Ear Mite Removal in the Santa Catalina Island Fox (Urocyon littoralis catalinae): Controlling Risk Factors for Cancer Development.

Ear mites (Otodectes cynotis) and ear canal tumors are highly prevalent among federally endangered Island foxes (Urocyon littoralis catalinae) living on Santa Catalina Island off the coast of Southern California. Since studies began in the 1990s, nearly all foxes examined were found to be infected with ear mites, and ceruminous gland tumors (carcinomas and adenomas) were detected in approximately half of all foxes ≥ 4 years of age. We hypothesized that reduction of ear mite infection would reduce otitis externa and ceruminous gland hyperplasia, a risk factor for tumor development. In this study, we conducted a randomized field trial to assess the impact of acaricide treatment on ear mite prevalence and intensity of infection, otitis externa, ceruminous gland hyperplasia, and mite-specific IgG and IgE antibody levels. Treatment was highly effective at eliminating mites and reducing otitis externa and ceruminous gland hyperplasia, and mite-specific IgG antibody levels were significantly lower among uninfected foxes. Ceruminous gland hyperplasia increased in the chronically infected, untreated foxes during the six month study. Our results provide compelling evidence that acaricide treatment is an effective means of reducing ear mites, and that mite removal in turn reduces ear lesions and mite-specific IgG antibody levels in Santa Catalina Island foxes. This study has advanced our understanding of the underlying pathogenesis which results in ceruminous gland tumors, and has helped inform management decisions that impact species conservation.

Tumors and tumorlike lesions of dog and cat ears.

Bacterial and fungal otitis constitutes most ear disease in companion animals. However, a wide spectrum of infectious and noninfectious disease processes involve the structures of the ear and are of primary diagnostic consideration in cases of recurrent otitis or those refractive to traditional treatments. This article discusses several common to reasonably rare neoplastic and nonneoplastic space-occupying lesions of the external, middle, and internal ear. Although some conditions present as unique entities, many present similar to or concurrent with otitis, and should be considered in cases of clinically unresponsive otitis.

Nonmelanoma skin cancer of the ear: frequency, patients' knowledge, and photoprotection practices.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common cancer in the world. Information about NMSC on the ear and photoprotection practices of the ear is limited. OBJECTIVE: To determine the frequency of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) at precise anatomical sites, with a special focus on the ear. To evaluate dermatology patients' knowledge about skin cancer, photoprotection practices, and use of photoprotection on the ear. METHODS: At a dermatology practice in Fresno, California, a retrospective chart review of 643 patients diagnosed with NMSC was performed and categorized into detailed anatomical sites. An anonymous questionnaire was given to patients aged 18 and older seen at this private practice. RESULTS: One thousand three hundred eleven NMSCs were biopsied and histologically confirmed. Of these, 538 were BCC (41%) and 773 (59%) were SCC. Seven hundred sixty-five tumors (58.4%) were on the head. The ear was the fifth most common site for NMSC on the head. The male:female ratio for NMSC of the ear was 17:1. There were 269 survey responses; 72.8% used sunscreen, but only 26.0% of those who used sunscreen always apply it to their ears. CONCLUSION: Directed public education about the ear as a high-risk, common site for NMSC is needed. The authors have indicated no significant interest with commercial supporters.

Tolerability of high-dose topical tretinoin: the Veterans Affairs Topical Tretinoin Chemoprevention Trial.

