Factors associated with survival in dogs with a histopathological diagnosis of hepatocellular carcinoma: 94 cases (2007–2018)

Background: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in dogs. Despite this, relatively few reports of this disease exist pertaining to prognostic factors and outcome. Aim: To evaluate factors associated with survival in dogs with all subtypes of HCC diagnosed on histopathology. Methods: A retrospective single institutional study was carried out on 94 client-owned dogs with a histopathologic diagnosis of HCC between 2007 and 2018 obtained by biopsy (21/94) or attempted definitive resection (73/94). Signalment, preoperative features, surgical findings, and postoperative outcomes were recorded. Associations between survival to discharge data were collected and univariable logistical regression was carried out. Kaplan–Meier survival analysis was carried out to identify negative risk factors for long-term prognosis. Results: The median survival time (MST) for all patients was 707 days (95% CI = 551–842). MST was not significantly different (p > 0.05) between patients who had suspected versus incidentally diagnosed HCC (695 vs. 775 days), between complete versus incomplete surgical margins (668 vs. 834 days), or between patients with massive subtype versus nodular/diffuse subtype (707 vs. 747 days). Logistical regression identified an association with the excision of the right medial lobe and risk of perioperative death (OR = 9.2, CI 1.5–55.9, p = 0.016). An American Society of Anesthesiologists score ≥4, disease present within the quadrate lobe, and elevated blood urea nitrogen, potassium or gamma-glutamyltransferase were identified as negative prognosticators during multivariable Cox regression. Preoperative imaging (ultrasound or CT) agreed with the surgical location in 91% of the cases. Preoperative cytology was consistent with a diagnosis of HCC in 15/32 (46.9%) cases. Conclusion: Type of diagnosis (incidental vs presumed), completeness of excision, and subtype were not associated with MST in this study. Preoperative identification of tumors within the central division may be related to a less favorable outcome. Results of preoperative cytology were not highly sensitive for identifying a malignancy.

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Combination of Tertiary Lymphoid Structure and Neutrophil-to-Lymphocyte Ratio Predicts Survival in Patients With Hepatocellular Carcinoma

Frontiers in Immunology ◽

10.3389/fimmu.2021.788640 ◽

2022 ◽

Vol 12 ◽

Author(s):

Shaodi Wen ◽

Yuzhong Chen ◽

Chupeng Hu ◽

Xiaoyue Du ◽

Jingwei Xia ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systemic Inflammation ◽

Cox Regression ◽

Primary Liver Cancer ◽

Paraffin Section ◽

Neutrophil To Lymphocyte Ratio ◽

Survival Prediction ◽

Cox Regression Analysis ◽

Lymphocyte Ratio ◽

Inflammation Parameters

BackgroundHepatocellular carcinoma (HCC) is the most common pathological type of primary liver cancer. The lack of prognosis indicators is one of the challenges in HCC. In this study, we investigated the combination of tertiary lymphoid structure (TLS) and several systemic inflammation parameters as a prognosis indicator for HCC.Materials and MethodsWe retrospectively recruited 126 postoperative patients with primary HCC. The paraffin section was collected for TLS density assessment. In addition, we collected the systemic inflammation parameters from peripheral blood samples. We evaluated the prognostic values of those parameters on overall survival (OS) using Kaplan-Meier curves, univariate and multivariate Cox regression. Last, we plotted a nomogram to predict the survival of HCC patients.ResultsWe first found TLS density was positively correlated with HCC patients’ survival (HR=0.16, 95% CI: 0.06 − 0.39, p < 0.0001), but the power of TLS density for survival prediction was found to be limited (AUC=0.776, 95% CI:0.772 − 0.806). Thus, we further introduced several systemic inflammation parameters for survival analysis, we found neutrophil-to-lymphocyte ratio (NLR) was positively associated with OS in univariate Cox regression analysis. However, the combination of TLS density and NLR better predicts patient’s survival (AUC=0.800, 95% CI: 0.698-0.902, p < 0.001) compared with using any single indicator alone. Last, we incorporated TLS density, NLR, and other parameters into the nomogram to provide a reproducible approach for survival prediction in HCC clinical practice.ConclusionThe combination of TLS density and NLR was shown to be a good predictor of HCC patient survival. It also provides a novel direction for the evaluation of immunotherapies in HCC.

