Histopathology of hepatocellular carcinoma - when and what

When do you need to take biopsies of the liver, and what information will you get is the topic of this review on hepatocellular carcinoma (HCC). If, clinically, the differential diagnosis of HCC after imaging is suggested, a biopsy has become obligatory as a diagnostic confirmation of HCC in the non-cirrhotic liver prior to definitive therapeutic interventions, as well as in a palliative therapy concept. In the case of hepatic lesions with an uncharacteristic contrast uptake, a biopsy should be performed immediately to confirm the diagnosis of HCC. After diagnosing HCC, a treatment strategy is evaluated. Further, the biopsy, or in case of surgical treatment, the resected tissue, shows us the different subtypes of HCC, with the steatohepatitic subtype being the most common and the lymphocyte-rich subtype being the least common. Further, the histological grade of HCC is determined according to the grading system of the WHO or the Edmonson and Steiner System. Through biopsies, HCC can be differentiated from intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma or metastases of other malignant tumors, especially metastases of the gastrointestinal tract. In summary, biopsies are fundamental in the diagnosis of HCC.

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

Background. Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. Methods. The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell’s C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models. Results. The overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% ( P > 0.05 ). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria ( P = 0.022 and P = 0.015 ). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria ( P = 0.340 ). Conclusion. The morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.

Development and Validation of Nomogram to Predict Very Early Recurrence of Combined Hepatocellular-Cholangiocarcinoma After Hepatic Resection: A Multi-Institutional Study

Background and Objectives Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER)(ie, recurrence within 6 months after surgery) of cHCC. Methods 131 consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multivariable logistic regression analysis. The model was internally and externally validated in an validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis and decision curve analysis (DCA). Results The VER nomogram contains microvascular invasion(MiVI), macrovascular invasion(MaVI) and CA19-9>25mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95%CI: 0.69 - 0.85 ) and 0.76 (95%CI:0.66 - 0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model are clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. Conclusions Our model demonstrated favorable performance in predicting VER in cHCC patients.

O-L05 Do Subsets of Patients with Intrahepatic Cholangiocarcinoma and Combined Hepatocellular-Cholangiocarcinoma Benefit from Transplantation? A Systematic Review, Proportional Meta-Analysis and Meta-Regression

Background Resection remains the main curative treatment option for intrahepatic cholangiocarcinoma (iCCA) and combined hepatocellular-cholangiocarcinoma (cHCC-CCA), however, outcomes are poor. Recent retrospective analyses of patients found to have incidental iCCA and cHCC-CCA following transplantation have suggested that transplantation may be superior to resection. We performed a systematic review and proportional meta-analysis to estimate the benefit of transplantation for iCCA and cHCC-CCA. Methods MEDLINE, EMBASE, Scopus, and Web of Science were searched from January 1990 to December 2020. All studies reporting patients with iCCA and cHCC-CCA undergoing transplantation were identified. A proportional meta-analysis was performed, pooling overall survival (OS), disease-free survival (DFS), and recurrence rates post-transplantation. Sub-group analyses were performed for patients with ‘early’ iCCA, ‘advanced’ iCCA, Goodman type I cHCC-CCA, and Goodman type II cHCC-CCA. Univariable meta-regression was completed assessing the impact of variables reported by at least five studies on OS and DFS at 5-years, as well as recurrence post-transplant. Results Twenty-eight studies including 489 patients were identified (249 with iCCA and 240 with cHCC-CCA). Pooled OS and DFS at 5-years were lower in the iCCA group, 30.2% (95% CI 18.6% – 43.1%) and 29.2% (95% CI 20.4% – 38.9%), compared to the cHCC-CCA group, 55.0% (95% CI 47.2% – 62.8%) and 43.2% (95% CI 30.2% – 56.7%). In the ‘early’ iCCA group, pooled OS at 5-years was 66.5% (95% CI 47.2% – 83.3%). When separated by Goodman type, those with type II tumours reported higher pooled OS, 69.7% (95% CI 57.8% – 80.5%), compared to type I tumours, 61.3% (95% CI 46.1 – 75.5). Univariable meta-regression found only microvascular invasion impacted overall survival at 5-years and recurrence following transplantation in the iCCA group. At 5-years there was a negative correlation between the proportion of patients found to have microvascular invasion and overall survival (Adjusted R2 = 0.89, p = 0.017). There was a positive correlation between the proportion of patients with microvascular invasion on explant pathology and recurrence following transplantation (Adjusted R2 = 0.76, p = 0.047). Conclusions Subsets of patients with iCCA and cHCC-CCA may benefit from liver transplantation. However, further research, including clinical trials exploring transplantation in 'early' disease and in comparison to resection, is required to conclude which subsets of patients will benefit most from transplantation.