tretinoin and Carcinoma--Basal-Cell

Topics: Adult; Benzoates; Bowen's Disease; Carcinoma, Basal Cell; Child; Etretinate; Female; Humans; Isotretinoin; Male; Precancerous Conditions; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Topics: Administration, Topical; Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Antineoplastic Agents; Carcinoma, Basal Cell; Chemoprevention; Female; Fluorouracil; Hospitals, Veterans; Humans; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Skin Neoplasms; Tretinoin

Invasive squamous cell carcinoma (SCC) of the skin is one of the most common cancers in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. We sought to determine the risk factors for invasive SCC on the face or ears in a high-risk population comprising 1,131 veterans in the Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial. Participants were required to have been diagnosed with at least two keratinocyte carcinomas (KCs) in the 5 years prior to enrollment. The median duration of follow-up was 3.7 years. Twenty-three percent of the participants developed a new invasive SCC, and the cumulative risk of invasive SCC was 30% at 5 years. The following factors independently predicted for new invasive SCCs: number of invasive SCCs and number of in situ SCCs in the 5 years prior to enrollment, actinic keratoses count at enrollment, a history of ever use of topical 5-fluorouracil, and total occupational time spent outdoors. In contrast, the use of angiotensin-convering enzyme inhibitors or angiotensin receptor blockers during the study and a history of warts anywhere on the body were found to protect against new invasive SCCs. These independent predictors remained the same for all SCCs (invasive and in situ combined). The number of basal cell carcinomas in the 5 years prior to enrollment, sunburns, sun sensitivity, and recreational sun exposure were not associated with new SCCs. These findings identify key risk factors for additional SCCs in patients with multiple prior KCs, and suggest that a history of warts may be associated with reduced SCC risk.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Risk Factors; Skin Neoplasms; Sunburn; Sunscreening Agents; Tretinoin; Veterans; Warts

Glucorticosteroids (GC) are potent anti-inflammatory medications with immunosuppressive property. Few retrospective studies have reported the increased risk of development of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) associated with GC use.. We aimed to assess the effect of oral GC use on the risk of BCC and SCC using prospective data.. We analysed data from the Veterans Affairs Topical Tretinoin Chemoprevention Trial, which followed up patients from 1998 to 2004. Exposure to oral GCs was defined as (1) use of any oral GCs at any point during follow-up and (2) use of GCs for a month or longer. Outcome was occurrence of new BCC or SCC. Cox proportional hazard models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).. Among the 1051 study participants, 148 patients (14%) had prednisone prescription filled during study period, and 63 (6%) used prednisone for over a month. A total of 472 patients (45%) developed at least one BCC during study: 394 (44%) among non-users of prednisone and 78 (53%) among any time users. The total number of new SCC was 309 (29%): 258 (29%) among non-users of prednisone and 51 (34%) among users. Among any time prednisone users, the adjusted HR was 1.11 (95% CI, 0.87-1.42) for BCC, and 1.05 (95% CI, 0.76-1.45) for SCC. Among those who used prednisone for 30 or more days, the HR was 1.26 (95% CI, 0.90-1.78) for BCC, and 1.03 (95% CI, 0.66-1.60) for SCC.. This study does not support the existence of association between use of oral GCs and risk of BCC or SCC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Male; Middle Aged; Prednisone; Skin Neoplasms; Tretinoin

Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs.

Topics: Administration, Topical; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Keratinocytes; Male; Middle Aged; Quality of Health Care; Risk Factors; Skin Neoplasms; Tretinoin; Veterans

Basal cell carcinoma (BCC) is the most common cancer in the United States today, and patients who have had one are likely to have multiple carcinomas over time. Predictors of new BCCs on the face and ears among those at very high risk have not been studied in detail. We sought to do so prospectively in the context of a 6-year trial. We found that the number of BCCs in the prior 5 years was the most important predictor. Age, sun sensitivity, occupational sun exposure before the age of 30 years (but not afterward), lower educational level, history of eczema, the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and more sunscreen use in the week, but not the 6 months, before enrollment were also independent predictors, but sunburns, baseline sun exposure, and other sun-protective measures, other skin cancers, and actinic keratoses were not. None of the eczema patients had a history of topical calcineurin use. The cumulative risk of BCC was 55% at 5 years. These findings document the key risk factors in this very high-risk population, suggesting that the history of eczema may increase the risk in those at high risk and that early sun exposure is important even in this group, and underscoring the need for chemopreventive strategies.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Basal Cell; Eczema; Educational Status; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Keratosis, Actinic; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Risk Factors; Skin Neoplasms; Sunlight; Sunscreening Agents; Tretinoin; Veterans

