which further activated Notch1 by separating the intracellular domain of Notch1 from its extracellular domain, leading to enhancement of CSC‐like properties and EMT. This signalling was associated with enhanced chemoresistance against gemcitabine and cisplatin. Inhibition of Tspan15 or ADAM10 is a promising therapeutic strategy in ICC, as Tspan15 or ADAM10 knockdown or treatment with ADAM10 inhibitor reduced chemoresistance and invasiveness by suppressing Notch1‐mediated CSC‐like properties and EMT.ConclusionsTspan15‐ADAM10‐Notch1 signalling is associated with aggressive tumour progression and poor prognosis in ICC.

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Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma

Cited by 13 publications

References 26 publications

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation

CS-iCCA, A New Clinically Based Staging System for Intrahepatic Cholangiocarcinoma: Establishment and External Validation

Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line, ICC-X2

Tspan15‐ADAM10 signalling enhances cancer stem cell‐like properties and induces chemoresistance via Notch1 activation in ICC

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