The Dominant Component and Clinicopathological Characteristics of Combined Hepatocellular-cholangiocarcinoma After Radical Resection.

Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare subtype of primary liver carcinoma, characterized by the unequivocal presence of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). However, its clinicopathological characteristics have not yet been thoroughly elucidated. In particular, cholangiolocellular carcinoma (CLC) was classified as a subtype of cHCC-CCA according to the 2010 World Health Organization (WHO) classification. However, according to the 2019 WHO classification, tumors displaying histological features consistent with CLC but lacking evidence of hepatocellular differentiation should be regarded as a distinct subtype of iCCA. Nevertheless, there may be notable differences in prognosis between CLC and iCCA, indicating the necessity for refining the classification when devising clinical treatment strategies. This study aimed to determine the clinicopathological features and prognostic factors of cHCC-CCAs following radical resection. Between January 2010 and September 2020, based on the 2010 WHO classification, we retrospectively studied the clinicopathological features and prognoses of patients with cHCC-CCAs in relation to the pathological dominant classification. The patients were classified according to the pathological dominant components of cHCC-CCA as HCC-dominant (HCC-D), iCCA-dominant (iCCA-D), or CLC-dominant (CLC-D). Data of 55 patients who underwent primary radical hepatectomy for cHCC-CCA were analyzed. The prevalences of each dominant classification were HCC-D, 21 (38.2%); iCCA-D, 11 (20.0%); and CLC-D, 23 (41.8%). Multivariate analysis showed that dominant classification was an independent risk factor for recurrence and cancer-specific survival (CSS). The dominant classification of cHCC-CCA has the potential to predict recurrence and CSS.

Matsubara K ，Kobayashi T ，Tadokoro T ，Namba Y ，Fukuhara S ，Oshita KO ，Honmyo N ，Kuroda S ，Arihiro K ，Ohdan H ... -  《-》

Postresection Outcomes of Combined Hepatocellular Carcinoma-Cholangiocarcinoma, Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Yoon YI ，Hwang S ，Lee YJ ，Kim KH ，Ahn CS ，Moon DB ，Ha TY ，Song GW ，Jung DH ，Lee JW ，Hong SM ，Yu ES ，Lee SG ... -  《-》

Comparing the clinicopathological characteristics of combined hepatocellular-cholangiocarcinoma with those of other primary liver cancers by use of the updated World Health Organization classification.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is an uncommon hepatic malignancy with a poor outcome. The 2019 World Health Organization (WHO) classification modified the definition and discarded the subtypes with stem cell features. However, the differences among cHCC-CCA, hepatocellular carcinoma (HCC), HCC with stem cell/progenitor features (HCCscf) and intrahepatic cholangiocarcinoma (iCCA) remain undetermined. The aim of this study was to investigate the characteristics of cHCC-CCA in comparison with those of other primary liver cancers by utilising the updated WHO classification. We retrospectively analysed 64 cHCC-CCA patients and 55 HCCscf patients from December 2007 to May 2018. Propensity score matching was conducted to compare these with HCC and iCCA patients. Clinicopathological characteristics, event-free survival and overall survival were evaluated with multivariate Cox proportional hazard regression. During a median follow-up of 55.9 months, cHCC-CCA patients had significantly poorer survival than HCCscf patients, and survival intermediate between that of HCC patients and that of iCCA patients. Hepatitis B virus (HBV) infection and high levels of tumour-infiltrating lymphocytes (TILs) were associated with favourable survival in cHCC-CCA patients. In the multivariate analysis, poor hepatic reserve, absence of HBV infection, stage IV disease and low levels of TILs were significant negative prognostic factors in cHCC-CCA patients. After being pooled with other primary liver cancers, cHCC-CCA and iCCA resulted in the worse survival. cHCC-CCA patients have survival intermediate between that of HCC patients and iCCA patients, and HBV infection and high levels of TILs predict favourable survival. Our study provides clinical correlations for the new 2019 WHO classification.

Yen CC ，Yen CJ ，Shan YS ，Lin YJ ，Liu IT ，Huang HY ，Yeh MM ，Chan SH ，Tsai HW ... -  《-》

Is nestin a diagnostic marker for combined hepatocellular-cholangiocarcinoma?

The type IV intermediate filament, nestin, may be a candidate diagnostic marker for combined hepatocellular-cholangiocarcinoma (cHCC-CCA). Therefore, the significance of nestin as a diagnostic marker for cHCC-CCA categorized by the World Health Organization (WHO) 2019 classification and its relationship with clinicopathological features were examined in the present study. Nestin expression was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 22 with small duct-type intrahepatic cholangiocarcinoma (iCCA), 20 with large duct-type iCCA and 35 with hepatocellular carcinoma (HCC). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in cHCC-CCA. Nestin expression was detected in significantly more patients with cHCC-CCA (66.7%) than in those with large duct-type iCCA (5%) (P < 0.01), HCC (2.9%) (P < 0.01) and small duct-type iCCA (40.9%) (P < 0.05). Nestin expression was partly associated with neural cell adhesion molecule (NCAM) and vimentin expression. Nestin expression was also observed in significantly more patients with small duct-type iCCA than in those with large duct-type iCCA and HCC (P < 0.01). Nestin-positive cHCC-CCA was characterized by a smaller tumour size, the more frequent presence of cholangiolocellular carcinoma (CLC) components, a higher rate of p53 overexpression and a higher rate of multiple genetic alterations (P < 0.05). Furthermore, p53 overexpression was associated with a higher histological grade and multiple genetic alterations (P < 0.05) in nestin-positive cHCC-CCA. Nestin may be a useful diagnostic marker for a specific subgroup of cHCC-CCA and small duct-type iCCA associated with CLC components, p53 mutations and multiple genetic alterations, which are related to stemness and multipotent differentiation.

Sasaki M ，Sato Y ，Nakanuma Y 《-》

Clinicopathological features and recurrence patterns of combined hepatocellular-cholangiocarcinoma.

Ishii T ，Ito T ，Sumiyoshi S ，Ogiso S ，Fukumitsu K ，Seo S ，Taura K ，Uemoto S ... -  《-》