Morbidity, Prognostic Factors, and Competing Risk Nomogram for Combined Hepatocellular-Cholangiocarcinoma

Chen, Xiaoyuan; Lu, Yiwei; Shi, Xiaoli; Chen, Xuejiao; Ding, Rong; Han, Guoyong; Zhang, Long; Ni, Chuangye; Zhao, Jie; Gao, Yun; Wang, Xuehao

doi:10.1155/2021/3002480

Cited by 4 publications

(4 citation statements)

References 64 publications

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“…These findings also explained the differences in some other variables, such as marital status, cancer history, and OCSD. Meanwhile, similar to intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma, fibrolamellar carcinoma tended to have a larger tumor size and higher probability of extrahepatic invasion (lymph node and distant metastasis) (29,30). However, these factors seemed not to be drivers of poor prognoses as expected.…”

Section: Discussionmentioning

confidence: 64%

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Chen

Shi

et al. 2022

Front. Oncol.

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BackgroundHepatocellular carcinoma (HCC) is a highly heterogeneous tumor with several rare pathological subtypes and which is still poorly understood. This study aimed to describe the epidemiological and clinical spectrum of five rare HCC subtypes and develop a competing risk nomogram for cancer-specific survival prediction.MethodsThe study cohort was recruited from the Surveillance, Epidemiology, and End Results database. The clinicopathological data of 50,218 patients histologically diagnosed with classic HCC and five rare subtypes (ICD-O-3 Histology Code = 8170/3-8175/3) between 2004 and 2018 were reviewed. The annual percent change (APC) was calculated utilizing Joinpoint regression. The nomogram was developed based on multivariable competing risk survival analyses. Akaike information criterion, Bayesian information criterion, C-index, calibration curve, and area under the receiver operating characteristic curve were obtained to evaluate the prognostic performance. A decision curve analysis was introduced to examine the clinical value of the models.ResultsDespite scirrhous carcinoma, which showed a decreasing trend (APC = -6.8%, P = 0.025), the morbidity of other rare subtypes remained stable from 2004 to 2018. The incidence-based mortality was plateau in all subtypes during the period. Clear cell carcinoma is the most common subtype (n = 551, 1.1%), followed by subtypes of fibrolamellar (n = 241, 0.5%), scirrhous (n = 82, 0.2%), spindle cell (n = 61, 0.1%), and pleomorphic (n = 17, ~0%). The patients with fibrolamellar carcinoma were younger and more likely to have a non-cirrhotic liver and better prognoses. Scirrhous carcinoma shared almost the same macro-clinical characteristics and outcomes as the classic HCC. Clear cell carcinoma tended to occur in the Asia-Pacific elderly male population, and more than half of them were large HCC (Size>5cm). Sarcomatoid (including spindle cell and pleomorphic) carcinoma was associated with a larger tumor size, poorer differentiation, and more dismal prognoses. The pathological subtype, T stage, M stage, surgery, alpha-fetoprotein, and cancer history were confirmed as the independent predictors in patients with rare subtypes. The nomogram showed good calibration, discrimination, and net benefits in clinical practice.ConclusionThe rare subtypes had unique clinicopathological features and biological behaviors compared with the classic HCC. Our findings could provide a valuable reference for clinicians. The constructed nomogram could predict the prognoses with good performance, which is meaningful to individualized management.

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Section: Discussionmentioning

confidence: 64%

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Chen

Shi

et al. 2022

Front. Oncol.

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“…According to the World Health Organization (WHO) classification of tumors of the digestive system (5 th edition), CHC is defined as PLC with both hepatocellular and cholangiocytic differentiation in the same tumor, which is consistent with the type 3 tumor proposed by Allen and Lisa (11) and the type 2 tumor described by Goodman et al (12). Due to its complexity, CHC exhibits mixed clinicopathological characteristics from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), creating challenges for diagnosis and clinical decision-making (4,(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 62%

Promising role of liver transplantation in patients with combined hepatocellular-cholangiocarcinoma: a propensity score matching analysis