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Risk of hepatocellular carcinoma and fibrosis evolution in hepatitis C patients with severe fibrosis or cirrhosis treated with direct acting antiviral agents

Acta Gastro Enterologica Belgica ◽

10.51821/84.1.420 ◽

2021 ◽

Vol 84 (1) ◽

pp. 25-32

Author(s):

C Hamoir ◽

Y Horsmans ◽

P Stärkel ◽

G Dahlqvist ◽

S Negrin Dastis ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C ◽

Incidence Rate ◽

Cox Regression ◽

Annual Incidence ◽

Annual Incidence Rate ◽

Factors Associated ◽

Genotype 2 ◽

Direct Acting ◽

Severe Fibrosis

Background and study aims : Cirrhosis associated to chronic hepatitis C virus (HCV) is one of the leading cause of hepatocellular carcinoma (HCC). The goal of our study was to evaluate first the risk and determinants of HCC and second the evolution of fibrosis in patients treated for HCV with advanced fibrosis stages who achieved sustained virological response (SVR) after direct-acting antivirals (DAA) treatment. Patients and methods : We conducted a prospective study on HCV patients with F3 or F4 Metavir fibrosis scores treated with DAA between October 2014 and February 2017. The annual incidence rate for HCC was calculated. We used Cox regression model in order to identify factors associated with HCC. Transient elastography (TE) was performed 12 and 24 months after the end of DAA treatment and non-invasive liver fibrosis biomarkers were performed twice a year during follow-up. Results : 143 patients with severe fibrosis or cirrhosis were enrolled in the study. 6 patients developed HCC. The annual incidence rate of HCC in our cohort was 2.7 per 100 patients. Risk factors associated with HCC after DAA were genotype 2 and steatosis. Overall TE values significantly decreased after DAA treatment with a median value prior to treatment of 16.9 kPa to a median of 10.8 kPa 24 months after the end of the treatment. Biological fibrosis scores also significantly decreased following viral eradication. Conclusions : DAA treatment does not seem to be associated with HCC promotion after HCV eradication in patients with severe fibrosis stages. DAA-induced SVR is associated with a reduced estimation of fibrosis.

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Noninvasive prediction of future macrovascular invasion occurrence in hepatocellular carcinoma based on quantitative imaging analysis: A multi-center study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14623 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14623-e14623

Author(s):

JingWei Wei ◽

Jie Tian ◽

Sirui Fu ◽

Ligong Lu

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Validation Cohort ◽

Quantitative Imaging ◽

Integrated Model ◽

Preoperative Imaging ◽

Rank Test ◽

Imaging Analysis ◽

Occurrence Time ◽

Training Cohort

e14623 Background: To investigate whether preoperative imaging-based analysis could help to predict future macrovascular invasion (MaVI) occurrence in hepatocellular carcinoma (HCC). Methods: A cohort of 224 patients with HCC was enrolled from five independent medical centers (training cohort: n = 154; independent validation cohort: n = 70). Predictive clinical factors were primarily selected by uni- and multi-variable analysis. CT-based imaging analysis was performed based on extraction of 1217 radiomic features. Recursive feature elimination and random forest (RF) were chosen as the optimal radiomics modelling algorithms. A clinical-radiomics integrated model was constructed by RF modelling. Cox-regression analyses further selected risk independent factors. Risk stratification was explored by Kaplan-Meier analysis with log-rank test, regarding to MaVI occurrence time (MOT), progression free survival (PFS) and overall survival (OS). Results: The clinical-radiomics integrated model could successfully predict MaVI occurrence with areas under curve of 0.920 (training cohort, 95% confidence index [CI]: 0.875-0.965) and 0.853 (validation cohort, 95% CI: 0.737-0.970). The radiomics signature added significant improvement to the integrated model in both training and validation cohorts with p-value of 0.009 and 0.008, respectively. Radiomic features: N25_ori_gldzm_IN (hazard ratio [HR]: 0.44; p = 0.001) and N25_Coif1_ngldm_DE (HR: 0.60; p = 0.016) were selected as independent risk factors associated with MaVI occurrence time. The cox-regression model could stratified patients into high-risk and low-risk groups in MOT (p < 0.001), PFS (p = 0.003), and OS (p = 0.007). Conclusions: The noninvasive quantitative imaging analysis could enable preoperative prediction of future MaVI occurrence in HCC with prognosis implication.

