Pelvic Laparoscopy

Reviewing the Literature

Prostate Cancer continued assay, which at cutoff points of 2.5 and 4.0 ng/mL had a sensitivity of 98% and 87% and a specificity of 5% and 16%, respectively. The sensitivity and specificity of the uPM3 test seemed to be best among men in the diagnostic “gray” zone of PSA between 4 and 10 ng/mL. Although the results of this assay seem promising, the fact that over 20% of patients had a noninformative assay is concerning. If these patients are included in the analysis, the “effective” sensitivity is reduced from 82% to 69%—a much less impressive result. uPM3, A New Molecular Urine Test for the Detection of Prostate Cancer Fradet Y, Saad F, Aprikian A, et al. Urology. 2004;64:311-315. This is the third study, and the only multicenter study, to examine the value of uPM3. Fradet and colleagues studied the uPM3 assay from 517 men undergoing prostate needle biopsy at 5 medical centers. Similar to the above study, a sizable percentage of men (14%) had noninformative uPM3 assay results. Therefore, data are presented only for the 443 men with usable data. The positive biopsy rate was 34%. Like the prior studies, no mention was made of the biopsy technique. The overall area under the ROC curve for predicting the presence of prostate cancer for the uPM3 test was 0.86— similar to the value seen in the prior study by this same group (see above). Use of a uPM3 cutoff point of 0.5 value of probability resulted in a sensitivity of 66% and specificity of 89% for predicting prostate cancer on biopsy. The uPM3 test functioned best among men with a PSA level less than 4 ng/mL, with a sensitivity of 74% and a specificity of 91%. In summary, these 3 studies suggest that the uPM3 test might have a reasonable sensitivity and specificity for detecting prostate cancer, which in some instances might be better than the sensitivity and specificity of PSA assay, The uPM3 test might have a reasonable sensitivity and specificity for detecting prostate cancer, which in some instances might be better than the sensitivity and specificity of PSA assay. The first issue is the loss of nearly 20% of patients who had noninformative data. The importance of this cannot be overstated. Our collective anecdotal experience in realworld practice using the commercially available uPM3 test suggests that the “noninformative” rate might actually be higher than 20%. The second major limitation is that unlike PSA, uPM3 seems to offer no prognostic value for the stage or grade of the cancer, though this has not been directly studied. Given that the overall prevalence of prostate cancer is extremely high, Carter’s recent statement in the New England Journal of Medicine should be recalled: “It is apparent that any approach that finds more cancers without quantifying the clinical significance of the detected disease will only increase overdiagnosis and overtreatment.”4 Future studies will be needed to assess whether a quantitative uPM3 test (rather than positive vs negative) will help preferentially detect higher-grade, high-stage cancers. In addition, it would be useful to know whether, among men with prostate cancer, uPM3 provides any prognostic value for predicting outcome, as PSA does. Ultimately, if these issues can be addressed, uPM3 seems to be a promising new prostate cancer biomarker. References 1. 2. 3. 4. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level
or  4.0 ng per milliliter. N Engl J Med. 2004;350:2239-2246. Bussemakers MJ, van Bokhoven A, Verhaegh GW, et al. DD3: a new prostatespecific gene, highly overexpressed in prostate cancer. Cancer Res. 1999;59: 5975-5979. Carter HB. Prostate cancers in men with low PSA levels—must we find them? N Engl J Med. 2004;350:2292-2294. Pelvic Laparoscopy Role of Fibrin in the Development of Surgical Adhesions Reviewed by Jacob Rajfer, MD Department of Urology, University of California at Los Angeles, Los Angeles, CA [Rev Urol. 2005;7(4):238-239] though larger studies are clearly needed. In addition, no data on free PSA, which might help improve the prognostic value of PSA, was presented in any of the studies. However, despite the fact that uPM3 is now commercially available, several limitations need to be addressed before uPM3 becomes the standard for prostate cancer screening. 238 VOL. 7 NO. 4 2005 REVIEWS IN UROLOGY © 2005 MedReviews, LLC ne of the major problems with intra-abdominal surgical procedures, including pelvic surgery, is the development of adhesions within the intra-abdominal space postoperatively. This is usually not a clinical issue O Pelvic Laparoscopy unless another intra-abdominal surgical procedure is to be performed at a later date or pain from the adhesions or a bowel obstruction develops. These intra-abdominal adhesions are the bane of every surgeon’s existence because they make a subsequent surgical procedure much more difficult, more labor intensive, and more prone to an intraabdominal injury. Just imagine if all intra-abdominal surgical procedures could be made adhesion free! Adhesions are fibrotic connections between two tissue planes—in the case of intra-abdominal adhesions, between two organs or an organ and the abdominal wall. The mechanisms by which fibrosis develops are beginning to be deciphered at the biochemical level. Most evidence points to the involvement of the fibrinolytic system in this process, and converging data from a variety of disciplines seem to suggest that a defective fibrinolytic system is intimately involved in or is actually responsible for the development of tissue fibrosis, including intra-abdominal adhesions. Surgery per se can lead to a local inflammatory response, which in turn may lead to the local depo- It may be hypothesized that the development of surgical adhesions or tissue fibrosis in general may be due to the failure of the fibrinolytic system to degrade the fibrin. sition of fibrin. Fibrin happens to be an extremely pro-fibrotic compound, and its continued presence (or a failure to remove the fibrin) seems to induce fibrosis.1,2 Therefore, it may be hypothesized that the development of surgical adhesions or tissue fibrosis in general may be due to the failure of the fibrinolytic system to degrade the fibrin. A Role for the Fibrinolytic System in Postsurgical Adhesion Formation Hellebrekers BWJ, Emeis JJ, Kooistra T, et al. Fert and Ster. 2005;83:122-129. In a group of 50 female patients undergoing pelvic laparoscopy for either an infertility evaluation or treatment of endometriosis, the presence or absence of adhesions was noted either at the first laparoscopy or at a second laparoscopy, when indicated. Measurements were made of soluble fibrin, PAI-1 (plasminogen activator inhibitor), tPA (tissue plasminogen activator), plasmin-antiplasmin complexes, and fibrin degradation products in the peritoneal fluid. Patients with adhesions had significantly higher concentrations of PAI-1, tPA, and plasminogen than those without adhesions. In patients who developed adhesions between an initial and subsequent laparoscopy, there was biochemical evidence of a defective fibrinolytic system in the peritoneal fluid. These observations suggest that the plasmin-fibrinogen system is operative in the development of adhesions and that it may be possible to prevent these abdominal adhesions by the use of fibrinolytic enhancers or inhibitors of PAI-1. The development of such a therapeutic regimen would be a major advancement in surgery, as the use of this regimen at the time of surgery would potentially lead to a decrease in surgical adhesions and their resulting clinical sequelae. References 1. 2. Davila HH, Magee TR, Zuniga FL, et al. Peyronie's disease associated with increase in plasminogen activator inhibitor in fibrotic plaque. Urology. 2005;65:645-648. Davila HH, Ferrini MG, Rajfer J, Gonzalez-Cadavid NF. Fibrin as an inducer of fibrosis in the tunica albuginea of the rat: a new animal model of Peyronie's disease. BJU Int. 2003;91:830-838. VOL. 7 NO. 4 2005 REVIEWS IN UROLOGY 239