Blog Archive

Αλέξανδρος Γ. Σφακιανάκης

Wednesday, February 17, 2021

Droplet digital PCR of tumor suppressor gene methylation in serial oral rinses of patients with head and neck squamous cell carcinoma

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) currently lacks sensitive approaches to detect cancer‐related traits in body fluid.

Methods

Methylation of tumor suppressor genes (TSGs) (PAX5, EDNRB, and DCC) were measured in the oral rinses from 50 HNSCC and 58 control subjects using droplet digital PCR (ddPCR). Diagnostic accuracies in detecting HNSCC and the detection rate of recurrence in the post‐treatment monitoring were analyzed.

Results

ddPCR TSG methylation detection in oral rinses for diagnosis of HNSCC had an AUC of 0.892 for PAX5, 0.753 for EDNRB, and 0.729 for DCC. Significant drop of TSG methylation was observed after completion of surgery (p < 0.01). 76.9% of the relapse cases had a pre‐emptive rebound of methylation above presurgery levels in at least one of the tested markers before confirmed recurrence.

Conclusions

Utilizing ddPCR for TSG methylation detection in oral rinses shows potential for detection and monitoring of HNSCC.

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Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma: Methodological issues

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Hepatitis C Virus RNA Transcript Associates with Prognosis in Non‐human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma

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Objective/Hypothesis

Hepatitis C virus (HCV) was reported to associate with head and neck squamous cell carcinoma (HNSCC) in many studies. However, its correlation with prognosis of non‐human papillomavirus (HPV) associated HNSCC remains unknown. Here, we sought to investigate clinical significance of HCV RNA transcript in non‐HPV associated HNSCC by analyzing corresponding RNA‐seq data.

Study Design

A retrospective cohort study.

Methods

Four hundred and forty‐eight non‐HPV associated HNSCC patients with aligned RNA‐seq and clinical follow‐up data were included and divided into two groups: low‐HCV and high‐HCV. Means of continuous variables and proportions of categorical variables were compared using independent sample t‐test and chi‐square test, respectively. Survival data were compared using Cox regression analysis, Kaplan–Meier curves, and log‐rank test. Expression of genome‐wide mRNAs and abundance of immune cells were compared using volcano plot and cell signature estimated score analysis.

Results

HCV RNA transcript negatively correlates with pathologic (P = .028) and clinical‐stage (P = .023), clinical N stage (P = .025), and nodal extracapsular spread (P = .042) and is an independent prognosis factor in non‐HPV associated HNSCC (HR = 1.488; 95% CI: 1.004–2.206; P = .048). Elevated expression of HCV improved 5‐year overall survival (43.6% vs. 53.2%; P = .035) in all non‐HPV associated HNSCC patients, the same as in male (46.6% vs. 58.7%; P = .049), clinical M0 stage (42.8% vs. 52.9%; P = .036), white (42.9% vs. 55.9%; P = .010), and histologic grade 1 to 2 subgroups (42.1% vs. 57.2%; P = .043). The expression of several immune‐related genes and abundance of some immune cells significantly changed with the increase of HCV RNA transcript, while HCV‐related oncogenes and tumor suppressor gene did not.

Conclusions

HCV RNA transcript is an independent favorable factor for prognosis of non‐HPV associated HNSCC.

Levels of Evidence

4 Laryngoscope, 2021

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Endoscopic Posterior Cricoid Split and Rib Graft Without Tracheostomy: Case and Literature Review

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Endoscopic posterior cricoid split and rib grafting (EPCS/RG) for the treatment of posterior laryngeal stenosis has some advantages over traditional open approaches, including improved surgical visualization and decreased morbidity. Many pediatric patients who undergo EPCS/RG have indwelling tracheostomy, which may be utilized to help manage the airway perioperatively. The role for de novo tracheostomy placement at the time of EPCS/RG is less clear. We present three cases from a tertiary children's hospital in which EPCS/RG was safely performed without tracheostomy. For patients with posterior laryngeal stenosis but without tracheostomy, EPCS/RG with endotracheal tube stenting might be a safe option. Laryngoscope, 2021

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Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document

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Thyroid, Volume 31, Issue 2, Page 156-182, February 2021.
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Tuesday, February 16, 2021

Expression of ACE2 and TMPRSS2 Proteins in the Upper and Lower Aerodigestive Tracts of Rats: Implications on COVID 19 Infections

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Objective

Patients with coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), exhibit not only respiratory symptoms but also symptoms of chemo‐sensitive disorders. Cellular entry of SARS‐CoV‐2 depends on the binding of its spike protein to a cellular receptor named angiotensin‐converting enzyme 2 (ACE2), and the subsequent spike protein‐priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS‐CoV‐2.

Methods

To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS‐CoV‐2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats.

Results

Co‐expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID‐19, such as the loss of taste, loss of olfaction, and respiratory dysfunction.

Conclusions

A wide range of organs have been speculated to be affected by SARS‐CoV‐2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID‐19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID‐19.

Level of Evidence

NA Laryngoscope, 131:E932–E939, 2021

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Outcomes of Primary Versus Salvage Surgery for Sinonasal Malignancies: A Population‐Based Analysis

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Objectives/Hypothesis

There exists a lack of consensus on the optimal sequence of treatment for many sinonasal malignancies (SNMs). This study compares the overall survival (OS) outcomes for primary surgery (PS) versus salvage surgery (SS) in SNM patients across stage, histology, and primary site.

Study Design

Retrospective database review.

Methods

The National Cancer Database was queried for all SNM cases treated with multimodal surgical and nonsurgical therapy between 2004 and 2015. Logistic regression identified predictors of SS. Cox proportional hazards models evaluated predictors of mortality, and Kaplan‐Meier log‐rank test assessed OS outcomes.

Results

Our SNM cohort consisted of 3,011 patients (PS = 2,804; SS = 207). SS patients had significantly longer postoperative hospital stays (P = .009) and increased rates of 30‐day (P < .001) and 90‐day mortality (P < .001) compared to PS. On multivariate logistic regression, predictors of undergoing SS included sinonasal undifferentiated carcinoma histology (odds ratio = 2.72; 95% confidence interval [CI]: 1.16‐6.66; P = .024). On multivariate Cox proportional hazards analyses among SS patients, late‐stage disease (hazard ratio [HR] = 4.80; 95% CI: 1.46‐15.8; P = .01) and positive surgical margins (HR = 2.31; 95% CI: 1.29‐4.13; P = .005) portended significantly worse OS. In the propensity score–matched cohort controlling for stage and histology, PS had significantly improved OS compared to SS (P = .007). Compared to SS, PS also had improved OS in subgroup analyses for patients with late‐stage disease (P = .026) and squamous cell carcinoma histology (P = .006).

Conclusions

In our SMN cohort, PS resulted in improved OS outcomes compared to SS independent of stage and histology. Consideration may be given to primary surgical resection for SMN whenever feasible, though a targeted, individualized approach is warranted.

Level of Evidence

3 Laryngoscope, 131:E710–E718, 2021

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