Clinical Briefs

By Louis Kuritzky, MD

Prevalence of Prostate Cancer Among Men with a Prostate-Specific Antigen Level < 4.0 ng/mL

The prostate cancer prevention trial enrolled 18, 882 men to evaluate whether an alpha-reductase inhibitor, finasteride, could prevent incident prostate cancer in men with normal PSA levels(< 3.0 ng/mL). Half of the men in this trial received placebo, but nonetheless subsequently underwent prostate biopsy at the end of the 7-year study. A PSA level of < 4.0 in asymptomatic men is commonly observed as the boundary for consideration of prostate cancer, although it has been recently suggested that the threshold be reduced to 2.5 ng/mL.

The end-of-study prostate biopsy identified prostate cancer in 15.2% of the 2950 men in the placebo group. Eighty percent of tumors identified had low Gleason scores (6 or less). There was a significant difference in PSA levels between the men who were determined to have prostate cancer and those with normal biopsies (PSA mean, 1.78 vs 1.34). Additionally, rate of rise of PSA was associated with risk of prostate cancer.

At first glance, such data might stimulate clinicians to consider lowering the threshold for prostate biopsy.

However, since the currently available trial data have not provided convincing evidence that intervention base upon PSA-screening has had a favorable effect upon all-cause mortality, whether more vigorous attention to lesser PSA levels will ultimately benefit men remains unknown.

Thompson IM, et al N Engl J Med 2004;350:2239-2246.

Mirtazapine for Reducing Nocturnal Itch in Patients with Chronic Pruritus

Pruritus is a commonplace complaint of persons with dermatological disorders like psoriasis, atopic dermatitis, and chronic urticaria. Nocturnal itch interrupts sleep and compromises quality of life. Traditional antihistamines offer some relief, but may be limited by daytime somnolence. The concept that antidepressants might be beneficial for pruritus is bolstered by the observation that doxepin, a tricyclic antidepressant, has been found to be a dramatically more potent histamine receptor blocker than even the most potent traditional antihistamines (eg, cetirizine, loratadine). Mirtazapine, an antidepressant, has been reported to effectively treat pruritus of cholestasis, lymphoma, and uremia.

Three patients with intractable pruritus (failed treatment with high dose antihistamines, and some other agents) responded promptly to mirtazapine 15 mg/d, including one patient who had not responded to doxepin. Mirtazapine has potent H1-antihistamine activity, but it is theorized that its adrenergic antagonism may also be involved in pruritus relief.

This small pilot trial provides hope that larger trials will confirm the efficacy of mirtazapine for this and other pruritus disorders.

Hundley JI, Yosipovitch G. J Am Acad Dermatol 2004;50:889-891

A Factorial Trial of Six Interventions for the Prevention of Postoperative Nausea and Vomiting

As many as 1 out of 3 post-surgical patients suffer nausea and vomiting (N&V), unless prophylaxed with antiemetic pharmacotherapy. Worldwide, 75 million persons per year undergo a surgical procedure requiring anesthesia, hence optimizing N&V outcomes is a epidemiologically compelling. Not only are the symptoms troublesome, but N&V leads to serious postsurgical consequences such as aspiration, wound dehiscence, and esophageal rupture.

Six different treatments, alone and in combination, were evaluated in 5199 patients: ondansetron, dexamethasone, droperidol, substituting propofol for other anesthetics, nitrous oxide omission from the multi-drug anesthetic regimen, , and remifentanil substitution for fentanyl.

The antiemetics (ondansetron, dexamethasone, droperidol) reduced N&V by about 26%, propofol by 19%, and nitrous oxide omission by 12%. Fentanyl substitution by remifentanil was not effective to reduce N&V. Combined interventions were additive to reduce N&V. Since all interventions except fentanyl substitution were beneficial, it is recommended that initial choice be based upon safety and cost.

Patients at low-risk might uncommonly require prophylaxis, whereas high-risk patients could benefit from a combination of treatments.

Apfel CC, et al N Engl J Med 2004;350: 2441-2451.

Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.