Fabio Beatrice

A Case-control Study on Occupational Risk Factors for Sino-nasal Cancer

Objectives: Sino-nasal cancer has been consistently associated with exposure to wood dust, leather dust, nickel and chromium compounds; for other occupational hazards, the findings are somewhat mixed. The aim of this study was to investigate the risk of sino-nasal epithelial cancer (SNEC) by histological type with prior exposure to suspected occupational risk factors and, in particular, those in metalworking. Methods: Between 1996 and 2000, incident cases were collected on a monthly basis from hospitals throughout the Piedmont region of Italy by the regional Sino-nasal Cancer Registry. A questionnaire on occupational history, completed by 113 cases and 336 hospital controls, was used to assign exposure to occupational hazards. The relationship between SNEC and cumulative exposure to these hazards was explored using unconditional logistic regression to statistically adjust for age, sex, smoking and co-exposures, allowing for a 10-year latency period. Results: The risk of adenocarcinoma was significantly increased with ever-exposure to wood dust (odds ratio; OR = 58.6), and to leather dust (OR = 32.8) and organic solvents (OR = 4.3) after controlling for wood dust, whereas ever-exposure to welding fumes (OR = 3.7) and arsenic (OR = 4.4) significantly increased the risk for squamous cell carcinoma. For each of these hazards, a significant increasing trend in risk across ordered cumulative exposure categories was found and, except for arsenic, a significantly increased risk with ever-exposure at low intensity. Treating cumulative exposure on a continuous scale, a significant effect of textile dusts was also observed for adenocarcinoma. For a mixed group of other histological types, a significant association was found with wood dust and organic solvents. Conclusions: Some occupational risk factors for SNEC were confirmed, and dose–response relationships were observed for other hazards that merit further investigation. The high risk for adenocarcinoma with low-intensity exposure to wood dust lends support for a reduction in the occupational threshold value.

Clinical and Biological Prognostic Factors in 179 Cases with Sinonasal Carcinoma Treated in the Italian Piedmont Region

Objectives: In spite of aggressive surgery and high-dose radiotherapy, the long-term survival of patients with sinonasal cancer remains disappointing. In this paper, we report data from 179 consecutive cases treated in the Italian Piedmont region between 1996 and 2000 according to a fixed protocol. Methods: Clinical and pathological data and the following biological parameters were analyzed: microvessel density and growth fraction by CD31 and Ki-67 positivity, respectively, and immunohistochemical expression of vascular endothelial growth factor (VEGF). Results: The median follow-up period was 75 months (range 45–108 months). Median overall survival was 26 months; 2- and 5-year overall survival rates were 52 and 36%, respectively. Patients with T1-T2 adenocarcinoma and squamous cell cancers (SCC) had better median survival than those with other lesions (p < 0.05). Patients treated with surgery with or without radiotherapy had better survival (p < 0.01), while chemotherapy had a marginally favorable effect (p = 0.09). The type of surgery and radiotherapy dose had no impact on survival; in contrast, there was a strong association between Ki-67 expression and microvessel density and overall survival (p < 0.05 and p = 0.039, respectively), while VEGF-C was a prognostic factor in SCC patients only (p < 0.05). Conclusions: In sinonasal cancer, tumor stage and histology have a clear impact on survival; surgery with or without radiotherapy represents the main choice of treatment for such tumors. The efficacy of neoadjuvant and concomitant chemoradiotherapy needs to be further investigated. The proliferative index and angiogenesis show a major role in the natural history of this cancer.

Induction chemotherapy with cisplatin and epirubicin followed by radiotherapy and concurrent cisplatin in locally advanced nasopharyngeal carcinoma observed in a non-endemic population

BACKGROUND AND PURPOSE Chemoradiotherapy (CRT) represents the main therapy choice in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). The aim of this study was the clinical evaluation of neoadjuvant chemotherapy (NACT) followed by CRT in a non-endemic population affected by advanced NPC. MATERIALS AND METHODS Patients with locoregionally advanced NPC were treated with three cycles of induction chemotherapy (CHT) with cisplatin (100 mg/m(2)) plus epirubicin (90 mg/m(2)), followed by cisplatin (100 mg/m(2)) and concomitant radiotherapy (70 Gy). RESULTS In 40 patients treated with such protocol, after the completion of induction CHT and CRT we observed the objective response rates of 90% and 100%, respectively. Treatment tolerability and toxicity were easily controllable. With a median follow-up time of 54 months, 3- and 5-year disease-free survival was 75% and 65% and 3- and 5-year overall survival was 84% and 77%. Three- and 5-year locoregional control was 82% and 70%, and 5-year distant metastases free survival was 75%. CONCLUSIONS NACT with cisplatin and epirubicin followed by concomitant CRT represents a feasible, efficient treatment for patients with advanced NPC. This regimen ensures an excellent locoregional disease control and overall survival with a low incidence of distant metastases.