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

To evaluate the relation of topical tretinoin, a commonly used retinoid cream, with all-cause mortality in the Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC). The planned outcome of this trial was risk of keratinocyte carcinoma, and systemic administration of certain retinoid compounds has been shown to reduce risk of this cancer but has also been associated with increased mortality risk among smokers.. The VATTC Trial was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up. Oversight was provided by multiple independent committees.. US Department of Veterans Affairs medical centers. Patients A total of 1131 veterans were randomized. Their mean age was 71 years. Patients with a very high estimated short-term risk of death were excluded. Interventions Application of tretinoin, 0.1%, or vehicle control cream twice daily to the face and ears.. Death, which was not contemplated as an end point in the original study design.. The intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group. Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death. After adjusting for these imbalances, the difference in mortality between the randomized groups remained statistically significant.. We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely.

Topics: Administration, Topical; Aged; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cause of Death; Double-Blind Method; Female; Humans; Male; 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

Photodamaged skin typically displays lentigines, actinic keratoses, wrinkles, and textural alteration. Chemical peeling has been used to treat these, but few controlled studies have been performed to determine its efficacy.. Our purpose was to compare the efficacy of a medium-depth chemical peel with and without tretinoin before and after treatment.. Sixteen men with actinic damage including actinic keratoses were treated with a 40% trichloroacetic acid(TCA) chemical peel. Half were pretreated for 6 weeks with topical tretinoin; they also used tretinoin after the peel. Photographs were obtained at baseline and at 6 weeks and 6 months after treatment. Changes in specific features were rated by a panel of three examiners.. Some improvement was noted in all patients. More rapid and even frosting was observed in the patients pretreated with tretinoin. Solar lentigines, actinic keratoses, and skin texture were the features of photoaging most affected; wrinkles were least affected. No statistically significant difference was found between patients treated with TCA and tretinoin (before and after peel) and those with TCA alone.. A medium-depth chemical peel with 40% TCA alone produced moderate improvement in some manifestations of actinic damage but had little effect on wrinkles. Treatment with tretinoin before and after TCA did not significantly enhance the efficacy of the peel.

Topics: Administration, Cutaneous; Bacteria; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemexfoliation; Follow-Up Studies; Humans; Keratolytic Agents; Keratosis; Lentigo; Male; Patient Satisfaction; Photography; Premedication; Sebum; Skin; Skin Aging; Skin Neoplasms; Tretinoin; Trichloroacetic Acid

To confirm reports that skin cancer can be prevented with retinoids, we conducted a three-year controlled prospective study of oral isotretinoin (also called 13-cis retinoic acid) in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal-cell or squamous-cell carcinomas. Patients were treated with isotretinoin at a dosage of 2 mg per kilogram of body weight per day for two years and then followed for an additional year, without the drug. Before, during, and after treatment, biopsies of all suspicious lesions were performed, and skin cancers were surgically removed. The patients had a total of 121 tumors (mean, 24; range, 8 to 43) in the two-year interval before treatment. During two years of treatment with isotretinoin, there were 25 tumors (mean, 5; range, 3 to 9), with an average reduction in skin cancers of 63 percent (P = 0.019). After the drug was discontinued, the tumor frequency increased a mean of 8.5-fold (range, 2- to 19-fold) over the frequency during treatment (P = 0.007). Although all patients experienced mucocutaneous toxic effects, and triglyceride, liver-function, or skeletal abnormalities developed in some, high-dose oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Clinical Trials as Topic; Female; Humans; Isotretinoin; Male; Prospective Studies; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Five patients with basal cell carcinoma received fenretinide. Two patients while receiving the drug had evidence of abnormal rod photoreceptor function that reversed rapidly on cessation of therapy. We speculate that fenretinide may interfere with the binding of vitamin A to opsin or with the transport of vitamin A.

