Initial Diagnosis Of Hepatocellular Carcinoma Research Articles

Abstract 7364: Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion

Abstract Introduction: Microvascular invasion (MVI) is a well-known prognostic factor in predicting cancer relapse after curative resection of resectable hepatocellular carcinoma (HCC).Therefore, there is a clear unmet need for a precision strategy based on cancer-specific multi-omics features to predict the MVI feature at the initial diagnosis of HCC. Methods: Using gene expression profiling for resected human HCC (Discovery cohort, n=240), we identified the transcriptomic signature predicting the MVI feature. Comprehensive analyses were performed using the dataset from the cancer dependency map (DepMap) project, including cancer-specific molecular characterization with multi-omics data, and drug sensitivity with compound screening, and integrative in-silico prediction methods to uncover MVI. The transcriptomic signature predicting the MVI feature were validated in independent translational cohorts (TCGA-LIHC; n=373, KOREA; n=188, TOKYO; n=183, MODENA; n=78, ZHONGSHAN; n=159). Results: The MVI signature with 1028 genes was identified from robust statistical testing from the discovery cohort, and robust validation for the prediction performance of the MVI signature showed significant accuracy in the validation cohort (AUC=0.865, p<0.01). Multi-omics analysis revealed aggressive tumor biology associated with the MVI signature and specified biomarkers. Conclusions: Integrative multi-omics profiling for resectable HCC uncovers biomarkers to predict MVI. A novel combination of biomarkers performs in sorting out the tumor with aggressive tumor biology. A precision strategy to discover resectable tumors beneficial from surgical resection can be established from consecutive clinical trials based on this translational study. Citation Format: Incheon Kang, Woo Young Kwon, Sung Hwan Lee. Comprehensive multi-omics analysis for resectable hepatocellular carcinoma uncovers biomarkers to predict microvascular invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7364.

Atezolizumab-associated myositis in a patient with unresectable hepatocellular carcinoma.

Combination treatment with atezolizumab and bevacizumab is the preferred first-line treatment for patients with unresectable or metastatic hepatocellular carcinoma with a Child-Pugh Class A liver function. Reactivation of the antitumor immune response with atezolizumab can result in the development of immune-related adverse events including colitis, skin rash, endocrinopathies, pneumonitis, and nephritis with renal dysfunction. However, the occurrence of myositis with immune checkpoint inhibitors is rare. We report on a 67-year-old male patient with an initial diagnosis of hepatocellular carcinoma, stage IV, unresectable with underlying cirrhosis who experienced atezolizumab-associated myositis. Utilization of the American Society of Clinical Oncology guideline on managing immune checkpoint inhibitors adverse events helped guide the ordering of pertinent labs for monitoring and pharmacologic treatment. In our case, atezolizumab-induced myositis was resolved via a combination of corticosteroids, intravenous immunoglobulins, and plasmapheresis. Recognition of the signs and symptoms of atezolizumab-associated myositis is recommended and utilization of the American Society of Clinical Oncology guideline to guide management and treatment of associated symptoms.

Conversion therapy for advanced hepatocellular carcinoma with vascular invasion: a comprehensive review.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and has a high mortality rate worldwide. The percentage of HCC patients with vascular invasion at the time of initial HCC diagnosis is 10%-40%. According to most guidelines, HCC with vascular invasion is classified as advanced stage, and resection is only suggested for a minority of such patients. Recently, advances in systemic and locoregional treatments for such patients have resulted in amazing response rates. Therefore, a "conversion therapy" strategy including systemic and locoregional treatments is proposed to select patients from an initially unresectable state to eventually undergo R0 resection. Recently, many studies have proven that conversion therapy followed by subsequent surgery is achievable in well-selected advanced HCC patients and can provide prolonged long-term outcomes. Based on published research, this review has summarized the clinical experience and evidence of conversion treatment in HCC patients with vascular invasion.

Mortality Evaluation and Life Expectancy Prediction of Patients with Hepatocellular Carcinoma with Data Mining.

