Rakefet Czerninski

Oral cancer over four decades: epidemiology, trends, histology, and survival by anatomical sites

BACKGROUND Oral cancer is one of the few life-threatening oral diseases. The subtypes and different sites of oral cancer has different etiology epidemiology and survival rate. Prevalence of the various anatomical oral sites provided potential baseline for improvement of clinical approach. METHODS Incidence and survival rates were derived from the Israel National Cancer Registry and included all registered data between 1970 and 2006. Oral cancer included the lips, tongue, buccal mucosa, gums, vestibulum, floor of the mouth, and palate. RESULTS Most prevalent oral cancer subtype was squamous cell carcinoma (SCC) among men above the age of 55 years. Females had a higher incidence of SCC in lateral border of tongue, gums and buccal mucosa. Lymphoma and sarcoma were the most prevalent under the age of 20. Melanomas and metastatic disease revealed the lowest survival rate, while invasive or infiltrating basal cell carcinoma in the lips had the highest rate. The highest oral survival rate was for the lip, and the lowest was for the tongue and gums. CONCLUSIONS Early detection of oral cancer is important for all the medical health team. Decrease in lip carcinoma may be a result of occupational or awareness changes and should be studied. Non-epithelial tumors under the age of 20 should be considered as a differential diagnosis. A basic oral examination should be included in all routine medical examinations, with emphasis on high-risk patients and high-risk oral sites.

Targeting Mammalian Target of Rapamycin by Rapamycin Prevents Tumor Progression in an Oral-Specific Chemical Carcinogenesis Model

The increased molecular understanding of cancerous growth may now afford the opportunity to develop novel therapies targeting specific dysregulated molecular mechanisms contributing to the progression of each cancer type. In this regard, the aberrant activation of Akt/mammalian target of rapamycin (mTOR) pathway is a frequent event in head and neck squamous cell carcinomas (HNSCC), thus representing a potential molecular target for the treatment of HNSCC patients. The ability to translate this emerging body of information into effective therapeutic strategies, however, has been hampered by the limited availability of animal models for oral malignancies. Here, we show that the administration in the drinking water to mice of 4-nitroquinoline-1 oxide, a DNA adduct-forming agent that serves as a surrogate of tobacco exposure, leads to the progressive appearance of preneoplastic and tumoral lesions in the tongue and oral mucosa, with 100% incidence after only 16 weeks of carcinogen exposure. Remarkably, many of these lesions evolve spontaneously into highly malignant SCCs few weeks after 4-nitroquinoline-1 oxide withdrawal. In this model, we have observed that the activation of the Akt-mTOR biochemical route represents an early event, which is already detectable in dysplastic lesions. Furthermore, we show that the inhibition of mTOR by the chronic administration of rapamycin halts the malignant conversion of precancerous lesions and promotes the regression of advanced carcinogen-induced SCCs. Together, these findings support the contribution of the mTOR signaling pathway to HNSCC progression and provide a strong rationale for the early evaluation of mTOR inhibitors as a molecular-targeted strategy for HNSCC chemoprevention and treatment.

A clinical evaluation of a novel liposomal carrier for acyclovir in the topical treatment of recurrent herpes labialis

In a 2-armed, double-blind, randomized clinical study, the efficacy in the treatment of recurrent herpes labialis of 5% acyclovir in a novel liposomal carrier (ethosome) was evaluated in comparison with that of a commercial 5% acyclovir cream (Zovirax cream) and that of a drug-free vehicle. Data were based on 61 herpetic episodes in 40 subjects. In a crossover arm in which the 2 active preparations were compared, the time to crusting of lesions was significantly shorter (P < .025) with the ethosomal acyclovir (1.8 days) than with the cream (3.5 days). Time to loss of crust was also significantly shorter (4.2 vs 5.9 days; P < .05). In a parallel arm in which all 3 preparations were compared, the time to crusting with the ethosomal acyclovir (1.6 days) was significantly shorter than the time with the acyclovir cream (4.3 days; P < .02) and the time with the drug-free vehicle (4.8 days; P < .005); in this arm, the shorter time to loss of crust for the ethosome (3.5 days), in comparison with the times for the cream (6.4 days) and the drug-free vehicle (6.1 days), did not reach statistical significance. Approximately 30% of all episodes treated with the ethosome were clinically abortive; this compared with 10% of those treated with the cream or the drug-free vehicle. No adverse effects were reported, other than minor burning sensations at the application site that lasted a few seconds after application and were evenly distributed between the investigated preparations. This pilot study suggests the improved clinical efficacy of the new liposomal preparation in comparison with Zovirax cream in the treatment of recurrent herpes labialis.