Topics: Adult; Antineoplastic Agents; Carcinoma, Basal Cell; Clinical Trials as Topic; Dark Adaptation; Electroretinography; Female; Fenretinide; Humans; Male; Middle Aged; Photoreceptor Cells; Retina; Tretinoin; Vision Disorders

In several studies between 1962 and 1978, topical tretinoin was proved capable of producing complete regression of actinic keratosis and basal cell carcinoma. But because its efficacy is not comparable to that of other modalities, topical tretinoin is currently used only as an adjunct to topical 5-fluorouracil in the treatment of actinic keratosis. One recent report found topical tretinoin ineffective in the chemoprevention of actinic keratosis. Although the oral synthetic retinoids isotretinoin and etretinate have been used in the prevention and treatment of cutaneous malignancy, the potential exists for chronic toxicity from the prolonged systemic therapy that appears necessary for maintaining the chemopreventive effect. For this reason, it may be appropriate to study further the preventive as well as therapeutic effects of topical tretinoin and other retinoids for actinic keratosis and skin cancer. If they prove safe and effective, the use of topical retinoids in the prevention and treatment of cutaneous tumors may be the most significant clinical application of these drugs.

Topics: Carcinoma, Basal Cell; Clinical Trials as Topic; Etretinate; Humans; Isotretinoin; Keratosis; Photosensitivity Disorders; Skin Neoplasms; Tretinoin; Urinary Bladder Neoplasms

Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven.. We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers.. This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis.. A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72).. The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Combined Modality Therapy; Cost-Benefit Analysis; Cryotherapy; Female; Fluorouracil; Humans; Imiquimod; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Skin Neoplasms; Treatment Outcome; Tretinoin

We analyzed the role of WIF1 in normal and acanthotic epidermis of 12-O-tetradecanoylphorbol-13-acetate (TPA) or all-trans-retinoic acid (ATRA)-treated and basal cell carcinoma (BCC)-bearing mice. WIF1 protein is located in the follicular infundibulum and interfollicular epidermis (IFE) in murine back skin. Within the hyperplastic epidermis of TPA- or ATRA-treated or BCC-bearing murine skin, WIF1 and Keratin 10 overlap in Ki67

Topics: Adaptor Proteins, Signal Transducing; Animals; Carcinoma, Basal Cell; Cell Proliferation; Culture Media, Conditioned; Epidermis; Gene Knockdown Techniques; HEK293 Cells; Humans; Keratinocytes; Mice; Neoplasms, Experimental; Primary Cell Culture; Skin Neoplasms; Tamoxifen; Tetradecanoylphorbol Acetate; Tretinoin

Xeroderma pigmentosum (XP) is a rare autosomal recessive dermatosis that is often complicated by multiple skin tumours at exposed locations, which are difficult to treat. We report a case of a 12-year-old girl with XP treated with oral retinoic acid and photodynamic therapy (PDT) with good clinical results. She had an 8-year history of multiple skin lesions that first appeared on her nasal dorsum, but gradually increased in size and spread to her entire face, neck, and upper limbs. Notably, the lesions became evidently aggravated after sun exposure. When she was 6 years old, sesame-seed-sized papules and plaques appeared, which were fragile and irregular in shape and would self-rupture, accompanied with slight itchiness and bloody exudate. Examination revealed multiple basal cell carcinomas. The tumours were treated with local carbon dioxide laser therapy combined with PDT. On the follow-up visit 2 months after the surgery, most of the skin lesions on her face had subsided. In cases of multiple tumours, PDT can be the treatment method of choice because it is less invasive, has less side effects, and does not damage the surrounding normal tissues.

Topics: Carcinoma, Basal Cell; Child; Drug Therapy, Combination; Face; Female; Hematoporphyrins; Humans; Lasers, Gas; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by widespread human papillomavirus (HPV) associated lesions and an increase susceptibility to cutaneous malignancies. A host of medications traditionally used to treat warty lesions have been used with variable results and limited success. To our knowledge, we describe the first reported case of a patient with Imiquimod resistant EV successfully treated with topical ingenol mebutate (Picato).. A patient with a 5 year history of EV failed to respond to a 6 week course of 5% imiquimod on the forehead and was subsequently treated with a 3 day course of 0.015% Picato gel which resulted in significant clinical improvement. A one month follow-up examination showed no reoccurrence of the lesions with the patient reporting continued satisfaction of the outcome.. Our case provides insight into the potential use of ingenol mebutate for EV patients unresponsive to traditional medical treatments.

