The effect of osteoprotegerin administration on the intra-tibial growth of the osteoblastic LuCaP 23.1 prostate cancer xenograft

Osteoprotegerin (OPG) plays a central role in controlling bone resorption. Exogenous administration of OPG has been shown to be effective in preventing osteolysis and limiting the growth of osteolytic metastasis. The objective of this study was to investigate the effects of OPG on osteoblastic prostate cancer (CaP) metastases in an animal model. LuCaP 23.1 cells were injected intra-tibially and Fc-OPG (6.0 mg/kg) was administered subcutaneously three times a week starting either 24 hours prior to cell injection (prevention regimen) or at 4 weeks post-injection (treatment regimen). Changes in bone mineral density at the tumor site were determined by dual x-ray absorptiometry. Tumor growth was monitored by evaluating serum prostate specific antigen (PSA). Fc-OPG did not inhibit establishment of osteoblastic bone lesions of LuCaP 23.1, but it decreased growth of the tumor cells, as determined by decreases in serum PSA levels of 73.0 ± 44.3% ( P < 0.001) and 78.3 ± 25.3% ( P < 0.001) under the treatment and prevention regimens, respectively, compared to the untreated tumor-bearing animals. Administration of Fc-OPG decreased the proliferative index by 35.0% ( P = 0.1838) in the treatment group, and 75.2% ( P = 0.0358) in the prevention group. The results of this study suggest a potential role for OPG in the treatment of established osteoblastic CaP bone metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42587/1/10585_2004_Article_2869.pd

Does teaching of robotic partial nephrectomy affect renal function and perioperative outcomes?

Partial nephrectomy (PN) represents the treatment of choice for localized renal tumor&lt;7cm. Minimally invasive approaches are considered standard of care in many institutions. Maintaining acceptable warm ischemic time (WIT) while teaching robotic PN (RPN) remains challenging. The goal of the present study was to assess the effect of teaching RPN on WIT and renal function in patients undergoing RPN. Patients undergoing RPN for cT1-T2 renal tumors were included. RENAL nephrometry score was used to adjust for tumor complexity. Glomerular filtration rates (GFR) were determined preoperatively, at day 2 and at ≥3-month follow-up. Patients in whom the attending surgeon (staff) performed tumorectomy and renorraphy were compared with those in whom the fellow performed these steps. Primary outcomes were WIT and GFR decrease at follow-up visit. Morbidity and margin positivity represented secondary outcomes. Overall, 69 patients (46 "staff" vs. 23 "fellow") were included. Patient׳s characteristics did not differ significantly between the 2 groups. In particular, RENAL score and preoperative GFR were similar between both groups. Mean WIT was 22±9 in the staff and 24±7 in the fellow group (P = 0.09). At follow-up, a GFR reduction of 9% was observed in the staff group vs. 13% in the fellow group (P = 0.38). Complication rates (13% vs. 17%, P = 0.63) and positive margins (9% vs. 4%, P = 0.47) did not differ significantly between staff and fellow. In our experience, teaching RPN with a strict supervision and stepwise standardized procedure was oncologically and functionally safe after 3 to 6 months of follow-up

Cost-effectiveness of multiparametric magnetic resonance imaging and targeted biopsy in diagnosing prostate cancer.

INTRODUCTION: Transrectal ultrasound-guided biopsy (TRUSGB) is the recommended approach to diagnose prostate cancer (PCa). Overdiagnosis and sampling errors represent major limitations. Magnetic resonance imaging (MRI)-targeted biopsy (MRTB) detects higher proportion of significant PCa and reduces diagnosis of insignificant PCa. Costs prevent MRTB from becoming the new standard in PCa diagnosis. The present study aimed at assessing whether added costs of MRI outweigh benefits of MRTB in a cost-utility model. MATERIALS AND METHODS: A Markov model was developed to estimate quality-adjusted life-year gained (QALY) and costs for 2 strategies (the standard 12-core TRUSGB strategy and the MRTB strategy) over 5, 10, 15, and 20 years. MRI was used as triage test in biopsy-naive men with clinical suspicion of PCa. The model takes into account probability of men harboring PCa, diagnostic accuracy of both procedures, and probability of being assigned to various treatment options. Direct medical costs based on health care system perspective were included. RESULTS: Following standard TRUSGB pathway, calculated cumulative effects at 5, 10, 15, and 20 years were 4.25, 7.17, 9.03, and 10.09 QALY, respectively. Cumulative effects in MRTB pathway were 4.29, 7.26, 9.17, and 10.26 QALY, correspondingly. Costs related to TRUSGB strategy were $8,027,$11,406, $14,883, and$17,587 at 5, 10, 15, and 20 years, respectively, as compared with $7,231,$10,450, $13,267, and$15,400 for the MRTB strategy. At 5, 10, 15, and 20 years, MRTB was the established dominant strategy. CONCLUSIONS: Incorporation of MRI and MRTB in PCa diagnosis and management represents a cost-effective measure at 5, 10, 15, and 20 years after initial diagnosis

