Faculty Bibliography

OBJECTIVE:To determine body composition predictors of skeletal integrity in overweight/obese subjects using dual energy X-ray absorptiometry (DXA). We hypothesized that visceral adiposity would be negatively, and lean mass positively, associated with DXA measures of skeletal integrity in obesity. MATERIALS AND METHODS/METHODS:Our study was institutional review board (IRB)-approved and Health Insurance Portability and Accountability Act (HIPAA)-compliant and written informed consent was obtained. We studied 82 overweight or obese, but otherwise healthy premenopausal women and men of similar age who were part of a clinical trial (mean age: 37 ± 10 years, mean BMI: 34 ± 7 kg/m(2)). All subjects underwent DXA of the spine and hip for assessment of bone mineral density (BMD), trabecular bone score (TBS), and hip structural analysis (HSA), and of the whole body for the assessment of body composition, including estimated visceral adipose tissue (VAT). RESULTS:Sixty-three subjects (77 %) had normal BMD and 19 subjects (23 %) had osteopenia. There were strong age-, sex-, and BMD-independent positive associations between lean mass and HSA parameters (r = 0.50 to r = 0.81, p < 0.0001), whereas there was no association with TBS. There were strong age-, sex- and BMD-independent inverse associations between total fat and VAT mass and TBS (r = -0.60 and r = -0.72, p < 0.0001 for both correlations), whereas there were no associations with HSA parameters. CONCLUSION/CONCLUSIONS:Lean mass is a positive predictor of hip geometry, whereas fat and VAT mass are negative predictors of trabecular microarchitecture in overweight/obese subjects.

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.

OBJECTIVES/OBJECTIVE:To assess CT-attenuation of abdominal adipose tissue and psoas muscle as predictors of mortality in patients with sarcomas of the extremities. METHODS:Our study was IRB approved and HIPAA compliant. The study group comprised 135 patients with history of extremity sarcoma (mean age: 53 ± 17 years) who underwent whole body PET/CT. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle attenuation (HU) was assessed on non-contrast, attenuation-correction CT. Clinical information including survival, tumour stage, sarcoma type, therapy and pre-existing comorbidities were recorded. Cox proportional hazard models were used to determine longitudinal associations between adipose tissue and muscle attenuation and mortality. RESULTS:There were 47 deaths over a mean follow-up period of 20 ± 17 months. Higher SAT and lower psoas attenuation were associated with increased mortality (p = 0.03 and p = 0.005, respectively), which remained significant after adjustment for age, BMI, sex, tumor stage, therapy, and comorbidities (p = 0.002 and p = 0.02, respectively). VAT attenuation was not associated with mortality. CONCLUSION/CONCLUSIONS:Attenuation of SAT and psoas muscle, assessed on non-contrast CT, are predictors of mortality in patients with extremity sarcomas, independent of other established prognostic factors, suggesting that adipose tissue and muscle attenuation could serve as novel biomarkers for mortality in patients with sarcomas. KEY POINTS/CONCLUSIONS:• CT-attenuation of adipose tissue and muscle predict mortality in sarcoma patients • CT-attenuation predicts mortality independent of established prognostic factors • Patients with sarcomas often undergo CT for staging or surveillance • Adipose tissue and muscle attenuation could serve as biomarkers for mortality.

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.

OBJECTIVES: The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration Whole-Body MRI (WB-MRI) Working Group reviewed the existing literature on WB-MRI, an emerging technology for assessing disease in patients with neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN), to recommend optimal image acquisition and analysis methods to enable WB-MRI as an endpoint in NF clinical trials. METHODS: A systematic process was used to review all published data about WB-MRI in NF syndromes to assess diagnostic accuracy, feasibility and reproducibility, and data about specific techniques for assessment of tumor burden, characterization of neoplasms, and response to therapy. RESULTS: WB-MRI at 1.5T or 3.0T is feasible for image acquisition. Short tau inversion recovery (STIR) sequence is used in all investigations to date, suggesting consensus about the utility of this sequence for detection of WB tumor burden in people with NF. There are insufficient data to support a consensus statement about the optimal imaging planes (axial vs coronal) or 2D vs 3D approaches. Functional imaging, although used in some NF studies, has not been systematically applied or evaluated. There are no comparative studies between regional vs WB-MRI or evaluations of WB-MRI reproducibility. CONCLUSIONS: WB-MRI is feasible for identifying tumors using both 1.5T and 3.0T systems. The STIR sequence is a core sequence. Additional investigation is needed to define the optimal approach for volumetric analysis, the reproducibility of WB-MRI in NF, and the diagnostic performance of WB-MRI vs regional MRI.

A 61-year-old woman with a medical history of intracerebral haemorrhage, hypertension, hyperlipidaemia and carotid stenosis presented to the emergency department with altered mental status 3 weeks after undergoing a vertical sleeve gastrectomy for severe obesity. She presented with a hypertensive emergency and a National Institutes of Health Stroke Scale of 4. CT of the head was unrevealing. MRI showed an abnormal signal within the bilateral posterior border-zone areas, with several foci in the parietal and occipital lobes, and thalami, suggestive of posterior reversible encephalopathy syndrome (PRES). The patient was initially placed on a labetalol drip and her preoperative antihypertensive medications--amlodipine, captopril, triamterene and hydrochlorothiazide--were gradually reintroduced. She returned to her baseline and was stable on discharge. Rapid withdrawal of antihypertensive medications in the early postoperative period of bariatric surgery was the aetiology of PRES in this patient. This case report discusses postoperative care of bariatric surgery patients having hypertension.

