Immunological and Molecular Correlates of Disease Recurrence after Liver Resection for Hepatocellular Carcinoma

The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in particular CD4 and CD8+ memory subsets within TIL was predictive of better overall survival (OS) and time to recurrence (TTR). Increased programmed death ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells were associated with shorter OS and TTR, respectively. By combined evaluation of infiltrating cell subsets along with mRNA profiling of immune and tumor related genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells as well as PDL1 expression as the best predictors of clinical outcome. HCC infiltrate is characterized by the expression of molecules with negative regulatory function that may favor tumor recurrence and poor survival

Exposure to animal suffering, adult attachment styles, and professional quality of life in a sample of Italian veterinarians.

Contextual and individual risk factors of veterinarians' professional quality of life are being debated. Research suggests that attachment styles are relevant predictors of professional quality of life; however, their role in work-related well-being of veterinarians is yet to be ascertained. In the present study, self-report measures on exposure to animal suffering, adult attachment styles, and professional quality of life were administered to 1,445 Italian veterinarians (70% females) aged 24 to 74 years old; sociodemographic information and information on workload were also collected. Female gender, higher levels of ordinary workload, on-call hours per week, exposure to animal suffering, together with fearful and preoccupied attachment styles were significantly associated with lower levels of veterinarians' quality of life. This suggests that work-related factors may combine with individual psychological features in promoting or disadvantaging the professional quality of life of veterinarians. Implications of these findings for promoting veterinarians' quality of life and directions for future research are discussed

Challenging suicide, burnout, and depression among veterinary practitioners and students: text mining and topics modelling analysis of the scientific literature

BACKGROUND: Worldwide, veterinary practitioners and students are reported to be at higher risk of suicide, burnout, and depression compared to other occupational groups. The aim of the current study was to apply text mining and topic modelling analysis on scientific literature regarding suicide, burnout, and depression among veterinary practitioners and students to extract meaningful and synthetic information. These statistical approaches can be used to comprehend more in deep the phenomena involving veterinarians and veterinary students and to suggest the potential changes needed in admission to veterinary school, veterinary curricula, and post-graduation initiatives as preventive actions. RESULTS: A systematic search protocol was set up to identify scientific literature that published on the topic from 1985 to 2019. Two-hundred-eleven records were selected with abstracts/texts submitted to text mining and topic modelling analysis. Student, stress, work, anim*, and euthanasia resulted the most frequent terms. Topics modelling allowed to differentiate groups of words and papers in 3 areas of interest: 1) students’ difficulties encountered during their studies that increase stress and anxiety impairing their psychological health; 2) exposure to death and euthanasia as risk factor for mental health; and 3) need of support among those providing medical and health care, and of supportive group work to cope with such profession. CONCLUSION: Based on the most frequent words included in the clouds and on the contents of the papers clusterised in them, some suggestions are interfered. It is emphasized that the veterinary curricula should include courses that prepare them early to deal with animal death and post-death grief of pet owners, to handle ethical dilemmas and moral stressors, to communicate with clients and staff members, to work in team, to balance work-family life and to promote individual and team resources. Specific courses for veterinary practitioners could keep them updated on their new roles and ways to handle them among functioning as potential feedbacks to monitor their psychological wellbeing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-021-03000-x

Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses

Radiofrequency thermal ablation (RFA) destroys tumoral tissue generating a local necrosis followed by marked inflammatory response with a dense T-cell infiltrate. In this study, we tested whether hepatocellular carcinoma thermal ablation can induce or enhance T-cell responses specific for hepatocellular carcinoma-associated antigens. Peripheral blood mononuclear cells derived from 20 patients with hepatocellular carcinoma were stimulated before and a month after RFA treatment with autologous hepatocellular carcinoma-derived protein lysates obtained before and immediately after RFA treatment. The effect of thermal ablation on memory T-cell responses to recall antigens [tetanus toxoid, protein purified derivative (PPD), Escherichia coli] was also assessed. T-cell reactivity was analyzed in an IFN-γ enzyme-linked immunospot assay and by intracellular IFN-γ staining. Treatment was followed by a significant increase of patients responsive either to tumor antigens derived from both the untreated hepatocellular carcinoma tissue (P < 0.05) and the necrotic tumor (P < 0.01) and by a higher frequency of circulating tumor-specific T cells. T-cell responses to recall antigens were also significantly augmented. Phenotypic analysis of circulating T and natural killer cells showed an increased expression of activation and cytotoxic surface markers. However, tumor-specific T-cell responses were not associated with protection from hepatocellular carcinoma relapse. Evidence of tumor immune escape was provided in one patient by the evidence that a new nodule of hepatocellular carcinoma recurrence was not recognized by T cells obtained at the time of RFA. In conclusion, RFA treatment generates the local conditions for activating the tumor-specific T-cell response. Although this effect is not sufficient for controlling hepatocellular carcinoma, it may represent the basis for the development of an adjuvant immunotherapy in patients undergoing RFA for primary and secondary liver tumors. ©2006 American Association for Cancer Research

Differential distribution of infiltrating cell subsets and mRNAs between nontumorous and tumorous liver tissue samples.

<p>A: infiltrating cell subsets B: mRNAs; white bars: nontumorous and grey bars: tumorous liver tissue samples. Significance levels are shown on top of each panel. The right y axis of the upper panel refers to iNKT/CD3.</p

Epidemiological, clinical and pathological characteristics of patients.

<p>TTR: time to recurrence; OS: overall survival; HR: hazard ratio; CI: confidence intervals; NA: not applicable.</p

Kaplan-Meier curves of overall survival (OS) among HCC patients.

<p>Prognostic significance of the frequency of tumor infiltrating lymphocytes (TIL) are shown in the upper part of the figure. mRNA expression of PDL1 in tumor and of CD8 and IFN-γ in nontumorous liver is shown in the lower part of the figure. Low, high: lower or higher than median value. P values were determined by the log-rank test.</p

Kaplan-Meier curves of time to recurrence (TTR) among HCC patients.

<p>Prognostic significance of the frequency of tumor (TIL) or nontumorous liver infiltrating lymphocytes (LIL) are shown in the upper part of the figure. mRNA expression in nontumourus liver of IFN-γ and EpCAM is shown in the lower part of the figure. A specific cut-off (above or below 2.5-fold reference normal liver) was applied to EpCAM mRNA. TL: total lymphocytes; low, high: lower or higher than median value. P values were determined by the log-rank test.</p