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 P. Pisani et al. S2 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.

SUMMARYThe potential for ocular allergic patients to have a site specific antigen sensitisation was investigated using vari ous diagnostic tests of allergen sensitivity in subjects with allergic conjunctivitis (AC: n = 135), vernal keratocon junctivitis (VK: n = 20), rhinoconjunctivitis (n = 20) or rhinitis (N = 10). In the AC and VK patients, skin tests and conjunctival provocation tests (CPT) were per formed, and the levels of specific IgE in serum and in tears were identified. A subgroup of 36 patients was also challenged with a nasal-specific provocation test (NPT).Results showed a poor correlation between skin test results and tear-specific IgE, and also between serum specific IgE and tear-specific IgE in both AC and VK patients (K <0.3). CPT and tear IgE were significantly correlated (K = 0.5) in the ocular allergic population. In patients with rhinoconjunctivitis or rhinitis, and in 10 normal subjects, results of CPT and NPT were in 100% agreement. Conversely, in patients with only conjunctiv itis, little correlation was found between the results of CPT and NPT (K = 0.3). Tear-specific IgE was the only positive diagnostic sign of antigen sensitivity in 35% of VK patients and 30% of AC patients. These results sug gest that the conjunctiva can be a uniquely sensitised tar get organ in allergic patients.Conjunctival or keratoconjunctival allergic disease may at times be the only manifestation of allergen sensitivity pre sented by patients. While systemic tests can be useful in the diagnosis of ocular allergy, in a consistent percentage of cases of ocular allergy, tests such as the skin test and serum total and specific IgE are negative or not signifi cant. 1 In these patients the detection of specific IgE in tears and the response to specific conjunctival provocation tests From:

Our data suggest that CCL26 and CCL24 are likely involved in the pathogenesis of chronic nasal hypereosinophilia, with a complex cooperation and different involvement of the various members of eotaxin family. Further studies are necessary to better understand the actual physiopathologic mechanism, possible clinical relevance, and therapeutic implications.

Our data suggest that early identification of inflammatory patterns and associated clinical factors in patients affected by chronic nonallergic sinonasal inflammation have a prognostic value that can help to identify patients with different risks of NP development. Our data confirm that detection of nasal eosinophilic inflammation represents an early marker for identification of a more aggressive inflammatory phenotype.

Our data confirm that GM-CSF is more frequently detectable in nasal lavages of patients affected by chronic sinonasal eosinophilic inflammation than in controls. Statistical analyses revealed a significant weakly-moderate correlation between GM-CSF levels in nasal lavage of all patients and percentage of eosinophil infiltration of nasal mucosa.