Mesenchymal stem cell therapy for laryngotracheal stenosis: A systematic review of preclinical studies

<div><p>Background</p><p>Laryngotracheal stenosis (LTS) can be either congenital or acquired. Laryngeal stenosis is most often encountered after prolonged intubation. The mechanism for stenosis following intubation is believed to be hypertrophic scarring. Mesenchymal stem cells (MSCs) therapy has shown promising results in regenerative medicine. We aimed to systematically review the literature on MSC therapy for stenosis of the conductive airways.</p><p>Methods</p><p>PubMed, EMBASE, Google Scholar and the Cochrane Library were systematically searched from January 1980–January 2017 with the purpose of identifying all studies addressing the effect of MSC therapy on the airway. We assessed effect on inflammation, fibrosis, and MSC as a component in tissue engineering for treating defects in the airway.</p><p>Results</p><p>We identified eleven studies (n = 256 animals) from eight countries evaluating the effect of MSCs as a regenerative therapy in the upper airways. The studies indicate that MSC therapy may lead to a more constructive inflammatory response as well as support tissue regeneration.</p><p>Conclusion</p><p>There may be a favorable effect of MSCs in inhibiting inflammation and as a component in tissue engineering. Given the heterogeneous nature of the included animal studies, any clear conclusion regarding the effect of tracheal stenosis in human subjects cannot be drawn. The included preclinical studies are however encouraging for further research.</p></div

Study results of the effect of MSCs on tissue engineering.

<p>Study results of the effect of MSCs on tissue engineering.</p

Overview of studies: MSCs and inflammation in the airways.

<p>Overview of studies: MSCs and inflammation in the airways.</p

Increasing incidence and survival of head and neck cancers in Denmark: a nation-wide study from 1980 to 2014

<p><b>Background:</b> The purpose of the study was to determine trends in age-adjusted incidence rates (AAIR) and survival probability in head and neck cancers (HNCs) in the Danish population from 1980 to 2014.</p> <p><b>Material and methods:</b> All patients registered with HNC in the nationwide Danish Cancer Registry from 1980 to 2014 were included. We evaluated the AAIR per 100,000 and the average annual percent change (AAPC). The relative survival probability at 5 years was calculated in relation to gender, anatomical location and histology, and we constructed age-period-cohort models of incidence.</p> <p><b>Results:</b> About 34,606 patients were included (64.7% men). The AAIR increased from 9.1 per 100,000 in 1980 to 17.4 per 100,000 in 2014 with an AAPC of 2.1%. The greatest incidence increase was observed in oropharyngeal cancer (AAPC: 5.4%) followed by hypopharyngeal cancer (AAPC: 4.2%). Adenocarcinomas had the highest AAPC (5.0%) followed by squamous cell carcinomas (AAPC: 2.0%). The AAPC was significantly higher in women (2.4%) compared with men (1.6%). For all HNC patients, the relative survival at 5 years rose significantly from 49.0% in 1980–1984 to 62.4% in 2010–2014. Women had a significantly higher survival than men with a relative survival of 61.7% compared to 50.0% in men. Laryngeal cancer had the best survival probability of cancers in the upper aerodigestive tract with hypopharyngeal cancer having the poorest survival.</p> <p><b>Conclusion:</b> This nation-wide study showed a significant rise in incidence of HNC for men and women along with a significant increase in relative survival. Oropharyngeal cancer had the highest increase in incidence followed by hypopharyngeal cancer which showed the poorest survival of HNCs.</p

Receiver operating characteristic curves of ultrasonic size measurements.

