Head and neck malignancy statistics at Kitasato University

We analyzed and reported on those patients with head and neck (H&N) malignancies who had visited our university within the last 30 years. The number of H&N patients registered per year has gradually increased with time and approximately 120 new patients have been registered annually in recent years. Age-adjusted morbidity has also increased gradually, from 7.06 to 10.55 per 100,000 citizens, in recent years. The population of Sagamihara city has gradually increased in parallel over the same period. Cancers of the pharynx, larynx and oral cavity are the three major H&N tumors. Squamous cell carcinoma was the most commonly seen pathological diagnosis, followed by malignant lymphoma. The 5-year crude survival rate for all patients was 50%. It is suggested that improving the survival rates of cancers of the oral cavity, nasal cavity and paranasal sinuses should be a prerequisite, in order to diminish H&N tumor deaths in Japan. A satisfactory survival rate for cancer of the paranasal sinuses has been achieved at Kitasato University and it is hoped that our modality will further prevail in the near future. Cancer of the oral cavity is visible and can be detected by a simple clinical examination. As H&N surgeons it is necessary to educate all physicians as to the importance of early detection of H&N tumors. We also need to encourage the public to reduce smoking and drinking in order to prevent a further increase in the number of H&N patients. Our assertions are based on the fact that the number of H&N patients in 2050 is estimated to be three times greater than that at present due to the increase in the population of elderly people (assuming the morbidity rate remains constant). Key words: alcohol, cancer trends, morbidity, predictions, tobacco.     

Non-steroidal Anti-inflammatory Drugs Induce Apoptosis in Head and Neck Cancer Cell Lines

Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit tumorigenesis in colorectal cancer due to the induction of apoptosis. Disturbances of cellular pathways ultimately leading to apoptosis may contribute to the process of neoplastic transformation and immortalization. In this study we wanted to determine the influence of different NSAIDs (indomethacin, ibuprofen and sodium salicylate) and hydrocortisone on Bcl-2 expression and the apoptotic behavior of head and neck tumor cell lines and normal oral keratinocytes. Bcl-2 expression was determined by monoclonal antibody staining and fluorescence-activated cell-sorting measurement. Apoptotic cells were visualized with a epifluorescence microscope after staining with CytoDeath M30 antibody. Indomethacin (1 mM) and ibuprofen (1 mM) significantly reduced Bcl-2 expression in the cancer cell lines tested and might be thought responsible for the observed increase in apoptosis. At all concentrations tested the influence of sodium salicylate and hydrocortisone on Bcl-2 expression was not significant. In contrast, the NSAIDs tested had only a minor influence on normal oral keratinocytes. Our results demonstrate a significant reduction in growth and an increase in apoptosis, possibly due to a reduction in Bcl-2 expression, after exposure to indomethacin and ibuprofen in the head and neck cancer cell lines tested.     

Comparative Evaluation of Chemoimmunoradiotherapy and Chemoradiotherapy in the Management of Advanced Head and Neck Cancer

50 patients of advanced squamous cell carcinoma of the head and neck were randomised cither to receive chemotherapy followed by radiation therapy or chemoimmunotherapy followed by radiotherapy. In the chemoimmunotherapy arm, the patients received recombinant interferon alpha 2b 3 M.U. subcutaneously, thrice a week on alterante days for 5 weeks from Day 1, Cisplatinum 70 mg/ m² on Day 1 and 21, and 5 — flurouracil 1000mg/m² on Day 1, 2, 3 and Day 21, 22, 23, followed by from Dav 36, radiotherapy'by Co bait 60 to a tumour dose of 65 Gy in 30 # over 6 weeks. In the control arm, patiens received Cisplatitnum 70 mg/ m² on Day 1 and Day 21, 5 flurouracil 1000 mg/ m² on Dav 1, 2, 3 and Day 21, 22, 23 followed by radiotherapy by Cobalt 60 to a tumour dose of 65 Gy in 30 # over 6 weeks from Day 36. Only Grade II and III toxicity was observed in the two arms which were manageable Patients treated with chemoimmunotherapy followed by radiotherapy showed 60% complete response, 20% partial response and 12% no change/ progressive disease; while the patients on the control arm treated with chemotherapy and radiotherapy showed 12% complete response 44% Partial response and 32% no change“ progressive disease. This trial concludes that chemoimmunotherapy followed by radiotherapy is an excellent alternative therapeutic strategy for the management of advanced head and neck cancers with manageable toxicity.     