Topics: Acitretin; Adult; Aminoquinolines; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diterpenes; Drug Resistance; Epidermodysplasia Verruciformis; Female; Gels; Humans; Imiquimod; Keratolytic Agents; Rare Diseases; Skin Neoplasms; Treatment Outcome; Tretinoin

Topics: Carcinoma, Basal Cell; Female; Humans; Male; Skin Neoplasms; Tretinoin

Given the high incidence of non-melanoma skin cancer (NMSC), a preventative intervention would be desirable. Except for regular sunscreen use, the quest for chemoprevention of NMSC in the general population has been unsuccessful. Weinstock et al. assessed the effects of 0.1% topical tretinoin on NMSC. Like earlier efforts at chemoprevention, this study failed to show therapeutic benefit. Future successful preventative strategies will likely rely on short-term, intermittent therapy or treatments used for other common indications.

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Female; Humans; Keratinocytes; Male; Skin Neoplasms; Tretinoin

Dyer et al. (this issue) assess the risk of new basal cell carcinoma (BCC) in the Veterans Affairs topical tretinoin chemoprevention trial, which included individuals with a history of at least two prior keratinocyte carcinomas. In addition to known risk factors for a future BCC, such as number of prior BCCs, a history of eczema and lower education levels were also associated with greater risk.

Topics: Carcinoma, Basal Cell; Female; Humans; Male; Skin Neoplasms; Tretinoin

Topics: Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Keratinocytes; Quality of Life; Randomized Controlled Trials as Topic; Skin Neoplasms; Tretinoin; United States; United States Department of Veterans Affairs

Topics: Adult; Amoxicillin-Potassium Clavulanate Combination; Benzoyl Peroxide; Carcinoma, Basal Cell; Cryosurgery; Dermatologic Agents; Drug Therapy, Combination; Humans; Male; Nevus, Pigmented; Skin Neoplasms; Syndrome; Toes; Tretinoin

Retinoic acid (RA) was topically applied to the skin of Sencar mice during the promotion phase of specific tumor induction protocols that produce papillomas at low (12-O-tetradecanoylphorbol-13-acetate promoted, TPA) or high (mezerein-promoted) risk for premalignant progression and malignant conversion. RA consistently reduced the yield of papillomas and carcinomas in both protocols, but the frequency of malignant conversion in papillomas that emerged during RA treatment was not reduced. When TPA was reapplied after cessation of RA treatment, the number of papillomas increased 2-fold, suggesting that RA had not eliminated initiated cells. In vitro, RA prevented the emergence of transformed keratinocytes in an assay that mimics malignant conversion, suggesting that RA can suppress conversion if applied during the stage of premalignant progression. Examination of tumor markers at weeks 14 and 22 of the tumor-induction experiments in vivo indicated that papillomas evolving during RA treatment exhibited a phenotype of high progression risk, even in the TPA-promoted groups. In the majority of these tumors, the alpha6beta4 integrin and retinoid X receptor alpha transcripts were detected suprabasally, indicating an advanced state of premalignant progression. RA-treated tumors also expressed higher levels of transcripts for transforming growth factor (TGF)-beta1 and localized TGF-beta1 peptide in the basal portions of the tumor fronds. Because up-regulated expression of TGF-beta1 suppresses papilloma formation, these studies suggest a mechanism whereby RA can prevent papilloma eruption via a TGF-beta intermediate, but papillomas resistant to RA may have altered TGF-beta signaling and progress to carcinomas at an increased frequency.

Topics: Administration, Topical; Animals; Anticarcinogenic Agents; Antineoplastic Agents; Biomarkers, Tumor; Carcinogens; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Disease Progression; Diterpenes; Female; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Inbred SENCAR; Papilloma; Phenotype; Precancerous Conditions; Receptors, Retinoic Acid; Retinoid X Receptors; Risk Factors; Skin Neoplasms; Terpenes; Tetradecanoylphorbol Acetate; Transcription Factors; Transforming Growth Factor beta; Tretinoin

The efficiency of topical tretinoin was examined in a patient with basal cell carcinomas (BCC) for which conventional means of removal was inappropriate.. Topical tretinoin was used to treat multiple arsenic-induced superficial BCCs in a 64-year-old woman. Topical tretinoin (0.05% twice daily) was administered to four lesions for 3 weeks followed by a 3-week interruption.. After three cycles of treatment clinical healing of all the lesions was observed. Histopathological examination of the lesional biopsies showed no evidence of a tumor. However, 9 months later all four lesions relapsed and surgical excision disclosed BCC.. The data indicate that topical tretinoin treatment of multiple superficial BCCs induces clinical and pathological regression of the lesions with a high rate of relapse. This report suggests that topical tretinoin is not an effective therapy for the cure of arsenic-induced superficial BCCs.

