CT-Guided Bone Biopsies in Metastatic Castration-Resistant Prostate Cancer: Factors Predictive of Maximum Tumor Yield.

PURPOSE: To evaluate the success rate of CT-guided bone biopsies in metastatic castration-resistant prostate cancer (mCRPC) and to investigate associated technical, imaging, and clinical parameters affecting diagnostic yields. MATERIALS AND METHODS: Eighty CT-guided bone biopsy specimens were obtained from 72 men (median age, 68 y; range, 49-89 y) enrolled in a multicenter trial to identify mechanisms of resistance in mCRPC. Successful biopsy was determined by histologic confirmation of tumor cells and successful isolation of RNA for molecular analysis. RESULTS: The overall success rate of CT-guided bone biopsies was 69% (55/80) based on histology and 64% (35/55) based on isolation of molecular material for RNA sequencing. Biopsies performed in lesions with areas of radiolucency had significantly higher diagnostic yields compared with lesions of predominantly dense sclerosis (95% vs 33%; P = .002) and lesions of predominantly subtle sclerosis (95% vs 65%; P = .04). Success rates increased in lesions with density ≤ 475 HU (79% for ≤ 475 HU vs 33% for > 475 HU; P = .001) and in lesions with ill-defined margins (76% for ill-defined margins vs 36% for well-circumscribed margins; P = .005). Alkaline phosphatase was the only clinical parameter to correlate significantly with diagnostic yield (83% for > 110 U/L vs 50% for ≤ 110 U/L; P = .001). CONCLUSIONS: Image-guided bone tumor biopsies can be successfully used to acquire cellular and molecular material for analyses in patients with osteoblastic prostate cancer metastases. Diagnostic yields are significantly increased in lesions with areas of radiolucency, density ≤ 475 HU, ill-defined margins, and interval growth and in patients with alkaline phosphatase > 110 U/L.

Locally aggressive and multifocal phosphaturic mesenchymal tumors: two unusual cases of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) has long been recognized as a clinical paraneoplastic syndrome. The identification of a unique histopathologic entity, the phosphaturic mesenchymal tumor (PMT), as a distinct etiology for TIO has been a more recent discovery. The majority of published cases describe a solitary, non-aggressive appearing soft tissue or osseous lesions in patients with osteomalacia; aggressive appearing or multifocal lesions appear to be exceedingly rare. These tumors characteristically secrete fibroblast growth factor 23 (FGF23). Elevated serum levels of FGF23 result in phosphate wasting and osteomalacia. In the majority of cases, laboratory abnormalities and clinical signs and symptoms of osteomalacia precede identification of the causative lesion by years. Following diagnosis, complete resection with wide margins to prevent local recurrence is most often curative. Imaging characteristics of PMT are diverse and remain incompletely defined, as the majority of previous publications are outside of the radiologic literature. We present multiple imaging modalities in two cases of patients with debilitating osteomalacia and unusual appearing PMTs: one with a locally aggressive lesion leading to pathologic fracture, the second presenting with exceedingly rare multifocal PMT.

MRI of the knee in adults.

MRI of the knee is a crucial component for evaluating symptomatic patients. An awareness of normal and abnormal appearances assists in clinical decision making. Chronic degenerative changes and focal traumatic injuries can sometimes be confused with one another, so differentiation is crucial. As technology continues to evolve, identifying early disease and preventing disease progression will become an integral part of MRI interpretation.

MRI of the shoulder in adults.

MRI can be used to assist in distinguishing pathology and anatomic disruptions adjacent to shoulder articulations and is a crucial tool in evaluating the symptomatic shoulder. The differentiation of traumatic and degenerative etiologies is important for patient management. A review of common adult degenerative and posttraumatic conditions can help familiarize general orthopaedic surgeons and sports medicine care providers to the perspective of shoulder specialists and musculoskeletal radiologists.

In vivo MRI of fresh stored osteochondral allograft transplantation with delayed gadolinium-enhanced MRI of cartilage: protocol considerations and recommendations.

