Faculty Bibliography

OBJECTIVE:To determine the association between adiposity, hormones, and cognition in young men with abdominal obesity. METHODS:In this cross-sectional observational study, 53 nondiabetic men with abdominal obesity (mean body mass index, 37.3 kg/m(2) ; age, 22-45 years) and normal intelligence underwent detailed measures of body composition, hormonal profiles, and cognition. Age- and education-adjusted performance in five cognitive domains was examined. RESULTS:Total fat percentage was negatively associated with visuospatial skills (P = 0.002) and visual memory (P = 0.012). Insulin resistance (homeostatic model assessment of insulin resistance) was also negatively associated with these domains (P = 0.05 and trend, P = 0.06, respectively). Total testosterone levels were negatively associated with executive function and verbal learning and memory (P = 0.04 for each), but free testosterone was not. Sex hormone-binding globulin (SHBG) was also inversely associated with performance in these domains (P = 0.015 and trend, P = 0.09, respectively). In a stepwise regression model including percentage fat, homeostatic model assessment of insulin resistance, SHBG, and free testosterone, SHBG was the only variable selected for executive function (P = 0.05) and showed a trend for verbal learning and memory (P = 0.09). CONCLUSIONS:Adiposity and insulin resistance were associated with worse function in visual domains. An unexpected negative association is reported between SHBG and cognitive measures, which seemed to be independent of free testosterone levels.

PURPOSE/OBJECTIVE:To investigate the composition, cross-sectional area (CSA), and hormonal correlates of different fat depots in women with anorexia nervosa (AN) and control subjects with normal weights to find out whether patients with AN have lower fat CSA but higher attenuation than did control subjects and whether these changes may be mediated by gonadal steroids, cortisol, and thyroid hormones. MATERIALS AND METHODS/METHODS:This study was institutional review board approved and HIPAA compliant. Written informed consent was obtained. Forty premenopausal women with AN and 40 normal-weight women of comparable age (mean age ± standard deviation, 26 years ± 5) were studied. All individuals underwent computed tomography of the abdomen and thigh with a calibration phantom. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), thigh SAT, and thigh intermuscular adipose tissue CSA and attenuation were quantified. Serum estradiol, thyroid hormones, and urinary free cortisol levels were assessed. Variables were compared by using analysis of variance. Associations were examined by using linear regression analysis. RESULTS:Women with AN had higher fat attenuation than did control subjects (-100.1 to -46.7 HU vs -117.6 to -61.8 HU, P < .0001), despite lower fat CSA (2.0-62.8 cm(2) vs 5.5-185.9 cm(2), P < .0001). VAT attenuation but not CSA was inversely associated with lowest prior lifetime body mass index in AN (r = -0.71, P = .006). Serum estradiol levels were inversely associated with fat attenuation (r = -0.34 to -0.61, P = .03 to <.0001) and were positively associated with fat CSA of all compartments (r = 0.42-0.64, P = .007 to <.0001). Thyroxine levels and urinary free cortisol levels were positively associated with thigh SAT attenuation (r = 0.64 [P = .006] and r = 0.68 [P = .0004], respectively) and were inversely associated with abdominal SAT and VAT CSA (r = -0.44 to -0.58, P = .04 to .02). CONCLUSION/CONCLUSIONS:Women with AN have differences in fat composition, with higher fat attenuation than that of control subjects, as well as low fat mass. VAT attenuation but not CSA is inversely associated with lowest prior lifetime body mass index, suggesting that fat attenuation may serve as a biomarker of prior and current disease status in AN.

PURPOSE/OBJECTIVE:To compare the lateral mortise and anterior midline approaches to fluoroscopically guided tibiotalar joint injections with respect to successful intra-articular needle placement, fluoroscopy time, radiation dose, and dose area product (DAP). MATERIALS AND METHODS/METHODS:This retrospective study was IRB-approved and HIPAA-compliant. 498 fluoroscopically guided tibiotalar joint injections were performed or supervised by one of nine staff radiologists from 11/1/2010-12/31/2013. The injection approach was determined by operator preference. Images were reviewed on a PACS workstation to determine the injection approach (lateral mortise versus anterior midline) and to confirm intra-articular needle placement. Fluoroscopy time (minutes), radiation dose (mGy), and DAP (μGy-m(2)) were recorded and compared using the student's t-test (fluoroscopy time) or the Wilcoxon rank sum test (radiation dose and DAP). RESULTS:There were 246 lateral mortise injections and 252 anterior midline injections. Two lateral mortise injections were excluded from further analysis because no contrast was administered. Intra-articular location of the needle tip was documented in 242/244 lateral mortise injections and 252/252 anterior midline injections. Mean fluoroscopy time was shorter for the lateral mortise group than the anterior midline group (0.7 ± 0.5 min versus 1.2 ± 0.8 min, P < 0.0001). Mean radiation dose and DAP were less for the lateral mortise group than the anterior midline group (2.1 ± 3.7 mGy versus 2.5 ± 3.5 mGy, P = 0.04; 11.5 ± 15.3 μGy-m(2) versus 13.5 ± 17.3 μGy-m(2), P = 0.006). CONCLUSION/CONCLUSIONS:Both injection approaches resulted in nearly 100% rates of intra-articular needle placement, but the lateral mortise approach used approximately 40% less fluoroscopy time and delivered 15% lower radiation dose and DAP to the patient.

