Hospital-specific antibiograms and antibiotic prophylaxis for prostate biopsies: a reexamination of AUA recommendations.

INTRODUCTION: To assess whether standard American Urological Association (AUA) and other recommendations for prostate biopsy prophylaxis provide sufficient coverage of common urinary organisms responsible for post biopsy infections by comparing local antibiograms in Philadelphia-area hospitals. MATERIALS AND METHODS: De-identified culture results derived from antibiograms were collected from six academic and community hospitals in the Philadelphia region. Analysis specifically focused on four major bacterial causes of urinary tract infection following prostate biopsy (Escherichia coli (E. coli), Klebsiella pneumoniae, Proteus mirabilis and Enterococcus faecalis) along with commonly recommended antibiotics including fluoroquinolones (FQ's), trimethoprim/sulfamethoxazole, ceftriaxone, and gentamicin. RESULTS: Bacterial sensitivities to each antibiotic across institutions showed variation in E.coli sensitivities to FQs (p < 0.001), trimethoprim/sulfamethoxazole (p < 0.001), ceftriaxone (p < 0.001) and gentamicin (p < 0.001). Klebsiella pneumoniae and Proteus mirabilis exhibited similar variations. Sensitivity comparisons for Enterococcus faecalis was unable to be performed due to absent or incomplete data across institutions. CONCLUSION: Institutional antibiograms vary within our regional hospitals. Standardized recommendations for commonly used antibiotic prophylaxis such as fluoroquinolones may be inadequate for peri-procedural prostate biopsy prophylaxis based on local resistance patterns. Valuable information about the potential effectiveness of antibiotic prophylaxis for prostate biopsies can be found in local institutional antibiograms, and should be consulted when considering antibiotic prophylaxis for prostate biopsy procedures.

Prostate Contrast Enhanced Transrectal Ultrasound Evaluation of the Prostate With Whole-Mount Prostatectomy Correlation.

OBJECTIVE: To investigate the diagnostic accuracy of contrast enhanced transrectal ultrasound (CE-TRUS) in comparison with whole-mount radical prostatectomy specimens. METHOD AND MATERIALS: Fifty-eight subjects who underwent CE-TRUS and subsequent radical prostatectomy with whole-mount pathology were included in the study. Each patient underwent evaluation with baseline TRUS and again during CE-TRUS with intravenous infusion of perflutren lipid microsphere (Definity, Lantheus Medical Imaging, N Billerica, MA). A subjective 5 point scale was used to rate each sextant of the prostate in 3 baseline imaging modes and in 5 contrast-enhanced imaging modes. Baseline TRUS and CE-TRUS findings were compared with digitized whole-mount findings. A clustered logistic regression model was computed to compare the area under the receiver operating characteristic curve (Az) for detection of prostate cancer by various modes of ultrasound imaging. RESULTS: Among the 58 whole-mount specimens, a maximum Gleason score of 6 was identified in 29 subjects, a score of 7 was identified in 24 and a score of 8 was identified in 5. The Az for baseline TRUS parameters was 0.55 for grayscale, 0.61 for color Doppler and 0.59 for power Doppler. CE-TRUS parameters demonstrated significant increases in Az with the highest Az for CE-power Doppler (0.66) and flash replenishment imaging (0.64) (P = .04 for comparison to baseline). The combination of CE-power Doppler and flash replenishment imaging resulted in improved Az compared with baseline imaging (0.70 vs 0.59, P= .006). CONCLUSION: Contrast-enhanced ultrasonography demonstrates greater diagnostic accuracy than baseline imaging. Diagnostic accuracy is further improved for "clinically significant" tumor volumes >1 cc.

Spatial distribution of biopsy cores and the detection of intra-lesion pathologic heterogeneity.