The epidemiology of malignant neoplasms of the nasal cavities,the paranasal sinuses and the middle ear in Canada

Summary Canadian patterns of morbidity and mortality from malignancies of the nasal cavities, the paranasal sinuses and the middle ear for the periods 1970–1980 and 1970–1984 have been examined. Age-standardized morbidity rates have not changed significantly during 1970–1980 for either males (P=0.65) or females (P=0.96). Analysis of age-specific morbidity rates revealed that rates of change for male rates have also remained stable during this period for all age groups studied (P>0.29). For females, rates of change for seven of eight age groups examined also failed to achieve statistical significance (P>0.30). However, rates for females aged 45–54 have shown an increase of 0.35 additional new cases per 1,000,000 population per year. This finding is of borderline significance (P=0.051). In contrast, age-standardied mortality rates have declined significantly during 1970–1984 by, on average, 0.08 and 0.07 fewer deaths per 1,000,000 population per year in males and females respectively. Analysis of age-specific mortality rates reveals that the declines in mortality are attributable to significant reductions in age-specific rates for males aged 65–74 and 85+ and females aged 0–24, 55–64, and 85+. In these groups rates have declined by as much as 4.1 fewer deaths per 1,000,000 population per year (P<0.045).     

Atypical Fibroxanthoma in Head and Neck

Atypical fibroxanthoma is a pleomorphic spindle cell tumor of the dermis and it''s been known to be a benign lesion clinically in spite of malignant histologic features. But recurrence is estimated at between 2%-20% and metastasis has been reported. We are about to describe a 70-year-old man with the lesion developed on the left infra-auricular area. The lesion was located superficially and is composed of compact pleomorphic spindle cells and several bizarre multinucleated giant cells. The patient was treated with wide excision. We would like to discuss about this case with a review of literatures.     

Statistics in scientific articles published in the European Annals of Otorhinolaryngology Head & Neck Diseases

ObjectivesTo evaluate biostatistics in scientific articles published in the European Annals of Otorhinolaryngology Head & Neck Diseases.Materials and methodsRetrospective analysis of 76 scientific articles published in 2018 and 2019. The main goal was to describe the percentage of articles using biostatistics and to explore for potential associations with the article's main characteristics. Secondary goals were, within the group of articles using statistical tests, to describe the type of statistics used, the assessment of normality in case of comparison of mean values, the p-value threshold for significance, the use of confidence intervals, and power analysis.ResultsStatistics were used in 73.7% of articles, without any significant association with main characteristics. Within the group of articles using statistics, the tests used were parametric, non-parametric and not specified in 77.7%, 51.4% and 1.8% of cases, respectively. Normality was checked in 14.2% of article using parametric tests to evaluate mean values. The p-value significance threshold was set at .05, .01, .005 levels and not defined in 60.7%, 1.8%, 1.8% and 35.7% of articles, respectively, while confidence intervals and power analyses were documented in 10.7% and 5.3%, respectively.ConclusionThis article underlines the need for better use of statistics in the European Annals of Otorhinolaryngology Head & Neck Diseases, to improve the quality of scientific articles published in the organ of written expression of the French and International French-speaking Societies of Otorhinolaryngology, and to support the ongoing move toward better medical science.     

