ABSTRACT
Importance: Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective: To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions: Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures: Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results: Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance: A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration: clinicaltrials.gov Identifier: NCT00847912.
Subject(s)
Carcinoma, Basal Cell/drug therapy , Carcinoma, Squamous Cell/drug therapy , Chemoprevention/methods , Fluorouracil/administration & dosage , Skin Neoplasms/drug therapy , Administration, Cutaneous , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/mortality , Carcinoma, Basal Cell/prevention & control , Carcinoma, Basal Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/prevention & control , Carcinoma, Squamous Cell/surgery , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Mohs Surgery/methods , Mohs Surgery/statistics & numerical data , Prognosis , Risk Assessment , Skin Cream/therapeutic use , Skin Neoplasms/mortality , Skin Neoplasms/prevention & control , Skin Neoplasms/surgery , Survival Analysis , Treatment OutcomeSubject(s)
Antimetabolites, Antineoplastic/administration & dosage , Fluorouracil/administration & dosage , Keratosis, Actinic/drug therapy , Precancerous Conditions/drug therapy , Administration, Cutaneous , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Facial Dermatoses/drug therapy , Facial Dermatoses/pathology , Female , Follow-Up Studies , Humans , Keratosis, Actinic/pathology , Male , Precancerous Conditions/pathology , Quality of Life , Severity of Illness Index , Treatment OutcomeSubject(s)
Military Personnel , Skin Neoplasms/epidemiology , Skin Neoplasms/prevention & control , Sunscreening Agents , Ultraviolet Rays/adverse effects , Adult , Afghan Campaign 2001- , Age Factors , Cross-Sectional Studies , Female , Humans , Iraq War, 2003-2011 , Male , Multivariate Analysis , Prevalence , Regression Analysis , Risk Assessment , Sex Factors , Skin Neoplasms/etiology , Sunburn/etiology , Sunburn/prevention & control , Time Factors , Veterans/statistics & numerical data , Young AdultABSTRACT
There have been many reports of mitochondrial DNA (mtDNA) mutations associated with human malignancies. We have observed allelic instability in UV-induced cutaneous tumors at the mt-Tr locus encoding the mitochondrial tRNA for arginine. We examined the effects of somatic alterations at this locus by modeling the change in a uniform nuclear background by generating cybrids harboring allelic variation at mt-Tr. We utilized the naturally occurring mtDNA variation at mt-Tr within the BALB/cJ (BALB) and C57BL/6J (B6) strains of Mus musculus to transfer their mitochondria into a mouse ρ(0) cell line that lacked its own mtDNA. The BALB haplotype containing the mt-Tr 9821insA allele produced significant changes in cellular respiration (resulting in lowered ATP production), but increased rates of cellular proliferation in cybrid cells. Furthermore, the mtDNA genotype associated with UV-induced tumors endowed the cybrid cells with a phenotype of resistance to UV-induced apoptosis and enhanced migration and invasion capabilities. These studies support a role for mtDNA changes in cancer.
Subject(s)
Allelic Imbalance , Cell Transformation, Neoplastic/genetics , DNA, Mitochondrial/genetics , Mitochondria/genetics , Alleles , Animals , Antioxidants/metabolism , Apoptosis/genetics , Arginine/genetics , Arginine/metabolism , Cell Line , Cell Movement/genetics , Cell Nucleus/genetics , Cell Proliferation , Cell Respiration/genetics , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Genetic Loci , Genetic Variation , Haplotypes/genetics , Hybrid Cells/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mitochondria/metabolism , Mutation/genetics , Neoplasm Invasiveness/genetics , Phenotype , RNA, Transfer/geneticsABSTRACT
Sweet's syndrome is an acute febrile neutrophilic dermatosis marked by attacks of painful, plaque-forming inflammatory papules accompanied by fever, arthralgias, peripheral leukocytosis, a diffuse dermal neutrophilic infiltrate, and prompt resolution of symptoms and lesions with glucocorticoid therapy. There are many reports of drug-induced Sweet's syndrome to various medications including all- trans -retinoic acid, carbamazepine, hydralazine, levonorgestrel/ethinyl estradiol, minocycline, trimethoprim/sulfamethoxazole, and granulocyte colony-stimulating factor. We describe the first known case of Sweet's syndrome induced by pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor with unique pharmacologic properties that may induce Sweet's syndrome in patients with no history of neutrophilic dermatoses associated with granulocyte colony-stimulating factor therapy.
Subject(s)
Blister/chemically induced , Granulocyte Colony-Stimulating Factor/adverse effects , Neutropenia/congenital , Sweet Syndrome/chemically induced , Blister/drug therapy , Filgrastim , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Leukocyte Count , Male , Middle Aged , Neutropenia/drug therapy , Neutrophils/cytology , Polyethylene Glycols , Recombinant ProteinsABSTRACT
Porphyria cutanea tarda (PCT) is associated with estrogen, certain medications, alcohol abuse, hepatitis viruses, and iron overload. Numerous studies have demonstrated an increased incidence of hepatitis C in patients with PCT; therefore, hepatitis screening should be routinely performed on these patients. On the other hand, although studies have long suspected hereditary hemochromatosis (HH) to be an underlying condition of PCT, many physicians have a low index of suspicion. Also, diagnosis of HH has been difficult until recently, when the gene mutation was identified. We present a case of a patient with PCT, hepatitis C, and alcoholism who was homozygous for the HH gene mutation.