Combined hepatocellular-cholangiocarcinoma: a population level analysis of incidence and mortality trends.

BACKGROUND: The purpose of this study was to explore trends in incidence, incidence-based (IB) mortality, and survival for combined hepatocellular-cholangiocarcinoma (cHCC-CC) utilizing a population-based database to attract people's attention to this disease. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was utilized to investigate the incidence and IB mortality for cHCC-CC from 2000 to 2014. Trends in age-adjusted incidence and IB mortality were characterized by the Joinpoint Regression program. The Kaplan-Meier method and log-rank test were utilized to implement survival analyses. Cox regression was utilized to estimate independent predictors of mortality. RESULTS: The incidence of cHCC-CC was 0.26 per 1,000,000 individuals in 2000 and 0.59 per 1,000,000 individuals in 2014, with an annual percent change (APC) (i.e., the extent of increase in incidence) of 3.84% (95% confidence interval [CI] 1.7-6.1; P < 0.05). The IB mortality also displayed a sustained increase (APC was 4.59%, 95% CI 1.9-7.4; P < 0.05). Compared to patients not undergoing surgery, patients undergoing surgical treatment experienced a significant increase in median survival (3 vs. 28 months; P < 0.001). However, the median survival decreased in patients with tumor size > 5 cm (20 vs. 9 months; P < 0.001). Based on univariate Cox regression analysis, African-American race, distant stage, regionalized stage, tumor size ≥ 5 cm, and no surgery were risk factors for death. CONCLUSIONS: We identified an overall steady increase in the incidence of cHCC-CC, which indicates that primary prevention strategies for cHCC-CC have not improved much in recent years and that cHCC-CC needs to be taken seriously.

Positive expression of Midkine predicts early recurrence and poor prognosis of initially resectable combined hepatocellular cholangiocarcinoma.

BACKGROUND: Post-surgical prognosis is usually poor for combined hepatocellular cholangiocarcinoma (CHCC-CC), a rare primary liver cancer. Although midkine (MK) is a prognostic biomarker for several known cancers, it is not known whether it can be used as such in resectable CHCC-CC. This study examined whether MK expression can predict recurrence and survival in patients with resectable CHCC-CC. METHODS: We retrospectively enrolled 52 patients with resectable CHCC-CC who had received curative hepatic resections. MK expression was assessed in post-surgical immunohistochemical studies of specimens in paraffin blocks. Clinical outcomes were analyzed from medical records. RESULTS: Two-year disease-free and three-year overall survival rates were 42.1% and 44.6%. MK was expressed in 30 patients. Univariate analysis showed patients positively expressing MK had a significantly poorer 2-year disease free and three-year overall survival. Multivariate analysis found positive MK expression independently predicted recurrence. CONCLUSIONS: Positive expression of MK predicts poor prognosis in patients with resectable CHCC-CC.

Surgical Strategies for Combined Hepatocellular-Cholangiocarcinoma (cHCC-CC).

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a tumor entity presenting features of hepatocellular and cholangiocellular epithelial differentiation. Due to the likeness between cHCC-CC, HCC and CC, accurate pretherapeutical diagnosis is challenging and advanced stages are prevalent. Radical oncological surgery is the only curative therapeutical option in patients with cHCC-CC. To reach this goal a profound understanding of this rare liver tumor is crucial. Factors such as clinicopathological characteristics, growth patterns and biological behavior are of central importance. To explore onco-surgical strategies and aspects for complete resection of cHCC-CC and to answer important key questions, an extensive review of the literature was conducted to answer the following questions: What are the best surgical options? Is there a significance for nonanatomical resections? Is there a prognostic value of concomitant lymphadenectomy? What about multimodal concepts in local advanced cHCC-CC? The role of minimally invasive liver surgery (MILS) including the role of robotic liver surgery for cHCC-CC will be discussed. While liver transplantation (LT) is standard for patients with unresectable HCC, the role of LT in cHCC-CC patients is still controversial. How can patients with high risk for early tumor recurrence be identified to avoid aggressive surgical treatment without clinical benefit? The comprehensive understanding of this challenging liver tumor will help to improve future treatment options for these patients.

Management of Locally Advanced or Metastatic Combined Hepatocellular Cholangiocarcinoma.

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy that comprises features of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Due to the rarity of this tumor, the treatment of choice has not yet been defined. For resectable disease, liver resection is the mainstay treatment. However, most patients relapse or display advanced disease and were not surgical candidates. Although the majority of patients are either primarily or secondarily treated in palliative intent, no guideline recommendations or prospective trial reports exist to allow reliable evaluation of debated treatment options. We review different locoregional or medical treatment options for advanced combined hepatocellular cholangiocarcinoma (cHCC-CC) in the neoadjuvant, adjuvant, or palliative setting and discuss the possibility of predictive biomarker-guided therapeutic options.

Diagnostic Performance of LI-RADS Version 2018 for Primary Liver Cancer in Patients With Liver Cirrhosis on Enhanced MRI.

Purpose: The study evaluated the diagnostic performance of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for differentiating hepatocellular carcinoma (HCC) from primary liver cancer in patients with liver cirrhosis based on the updated 2019 WHO classification. Materials and Methods: From 2016 to 2021, 300 patients with surgically confirmed primary liver cancer (PLC) and liver cirrhosis based on the updated 2019 WHO classification were eligible for this retrospective study (100 cases in each of three groups including HCC, ICC, and cHCC-CCA). Two radiologists were blinded to the final diagnosis and independently assigned an LI-RADS category to each liver nodule. The diagnostic performances of the LR-5 category (definitely HCC), and the LR-M category (probably or definitely malignant, but not specific for HCC) were calculated in overall and small observations (<20 mm). Comparisons between groups of categorical variables were performed by one-way analysis of variance and the Chi-squared or Fisher's exact test. Results: The mean age of 300 patients (226 men and 74 women) was 57.40 ± 11.05 years. The sensitivity and specificity of the LR-5 category for differentiating HCCs from other primary liver cancers were 81% (81 of 100) and 82% (164 of 200), respectively. The LR-M category had a sensitivity of 63% (126 of 200) for diagnosing non-HCCs (ICCs and cHCC-CCAs), with a specificity of 90% (90 of 100). The LR-5 category had a sensitivity of 82.5% (33 of 40) for diagnosing HCCs in small observations (<20 mm) with a specificity of 76.6% (59 of 77). On the contrary, LR-M demonstrated slightly higher specificity (93.8%) and sensitivity (73.8%) for diagnosing non-HCCs with tumor size <20 mm. Conclusion: The LR-5 category as well as the LR-M category of Liver Imaging Reporting and Data System (LI-RADS) version 2018 can effectively distinguish hepatocellular carcinoma from other primary hepatic malignancies in patients with liver cirrhosis, especially for small observations (<20 mm).