<p>Shows receiver operating characteristic (ROC) curves for different ultrasonic size measurements: short axial diameter (area under curve, AUC: 0.752), long axial diameter (AUC. 0.685), length (AUC: 0.651), S/L ratio (AUC: 0.603) and ellipsoid volume (AUC: 0.717) as predictors of metastases on a node-by-node basis (N = 318).</p

Mesenchymal Stem Cell Therapy for the Treatment of Vocal Fold Scarring: A Systematic Review of Preclinical Studies

<div><p>Objectives</p><p>Therapy with mesenchymal stem cells exhibits potential for the development of novel interventions for many diseases and injuries. The use of mesenchymal stem cells in regenerative therapy for vocal fold scarring exhibited promising results to reduce stiffness and enhance the biomechanical properties of injured vocal folds. This study evaluated the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring.</p><p>Data Sources</p><p>PubMed, Embase, the Cochrane Library and Google Scholar were searched.</p><p>Methods</p><p>Controlled studies that assessed the biomechanical effects of mesenchymal stem cell therapy for the treatment of vocal fold scarring were included. Primary outcomes were viscoelastic properties and mucosal wave amplitude.</p><p>Results</p><p>Seven preclinical animal studies (n = 152 single vocal folds) were eligible for inclusion. Evaluation of viscoelastic parameters revealed a decreased dynamic viscosity (η’) and elastic modulus (G’), i.e., decreased resistance and stiffness, in scarred vocal folds treated with mesenchymal stem cells compared to non-treated scarred vocal folds. Mucosal wave amplitude was increased in scarred vocal folds treated with mesenchymal stem cells vs. non-treated scarred vocal folds.</p><p>Conclusion</p><p>The results from these studies suggest an increased regenerative effect of therapy with mesenchymal stem cells for scarred vocal folds and are encouraging for further clinical studies.</p></div

Flowchart for 51 patients who were clinically lymph node negative (cN0).

<p>Shows the distribution of neck treatment between selective neck dissection (SND) or sentinel node biopsy (SNB) and the subsequent pathological nodal findings: lymph node metastases (pN+) or pathologically lymph node negative (pN0).</p

Incidence and survival of oropharyngeal cancer in Denmark: a nation-wide, population-based study from 1980 to 2014

<p><b>Background:</b> Oropharyngeal carcinomas (OPCs) constitute a significant and increasing proportion of head and neck carcinomas and are an important global cause of morbidity and mortality. The purpose of this study was to determine trends in incidence and survival in OPC in the Danish population from 1980 to 2014.</p> <p><b>Methods:</b> This study included all patients registered in the nationwide Danish Cancer Registry over the period 1980–2014. The age-adjusted incidence rates (AAIR) per 100,000, annual percentage change (APC) and average annual percent change (AAPC) were evaluated. Five-year relative survival (RS) was calculated with Cox regression analyses in relation to gender, anatomical location and histology.</p> <p><b>Results:</b> A total of 6555 patients (69% male) were included, with a median age at diagnosis of 60 years. The AAIR of patients with OPC increased from 0.815 per 100,000 in 1980 to 4.51 per 100,000 in 2014 with an AAPC of 5.3. The 5-year RS increased significantly from 33.1% over the period 1980–1984 to 58.5% (25.4% points) over the period 2010–2014. With no significant difference stratified for gender. Tumors located at the palatine tonsils (<i>n</i> = 3333) and salivary gland OPC (<i>n</i> = 90) had significantly better survival compared with other sub-locations and histology subtypes. In the APC model the birth cohort effect rate ratio increased until 1925 and then decreased until 1935 from which point it increased in the last cohorts.</p> <p><b>Conclusions:</b> In this population-based study, we observed a significant increase in the incidence of OPCs and in the RS for OPC. We also identified a profound birth cohort effect on the incidence.</p

Additional file 3: of Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature

Figure S2. MATH scores. Example of the mutant-allele tumor heterogeneity (MATH) scores, as a measure of tumor heterogeneity. The higher the math-score the higher the tumor heterogeneity. Mid right: Histogram of the MATH-score in the entire cohort. (JPG 201 kb

Sensitivity, specificity, PPV and NPV for different short axial diameter cut-offs.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090360#pone-0090360-t001" target="_blank">Table 1</a> shows the sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) for different cut-off values of ultrasonically measured short axial diameter. A one millimetre larger cut-off was used for LNs in level IB and IIA.</p