Jeffrey A. Stern

Monocyte Chemoattractant Protein-1 and Macrophage Inflammatory Protein-1α as Possible Biomarkers for the Chronic Pelvic Pain Syndrome

PURPOSE The chronic pelvic pain syndrome is characterized by pelvic pain, voiding symptoms and varying degrees of inflammation within expressed prostatic secretions. We evaluated the chemokines monocyte chemoattractant protein 1 (CCL2) and macrophage inflammatory protein-1alpha (CCL3) in expressed prostatic secretions to identify marker increases associated with inflammatory (IIIA) and noninflammatory (IIIB) chronic pelvic pain syndrome. In addition, chemokine levels were correlated with clinical pain as determined by the National Institutes of Health chronic prostatitis symptom index. MATERIALS AND METHODS Expressed prostatic secretions were collected by digital rectal examination, and evaluated by enzyme linked immunosorbent assays for monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha in 154 patients including controls (13), those with benign prostatic hyperplasia (54), chronic pelvic pain syndrome IIIA (37) and IIIB (50). Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha levels were compared between IIIA, IIIB and the control subgroups, and correlated against the chronic prostatitis symptom index and pain subscore using a Spearman test. RESULTS Mean levels of monocyte chemoattractant protein 1 in the control, inflammatory benign prostatic hyperplasia, noninflammatory benign prostatic hyperplasia, inflammatory chronic pelvic pain syndrome and noninflammatory chronic pelvic pain syndrome were 599.4, 886.0, 1,636.5, 3,261.2 and 2,272.7 pg/ml, respectively. Mean levels of macrophage inflammatory protein-1alpha in the control, inflammatory benign prostatic hyperplasia, noninflammatory benign prostatic hyperplasia, IIIA chronic pelvic pain syndrome and IIIB chronic pelvic pain syndrome were 140.1, 299.4, 238.7, 1,057.8 and 978.4 pg/ml, respectively. For each cytokine both chronic pelvic pain syndrome subtypes had statistically higher levels than the control group and patients with benign prostatic hyperplasia (p = 0.0002). Receiver operating curves using monocyte chemoattractant protein 1 levels greater than 704 pg/ml and macrophage inflammatory protein-1alpha greater than 146 pg/ml identified patients with chronic pelvic pain syndrome with an accuracy of 90% from control patients. Macrophage inflammatory protein-1alpha levels (p = 0.0007) correlated with the pain subscore of the chronic prostatitis symptom index while monocyte chemoattractant protein 1 (p = 0.71) did not. CONCLUSIONS Monocyte chemoattractant protein 1 and macrophage inflammatory protein-1alpha within the prostatic fluid in both chronic pelvic pain syndrome subtypes provide candidate future biomarkers for chronic pelvic pain syndrome. In addition, macrophage inflammatory protein-1alpha increase in expressed prostatic secretions provides a new marker for clinical pain in chronic pelvic pain syndrome patients. Given these findings prostatic dysfunction likely has a role in the pathophysiology of this syndrome. These chemokines may serve as effective diagnostic markers and modulators against the chemokines could provide an attractive treatment strategy in individuals with chronic pelvic pain syndrome.

LONG-TERM RESULTS OF THE STAMEY BLADDER NECK SUSPENSION: DIRECT COMPARISON WITH THE MARSHALL-MARCHETTI-KRANTZ PROCEDURE

PURPOSE We performed followup of a cohort of women who underwent the Stamey endoscopic needle suspension (group 1) or the Marshall-Marchetti-Krantz vesicourethropexy (group 2) between 1975 and 1983. MATERIALS AND METHODS Telephone interviews were performed to assess current continence status and time to failure. Risk factors for recurrence of incontinence were correlated with long-term results. RESULTS Long-term data were obtained for 32 of 41 women (78%) in group 1 and 36 of 54 (67%) in group 2. Range of followup was 9.4 to 19.9 years (median 15.0, mean 15.2) in group 1 and 13.2 to 21.9 (median 16.8, mean 17.0) in group 2. Of group 1 patients 44% remained dry compared to 33% of group 2 patients. Persistent local side effects were reported by 9% of group 1 and 0% of group 2. Urinary urgency was present in 70% of group 1 patients and 23% of group 2. There was no relationship between long-term operative success and age at surgery, degree of preoperative incontinence, parity, obesity, prior incontinence surgery or prior hysterectomy for either procedure. CONCLUSIONS The Stamey and the Marshall-Marchetti-Krantz procedures yield high initial cure rates with progressive, parallel declines in continence status with time.

