Bilateral cavernous sinus and ophthalmic vein thrombosis secondary to Trueperella pyogenes rhinosinusitis.

Ophthalmic vein thrombosis is a severe clinical entity with proptosis, eyelid swelling, orbital pain and reduction of visual acuity; its incidence is rare with 3-4 cases /million /year. Clinical manifestations result from venous congestion caused by septic (orbital cellulitis) or aseptic aetiologies (coagulopathies, trauma) and in some cases it could be associated with cavernous sinus thrombosis. In this paper, we describe a case report unique in the literature, of bilateral cavernous sinus and ophthalmic veins thrombosis due to both septic and aseptic causes characterized by unilateral sphenoid sinusitis sustained by Trueperella pyogenes infection. Trueperella pyogenes is an opportunistic animal pathogen, and its infections occur in both domestic and wild animals worldwide but are rare in humans; this is the first instance of human infection in the head and neck with an unknown hypercoagulable state.

Metastases to the parotid glands: An institutional experience.

BACKGROUND: Metastatic lesions to the salivary gland are rare and mostly affect the parotids. Metastases represent 8% of all malignant lesions of the parotid gland. Around 80% originate from squamous cell carcinomas (SCC) of the head and neck region. Fine needle aspiration (FNA) plays a crucial role in distinguishing primary salivary gland lesions from metastases. Herein we describe our series of metastases to the parotid glands. MATERIALS AND METHODS: We analysed 630 parotid gland FNAs over a decade including conventional and liquid-based cytology specimens. Ancillary techniques such as immunocytochemistry (ICC) were conducted on cell blocks. RESULTS: Eighty (12.4%) cases were malignant lesions, of which 53 (63.75%) were metastases including 24% melanoma, 22.6% SCC, 19% renal carcinomas, 7.5% breast carcinomas, 11.3% lung, 9% intestinal and 1.8% testicular, malignant solitary fibrous tumour and Merkel cell carcinoma. The 53 cases, classified according to the Milan system for salivary cytopathology, belonged to 5 Suspicious for malignancy (SFM) and 48 malignant (M) categories. Forty had a known history of primary malignancy (75.4%), while 13 were suspicious to be a metastatic localisation (24.5%), distributed as 5SFM (2SCC and 3Melanoma) and 8 M. A combination of clinical history, cytomorphology and ICC identified 100% of them. CONCLUSIONS: Fine needle aspiration plays a central role in the diagnostic workup of patients with metastatic lesions to their parotid glands, thereby defining the correct management. Diagnostic accuracy may be enhanced by applying ICC. Although melanoma and SCC are the most common histological types, several other malignancies may also metastasize to the parotid glands and should be kept into consideration.

Early and Long-Term Ototoxicity Noted in Children Due to Platinum Compounds: Prevalence and Risk Factors.

BACKGROUND: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression. METHODS: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed. We collected data relating to audiometry conducted annually from the end of treatment and for at least 5 subsequent years, as well as information concerning the oncological history and comorbidities. RESULTS: At the end of the treatment, 17 patients (32.08%) presented ototoxicity, according to the Boston SIOP Ototoxicity Scale; the risk factors included a higher serum creatinine value at diagnosis, having undergone cranial radiotherapy, and needing magnesium supplementation. After 5 years from the end of the treatment, the number of patients with exhibiting ototoxicity was 31 (58.5%); the factors that influenced the onset/progression of the damage were having undergone radiotherapy (HR 1.23; p < 0.01) and having received therapy with aminoglycosides (HR 1.27; p < 0.01). CONCLUSIONS: Ototoxicity caused by platinum compounds can occur even after the conclusion of the treatments, and the factors affecting its progression are radiotherapy and the aminoglycosides therapy.

Bioradiotherapy with Cetuximab May Reduce the Risk of Neck Node Relapse in Locoregionally Advanced Laryngeal Glottic Carcinoma: May HER1-Profile Be Useful in the Bioselection of Patients?