The complexity of systemic variables and comorbidities makes it difficult to determine the best treatment for patients with hepatocellular carcinoma (HCC). It is impossible to perform a multidimensional evaluation of every patient, but the development of guidelines based on analyses of said complexities would be the next best option. Whereas conventional statistics are often inadequate for developing multivariate predictive models, data mining has proven more capable. Patients, methods and findings: Clinical profiles and treatment responses of 537 patients diagnosed with Barcelona Clinic Liver Cancer stages B and C from 2009 to 2019 were retrospectively analyzed using 4 decision tree algorithms. A combination of 19 treatments, 7 biomarkers, and 4 states of hepatitis was tested to determine which combinations would result in survival times greater than a year in duration. Just 2 of the algorithms produced complete models through single trees, which made them only the ones suitable for clinical judgement. A combination of alpha fetoprotein ≤210.5 mcg/L, glutamic oxaloacetic transaminase ≤1.13 µkat/L, and total bilirubin ≤ 0.0283 mmol/L was shown to be a good predictor of survival >1 year, and the most effective treatments for such patients were radio-frequency ablation (RFA) and transarterial chemoembolization (TACE) with radiation therapy (RT). In patients without this combination, the best treatments were RFA, TACE with RT and targeted drug therapy, and TACE with targeted drug therapy and immunotherapy. The main limitation of this study was its small sample. With a small sample size, we may have developed a less reliable model system, failing to produce any clinically important results or outcomes. Data mining can produce models to help clinicians predict survival time at the time of initial HCC diagnosis and then choose the most suitable treatment.

Salvage Ablative Radiation Therapy for Isolated Intraabdominal Recurrences of Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> The standard of care for extrahepatic hepatocellular carcinoma (HCC) is a systemic therapy. However, some patients present with limited intra-abdominal disease that might benefit from local ablative radiation therapy (RT) with, or instead of, systemic therapy. This study explores outcomes of ablative RT for isolated intra-abdominal recurrences from HCC. <h3>Materials/Methods</h3> A single-institution retrospective chart review was conducted from 2013 to 2021. Inclusion criteria were any patient with HCC that had limited disease in an abdominal lymph node (LN) or adrenal gland (AG) treated with salvage ablative RT. The primary outcome was local control (LC) in the target lesion. Secondary outcomes were progression-free survival (PFS) and overall survival (OS) from the time of recurrence after completing RT. <h3>Results</h3> 31 patients met inclusion criteria, of which 21 (67.7%) had a recurrence in a LN while 10 (32.2%) had recurrences in an AG. 19 (90%) of LN recurrences were in the portal region. The median time from initial HCC diagnosis to extrahepatic recurrence was 18 months (range 0 to 152 months). Among all patients, 21 patients received immunotherapy (prior, concurrent, or after) in addition to salvage RT. 27 (87.1%) patients received salvage SBRT, and 4 (12.9%) patients received fractionated RT. The median dose was 4500 in 5 fractions. LC, as defined as no progression in target lesion, was 100%. The median PFS, defined by recurrence or death, was 18 months. The median OS was 29 months. There was a statistical difference in OS in patients that received IO and RT vs. RT alone (p=0.038) in favor of RT alone. There was no significant difference in OS for a LN recurrence versus salvage RT for an AG recurrence (p=0.389). <h3>Conclusion</h3> Salvage ablative RT, with or without immunotherapy, can produce meaningful PFS and OS in well-selected patients with limited intra-abdominal extrahepatic recurrence of HCC. This benefit appears the same for LN recurrences and AG metastases and might be independent of immunotherapy. Prospective data are needed to verify these results.

S3186 The Imaging Negative Hepatic Lesions: A Rare Case of Infiltrative Hepatocellular Carcinoma