BACKGROUND:Surgery with high-dose radiation and high-dose radiation alone for sacral chordomas have shown promising local control rates. However, we have noted frequent sacral insufficiency fractures and perceived this rate to be higher than previously reported. QUESTIONS/PURPOSES/OBJECTIVE:We wished (1) to characterize the incidence of sacral insufficiency fractures in patients with chordomas of the sacrum who received high-dose radiation, and (2) to determine whether patients treated with surgery plus high-dose radiation or high-dose radiation alone are more likely to experience a sacral fracture, and to compare time to fracture in these groups. METHODS:Sixty-two patients who received high-dose radiation for sacral chordomas with (n = 44) or without surgical resection (n = 18) between 1992 and 2013 were included in this retrospective study. At our institution, sacral chordomas generally are treated by preoperative radiotherapy, followed by en bloc resection, and postoperative radiotherapy. Radiation alone, with an intent to cure, is offered to patients who otherwise are not good surgical candidates or patients who elect radiotherapy based on tumor location and the anticipated morbidity after surgery (such as sexual, bowel, or bladder dysfunction). MRI and CT scans were evaluated for evidence of sacral insufficiency fractures. Complete followup was available at a minimum of 2 years (or until fracture or death) for all 18 patients who underwent radiation alone, whereas 14% (six of 44 patients) in the surgery plus radiation group (9% [three of 33] after high sacrectomy and 27% [three of 11] after low sacrectomy) were lost to followup before 2 years. RESULTS:Sacral insufficiency fractures occurred in 29 of the 62 patients (47%). A total of 25 of 33 patients (76%) with high sacrectomy had fractures develop compared with zero of 11 (0%) after low sacrectomy, and four of the 18 patients (22%) who had high-dose radiation alone (p < 0.001). The fracture rate was greater in the high sacrectomy group than in the low sacrectomy group (p < 0.001) and the radiation only group (p < 0.001). There was no difference with the numbers evaluated in fracture probability between patients in the low-sacrectomy group and those treated with radiation alone (p = 0.112). The fracture-free survival probability was 0.99 for the low sacrectomy group at all times as there were no insufficiency fractures in this group; the 1-year fracture-free survival probability was 0.53 (95% CI, 0.35-0.69) after high sacrectomy, 0.83 (95% CI, 0.57-0.94) after radiation alone; the 2-year fracture-free survival probability was 0.36 (95% CI, 0.19-0.52) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone; and the 5-year fracture-free survival probability was 0.14 (95% CI, 0.04-0.30) after high sacrectomy and 0.77 (95% CI, 0.50-0.91) after radiation alone. CONCLUSIONS:Acknowledging the limitations of potential differences in baseline and followup among treatment groups in our study, we found that almost ½ of our patients experienced an insufficiency fracture. We found that the fracture rate was greater in the surgery group compared with the radiation alone group and that high sacrectomy accounted for all fractures in the surgery group. These findings can be used to inform patients and also support the need for further research to elucidate the influence of high-dose radiation on bone quality. LEVEL OF EVIDENCE/METHODS:Level III, therapeutic study.

OBJECTIVE:To assess short- and long-term reproducibility of marrow adipose tissue (MAT) quantification by 1H-MR spectroscopy. MATERIALS AND METHODS/METHODS:Our study was IRB-approved and HIPAA compliant. Written informed consent was obtained. We studied 20 overweight/obese but otherwise healthy subjects (12 female, 8 male) with a mean age of 37 ± 6 years. All subjects underwent proton magnetic resonance spectroscopy (1H-MRS) of the fourth lumbar vertebral body using a single-voxel point-resolved spatially localized spectroscopy sequence without water suppression at 3 T. Measurements were repeated after 6 weeks and 6 months using identical scanning protocols. The following clinical parameters were collected, weight, BMI, exercise status, and trabecular bone mineral density (BMD), by quantitative computed tomography. Short- (baseline, 6 weeks) and long-term (baseline, 6 months) reproducibility of MAT was assessed by the coefficient of variance (CV), standard deviation (SD), and interclass correlation coefficients (ICCs). Short- and long-term changes in clinical parameters were assessed by paired t-test. RESULTS:For short-term reproducibility between baseline and 6-week scans, the CV was 9.9 %, SD was 0.08, and ICC was 0.97 (95 % CI 0.94-099). For long-term reproducibility between baseline and 6-month scans, the CV was 12.0 %, SD was 0.10, and ICC was 0.95 (95 % CI 0.88 to 0.98). There was no significant short- or long-term change in clinical parameters (weight, BMI, exercise status, BMD) (p > 0.2). CONCLUSION/CONCLUSIONS:1H-MRS is a reproducible method for short- and long-term quantification of MAT. Our results can guide sample size calculations for interventional and longitudinal studies.