Topics: Administration, Cutaneous; Carcinoma, Basal Cell; Female; Humans; Middle Aged; Skin Neoplasms; Tretinoin

To confirm reports that skin cancer can be prevented with retinoid treatment, a three-year controlled prospective study was conducted of oral isotretinoin in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal cell or squamous cell carcinomas. Patients were treated with isotretinoin, 2 mg/kg per day for two years, and then evaluated for an additional year without using the drug. Before, during, and after treatment, biopsy specimens of all suspicious lesions were examined, and skin cancers were removed surgically. The patients had a total of 121 tumors in the two years before treatment. During two years of treatment with isotretinoin, there were twenty-five tumors, with an average reduction in skin cancers of 63 percent (p = 0.019). After use of the drug was discontinued, the tumor frequency increased a mean of 8.5 times over the frequency during treatment (p = 0.007). Although all patients experienced mucocutaneous toxic effects, and abnormalities in triglyceride levels, results of liver function tests, or skeletal findings occurred in some, high-dosage oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Twelve patients with multiple basal cell carcinomas resulting from varying causes were treated with high-dose oral isotretinoin (mean daily dosage: 3.1 mg/kg/day) for a mean of 8 months. Of the 270 tumors monitored in these patients, only 8% underwent complete clinical and histologic regression. All patients developed moderate to severe acute toxicities, leading five patients to withdraw from the study. Retinoid skeletal toxicity was identified in two patients who were examined after long-term therapy. Lower doses of isotretinoin (0.25 to 1.5 mg/kg/day) were ineffective for chemotherapy but demonstrated a chemopreventive effect in a subset of three patients who received these lower doses for 3 to 8 years. Two of these three patients have been observed after discontinuation of therapy. In one patient with a history of arsenic exposure, only one new tumor has appeared in a 27-month posttreatment observation period; in the other patient with the nevoid basal cell carcinoma syndrome, 29 new tumors have appeared within a 13-month period. This suggests that the need for long-term maintenance therapy with isotretinoin for chemoprevention of basal cell carcinoma may depend on the underlying cause of the skin cancers.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Basal Cell; Female; Humans; Isomerism; Isotretinoin; Male; Middle Aged; Neoplasms, Multiple Primary; Remission Induction; Skin Neoplasms; Tretinoin

A group of 50 patients with basal cell carcinoma of the face was treated by 13-cis-retinoic acid. The treatment resulted in diminution of the tumors. Complete regression was observed in 4 cases. Histological examination revealed necrosis of cancer cells and mononuclear infiltration into the treated tumors. In the group with weak clinical and histological reaction to the treatment all basal cell carcinomas were of adenoid type. A better effect was observed in the group with lower serum retinol level. This treatment method seems to be supplementary to surgery in prevention of the tumor recurrence.

Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Basal Cell; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms; Tretinoin; Vitamin A

Two patients with multiple basal cell carcinomas, due either to the nevoid basal cell carcinoma syndrome (NBCCS) or arsenical insecticide exposure, were treated with oral isotretinoin for 7 or 8 years, respectively. Gradually decreasing dosage levels were employed. During the initial courses of therapy, high doses (2.0-3.0 mg/kg/day) were intended as chemotherapy. In these patients only 6 of 40 (15%) lesions underwent complete clinical regression. In subsequent courses aimed at chemoprevention, the dose was progressively reduced from 1.5 to 0.25 mg/kg/day. During therapy, no new lesions were observed in the patient with the arsenical exposure. The NBCCS patient developed 1 new lesion during therapy at 1.0 mg/kg/day, 1 new lesion at 0.5 mg/kg/day and 5 new lesions at 0.25 mg/kg/day. Treatment was discontinued and the patient with the arsenic exposure developed his first new tumor 17 months afterwards; in contrast, the NBCCS patient developed 29 tumors within 13 months. These findings suggest that long-term therapy with isotretinoin is needed for the continuation of the cancer chemopreventive effect. However, the need for continuous rather than intermittent maintenance therapy, and the determination of the optimal dose for this purpose may depend on the etiology of the multiple carcinomas and on the tolerability of the lowest effective dose by the individual patient. With these encouraging data, it now appears appropriate to expand this pilot study and perform larger trials to determine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.

