Roy Hod

Hyaluronan-grafted particle clusters loaded with Mitomycin C as selective nanovectors for primary head and neck cancers.

CD44, a well-documented cell surface receptor, is involved in cell proliferation, migration, signaling, adhesion, differentiation and angiogenesis, which are important properties for normal and cancerous cell function. We recently developed particle clusters coated with hyaluronan (termed gagomers; GAG), and showed that they can deliver the insoluble drug paclitaxel directly into CD44-over-expressing tumors in a mouse tumor model. Here, we tested primary head and neck cancers (HNC) and normal cells taken from the same patient, and found that although CD44 expression in both types of cells was high, GAGs bind only to the cancerous cells in a selective manner. We next formulated the anti cancer agent mitomycin C (MMC) in the GAGs. MMC-based chemoradiation is a potential treatment for HNC, however, due to patients toxicity, MMC is not part of the standard treatment of HNC. MMC encapsulation efficiency was about 70% with a half-life drug efflux of 1.2 ± 0.3 days. The Ex vivo study of the targeted MMC-GAG showed significant increase in the therapeutic effect on HNC cells (compared to free MMC), while it had no effect on normal cells taken from the same patient. These results demonstrate the specificity of the nanovectors towards head and neck cancers, which might be applicable as future therapy to many CD44-expressing tumors.

Outcome of oral tongue squamous cell carcinoma in patients with and without known risk factors.

BACKGROUND Tobacco smoking and high alcohol consumption are considered major risk factors of oral tongue squamous cell carcinoma. This study compared disease outcome between patients with and without known risk factors. METHODS Patients with oral tongue squamous cell carcinoma treated at two major medical centers from 1994 to 2008 were identified by cancer registry search. The medical files were reviewed for background-and-disease-related data, risk factors, and outcome. RESULTS The study sample consisted of 291 patients: 175 had a history of heavy tobacco smoking and alcohol abuse and 116 did not. Comparison of the patients without risk factors between the two centers yielded no differences in background features. Men accounted for 74% of the total patients with risk factors and comprised 77% of the risk-factor group. The risk-factor group was characterized by a significantly higher mean tumor grade (p=0.0001) and greater tumor depth of invasion (p=0.022) than the non-risk-factor group. The 5-year local and regional control rates were 85.3% and 74%, respectively, with no significant difference between the groups. The 5-year overall survival rate was 68% in the risk-factor group and 64% in the non-risk-factor group (p=NS). Separate analysis of patients aged <40 years at diagnosis revealed a worse overall (p=0.015) and disease-free survival (p=0.038) in those without risk factors. CONCLUSIONS The outcome of oral tongue carcinoma is similar in patients with and without risk factors. The worse prognosis in younger patients (<40 years) without risk factors suggests that the pathogenesis in these cases involves factors other than smoking and alcohol.

Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome.

Clin. Otolaryngol. 2010, 35, 307–312

ORIGINAL ARTICLE: Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome

Clin. Otolaryngol. 2010, 35, 307–312

Carcinoma of the oral tongue in patients younger than 30 years: Comparison with patients older than 60 years

OBJECTIVES The incidence of oral tongue squamous cell carcinoma is rising in young patients. This study evaluated the clinical, pathological, and prognostic characteristics of oral tongue squamous cell carcinoma in the under-30-year age group. MATERIALS AND METHODS The computerized database of the Department of Otolaryngology-Head and Neck Surgery of a tertiary, university-affiliated medical center was searched for all patients with oral tongue squamous cell carcinoma treated by glossectomy with curative intent in 1996-2012. Data were collected by chart review. RESULTS Of the 113 patients identified, 16 (14%) were aged ⩽30years at presentation and 62 (55%) >60years. Mean follow-up time was 30months. Comparison by age group revealed no sex predilection and no differences in histologic grade or rates of advanced T-stage, perineural and vascular invasion, or nodal extracapsular extension. Rates of node-positive disease were 75% in the younger group and 19% in the older group (p<0.001). Kaplan-Meier analysis yielded no between-group difference in disease-free or overall survival. Recurrence was documented in a similar proportion of patients (38% and 29.9%, respectively), but half the recurrences in the younger group were distant versus none in the older group (p=0.01) All younger patients with recurrent disease died within 16months of its appearance compared to 50% 3-year disease-specific survival in the older group. CONCLUSIONS Oral tongue squamous cell carcinoma is more advanced at presentation in younger than in older patients, with higher rates of regional metastases and distant failure. Recurrent disease is more aggressive, with a fatality rate of 100%.

