Distal Aortic Malperfusion Exacerbated by Antegrade Stent-Graft Placement During Hybrid Repair of Acute DeBakey Type I Aortic Dissection

We present the case of an acute DeBakey type I aortic dissection with malperfusion. The patient underwent valve resuspension, ascending aortic and partial arch replacement, debranching of the innominate artery, and placement of a small-diameter stent within the left common carotid artery, after which antegrade deployment of a stent-graft into the proximal descending thoracic aorta was performed to expand the true lumen. Distal malperfusion was exacerbated by the stent-graft''s traversal into the false lumen, necessitating further endovascular repair to reestablish flow to the distal aorta. Mitigation before stent-graft placement (for example, inserting a wire within the true lumen under fluoroscopic guidance to ensure stent-graft placement in the true lumen) and prompt corrective procedures are paramount, given the grim consequences of prolonged distal ischemia.     

Deregulation of Epigenetic Mechanisms by the Hepatitis B Virus X Protein in Hepatocarcinogenesis

This review focuses on the significance of deregulation of epigenetic mechanisms by the hepatitis B virus (HBV) X protein in hepatocarcinogenesis and HBV replication. Epigenetic mechanisms, DNA methylation, and specific histone modifications, e.g., trimethylation of H3 on lysine-27 or lysine-4, maintain ‘cellular memory’ by silencing expression of lineage-inducing factors in stem cells and conversely, of pluripotency factors in differentiated cells. The X protein has been reported to induce expression of DNA methyltransferases (DNMTs), likely promoting epigenetic changes during hepatocarcinogenesis. Furthermore, in cellular and animal models of X-mediated oncogenic transformation, protein levels of chromatin modifying proteins Suz12 and Znf198 are down-regulated. Suz12 is essential for the Polycomb Repressive Complex 2 (PRC2) mediating the repressive trimethylation of H3 on lysine-27 (H3K27me3). Znf198, stabilizes the LSD1-CoREST-HDAC complex that removes, via lysine demethylase1 (LSD1), the activating trimethylation of H3 on lysine-4 (H3K4me3). Down-regulation of Suz12 also occurs in liver tumors of woodchucks chronically infected by woodchuck hepatitis virus, an animal model recapitulating HBV-mediated hepatocarcinogenesis in humans. Significantly, subgroups of HBV-induced liver cancer re-express hepatoblast and fetal markers, and imprinted genes, suggesting hepatocyte reprogramming during oncogenic transformation. Lastly, down-regulation of Suz12 and Znf198 enhances HBV replication. Collectively, these observations suggest deregulation of epigenetic mechanisms by HBV X protein influences both the viral cycle and the host cell.     

Epigenetics in hepatocellular carcinoma: An update and future therapy perspectives

Hepatocellular carcinoma(HCC),the predominant form of adult liver malignancies,is a global health concern.Its dismal prognosis has prompted recent significant advances in the understanding of its etiology and pathogenesis.The deregulation of epigenetic mechanisms,which maintain heritable gene expression changes and chromatin organization,is implicated in the development of multiple cancers,including HCC.This review summarizes the current knowledge of epigenetic mechanisms in the pathogenesis of HCC,with an emphasis on HCC mediated by chronic hepatitis B virus infection.This review also discusses the encouraging outcomes and lessons learnt from epigenetic therapies for hematological and other solid cancers,and highlights the future potential of similar therapies in the treatment of HCC.     

Left Ventricular Aneurysm Repair with Use of a Bovine Pericardial Patch

Left ventricular aneurysm, which can impair systolic function, has a reported incidence of 10% to 35% in patients after myocardial infarction. In a 58-year-old woman who had a history of myocardial infarction, we excised a large left ventricular aneurysm and restored left ventricular geometry with use of a bovine pericardial patch. The aneurysm''s characteristics and the patient''s preoperative left ventricular ejection fraction of 0.25 had indicated surgical intervention. The patient had an uneventful postoperative course, and her left ventricular ejection fraction was 0.50 to 0.55 on the 4th postoperative day. This case illustrates the value of surgical treatment for patients who have a debilitating left ventricular aneurysm.     