Genetics/epigenetics of oral premalignancy: current status and future research*

Squamous cell carcinoma (SCC) of the oral and oropharyngeal region is the sixth most common malignancy in the world today. Despite numerous advances in treatment, long-term survival from this disease remains poor. Early detection can decrease both morbidity and mortality associated with this neoplasm. However, screening for potentially malignant disease is typically confounded by difficulty in discriminating between reactive/inflammatory lesions vs those lesions that are premalignant in nature. Furthermore, the histologic diagnosis of dysplasia can be subjective and is thus prone to a considerable range of interpretation. Similarly, no definitive, validated criteria exist for predicting which dysplastic lesions are most likely to progress to cancer over time. Given this state of science, the presence of dysplasia can only be used to indicate that an oral lesion may have an increased risk of malignant transformation. Molecular biomarkers capable of identifying the subset of lesions likely to progress to cancer are required to eliminate this clinical diagnostic dilemma. The purpose of this review is to assess the current state of knowledge regarding genetic/epigenetic alterations observed in oral mucosal premalignancy. In addition, recommendations for future research studies directed at defining the predictive capacity of specific biomarkers in this modeling are presented.

Chemical Carcinogenesis Models for Evaluating Molecular-Targeted Prevention and Treatment of Oral Cancer

Editors Note: Cancer Prevention Research is dedicated to presenting leading-edge work in cancer prevention-related models of carcinogenesis. This minireview details the evolution and development of a mouse model of 4-nitroquinoline-1 oxide (4NQO)-induced oral carcinogenesis, thus extending

Mental nerve neuropathy : patient characteristics and neurosensory changes

OBJECTIVES The objective of this study was to analyze the etiological factors and neurosensory signatures of patients attending with a primary complaint of numb chin. METHODS Charts of 27 patients referred to Hadassah School of Dental Medicine, Jerusalem, Israel, with a complaint of unilateral numbness or paresthesias of the chin were reviewed. Demographic and etiologic data and special tests, including imaging, that were prescribed as necessary for the treatment protocol were evaluated. The neurosensory evaluation protocol included assessment of detection thresholds to electrical stimulation (assessing large myelinated nerve fibers) and heat (assessing thin unmyelinated nerve fibers) in the mental and infraorbital nerves regions bilaterally. Data from 8 healthy, age and sex-matched subjects who underwent similar sensory testing served as the control group. RESULTS Invasive dental procedures (eg, extractions, implants) were the etiologic factor in 63% of the cases. Inflammatory pathoses (15%) (eg, periapical periodontitis or infection), and malignant lesions (22%) were identified as causative in the remaining patients. Frank nerve injury due to advanced malignant processes was characterized by significantly elevated heat and electrical thresholds (hyposensitivity). Inflammatory process was accompanied by reduced electrical detection thresholds (hypersensitivity). CONCLUSIONS This study concurs with previous studies that sensory hyposensitivity accompanies nerve damage. Accordingly, quantitative sensory testing may contribute to the diagnostic process of patients with mental nerve neuropathy. In this sample of patients, the most common cause for mental nerve neuropathy was dental treatment followed by malignant metastasis.

