Prostate Specific Antigen Nadir of 0.1 or Less Is a Predictor of Treatment Success in Men Undergoing Salvage Whole Prostate Gland Cryoablation.

PURPOSE: To assess factors that affect prostate biopsy results following salvage whole gland cryoablation. PATIENTS AND METHODS: One hundred seventy-four patients underwent prostate biopsy following salvage whole gland cryoablation of the prostate in the Cryo-OnLine Database registry. Wilcoxon rank-sum and χ2 tests and logistic regression analysis were used to assess predictors of positive biopsy. Prostate specific antigen (PSA) nadir was divided into a statistical tertile for comparisons between different nadir PSA cut points. RESULTS: Fifty-two of 174 (29.9%) of this highly select group of men who underwent biopsy had a posttreatment biopsy demonstrating malignant cancer. Men who had positive biopsy following salvage therapy had significantly higher median nadir PSA, shorter median time to prostate biopsy, and shorter median time to biochemical failure. Compared to the lowest tertile (PSA nadir defined as ≤0.1 ng/mL), PSA in the second tertile (0.11-0.8 ng/mL) and third tertile (>0.8 ng/mL) demonstrated increased odds ratio (OR) for positive biopsy, 4.34 (95% confidence interval [CI] 1.66, 11.4, p = 0.003) and 2.81 (95% CI 1.14, 7.00, p = 0.02), respectively, in adjusted models. In addition, men with a presalvage PSA >20 (OR 7.65; 95% CI 2.03, 28.9; p = 0.003) and Gleason score ≥8 (OR 2.26; 95% CI 0.93, 5.47; p = 0.07) had a higher OR of positive biopsy. CONCLUSIONS: Nadir PSA of 0.1 ng/mL or less following salvage cryotherapy is predictive of treatment success. Routine biopsy should be reserved for men with nadir PSA >0.1 ng/mL and patients with high risk features of prostate cancer before salvage cryoablation.

Cadaveric anatomy of pelvic fracture urethral distraction injury: most injuries are distal to the external urinary sphincter.

PURPOSE: The anatomy of posterior urethral distraction injuries is controversial. We present a cadaver study of posterior urethral distraction injuries. To our knowledge this is the first study that establishes that the most common location is distal to the external urinary sphincter. MATERIALS AND METHODS: We performed an autopsy review of 10 male patients with posterior urethral distraction injuries. RESULTS: Urethral disruption occurred distal to the external urinary sphincter in 7 of 10 patients. It appeared to occur when the anterior pelvic ring and urogenital diaphragm complex were displaced caudal and rostrally, tearing the urogenital diaphragm off of the urethra. The average inner mucosal defect +/- SD was 3.5 +/- 0.5 cm, while the defect between the outer urethral layer (tunica of the spongiosum) was 2.0 +/- 0.2 cm due to mucosal retraction. Simple and complex injuries could be observed, according to the clinical classification proposed by Turner-Warwick in 1989. Simple injuries had less significant dislocation of the symphysis, general maintenance of urethral continuity and slightly shorter mucosal distraction (3.3 cm). Complex disruptions had significant symphyseal dislocation, complete disassociation of the urethral ends (often with interposition of other tissues) and a slightly longer mucosal distraction (3.8 cm). CONCLUSIONS: Posterior urethral distraction injuries appear to most commonly occur distal to the urogenital diaphragm, contrary to classic teaching. These injuries are on average between 3 and 4 cm, and they are more significant dorsal than ventral. They appear to occur as simple or complex injuries, mirroring the clinical findings seen in clinically simple and complex urethral strictures.

The treatment of posterior urethral disruption associated with pelvic fractures: comparative experience of early realignment versus delayed urethroplasty.

PURPOSE: Urological treatment of the patient with severe mechanical trauma and urethral disruption remains controversial. Debate continues regarding the advisability of early realignment vs delayed open urethroplasty. We analyzed our experience with 96 patients to determine the long-term results of the 2 approaches. MATERIALS AND METHODS: We retrospectively reviewed the records of 191 men with posterior urethral disruption after severe blunt pelvic injury between 1984 and 2001, of whom 96 survived. Data on 57 patients who underwent early realignment were compared to those on 39 treated with delayed urethroplasty with an average 8.8-year followup (range 1 to 22). All patients were evaluated postoperatively for incontinence, impotence and urethral strictures. RESULTS: The majority of patients had severe concomitant organ injuries (78%) and severe pelvic fractures (76%). The overall mortality rate was 51%. Diagnosis of urethral rupture was based on clinical findings and retrograde urethrography. Strictures developed in 49% of the early realignment group and in 100% of the suprapubic tube group. Impotence (33.6%) and incontinence (17.7%) were less frequent in the early realignment group than in the delayed reconstruction group (42.1% and 24.9%, respectively). Patients with delayed reconstruction underwent an average of 3.1 procedures compared with an average of 1.6 in the early realignment group. CONCLUSIONS: Early realignment may provide better outcomes than delayed open urethroplasty after posterior urethral disruption. Increased complications are not seen and, although it can be inconvenient in the massively injured patient, it appears to be a worthwhile maneuver.

Route of administration influences the antitumor effects of bone marrow-derived dendritic cells engineered to produce interleukin-12 in a metastatic mouse prostate cancer model.

Gene-modified dendritic cells (DC) provide unique therapeutic strategies for prostate cancer; however, the comparative evaluation of specific delivery options using appropriate preclinical models has not been described. In this study, bone marrow-derived DC were genetically engineered to express high levels of interleukin-12 (IL-12) with or without the costimulatory molecule B7-1, by ex vivo infection with recombinant adenoviral vectors. We used an orthotopic metastatic mouse prostate cancer preclinical model (178-2 BMA) to compare two therapeutic protocols for DC delivery, in situ and subcutaneous. DC were generated from bone marrow of syngeneic 129/Sv mice by culturing in the presence of GM-CSF and IL-4. In vitro DC/IL-12 or DC/IL-12/B7 produced high levels of biologically active IL-12. In situ delivery of DC/IL-12 or DC/IL-12/B7 induced a significant suppression of primary tumor growth compared to DC/beta gal controls (P=.0328 and P=.0019, respectively), as well as reduced numbers of spontaneous lung metastatic nodules (P=.1404 and P=.0335, respectively). In survival experiments, in situ DC/IL-12 injection demonstrated a small but statistically significant advantage (P=.0041). Subcutaneous, tumor lysate pulsed DC/IL-12 significantly decreased tumor size (P=.0152) and increased survival (P=0.0433) compared to HBSS controls but the decrease in the number of spontaneous lung metastases did not achieve statistical significance. Both in situ and subcutaneous treatments enhanced cytolytic activities of natural killer (NK) cells and cytotoxic T lymphocytes (CTL). In this preclinical model, gene-modified DC-based intratumoral immunotherapy was shown to be an effective therapeutic strategy for locally advanced prostate cancer based on tumor growth suppression, inhibition of metastasis and survival improvement.