Tissue and circulating PD-L2: moving from health and immune-mediated diseases to head and neck oncology.

Amongst the chief targets of immune-checkpoint inhibitors (ICIs), namely the Programmed cell death protein 1 (PD-1)/PD-Ligands (Ls) axis, most research has focused on PD-L1, while to date PD-L2 is still under-investigated. However, emerging data support PD-L2 relevant expression in malignancies of the head and neck area, mostly in head and neck squamous cell carcinoma (HNSCC) and salivary gland cancers (SGCs). In this context, ICIs have achieved highly heterogeneous outcomes, emphasizing an urgent need for the identification of predictive biomarkers. With the present review, we aimed at describing PD-L2 biological significance by focusing on its tissue expression, its binding to PD-1 and RGMb receptors, and its impact on physiological and anti-cancer immune response. Specifically, we reported PD-L2 expression rates and significant clinical correlates among different head and neck cancer histotypes. Finally, we described the biology of soluble PD-L2 form and its potential application as a prognostic and/or predictive circulating biomarker.

A pre-operative prognostic score for the selection of patients for salvage surgery after recurrent head and neck squamous cell carcinomas.

Salvage surgery in recurrent head and neck squamous cell carcinoma has a poor outcome, both in terms of survival and quality of life. Therefore, the identification of pre-operative prognostic factors to improve the selection of patients who could benefit the most from salvage surgery is clinically relevant. The present study is a single-center retrospective analysis of 164 patients treated with salvage surgery after recurrence of head and neck cancer. Progression free survival and overall survival were calculated through Kaplan-Meier method. Hazard risk (HR) and corresponding confidence intervals (CI) were estimated through Cox proportional hazard model, adjusting for potential confounders. Significant predictors were combined into a prognostic score, attributing one point to each factor. Progression-free survival and overall survival were respectively 50.3% and 56.5% at 2 years, and 36.6% and 44.2% at 5 years. Four pre-operative factors were independently associated with poor prognosis: age > 70 years (HR = 2.18; 95% CI 1.27-3.73), initial stage IV (HR = 2.37; 95% CI 1.18-4.76), disease free interval < 12 months (HR = 1.72; 95% CI 1.01-2.94), and loco-regional recurrence (HR = 2.22; 95% CI 1.22-4.04). No post operative factor was associated with oncologic outcomes. Patients with 3-4 unfavorable factors showed a 5-year overall survival of 0.0% compared to 65.7% in those with 0-1 unfavorable factors (HR = 5.61; 95% CI 2.89-10.92). Despite the low number of patients, 3-4 unfavorable factors were associated to worse prognosis in all sub-sites. In conclusion, age > 70 years, initial stage IV, disease-free interval < 12 months, and loco-regional recurrence are strong independent pre-operative predictors of poor outcome in patients undergoing salvage surgery. Patients with two or more of these factors should be informed about the low success rate after salvage surgery and alternative treatments should be considered.

ß-Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma.

AIM: The novel primary end-point of the present study was to ascertain ß-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of ß-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. METHODS: The expression of ß-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. RESULTS: Statistical analysis showed no significant associations between ß-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and ß-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). CONCLUSIONS: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and ß-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how ß-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.

Recurrent Kaposi sarcoma associated with Koebner phenomenon in two HIV-seronegative patients: Two case reports and a review of the literature.

RATIONALE: Koebner phenomenon is occasionally reported in patients affected by classic Kaposi sarcoma (KS). PATIENT CONCERNS: Here, we report 2 cases of KS associated with Koebner phenomenon and the correlation of human herpesvirus 8 molecular analysis with the clinical outcome. INTERVENTIONS: In the first case, a patient with a history of sporadic cutaneous KS developed a recurrent lesion at the laryngeal tract, the site of a previous nodulectomy. In our second case, immunodeficiency induced by chemotherapy triggered the development of KS and Koebner phenomenon was limited to the skin at the site of safenectomy. LESSONS: Our observations suggest that careful planning of surgical treatment is required in immunocompetent and immunocompromised patients with a medical history of KS. Moreover, mucosal sites (both respiratory and in the gastrointestinal tract) should be considered as potential sites for KS development.

