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To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). We analyzed 56 patients with advanced LSCC divided into two groups according to their prognosis: the first group relapsed within 24 months after treatment, the second group had no evidence of disease at 2 years. The presence of stromal tumor infiltrating lymphocytes (TILs) at the tumor-host border was investigated. In 43 patients we evaluated the expression of 395 genes related to immune system activation through a next generation sequencing panel. Priority-LASSO models and clustering analyses were integrated with multivariate Cox proportional hazard modeling to identify independent genes associated with relapse and estimate hazard ratios in relation to gene expression and TILs. TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. In patients with lymph node metastases and advanced T stage (pT4), the expression of other genes was altered. Low TILs count was highly associated with relapse within 2 years (p 0.001). Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. Evaluation of patients' immune profile could be useful for prognosis and future therapeutic approaches towards personalized therapy.

In this contribution, the synthesis and the unusual aggregation/deaggregation properties in solution of two dinuclear ZnII Schiff-base complexes of tetradentate Schiff-base units, having non-conjugated spacers between each molecular unit, are reported in comparison to the mononuclear model complex. Through detailed 1H NMR, DOSY NMR, optical absorption, fluorescence emission, and multivariate analysis of optical absorption data, emerge some interesting findings. In solution of non-coordinating solvents, these Lewis acidic species are characterized as monomers stabilized by formation of intramolecular aggregates, having distinct spectroscopic properties in comparison to intermolecular aggregates derived from the mononuclear model analogue. Instead, in coordinating solvents they exhibit a typical behaviour, with formation of stable adducts showing a strong fluorescence. Deaggregation studies using pyridine as reference Lewis base allowed establishing a larger thermodynamic stability of these intramolecular aggregates, in comparison to intermolecular aggregates, even larger than that of aggregates of conjugated multinuclear complexes. The combined analysis of spectroscopic data upon deaggregation with ditopic Lewis bases unambiguously demonstrated the formation of stable 1 : 1 adducts, with higher binding constants in comparison to those related to monotopic species. Therefore, the present Lewis acidic, dinuclear complexes behave as molecular tweezers of ditopic guests having a strong Lewis basicity.

La malattia metastatica in oncologia testa-collo.Il distretto testa e collo rappresenta una delle più comuni sedi di insorgenza di malattie oncologiche, con una percentuale di disseminazioni metastatiche elevata tanto a livello loco-regionale quanto a distanza. La prognosi di questi tumori è strettamente legata ad alcuni fattori principali: a) lo stadio della malattia; b) le recidive loco-regionali; c) le metastasi a distanza. Nei tumori della testa e del collo le metastasi a distanza sono presenti in circa il 10% dei casi al momento della prima diagnosi e si rendono evidenti nel corso della malattia in un ulteriore 20%-30% dei casi. Quando una metastasi a distanza a partenza da un tumore della testa e del collo si rende evidente, la prognosi viene usualmente considerata infausta, con una sopravvivenza media stimabile intorno ai 10 mesi. Scopo del presente lavoro è quello di fornire un up-todate aggiornato ed esaustivo in tema di metastasi a distanza in oncologia cervico-cefalica alla luce delle più recenti conoscenze. Concetti di recente acquisizione quali l’assetto molecolare dei tumori, le possibili interazioni tra cellule tumorali e tessuti, le peculiarità della malattia oligometastatica, il ruolo dell’immunoterapia… stanno profondamente cambiando l’approccio terapeutico in questi pazienti, con interessanti ricadute in tema di controllo di malattia. I primi capitoli sono dedicati alla storia naturale ed all’epidemiologia delle metastasi a distanza nei tumori della testa e del collo ed al loro inquadramento diagnostico anatomo-patologico e radiologico. Nei capitoli successivi vengono focalizzate le più rilevanti peculiarità cliniche con particolare attenzione agli argomenti di recente attualità quali le metastasi a distanza da tumori EBV ed HPV positivi ed il concetto di malattia oligometastatica. Ampio spazio viene destinato alle varie opzioni terapeutiche con particolare attenzione al sempre più rilevante ruolo dell’immunoterapia ed allo sviluppo di nuove tecnologie terapeutiche. In conclusione, vengono focalizzate le problematiche etico-cliniche legate al concetto di fragilità del paziente oncologico e le crescenti difficoltà di una sostenibile governance socio-economica.The head and neck district represents one of the most frequent sites of cancer, and the percentage of metastases is very high in both loco-regional and distant areas. Prognosis refers to several factors: a) stage of disease; b) loco-regional relapses; c) distant metastasis. At diagnosis, distant metastases of head and neck cancers are present in about 10% of cases with an additional 20-30% developing metastases during the course of their disease. Diagnosis of distant metastases is associated with unfavorable prognosis, with a median survival of about 10 months. The aim of the present review is to provide an update on distant metastasis in head and neck oncology. Recent achievements in molecular profiling, interaction between neoplastic tissue and the tumor microenvironment, oligometastatic disease concepts, and the role of immunotherapy have all deeply changed the therapeutic approach and disease control. Firstly, we approach topics such as natural history, epidemiology of distant metastases and relevant pathological and radiological aspects. Focus is then placed on the most relevant clinical aspects; particular attention is reserved to tumours with distant metastasis and positive for EBV and HPV, and the oligometastatic concept. A substantial part of the review is dedicated to different therapeutic approaches. We highlight the role of immunotherapy and the potential effects of innovative technologies. Lastly, we present ethical and clinical perspectives related to frailty in oncological patients and emerging difficulties in sustainable socio-economical governance.