Is Human Saliva an Indicator of the Adverse Health Effects of Using Mobile Phones

Increasing use of mobile phones creates growing concerns regarding harmful effects of radiofrequency nonionizing electromagnetic radiation on human tissues located close to the ear, where phones are commonly held for long periods of time. We studied 20 subjects in the mobile-phone group who had a mean duration of mobile phone use of 12.5 years (range 8-15) and a mean time use of 29.6 h per month (range 8-100). Deaf individuals served as controls. We compared salivary outcomes (secretion, oxidative damage indices, flow rate, and composition) between mobile phone users and nonusers. We report a significant increase in all salivary oxidative stress indices studied in mobile phone users. Salivary flow, total protein, albumin, and amylase activity were decreased in mobile phone users. These observations lead to the hypothesis that the use of mobile phones may cause oxidative stress and modify salivary function.

Effect of cochlear window fixation on air- and bone-conduction thresholds.

Hypothesis In the absence of patent cochlear windows, cochlear fluid inertia depends on the presence of a “third window” as a major component of the bone-conduction response. Background Studies have shown conflicting results regarding changes in air and bone conduction whenever, the round window, oval window, or both windows were occluded. Method The study was performed in a tertiary university-affiliated medical center. Auditory brain responses to clicks and 1-kHz tone bursts delivered by air and bone conduction were tested in 5 adult-size fat sand rats. The round window membrane (total, 7 ears) was sealed with Super Glue, and auditory brain response testing was repeated. Thereafter, the stapes footplate was firmly fixated, and auditory brain responses were recorded for a third time. Results Round-window fixation induced a significant increase in air-conduction thresholds to clicks from 36.4 ± 0.9 to 69.3 ± 4.1 dB SPL, with no significant change in bone-conduction thresholds. When the stapes footplate was immobilized as well, air conduction increased by another 20 dB, on average, with no change in bone conduction. A similar deterioration was seen in response to 1 kHz stimulus. Conclusion These findings support and complement earlier studies in the same animal model, suggesting that when the pressure outlet through the cochlear windows are abolished, still bone conduction displaces the cochlear partition probably because of a functioning “third window.”

Early tongue carcinoma: Analysis of failure

Failure rate of surgery for early tongue carcinoma remains high. We sought to identify patterns of failure and recurrence risk factors.

Squamous cell carcinoma of the oral tongue in patients over 75 years old

Background and aims: Squamous cell carcinoma (SCC) of the oral tongue is one of the most frequent head and neck cancers. The over-70-year age group is the fastest growing segment of the population. Age, however, is not considered a prognostic factor in oral tongue SCC. This study investigated the clinical and histopathological characteristics, disease course, and outcome of SCC of the oral tongue in patients over 75 years old compared with younger patients. Methods: We reviewed the files of 85 patients with histologically proven SCC of the oral tongue who were treated in our department in 1992-2007 and followed for a minimum of 2 years. Findings were compared between those aged 75 years or more and younger patients. Results: Twenty-eight patients (33%) were aged 75 to 94 years (average 80.5±4.5 yrs), including 14 who were over 80 years old, and 57 patients were aged 15-74 years (average 51.1±18.2 yrs). No statistically significant differences were found between the groups in clinical or histopathological characteristics or patient outcome. The 5-year disease-free survival rate was 65% for patients over 75 and 58% for younger patients. Corresponding rates for 5-year disease-specific survival were 69% and 70%. These differences were not statistically significant. Conclusions: Patients over 75 with oral tongue SCC should be managed like younger patients in terms of clinical staging and co-morbidities. They should be given a chance for treatment, as their prognosis is no different from that of younger patients.

ORIGINAL ARTICLE: Squamous cell carcinoma of the oral tongue in patients younger than 30 years: clinicopathologic features and outcome: Oral tongue SCC in under-30 age group

Clin. Otolaryngol. 2010, 35, 307–312