Multivariate approach to investigating prognostic factors in deep neck infections.

Deep neck infections (DNI) spread along fascial planes and involve neck spaces. Very few studies have investigated potentially prognostic factors using multivariate statistical models. Our aim was to analyze 282 consecutive cases of DNI using multivariate (logistic) statistical models to identify independent significant factors influencing prognosis in terms of complications and long-term hospitalization (>6 days). In our series, only involvement of more than one neck space was independently significant in prognosticating complications of DNI (odds ratio [OR] 2.46). The presence of comorbidities (OR 2.13), non-odontogenic sites of origin (OR 1.88), leukocyte counts above 11.0 cells × 10(9)/L at presentation (OR 3.57), and the need for both medical and surgical treatments (OR 4.66) was significantly and independently prognostic of long hospital stays. Multivariate analysis can distinguish between risk factors and their relative contribution to outcome. The few published studies using multivariate models to analyze DNI prognosis considered quite large cohorts, but no clinical variables persistently revealed an independent significant prognostic role. This evidence seems to underscore the complex interdependence of several clinical variables in contributing to DNI prognosis, and the heterogeneity of the diagnostic/therapeutic approaches adopted.

Smoking and chronic rhinitis: effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water: A prospective, randomized, double-blind study.

PURPOSE: Smoking is a self-destructive behavior that is known to induce remodeling of the lower airways, leading to squamous metaplasia, but little is known about its effects on the nose and paranasal sinuses. Nasal irrigations are often mentioned as measures for treating sinonasal inflammations. The purpose of our study was to compare the effects of nasal irrigations with sulfurous-arsenical-ferruginous thermal water or isotonic sodium chloride solution in smokers with nonallergic chronic rhinosinusitis, based on clinical and olfactory evidence. MATERIALS AND METHODS: The present study was a prospective, randomized, double-blind study performed in a tertiary academic referral center. Seventy smokers with nonallergic chronic rhinitis were enrolled. Nasal endoscopy, rhinomanometry, nasal cytology, and odor threshold measurements were performed in subjects randomized to daily nasal irrigations with either thermal water or isotonic sodium chloride solution for 1 month. RESULTS: Immediately after the treatment, the thermal water irrigations revealed a positive pharmacologic action, judging from a tendency toward lower nasal resistances (P = .07) and larger numbers of ciliated cells in the patients treated (P = .003). Endoscopic findings in the thermal water group were still better than in the control group a further 2 months later (P = .03). CONCLUSIONS: Our results indicate that nasal irrigations with thermal water had a good effect on endoscopic objective signs, nasal resistances, and epithelial trophism.

mTOR expression and prognosis in elderly patients with laryngeal carcinoma: uni- and multivariate analyses.

Cancer is common in the elderly, who may also be frail, which can complicate the choice of the best therapeutic approach. We sought to examine whether the serine-threonine kinase mTOR, a "master switch" in cancer cells that modulates metabolism, the cell cycle, and apoptosis, might help in clinical decision-making. The aim of the present study was thus to assess the potential prognostic role of mTOR in elderly patients with laryngeal carcinoma (LSCC). mTOR expression was determined immunohistochemically in 54 consecutive elderly (≥65 years old) patients with LSCC. On univariate analysis, nodal involvement and pathological stage correlated strongly with the elderly LSCC patients' prognosis in terms of disease recurrence rate and disease-free survival (DFS). Patients whose mTOR expression was >35.3% had a significantly higher recurrence rate (p=0.003) and shorter DFS (p=0.013). In the multivariate model, N status (p=0.001) and mTOR expression (p=0.026) maintained an independent prognostic significance in relation to DFS. mTOR probably influences the aggressive LSCC phenotype in elderly patients and its expression in elderly LSCC cases can be considered a prognostic marker potentially useful for identifying patients at higher risk of disease recurrence, and N0 patients at higher risk of recurrence who may benefit from more aggressive treatment. Since rapalogs (as mTOR inhibitors) might have an effect on LSCC, further investigations are needed to ascertain these agents' role in therapeutic strategies for advanced LSCC in elderly patients.