Suppressive roles of calreticulin in prostate cancer growth and metastasis.

Calreticulin is an essential, multifunctional Ca(2+)-binding protein that participates in the regulation of intracellular Ca(2+) homeostasis, cell adhesion, and chaperoning. Calreticulin is abundantly expressed and regulated by androgens in prostate epithelial cells. Given the importance of both calreticulin in multiple essential cellular activities and androgens in prostate cancer, we investigated the possibility of a role for calreticulin in prostate cancer progression. Immunohistochemistry revealed the down-regulation of calreticulin in a subset of human prostate cancer specimens. Prostate cancer cells overexpressing exogenous calreticulin produced fewer colonies in both monolayer culture and soft agar. Furthermore, calreticulin overexpression also inhibited tumor growth in the orthotopic PC3 xenograft tumor model and macroscopic lung metastasis in the rat Dunning AT3.1 prostate tumor model. To address the potential mechanism of calreticulin suppression of prostate cancer, we generated calreticulin mutants with different functional domains deleted. The calreticulin mutants containing the P-domain, which binds to other endoplasmic reticulum chaperone proteins, were sufficient for the suppression of PC3 growth in colony formation assays. Overall, our data support the hypothesis that calreticulin inhibits growth and/or metastasis of prostate cancer cells and that this suppression requires the P-domain.

TissueLink™ Device for Laparoscopic Nephron-Sparing Surgery

BACKGROUND AND PURPOSE One of the most challenging aspects of laparoscopic partial nephrectomy is achieving adequate control of bleeding from the tumor bed. We report our initial experience with laparoscopic nephron-sparing surgery using the TissueLink floating-ball radiofrequency dissector. PATIENTS AND METHODS From March 2002 to April 2003, we performed 14 purely laparoscopic nephron-sparing nephrectomies using the floating-ball device on 11 patients. RESULTS The mean operative time was 124 minutes (range 90-210 minutes). The mean estimated blood loss was 168 mL (range 20-600 mL). One patient had a small urine leak and was sent home with the drain in place. CONCLUSIONS We successfully treated 14 small renal lesions using the TissueLink floating-ball device. The procedure was performed in an expeditious fashion with minimal blood loss. Long-term follow-up is required to determine the oncologic efficacy.

Osteomyelitis of the pubis: a complication of a chronic indwelling catheter

Pubic osteomyelitis typically occurs after pelvic surgery or trauma. We present a case of pubic osteomyelitis ensuing from a chronic indwelling (for 8 years) urethral catheter in a 40-year-old woman. She presented initially with fever of unknown origin, and broad-spectrum antimicrobial therapy was initiated. Computed tomography of the abdomen and pelvis ultimately revealed cortical destruction of the pubic symphysis, and open biopsy confirmed osteomyelitis. Osteomyelitis of the pubis is a rare entity that typically results from bacteremia, trauma, or the spread of an adjacent focus of infection from previous pelvic surgery. To our knowledge, this is the first report of pubic osteomyelitis resulting from a chronic indwelling urethral catheter.

Pneumothorax Masked by Subcutaneous Emphysema after Laparoscopic Nephrectomy

An 81-year-old man with an enhancing upper-pole renal mass underwent laparoscopic nephrectomy via a retroperitoneal approach. Postoperatively, his systolic blood pressure declined to 72 mm Hg, and arterial blood gas analysis suggested acute respiratory acidosis. Chest radiography suggested subcutaneous emphysema, but a CT scan showed tension pneumothorax. This case illustrates the difficulties in interpretation of chest films caused by the subcutaneous air that is routinely present after laparoscopic procedures.