OBJECTIVES: The objective of this study was to determine if spatial distribution of multiparametric magnetic resonance imaging-transrectal ultrasound (mpMRI-TRUS) fusion biopsy cores to the index lesion reveals trends in the detection of intra-lesion Gleason heterogeneity and a more optimal prostate biopsy strategy. METHODS: Index lesion was the lesion with longest diameter on T2-weighted (T2W)-MRI. In cohort 1, fusion biopsy cores biopsies were taken in areas in the center of the target as well as 1 cm laterally on each side. For cohort 2, targeted biopsies were taken from the center of the lesion only. Heterogeneity was defined as difference in maximum Gleason score obtained from fusion cores in the center of the index lesion versus cores obtained from the periphery (cohort 1), or any difference in maximum Gleason score obtained from fusion cores targeted to the index lesion (cohort 2) compared with systematic 12 cores TRUS biopsy. RESULTS: Ninety-nine consecutive patients (35 and 64 in cohorts 1 and 2, respectively) with median age (SD) and prostate-specific antigen (PSA) of 66.9 (±5.9) and 9.7 (±8.2) respectively, were included. Age, PSA, Prostate Imaging Reporting and Data System (PI-RADS) score, and preoperative MRI lesion size were not significantly different between cohorts. Gleason heterogeneity was observed at a significantly higher rate in cohort 1 versus cohort 2 (58% versus 24%; p = 0.041). In cohort 1, cores obtained from the center of the lesion had higher Gleason score than cores obtained from the periphery of the targeted lesion in 57% of cases. CONCLUSIONS: We demonstrate that there is observable tumor heterogeneity in biopsy specimens, and that increased number of cores, as well as cores focused on the center and periphery of the largest lesion in the prostate, provide more comprehensive diagnostic information about the patient's clinical risk category than taking nonspecific cores targeted within the tumor.

Long Term Surveillance of Renal Cell Carcinoma Recurrence Following Ablation using 2D and 3D Contrast-Enhanced Ultrasound.

OBJECTIVE: To evaluate efficacy of using 2D and 3D contrast enhanced ultrasound (CEUS) for surveillance of RCC recurrence in patients post-ablation and identify imaging hallmarks of recurrence. METHODS: 53 patients >8 months post ablation of RCC provided informed consent for this IRB approved study. Patients received 2D and 3D CEUS examinations with Optison (GE Healthcare). Three radiologists of varying CEUS experience described enhancement characteristics, made a diagnosis of recurrence/no-recurrence, and quantified their diagnostic confidence levels. RESULTS: Cases of RCC recurrence showed full ablation cavity enhancement with equal arrival times and intensity compared to the renal cortex. Lack of recurrence was characterized as a complete lack of enhancement within the cavity, or delayed enhancement stemming from the periphery of the ablation cavity. Sensitivity for detecting RCC recurrence was 100% for all readers and specificity was 90%-94%. Reader agreement ranged from 88% to 96%. No significant improvements were achieved with the addition of 3D CEUS, and its inclusion resulted in decreased reader confidence. CONCLUSION: Contrast-enhanced ultrasound successfully identified all cases of RCC recurrence in this study. Importantly, some patients with complete response to treatment developed delayed enhancement at the periphery of the ablation cavity over time, corresponding to fat necrosis, scarring or granulation tissue within the ablation cavity.

Prospective comparison of PI-RADS version 2 and qualitative in-house categorization system in detection of prostate cancer.

BACKGROUND: Prostate Imaging-Reporting and Data System v. 2 (PI-RADSv2) provides standardized nomenclature for interpretation of prostate multiparametric MRI (mpMRI). Inclusion of additional features for categorization may provide benefit to stratification of disease. PURPOSE: To prospectively compare PI-RADSv2 to a qualitative in-house system for detecting prostate cancer on mpMRI. STUDY TYPE: Prospective. POPULATION: In all, 338 patients who underwent mpMRI May 2015-May 2016, with subsequent MRI/transrectal ultrasound fusion-guided biopsy. FIELD STRENGTH: 3T mpMRI (T2 W, diffusion-weighted [DW], apparent diffusion coefficient [ADC] map, b-2000 DWI acquisition, and dynamic contrast-enhanced [DCE] MRI). ASSESSMENT: One genitourinary radiologist prospectively read mpMRIs using both in-house and PI-RADSv2 5-category systems. STATISTICAL TEST: In lesion-based analysis, overall and clinically significant (CS) tumor detection rates (TDR) were calculated for all PI-RADSv2 and in-house categories. The ability of each scoring system to detect cancer was assessed by area under receiver operator characteristic curve (AUC). Within each PI-RADSv2 category, lesions were further stratified by their in-house categories to determine if TDRs can be increased by combining features of both systems. RESULTS: In 338 patients (median prostate-specific antigen [PSA] 6.5 [0.6-113.6] ng/mL; age 64 [44-84] years), 733 lesions were identified (47% tumor-positive). Predictive abilities of both systems were comparable for all (AUC 76-78%) and CS cancers (AUCs 79%). The in-house system had higher overall and CS TDRs than PI-RADSv2 for categories 3 and 4 (P < 0.01 for both), with the greatest difference between the scoring systems seen in lesions scored category 4 (CS TDRs: in-house 65%, PI-RADSv2 22.1%). For lesions categorized as PI-RADSv2 = 4, characterization of suspicious/indeterminate extraprostatic extension (EPE) and equivocal findings across all mpMRI sequences contributed to significantly different TDRs for both systems (TDR range 19-75%, P < 0.05). DATA CONCLUSION: PI-RADSv2 behaves similarly to an existing validated system that relies on the number of sequences on which a lesion is seen. This prospective evaluation suggests that sequence positivity and suspicion of EPE can enhance PI-RADSv2 category 4 cancer detection. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1326-1335.