Initial single-centre Canadian experience with 18F-fluoromethylcholine positron emission tomography-computed tomography (18F-FCH PET/CT) for biochemical recurrence in prostate cancer patients initially treated with curative intent.

We sought to determine predictive factors (patient and prostate-specific antigen [PSA] characteristics) for 18F-fluoromethylcholine positron emission tomography-computed tomography (18F-FCH PET/CT) positivity in the context of biochemical recurrence after local treatment of prostate cancer (PCa) with curative intent. This is a retrospective study including 60 18F-FCH PET/CT scans of patients with biochemical recurrence after initial radical prostatectomy (RP), external beam radiation therapy (EBRT), or focal high-intensity focused ultrasound (HIFU) with curative intent. The results were compared to findings on magnetic resonance imaging (MRI), computed tomography (CT), bone scan (BS), and histological analysis when available. Univariate analysis was performed to correlate results with patient characteristics. Thirty-eight (63.3%) scans were positive, 17 (28.3%) negative, and 5 (8.3%) equivocal. Of the positive scans, 16 demonstrated local recurrence, 12 regional/distant lymph nodes, five bone metastasis, and five local and distant recurrences. Among the 22 PET/CTs showing metastasis, conventional imaging was performed in 16 patients (72.7%). Of these, it demonstrated the lesion(s) found on PET/CT in eight patients (50.0%), was negative in seven (43.8%), and equivocal in one (6.3%). The trigger PSA (p=0.04), prostate-specific antigen velocity (PSAV) (p=0.03), and prostate-specific antigen doubling time (PSADT) (p=0.046) were significantly different when comparing positive and negative scans. Patients with positive scans were more likely to have received EBRT initially (odds ratio [OR] 11.0, 95% confidence interval [CI] 2.2-55.3). A trigger PSA of 2.6 ng/mL had a sensitivity of 84% and specificity of 65% for a positive scan. PET/CT changed the clinical management plan in 17 patients (28.3%). 18F-FCH PET/CT demonstrates a high detection rate for local and distant recurrences after localized PCa treatment. A trigger PSA above 2.6 ng/mL seems optimal for appropriate patient selection

Accuracy of cognitive MRI-targeted biopsy in hitting prostate cancer-positive regions of interest.

Prostate cancer (PCa) diagnosis relies on clinical suspicion leading to systematic transrectal ultrasound-guided biopsy (TRUSGB). Multiparametric magnetic resonance imaging (mpMRI) allows for targeted biopsy of suspicious areas of the prostate instead of random 12-core biopsy. This method has been shown to be more accurate in detecting significant PCa. However, the precise spatial accuracy of cognitive targeting is unknown. Consecutive patients undergoing mpMRI-targeted TRUSGB with cognitive registration (MRTB-COG) followed by robot-assisted radical prostatectomy were included in the present analysis. The regions of interest (ROIs) involved by the index lesion reported on mpMRI were subsequently targeted by two experienced urologists using the cognitive approach. The 27 ROIs were used as spatial reference. Mapping on radical prostatectomy specimen was used as reference to determine true-positive mpMRI findings. Per core correlation analysis was performed. Forty patients were included. Overall, 40 index lesions involving 137 ROIs (mean ROIs per index lesion 3.43) were identified on MRI. After correlating these findings with final pathology, 117 ROIs (85 %) were considered as true-positive lesions. A total of 102 biopsy cores directed toward such true-positive ROIs were available for final analysis. Cognitive targeted biopsy hit the target in 82 % of the cases (84/102). The only identified risk factor for missing the target was an anterior situated ROI (p = 0.01). In experienced hands, cognitive MRTB-COG allows for an accuracy of 82 % in hitting the correct target, given that it is a true-positive lesion. Anterior tumors are less likely to be successfully targeted