La tossicità delle ghiandole salivari rappresenta un noto effetto indesiderato dello iodio radioattivo (I) utilizzato per il trattamento di neoplasie tiroidee, con una prevalenza che varia dal 2% al 67% della popolazione esposta. Recentemente, la scialoendoscopia è stata introdotta come un interessante strumento diagnostico e terapeutico per la gestione dei pazienti affetti da scialoadenite radioiodio-indotta non responsiva ai trattamenti medici standard. L’obiettivo della presente revisione è stato valutare l’influenza di questa procedura sulla storia clinica di pazienti affetti da scialoadenite conseguente a trattamento con radioiodio. Complessivamente, la revisione ha incluso 8 studi, 122 pazienti e 264 scialoendoscopie. Le stenosi duttali ed i tappi mucosi hanno rappresentato l’85.7% dei reperti endoscopici, sostenendo il ruolo dell’ostruzione duttale nella fisiopatologia della scialoadenite da radioiodio. Circa l’89.3% dei pazienti riportarono una risoluzione parziale o completa degli episodi di scialoadenite ricorrente, senza complicanze post-operatorie maggiori. Un solo caso è stato sottoposto a parotidectomia per fallimento del trattamento scialoendoscopico e persistenza dei sintomi. Tuttavia, i risultati della letteratura riguardarono principalmente valutazioni soggettive e solamente in due esperienze cliniche furono prese in considerazione misure oggettive con risultati discordanti. La xerostomia fu analizzata in pochi studi, con benefici differenti rispetto ai sintomi ostruttivi. La tempistica ideale per la videoendoscopia delle ghiandole salivari necessita di ulteriori analisi, al fine di definire la miglior gestione delle scialoadeniti ostruttive radioiodio-indotte.

Lembo d’avambraccio radiale vs lembo d’avambraccio ulnare: uno studio preliminare sulla morbilità del sito donatore.L’obiettivo di questo studio era di confrontare la morbilità del sito donatore dopo chirurgia ricostruttiva con il lembo libero d’avambraccio ulnare (UFFF) e il lembo libero d’avambraccio radiale (RFFF) con metodiche soggettive. Il UFFF e il RFFF sono stati utilizzati per la ricostruzione del difetti dei tessuti molli della testa e del collo in 30 pazienti (20 M e 10 F; range d’età 28-75 anni), affetti da carcinoma squamocellulare della testa e del collo. Il questionario sulla disabilità per l’arto superiore DASH è stato usato per valutare la morbilità del sito donatore. L’analisi del punteggio DASH dei pazienti ha dimostrato una mediana del punteggio totale DASH di 9,17. Non sono state osservate differenze significative per i valori mediani dei gruppi RFFF e UFFF (7,14 vs 10, rispettivamente) e per i valori ottenuti dai maschi e dalle femmine (5 vs 13,3, rispettivamente). Il UFFF può essere considerato una valida alternativa al RFFF per la ricostruzione dei difetti dei tessuti molli del distretto testa-collo; è affidabile, semplice da trapiantare e non causa maggiori morbilità del sito donatore come dimostrato dal questionario DASH.The objective of this study was to compare donor site morbidity after reconstructive surgery with Ulnar Forearm Free Flap (UFFF) and Radial Forearm Free Flap (RFFF) with subjective methods. The UFFF and the RFFF were applied for reconstruction of soft tissue defects of the head and neck region in 30 patients (20 M and 10 F; age range 28-75 years) affected by head and neck squamous cell carcinoma. The Disability of Arm, Shoulder and Hand (DASH) questionnaire was used to assess morbidity of the donor site. Analysis of the patients’ DASH scores showed an overall median DASH total score of 9.17. No significant differences were observed for median values of the RFFF and UFFF groups (7.14 vs 10 respectively) or for the values in males and females (5 vs 13.3 respectively). The UFFF can be considered a valid alternative to the RFFF for reconstruction of soft tissue defects of the head and neck area; it is safe, easy to harvest and is not associated with major morbidities of the donor site as demonstrated by the DASH questionnaire.