Differences in telomerase activity between colon and rectal cancer

Background

Colorectal cancer is one of the most common cancers and the third leading cause of cancer death in both sexes. The disease progresses as a multistep process and is associated with genetic alterations. One of the characteristic features of cancer is telomerase activation. We sought to evaluate the differences in telomerase activity between colon cancer and adjacent normal tissue and to correlate the differences in telomerase activity between different locations with clinicopathological factors and survival.

Methods

Matched colon tumour samples and adjacent normal mucosa samples 10 cm away from the tumour were collected during colectomy. We assessed telomerase activity using real time polymerase chain reaction. Several pathological characteristics of tumours, including p53, Ki-67, p21, bcl2 and MLH1 expression were also studied.

Results

We collected samples from 49 patients. There was a significantly higher telomerase activity in colon cancer tissue than normal tissue. Adenocarcinomas of the right colon express significantly higher telomerase than left-side cancers. Colon cancers and their adjacent normal tissue had significantly more telomerase and were more positive to MLH1 than rectal cancers. The expression of p53 negatively correlated to telomerase activity and was linked to better patient survival.

Conclusion

Colon and rectal cancers seem to have different telomerase and MLH1 profiles, and this could be another factor for their different biologic and clinical behaviour and progression. These results support the idea that the large bowel cannot be considered a uniform organ, at least in the biology of cancer.     

Glucocorticoids promote a glioma stem cell‐like phenotype and resistance to chemotherapy in human glioblastoma primary cells: Biological and prognostic significance

Glioma stem cells (GSCs) are glioblastoma (GBM) cells that are resistant to therapy and can give rise to recurrent tumors. The identification of patient‐related factors that support GSCs is thus necessary to design effective therapies for GBM patients. Glucocorticoids (GCs) are used to treat GBM‐associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, which has been linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and GSCs. Here, we treated primary human GBM cells with dexamethasone and evaluated GC‐driven changes in cell morphology, proliferation, migration, gene expression, secretory activity and growth as neurospheres. Dexamethasone treatment of GBM cells appeared to promote the development of a GSC‐like phenotype and conferred resistance to physiological stress and chemotherapy. We also analyzed a potential correlation between GC treatment and tumor recurrence after surgical excision in a population‐based consecutive cohort of 48 GBM patients, adjusted for differences in known prognostic factors concerning baseline and treatment characteristics. In this cohort, we found a negative correlation between GC intake and progression‐free survival, regardless of the MGMT methylation status. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and may support a GSC population, which could contribute to tumor recurrence and the poor prognosis of the disease.     

Validation of the revised Bakas Caregiving Outcomes Scale in Greek caregivers of patients with advanced cancer receiving palliative radiotherapy

Purpose

Caregiver burden considerably affects the lives of families providing care to people with advanced cancer. The aim of this study was to validate the Greek translation of the revised Bakas Caregiving Outcomes Scale (BCOS) with a sample of informal caregivers of people with advanced cancer receiving outpatient palliative radiotherapy.

Methods

Following a formal “forward–backward” method to translate the original BCOS into Greek, the scale was administered to 100 consecutive family caregivers. Participants also completed the Greek Hospital Anxiety and Depression Scale (G-HADS) and five quality-of-life related linear analogue scale assessment (LASA) scales. Validity and reliability analyses were performed.

Results

The Cronbach’s α coefficient for the total BCOS score was 0.83. Test–retest reliability analysis in a subgroup of caregivers (n?=?40) revealed good short-term stability over a 2-week interval. Exploratory factor analysis generated a one-factor structure for the Greek translation, which was further confirmed through confirmatory factor analysis. Construct validity was supported through the scale’s high correlations with G-HADS anxiety (?0.524; p?<?0.001) and depression (?0.533; p?<?0.001) scores, and LASA quality of life scores (0.696; p?<?0.001). The BCOS discriminated well between groups of caregivers with different levels of quality of life. A total score of 52.5 offered high sensitivity (91 %) and specificity (86 %) in detecting highly burdened caregivers.

Conclusions

The Greek version of the BCOS is a psychometrically sound instrument that can be usefully implemented into clinical practice to identify family caregivers in need for support, and stimulate relevant research in our country.