BACKGROUND: Topical tretinoin is a medication commonly used for acne that has potential application in the long-term treatment of photodamaged skin. However, there are few published data regarding the tolerability of high-dose tretinoin with long-term use. OBJECTIVES: To assess the long-term tolerability of tretinoin 0.1% cream. METHODS: A randomized, multicentre, double-blind, controlled trial for chemoprevention of keratinocyte carcinomas (i.e. basal cell or squamous cell carcinomas) using topical tretinoin cream to the face and ears was conducted. All participants were veterans and had a history of two or more keratinocyte carcinomas over the previous 5 years. Participants were examined (by a study dermatologist) and interviewed every 6 months (for up to 5.5 years to May 2004). Treatment comprised tretinoin 0.1% cream or vehicle control cream once daily, then twice daily as tolerated. Participants were instructed to step down application frequency to once daily or less if twice daily was not tolerated. The main outcome measures were reported side-effects, frequency of cream application and attendance at study visits. Appropriate data were available for four of the six clinical sites of this trial. RESULTS: Data from 736 randomized participants (mean age 71 years; 97% men) from four clinical sites were analysed. The tretinoin group more commonly reported one or more side-effects at the 6-month follow-up than the control group (61% vs. 42%, P < 0.0001). Side-effects decreased over time in both groups, but to a greater extent in the tretinoin group, and the difference became nonsignificant at 30 months. Burning was the most common side-effect (39% tretinoin vs. 17% control, P < 0.0001). There was no difference in severity of side-effects among those affected. Of the participants who reported burning in either group, most reported mild burning; only 11% of those with burning in the tretinoin group reported it as severe (mild 62% tretinoin vs. 70% placebo; severe 11% vs. 5%; P = 0.4). Itching (24% vs. 16%, P = 0.01) and other local cutaneous reactions (12% vs. 6%, P = 0.01) were also more commonly reported by the tretinoin group at 6 months. There was no difference in numbness (2% vs. 2%, P = 0.9). Participants in the tretinoin group were less likely to apply cream twice daily at 6 months (29% vs. 43%, P = 0.0002). This difference persisted over the entire duration of follow-up. There was little difference between groups in attendance at study visits or completion of telephone interviews (92% vs. 95%, P = 0.06). No unexpected adverse events were reported. CONCLUSIONS: Overall, the tolerability level of topical tretinoin was high in this study population, with almost 40% of the tretinoin group reporting no side-effects, and the majority (67%) tolerating at least once-daily dosing at 6-month follow-up. High-dose topical tretinoin is feasible for long-term use in this population.

Association between statin use and risk for keratinocyte carcinoma in the veterans affairs topical tretinoin chemoprevention trial.

BACKGROUND: Recent evidence suggests that statins may prevent cancer. OBJECTIVE: To quantify the association between statin use and the occurrence of keratinocyte carcinoma in high-risk veterans. DESIGN: Cohort study. SETTING: 6 Veterans Affairs medical centers. PARTICIPANTS: 1037 participants of the Veterans Affairs Topical Tretinoin Chemoprevention Trial, a randomized, multicenter, double-blind, vehicle-controlled trial of topical tretinoin, 0.1%, for prevention of keratinocyte carcinoma conducted from November 1998 to November 2004. MEASUREMENTS: Time to first occurrence of keratinocyte carcinoma on the face or ears. Participants using a statin at randomization, according to the Veterans Affairs Pharmacy Benefits Management database, were considered exposed. Study dermatologists conducted physical examinations at baseline and every 6 months during follow-up. The association between statin use at randomization and the outcome was evaluated by using propensity score matching (n = 608) and Cox proportional hazards regression (n = 1037). RESULTS: Among the 1037 participants, 37% used a statin at randomization (n = 397) for a median duration of at least 900 days over a median follow-up of 3.5 years. In the propensity score-matched analysis, statin use at randomization was not associated with keratinocyte carcinoma (rate ratio, 0.92 [95% CI, 0.73 to 1.16]), a finding that was consistent with the estimates derived from the Cox proportional hazards regression (rate ratio, 0.84 [CI, 0.70 to 1.02]). LIMITATIONS: The extent of residual confounding is unknown, and the confidence bounds around the measures of association were wide. These data may not be generalizable to lower-risk populations. CONCLUSION: These data show no conclusive or consistent relationship between long-term statin use and risk for keratinocyte carcinoma.

Long-term control of vestibular schwannoma after a translabyrinthine complete removal.

OBJECTIVE: The goal of this study was to determine the rate of recurrent vestibular schwannoma after a total removal via the translabyrinthine approach. PATIENTS: Between 1973 and 1995, 346 patients were operated on by a translabyrinthine approach. Ninety-one patients were included in a retrospective study for follow-up of 5 years or longer. RESULTS: The mean follow-up period for magnetic resonance imaging (MRI) examination was obtained after mean of 11 years in 91 patients. None of the 91 patients experienced a recurrent vestibular schwannoma on MRI. CONCLUSION: The translabyrinthine approach is a safe procedure for total definitive removal of a vestibular schwannoma and permitted the absence of tumoral recurrence in our series of 91 patients. A single gadolinium-enhanced MRI scan 5 years after surgery is advised in case of total removal. In case of any doubt about the quality of the tumoral removal, a proposed MRI follow-up schedule within 2 years and 5 years of surgery is an initial baseline pattern, and possibly thereafter repeated MRI examinations on clinical grounds.

