Basal-Cell Carcinoma Rubin, Adam I; Chen, Elbert H; Ratner, Désirée
The New England journal of medicine,
11/2005, Letnik:
353, Številka:
21
Journal Article
Recenzirano
Basal-cell carcinoma is the most common malignant tumor, and its incidence is increasing. This review explains the treatment options, including four surgical approaches, topical therapy, photodynamic ...therapy, and radiation. Recent research on the pathogenesis is also summarized.
This review explains the treatment options, including four surgical approaches, topical therapy, photodynamic therapy, and radiation. Recent research on pathogenesis is also summarized.
According to the American Cancer Society, skin cancer is the most common cancer, accounting for about half of all cancers in the United States. More than 1 million cases of skin cancer will be diagnosed in the United States this year.
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Basal-cell carcinomas constitute approximately 80 percent of all nonmelanoma skin cancers. This article addresses cutaneous basal-cell carcinoma, which should be differentiated from the uncommon basal-cell carcinoma or basaloid carcinoma that arises in sites such as the prostate, pancreas, lung, cervix, salivary gland, thymus, and anal canal.
Incidence
The absolute incidence of basal-cell carcinoma is difficult to determine, since nonmelanoma . . .
IMPORTANCE: Risk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods. OBJECTIVE: To estimate the risk up to 10 ...years and identify risk factors for cSCC development. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK. EXPOSURES: Patients with AK and control participants were followed up for up to 10 years for incidence of cSCC. MAIN OUTCOMES AND MEASURES: Incident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs. RESULTS: The study included 220 236 patients with AK and 220 236 matched control patients (mean SD age, 64.1 12.2 years; 231 248 52.5% female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72). CONCLUSIONS AND RELEVANCE: The results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.
Current concepts : Basal-cell carcinoma RUBIN, Adam I; CHEN, Elbert H; RATNER, Desiree
The New England journal of medicine,
11/2005, Letnik:
353, Številka:
21
Journal Article
Background. There are several options for closure of a given surgical defect after tumor extirpation is confirmed. Flap reconstruction is one of these options.
Objective. The purpose of this article ...is to introduce the three basic types of flap movement: advancement, rotation, and transposition.
Methods. Five similar defects located on the nasal sidewall were repaired, each using a different flap design.
Results. The optimal flap design for a given defect on a particular patient is based on the answers to a series of questions: Where is the available tissue reservoir? How can tissue be mobilized from the reservoir to cover the defect? How do the resulting tension vectors affect critical structures? Where are the final incision lines?
Conclusion. Many factors must be evaluated before determining a method of reconstruction. Flap reconstruction requires a thorough understanding of anatomy and tissue movement.
BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is an unusual soft-tissue tumor with a propensity for subclinical extension and local recurrence. Surgical excision, even with tissue-sparing ...techniques, may cause significant deformity or disability because of the infiltrative nature of DFSP. In this study, we evaluate retrospective data obtained from 4 patients with locally advanced or recurrent DFSP who received neoadjuvant imatinib mesylate therapy before undergoing Mohs micrographic surgery. OBSERVATIONS Patients treated with neoadjuvant imatinib therapy had an average tumor size reduction of 36.9%. This clinical response was paralleled by histopathologic changes, including decreased cellularity in 100% of the total area as well as significant hyalinization. Imatinib therapy for DFSP before Mohs micrographic surgery was associated with 100% local control at a maximum follow-up of 4 years. CONCLUSIONS Neoadjuvant imatinib therapy is a well-tolerated, novel approach to DFSP that reduces tumor burden and facilitates resection. Larger prospective studies are needed to confirm and expand on these results.Arch Dermatol. 2009;145(7):792-796-->
Interleukin-12 (IL-12) is a key immunoregulatory cytokine that promotes Th1 differentiation and cell-mediated immune responses. The transcription factor STAT4 (signal transducer and activator of ...transcription 4) is an important element in mediating IL-12 signals, as evidenced by the fact that STAT4−/− mice display impaired responsiveness to IL-12 and deficient Th1 differentiation. STAT4 is inducibly phosphorylated on tyrosine and serine in response to IL-12, but the kinase(s) responsible for the latter event is unknown. Here we show that IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity. In addition, we show that mutation of tyrosine 693 abrogates IL-12–induced STAT4 tyrosine phosphorylation and transcriptional activity. Although the site surrounding serine 721 is an optimum consensus sequence for mitogen-activated family of protein kinases (MAPKs)-mediated phosphorylation, we demonstrate that IL-12 does not induce extracellular signal-regulated kinase (ERK) or c-Jun N-terminal kinase (JNK) activation in T and natural killer (NK) cells and that IL-12–induced STAT4 transcriptional activity is not affected by these kinases. Rather, we show that IL-12 induces p38 activation. Moreover, we demonstrate that p38α and its upstream activator, MKK6, phosphorylate STAT4 on serine 721, and are required for STAT4 full transcriptional activity induced by IL-12, establishing the MKK6/p38α/STAT4 pathway as an important mediator of IL-12 actions.