The role of CIP2A in oral squamous cell carcinoma

Commentary to: CIP2A expression and localization in oral carcinoma and dysplasia Joseph Katz, Andrew Jakymiw, Monet K. Ducksworth, Carol M. Stewart, Indraneel Bhattacharyya, Seunghee Cha and Edward K.L. Chan

Oral Lichen Planus and Dental Implants – A Retrospective Study

OBJECTIVES To examine whether oral lichen planus (OLP) affects the success rate of dental implants and if the manifestations of OLP are altered by implant-borne prostheses. MATERIALS AND METHODS OLP patients, treated in the oral medicine department, with (the study group) and without (control group) dental implants were included. Pocket depth, mobility, bleeding on probing, erythema, pain and radiolucency around the implants, as well as clinical findings and OLP symptoms were recorded. Follow-up ranged from 12-24 months. Ordinal variables and visual analog scale score were compared using the Mann-Whitney test. The significance of the trend within each of the groups was assed using the Friedman test. Categorical variables were compared using Pearson chi-squared test and Fishers exact test. RESULTS Fourteen patients in the study group with 1-15 implants per patient and 15 in the control group were included. No implant failures were recorded. Comparison between the clinical manifestations of OLP in both groups did not reveal any significant differences. CONCLUSIONS Success of implant rehabilitation among treated OLP patients does not seem to be different from the success rate in the general population. Nor does implant placement influence the disease manifestations.Objectives: To examine whether oral lichen planus (OLP) affects the success rate of dental implants and if the manifestations of OLP are altered by implant-borne prostheses. Materials and Methods: OLP patients, treated in the oral medicine department, with (the study group) and without (control group) dental implants were included. Pocket depth, mobility, bleeding on probing, erythema, pain and radiolucency around the implants, as well as clinical findings and OLP symptoms were recorded. Follow-up ranged from 12–24 months. Ordinal variables and visual analog scale score were compared using the Mann–Whitney test. The significance of the trend within each of the groups was assed using the Friedman test. Categorical variables were compared using Pearson chi-squared test and Fishers exact test. Results: Fourteen patients in the study group with 1–15 implants per patient and 15 in the control group were included. No implant failures were recorded. Comparison between the clinical manifestations of OLP in both groups did not reveal any significant differences. Conclusions: Success of implant rehabilitation among treated OLP patients does not seem to be different from the success rate in the general population. Nor does implant placement influence the disease manifestations.

Exceptional oral manifestations of amyloid light chain protein (AL) systemic amyloidosis.

Oral amyloidosis is usually presented in the tongue and is often associated with multiple myeloma. We present three patients with unusual oral manifestations of primary amyloidosis, which to the best of our knowledge have not been previously published. In two cases the oral manifestation was overt at the time of diagnosis and all cases ended in patient mortality. Since these oral manifestations can contribute to the diagnosis of systemic amyloidosis, clinicians should be made aware of them. Future research should assess the significance of oral manifestation as a prognostic indicator.

A 78-year-old woman with bilateral tongue necrosis

A 78-year-old woman presented to the emergency department complaining of a sore tongue. Her medical history included essential hypertension managed with atenolol, 100 mg/d, and enalapril, 5 mg/d, osteoporosis managed with calcium and vitamin D (with no past bisphosphonate treatment), and gastroesophageal reflux disease managed with omeprazole, 20 mg/d. Seventeen years before admission, she had suffered from ovarian carcinoma that was treated by chemotherapy and oophorectomy without therapeutic irradiation. She had no known hypersensitivities or drug allergies. The patient reported pain of the right head, neck, face, and shoulder (ranked 8 on a 0 to 10 visual analog scale, with “10” the most painful), especially while eating. She also reported fatigue, and visual blurring that had developed 2 months before, weight loss over the preceding 8 weeks (from 67 to 60 kg; a 10.4% reduction), and tongue pain of 4-weeks’ duration, which she rated as 10 on a 10-point scale. Ten days before presentation at the emergency room, she had undergone a complete blood count (CBC) and computed tomography (CT) of the head to rule out any underlying systemic conditions and space-occupying lesions. CBC and CT results at that time were normal, except for a mild anemia (hemoglo-