17ß-estradiol protects human skin fibroblasts and keratinocytes against oxidative damage.

BACKGROUND: Reactive oxygen species (ROS) cause severe damage to extracellular matrix and to molecular structure of DNA, proteins and lipids. Accumulation of these molecular changes apparently constitutes the basis of cell ageing. 17b-estradiol (E2) has a key role in skin ageing homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years. Oestrogens improve many aspects of the skin such as skin thickness, vascularization, collagen content and quality. Despite these clinical evidences, the effects of oestrogens on skin at the cellular level need further clarification. MATERIALS AND METHODS: HaCaT and human fibroblasts were cultured under various conditions with E2 and H2 O2 ; then were subjected to immunofluorescence and western blot analysis. Lipoperoxidation was investigated using BODIPY. RESULTS: In human fibroblasts oxidative stress decreases procollagen-I synthesis, while E2 significantly increases it. Fibroblasts and HaCaT cells viability in the presence of E2 demonstrates a notably increased resistance to H2 O2 effects. Furthermore E2 is able to counteract H2 O2 -mediated lipoperoxidation and DNA oxidative damage in skin cells. DISCUSSION: In this study we highlight that the menopause-associated oestrogens decline is involved in reduced collagen production and that E2 could counteract the detrimental effects of oxidative stress on the dermal compartment during skin aging. Furthermore, our data show that physiological concentrations of oestrogens are able to interfere with ROS-mediated cell viability reduction and to protect human skin cells against oxidative damage to cellular membranes and nucleic acids structure. CONCLUSION: Our experimental data show that the presence of 17ß-estradiol may protect skin cells against oxidative damage and that the dramatic lowering of oestrogen levels during menopause, could render skin more susceptible to oxidative damage.

Risk factors for distant metastases from carcinoma of the parotid gland.

BACKGROUND: Distant metastases (DM) have become an increasingly common cause of death in cancer patients because of the increasing therapeutic control of locoregional disease. However, little data exist regarding the role of clinical factors in predicting the likelihood of DM in patients with carcinoma of the parotid gland. METHODS: To analyze the incidence of DM and the factors involved in developing DM, the authors retrospectively studied clinical and survival data from 124 consecutive patients with parotid gland carcinoma who were surgically treated at the Institute of Otolaryngology of the University of Florence. RESULTS: DM occurred in 33 of 124 patients (26.6%). Patients with high grade carcinoma had a higher occurrence of DM than those with low grade disease (30.6% vs. 17.9%; P = 0.033). The presence or absence of tumor positive cervical lymph nodes in dissection specimens significantly influenced the occurrence of DM (68.2% vs. 23.7%) (P = 0.007), as well as the number of histologically positive cervical lymph nodes (P = 0.014). Clinical signs of local tumor extension, particularly facial nerve impairment, were found to be associated with a higher rate of DM (P = 0.008). Moreover, tumor size (P = 0.0216) and clinical stage (P = 0.010) were prognostically significant in predicting the incidence of DM. Interestingly, locoregional tumor failure (P = 0.096) did not affect the risk of DM. Multivariate Cox proportional hazards analysis showed that clinical stage and facial nerve infiltration were the most important factors in predicting the risk of DMs (P = 0.010; hazard ratio [HR]: 3.75; 95% confidence interval [CI]: 1.14-13.05 and P = 0.041; HR: 2.75; 95% CI: 1.04-7.30, respectively). CONCLUSIONS: Tumor stage and local aggressiveness were found to be the major prognostic factors in predicting the risk of distant failure in patients with carcinoma of the parotid gland.

Treatment of the clinically negative neck in laryngeal cancer patients.

BACKGROUND: Elective treatment of the NO neck in patients with laryngeal cancer remains a controversial issue. We reviewed our experience with patients who had neck dissection for NO laryngeal carcinoma with occult metastases in order to compare elective lymphadenectomy results with those achieved with therapeutic neck dissection performed subsequently when occult disease became clinically evident. METHODS: We retrospectively analyzed 150 NO laryngeal cancer patients who after a neck dissection had histologically positive lymph nodes and 5-year minimum follow-up. This population was divided in two subsets, including: 54 NO patients with occult neck metastases who had an elective neck surgery (ED); 96 initially NO patients who had a subsequent therapeutic neck dissection when nodal involvement became clinically detectable (STD). The two groups were compared with respect to the pattern of nodal metastasis and sites of treatment failures and also in terms of absolute, determinate, and actuarial survival. RESULTS: Overall absolute survival was 72.2% in the elective dissected (ED) group, compared with 54.1% in the group of subsequent therapeutic dissected (STD) patients (p = 0.075). Determinate survival was 74.0% after ED and 59.3% after STD (p = 0.17). Actuarial curves by the Kaplan-Meier method did not show any statistically significant differences among the two groups analyzed (logrank test, p = 0.54). Accordingly, Cox multivariate analysis confirmed that neck treatment policy had no prognostic impact on survival in our NO laryngeal cancer patients. However, a higher proportion of STD patients died of metastases at distant sites compared with ED patients (21.9% vs 7.4%, respectively) (p = 0.02). CONCLUSIONS: Elective lymphadenectomy does not significantly improve survival in NO laryngeal cancer patients with occult disease compared with those undergoing a therapeutic neck dissection when metastases subsequently appear.