Introduction: Hepatocellular Carcinoma (HCC) is the 6th most common cancer and the 4th leading cause of cancer-related death worldwide. The infiltrative subtype is the most difficult to diagnose with imaging because of its inherently ill-defined micronodules involving a segment or entire hepatic parenchyma without a distinguishable mass. Prognosis is poor and estimated at a 5-year survival rate of < 20%. Diagnosis of HCC requires a sensitive imaging test. In situations where imaging is not able to identify a mass, EUS-FNA has been shown to have a higher detection rate. Case Description/Methods: A 61-year-old female with a past medical history of HCV cirrhosis with sustained virology response (SVR), presented with abdominal pain and worsening lower extremity edema. Remarkable examination findings include a distended abdomen and bilateral pitting lower extremity edema. Significant work up showed platelet of 109k/cmm (150-440), AST of 159 unit/l (15-37), total bilirubin of 1.2mg/dl (0.2-1.0), AFP of >20,000ng/ml (0.5-8.0), peritoneal fluid cytology was negative. A right upper quadrant ultrasound, CT, and MRI showed no hepatic mass, Fig CD. With markedly elevated AFP and a high suspicion for HCC, the patient had EGD-EUS guided fine-needle aspiration showing multiple infiltrative hepatic lesions, Fig E. The biopsy report showed malignant cells positive for AFP with cells reactive for glypican-3 and negative for Hep-Par1 (Fig A), supporting the diagnosis of HCC. The patient was referred to oncology and a month later, she died. Discussion: SVR is associated with decreased risk of HCC, however, with a cirrhotic liver, patients still have an absolute risk of developing HCC. Initial diagnosis of HCC can be obtained non-invasively using abdominal ultrasound, CT, MRI, and EUS-FNA. Abdominal ultrasound is the best imaging modality recommended for HCC surveillance because it is readily available. However, its sensitivity for detecting early HCC is about 47%. AFP cut-off level of > 20ng/ml has a sensitivity of about 60% with low specificity. A level of > 400ng/ml is diagnostic for HCC with a specificity of almost 100%. Incremental changes in AFP are associated with an increased mortality rate. The median survival rate of infiltrative HCC with AFP of > 400 is estimated to be about 5 months. EUS is superior to CT in detecting small hepatic lesions, with a sensitivity of 100% compared to 71% of CT. We recommend that EUS be considered an integral modality while investigating the diagnosis of infiltrative HCC.Figure 1.: Fig A showing Hepatocellular carcinoma, 200x. Glypican-3 immunostain shows strong, diffuse staining in HCC (A). Background non-neoplastic liver is negative (B). Fig C is the cirrhotic liver with no identifiable mass. Fig D shows fluid around the liver and spleen. Fig E is the EUS showing multiple infiltrative hepatic lesions.

Integrative multi-omics profiling for resectable hepatocellular carcinoma uncovers clinically available serum biomarkers to predict microvascular invasion

Microvascular invasion (MVI) is a well-known prognostic factor to predict cancer relapse after curative resection of resectable hepatocellular carcinoma (HCC). It is mandatory to uncover clinically available serum biomarkers to predict the MVI feature at the initial diagnosis of HCC. Using gene expression profiling for resected human HCC (Discovery cohort, n = 240), we identified transcriptomic signature predicting the MVI feature. Repeated validation for the MVI signature performed using the Bayesian covariate compound predictor method at the multiple independent cohorts (Six Validation cohorts, n = 1,263). Serum biomarker dataset from the patients of TCGA-LIHC samples correlated with the MVI signature. The MVI signature with 1028 genes was identified from robust statistical testing from the discovery cohort, and robust validation for the prediction performance of the MVI signature showed significant accuracy in the validation cohort (AUC = 0.865, p < 0.01). Multi-omics analysis revealed aggressive tumor biology associated with the MVI signature regarding FOXM1, CD24, and MYC downstream pathways. A diagnostic panel from integrating significant serum biomarkers to predict MVI was identified from stepwise regression (p < 0.001). Comprehensive analysis of drug-sensitivity for the MVI signature was performed by integrative in-silico prediction methods using the dataset from Cancer Dependency Map project. Integrative multi-omics profiling for resectable HCC uncovers clinically available serum biomarkers to predict MVI without a surgical specimen. A novel combination of serum biomarkers shows high performance in sorting out the tumor with aggressive tumor biology. Precision strategy to discover resectable tumors beneficial from surgical resection can be established from consecutive clinical trials based on this translational study.

Hepatic vein tumor thrombosis in patients with hepatocellular carcinoma: Prevalence and clinical significance.

