The long-term outcomes of cardiac implantable electronic devices implanted via the femoral route.

BACKGROUND: Conventional superior access for cardiac implantable electronic devices (CIEDs) is not always possible and femoral CIEDs (F-CIED) are an alternative option when leadless systems are not suitable. The long-term outcomes and extraction experiences with F-CIEDs, in particular complex F-CIED (ICD/CRT devices), remain poorly understood. METHODS: Patients referred for F-CIEDs implantation between 2002 and 2019 at two tertiary centers were included. Early complications were defined as ≤30 days following implant and late complications >30 days. RESULTS: Thirty-one patients (66% male; age 56 ± 20 years; 35% [11] patients with congenital heart disease) were implanted with F-CIEDs (10 ICD/CRT and 21 pacemakers). Early complications were observed in 6.5% of patients: two lead displacements. Late complications at 6.8 ± 4.4 years occurred in 29.0% of patients. This was higher with complex F-CIED compared to simple F-CIED (60.0% vs. 14.3%, p = .02). Late complications were predominantly generator site related (n = 8, 25.8%) including seven infections/erosions and one generator migration. Eight femoral generators and 14 leads (median duration in situ seven [range 6-11] years) were extracted without complication. CONCLUSIONS: Procedural success with F-CIEDs is high with clinically acceptable early complication rates. There is a notable risk of late complications, particularly involving the generator site of complex devices following repeat femoral procedures. Extraction of chronic F-CIED in experienced centers is feasible and safe.

Chromosome 7 Multiplication in EGFR-positive Lung Carcinomas Based on Tissue Microarray Analysis.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR) over-activation is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Our aim was to investigate the role of chromosome 7 multiplication with regard to its influence in EGFR expression, combined or not with gene amplification. MATERIALS AND METHODS: Using tissue microarray technology, fifty (n=50) primary NSCLCs were cored and re-embedded into the final recipient block. Immunohistochemistry (IHC) and also chromogenic in situ hybridization (CISH) were performed. RESULTS: EGFR expression at any level was detected in 40/50 (80%) cores. Over-expression was observed in 23/40 (57.5%) cases. Gene amplification was identified in 11/50 (22%) cases whereas chromosome 7 polysomy in 8/50 (16%) cases. Pure chromosome 7 multiplication alone led to low or moderate levels of expression. Overall EGFR expression was correlated with gene (p=0.001) and interestingly with chromosome 7 centromere numerical imbalances (p=0.004). CONCLUSION: EGFR expression is associated not only with amplification, but also with chromosome 7 centromere multiple copies. Chromosome 7 multiplication -due to centromere region amplification or true polysomy- is critical for applying monoclonal antibody targeted therapeutic strategies excluding the pure non-amplified cases.

EGFR gene deregulation mechanisms in lung adenocarcinoma: A molecular review.

For the last two decades, evolution in molecular biology has expanded our knowledge in decoding a broad spectrum of genomic imbalances that progressively lead normal cells to a neoplastic state and finally to complete malignant transformation. Concerning oncogenes and signaling transduction pathways mediated by them, identification of specific gene alterations remains a critical process for handling patients by applying targeted therapeutic regimens. The epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in regulating cell proliferation, differentiation and apoptosis in normal cells. EGFR mutations and amplification represent the gene's main deregulation mechanisms in cancers of different histo-genetic origin. Furthermore, intra-cancer molecular heterogeneity due to clonal rise and expansion mainly explains the variable resistance to novel anti-EGFR monoclonal antibody (mAb), and also tyrosine kinase inhibitors (TKIs). According to recently published 2015 WHO new classification, lung cancer is the leading cause of death related to cancer and its incidence is still on the increase worldwide. The majority of patients suffering from lung cancer are diagnosed with epithelial tumors (adenocarcinoma predominantly and squamous cell carcinoma represent ∼85% of all pathologically defined lung cancer cases). In those patients, EGFR-activating somatic mutations in exons 18/19/20/21 modify patients' sensitivity (i.e. exon 21 L858R, exon 19 LREA deletion) or resistance (ie exon 20 T790M and/or insertion) to TKI mediated targeted therapeutic strategies. Additionally, the role of specific micro-RNAs that affect EGFR regulation is under investigation. In the current review, we focused on EGFR gene/protein structural and functional aspects and the corresponding alterations that occur mainly in lung adenocarcinoma to critically modify its molecular landscape.

Molecular assays in detecting EGFR gene aberrations: an updated HER2-dependent algorithm for interpreting gene signals; a short technical report.

Purpose: Among oncogenes that have already been identified and cloned, Epidermal Growth Factor Receptor (EGFR) remains one of the most significant. Understanding its deregulation mechanisms improves critically patients' selection for personalized therapies based on modern molecular biology and oncology guidelines. Anti-EGFR targeted therapeutic strategies have been developed based on specific genetic profiles and applied in subgroups of patients suffering by solid cancers of different histogenetic origin. Detection of specific EGFR somatic mutations leads to tyrosine kinase inhibitors (TKIs) application in subsets of them. Concerning EGFR gene numerical imbalances, identification of pure gene amplification is critical for targeting the molecule via monoclonal antibodies (mAbs). In the current technical paper we demonstrate the main molecular methods applied in EGFR analyses focused also on new data in interpreting numerical imbalances based on ASCO/ACAP guidelines for HER2 in situ hybridization (ISH) clarifications.

Chromosome 7 deregulation in non-small cell lung carcinoma molecular landscape.

Lung cancer exhibits an increasing incidence and a high mortality rate worldwide. Non-small cell lung carcinoma (NSCLC)constitutes the majority of patients with lung cancer (about 85% of all pathologically defined lung cancer cases). A broad spectrum of genomic imbalances, including chromosome polysomy/aneuploidy or specific gene deregulation mechanisms, such as point mutations, deletions and amplifications has been already identified in the corresponding patients, modifying their response rates to novel targeted therapeutic regimens, and affecting also their life span. Among all chromosomes, chromosome 7 seems to play a critical role in NSCLC development and progression. Aberrations in significant genes located on it, such as EGFR, cMET, BRAF combined with numerical abnormalities of the whole chromosome are cytogenetic events that lead to specific molecular signatures in patients with NSCLC. Detection of these chromosome/gene imbalances based on polymerase chain reaction (PCR) and in situ hybridization provides to oncologists the right genetic substrate for handling these patients in a rational therapeutic way regarding their isolated molecular profile. In the current paper, we present the structural and functional profile of chromosome 7 focused on its alterations in NSCLC.