Cd34 Immunostaining Adds Specificity To Microvascular invasion Analysis in Hepatocellular Carcinoma.

Introduction: Hepatocellular carcinoma is the most common primary neoplasia of the liver. Microvascular invasion predicts outcome and defines tumor staging. However, its diagnosis is still a challenge. The present study aims to evaluate inter and intraobserver agreement in identifying the presence of microvascular invasion using conventional and immunohistochemistry histology. Methods: Three pathologists performed the analysis of 76 hepatocellular carcinoma explants to characterize the presence of microvascular invasion using the hematoxylin/eosin stain and immunohistochemistry for CD34. The evaluations were made individually, in two distinct moments. Results were analyzed by the Kappa's coefficient and ROC curves. Results: Our study demonstrated similar agreement for microvascular invasion between hematoxylin/eosin and CD34 methods. However, the intraobserver agreement values for both methods were higher than the interobserver ones. The accuracy of CD34 in relation to hematoxylin/eosin by ROC curves in intraobserver analysis tends to a high specificity, ranging from 82.1 to almost 100%, with sensitivity of 46.9% to 81.1%. In interobserver analysis, CD34 also has a high specificity (84.3% to 85.5%) while its sensitivity is a little shorter (81.2% to 84.3%). Conclusion: Intraobserver higher agreement allows us to suppose that pathologists employed own criteria to evaluate vascular invasion, reinforcing the need of standardization. ROC Curves analysis showed that the CD34 method is more specific than sensitive. Therefore, immunohistochemistry for CD34 should not be used routinely, but it could be useful to help confirming invasion previously seen by conventional histology.

Impact of Brazilian expanded criteria for liver transplantation in patients with hepatocellular carcinoma: a multicenter study.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the main indications for orthotopic liver transplantation (OLT). In Brazil, selection criteria for HCC is an expanded version of the Milan Criteria (MC), the so-called "Brazilian Milan Criteria" (BMC). Our aims were to evaluate post-OLT outcomes in patients with HCC and analyze the BMC performance. MATERIALS AND METHODS: We conducted a multicenter, retrospective cohort study, analyzing medical records of 1,059 liver transplant recipients with HCC. Tumor was staged according to MC and BMC and correlated with overall survival (OS) and disease-free survival (DFS). We compared the ability of MC and BMC to predict OS and DFS using Delta C-statistic. RESULTS: Post-OLT OS were 63% in five years and HCC recurrence was observed in 8% of patients. At diagnosis, 85% of patients were within MC. Patients within MC at diagnosis and in the explant showed a higher OS and DFS than patients outside MC and within BMC and patients outside both criteria (p < 0.001). Patients outside MC in the explant had an increased risk of tumor recurrence (HR: 3.78; p < 0.001) and poor survival (HR:1.77; p = 0.003). The BMC presented a lower performance than MC in properly classifying patients regarding recurrence risk. CONCLUSIONS: In a large Brazilian cohort of HCC patients submitted to liver transplantation, we observed satisfactory overall survival and recurrence rates. However, patients transplanted within the Brazilian expanded criteria had lower OS and DFS when compared to patients within MC, which may generate future discussions regarding the criteria currently used.

Recurrence of hepatocellular carcinoma after liver transplantation: Prognostic and predictive factors of survival in a Latin American cohort.

BACKGROUND & AIM: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has a poor prognosis, and the adjusted effect of different treatments on post-recurrence survival (PRS) has not been well defined. This study aims to evaluate prognostic and predictive variables associated with PRS. METHODS: This Latin American multicenter retrospective cohort study included HCC patients who underwent LT between the years 2005-2018. We evaluated the effect of baseline characteristics at time of HCC recurrence diagnosis and PRS (Cox regression analysis). Early recurrences were those occurring within 12 months of LT. To evaluate the adjusted treatment effect for HCC recurrence, a propensity score matching analysis was performed to assess the probability of having received any specific treatment for recurrence. RESULTS: From a total of 1085 transplanted HCC patients, the cumulative incidence of recurrence was 16.6% (CI 13.5-20.3), with median time to recurrence of 13.0 months (IQR 6.0-26.0). Factors independently associated with PRS were early recurrence (47.6%), treatment with sorafenib and surgery/trans-arterial chemoembolization (TACE). Patients who underwent any treatment presented "early recurrences" less frequently, and more extrahepatic metastasis. This unbalanced distribution was included in the propensity score matching, with correct calibration and discrimination (receiving operator curve of 0.81 [CI 0.72;0.88]). After matching, the adjusted effect on PRS for any treatment was HR of 0.2 (0.10;0.33); P < .0001, for sorafenib therapy HR of 0.4 (0.27;0.77); P = .003, and for surgery/TACE HR of 0.4 (0.18;0.78); P = .009. CONCLUSION: Although early recurrence was associated with worse outcome, even in this population, systemic or locoregional treatments were associated with better PRS.