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Population-Based analysis for newly diagnosed hepatocellular carcinoma with brain metastases

10.21203/rs.2.17900/v1 ◽

2019 ◽

Author(s):

Jincheng Feng ◽

Georgios Polychronidis ◽

Ulrike Heger ◽

Arianeb Mehrabi ◽

Katrin Hoffmann

Keyword(s):

Hepatocellular Carcinoma ◽

Bone Metastasis ◽

Brain Metastases ◽

Cox Regression ◽

Population Based ◽

Rank Test ◽

Newly Diagnosed ◽

Cancer Specific Survival ◽

Factors Associated ◽

Increased Risk

Abstract Background: There is little population-based data on hepatocellular carcinoma (HCC) with brain metastases at initial diagnosis published. This study aimed to estimate incidence of brain metastases in initial metastatic HCC and its impact on prognosis. Methods: Newly diagnosed HCC cases from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were screened for the presence of brain metastases. Data were stratified by age and ethnicity. Multivariable logistic and Cox regression were used to identify factors associated with brain metastases and factors associated with overall survival (OS) and cancer-specific survival (CSS), respectively. Kaplan-Meier method and log-rank test were used for survival analysis. Results : 141 cases presenting with brain metastases were identified, accounting for 0.35% of all HCC cases and 2.37% of cases with metastatic HCC disease. The incidence rate was highest among cases with age 50-59 (2.74%), respectively. Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African American patients presented significantly lower disease-specific survival (median time: 1month; interquartile range (IQR):0-3.0 months). Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases (odds ratio (OR) 12.62, 95%CI 8.40-18.97), but not associated with worse OS and CSS among brain metastases cases. Conclusions: The study shows population-based incidence and survival of brain metastases at diagnosis of HCC. Brain metastases are most prevalent in initial metastatic HCC patients with lung or bone metastasis. The results may contribute to consider screening of the brain among HCC with initial lung or bone metastasis.

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Hepatic adrenal rest tumor in a patient with multifactorial liver cirrhosis: a case report with CT and MRI findings and pathologic correlation

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-021-00657-0 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Piero Boraschi ◽

Francesca Turini ◽

Francescamaria Donati ◽

Francesca Peruzzi ◽

Annamaria Bartolucci ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Broad Ligament ◽

Cirrhotic Liver ◽

Arterial Phase ◽

Histopathological Diagnosis ◽

Adrenal Rest Tumor ◽

Right Lobe ◽

Adrenal Rest ◽

The Right

Abstract Background Adrenal rest tumor is an ectopic collection of adrenocortical cells in an extra-adrenal site, more frequently located around the kidney, retroperitoneum, spermatic cord, para-testicular region and broad ligament, but very rarely occurring also in the liver. Hepatic adrenal rest tumor poses a diagnostic challenge in differentiating it from hepatocellular carcinoma, particularly in a cirrhotic liver. Case presentation An 83-years-old male was referred to our hospital by his family doctor for hepatological evaluation due to multifactorial liver cirrhosis. Ultrasound revealed a centimetric hypoechoic nodule in the VI hepatic segment in the context of a liver with signs of cirrhosis and steatosis. The patient first underwent MRI and then CT, which showed a fat containing focal liver lesion in the subcapsular location of the right lobe, strictly adjacent to the homolateral adrenal gland. The nodule was hypervascular in the arterial phase, washed out in the portal-venous and transitional phases, resulting hypointense in the hepato-biliary phase at MR imaging. In the suspicion of a hepatocellular carcinoma, the nodule was surgically removed, and the patient’s postoperative course was unremarkable. The final histopathological diagnosis was of adrenal rest tumor of the liver. Conclusions Hepatic adrenal rest tumor is an extremely rare hepatic tumor, often without any clinical manifestation, that can also occur in the cirrhotic liver as in our case. Although there are not specific imaging findings, the possible diagnosis of HART should be considered when we observe a well-defined lesion in the subcapsular location of the right lobe, with fat containing, hypervascularity after contrast medium injection and vascular supply from the right hepatic artery.