OBJECTIVE:To study non-diagnostic CT-guided musculoskeletal biopsies and take steps to minimize them. Specifically we asked: (1) What malignant diagnoses have a higher non-diagnostic rate? (2) What factors of a non-diagnostic biopsy may warrant more aggressive pursuit? (3) Do intra-procedural frozen pathology (FP) or point-of-care (POC) cytology reduce the non-diagnostic biopsy rate? MATERIALS AND METHODS/METHODS:This study was IRB-approved and HIPAA-compliant. We retrospectively reviewed 963 consecutive CT-guided musculoskeletal biopsies. We categorized pathology results as malignant, benign, or non-diagnostic and recorded use of FP or POC cytology. Initial biopsy indication, final diagnosis, method of obtaining the final diagnosis of non-diagnostic biopsies, age of the patient, and years of biopsy attending experience were recorded. Groups were compared using Pearson's χ(2) test or Fisher's exact test. RESULTS:In all, 140 of 963 (15%) biopsies were non-diagnostic. Lymphoma resulted in more non-diagnostic biopsies (P < 0.0001). While 67% of non-diagnostic biopsies yielded benign diagnoses, 33% yielded malignant diagnoses. Patients whose percutaneous biopsy was indicated due to the clinical context without malignancy history almost always generated benign results (96%). Whereas 56% of biopsies whose indication was an imaging finding of a treatable lesion were malignant, 20% of biopsies whose indication was a history of malignancy were malignant. There was no statistically significant difference in the nondiagnostic biopsy rates of pediatric versus adult patients (P = 0.8) and of biopsy attendings with fewer versus more years of experience (P = 0.5). The non-diagnostic rates of biopsies with FP (8%), POC cytology (25%), or neither (24%) were significantly different (P < 0.0001). CONCLUSION/CONCLUSIONS:Lymphoma is the malignant diagnosis most likely to result in a non-diagnostic biopsy. If the clinical and radiologic suspicion for malignancy is high, repeat biopsy is warranted. If the clinical context suggests a benign lesion, a non-diagnostic biopsy may be considered reassuring. Frozen pathology may decrease the non-diagnostic biopsy rate.

The medial cuneiform, namely the curvature and angulation of its distal facet with metatarsal 1, is crucial as a stabilizer in bipedal locomotion and an axis upon which the great toe medially deviates during arboreal locomotion in extant apes. Previous work has shown that facet curvature and angulation in adult dry-bone specimens can distinguish African apes from Homo, and can even distinguish among species of Gorilla. This study provides the first ontogenetic assessment of medial cuneiform curvature and angulation in juvenile (n = 68) and adult specimens (n = 102) using computed tomography in humans and extant ape specimens, including Pongo. Our data find that modern human juveniles initially have a convex and slightly medially oriented osseous surface of the developing medial cuneiform distal facet that flattens and becomes more distally oriented with age. The same pattern (though of a different magnitude) occurs developmentally in the chimpanzee medial cuneiform, but not in Gorilla or Pongo, whose medial cuneiform facet angulation remains unchanged ontogenetically. These data suggest that the medial cuneiform ossifies in a distinguishable pattern between Pongo, Gorilla, Pan, and Homo, which may in part be due to subtle differences in the loading environment at the hallucal tarsometatarsal joint-a finding that has important implications for interpreting fossil medial cuneiforms.

OBJECTIVE:To measure FDG uptake in visceral (VAT) and subcutaneous (SAT) adipose tissue of metabolically healthy obese (MHO) and metabolically abnormal obese (MAO) compared to metabolically healthy lean (MHL) subjects. Given that MHO has increased metabolic risk, it was hypothesized that MHO and MAO display similar VAT FDG uptake. METHODS:The 18F-FDG-PET/CT studies of 141 adults (n = 60 MHL, n = 20 MHO, n = 61 MAO) were examined to determine VAT and SAT volumes and FDG uptake. Data on CVD risk factors (BMI, abdominal circumference, blood pressure, serum lipids, and fasting plasma glucose) were collected. RESULTS:MHO and MAO had similar VAT FDG uptake (P = 0.74), both significantly lower than MHL (P < 0.01) independent of age and gender. SAT FDG uptake was similar across all groups (P > 0.2) independent of age and gender. In all groups, VAT FDG uptake was higher than SAT (P < 0.0001). In separate sub-analyses of obese groups, VAT FDG uptake was more broadly negatively associated with whole-body adiposity than SAT FDG uptake, and FDG uptake in abdominal adipose depots was positively associated with liver density (P < 0.05). CONCLUSIONS:FDG uptake in VAT of MHO is similar to MAO and lower than MHL, suggesting these subjects may present similar VAT dysfunction.

We aimed to test the hypothesis that noninvasive fat density by computed tomography (CT) increases after Roux-en-Y gastric bypass (RYGB) and correlates with improved cardiometabolic risk. We examined 21 obese adults before and 12 months after RYGB and 16 obese nonsurgical controls followed for 12 months. Visceral (VAT) and subcutaneous adipose tissue (SAT) density increased after RYGB (P < 0.0001) while remaining stable in controls (P ≥ 0.1). In RYGB subjects, 12-month increase in VAT density correlated with decreased C-reactive protein (CRP) independent of change in VAT area or BMI (both P < 0.05). Twelve-month increase in SAT density correlated with increased HDL cholesterol independent of change in SAT area (P = 0.048), BMI (P = 0.03), or statin use (P = 0.002), and 1 unit increase in SAT density had increased odds of higher total abdominal fat loss (P = 0.002).