Glutathione S‐Transferase π in Squamous Cell Carcinoma of the Head and Neck

Objectives/Hypothesis Oxidative/reductive (redox) DNA damage from radical species such as nitric oxide (NO·) are increasingly being implicated in the development of cancer. Moreover, redox‐protective cellular mechanisms, such as glutathione S‐transferase, may determine cellular susceptibility to this redox‐mediated damage. Methods Formalin‐fixed, paraffin‐embedded tissue samples of 11 normal oral mucosa, 15 reactive/dysplastic lesions, and 131 head and neck squamous cell carcinomas (HNSCCs) were immunohistochemically stained using a polyclonal antibody against glutathione S‐transferase π (GST‐π). Slides were reviewed in a blinded fashion by the study pathologist (g.k.h.) and intensity was graded, noting the pattern of immunostaining. These staining characteristics were compared with those obtained using monoclonal antibodies against endothelial constitutive nitric oxide synthase (ecNOS) and nitrotyrosine, a marker of NO·'s pathological nitrosylation of proteins on serial sections of the same tissue. Patient charts were reviewed and clinical data collected. Results The expression of GST‐π was significantly increased in reactive/dysplastic and HNSCC samples compared with normal squamous mucosa (P < .001 for both). Furthermore, among the carcinomas the expression of GST‐π was significantly increased in higher‐grade lesions (P < .02). The expression of GST‐π correlated highly with the expression of ecNOS and nitrotyrosine (P < .0001 for both). Conclusions These findings demonstrate that GST‐π is upregulated in conjunction with the NO·‐generating ecNOS isoform and implicate GST‐π in protecting HNSCC from the cytotoxic effects of high concentrations of NO· found in the tumor bed.     

Gene Therapy for Head and Neck Cancer

Objectives/Hypothesis New treatment methods are needed for head and neck cancer to improve survival without increasing morbidity. Gene therapy is a potential method of improving patient outcome. Progress in gene therapy for cancer is reviewed with emphasis on the limitations of vector technology and treatment strategies. Given the current technological vector limitations in transmitting the therapeutic genes, treatments that require the fewest number of cells to be altered by the new gene are optimal. Therefore an immune‐based gene therapy strategy was selected in which the tumors were transfected with the gene for an alloantigen, human leukocyte antigen (HLA)–B7, a class I major histocompatibility complex (MHC). This would restore an antigen presentation mechanism in the tumor to induce an antitumor response. This gene therapy strategy was tested in patients with advanced, unresectable head and neck cancer. Study Design Prospective trial. Methods Twenty patients with advanced head and neck cancer who had failed conventional therapy and did not e‐press HLA‐B7 were treated with gene therapy using a lipid vector by direct intratumoral injection. The gene therapy product contained the HLA‐B7 gene and the β2‐microglobulin gene, which permits complete e‐pression of the class I MHC at the cell surface. Patients were assessed for any adverse effects, for changes in tumor size, for time to disease progression, and for survival. Biopsy specimens were assessed for pathological response, HLA‐B7 e‐pression, apoptosis, cellular proliferation, CD‐8 cells, granzyme, and p53 status. Results There were no adverse effects from the gene therapy. At 16 weeks after beginning gene therapy, four patients had a partial response and two patients had stable disease. Two of the tumors completely responded clinically, but tumor was still seen on pathological examination. The time to disease progression in the responding patients was 20 to 80 weeks. The median survival in patients who completed gene therapy was 54 weeks, compared with 21 weeks in patients whose tumors progressed after the first cycle of treatment. One patient survived for 106 weeks without any additional therapy. HLA‐B7 was demonstrated in the treated tumors, and increased apoptosis was seen in the responding tumors. Conclusion Significant advances have been made in the field of gene therapy for cancer. Alloantigen gene therapy has had efficacy in the treatment of cancer and can induce tumor responses in head and neck tumors. Alloantigen gene therapy has significant potential as an adjunctive treatment of head and neck cancer.     

Electroporation Therapy in Head and Neck Cancer

Objective—To prove the efficacy of electroporation therapy (EPT) in T1 and T2 squamous cell cancers of the oral cavity and oropharynx. Material and Methods—Twelve patients were treated with EPT within the framework of a European trial. Tumors were infiltrated with a bleomycin solution and subsequently treated with EPT. Four weeks after treatment the necrotic mass at the site of the former tumor was resected with save margins and accurately examined histologically. Results—Whereas 10 specimens were completely free of cancer cells, 2 cases showed viable tumor cells. Conclusion—EPT has the potential to serve as an interesting alternative in the treatment of head and neck cancer.