BackgroundThere is strong evidence that portal vein tumor thrombosis (PVTT) is associated with poor survival in patients with hepatocellular carcinoma (HCC). However, data regarding the clinical significance of hepatic vein tumor thrombosis (HVTT) is rare, particularly in Western patients.ObjectiveTo determine the HVTT prevalence in a Western patient population and its impact on survival.MethodsWe included 1310 patients with HCC treated in our tertiary referral center between January 2005 and December 2016. HVTT and PVTT were diagnosed with contrast‐enhanced cross‐sectional imaging. Overall survival (OS) was calculated starting from the initial HCC diagnosis, and in a second step, starting from the first appearance of vascular invasion.ResultsWe observed macrovascular invasion (MVI) in 519 patients who suffered from either isolated HVTT (n = 40), isolated PVTT (n = 352), or both combined (HVTT + PVTT) (n = 127). Calculated from the initial HCC diagnosis, the median OS for patients with isolated HVTT was significantly shorter than that of patients without MVI (13.3 vs. 32.5 months, p < 0.001). Calculated from the first appearance of MVI, the median OS was similar among patients with isolated HVTT (6.5 months), isolated PVTT (5 months), and HVTT + PVTT (5 months). Multivariate analysis confirmed HVTT as an independent risk factor for poor survival.ConclusionsHVTT may be more common than typically reported. In most patients, it was accompanied by PVTT. Isolated HVTT occurred less frequently and later than isolated PVTT; however, once developed, it had the same deleterious impact on survival. Therefore, patients with HVTT should be classified as advanced stage of HCC.

Characteristics and Prognosis of De Novo Hepatocellular Carcinoma After Sustained Virologic Response.

Hepatocellular carcinoma (HCC) can de novo develop in patients with chronic hepatitis C even after the achievement of sustained virologic response (SVR). We characterized de novo HCC after SVR, comparing it with HCC that developed in patients during persistent hepatitis C virus (HCV) infection. Characteristics, survival rates, and recurrence rates after curative treatment in 178 patients who developed initial HCC after SVR diagnosed between 2014 and 2020 were compared with those of 127 patients with initial HCC that developed during persistent HCV infection diagnosed between 2011 and 2015; HCC was detected under surveillance in both groups. HCC was less advanced and liver function worsened less in patients with SVR than in patients with persistent HCV. The survival rate after diagnosis was significantly higher for patients with SVR than for patients with persistent HCV (1‐, 3‐, and 5‐year survival rates, 98.2%, 92.5%, and 86.8% versus 89.5%, 74.7%, and 60.8%, respectively; P < 0.001). By contrast, the recurrence rate after curative treatment was similar between groups (1‐, 3‐, and 5‐year recurrence rates, 11.6%, 54.6%, and 60.4% versus 24.0%, 46.7%, and 50.4%, respectively; P = 0.7484). Liver function improved between initial HCC diagnosis and recurrence in patients with SVR (P = 0.0191), whereas it worsened in the control group (P < 0.001). In addition, patients with SVR could receive curative treatment for recurrence more frequently than patients with persistent HCV (80.4% versus 47.8%, respectively; P = 0.0008). Conclusion: Survival of patients with de novo HCC after SVR was significantly higher than that of patients in whom HCC developed during persistent HCV infection, despite similar rates of recurrence after curative treatment. A higher prevalence of curative treatment for recurrent HCC and improved liver function contributed to this result.

Surgical resection of early stage hepatocellular carcinoma: balancing tumor biology with the host liver.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. In early stage HCC, current practice guidelines recommend surgical resection with 5-year overall survival (OS) rates approaching 60%. Due to heterogeneity of the patient population and underutilization of HCC screening, in the past only 10-37% of patients were eligible for surgical resection at the time of initial HCC diagnosis. With recent implementation of HCC screening programs resulting in earlier diagnosis, the number of patients that might be candidates for curative surgical resection has increased. Factors determining outcome following HCC diagnosis are complex and heterogenous in nature and treatment decisions should be based on both tumor- and patient-related factors. Tumor characteristics including tumor size, macrovascular invasion (MVI), and multifocality must be balanced against measures of liver dysfunction including portal hypertension, liver function, and future liver remnant (FLR) to assess the applicability of hepatic resection in patients newly diagnosed with HCC. The aim of this article is to review the indications for curative HCC surgical resection as it pertains to underlying tumor- and patient-related factors. We also discuss adjunctive therapies that may allow for an increased role for hepatic resection in HCC patients with early stage disease who are ineligible for upfront resection due to small liver remnant size.