The aim of the study was to evaluate survival in patients with advanced glottic laryngeal squamous cell carcinoma treated by bioradiotherapy (BioRT) with cetuximab and eventual salvage surgery (group A, n = 66) or upfront surgery (total laryngectomy or near-total laryngectomy) with or without postoperative radiotherapy (PORT) (group B, n = 66). The predictive role of HER1 expression in the bioselection of tumors was evaluated. Relapse-free (RFS), metastasis-free (MFS), overall (OS) survivals, salvageability, and rates of larynx preservation were analyzed. The two groups were balanced by propensity score method on their baseline characteristics. No significant differences in RFS and OS were found, while MFS results were significantly higher in group A (p = 0.04). Group A showed a 22% reduction in the probability of nodal metastasis (p = 0.0023), mostly in tumors with higher HER1 expression. The salvageability with TL at 3 years was 54% after prior BioRT and 18% after prior upfront NTL (p < 0.05). BioRT with cetuximab showed a reduction in the risk of lymph node relapse, particularly in the case of HER1 positive tumors, and it allowed to achieve a higher rate of functional larynx preservation and a higher salvageability compared with upfront surgery. HER1 analysis could be clinically useful in the bioselection of tumors that may benefit from BioRT with cetuximab, particularly in those with neck node metastatic propensity.

Parathyroid hormone-related peptide and parathyroid hormone-related peptide receptor type 1 in locally advanced laryngeal cancer as prognostic indicators of relapse and survival.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) overexpression and poor patient outcome have been reported for many human tumors, but no studies are available in laryngeal cancer. Therefore, we studied the expression of PTHrP and its receptor, parathyroid hormone-related peptide receptor type 1 (PTH1R), in primary locally advanced laryngeal squamous cell carcinomas (LALSCC) also in relation to the clinical outcome of patients. METHODS: We conducted a retrospective exploratory study, using immunohistochemistry, on PTHrP, PTH1R and HER1 expressions in LALSCC of 66 patients treated with bio-radiotherapy with cetuximab. RESULTS: The expressions of PTHrP and PTH1R in LALSCC were associated with the degree of tumor differentiation (p = 0.01 and 0.04, respectively). Poorly differentiated tumors, with worse prognosis, expressed PTHrP at nuclear level and were PTH1R negative. PTHrP and PTH1R were expressed at cytoplasmic level in normal larynx epithelium and more differentiated laryngeal cancer cells, suggesting an autocrine/paracrine role of PTHrP in squamous cell differentiation of well differentiated tumors with good prognosis. Eighty-one percent HER1 positive tumors expressed PTHrP (p < 0.0001), mainly at nuclear level, consistent with the known up-regulation of PTHrP gene by HER1 signaling. In multivariable analyses, patients with PTHrP positive tumors had a higher relative risk of relapse (HR = 5.49; CI 95% = 1.62-22.24; p = 0.006) and survival (HR = 8.21; CI 95% = 1.19-105.00; p = 0.031) while those with PTH1R positive tumors showed a lower relative risk of relapse (HR = 0.18; CI 95% = 0.04-0.62; p = 0.002) and survival (HR = 0.18; CI 95% = 0.04-0.91; p = 0.029). CONCLUSIONS: In LALSCC nuclear PTHrP and absence of PTH1R expressions could be useful in predicting response and/or resistance to cetuximab in combined therapies, contributing to an aggressive behavior of tumor cells downstream to HER1.

Long-term auditory follow-up in the management of pediatric platinum-induced ototoxicity.

PURPOSE: Irreversible bilateral sensorineural hearing loss is a common side effect of platinum compounds. Because of the extended overall survival, a prolonged hearing surveillance and management of hearing impairments are emerging concerns for pediatric oncology. METHODS: In this retrospective observational study, we enrolled 38 children out of 116 treated at our institution by chemotherapy (cisplatin and/or carboplatin) with or without irradiation between 2007 and 2014, submitted to hearing monitoring before every cycle of chemotherapy, and who completed a 5-year long-term audiological follow-up. Chemotherapy regimens, demographic findings, cumulative doses, and cranial irradiation were compared. RESULTS: At the end of 5-year follow-up, ototoxicity was significantly increased compared to that observed at the end of chemotherapy (52.5% vs 39.5%, p < 0.001). A late onset of hearing loss was experienced in 13.1% of children, while in 26.3% progressive hearing loss was measured. Deafness at the end of chemotherapy and irradiation were significant prognostic factors for late ototoxicity outcomes (Odds Ratio 7.2-CI 1.67-31.1-p < 0.01 and 5.25-CI 1.26-21.86-p < 0.01 respectively). No significant differences were found between cisplatin and combined treatment (i.e., cisplatin shifted to carboplatin during monitoring for the onset of ototoxicity) and ototoxicity was not associated with platinum compounds cumulative dose (p > 0.05). 13.1% of children needed hearing aids at the end of follow-up. CONCLUSION: Long-term monitoring of at least 5 years prevents the harmful effects of hearing deprivation identifying late onset/progressive hearing loss after platinum compound chemotherapy in children thanks to early hearing rehabilitation, especially in those who underwent multimodal therapy or subjected to irradiation.

