Efficacy and safety of endovascular brachytherapy combined with transarterial chemoembolization for the treatment of hepatocellular carcinoma patients with type III or IV portal vein tumor thrombosis

Background: The purpose of this study was to evaluate the efficacy and safety of endovascular brachytherapy (EVBT) combined with transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC) complicated with type III OR IV portal vein tumor thrombosis (PVTT) and to further analyze the prognostic predictors for the patients with HCC and PVTT.
Methods: We retrospectively analyzed the medical records of 54 patients who were diagnosed with HCC complicated with type III or IV PVTT and received EVBT combined with modified TACE treatment from January 2017 to June 2019. Adverse events, treatment response, overall survival (OS), progression-free survival (PFS), and stent patency were analysed to evaluate the efficacy and safety of this treatment. The independent prognostic predictors of OS were also statistically analyzed by the cox regression model.
Results: No adverse events occurred in the enrolled patients receiving EVBT combined with TACE treatment. The objective response and disease control rates were 42.6% and 96.3% respectively within 4 weeks after the treatment. The median OS and PFS were 209 days and 138 days, respectively. Cumulative stent patency rate was 70.4% at the last follow-up. AFP ≥ 400 ng/ml, ECOG PS > 1, Child Pugh grade B, and non-hemihepatic HCC were independent risk predictors to https://biodas.org/ evaluate the OS of HCC patient with type III or IV PVTT.
Conclusions: EVBT combined with TACE was a relatively effective and safe strategy to treat HCC patients with type III or IV PVTT.

Dual immune checkpoint blockade in hepatocellular carcinoma: where do we stand?

Hepatocellular carcinoma (HCC) represents the fourth most common cause of cancer-related death. Surgery, local ablative therapies and liver transplantation are the only potentially curative strategies, but the majority of patients present with advanced disease at diagnosis or develop recurrence after surgery.
In recent years, immunotherapy for HCC has received growing interest, and one of the most promising strategies is the association of two immune checkpoint inhibitors (ICIs), which has already demonstrated its potential in other solid tumors such as melanoma and renal cell carcinoma. Herein, we discuss the role and the biologic rationale of dual immune checkpoint blockade in HCC patients, focusing on the two ICI combinations: nivolumab plus ipilimumab and durvalumab plus tremelimumab.

Exposome and Skin. Part 2. The Influential Role of the Exposome, Beyond UVR, in Actinic Keratosis, Bowen’s Disease and Squamous Cell Carcinoma: A Proposal

Actinic keratosis (AK) is the main risk factor for the development of cutaneous invasive squamous cell carcinoma (SCC). It represents the first sign of severe chronic ultraviolet radiation exposure, which has a clear significant effect. Nevertheless, the skin is exposed to many other exposome factors which should be thoroughly considered. Our aim was to assess the impact of exposome factors other than ultraviolet radiation (UVR) on the etiopathology of AK and Bowen’s disease (BD) and progression of AK to SCC and to design tailored prevention strategies.
We performed an exhaustive literature search in September 2021 through PubMed on the impact of exposome factors other than UVR on AK, BD and SCC. We conducted several parallel searches combining terms of the following topics: AK, BD, SCC and microbiome, hormones, nutrition, alcohol, tobacco, viral infections, chemical contaminants and air pollution. Notably, skin microbiome studies have shown how Staphylococcus aureus infections are associated with AK and AK-to-SCC progression by the production of chronic inflammation. Nutritional studies have demonstrated how a caloric restriction in fat intake, oral nicotinamide and moderate consumption of wine significantly reduce the number of premalignant keratoses and SCC.
Regarding lifestyle factors, both alcohol and smoking are associated with the development of SCC in a dose-dependent manner. Relevant environmental factors are viral infections and chemical contaminants. Human papillomavirus infections induce deregulation of cellular proliferation and are associated with AK, BD and SCC. In addition to outdoor jobs, occupations such as industrial processing and farming also increase the risk of developing keratoses and SCC. The exposome of AK will undoubtedly help the understanding of its etiopathology and possible progression to SCC and will serve as a basis to design tailored prevention strategies.

A Genome-Wide Investigation of Effects of Aberrant DNA Methylation on the Usage of Alternative Promoters in Hepatocellular Carcinoma

Background: The alternative usage of promoters provides a way to regulate gene expression, has a significant influence on the transcriptome, and contributes to the cellular transformation of cancer. However, the function of alternative promoters (APs) in hepatocellular carcinoma (HCC) has not been systematically studied yet. In addition, the potential mechanism of regulation to the usage of APs remains unclear. DNA methylation, one of the most aberrant epigenetic modifications in cancers, is known to regulate transcriptional activity. Whether DNA methylation regulates the usage of APs needs to be explored. Here, we aim to investigate the effects of DNA methylation on usage of APs in HCC.
Methods: Promoter activities were calculated based on RNA-seq data. Functional enrichment analysis was implemented to conduct GO terms. Correlation tests were used to detect the correlation between promoter activity and methylation status. The LASSO regression model was used to generate a diagnostic model. Kaplan-Meier analysis was used to compare the overall survival between high and low methylation groups. RNA-seq and whole-genome bisulfite sequencing (WGBS) in HCC samples were performed to validate the correlation of promoter activity and methylation.
Results: We identified 855 APs in total, which could be well used to distinguish cancer from normal samples. The correlation of promoter activity and DNA methylation in APs was observed, and the APs with negative correlation were defined as methylation-regulated APs (mrAPs). Six mrAPs were identified to generate a diagnostic model with good performance (AUC = 0.97). Notably, the majority of mrAPs had CpG sites that could be used to predict clinical outcomes by methylation status. Finally, we verified 85.6% of promoter activity variation and 92.3% of methylation changes in our paired RNA-seq and WGBS samples, respectively. The negative correlation between promoter activity and methylation status was further confirmed in our HCC samples.
Conclusion: The aberrant methylation status plays a critical role in the precision usage of APs in HCC, which sheds light on the mechanism of cancer development and provides a new insight into cancer screening and treatment.

A case of locally advanced adenosquamous carcinoma of the cecum with long-term survival

A 63-year-old woman was admitted to our hospital with a right lower abdominal mass and general fatigue. Preoperative examination suggested a large ovarian tumor or cecal carcinoma. However, her intraoperative diagnosis was colon cancer; we therefore performed an ileocecal resection with oophorectomy. The tumor was pathologically diagnosed as adenosquamous carcinoma T4bN1M-stage IIIa.
We administrated CapeOX adjuvant chemotherapy for 6 months. Adenosquamous carcinoma is extremely rare, at around 0.1% of all colorectal cancers, and usually has a poor prognosis. The patient is still alive without recurrence after 84 post-operative months, even with later developments of metachronous early colorectal cancer and breast cancer. We herein report a rare case of cecal ASC with good prognosis.