Clinical significance of radiotherapy before and/or during nivolumab treatment in hepatocellular carcinoma.

BackgroundThis study aimed to investigate the clinical significance of previous and/or concurrent application of radiotherapy (RT) in the course of nivolumab treatment for advanced hepatocellular carcinoma (HCC).MethodsPatients with advanced HCC who received nivolumab treatment between March 2017 and May 2018. were included. Nivolumab treatment was indicated in patients who did not respond to conventional therapy including locoregional therapy and/or sorafenib. RT was performed when necessary for curative/palliative purpose.ResultsAmong the 76 HCC patients who received nivolumab, 54 (71.1%) had received RT for HCC before and/or during the treatment. The period from initial HCC diagnosis to nivolumab treatment was significantly longer (P = .007) and the rate of undergoing transarterial chemoembolization (TACE; P = .006) and sorafenib treatment (P = .007) was significantly higher in patients who received previous/concurrent RT than in those who did not. Nivolumab‐related toxicities were generally tolerable regardless of the history of RT. During the follow‐up, 39 (51.3%) patients died and 54 (71.1%) patients experienced disease progression according to the RECIST v1.1. Patients who had received previous/concurrent RT had a significantly longer progression‐free survival (PFS; P = .008) and overall survival (OS; P = .007) than those who did not receive RT; however, this trend was not observed in patients with a history of radiofrequency ablation or TACE (all P > .05).ConclusionPrevious and/or concurrent application of RT in the course of nivolumab treatment was related with longer PFS and OS in advanced HCC patients. Nonetheless, further clinical studies are warranted to confirm our findings.

2955 Nearly One-Half of Patients With Recurrence of Hepatocellular Carcinoma Did Not Receive Any HCC-Directed Surgical Therapies: An Analysis of the 1973-2015 Surveillance Epidemiology and End Results Cancer Database

INTRODUCTION: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality with high rates of recurrence despite treatment. The characteristics and outcomes of HCC recurrence are not well studied. We utilize a national cancer registry to evaluate predictors of overall survival in recurrent HCC. METHODS: Using National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer registry, we retrospectively evaluated U.S. adults with recurrence of HCC from 1973-2015. HCC tumor stage was assessed with the SEER historic staging system (localized, regional, distant) and HCC treatment was assessed using SEER's site-specific surgery variable (no treatment, locoregional therapy, surgical resection, and liver transplantation (LT)). Overall survival was evaluated using Kaplan Meier and Cox proportional hazards models. RESULTS: Among 275 patients with recurrence of HCC (76.7% male, mean age at initial HCC diagnosis 61 ± 11 years, 48.7% non-Hispanic white, 14.9% Hispanic, 7.6% African American, 27.6% Asian/Pacific Islanders), the majority of patients had localized stage at initial HCC diagnosis (76.4%). At time of HCC recurrence, the proportion of patients with distant/advanced stage was 4 times higher than at initial diagnosis (8.7% vs. 2.2%, P &lt; 0.01). At initial HCC diagnosis, 24.6% did not receive any HCC-directed surgical therapies. At the time of recurrence, overall treatment rates were significantly lower, with 46.6% not receiving any HCC-directed surgical therapies and only 28.7% receiving surgical resection or LT. Median survival was 98 months (95% CI 85-118) after initial HCC diagnosis and 36 months (95% CI 31-48) after HCC recurrence. Significantly higher risk of death was associated with increasing age at time of HCC diagnosis (HR 1.02, 95% CI 1.01–1.04, P &lt; 0.01) and distant stage at diagnosis of recurrence compared to localized stage (HR 2.11, 95% CI 1.26-3.53, P &lt; 0.01). There was a trend towards lower risk of death in Asians compared to non-Hispanic whites (HR 0.67, 95% CI 0.44-1.03, P = 0.07). Receipt of any HCC-directed surgical therapy either for the initial HCC or HCC recurrence was associated with significantly lower risk of death. CONCLUSION: Among U.S. adults who developed recurrence of HCC, nearly half did not receive any HCC-directed surgical therapy at time of HCC recurrence. Older age and more advanced tumor stage at recurrence were associated with significantly higher risk of death despite HCC treatment.