Somewhat paradoxically, fracture risk, which depends on applied loads and bone strength, is elevated in both anorexia nervosa and obesity at certain skeletal sites. Factor-of-risk (Φ), the ratio of applied load to bone strength, is a biomechanically based method to estimate fracture risk; theoretically, higher Φ reflects increased fracture risk. We estimated vertebral strength (linear combination of integral volumetric bone mineral density [Int.vBMD] and cross-sectional area from quantitative computed tomography [QCT]), vertebral compressive loads, and Φ at L4 in 176 women (65 anorexia nervosa, 45 lean controls, and 66 obese). Using biomechanical models, applied loads were estimated for: 1) standing; 2) arms flexed 90°, holding 5 kg in each hand (holding); 3) 45° trunk flexion, 5 kg in each hand (lifting); 4) 20° trunk right lateral bend, 10 kg in right hand (bending). We also investigated associations of Int.vBMD and vertebral strength with lean mass (from dual-energy X-ray absorptiometry [DXA]) and visceral adipose tissue (VAT, from QCT). Women with anorexia nervosa had lower, whereas obese women had similar, Int.vBMD and estimated vertebral strength compared with controls. Vertebral loads were highest in obesity and lowest in anorexia nervosa for standing, holding, and lifting (p < 0.0001) but were highest in anorexia nervosa for bending (p < 0.02). Obese women had highest Φ for standing and lifting, whereas women with anorexia nervosa had highest Φ for bending (p < 0.0001). Obese and anorexia nervosa subjects had higher Φ for holding than controls (p < 0.03). Int.vBMD and estimated vertebral strength were associated positively with lean mass (R = 0.28 to 0.45, p ≤ 0.0001) in all groups combined and negatively with VAT (R = -[0.36 to 0.38], p < 0.003) within the obese group. Therefore, women with anorexia nervosa had higher estimated vertebral fracture risk (Φ) for holding and bending because of inferior vertebral strength. Despite similar vertebral strength as controls, obese women had higher vertebral fracture risk for standing, holding, and lifting because of higher applied loads from higher body weight. Examining the load-to-strength ratio helps explain increased fracture risk in both low-weight and obese women.

OBJECTIVE:To compare prevalence and patterns of intravertebral collateral enhancement in patients with and without central venous obstruction (CVO). MATERIALS AND METHODS/METHODS:Chest CTs performed between 1/1/2000 and 12/15/2012 with reports containing terms indicating CVO were identified. All contrast enhanced CTs were examined for the presence of CVO and collateral venous pathways. If intravertebral collateral enhancement was present, the pattern was recorded as nodular, linear, or both. RESULTS:In 209 suspected cases of CVO, 53 (25 %) were confirmed with obstruction and 156 (75 %) were without obstruction. In patients with CVO, 47 % (25/53) demonstrated collateral venous flow through an intravertebral marrow pathway compared to 5 % (8/156) of patients without CVO (P < 0.0001). The most common level of enhancement was the upper thoracic spine, involving only the vertebral body. Nodular, linear, and combined nodular-linear enhancement patterns were seen with similar frequency. Nodular intravertebral collateral enhancement was mistaken for sclerotic metastases in 33 % (3/9) of cases. CONCLUSION/CONCLUSIONS:Intravertebral collateral enhancement was seen in almost half the patients with CVO and when nodular enhancement is present, it is important to differentiate between metastatic lesions and enhancement related to CVO.