Prognostic significance of clinically false positive cervical lymph nodes in patients with laryngeal carcinoma.

BACKGROUND: A significant proportion of clinically positive palpable cervical lymph nodes in patients with head and neck cancer are histologically benign. The biologic and prognostic significance of this reactive lymph node enlargement has not been fully clarified. METHODS: In this study, the incidence of clinically positive microscopically negative cervical lymph nodes in a series of 902 patients who had neck procedures as a part of their primary treatment for N0-2 laryngeal cancer was analyzed and survival rates of 342 patients with true negative lymph nodes (N0- necks) were compared with those of 106 patients with clinically false positive lymph nodes (N1-2b- necks). In 86 patients with false positive lymph nodes, a histopathologic analysis was performed to determine the histomorphologic pattern of the enlarged lymph nodes and to evaluate which parameters, if any, correlated with 5-year patient survival. RESULTS: Overall actuarial survival did not differ significantly in the two groups. However, the actuarial survival curves in the false positive group were clearly better compared with those of the true negative group with more advanced laryngeal cancers, particularly T4 lesions (P < 0.05). Interestingly, the analysis of pattern of recurrence showed a higher incidence of distant metastases in false positive patients with advanced stage laryngeal cancer than in true negative subjects. In addition, the histologic examination of 375 enlarged hyperplastic cervical lymph nodes from 86 neck specimens showed the prevalence of sinus histiocytosis in the false positive group and its favorable prognostic significance. No statistically significant differences with regard to the number and size of enlarged lymph nodes were found. On the contrary, lymph node location seems to have a prognostic impact on survival and the reactive benign enlargement of a digastric lymph node is a possible poor prognostic factor. CONCLUSIONS: Survival of patients with clinically false positive, histologically benign hyperplastic cervical lymph nodes who have more advanced laryngeal carcinoma is higher than clinically negative patients, suggesting that the presence of palpable benign nodes may be a sign of the host's immune activation, with favorable prognostic significance.

[Comparison of the results of surgery and radiotherapy in 175 cases of T2 glottic carcinoma: 116 operated and 59 irradiated cases]. / Confronto fra i risultati della chirurgia e della radioterapia in 175 carcinomi T2 glottici: 116 casi operati e 59 irradiati.

The results were analyzed of 175 patients with glottic squamous cell carcinomas who were treated with curative purposes (1970-1986). One hundred and sixteen of them underwent surgery at the Otolaryngology Department of the University of Florence, and 59 were treated by radiation therapy at the Florence University and Hospital Departments of Radiotherapy. In the surgical series 78 cases were treated with radical surgery and 38 with conservative surgery. All patients were staged according to TNM system (UICC 1978) as T2. Overall 10-year local control rates were 74% for the surgical series and 69% for the cases treated by radiation therapy. After salvage therapy 10-year survival rates were 83% and 76%, respectively. The analysis of the results showed no statistically significant difference. In the group treated by radical surgery 80% local control was observed, versus 66% in the cases treated with conservative surgery. 10-year survival rate was higher in the latter group (89% versus 81%) because of better results of salvage therapy: 7 of 10 recurrences were salvaged with the second treatment. Several prognostic factors were evaluated, i.e., T extent, anterior commissure involvement, subglottic invasion, vocal cord mobility impairment, and ventricular involvement. Anterior commissure involvement was the main factor affecting outcome in the surgical series: in the presence of this factor, 64% 10-year local control was observed versus 85% in the patients without commissure involvement. This factor proved more important in the patients treated with conservative surgery (10-year control: 42% versus 88%) than in those undergoing radical surgery (78% versus 85%). Anterior commissure involvement and the number of involved subsites were found to worsen prognosis in the series treated by radiation therapy: cases with anterior commissure involvement had 59% 10-year local control versus 83%. The cases with a deeper spread had 60% local control versus 75%. Vocal cord mobility impairment was a less important prognostic factor in both series. Our results suggest radiation therapy as a valuable method in the treatment of the small T2 laryngeal cancers which are not suitable for conservative surgery.

Cerebrospinal fluid rhinorrhea and unilateral nasal polyposis: a case report.

We report a case of cerebrospinal fluid (CSF) rhinorrhea and unilateral polyposis in a 53-year-old woman. The clinical features, tomograms, and CT scan with Metrizamide infusion are examined. The analysis of this case evidences that: 1) A CSF can occur also after a long time (3 years) following a head injury; 2) CT cisternography with Metrizamide can demonstrate a leakage, but not always the fluid egress from the intracranial cavity; and 3) A CSF rhinorrhea may be the primary cause and not an occasional association or complication of a reactive phlogistic nasal disease.