The protocol for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was adapted for the evaluation of transplanted osteochondral allograft cartilage. Eight patients with focal grade 4 cartilage defects of the femoral condyle were treated with single cylindrical osteochondral allografts. At 1 and 2 years, dGEMRIC image sequences were acquired and regions of interest (ROIs) were drawn in repair and native control cartilage. Mean T1 values of region of interest were used to calculate established dGEMRIC metrics. The correlation was measured between the ΔR1 and R1 -Post metrics for repair and native cartilage. T1 times were measured in deep and superficial zones of cartilage. A strong correlation was identified between full-thickness, deep, and superficial ΔR1 and R1 -Post values for native cartilage and repair cartilage for all years (range: 0.893-1.0). The mean T1 times and ΔR1 rate between deep and superficial regions of articular cartilage were statistically different for all regions of the distal femora analyzed at 1 year and 2 years after osteochondral allograft transplantation (P<0.05). The dGEMRIC pre-Gadolinium scan is unnecessary when evaluating transplanted osteochondral allograft cartilage. The observation of stratified T1 and ΔR1 values indicates a need to re-evaluate the methodology behind the placement of region of interest in dGEMRIC.

Signal polarity restoration in a 3D inversion recovery sequence used with delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC).

PURPOSE: To develop an image reconstruction algorithm that restores the signal polarity in a three-dimensional inversion-recovery (3D-IR) sequence used in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). This approach effectively doubles the dynamic range of data used for T1 curve fitting. MATERIALS AND METHODS: We applied this reconstruction algorithm to a 3D-IR TFE sequence used for T1 mapping, validated the technique in a phantom study, and performed T1-map calculations in postosteochondral allograft transplant (OAT) patients. In addition, we performed a signal simulation study to assess the algorithm's capability to reduce the number of inversion times used in the 3D-IR TFE sequence. RESULTS: In comparison to a standard T1-mapping algorithm that uses the magnitude of the MRI signal, the proposed algorithm improves the reliability of T1 relaxation fits to the inversion-recovery three-parameter function. The signal simulation study shows that the number of TI inversion times can be reduced to as few as four, without compromising the accuracy of T1 calculations. CONCLUSION: This algorithm can be applied to any 2D- or 3D-IR acquisition sequence used in conjunction with dGEMRIC. Application of the algorithm improves the reliability of T1 calculations and allows the number of TIs to be reduced, leading to shorter scan times in dGEMRIC.

Molecular Testing in Patients With Castration-Resistant Prostate Cancer and Its Impact on Clinical Decision Making.

PURPOSE: Metastatic castration-resistant prostate cancer (CRPC) is the lethal form of the disease. Many groups have performed mutational or immunohistochemistry (IHC) testing in metastatic CRPC to identify treatment targets. However, the frequency with which mutational or IHC data have an impact on clinical decision making and the outcomes of molecularly guided therapy in CRPC are largely unknown. We report our institution's experience with mutational and IHC testing in patients with metastatic CRPC and its impact on clinical decision making and patient outcomes. METHODS: Between 2012 and 2015, 59 patients with CRPC underwent metastatic tissue biopsies and were genotyped with a 37-cancer gene panel in a Clinical Laboratory Improvement Amendments-certified laboratory. PTEN expression by IHC testing was also measured in 35 of these samples. A retrospective chart review was performed to determine whether the genomic information was acted upon and the outcome of patients whose treatment was guided by molecular testing. RESULTS: Forty-six of 59 patients with CRPC (78.0%) had biopsies with adequate tumor for mutational testing. Thirty-one of 46 subjects (67.4%) had mutations identified by sequencing. Of the 35 patients with CRPC whose biopsies were evaluated for PTEN expression by IHC testing, 13 had PTEN loss. Two patients had treatment on the basis of molecular testing, and one of these subjects had greater tumor control with molecularly guided therapy than his immediate prior therapy. CONCLUSION: Targeted sequencing and IHC can identify clinically informative molecular abnormalities in CRPC. Despite this, a small minority of patients in our series underwent therapies guided by mutational or IHC testing. Actionability of abnormalities identified in metastatic CRPC may be improved with access to clinical trials, insurance approval for unapproved uses of existing anticancer drugs, and larger gene sequencing panels that include more frequently mutated genes.