Giant cell tumor (GCT) of bone is a locally aggressive benign neoplasm characterized by an abundance of osteoclastic giant cells that are induced by the neoplastic mononuclear cells; the latter express high levels of receptor activator of nuclear factor κ-B ligand (RANKL). Denosumab, a RANKL inhibitor, which is clinically used to treat GCT, leads to a marked alteration in the histologic appearance of the tumor with giant cell depletion and new bone deposition, leading to substantial histologic overlap with other primary tumors of bone. Most significantly, denosumab-treated GCT (tGCT) with abundant bone deposition may mimic de novo osteosarcoma, or GCT that has undergone malignant transformation. To histologically characterize tGCT, we identified 9 cases of GCT biopsied or resected after denosumab treatment. tGCT cases included 16 specimens from 9 patients including 6 female and 3 male individuals aged 16 to 47 (median 32) years. Duration of treatment varied from 2 to 55 months. We compared these tumors with malignant neoplasms arising in GCTs (n=9). The histology of tGCT was variable but appeared to relate to the length of therapy. All tGCTs showed marked giant cell depletion. Early lesions were highly cellular, and the combination of cellularity, atypia, and haphazard bone deposition caused the lesion to resemble high-grade osteosarcoma. Unlike de novo high-grade osteosarcoma or malignancies arising in GCT, however, tGCT showed less severe atypia, reduced mitotic activity, and lack of infiltrative growth pattern. Tumor in patients on prolonged therapy showed decreased cellularity and abundant new bone, deposited as broad, rounded cords or long, curvilinear arrays. The latter morphology was reminiscent of low-grade central osteosarcoma, but, unlike low-grade central osteosarcoma, tGCT was negative for MDM2 and again lacked an infiltrative growth pattern. Overall, tGCT may have a wide range of morphologic appearances. Because the treated tumors bear little resemblance to their pretreatment counterparts, careful attention to the history of denosumab administration is crucial to avoid a misdiagnosis with an important impact on therapy. Unlike malignant GCTs, tGCTs lack significant nuclear atypia, mitotic activity, and infiltration of preexisting bone, but instead show a unique pattern of intralesional bone deposition.

BACKGROUND:Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is commonly performed for cancer staging, as it can detect metastatic disease in multiple organ systems. However, there has been some controversy in the scientific literature when comparing FDG PET/CT and technetium-99 m-bone scintigraphy (bone scan) for the detection of skeletal metastases. PURPOSE/OBJECTIVE:To compare the accuracy of FDG PET/CT with bone scan for the detection of skeletal metastases. MATERIAL AND METHODS/METHODS:The study group comprised 202 adult cancer patients who underwent both FDG PET/CT and bone scan within 31 days for staging. Bone scans and FDG PET/CT were evaluated by two musculoskeletal radiologists for the presence and location of skeletal metastatic disease. Confirmation of the final diagnosis was based on the CT or magnetic resonance imaging (MRI) appearance, follow-up imaging, or histology. RESULTS:The sensitivity, specificity, and accuracy for detecting skeletal metastatic disease of FDG PET/CT were 97%, 98%, and 98%, respectively, and of bone scan were 83%, 98%, and 93%, respectively. The lesions that bone scan most commonly missed were located in the pelvis, spine, and sacrum. FDG PET/CT missed mostly lesions that were outside of the field of view, but in all of these cases the patient had additional sites of skeletal metastatic disease. Bone scan falsely identified six metastatic lesions and FDG PET/CT falsely identified three metastatic lesions. CONCLUSION/CONCLUSIONS:FDG PET/CT is an accurate technique for detection of skeletal metastases, and is superior to bone scan, especially in the spine and pelvis.

BACKGROUND:Obesity is prevalent among adolescents and is associated with serious health consequences. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are bariatric procedures that cause significant weight loss in adults and are increasingly being performed in adolescents with morbid obesity. Data comparing outcomes of RYGB vs. SG in this age-group are scarce. This study aims to compare short-term (1-6 months) and longer-term (7-18 months) body mass index (BMI) and biochemical outcomes following RYGB and SG in adolescents/young adults. METHODS:A retrospective study using data extracted from medical records of patients 16-21 years who underwent RYGB or SG between 2012 and 2014 at a tertiary care academic medical center. RESULTS:Forty-six patients were included in this study: 24 underwent RYGB and 22 underwent SG. Groups did not differ for baseline age, sex, race, or BMI. BMI reductions were significant at 1-6 months and 7-18 months within groups (p < 0.0001), but did not differ by surgery type (p = 0.65 and 0.09, for 1-6 months and 7-18 months, respectively). Over 7-18 months, within-group improvement in low-density lipoprotein (LDL) (-24 ± 6 in RYGB, p = 0.003, vs. -7 ± 9 mg/dl in SG, p = 0.50) and non-high-density lipoprotein (non-HDL) cholesterol (-23 ± 8 in RYGB, p = 0.02, vs. -12 ± 7 in SG, p = 0.18) appeared to be of greater magnitude following RYGB. However, differences between groups did not reach statistical significance. When divided by non-alcoholic steatohepatitis stages (NASH), patients with Stage II-III NASH had greater reductions in alanine aminotransferase levels vs. those with Stage 0-I NASH (-45 ± 18 vs. -9 ± 3, p = 0.01) after 7-18 months. RYGB and SG groups did not differ for the magnitude of post-surgical changes in liver enzymes. CONCLUSION/CONCLUSIONS:RYGB and SG did not differ for the magnitude of BMI reduction across groups, though changes trended higher following RYGB. Further prospective studies are needed to confirm these findings.