Kaposiform hemangioendothelioma of the external auditory canal in an adult.

BACKGROUND: Kaposiform hemangioendothelioma is an uncommon vascular tumor initially reported to occur exclusively in children. METHODS: The presentation, pathologic evaluation, and management of an unusual case of kaposiform hemangioendothelioma is presented and discussed. RESULTS: A 27-year-old HIV-negative man was initially seen with a reddish nodule located in the outer third of the external auditory canal. Histologically, the tumor was composed of spindle-shaped cells arranged in short fascicles associated with small endothelial-like vascular spaces, similar in appearance to Kaposi's sarcoma. The lesion was locally excised but recurred 1 month later; then radiation therapy was performed. The patient remains well at 5-year follow-up. CONCLUSIONS: Recognition of kaposiform hemangioendothelioma is important to avoid possible confusion with a variety of vascular neoplasms with different biologic potential. This case presented some diagnostic difficulty because of the age of the patient and the unusual location of the lesion and had to be mainly distinguished from Kaposi's sarcoma.

Distant metastases from ear and temporal bone cancer.

Cancers of the temporal bone are rare. Cervical metastases occur in approximately 10% of cases and are much more likely once disease extends beyond the confines of the temporal bone. Nonlymphatic spread of squamous cell carcinoma is usually a late event resulting in metastatic deposits in the lung, bone, liver and brain. This chapter discusses detection of distant metastases and provides a recommended schedule for interval patient evaluation.

Inhibitory effects of freeze-dried milk fermented by selected Lactobacillus bulgaricus strains on carcinogenesis induced by 1,2-dimethylhydrazine in rats and by diethylnitrosamine in hamsters.

Fermented milk products might be used for cancer chemoprevention due to their putative anticarcinogenic and antitumor activities. The diet was supplemented with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B 144 (product FFM.B 144) added throughout the experiment at doses of 1.3 g and 2.5 g per rat, 5 times a week starting 3 weeks before the first carcinogen injection. This treatment significantly inhibited, by 26.2-28.6% and by 34.2%, the total intestinal carcinogenesis induced by 1,2-dimethylhydrazine (DMH, 21 mg/kg, s.c., once per week for 20 weeks) in male and female BD6 rats, respectively. FFM.B144 decreased the tumor incidence and multiplicity in large bowel, caecum, and duodenum. Protective effects were better expressed in female animals, with exception of that observed in duodenum. Supplementation of diet with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B5 (product FFM.B5) inhibited DMH-induced carcinogenesis only in the large bowel, but had no significant protective effect when all intestinal tumors were taken into account. However, both freeze-dried products favorably shifted the differentiation of large bowel tumors by increasing the proportion of benign and highly differentiated malignant tumors and decreasing in parallel the number of poorly differentiated carcinomas without influencing the tumor size. A lower number of cases with visible mesenterial metastasis was also observed in FFM-treated rats. In addition, both FFM.B 144 and FFM.B5 significantly inhibited, by 26-33%, the induction in the same rats of ear-duct tumors. FFM.B144 but not FFM.B5 was also effective in inhibiting the tracheal carcinogenesis induced in Syrian golden hamsters by diethylnitrosamine (DEN, 100 mg/kg, two s.c. injections), the protective effect being better expressed in female animals. The anticarcinogenic potential of some fermented milk products might be exploited in chemoprevention of cancer in humans.

Local hypertrophic/hyperplastic changes of keratinizing squamous epithelium of pinna induced by concanavalin A and other immunomodulators in mice.

