This Month in Investigative Urology

Article Outline

• Annexin A3 in Urine As Marker for Prostate Cancer
• Diagnostic Value of Cell-Free Circulating DNA in Testicular Germ Cell Cancer
• GRC-6211 Counteracts Bladder Overactivity and Noxious Input Induced by Cystitis
• Comparative In Vivo Study of Lymphatic Sealing Devices
• Pubo-Urethral Ligament Injury in Female Rats as a Model of Chronic Stress Urinary Incontinence
• Copyright

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Annexin A3 in Urine As Marker for Prostate Cancer 

In patients with prostate cancer the early diagnosis of tumors with a high risk of progression is of the utmost importance, and there is an urgent clinical need to avoid unnecessary biopsies and subsequent overtreatment. Schostak et al (page 343) from Berlin, Germany validated annexin A3 (ANXA3) as a diagnostic marker for prostatic disease in 591 patients with a negative digital rectal examination and low prostate specific antigen (PSA). Urine was obtained directly after digital rectal examination and analyzed quantitatively for ANXA3 by Western blot. Statistical analyses included combinations of ANXA3 with total, percent free, complex and percent complex PSA.

Combined readouts of PSA and urinary ANXA3 were superior to all others. ANXA3 was found to have an inverse relationship to cancer and, therefore, the specificity is much better than that of PSA. The authors concluded that ANXA3 quantification in urine provides a novel, noninvasive biomarker of high specificity. ANXA3 is complementary to PSA and has the potential to avoid unnecessary biopsies, particularly in patients with a negative digital rectal examination and low PSA.

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Diagnostic Value of Cell-Free Circulating DNA in Testicular Germ Cell Cancer 

Testicular germ cell cancer represents approximately 1% of the malignant neoplasms found in the male population. Conventional serum tumor markers are increased in only approximately 60% of testicular cancer cases and additional serum markers would facilitate the clinical management of these cases. Cell-free DNA represents an interesting universal tumor marker. Ellinger et al (page 363) from Munich, Germany isolated cell-free DNA in serum from 74 patients with testicular cancer (seminoma 39, nonseminoma 35) and compared DNA levels as well as fragmentation patterns with those in healthy individuals (35).

ACTB-106/ACTB-193/ACTB-384 fragment levels were significantly increased, and DNA integrity was significantly decreased in patients with cancer compared to healthy individuals with no differences between those with seminoma or nonseminoma. Cell-free DNA levels distinguished between patients with cancer and healthy individuals (sensitivity 87%, specificity 97%). The authors concluded that cell-free DNA levels are increased in patients with testicular cancer and allow the accurate determination of healthy individuals. The high sensitivity of cell-free DNA could facilitate the treatment of these patients, especially those with nonincreased conventional tumor markers.

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GRC-6211 Counteracts Bladder Overactivity and Noxious Input Induced by Cystitis 

Previous investigations have shown that the TRPV1 receptor is essential for the generation of noxious input and bladder reflex overactivity induced by cystitis. Charrua et al (page 379) from Porto, Portugal investigated the effects of a novel, orally active TRPV1 receptor antagonist on bladder function in normal rats and in various rat models of inflammation. Cystometry was performed in urethane anesthetized animals in which bladder overactivity was induced by intravesical capsaicin or acetic acid, and spinal c-fos expression was investigated after intravesical acetic acid instillation. Reflex bladder activity was unchanged after low doses of the TRPV1 antagonist. However, at a high concentration bladder contractions were transiently suppressed in normal rats but not in mice lacking the TRPV1 receptor. Low concentrations of the antagonist completely prevented the effects of intravesical capsaicin and decreased the overactivity induced by intravesical acetic acid. C-fos expression induced by intravesical acetic acid was reduced by the antagonist. The authors concluded that CRC-6211 counteracts bladder overactivity and noxious input induced by cystitis, that high doses also suppress normal bladder activity by a TRPV1 mediated mechanism and that the TRPV1 antagonist may be useful in patients with cystitis.

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Comparative In Vivo Study of Lymphatic Sealing Devices 

Chylous ascites and lymphocele formation are known complications of complex oncological procedures performed via a laparoscopic approach. Several devices are available to facilitate dissection and hemostasis during such surgery, and have been well studied in their ability to seal blood vessels. Box et al (page 387) from Orange, California documented and compared the quality of lymphatic sealing by each of 4 commonly used laparoscopic dissection devices. The LigaSure™ V with the ForceTriad™ Generator, Trissector™ and EnSeal™ are bipolar devices while the Harmonic ACE™ Scalpel uses ultrasonic energy. As a fifth device standard laparoscopic scissors (Ethicon Endosurgery) connected to a monopolar electrocautery unit were used. The experiments were performed on the thoracic duct of anesthetized pigs. In 1 group of animals the duct was cannulated for determination of burst pressure and in another group the seals produced were sent for histopathological evaluation. No acute seal failures were observed with any of the bipolar devices or the harmonic shears. However, 2 (33%) immediate failures were seen with the monopolar scissors. Histopathological evaluation revealed that the LigaSure caused less thermal damage than the Trissector and EnSeal. The authors concluded that each of the devices tested, with the exception of the monopolar scissors, consistently produced a supraphysiological seal and should be suitable for sealing lymphatic vessels during laparoscopic surgery.

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Pubo-Urethral Ligament Injury in Female Rats as a Model of Chronic Stress Urinary Incontinence 

Urinary incontinence affects 40% of women in the United States and stress urinary incontinence (SUI) accounts for the majority. Deficient pubo-urethral ligament (PUL) may lead to urethral mobility, SUI or mixed urinary continence. Kefer et al (page 397) from Cleveland, Ohio examined the long-term effects of PUL deficiency in female rats as a potential model for SUI. They compared the results with those of pudendal nerve transection (PNT), an established model of SUI, and with those of sham PUL. Leak point pressure was the primary outcome parameter. The results showed that 20 days after PUL transection leak point pressure was significantly decreased (compared to sham). The decrease was comparable to that caused by PNT. The absence of PUL was verified by histology. The authors concluded that deficiency of PUL in the female rat induced long-term SUI comparable to that of PNT, and suggested that their model could be used for investigation of the mechanisms of SUI in the female.