Chen¹,

Sun²,

Lu³

et al. 2022

Ann Transl Med

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Background: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare but vital heterogeneous histological subtype of primary liver cancer (PLC) with no standardized treatment strategy. This study aimed to preliminarily investigate the role of liver transplantation (LT) in CHC and develop a novel risk scoring model (RSM) to evaluate the benefits of transplantation. Methods:The study cohort was taken from the Surveillance, Epidemiology, and End Results database.The annual percent change (APC) in incidence or ratio was calculated utilizing the Joinpoint regression.Propensity score matching (PSM) was introduced to reduce the selection bias between groups. A novel RSM was developed based on the independent prognostic factors identified by the Cox regression model.The predictive performance of the RSM was compared with the Milan Criteria and the UCSF Criteria, respectively.Results: A total of 223 CHC patients were enrolled, and 60 (26.9%) of them received LT. The incidencebased mortality did not decrease between 2004 and 2015 (APC =1.7%, P=0.195). Although LT was considered an independent protective predictor for CHC, it showed a declining ratio from 33.3% in 2004 to 15.4% in 2015 (APC =−8.9%, P=0.012). The LT recipients had better outcomes than others who underwent hepatectomy or local destruction (P<0.05). Compared with other subtypes of PLC, the posttransplantation prognoses of CHC patients were similar to those with hepatocellular carcinoma (P>0.05) but significantly better than those with intrahepatic cholangiocarcinoma (ICC) (P<0.05). Based on the RSM (vascular invasion: 1 point; tumor size >2 cm: 1 point; multiple tumors: 2 points), patients were stratified into two prognostic subgroups: the low-risk (scoring ≤2) and the high-risk (scoring >2 or extrahepatic metastasis) groups. Patients in the low-risk group were more likely to benefit from LT. The predictive performance of the RSM outperformed the Milan and UCSF Criteria in both the training and validation sets.Conclusions: Therapeutic strategies for CHC should be further improved. Patients with CHC should also be considered potential LT candidates. The novel RSM could be helpful to stratify patients and assist clinical decision-making.

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“…Nevertheless, more attention still should be given to developing better therapeutic strategies to further improve the prognosis of HCC. Different from intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma (CHC), LNM represents a rare but equally aggressive biological behavior of HCC, secondary only to the lung as the destination that most commonly develops extrahepatic metastasis (9,29,30). The incidence of LNM varies in different clinical observational studies, from 1.2% to 15.3% (10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Development and Validation Of A Model To Predict Regional Ly...mentioning

confidence: 99%

Development and Validation of a Novel Model to Predict Regional Lymph Node Metastasis in Patients With Hepatocellular Carcinoma

Chen

Shi

et al. 2022

Front. Oncol.

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BackgroundThe evaluation of the nodal status of hepatocellular carcinoma (HCC) is a classic but controversial topic. This study aimed to investigate the incidence of lymph node metastasis (LNM), explore the role of lymph node dissection (LND), and develop and validate a novel model to predict LNM in patients with HCC, not other specified (NOS).MethodsThe study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) was calculated using the Joinpoint regression. Survival analyses adopted the competing risk model. The nomogram was constructed based on the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm and validated by calibration curves. The area under the receiver operating characteristic curve (AUROC) was obtained to compare prognostic performance. Decision curve and clinical impact curve analyses were introduced to examine the clinical value of the models.ResultsA total of 8,829 patients were finally enrolled in this study, and 1,346 (15.2%) patients received LND. The LND rate showed no noticeable fluctuation in the last decade, with an APC of 0.5% (P=0.593). LNM was identified in 56 (4.2%) patients and confirmed an independent prognostic factor of HCC patients (P=0.005). There were 2,497 lymph nodes retrieved, and 93 (3.7%) of them were positive. After propensity score matching, LND indicated no direct oncologic benefit and did not worsen competing risks. Moreover, an increased number of lymph nodes retrieved could not improve prognoses. 1,346 patients with LND were further randomly divided into the training and validation sets with the ratio of 1:1. Race, tumor size, clinical T stage, extrahepatic bile duct invasion, and tumor grade were independent risk factors for LNM. The constructed model was well calibrated and showed good discrimination power and net benefits in clinical practice.ConclusionLNM is an independent prognostic factor in HCC, but routine LND seems to be unnecessary in HCC patients. The constructed model could predict the presence of LNM in HCC patients with good performance, which is meaningful to patient stratification and individual treatment strategies optimization.

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Morbidity, Prognostic Factors, and Competing Risk Nomogram for Combined Hepatocellular-Cholangiocarcinoma

Cited by 4 publications

References 64 publications

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Epidemiological and Clinical Characteristics of Five Rare Pathological Subtypes of Hepatocellular Carcinoma

Promising role of liver transplantation in patients with combined hepatocellular-cholangiocarcinoma: a propensity score matching analysis

Development and Validation of a Novel Model to Predict Regional Lymph Node Metastasis in Patients With Hepatocellular Carcinoma

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