Interleukin-12 (IL-12) is a key immunoregulatory cytokine that promotes Th1 differentiation and cell-mediated immune responses. The transcription factor STAT4 (signal transducer and activator of ...transcription 4) is an important element in mediating IL-12 signals, as evidenced by the fact that STAT4−/− mice display impaired responsiveness to IL-12 and deficient Th1 differentiation. STAT4 is inducibly phosphorylated on tyrosine and serine in response to IL-12, but the kinase(s) responsible for the latter event is unknown. Here we show that IL-12 induces STAT4 phosphorylation on serine 721 and that mutation of serine 721 interferes with STAT4 transcriptional activity. In addition, we show that mutation of tyrosine 693 abrogates IL-12–induced STAT4 tyrosine phosphorylation and transcriptional activity. Although the site surrounding serine 721 is an optimum consensus sequence for mitogen-activated family of protein kinases (MAPKs)-mediated phosphorylation, we demonstrate that IL-12 does not induce extracellular signal-regulated kinase (ERK) or c-Jun N-terminal kinase (JNK) activation in T and natural killer (NK) cells and that IL-12–induced STAT4 transcriptional activity is not affected by these kinases. Rather, we show that IL-12 induces p38 activation. Moreover, we demonstrate that p38α and its upstream activator, MKK6, phosphorylate STAT4 on serine 721, and are required for STAT4 full transcriptional activity induced by IL-12, establishing the MKK6/p38α/STAT4 pathway as an important mediator of IL-12 actions.
Basal-Cell Carcinoma De Giorgi, Vincenzo; Massi, Daniela; Lotti, Torello
The New England journal of medicine,
02/2006, Letnik:
354, Številka:
7
Journal Article
Recenzirano
To the Editor: The excellent review by Rubin et al. of basal-cell carcinoma (Nov. 24 issue)
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considers the genital area an unusual site for basal-cell carcinomas. In our view, this site, especially ...the vulva, is neither unusual nor random. Like melanoma,
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even basal-cell carcinomas appear in sun-shielded areas such as the vulva, challenging the conventional knowledge that associates these cancers with ultraviolet radiation.
Vulvar basal-cell carcinoma typically includes poor pigmentation and, often, a clinical appearance that mimics eczema or psoriasis.
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The dominant symptom, itching, often induces both patients and doctors to dismiss the condition as a simple irritation or intertrigo. . . .
The discovery of JAKs and STATs provided long-awaited clues to the mechanism of cytokine signal transduction. A recent meeting
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The Keystone Symposium on Signal Transduction by JAKs and STATs was ...held at Tamarron, CO, USA, on 3–8 February 1998.
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reviewed the current state of JAK/STAT biology and discussed new advances that offer novel insights into cytokine signaling.
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