The local cytokine and growth factor response to recombinant human bone morphogenetic protein-2 (rhBMP-2) after spinal fusion.

BACKGROUND CONTEXT: The systemic response regarding cytokine expression after the application of recombinant human bone morphogenetic protein-2 (rhBMP-2) in a rat spinal fusion model has recently been defined, but the local response has not been defined. Defining the local cytokine and growth factor response at the fusion site will help explain the roles of these molecules in the fusion process, as well as that of rhBMP-2. Our hypothesis is that the application of rhBMP-2 to the fusion site will alter the local levels of cytokines and growth factors throughout the fusion process, in a manner that is different from the systemic response, given the tissue-specific effects of rhBMP-2. PURPOSE: The purpose of this study was to evaluate the local cytokine and growth factor response after the application of rhBMP-2 in a rat spinal fusion model. STUDY DESIGN/SETTING: This was a basic science animal model study. METHODS: This study was partially funded by a physician-sponsored grant from Medtronic. A total of 135 Wistar rats (age 8 weeks, weighing approximately 300-400 g) underwent L4-L5 posterolateral intertransverse fusion with demineralized bone graft (approximately 0.4-cm3 rat demineralized bone matrix [DBM] per side). In the first group, 10 µg of rhBMP-2 on an allograft collagen sponge (ACS) was added to the fusion site with approximately 0.4-cm3 rat DBM per side. In the second group, 100 µg of rhBMP-2 on an ACS was added to the fusion site with approximately 0.4-cm3 rat DBM per side, and the third experiment was the control group, which consisted of only an ACS plus 0.4-cm3 DBM per side. There were nine groups of five animals each per experiment. Each group was sacrificed at time points up to 4 weeks (1, 6, 24, and 48 hours, and 4, 7, 14, 21, and 28 days after surgery). At sacrifice, the DBM, transverse processes, and any new bone formed were harvested, immediately frozen in liquid nitrogen, and prepared for protein extraction. ELISA was performed to compare the levels of various cytokines (interleukin [IL]-1ß, tumor necrosis factor alpha, IL-6, IL-1RA [IL-1 receptor antagonist], IL-4, and IL-10) and growth factors (vascular endothelial growth factor [VEGF], endothelia growth factor [EGF], insulin-like growth factor-1 [IGF-1], platelet derived growth factor [PDGF], transforming growth factor beta [TGF-ß]) that are known to be involved in the fusion-fracture healing process. Fusion was evaluated on the rats sacrificed at 28 days by manual palpation and microcomputed tomography (microCT) by two independent observers. RESULTS: The expression of cytokines and growth factors varied throughout the fusion process at each time point. In the groups treated with rh-BMP-2, IL-6 and IL-1RA had higher expression in the early time points (1 and 6 hours). Tumor necrosis factor alpha demonstrated significantly lower expression in the groups treated with rhBMP-2 at Days 1, 2, and 4. At the early time points (1 and 6 hours), in the groups treated with rhBMP-2, all of the growth factors IGF-1, VEGF, platelet derived growth factor AB (PDGF-AB), TGF-ß had equal or lower expression compared with controls. At 24 hours, there was a peak in IGF-1, VEGF, and PDGF-AB. These growth factors then declined, with IGF-1 and PDGF-AB having a second peak at Day 7. At 4 weeks, all of the rhBMP-2-treated animals fused based on manual palpation and microCT. The control group had four of five rats fused based on manual palpation and two of five rats based on microCT. CONCLUSIONS: There is significant variability in the expression of cytokines throughout the fusion process after treatment with rhBMP-2. The inflammatory response appears to peak early (1 and 6 hours), followed by a significant decrease with rhBMP-2 treatment. However, the growth factor expression appears to be suppressed early (1 and 6 hours), followed by a peak at 24 hours, and a second peak at Day 7.