Background: This study aimed to explore the prevalence of breastfeeding at birth points in Sicily and the relevance of the factors influencing the adoption of exclusive breastfeeding during hospitalization linked to childbirth. Methods: A survey was conducted to monitor the prevalence of breastfeeding in seven out of nine facilities providing maternity services in the province of Catania (Sicily, Southern Italy) in the years 2016–2018. An online questionnaire was administered using an electronic tablet by the midwife to the mother after discharge. Results: Women who had a higher educational qualification breastfed in a greater proportion (59.6%, odds ratio OR 0.60 for abandoning breastfeeding). Having had a caesarean section moderately impaired breastfeeding uptake, with an almost double chance of declining exclusive breastfeeding (OR = 1.74). Starting breastfeeding within 1 h from delivery showed a significant facilitating effect (OR = 0.58). Rooming-in had a strong facilitating effect on exclusive breastfeeding. A breastfeeding advocacy program was shown to protect from abandoning breastfeeding. Conclusions: It is important to offer in all hospitals the possibility and support for breastfeeding in the first moments after childbirth to increase the number of those who will then continue with exclusive breastfeeding.

The purpose of this study was to assess the validity of CO2 laser cordectomy in the treatment of early glottic cancer and to determine the impact of margin status on disease-free survival and of the operation on voice quality. This is a retrospective review of 169 patients. Quantitative and qualitative variables were statistically compared. The impact on overall and disease-free survivals of different variables was calculated by univariate and multivariate analyses. Ten-year overall and disease free-survivals were 75 % and 60 %, respectively. Age and clinical stage showed a significant negative impact on overall survival, while margin status both on overall and disease-free survivals. The degree of dysphonia was directly related to the extension of the resection. This series confirms the good oncologic and functional outcomes of laser surgery for Tis, T1 and selected T2 glottic tumors. Patients with positive margins should undergo a further treatment or a very close follow-up.

Background The purpose of this study was to assess the value of narrow band imaging (NBI) endoscopy in the diagnosis of pharyngolaryngeal lesions and to demonstrate the validity of a new NBI-based classification of their vascular pattern. Methods From 2009 to 2011, 248 patients with pharyngolaryngeal lesions underwent NBI-endoscopic evaluation. NBI findings were classified into 5 types according to the Ni classification and were compared with histopathological reports. Sensitivity, specificity, accuracy, and positive predictive value (PPV) and negative predictive value (NPV) were calculated. Results Sensitivity, specificity, accuracy, PPV, and NPV were 97.4%, 84.6%, 92.7%, 91.6%, and 95.1%, respectively. Ninety-eight percent of histologically malignant lesions corresponded to type V endoscopic pattern, whereas 84.8% of the non-neoplastic lesions corresponded to a type I to IV pattern. Conclusion The NBI ability to detect changes in the mucosal microvasculature can be useful for distinguishing nonmalignant from malignant lesions. An internationally accepted NBI-endoscopic classification may contribute to the further definition of the diagnostic validity of this technique. © 2014 Wiley Periodicals, Inc. Head Neck 37: 215-222, 2015

We generalize Nakamaye's description, via intersection theory, of the augmented base locus of a big and nef divisor on a normal pair with log-canonical singularities or, more generally, on a normal variety with non-lc locus of dimension at most 1. We also generalize Ein-Lazarsfeld-Mustata-Nakamaye-Popa's description, in terms of valuations, of the subvarieties of the restricted base locus of a big divisor on a normal pair with klt singularities.