Hepatocellular carcinoma recurrence after liver transplantation in a Brazilian multicenter study: clinical profile and prognostic factors of survival.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for patients with unresectable early hepatocellular carcinoma (HCC). Post-LT HCC recurrence rates range from 8 to 20% and still impact on overall survival (OS). The aim of our study was to evaluate the impact of HCC recurrence on post-LT survival and analyze prognostic factors among those patients with recurrence. PATIENTS AND METHODS: We carried out a national, multicenter, retrospective cohort study in Brazil. Medical records of 1119 LT recipients with HCC were collected. Data from patients with post-LT HCC recurrence were analyzed and correlated with post-relapse survival. RESULTS: OS of the 1119 patients included in the study was 63% over 5 years. Post-LT HCC recurrence occurred in 86 (8%) patients. The mean time to recurrence was 12 months. Sites of recurrence were extrahepatic in 55%, hepatic in 27%, and both hepatic and extrahepatic in 18%. Recurrence treatment was performed in 50 (64%) cases, mostly with sorafenib. Post-relapse survival rates were 34% at 1 year and 13% at 5 years. Univariable analysis identified α-fetoprotein more than 1000 ng/ml at relapse, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years as prognostic factors. In multivariable analysis, recurrence treatment, extrahepatic location, and time to recurrence more than 2 years were independent predictors of better survival. CONCLUSION: In a large Brazilian cohort of LT recipients with HCC, post-LT HCC recurrence occurred in 8% and impacted significantly on the OS. Patients with early recurrence presented a worse prognosis. However, treatment of recurrence improved outcomes, highlighting the importance of early diagnosis.

Excesso de peso em pacientes submetidos ao transplante hepático / Overweight in liver transplant recipients

Esta revisão tem por objetivo descrever a incidência e prevalência de excesso de peso, sobrepeso e obesidade pós-transplante hepático e as consequências associadas a ele. Foi realizada revisão bibliográfica com consulta nas bases Medline/Pubmed, SciELO, EMBASE, LILACS com o cruzamento dos seguintes descritores: transplante hepático; sobrepeso; obesidade; ganho de peso. O excesso de peso é incidente em mais de 60% dos pacientes submetidos ao transplante hepático e as taxas de obesidade ultrapassam 20% já no primeiro ano do pós-operatório, período em que ocorre o maior ganho de peso relativo. Estudos revelaram que entre 60% e 70% dos pacientes submetidos ao transplante de fígado apresentam excesso de peso após o terceiro ano e quase 90% deles com obesidade abdominal. Os fatores associados são os mais variados, dentre os quais se destacam maior idade, história familiar de excesso de peso, excesso de peso anterior à doença hepática, dentre outros. A contribuição da medicação imunossupressora ainda permanece controversa. Dentre as consequências do excesso de peso estão a esteatose hepática, esteatohepatite, diabete melito, hipertensão, dislipidemias, doenças cardiovasculares e morte.

This review aims to describe the incidence and prevalence of overweight and obesity after liver transplantation and the consequences associated with it. Literature review consultation was conducted in Medline / PubMed, SciELO, EMBASE and LILACS, with the combination of the following keywords: liver transplantation, overweight, obesity, weight gain. Overweight is incident on more than 60% of patients undergoing liver transplantation and obesity rates exceed 20% in the first year after surgery, during which occurs the largest relative weight gain. Studies have shown that between 60% and 70% of patients undergoing liver transplantation are overweight after the third year, 90% with abdominal obesity. Associated factors are, among others, advanced age, family history of overweight and excess weight prior to liver disease. The contribution of immunosuppressive medication remains controversial. Some of the consequences of overweight are liver steatosis, steatohepatitis, diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease and death.

Overweight in liver transplant recipients.

This review aims to describe the incidence and prevalence of overweight and obesity after liver transplantation and the consequences associated with it. Literature review consultation was conducted in Medline / PubMed, SciELO, EMBASE and LILACS, with the combination of the following keywords: liver transplantation, overweight, obesity, weight gain. Overweight is incident on more than 60% of patients undergoing liver transplantation and obesity rates exceed 20% in the first year after surgery, during which occurs the largest relative weight gain. Studies have shown that between 60% and 70% of patients undergoing liver transplantation are overweight after the third year, 90% with abdominal obesity. Associated factors are, among others, advanced age, family history of overweight and excess weight prior to liver disease. The contribution of immunosuppressive medication remains controversial. Some of the consequences of overweight are liver steatosis, steatohepatitis, diabetes mellitus, hypertension, dyslipidemia, cardiovascular disease and death.