Faculty Bibliography

BACKGROUND:There are limited predictors of prognosis in patients with clinically non-functioning pituitary adenomas (NFPAs). We hypothesized that MRI texture analysis may predict tumor recurrence or progression in patients with NFPAs undergoing transsphenoidal pituitary surgery (TSS). OBJECTIVE:To characterize texture parameters on preoperative MRI examinations in patients with NFPAs in relation to prognosis. METHODS:Retrospective study of patients with NFPAs who underwent TSS at our institution between 2009 and 2010. Clinical, radiological and histopathological data were extracted from electronic medical records. MRI texture analysis was performed on coronal T1-weighted non-enhanced MR images using ImageJ (NIH). MRI texture parameters were used to predict tumor recurrence or progression. Both logistic regression and Cox proportional hazard analyses were conducted to adjust for potential confounders. RESULTS: = 0.034) for recurrence or progression in comparison with tumors below the median. CONCLUSIONS:Our data suggest that MRI texture analysis can predict the risk of tumor recurrence or progression in patients with NFPAs.

OBJECTIVE:To evaluate the significance of biceps tendon (BT) displacement and peri-bicipital hematoma on MRI in subjects with pectoralis major (PM) tears. We hypothesized that these features might be associated with tear severity at surgery. MATERIALS AND METHODS/METHODS:We retrospectively identified MRI cases with PM injury and reviewed clinical, imaging, and surgical records. MR images were reviewed independently by two musculoskeletal radiologists to determine anterior displacement of BT (BT-disp, in mm) and the presence of triangular-shaped peri-bicipital hematoma. Data were compared with an age- and sex-matched control group and correlated with surgical reports grouped by tear severity. RESULTS:We identified 46 subjects with PM injury (43 men, 3 women; mean age 34 ± 9 years), 26 of whom underwent surgical reconstruction, and 20 matched controls (P > 0.2). BT-disp was significantly higher in PM injury vs controls (P = 0.003), and in tendon vs myotendinous (MT) junction PM tears (P < 0.0001); however, MT junction tears vs controls were similar (P = 0.98). Higher BT-disp and presence of peri-bicipital hematoma correlated significantly with surgical reports describing full-thickness complete tears. BT-disp > 4.5 mm had 86% sensitivity and 75% specificity to detect the most severe tears on surgical reports, whereas the presence of peri-bicipital hematoma was the strongest predictor among both parameters. CONCLUSION/CONCLUSIONS:Anterior BT displacement and peri-bicipital hematoma are helpful indicators of full-thickness complete tears at the humeral insertion.

The functional and evolutionary implications of primitive retentions in early hominin feet have been under debate since the discovery of Australopithecus afarensis. Ontogeny can provide insight into adult phenotypes, but juvenile early hominin foot fossils are exceptionally rare. We analyze a nearly complete, 3.32-million-year-old juvenile foot of A. afarensis (DIK-1-1f). We show that juvenile A. afarensis individuals already had many of the bipedal features found in adult specimens. However, they also had medial cuneiform traits associated with increased hallucal mobility and a more gracile calcaneal tuber, which is unexpected on the basis of known adult morphologies. Selection for traits functionally associated with juvenile pedal grasping may provide a new perspective on their retention in the more terrestrial adult A. afarensis.

BACKGROUND:Body composition differs between men and women, with women having proportionally more fat mass and men more muscle mass. Although men and women are both susceptible to obesity, health consequences differ between the sexes. The purpose of our study was to assess sex differences in body composition using anatomic and functional imaging techniques, and its relationship to cardiometabolic risk markers in subjects with overweight/obesity. METHODS:). Subjects underwent dual-energy X-ray absorptiometry (DXA) and computed tomography (CT) for fat and muscle mass, proton MR spectroscopy (1H-MRS) for intrahepatic (IHL) and intramyocellular lipids (IMCL), an oral glucose tolerance test, serum insulin, lipids, and inflammatory markers. Men and women were compared by Wilcoxon signed rank test. Linear correlation and multivariate analyses between body composition and cardiometabolic risk markers were performed. RESULTS:Women and men were of similar mean age and BMI (p ≥ 0.2). Women had higher %fat mass, extremity fat, and lower lean mass compared to men (p ≤ 0.0005). However, men had higher visceral adipose tissue (VAT) and IMCL and higher age-and BMI-adjusted IHL (p < 0.05). At similar age and BMI, men had a more detrimental cardiometabolic risk profile compared to women (p < 0.01). However, VAT in women, and IMCL in men, were more strongly associated with cardiometabolic risk markers, while more lower extremity fat was associated with a more favorable cardiometabolic profile in women compared to men (p ≤ 0.03). CONCLUSIONS:Although the male pattern of fat distribution is associated with a more detrimental cardiometabolic risk profile compared to women of similar age and BMI, VAT is more strongly associated with cardiometabolic risk markers in women, while IMCL are more detrimental in men. Lower extremity fat is relatively protective, in women more than in men. This suggests that detailed anatomic and functional imaging, rather than BMI, provides a more complete understanding of metabolic risk associated with sex differences in fat distribution.

