Biology subjects

Costantino, P.

Publications and source records attributed to Costantino, P..

5 recordsLinked to original sources

bioRxiv2018

Detection of HPV16, HPV18, p16, and E6/E7 MRNA in Nasopharyngeal Cancer: A Systematic Review and Meta-Analysis

IntroductionHuman Papilloma Virus (HPV) associated head and neck cancers, particularly oropharyngeal cancers (OPC), have a superior prognosis to HPV negative cancers. A literature review did not find any studies that analyzed HPV 16, HPV 18 DNA and p16 in the nasopharynx subsite, although it has been reported in the oropharynx. The detection of HPV DNA and p16 in the nasopharynx could have implications for the treatment of NPC. To date no one has reported the detection or concordance rates of HPV associated markers in nasopharyngeal carcinoma (NPC).\n\nMethodsA literature search was undertaken on Medline, EMBASE, Scopus, and the Cochrane Library to identify studies that used PCR and ISH for detection of HPV DNA and p16 in the nasopharynx. We included studies published between 1992 and 2017 that reported the prognostic impact of HPV DNA and/or p16, treated HPV and p16 as categorical variables with at least 10 patients who tested for p16 and/or HPV16/HPV18 DNA in NPC, irrespective of HPV status. We then collected information from many parameters, and performed a meta-analysis to produce pooled prevalence estimates and explored sources of heterogeneity\n\nResults21 studies published between 1992 and 2017 were selected for meta-analysis, with sample sizes ranging from 10 to 1328. The total (random effects) pooled detection of any HPV marker in NPC patients was 19.7% (95% CI: 12.56 to 28.00). The total (random effects) pooled detection of p16 positivity in NPC patients was 23.98% (95% CI: 14.82 to 34.54). The total (random effects) pooled detection of HPV DNA in NPC patients, detected by ISH, was 14.43% (95% CI: 10.13 to 19.33) and for HPV DNA in NPC patients including E6/E7 was 18.13% (95% CI: 11.45 to 25.94). The total (random effects) pooled detection of HPV DNA in NPC patients was 18.13% (95% CI: 11.45 to 25.94). The total (random effects) pooled detection of EBV positivity in NPC patients was 76.21% (95% CI: 66.40 to 84.80). Heterogeneity was high for all of the results. The attributable fraction of p16+ and HPV DNA+ in NPC is 0.029. The attributable fraction of EBV positive and HPV - in NPC is 0.827. The attributable fraction of EBV negative and HPV - in NPC is 0.0639. The attributable fraction of EBV negative and HPV + in NPC is 0.085. The attributable fraction of EBV positive and HPV + in NPC is 0.023. The attributable fraction of HPV positive and mRNA+ in NPC was 0.115. The attributable fraction of p16 in NPC was 0.123.\n\nDiscussionThis is the first study that contributes to the concordance and detection rates of HPV related markers in NPC.\n\nLimitationsMost of the studies included were of Asian extraction. Most of the papers also did not test for E6/E7 RNA and therefore we are unsure of the amount of active E6/E7 RNA in NPC.

cancer biology↗

bioRxiv2018

Investigation of the Relationship between Markers of Systemic Inflammatory Response and Head and Neck Tumor Characteristics

BackgroundMarkers of systemic inflammation have been hypothesized to reflect the underlying tumor microenvironment, and have recently been shown to be associated with advanced tumor grade, T and N stages.\n\nAims/ObjectiveThe objective of this study was to evaluate the relationship between head and neck cancer (HNC) tumor characteristics and routine pretreatment inflammatory markers: the platelet lymphocyte ratio (PLR), the neutrophil to lymphocyte ratio (NLR), and the lymphocyte to monocyte ratio (LMR).\n\nMaterials and MethodsThis is a retrospective cohort study. The tumor characteristics collected were tumor differentiation, T stage, N stage. The relationship between the inflammatory markers and tumor characteristics was analyzed.\n\nResultsA total of 122 patients were enrolled from 2010-2016. An elevated PLR was found to be significantly associated with advanced T stage (rho=0.191, p=0.00347), and N stage (ANOVA, p=0.005). None of the other inflammatory markers (NLR, LMR) were associated with T stage or N stage. No markers were associated with tumor differentiation.\n\nConclusion and significanceWe found that an PLR is significantly associated with advanced tumor and nodal stage. We were unable to find any tumor associations with the other inflammatory markers (NLR, LMR).

cancer biology↗

bioRxiv2017

Analysis of Bone Healing with a Novel Bone Wax Substitute Compared to Bone Wax in a Porcine Bone Defect Model