Nuclear HER3 expression improves the prognostic stratification of patients with HER1 positive advanced laryngeal squamous cell carcinoma.

BACKGROUND: Compared to the other members of human epidermal growth factor family receptors (HER), the role of HER3 has not been well defined in laryngeal cancer. The predictive and prognostic role of HER3 has been the focus of clinical attention but the research findings are contradictory, especially in laryngeal squamous cell carcinoma (LSCC). The variable localization of HER3 within cancer cells and the role of HER3 in primary and acquired resistance to HER1-targeted therapies remain unclear. METHODS: We performed a retrospective analysis of two cohorts of 66 homogeneous consecutive untreated primary advanced LSCC patients, in which co-expression of HER1, HER2 and HER3 receptors was investigated by semi-quantitative immunohistochemistry. The association of their pattern of expression with survival was evaluated by Kaplan-Meier and Cox's proportional hazard analyses. Multivariable Cox proportional hazards models were developed to predict median 2- and 3-year RFS and 2.5- and 5-year OS. The Akaike information criterion technique and backwards stepwise procedure were used for model selections. The performance of the final Cox models was assessed with respect to calibration and discrimination. RESULTS: Immunohistochemical labeling for HER1 and HER2 was localized both in the cell membrane and in the cytoplasm, while HER3 labeling was observed both in the cell cytoplasm and in the nucleus. HER3 expression was inversely correlated with HER1 positivity. The expression patterns of HERs were associated with tumor differentiation. In both cohorts of patients, HER1 expression was associated with reduced relapse-free (RFS) and overall survival (OS). In HER1 positive tumors, the co-expression with nuclear HER3 was associated with better RFS and OS, compared with HER3 negative tumors or tumors expressing HER3 at cytoplasmic level. HER3 expressing tumors had a higher Geminin/MCM7 ratio than HER3 negative ones, regardless of HER1 co-expression. Multivariable analyses identified age at diagnosis, tumor site, HER1, HER3 and age at diagnosis, tumor stage, HER1, HER3, as covariates significantly associated with RFS and OS, respectively. Bootstrapping verified the good fitness of these models for predicting survivals and the optimism-corrected C-indices were 0.76 and 0.77 for RFS and OS, respectively. CONCLUSIONS: Nuclear HER3 expression was strongly associated with favourable prognosis and allows to improve the prognostic stratification of patients with HER1 positive advanced LSCC carcinoma.

Tinnitus and Neuropsychological Dysfunction in the Elderly: A Systematic Review on Possible Links.

INTRODUCTION: Tinnitus is a common and disabling symptom often associated with hearing loss. While clinical practice frequently shows that a certain degree of psychological discomfort often characterizes tinnitus suffers, it has been recently suggested in adults as a determining factor for cognitive decline affecting attention and memory domains. The aim of our systematic review was to provide evidence for a link between tinnitus, psychological distress, and cognitive dysfunction in older patients and to focus on putative mechanisms of this relationship. METHODS: We performed a systematic review, finally including 192 articles that were screened. This resulted in 12 manuscripts of which the full texts were included in a qualitative analysis. RESULTS: The association between tinnitus and psychological distress, mainly depression, has been demonstrated in older patients, although only few studies addressed the aged population. Limited studies on cognitive dysfunction in aged patients affected by chronic tinnitus are hardly comparable, as they use different methods to validate cognitive impairment. Actual evidence does not allow us with certainty to establish if tinnitus matters as an independent risk factor for cognitive impairment or evolution to dementia. CONCLUSION: Tinnitus, which is usually associated with age-related hearing loss, might negatively affect emotional wellbeing and cognitive capacities in older people, but further studies are required to improve the evidence.