The effect of obesity on the anatomical relationship of the popliteal artery and tibial nerve in the proximal and distal popliteal fossa: relevance to popliteal sciatic nerve block and a traceback technique using the popliteal artery.

STUDY OBJECTIVE: To determine the effect of body mass index (BMI) on the relationship of the popliteal artery to the sciatic and tibial nerves in the popliteal fossa. DESIGN: Prospective, observational study. SETTING: University medical center. SUBJECTS: One hundred patients scheduled for magnetic resonance imaging scans of the knee. MEASUREMENTS: BMI was recorded and magnetic resonance imaging scans were assessed at 3 different measurement points along the femur for the distance and angle between the popliteal artery and tibial nerve, or sciatic nerve if the sciatic nerve had not bifurcated at the measurement point. MAIN RESULTS: At the distal femur, the tibial nerve was a mean of 2.9 mm from the popliteal artery. The nerve was consistently posterior to the artery; however, it was variably located medial or lateral to the artery. At the 5- and 8-cm measurement points, the nerve was 10.0 and 16.1 mm (SD, 4.1 and 5.2 mm), and 31° and 44° (SD, 15° and 16°) lateral to the popliteal artery, respectively. Zero degree was defined as directly posterior to the artery. Increasing BMI was correlated with increasing distance between the nerve and the artery at the 5- and 8-cm measurement points (r= 0.36 P> |t| .000 and .45 P> |t| .002). CONCLUSIONS: At 5 cm proximal to the distal femoral condyles, the popliteal artery is a reliable sonographic landmark to locate the tibial nerve due to the close proximity and consistent location of the nerve 1 cm posterolateral to the artery, with only a moderate effect of BMI.

Temporal in vivo assessment of fresh osteochondral allograft transplants to the distal aspect of the femur by dGEMRIC (delayed gadolinium-enhanced MRI of cartilage) and zonal T2 mapping MRI.

BACKGROUND: Zonal T2 mapping and dGEMRIC (delayed gadolinium-enhanced magnetic resonance imaging of cartilage) are diagnostic quantitative techniques to evaluate the biochemical health of articular cartilage. We adapted these techniques to investigate the results of osteochondral allograft transplantation and correlated the findings with patient-reported outcomes. METHODS: Nine patients with contained ICRS (International Cartilage Repair Society) grade-4 defects of the articular portion of a femoral condyle were treated with fresh osteochondral allografts and were evaluated prospectively with dGEMRIC and T2 mapping before and after gadolinium administration. The KOOS (Knee Injury Osteoarthritis Outcome Score) and IKDC (International Knee Documentation Committee) subjective scores were obtained at baseline and at one and two years postoperatively. For quantitative T2 mapping, regions of interest were drawn in the deep and superficial layers of allograft and control cartilage. For dGEMRIC analyses, the relaxation rate, post-gadolinium change in relaxation rate, and ratio between changes in the allograft and control regions of interest were calculated from T1 values. RESULTS: The mean ratio between the post-gadolinium changes in the allograft and control cartilage was 1.13 at one year and 1.55 at two years, and the ratio increased in eight of nine patients from one to two years. There was no difference between the mean T2 values in the deep zone of the allograft and control cartilage at one or two years (p > 0.05), but mean T2 values were higher in the superficial zone of the allograft cartilage at one (p < 0.0001) and two (p < 0.028) years. The mean improvement from baseline was significant at one and two years for the IKDC and all five KOOS subdomains (p < 0.05). All or nearly all patients showed improvements in all clinical outcomes scores at one year. CONCLUSIONS: Functional MRI techniques can be applied to noninvasively assess the biochemical health of cartilage after osteochondral allograft transplantation. The MRI findings correlated with certain patient-reported outcomes in the early postoperative period. Relative glycosaminoglycan content and the collagen structure of allograft cartilage may undergo time-dependent degeneration. A patient's perception of clinical outcome and quality of life is likely multifactorial and is impacted by more than the health of the allograft cartilage.