BackgroundBone wax is used in surgery as a hemostatic device for bone. Despite its good functional capacity as a bone hemostat, Bone wax materials often have very poor long-term interactions with bone. This study describes a novel composite of hydroxyapatite (HA) and biodegradable poly-lactic acid (PLA) with wax-like handling properties (OsteoStat). The goal was to compare qualitative and quantitative measures between OsteoStat versus Bone wax.\n\nMethodsThe porcine critical size defect model was chosen in this study. OsteoStat and Bone wax were introduced into separate critical size defects located in the femur and humerus of a single porcine specimen. After a duration of 6 weeks, the defect sites were harvested for clinical, histological, and histomorphometric analysis.\n\nResultsBoth groups had effective hemostatic action when introduced into the defects. Analysis of the histomorphometric data revealed that the amount of new bone was significantly greater at 6 weeks in the OsteoStat group (38.05%) versus the Bone wax group (11.88%), p=0.028. OsteoStat also demonstrated less soft tissue and less test material remaining in the defect sites; however, this was not statistically significant.\n\nConclusionsWe speculate that the incomplete biodegradation of Bone wax as well as its intrinsic inflammatory properties may have retarded osseous regeneration and promoted fibrosis. In contrast, well known biodegradation pathways for PLA combined with the HA component of OsteoStat may have accounted for the positive results of OsteoStat compared to Bone wax. It is important that bone hemostat substances have biocompatible, osteoconductive, hemostatic, as well as good handling properties.

bioengineering↗

bioRxiv2017

The Neutrophil-to-Lymphocyte Ratio as a Prognostic Indicator in Head and Neck Cancer: A Systematic Review and Meta-Analysis

BackgroundThe aim of this systematic review and meta-analysis was to investigate the relationship between the Neutrophil-to-Lymphocyte Ratio (NLR) and prognosis in HNC.\n\nMethodsStudies were identified from Pubmed, Embase, Scopus, and the Cochrane Library. A systematic review and meta-analysis were performed to generate the pooled hazard ratios (HR) for overall survival (OS), disease free survival (DFS), and progression free survival (PFS).\n\nResultsOur analysis combined the results of over 6770 patients in 26 cohorts (25 studies). The pooled data demonstrated that an elevated NLR significantly predicted poorer OS, DFS, and PFS. Heterogeneity was found for OS, PFS, and marginally for DFS. Subgroup analysis in OS demonstrated that elevated NLR remained an indicator of poor prognosis.\n\nConclusionsElevated pretreatment NLR is a prognostic marker for HNC. It represents a simple and easily obtained marker that could be used to stratify groups of high-risk patients that might benefit from adjuvant therapy.

cancer biology↗

bioRxiv2017

Venous Thromboembolism Risk in Head and Neck Cancer: Significance of the Preoperative Platelet-to-Lymphocyte Ratio

Abstract (250 limit)O_ST_ABSObjectiveC_ST_ABSWe aimed to investigate the association between the preoperative platelet-to-lymphocyte ratio (PLR) and venous thromboembolism (VTE) in head and neck cancer (HNC) patients undergoing major surgery.\n\nStudy DesignRetrospective cohort study\n\nSettingAcademic tertiary hospital from 2011 to 2017\n\nSubjects and MethodsPatients with confirmed HNC undergoing major surgery were included in this study. The preoperative PLR was recorded for all patients. Known VTE risk factors, including age, sex, smoking, BMI, prior VTE, and anticoagulation were also recorded. Risk factors were screened in univariate analysis using Wilcoxons rank sum test and {chi}2 test (Bonferroni corrected). Significant covariates were subsequently included in a multivariate regression model. Bootstrap techniques were used to obtain credible confidence intervals (CI).\n\nResultsThere were 306 patients enrolled with 7 cases of VTE (6 DVTs and 1 PE). On univariate analysis, length of stay (p = 0.0026), length of surgery (p = 0.0029), and PLR (p = 0.0002) were founded to have significant associations with VTE. A Receiver Operator Characteristic (ROC) curve was constructed, that yielded an AUROC of 0.905 (95% CI: 0.82 - 0.98). Using an optimized cutoff, the multivariate model showed that length of surgery ({beta} 95% CI: 0.0001 - 0.0006; p = 0.0056), and PLR ({beta} 95% CI: 5.3256 - 5.3868; p < 0.0001) were significant independent predictors of VTE.\n\nConclusionThis exploratory pilot study has shown that PLR offers a potentially accurate risk stratification measure as an adjunct to current tools in VTE risk prediction, without additional cost to health systems.\n\nOral PresentationThis data was presented as an oral presentation at the Annual American Academy of Otolaryngology - Head and Neck Surgery (AAO-HNSF) Meeting, 13th September 2017

cancer biology↗