Topics: Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Humans; Isotretinoin; Male; Middle Aged; Neoplasms, Multiple Primary; Prognosis; Skin Neoplasms; Tretinoin

Patients with basal cell carcinoma were treated locally with 13-cis-retinoic acid. Disappearance of the tumors was observed in two of fifteen patients. Thirteen patients whose tumors diminished after the treatment were finally managed surgically. Biopsy specimens were examined histopathologically and by autoradiography. Treated tumors showed reduction of labeling indices as compared with the nontreated group.

Topics: Adult; Aged; Carcinoma, Basal Cell; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms; Tretinoin

A histologically confirmed, clinically inapparent and reversible hepatitis occurred in 2 patients (1 psoriasis, 1 basal cell nevus syndrome) within the first months after introduction of etretinate therapy. Causes of hepatitis other than etretinate were not found. Reintroduction of etretinate resulted in reactivation and/or persistence of the hepatitis in both patients. These data strongly suggest that the hepatitis in both patients was caused by etretinate. Later the basal cell nevus syndrome patient was given 13-cis-retinoic acid, which caused no liver test disturbances during a follow-up period of 6 months.

Topics: Aged; Basal Cell Nevus Syndrome; Biopsy; Carcinoma, Basal Cell; Chemical and Drug Induced Liver Injury; Etretinate; Female; Humans; Liver; Middle Aged; Psoriasis; Tretinoin

Three patients with multiple basal cell carcinomas, due either to excessive sunlight exposure, the nevoid basal cell carcinoma syndrome, or arsenical insecticide exposure, were treated with oral isotretinoin for 2 1/2 to 4 years. Although higher doses were used initially, approximately 1.5 mg/kg/day was used for long-term therapy in all three patients. Therapeutic effects on existing tumors varied between each patient, and only nine of sixty-five lesions underwent complete clinical regression. No tumors enlarged in two patients; a few tumors enlarged slightly in the third patient, particularly during the later courses of therapy when isotretinoin was given at lower dosage. No new lesions have been observed in any of these three patients. With these encouraging preliminary data, it now may be appropriate to perform larger trials for longer periods of time to determine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.

Topics: Aged; Carcinoma, Basal Cell; Humans; Isomerism; Isotretinoin; Male; Middle Aged; Neoplasms, Multiple Primary; Skin Neoplasms; Tretinoin

Topics: Adult; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Cell Transformation, Neoplastic; Etretinate; Facial Neoplasms; Humans; Male; Tretinoin

Although much recent work suggests that retinoids can prevent the development of epithelial cancers, their mechanism of action remains unknown. Since malignancy has been associated with alterations in gap junctions, desmosomes, microfilaments, and hemidesmosomes, the authors examined freeze-fracture replicas and thin sections of cell membranes of: (1) 11 basal cell cancers (BCC) treated twice daily for two weeks with topical 1.0% retinoid acid (RA); (2) 21 BCC treated for 2 to 17 weeks with oral 13-cis retinoic acid (CRA) (1.0-8.0 mg/kg/day); and (3) 17 BCC prior to retinoid treatment and/or after applications of vehicle alone. Both thin sections and replicas were examined and photographed in a single-blind fashion, and the density and size distribution of gap junctions and desmosomes were computed planimetrically. Topical RA treatment induced a two-fold increase in gap junction density (P less than 0.025) over controls. In contrast, RA produced a concurrent = 35% decrease in desmosome density. Systemic CRA did not significantly alter either gap junction or desmosome density or size. Finally, neither RA nor CRA treatment appeared to influence hemidesmosome or microfilament populations. Structural changes in both treatment groups did not correlate with either tumor regression or inflammation. Topical and systemic retinoids may exert their antineoplastic activity by different cellular mechanisms.