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Gingival metastasis from primary hepatocellular carcinoma: a case report and literature review of 30 cases

BMC Cancer ◽

10.1186/s12885-019-6020-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Yating Hou ◽

Weiping Deng ◽

Gang Deng ◽

Linhui Hu ◽

Chao Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Literature Review ◽

Primary Liver Cancer ◽

Primary Hepatocellular Carcinoma ◽

Survival Times ◽

Local Pressure ◽

Gingival Metastasis ◽

Survival Expectations ◽

The Right

Abstract Background Gingival metastasis from primary hepatocellular cancer (HCC) is rare, highly malignant, and generally has no distinct symptoms. Not performing a biopsy can lead to misdiagnosis. This article reports an 87-year-old male with gingival metastasis from HCC. To gain a better insight into this disease, we also conducted a literature review of 30 cases and discussed the clinical and pathological characteristics, diagnosis, treatment and prognosis of this unusual form of liver cancer. Case presentation An 87-year-old man was hospitalized with a chief complaint of chronic constipation and diffuse lower extremity edema. His past medical history included a three-year hepatitis B infection and a cerebral infarction 17 years prior. Imaging examination detected a massive hepatocellular carcinoma in the right liver lobe and multiple metastases in the lungs. Oral examinations revealed a reddish, cherry-sized exophytic mass on the right upper gum. The mass was tentatively diagnosed as a primary gingival tumor and was ultimately confirmed by biopsy as a metastatic carcinoma originating in the liver. The patient decided, with his guardians, to receive palliative care and not to remove the mass. Unfortunately, the patient accidentally bit the mass open; profuse bleeding ensued and local pressure exerted a poor hemostatic effect. The patient’s condition worsened, and he eventually died of multiple organ failure. We also performed a literature review and discussed 30 cases of gingival metastases from HCC. The findings indicated that these lesions affected males more than females, with a ratio of 6:1, and infiltrated the upper gingivae (63.1%) more than the lower gingivae (36.7%). Survival analysis indicated that the overall survival for patients with upper gingival metastasis was worse than for those with lower gingival metastasis, and patients receiving treatments for primary liver cancer or metastatic gingival tumors had better overall or truncated survival times. Conclusion Gingival metastasis from primary hepatocellular carcinoma is rare, and its diagnosis has presented challenges to clinicians. To avoid a potential misdiagnosis, a biopsy is mandatory regardless of whether a primary cancer is located. Early diagnosis and treatment for primary liver cancer or metastatic gingival lesions may improve survival expectations.

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An Autophagy-Related Gene-Based Prognostic Risk Signature for Hepatocellular Carcinoma: Construction and Validation

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/5770228 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Rui Feng ◽

Jian Li ◽

Weiling Xuan ◽

Hanbo Liu ◽

Dexin Cheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Differential Expression ◽

Prognostic Model ◽

Risk Model ◽

Cox Regression ◽

Primary Liver Cancer ◽

Univariate Analysis ◽

Differential Expression Analysis ◽

Cox Regression Analysis

Background. Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer. Treatment is dramatically difficult due to its high complexity and poor prognosis. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into novel biomarkers for HCC. Methods. Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. These genes were subjected to GO and KEGG pathway analyses. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by the ICGC validation set. Results. To sum up, 42 differential genes relevant to autophagy were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model constituted 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, and FKBP1A. Validation confirmed the accuracy and independence of this model in predicting the HCC patient’s prognosis. Conclusion. A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.

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Bilateral orbital metastasis as an initial presentation of hepatocellular carcinoma

Asian Journal of Ophthalmology ◽

10.35119/asjoo.v17i3.708 ◽

2020 ◽

Vol 17 (3) ◽

pp. 302-310

Author(s):

Kay Thi Myint ◽

Ko Ko Thant ◽

Moe Thazin

Keyword(s):

Hepatocellular Carcinoma ◽

Bone Lesions ◽

Histopathological Diagnosis ◽

Orbital Metastasis ◽

Initial Manifestation ◽

Bilateral Involvement ◽

Corrected Visual Acuity ◽

Lytic Bone Lesions ◽

Soft Tissue Masses ◽

The Right

Purpose: To describe a case of biopsy-confirmed bilateral orbital metastasis of previously undiagnosed hepatocellular carcinoma, presenting with bilateral proptosis. Case description: A 57-year-old man presented with painless bilateral proptosis over 2 months. At presentation, the best-corrected visual acuity was 20/60 in the right eye and 20/20 in the left eye. Ocular examination revealed bilateral asymmetrical non-axial proptosis with Hertel exophthalmometer reading of 24 mm in the right eye and 22 mm in the left eye. There was mild inferior displacement in both eyes. Apart from mild exposure keratopathy in the right eye, both anterior and posterior segment examinations were not remarkable. Orbital computerized tomography (CT) scan showed soft tissue masses in the superotemporal quadrants of both orbits associated with lytic bone lesions. An orbital biopsy confirmed that it was metastatic hepatocellular carcinoma (HCC). Ultrasound abdomen revealed multifocal HCC with underlying cirrhosis. We planned for further investigations such as hepatitis serology, alfa-fetoprotein, and CT abdomen, but he refused to proceed with investigations and treatment. Conclusion: Orbital metastasis, more so as a bilateral involvement, is a rare phenomenon. It may present as an initial manifestation of undiagnosed systemic cancer. Orbital metastasis should be considered when diagnosing patients with bilateral proptosis, and orbital biopsy is crucial for histopathological diagnosis.