1007 Sex-Specific and Ethnicity-Specific Disparities in Receipt of Hepatocellular Carcinoma (HCC) Treatment Among a Cohort of Patients Who Developed HCC Recurrence

INTRODUCTION: Despite receiving cancer-directed therapies, there is a high rate of cancer recurrence among patients with hepatocellular carcinoma (HCC). Our study aims to focus on the subset of patients with HCC recurrence to evaluate sex- and ethnicity-specific disparities in receipt of treatment. METHODS: Adults with HCC who developed HCC recurrence were identified using 1973-2015 U.S. National Cancer Institute’s Surveillance, Epidemiology, and End Results cancer registry. HCC tumor stage was assessed with the SEER historic staging system (localized, regional, distant) and HCC treatment received was assessed with SEER’s site-specific surgery variable (no treatment, locoregional therapy, surgical resection, and liver transplantation (LT)). Comparisons of tumor stage at diagnosis and receipt of HCC treatment between groups were assessed using chi-square testing and multivariate logistic regression models. RESULTS: Among 275 patients with recurrence of HCC (76.7% male, 48.7% non-Hispanic Whites, 14.9% Hispanic, 27.6% Asian/Pacific Islanders), 24.6% did not receive any HCC-directed surgical treatment, 21.9% received locoregional therapies, 42.3% surgical resection, and 11.2% LT. Compared to women, men were significantly less likely to receive any HCC treatment after initial diagnosis of HCC (OR 0.33, 95% CI 0.14-0.76, P = 0.01), including surgical resection or LT (OR 0.53, 95% CI 0.29-0.96, P = 0.037). Compared to non-Hispanic Whites, significantly lower rates of any HCC treatment were observed in Hispanics (OR 0.40, 95% CI 0.19-0.84, P = 0.015) and higher rates of treatment were seen in Asian/Pacific Islanders (OR 2.28, 95% CI 1.02-5.12, P = 0.045). On multivariate analysis, there were significantly lower odds of receiving any therapy for the initial HCC diagnosis in men vs. women (OR 0.27, 95% CI 0.11-0.68, P &lt; 0.01) and in Hispanics vs. non-Hispanic Whites (OR 0.32, 95% CI 0.15-0.72, P &lt; 0.01). Asian/Pacific Islanders were more likely to receive treatment compared to non-Hispanic Whites (OR 2.72, 95% CI 1.15-6.44, P = 0.023). There were no significant differences in receipt of treatment for the HCC recurrence based on sex or ethnicity. CONCLUSION: Among U.S. adults with HCC who developed HCC recurrence, nearly one quarter did not receive any HCC-directed surgical therapies at initial diagnosis. Men and Hispanics were significantly less likely to receive any HCC-directed therapies for the initial HCC diagnosis.

Advanced Hepatocellular Carcinoma with Bone Metastases: Prevalence, Associated Factors, and Survival Estimation.

BackgroundThe objective of the present research was to explore the prevalence, risk, and prognostic factors associated with bone metastases (BM) in newly diagnosed hepatocellular carcinoma (HCC) patients.Material/MethodsFrom 36 507 HCC patients who were registered in Surveillance, Epidemiology, and End Results (SEER) database, we enrolled 1263 with BM at the initial diagnosis of HCC from 2010 to 2014. Kaplan-Meier curves and log-rank tests were used to estimate overall survival for different subgroups. Univariate and multivariate logistic and Cox regression analyses were performed to identify risk factors and independent prognostic factors for BM.ResultsA total of 1567 (4.29%) HCC patients were detected with BM at initial diagnosis. Male sex, unmarried status, higher T stage, lymph node involvement, intrahepatic metastases, and extrahepatic metastases (lung or brain) were positively associated with BM. The median survival of the patients was 3.00 months (95% CI: 2.77–3.24 months). Marital status and primary tumor surgery were independently associated with the better survival.ConclusionsA list of factors associated with BM occurrence and the prognosis of the advanced HCC patients with BM were found. These associated factors may provide a reference for BM screening in HCC and guide prophylactic treatment in clinical settings.