Topics: Administration, Topical; Adult; Aged; Carcinoma, Basal Cell; Cell Membrane; Desmosomes; Freeze Fracturing; Humans; Intercellular Junctions; Male; Middle Aged; Skin Neoplasms; Tretinoin; Vitamin A

Topics: Animals; Carcinoma, Basal Cell; Cell Division; Humans; Mice; Ornithine Decarboxylase; Skin; Skin Neoplasms; T-Lymphocytes; Tretinoin; Ultraviolet Rays

Topics: Administration, Topical; Aged; Biopsy; Carcinoma, Basal Cell; Cell Membrane; Desmosomes; Freeze Fracturing; Humans; Intercellular Junctions; Male; Microscopy, Electron; Middle Aged; Tretinoin

Beneficial effects of oral retinoids in prophylaxis of epithelial neoplasias have been demonstrated by experimental works. In this study oral retinoid (RO 10-9359) was used in human dermatosis with high frequency of cutaneous malignancies: xeroderma pigmentosum with or without malignant neoplasias, Mibelli's porokeratosis with multifocal malignant degeneration, basal cell naevus syndrome with basal cell carcinomas, familial epithelioma of Ferguson-Smith and actinic keratosis. This work started in december 1977. Visible epitheliomas have been treated before trial. Initial dose of retinoid was 1 mg/kg daily, decreased depending on individual tolerance. Results were appreciated by comparising number of epitheliomas observed in years preceding retinoid therapy and number of them appearing during treatment; in two familial cases (basal cell naevus syndrom in twins and xeroderma pigmentosum in two brothers) comparison was made between treated and untreated patients. First results are very promising: an excellent response on solar keratosis is noted; epitheliomas occurrence seems actually to be prevented or delayed by oral retinoid therapy. Of course more numerous cases, a longer time, periods without treatment are necessary to confirm these interesting first results. On the other hand drug is not with this dose active on already constituted carcinomas.

Topics: Adolescent; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Etretinate; Female; Humans; Keratosis; Male; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Epithelium; Etretinate; Humans; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A

Blepharoconjunctivitis developed as a side-effect of treatment of patients with basal cell carcinomas, keratinizing dermatoses, and cystic acne with oral 13-cis-retinoic acid. Forty-two of the 97 dermatologic patients had signs and symptoms of blepharoconjunctivitis that were dose related and abated one week after discontinuation of the medication. About half of the patients had a history of similar symptoms prior to treatment. Staphylococcus aureus was present in eye cultures of 73% to 79% of the patients, whether symptomatic or not. Patients whose clinical appearance was that of staphylococcal blepharoconjunctivitis and whose cultures grew S aureus were successfully treated with topical erythromycin ointment to the lids even while being treated with the 13-cis-retinoic acid.

Topics: Acne Vulgaris; Blepharitis; Carcinoma, Basal Cell; Conjunctivitis; Erythromycin; Eyelid Diseases; Humans; Keratosis; Skin Diseases; Skin Neoplasms; Staphylococcal Infections; Tretinoin

Topics: Acne Vulgaris; Administration, Oral; Carcinoma, Basal Cell; Darier Disease; Drug Evaluation; Humans; Ichthyosis; Pityriasis Rubra Pilaris; Skin Neoplasms; Tretinoin; Vitamin A

15 patients with superficial basaliomas or premalignant epithelial neoplastic disorders (actinic keratosis, leukoplakia, Bowen's disease) were treated locally over three weeks with retinoic acid (RA) alone or in combination with 5-fluorouracil (5-FU). In 11 cases the lesions disappeared clinically, however, only 5 patients proved to be cured by histological examination. 4 of them were treated with RA combined with 5-FU. There was a decrease of the 3H-index after the first week and an increase after the third week of treatment. These findings suggest, that RA inhibits the proliferation of neoplastic keratinocytes and stimulates the proliferation of normal epidermal cells. Retinoic acid, therefore, has an inhibitory effect on epithelial neoplasias, particularly in combination with 5-FU. Since local therapy with RA and 5-FU is not sufficient for routine clinical purposes in all cases, their use should be restricted to selected patients.

Topics: Aged; Carcinoma, Basal Cell; Drug Therapy, Combination; Female; Fluorouracil; Humans; Keratosis; Leukoplakia; Light; Lip Neoplasms; Male; Middle Aged; Mouth Neoplasms; Neoplasms, Radiation-Induced; Precancerous Conditions; Scalp; Skin Neoplasms; Thorax; Tretinoin; Vitamin A

Topics: Adolescent; Adult; Carcinoma, Basal Cell; Humans; Middle Aged; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A

Topics: Animals; Carcinoma, Basal Cell; Humans; Neoplasms, Experimental; Papilloma; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Tretinoin; Vitamin A; Vitamin A Deficiency