Diagnosis of prostate cancer: repeated transrectal prostate biopsy or transurethral resection.

BACKGROUND: Transrectal ultrasound-guided biopsy of the prostate is the major method by which prostate cancer is diagnosed. However, many patients might be overlooked with the initial biopsy. Not uncommonly, patients need repeated biopsies when they continue to exhibit suspicious clinical signs. This may cause psychological stress to both patients and doctors. The purpose of this study was to determine how many repeat transrectal biopsies are adequate for prostate cancer detection and when to switch to transurethral resection. METHODS: We retrospectively studied a cohort of 2,996 patients who had undergone prostate biopsy. If the biopsy specimen was negative for malignancy, patients were given the choice of either being managed with observation or undergoing transurethral resection of the prostate (TURP) if indicated. If there was a high suspicion of cancer, patients were advised to undergo additional biopsies. The primary endpoint of this study was a diagnosis of cancer. RESULTS: The cancer detection rate was 22.9% (685 of 2,996 patients) in specimens taken during the first transrectal biopsy, 8.7% in those taken during the second biopsy (32 of 336 patients), and 6.1% in those taken during the third biopsy (6 of 98 patients). The cancer detection rate of TURP after 1 negative biopsy result was 9.3% (35 of 375 patients), and that after 2 negative biopsy results was 17.1% (6 of 35 patients). TURP-derived specimens that were pathologically diagnosed as malignant had lower Gleason grade on average, no matter how many repeat biopsies there were in patients whose previous transrectal biopsy specimens were negative for malignancy (p=0.002 for 2 negative biopsy results and p=0.007 for 3 negative biopsy results). CONCLUSION: The chance of detecting malignancy beyond a third transrectal biopsy procedure is low. TURP, therefore, might be an alternative procedure for obtaining tissue for pathologic diagnosis, especially in patients with rising prostate-specific antigen levels and comorbid illnesses such as obstructive symptoms.

Homodimeric tacrine congeners as acetylcholinesterase inhibitors.

In the search for highly selective and potent derivatives of tacrine (1a), a number of homodimeric tacrine congeners were synthesized and conducted for their effects on rat acetylcholinesterase (AChE) and human butyrylcholinesterase (BChE) inhibitions. Heptylene-linked bis-(6-chloro)tacrine (3h) was found up to 3000- and 3-fold more potent in inhibiting rat AChE than tacrine and the unsubstituted bis-tacrine 3b, respectively. Changes in the size of the carbocyclic ring of the dimeric tacrine reduced both the selectivity and the potency of AChE inhibition as compared to 3b. Inserting an aza into the tacrine nucleus as the desired isosteres 3j-m resulted in moderate potency but tended to be detrimental to selectivity. The pronounced enhancement of AChE inhibition potency and AChE/BChE selectivity was achieved with incorporation of a halogen at the 6-position of homodimeric tacrines. The assay results of 3a-m also provided evidence that the 7-methylene tether tended to be optimal to AChE inhibition potency.