COMPARISON OF IMAGE FINDINGS WITH HISTOPATHOLOGICAL DIAGNOSIS ON ULTRASOUND GUIDED PERCUTANEOUS LIVER BIOPSY IN RELATION TO HEPATOCELLULAR CARCINOMA

ABSTRACTOBJECTIVES: To compare the image findings with histopathological diagnosis on ultrasound guided (USG) percutaneous biopsies of liver lesions in relation to hepatocellular carcinoma (HCC) and to assess the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in evolution of HCC.METHODS: This descriptive cross-sectional study included biopsies performed on patients reporting to Kuwait Teaching Hospital, Peshawar, Pakistan from 01-07-2017 to 30-09-2017. The patient selection was based on findings on various image modalities like triphasic liver computed tomography (CT) or dynamic magnetic resonance imaging (MRI), in which percutaneous liver biopsy was indicated. The biopsies were routinely processed for histological examination on hematoxyllin and eosin stain and application of immunohistochemical stains for detecting HCC.RESULTS: A total number of 82 USG percutaneous biopsies were performed on various sites out of which 41 (50%) were performed on liver lesions. On imaging 12 (30%) were diagnosed as hepatocellular carcinoma whereas 16 (39%) cases were confirmed on histopathology, which either showed Hep-Par-1 or arginase positivity. On imaging 11/16 (68.75%) were either diagnosed as HCC or were suspicious of it. A sensitivity of 75% and specificity of 95% was calculated for diagnosis of HCC on imaging. The correlation between image and biopsy diagnosis of HCC was statistically significant (p value 0.05).CONCLUSION: The present study concludes that Image findings are helpful in the initial diagnosis of HCC which shows an increasing trend to be associated HCV as compared to HBV with a remarkably declining trend.KEY WORDS: Image-Guided Biopsy (MeSH); Ultrasonography (MeSH); Liver (MeSH); Carcinoma, Hepatocellular (MeSH); Hepacivirus (MeSH); Hepatitis B virus (MeSH); Immunohistochemistry (MeSH); Histology (MeSH).

Tailored treatment of patients with hepatocellular carcinoma with portal vein invasion: experience from a multidisciplinary hepatobiliary tumor program within a NCI comprehensive cancer center.

Hepatocellular carcinoma (HCC) with portal vein invasion (PVI) has a poor prognosis with limited treatment options. Intra-arterial brachytherapy (IAB) and transarterial chemoembolization (TACE) yield local control but risk accelerating liver dysfunction. The outcomes, survival, and safety of selective liver-directed treatment are reported. Thirty-seven consecutive patients with HCC and PVI treated between 2009 and 2015 were reviewed from a prospectively collected database. Univariate analysis, Kaplan-Meier plots using the log-rank method, and multivariate analyses were performed. Statistical significance was defined as P<0.05. Overall survival was reported in months (median; 95% CI). Most patients (59%) had PVI identified at initial HCC diagnosis. The liver-directed therapy group (n=22) demonstrated a survival advantage versus the systemic/supportive care group (n=14) [23.6 (5.8, 30.9) vs. 6.0 (3.5, 8.8) months]. Patients indicated for liver directed therapy had unilateral liver involvement (100% vs. 43%, P<0.0001), lower median alkaline phosphatase (105.5 vs. 208.0, P=0.002), and lower mean Child-Turcotte-Pugh (CTP) score (5.9 vs. 7.2, P=0.04) and tolerated treatment without serious complications. In HCC patients presenting with PVI, liver-directed therapy was safely performed in patients with limited venous involvement and preserved liver function. Liver-directed therapy extended survival for these patients indicated for palliative chemotherapy by traditional guidelines.

Combined hepatocarcinoma-cholangiocarcinoma in patients treated as hepatocarcinoma