Intradermal administration of concanavalin A, a potent T-cell mitogen, into an ear lap resulted in activation of chondrogenesis and stimulation of epidermis proliferation. This proliferation is sometimes invasive in character (pearls and epidermal nests form in the underlying connective tissue) but never turns into true cancerous lesions. This reaction can be delayed, but not prevented, by the prostaglandin inhibitor indomethacin. Stimulation of epidermis proliferation was also caused by administration of other immunomodulators, such as carrageenan type IV, Moloney sarcoma development, and rarely in the course of GvHr, but to much lesser degree than with concanavalin A. It is suggested that the same growth factors, which are mediators of local chondrocyte stimulation, are also mediators of keratinocyte activation.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate-caused tumor promotion in benzo[a]pyrene-initiated CD-1 mouse skin by geniposide.

The effects of topical application of geniposide on 12-o-tetradecanoylphorbol-13-acetate(TPA)-induced promotion of skin tumors, hyperplasia, ornithine decarboxylase (ODC) and inflammation were evaluated in female CD-1 mice. Topical application of geniposide (0.2 to 1.0 mumol) with TPA (15 nmol) twice weekly for 20 weeks to mice previously initiated with benzo[a]pyrene (B[a]P) inhibited the number of TPA-induced tumor per mouse by 84 or 89%, respectively. Pre-application of the same amount of geniposide also afforded significant protection against TPA-induced hyperplasia in the ear skin. Topical application of geniposide inhibited tumor promoter-caused induction of epidermal ODC activity by TPA (5 nmol). The topical application of geniposide (0.2 or 1.0 mumol) inhibited TPA-induced edema of mouse ears by 41 or 43%, respectively. Pretreatment of mouse skin with various amounts of geniposide caused inhibition of hydrogen peroxide (H2O2) and myeloperoxidase (MPO) formation by TPA. These results indicate that geniposide possesses potential as a cancer chemopreventive agent against tumor promotion.

Effects of aminothiols in 2-acetylaminofluorene-treated rats. I. Damage and repair of liver DNA, hyperplastic foci, and Zymbal gland tumors.

One hundred and seventy-nine male Wistar rats were divided into 6 groups and fed with a standard diet supplemented with 0.05% 2-acetylaminofluorene (2AAF) and/or 0.1% glutathione (GSH) or N-acetyl-L-cysteine (NAC). Each treatment cycle lasted for 3 weeks, followed by 1 week of standard meal. After 4 cycles, survival was 100% in the 3 control groups, and 86.0, 100 and 91.7%, in the groups receiving 2AAF, 2AAF plus GSH, and 2AAF plus NAC, respectively. After an additional 4-8 weeks, all the 5 surviving rats fed with 2AAF exhibited deforming ear tumors, which on histological examination were classified as sebaceous squamocellular carcinomas of Zymbal glands. No such tumors were detectable in control groups, nor in the 16 surviving rats fed with 2AAF plus GSH or NAC. In the liver, 2AAF produced significant DNA damage at the 3rd week of each cycle, which was partially repaired during the week of standard meal feeding. Moreover, 2AAF determined the appearance of gamma-glutamyl transpeptidase-positive foci, which tended to increase with time both in number and in size. GSH and NAC exerted similar protective effects on these phenomena, but only at early stages of the experimental model used.

Inhibition of N-2-fluorenylacetamide-induced mammary tumorigenesis in rats by dietary polybrominated biphenyls.

Female SD rats were maintained for approximately 1 year on diets containing 300 ppm N-2-fluorenylacetamide (2-FAA), 50 ppm polybrominated biphenyls (PBB), or a combination of these chemicals (PBB + 2-FAA). Ingestion of 2-FAA significantly reduced the average survival time of the rats; this effect was virtually blocked by the simultaneous ingestion of PBB. Simultaneous ingestion of PBB also significantly reduced the overall incidence of 2-FAA-induced tumors during the examination period. The lower incidence of tumorigenesis was accompanied by an increase in the latency time for tumor induction; tumors were found in 100% of the animals given 2-FAA after 29 weeks of carcinogen ingestion, whereas only 50% of the PBB + 2-FAA-fed animals had tumors at the end of the experiment (53 wk of carcinogen ingestion). PBB significantly reduced the incidence of 2-FAA-induced tumors at nonhepatic locations (mammary gland and ear duct) but did not affect the incidence of hepatic tumors to a statistically significant extent. PBB ingestion did not significantly increase the incidence of tumors when compared with controls; 1 tumor was found in 1 of 12 rats fed 50 ppm PBB for 57 weeks, and no tumors were detected in 8 controls.