The expression of VEGF and cyclin D1/EGFR in common primary liver carcinomas in Egypt: an immunohistochemical study.

Background: The most common types of primary malignant liver tumours are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Treatment options for patients who are inoperable/advanced, or recurring are challenging. Cyclin D1, epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGR) are common carcinogenic proteins that have potential therapeutic targets in various cancers. They have been implicated in the development of HCC and CCA. In this study, we aimed to evaluate the oncogenic function expression of cyclin D1, EGFR and VEGF in HCC and CCA of Egyptian patients. This could help to validate their therapeutic potential. Material and methods: Tumour cases were selected from 82 cases of primary liver carcinomas, with 58 cases being from HCC and 24 cases from CCA compared to 51 non-tumour adjacent liver cases and 18 from normal liver tissue. The immunohistochemical study of cyclin D1, EGFR and VEGR was conducted. Results: Cyclin D1, EGFR and VEGF are overexpressed in HCC and CCA as compared to the control group (p < 0.001). Cyclin D1 was related to well-differentiated grade and early pathologic stage in HCC (p = 0.016 and p = 0.042, respectively). The well-differentiated grade showed significantly higher VEGF levels (p = 0.04). In the CCA group, however, EGFR was strongly related to high tumour size (p = 0.047). EGFR and VEGF were overexpressed in HCC raised in the non-cirrhotic liver compared to those developed in post-hepatitic liver cirrhosis (p = 0.003 and p = 0.014). Conclusion: Cyclin D1, EGFR and VEGF shared significant overexpression in HCC and CCA. EGFR and VEGF may play an oncogenic function in the development of HCC in non-cirrhotic liver. Furthermore, cyclin D1 and VEGF may play a good prognostic function in HCC, but EGFR may play a bad prognostic role in CCA.

The clinicopathological and prognostic factors of hepatocellular carcinoma: a 10-year tertiary center experience in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major health problem despite the emergence of several preventive and therapeutic modalities. HCC has heterogeneous and wide morpho-molecular patterns, resulting in unique clinical and prognostic criteria. Therefore, we aimed to study the clinical and pathological criteria of HCC to update the morpho-molecular classifications and provide a guide to the diagnosis of this disease. METHODS: Five hundred thirty pathologically analyzed HCC cases were included in this study. The clinical and survival data of these cases were collected. RESULTS: Hepatitis C virus is still the dominant cause of HCC in Egypt. Post-direct-acting antiviral agent HCC showed an aggressive course compared to interferon-related HCC. Old age, male gender, elevated alpha-fetoprotein level, tumor size, and background liver were important prognostic parameters. Special HCC variants have characteristic clinical, laboratory, radiological, prognostic, and survival data. Tumor-infiltrating lymphocytes rather than neutrophil-rich HCC have an excellent prognosis. CONCLUSIONS: HCC is a heterogenous tumor with diverse clinical, pathological, and prognostic parameters. Incorporating the clinicopathological profile per specific subtype is essential in the treatment decision of patients with HCC. TRIAL REGISTRATION: This was a retrospective study that included 530 HCC cases eligible for analysis. The cases were obtained from the archives of the Pathology Department, during the period between January 2010 and December 2019. Clinical and survival data were collected from the patients' medical records after approval by the institutional review board (IRB No. 246/2021) of Liver National Institute, Menoufia University. The research followed the guidelines outlined in the Declaration of Helsinki and registered on ClinicalTrials.gov (NCT05047146).

Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

BACKGROUND AND AIM: Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). METHODS: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. RESULTS: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC. CONCLUSION: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

Post direct acting anti-viral agents associated primary hepatic Castleman's disease: A case report.

Castleman's disease (CD) is a primary lymphoproliferative disorder of the lymph nodes with rare extra-nodal primary affection. PRESENTATION OF CASE: Here we present a case of primary hepatic CD associated with hepatocellular carcinoma (HCC). DISCUSSION: Sixty-two years old, male received direct-acting antiviral agents (DAAs) for HCV infection. Follow up revealed sustained virologic response; however, three hepatic focal lesions were accidently discovered. Triphasic CT confirmed the HCC nature of two masses while the other mass remained undiagnosed. Surgical intervention was the treatment of choice, and pathological examination showed a fairly circumscribed mass formed of angiolymphoid hyperplasia displayed atrophic germinal center, expanded mantle zone, and variable hyalinization. The radiological evaluation of lymph nodes was unremarkable. The patient is 40 months alive after resection, with no further management advised. CONCLUSION: The immune-modulatory effect of DAAs may induce hepatic CD development in a cirrhotic patient, necessitating further studies. A new radiologic finding was observed in the present case in the form of vessels traversing through the lesion with no attenuation or occlusion. Pathology remains the gold standard in the diagnosis of CD.