tretinoin and Ear-Neoplasms

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Cranial Irradiation; Daunorubicin; Ear Neoplasms; Humans; Injections, Spinal; Leukemia, Myelomonocytic, Acute; Male; Oxides; Radiography; Remission Induction; Sarcoma, Myeloid; Tretinoin

A 41-year-old man was given a diagnosis with of acute promyelocytic leukemia (APL) in August 1994. A chromosome analysis showed 46, XY, t(15; 17) and 47, XY, idem, +8 at that time. Because initial induction chemotherapy (BHAC-DMP) has not been successful, the patient was given 45 mg/m2 of all-trans retinoic acid (ATRA) and achieved complete remission (CR) after 26 days on this regimen. Following intensified chemotherapy, he received an autologous peripheral blood stem cell transplant (PBSCT) with high-dose busulfan and cyclophosphamide in April 1995. Competitive RT-PCR for PML-RAR alpha mRNA did not find any of APL cells in the collected stem-cell fraction. Although the patient remained in CR without therapy, a myeloblastoma was found in his left external auditory canal in August 1996. Recurrence in bone marrow, moreover, was discovered the following month. A chromosome analysis of bone marrow cells showed 47, XY, t(15; 17), +8 at this time. Thus, the extramedullary relapse developed after autologous PBSCT. This case provides information linking ATRA to the development of extramedullary relapse in patients with APL.

Topics: Adult; Antineoplastic Agents; Combined Modality Therapy; Ear Canal; Ear Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Promyelocytic, Acute; Male; Recurrence; Tretinoin

Recent evidence suggests that statins may prevent cancer.. To quantify the association between statin use and the occurrence of keratinocyte carcinoma in high-risk veterans.. Cohort study.. 6 Veterans Affairs medical centers.. 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.. 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).. 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]).. 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.. These data show no conclusive or consistent relationship between long-term statin use and risk for keratinocyte carcinoma.

Topics: Administration, Topical; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Confounding Factors, Epidemiologic; Double-Blind Method; Drug Administration Schedule; Ear Neoplasms; Facial Neoplasms; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Risk Factors; Skin Neoplasms; Tretinoin

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.. To assess the long-term tolerability of tretinoin 0.1% cream.. 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.. 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.. 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.

Topics: Administration, Topical; Aged; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Ear Neoplasms; Ear, External; Facial Neoplasms; Female; Humans; Male; Skin Neoplasms; Time Factors; Treatment Outcome; Tretinoin; Veterans

We sought to determine the interobserver reliability of the histopathologic diagnosis of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) (keratinocyte carcinomas) in the setting of a Department of Veteran Affairs multicenter chemoprevention study.. Interobserver concordance was assessed by blinded review of histopathologic slides by study dermatopathologists.. Overall interobserver agreement between the two dermatopathogists was kappa = 0.69 (95% confidence interval [CI] 0.67-0.69). The dermatopathologists' interobserver agreement was highest for basal cell carcinoma at kappa = 0.88 (95% CI 0.84-0.91) and for a diagnostic category in the SCC-actinic keratosis spectrum at kappa = 0.80 (95% CI 0.73-0.86). The largest disagreements between the two reference dermatopathologists were regarding the categories of invasive SCC at kappa = 0.62 (95% CI 0.52-0.72), SCC in situ at kappa = 0.42 (95% CI 0.29-0.56), and actinic keratosis at kappa = 0.51 (95% CI 0.40-0.62). Agreement between the local pathologists and central reference dermatopathologists were similar to the agreement between the central dermatopathologists. The morphea subtype of basal cell carcinoma was the only reliably diagnosed subtype (kappa = 0.79, 95% CI 0.51-1.00), and tumor depth was reliably measured.. A limitation of this study was the use of only two reference dermatopathologists.. Because of the impact on physician decision making and patient care, researchers and clinicians need to be aware of reliability of histopathology results, particularly pertaining to the SCC and actinic keratosis spectrum.

Topics: Biopsy; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Ear Neoplasms; Facial Neoplasms; Humans; Keratinocytes; Keratolytic Agents; Keratosis; Neoplasm Invasiveness; Observer Variation; Photosensitivity Disorders; Reproducibility of Results; Tretinoin

Topics: Antineoplastic Agents; Arsenic Trioxide; Arsenicals; Child; Ear Canal; Ear Neoplasms; Female; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Oxides; Tretinoin

Topics: Adult; Antineoplastic Agents; Bone Marrow; Ear Neoplasms; Female; Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Promyelocytic, Acute; Recurrence; Sarcoma, Myeloid; Transplantation, Homologous; Tretinoin

A 43-year-old man was admitted because of gingival bleeding. A diagnosis of acute promyelocytic leukemia (APL) was made. He was given combination chemotherapy including all-trans retinoic acid (ATRA). During the myelosuppression stage, the patient developed Fournier's gangrene of the scrotum. He achieved complete remission and underwent a hemicastration procedure. Seven months later, bilateral external ear tumors developed. Biopsy specimens of the tumors revealed infiltration of APL cells. A second remission was obtained by chemotherapy including ATRA. However, bilateral ear tumors developed again 5 months later despite indications of normal marrow without proliferation of leukemic blasts. Irradiation successfully reduced the ear tumors, but the patient died of cerebral hemorrhage from a left frontal extramedullary tumor. This was a rare case of APL accompanied by Fournier's gangrene of the scrotum during ATRA treatment, and by extramedullary tumors of the external ear and brain during leukemic relapse.

Topics: Adult; Ear Neoplasms; Fournier Gangrene; Genital Diseases, Male; Humans; Leukemia, Promyelocytic, Acute; Male; Neoplasms, Second Primary; Scrotum; Tretinoin

After ten times monthly, subcutaneous, injections of 30 mg/kg 1,2-dimethylhydrazine (DMH) to Sprague-Dawley-rats, malignant tumors were found in approximately 90% of the animals after a mean induction period of approximately 330 days. Injections were started on the 2nd day of life and maintained during 10 months. 72% of the tumors induced were formed in the colon, 17% were squamous cell carcinomas of the ear duct, adenosarcomas of the kidney and hepatocellular carcinomas were found in 13 and 11% of the animals, respectively. Additional treatment with immunodepressive (cyclophosphamide, methotrexat, hydrocortisone) and immunostimulating substances (BCG, albumin, vitamin A-acid) as well as an enzyme-stimulating agent (Luminal) did not alter incidences and induction periods of tumors. After application of a vegetarian diet, the rate of liver and kidney tumors was diminished significantly and induction periods of intestinal and ear duct tumors increased.

Topics: Animals; BCG Vaccine; Diet; Dimethylhydrazines; Ear Neoplasms; Female; Hydrazines; Immunosuppressive Agents; Intestinal Neoplasms; Kidney Neoplasms; Liver Neoplasms; Male; Neoplasms, Experimental; Phenobarbital; Rats; Serum Albumin; Tretinoin