Introduction: Mixed Hepatocarcinoma-cholangiocarcinoma is a rare tumor with difficult diagnosis, sharing genetic, molecular, clinical, analytical and even radiological similarities. Since immunohistochemistry is necessary for its definitive diagnosis and the worst prognosis, it poses a challenge for diagnosis and an early treatment. We analyze the results of this tumors among transplanted and resected patients from January 2011 to August 2017, evaluating clinical, radiological, and analytical aspects, as well as the role of Immunohistochemistry in the pathological diagnosis. Methods: We made a retrospective analysis of resected and liver transplanted since January 2011, through a review of the pathological results database. The 3 selected cases were evaluated by optical microscopy by two pathologists and the images of arteriography with chemoembilization by a radiologist. Results: The 3 patients were male, with a mean age of 62 years, a history of alcoholism, carriers of HIV, HBV and / or HCV. With the initial diagnosis of hepatocellular carcinoma on the cirrhotic liver, transarterial chemoembolization was performed for "downstage” during the waiting list trying to meet the Milan Criteria for the Liver Transplant. Two of them were transplanted and one was resected laparoscopically. Regarding the pathological examination, immunihistochemistry revealed a definitive diagnosis of Classical Combined Hepato-Cholangiocarcinoma according to the WHO classification. Everyone is free of disease at the present time. Conclusions: Hepato-Cholangiocarcinoma is an infrequent tumor, diagnosed exclusively by its immunohistochemical pattern. Despite the diversity of published results, resection and liver transplantation are the curative alternatives that can be proposed in these cases.

Calcium channel α2δ1 subunit as a novel biomarker for diagnosis of hepatocellular carcinoma.

Objective:Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. The identification of new simple, inexpensive and highly accurate markers for HCC diagnosis and screening is needed. This case-control study evaluates the role of annexin A2 and voltage-gated calcium channels α2δ1 subunit as serum biomarkers for HCC diagnosis.Methods:The study comprised three groups: group 1, 50 patients with an initial diagnosis of HCC associated with chronic hepatitis C virus infection; group 2, 25 patients diagnosed with chronic hepatitis C virus infection and cirrhosis without any evidence of HCC; and group 3, 15 healthy controls. All participants were subjected to clinical and laboratory investigations, and radiological scanning. The serum levels of alpha-fetoprotein (AFP), annexin A2, and the α2δ1 subunit were evaluated by using ELISA technique.Results:The serum levels of annexin A2 significantly increased in patients with HCC (10.4±2.5 ng/mL; P<0.001) or with cirrhosis (9.31±1.8 ng/mL;P<0.001) comparing to that of healthy controls (0.296±0.09 ng/mL). However, there was no significant difference in serum annexin A2 levels in patients with HCC comparing to those with cirrhosis. Serum α2δ1 subunit significantly increased in patients with HCC (20.12±3.7 ng/mL) comparing to that in patients with cirrhosis (10.41±3.4 ng/mL,P<0.001) and healthy controls (10.2±2.9 ng/mL,P<0.001). Conclusions:The serum α2δ1 subunit may function as a new biomarker for HCC diagnosis. Conversely, serum annexin A2 has low diagnostic value as an HCC marker, especially in patients with underlying cirrhosis.

Wait Time of Less Than 6 and Greater Than 18 Months Predicts Hepatocellular Carcinoma Recurrence After Liver Transplantation

It has been postulated that short wait time before liver transplant (LT) for hepatocellular carcinoma (HCC) results in the inclusion of tumors with aggressive biology, but prolonged wait time could result in a shift to more aggressive tumor behavior. We therefore test the hypothesis that a wait time "sweet spot" exists with a lower risk for HCC recurrence compared with the other 2 extremes. This multicenter study included 911 patients from 3 LT centers with short, medium, and long wait times (median of 4, 7, and 13 months, respectively) who received Model for End Stage Liver Disease exception listing for HCC from 2002 to 2012. Wait time, defined as time from initial HCC diagnosis to LT, was less than 6 months in 32.4%, 6 to 18 months in 53.7%, and greater than 18 months in 13.9%. Waitlist dropout was observed in 18.4% at a median of 11.3 months. Probability of HCC recurrence at 1 and 5 years were 6.4% and 15.5% with wait time of less than 6 or greater than 18 months (n = 343) versus 4.5% and 9.8% with wait time of 6 to 18 months (n = 397), respectively (P = 0.049). When only pre-LT factors were considered, wait time of less than 6 or greater than 18 months (HR, 1.6; P = 0.043) and AFP greater than 400 at HCC diagnosis (HR, 3.0; P < 0.001) predicted HCC recurrence in multivariable analysis. This large multicenter study provides evidence of an association between very short (<6 months) or very long (>18 months) wait times and an increased risk for HCC recurrence post-LT. The so-called sweet spot of 6 to 18 months should be the target to minimize HCC recurrence.

The Case Files

The Case Files