Occupational risk factors for sinonasal inverted papilloma: a case-control study.

Objectives Sinonasal inverted papilloma (IP) is an uncommon benign tumour characterised by frequent recurrence and, in approximately 10% of cases, by neoplastic transformation. IP aetiology is unknown but human papillomavirus is detectable in about one quarter of tumours. As some occupational hazards have been reported to be possible risk factors for IP, the aim of this study was to assess risk for sinonasal IP associated with prior exposure to suspected occupational risk factors for sinonasal malignancies. Methods Between 1996 and 2007, data on incident cases were collected from hospitals throughout the Piedmont region of Italy by the regional sinonasal cancer registry. A questionnaire on occupational history, completed by 127 cases and 337 hospital controls, was used to assign previous exposure to a list of 17 occupational hazards. The relationship between IP and cumulative exposure to these hazards was explored using unconditional logistic regression to statistically adjust for age, sex, area of residence, smoking and co-exposures. Results The risk of IP was significantly increased for ever exposure to welding fumes (OR 2.14) and organic solvents (OR 2.11) after controlling for potential confounders. For organic solvents only, a significant association with continuous cumulative exposure and a significant trend in risk across ordered cumulative exposure categories was found. Conclusions The present study revealed a significant association and a significant dose–response relationship between occupational exposure to organic solvents and IP. The lack of a dose–response relationship for welding fumes suggests that the observed association with ever exposure should be interpreted with caution.

Expression of epidermal growth factor receptor and transforming growth factor α in human larynx carcinoma

Altered expression of growth factors and growth factor receptors is frequently described in human tumors and human tumor cell lines. This further supports the hypothesis that oncogenesis is due to the subversion of mitogen-responsive pathways. The aim of this study was to investigate the expression of epidermal growth factor receptor (EGFR) and transforming growth factor alpha (TGF alpha) in 13 larynx carcinomas and 2 carcinomas of the oral cavity. We found receptor overexpression in 7 out of 15 tumors at mRNA and/or protein level but low expression in the majority of the normal adjacent tissues. TGF alpha was expressed only in 1 case, but no tyrosine kinase activity of the receptor was detected by antiphosphotyrosine antibody.

Natural killer-mediated cytotoxicity in patients with laryngeal carcinoma

Natural killer (NK)-mediated cytotoxicity against the K562 cell line was evaluated in normal subjects and in patients with laryngeal cancer. Results showed reduced lymphocyte cytotoxicity in patients with neoplastic disease and further reduction in NK activity following postoperative radiation therapy. The authors discuss the possibility of using this test in the immunological monitoring of patients with laryngeal carcinoma.

Apheresis as rescue therapy in a severe case of sudden hearing loss

A 23-year-old man complained of progressive left ear hearing loss and tinnitus and was unsuccessfully treated with steroids and mannitol. Four months later he presented with sudden, severe, asymmetrical, bilateral sensorineural hearing loss. The results of the laboratory workup were normal except for antinuclear autoantibodies. Auditory brain stem responses showed absent peak and interpeak latencies on both sides. The combination of plasma exchange with high doses of steroids resulted in a definite improvement. Plasmapheresis combined with steroid administration can be used as secondline therapy in idiopathic, sudden sensorineural hearing loss.

Specific lymphokine responses in cervical nodes of patients with laryngeal cancer

The role of lymphokines in modulating the immune response in patients suffering from neoplastic disease is still controversial. Recent studies indicate that in patients with head and neck cancer, a decrease in LIF (leukocyte migration inhibiting factor) production is usually present in advanced disease. In this study, the authors investigate:

Evaluation of blocking mechanisms against immunological responses in patients with laryngeal carcinoma

The specific tumor‐induced leukocyte inhibition factor (LIF) production in laryngeal cancer patients has been investigated before and after the removal of adherent cells in order to evaluate the existence of a suppressor activity; 20 patients served as subject. The LIF production, after challenging the lymphocytes with 3MKC1 autologous tumor extracts, was significant in 12 patients and showed a further significant increase after the removal of adherent cells. In 3 patients with no previous significant LIF production, there was a conversion to significance when the adherent cells were removed. The other patients did not show any significant variation. These data seem to suggest the existence of a suppressor activity exerted by adherent cells in laryngeal cancer patients on LIF production.