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Identification of potential crucial genes associated with the pathogenesis and prognosis of liver hepatocellular carcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-206979 ◽

2020 ◽

pp. jclinpath-2020-206979

Author(s):

Laner Shi ◽

Xin Shang ◽

Kechao Nie ◽

Zhiqin Lin ◽

Meisi Zheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Primary Liver Cancer ◽

Interaction Network ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Medical Decision ◽

Pathway Enrichment Analysis ◽

New Biomarkers ◽

Liver Hepatocellular Carcinoma

AimsLiver hepatocellular carcinoma (LIHC) is the main manifestation of primary liver cancer, with low survival rate and poor prognosis. Medical decision-making process of LIHC is so complex that new biomarkers for diagnosis and prognosis have yet to be explored, this study aimed to identify the genes involved in the pathophysiology of LIHC and biomarkers that can be used to predict the prognosis of LIHC.MethodsSix Gene Expression Omnibus (GEO) datasets selected from GEO were screened and integrated to find out the differential expression genes (DEGs) obtained from LIHC and normal hepatic tissues. The Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment analysis of DEGs was implemented by DAVID. The Protein–protein interaction network was performed via STRING. In addition, Cox regression model was used to construct a gene prognostic signature.ResultsWe ascertained 10 hub genes, nine of them (CDK1, CDC20, CCNB1, Thymidylate synthetase, Nuclear division cycle80, NUF2, MAD2L1, CCNA2 and BIRC5) as biomarkers of progression in LIHC patients. We also build a six gene prognosis signature (SOCS2, GAS2L3, NLRP5, TAF3, UTP11 and GAGE2A), which can be implemented to predict over survival effectively.ConclusionsWe revealed promising genes that may participate in the pathophysiology of LIHC, and found available biomarkers for LIHC prognosis prediction, which were significant for researchers to further understand the molecular basis of LIHC and direct the synthesis medicine of LIHC.

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Population-Based analysis for newly diagnosed hepatocellular carcinoma with brain metastases

10.21203/rs.2.17900/v2 ◽

2020 ◽

Author(s):

Jincheng Feng ◽

Georgios Polychronidis ◽

Ulrike Heger ◽

Arianeb Mehrabi ◽

Katrin Hoffmann

Keyword(s):

Hepatocellular Carcinoma ◽

Bone Metastasis ◽

Brain Metastases ◽

Cox Regression ◽

Population Based ◽

Rank Test ◽

Newly Diagnosed ◽

Cancer Specific Survival ◽

Factors Associated ◽

Increased Risk

Abstract Background: There is little population-based data on hepatocellular carcinoma (HCC) with brain metastases at initial diagnosis published. This study aimed to estimate incidence of brain metastases in initial metastatic HCC and its impact on prognosis.Methods: Newly diagnosed HCC cases from 2010 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were screened for the presence of brain metastases. Data were stratified by age and ethnicity. Multivariable logistic and Cox regression were used to identify factors associated with brain metastases and factors associated with overall survival (OS) and cancer-specific survival (CSS), respectively. Kaplan-Meier method and log-rank test were used for survival analysis.Results: 141 cases presenting with brain metastases were identified, accounting for 0.35% of all HCC cases and 2.37% of cases with metastatic HCC disease. The incidence rate was highest among cases with age 50-59 (2.74%), respectively. Ethnicity was not associated with the presence of brain metastases at the time of HCC diagnosis. However, African American patients presented significantly lower disease-specific survival (median time: 1month; interquartile range (IQR):0-3.0 months). Initial lung or bone metastasis was independently associated with an increased risk of the presence of brain metastases (odds ratio (OR) 12.62, 95%CI 8.40-18.97), but not associated with worse OS and CSS among brain metastases cases. Conclusions: The study shows population-based incidence and survival of brain metastases at diagnosis of HCC. Brain metastases are most prevalent in initial metastatic HCC patients with lung or bone metastasis. The results may contribute to consider screening of the brain among HCC with initial lung or bone metastasis.

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