The purpose of this study was to assess the validity of CO2 laser cordectomy in the treatment of early glottic cancer and to determine the impact of margin status on disease-free survival and of the operation on voice quality. This is a retrospective review of 169 patients. Quantitative and qualitative variables were statistically compared. The impact on overall and disease-free survivals of different variables was calculated by univariate and multivariate analyses. Ten-year overall and disease free-survivals were 75 % and 60 %, respectively. Age and clinical stage showed a significant negative impact on overall survival, while margin status both on overall and disease-free survivals. The degree of dysphonia was directly related to the extension of the resection. This series confirms the good oncologic and functional outcomes of laser surgery for Tis, T1 and selected T2 glottic tumors. Patients with positive margins should undergo a further treatment or a very close follow-up.

We study Bezier-like formulas with weights in geometric algebra for parametrizing a special class of rational surfaces in isotropic 3-space. These formulas are useful for constructing isotropic-Mobius invariant surfaces that are dual to rational offset surfaces in euclidean 3-space. Our focus is on bilinear Clifford-Bezier patches. We derive their implicitization formula and characterize them as patches on special quartic surfaces called isotropic cyclides. Finally we present one modeling application with rational surfaces admitting rational offsets.

The purpose of this study was to assess the value of narrow band imaging (NBI) endoscopy in the diagnosis of pharyngolaryngeal lesions and to demonstrate the validity of a new NBI-based classification of their vascular pattern.From 2009 to 2011, 248 patients with pharyngolaryngeal lesions underwent NBI-endoscopic evaluation. NBI findings were classified into 5 types according to the Ni classification and were compared with histopathological reports. Sensitivity, specificity, accuracy, and positive predictive value (PPV) and negative predictive value (NPV) were calculated.Sensitivity, specificity, accuracy, PPV, and NPV were 97.4%, 84.6%, 92.7%, 91.6%, and 95.1%, respectively. Ninety-eight percent of histologically malignant lesions corresponded to type V endoscopic pattern, whereas 84.8% of the non-neoplastic lesions corresponded to a type I to IV pattern.The NBI ability to detect changes in the mucosal microvasculature can be useful for distinguishing nonmalignant from malignant lesions. An internationally accepted NBI-endoscopic classification may contribute to the further definition of the diagnostic validity of this technique.

We extend to normal projective varieties defined over an arbitrary algebraically closed field a result of Ein, Lazarsfeld, Musta\c{t}\u{a}, Nakamaye and Popa characterizing the augmented base locus (aka non-ample locus) of a line bundle on a smooth projective complex variety as the union of subvarieties on which the restricted volume vanishes. We also give a proof of the folklore fact that the complement of the augmented base locus is the largest open subset on which the Kodaira map defined by large and divisible multiples of the line bundle is an isomorphism., Comment: 7 pages. v2: we made a small modification of the statement of Lemma 2.4, a few minor corrections and updated references

We study the cone of Moriwaki divisors on \bar{M}_g by means of augmented base loci. Using a result of Moriwaki, we prove that an R-divisor D satisfies the strict Moriwaki inequalities if and only if the augmented base locus of D is contained in the boundary of \bar{M}_g. Then we draw some interesting consequences on the Zariski decomposition of divisors on \bar{M}_g, on the minimal model program of \bar{M}_g and on the log canonical models \bar{M}_g(\alpha)., Comment: 14 pages. v2: minor revision. v3: Statements of Corollaries 3 and 4 made more precise. Lemmas 2.1 and 2.3 stated and proved in arbitrary characteristic. Added Lemma 3.2. Added subsection 3.1 to explain in detail what is missing in order to extend our results over a field of positive characteristic. Final version, to appear in Michigan Mathematical Journal

We prove that the non-nef locus and the restricted base locus of a pseudoeffective divisor coincide on KLT pairs. We also extend to KLT pairs F. Russo's characterization of nef and abundant divisors by means of asymptotic multiplier ideals., Improved exposition. To appear in "Math. Z."

We study graded rings associated to big divisors on LC pairs whose difference with the log-canonical divisor is nef. For divisors that are positive enough at the LC centers of the pair, we prove the finite generation of such rings if the pair is DLT or the dimension is low, given that a Zariski decomposition exists., v4: exposition and organization of the paper improved. To appear in "Math. Proc. Camb. Phil.Soc."