Risk of Upgrading from Prostate Biopsy to Radical Prostatectomy Pathology-Does Saturation Biopsy of Index Lesion during Multiparametric Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy Help?

PURPOSE: We sought to determine whether saturation of the index lesion during magnetic resonance imaging-transrectal ultrasound fusion guided biopsy would decrease the rate of pathological upgrading from biopsy to radical prostatectomy. MATERIALS AND METHODS: We analyzed a prospectively maintained, single institution database for patients who underwent fusion and systematic biopsy followed by radical prostatectomy in 2010 to 2016. Index lesion was defined as the lesion with largest diameter on T2-weighted magnetic resonance imaging. In patients with a saturated index lesion transrectal fusion biopsy targets were obtained at 6 mm intervals along the long axis of the index lesion. In patients with a nonsaturated index lesion only 1 target was obtained from the lesion. Gleason 6, 7 and 8-10 were defined as low, intermediate and high risk, respectively. RESULTS: Included in the study were 208 consecutive patients, including 86 with a saturated and 122 with a nonsaturated lesion. Median patient age was 62.0 years (IQR 10.0) and median prostate specific antigen was 7.1 ng/ml (IQR 8.0). The median number of biopsy cores per index lesion was higher in the saturated lesion group (4 vs 2, p <0.001). The risk category upgrade rate from systematic only, fusion only, and combined fusion and systematic biopsy results to prostatectomy was 40.9%, 23.6% and 13.8%, respectively. The risk category upgrade from combined fusion and systematic biopsy results was lower in the saturated than in the nonsaturated lesion group (7% vs 18%, p = 0.021). There was no difference in the upgrade rate based on systematic biopsy between the 2 groups. However, fusion biopsy results were significantly less upgraded in the saturated lesion group (Gleason upgrade 20.9% vs 36.9%, p = 0.014 and risk category upgrade 14% vs 30.3%, p = 0.006). CONCLUSIONS: Our results demonstrate that saturation of the index lesion significantly decreases the risk of upgrading on radical prostatectomy by minimizing the impact of tumor heterogeneity.

Outcome of a Resident Spine Surgical Skills Training Program.

STUDY DESIGN: Cadaver training lab. OBJECTIVE: To determine if a technical cadaver skills training lab for spinal surgery increases resident confidence, satisfaction in training, and perception of operating room safety. SUMMARY OF BACKGROUND DATA: Resident training is an important topic in the setting of work hour reform. The use of supplemental materials such as videos, sawbones, and simulators may become important to adequately train orthopedic residents. At present, there are no established curricula for training orthopedic surgery residents on anatomy and common procedures encountered during a spinal surgery rotation. METHODS: Residents were assembled into teams of a PGY-5 and PGY-2 and/or PGY-1 to perform dissection and procedures on 5 fresh-frozen spine cadavers. With attending and spine fellow supervision, residents performed anterior cervical, posterior cervical, and posterior thoracolumbar surgical exposure, decompression, and fusion procedures in the operating room using surgical tools and instrumentation. Residents were then queried about their confidence levels, satisfaction in training, and perception of safety using a Likert scale (0-10). Strong agreement (scores ≥8) and strong disagreement (scores ≤3) and correlations were evaluated. RESULTS: Seventeen residents completed the training program (7 PGY-1s, 2 PGY-2s, and 8 PGY-5s). After the training, the majority of residents strongly agreed that they had an increased confidence of their own abilities (59%). A significant majority (65%) of residents strongly agreed that they were satisfied with the benefits provided by the training program. Compared with other methods of education, residents strongly agreed that the training was more helpful than textbook chapters (94%), sawbones (94%), web-based training (94%), or a virtual-based (completely electronic) training (94%). After the training, residents strongly agreed that the training improved feelings of preparation (47%), safety (41%), and ability to prevent intraoperative errors (41%). The vast majority of residents strongly agreed "Before performing surgery on me, I would want a resident to perform this cadaveric training" (88%). CONCLUSIONS: These results demonstrate that team-based, cadaveric training with adequate attending supervision, before onset of a spine surgical rotation, may lead to high resident confidence, satisfaction in training, and perception of patient safety.