Clinical Briefs
By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.
A New Intervention for Actinic Keratoses: Ingenol Mebutate Gel
Source: Rosen RH, et al. J Am Acad Dermatol 2012;66:486-493.
Actinic keratoses (AK) is biologically in situ squamous cell carcinoma, with the potential to become invasive in a minority of cases. However, because an individual patient may have many AK and it is not possible with certainty to identify which lesions are more likely to progress, it has been recommended that removal of AK be performed whenever possible. In the primary care setting, the three most prominent methods of destruction are cryotherapy, immune activators (e.g., imiquimod cream), and antimetabolites (e.g., 5-fluorouracil cream). Each of these methods has substantial limitations; for instance, the inflammatory response to appropriate use of imiquimod or 5-fluorouracil may be both painful and (at least transiently) cosmetically unwieldy. Additionally, traditional regimens of commonly used topicals require multiple applications over several weeks or more.
Ingenol mebutate (ING) is a recently approved topical agent that works by induction of lesion necrosis as well as by activation of antibody-directed cellular cytotoxic pathways. What this does for AK is produce a prompt and immediate kill effect on abnormal cells (within a few hours), which is coupled with a drug-mediated activation of B-cells that binds to abnormal (precancerous) cells over subsequent days and destroys them. This dual mechanism provides for short treatment regimens (2-3 days), with persistent post-treatment effects that obliterate evolving AK. The tolerability profile of ingenol, coupled with its dual mechanism of action and ease of administration, may give it a priority role in topical therapies for AK, although the clearance rates with the new product are not yet established to be at parity with older agents until head-to-head comparator trials are performed.
Colon Cancer Screening: Getting the Right Test Done
Source: Quintero E, et al. N Engl J Med 2012;366:697-706.
In its most recent update on colorectal cancer screening (CCS), the American Cancer Society, in concert with other interested parties, suggested that the best screening test for CCS is the one a person can get done. This is because in comparison to the other more widely used screenings (e.g., mammography, PAP testing, PSA), adoption of colonoscopy has been somewhat disappointing.
Fecal immunochemical testing (FIT) of the stool incorporates many of the advantages and circumvents some of the limitations of other screening tools. For instance, the specificity of FIT for human hemoglobin eliminates special dietary restrictions. Additionally, the presence of blood from the upper GI tract does not typically induce a positive result with FIT, eliminating unnecessary evaluation of the colon when upper GI blood is the cause.
Quintero et al report on initial results of the first wave of a comparison between FIT and colonoscopy in a very large population (n = 53,102) of asymptomatic adults age 50-69 years who were randomized to either traditional colonoscopy every 10 years or FIT every 2 years. FIT-positive patients were followed up with colonoscopy.
As is perhaps not surprising, compliance with FIT was about 30% greater than with colonoscopy. Colon cancer was detected in 0.1% of each group; however, the rate of detection of advanced adenomas was more than twice as high in the colonoscopy group (1.9% vs 0.9%).
These preliminary results are encouraging that a method for which patients find more advocacy FIT might find a more prominent role in CCS, especially when patients find other screening tools unacceptable. Because these results are preliminary (first 2-3 years of follow-up), we will likely need to wait until final results are completed in 2021 before the question of the role of FIT can be definitively answered.
Actinic keratoses (AK) is biologically in situ squamous cell carcinoma, with the potential to become invasive in a minority of cases.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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