OBJECTIVE:Overweight/obesity is characterized by decreased growth hormone (GH) secretion whereas circulating IGF-I levels are less severely reduced. Yet, the activity of the circulating IGF-system appears to be normal in overweight/obese subjects, as estimated by the ability of serum to activate the IGF-I receptor in vitro (bioactive IGF). We hypothesized that preservation of bioactive IGF in overweight/obese women is regulated by an insulin-mediated suppression of IGF-binding protein-1 (IGFBP-1) and IGFBP-2, and by suppression of IGFBP-3, mediated by low GH. We additionally hypothesized that increases in bioactive IGF would drive changes in body composition with low-dose GH administration. DESIGN:Cross-sectional analysis and 3-month interim analysis of a 6-month randomized, placebo-controlled study of GH administration in 50 overweight/obese women without diabetes mellitus. Bioactive IGF (kinase receptor activation assay) and body composition (DXA) were measured. RESULTS:Prior to treatment, IGFBP-3 (r = -0.33, p = 0.02), but neither IGFBP-1 nor IGFBP-2, associated inversely with bioactive IGF. In multivariate analysis, lower IGFBP-3 correlated with lower peak stimulated GH (r = 0.45, p = 0.05) and higher insulin sensitivity (r = -0.74, p = 0.003). GH administration resulted in an increase in mean serum IGF-I concentrations (144 ± 56 to 269 ± 66 μg/L, p < 0.0001) and bioactive IGF (1.29 ± 0.39 to 2.60 ± 1.12 μg/L, p < 0.0001). The treatment-related increase in bioactive IGF, but not total IGF-I concentration, predicted an increase in lean mass (r = 0.31, p = 0.03) and decrease in total adipose tissue/BMI (r = -0.43, p = 0.003). CONCLUSIONS:Our data suggest that in overweight/obesity, insulin sensitivity and GH have opposing effects on IGF bioactivity through effects on IGFBP-3. Furthermore, increases in bioactive IGF, rather than IGF-I concentration, predicted GH administration-related body composition changes. CLINICAL TRIAL REGISTRATION NUMBER:NCT00131378.

Perivascular epithelioid cell tumor (PEComa), mesenchymal tumors morphologically characterized by epithelioid cells, coexpress melanocytic and muscle markers. Herein, we describe a heretofore-undescribed tuberous sclerosis complex (TSC)-related neoplasm, morphologically resembling a soft tissue fibroma-like lesion, but showing an immunophenotype resembling PEComa. We identified 3 soft tissue fibroma-like lesions in individuals with TSC. We also evaluated 6 TSC-related periungual fibroma as well as a range of non-TSC fibroma-like lesions (n=19). Immunohistochemistry for HMB-45, desmin, smooth muscle actin, TFE3, and S100 was performed on the TSC-related fibromas. Periungual fibromas and non-TSC fibroma-like lesions were also stained for HMB-45. All 3 TSC patients were female, ranging in age from 4 to 51 years (mean, 26.7 y). Two tumors were located in extremities and 1 on the chest wall. The tumors showed elongated to stellate spindle-shape cells, prominent collagenous background, and lacked mitotic activity and cytologic atypia. Immunohistochemically, all 3 tumors were positive for HMB-45; smooth muscle actin or desmin was positive in both tumors tested. TFE3 was negative. All patients were alive with no evidence of disease with median follow-up of 55 months (range, 6 to 131 mo). Non-TSC fibroma-like lesions and oral and periungual fibromas were negative for HMB-45. Fibroma-like PEComa, a newly recognized soft tissue tumor with a strong association with TSC, mimics soft tissue fibroma but shows reactivity with melanocytic markers.

PURPOSE:C]PBR28 under thermoneutral conditions. PROCEDURES:C]PBR28 at room temperature. Thirty-minute static PET images were reconstructed from the data obtained 60-90 min after the injection of the tracer. RESULTS:for muscle and subcutaneous adipose tissue was 0.79 (± 0.1) and 0.18 (± 0.04), respectively. CONCLUSIONS:C]PBR28, a widely available TSPO-specific PET tracer, can be used for imaging human BAT mass under thermoneutral conditions.

Background Recent studies have suggested that the quantity and quality of adipose tissue and muscle, assessed on non-contrast computed tomography (CT), may serve as imaging biomarkers of survival in patients with and without neoplasms. Purpose To assess body composition measures that could serve as predictors of therapy response in patients with extremity soft tissue sarcomas treated with radiation therapy and surgery. Material and Methods The study was IRB-approved. Sixty patients had a history of extremity soft tissue sarcoma and underwent FDG-PET/CT prior to radiation therapy and surgical resection. Cross-sectional areas and CT attenuation (HU) of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle were assessed on non-contrast CT. Clinical information on predictors of tumor recurrence and post-surgical wound infections were recorded. Cox proportional hazard models were used to determine longitudinal associations between body composition and tumor recurrence/wound infections. Results Twenty-three tumor recurrences occurred over a follow-up period of 43 ± 35 months. Higher SAT and lower psoas attenuation were associated with tumor recurrence which remained significant after adjustment for covariates ( P ≤ 0.01). There were 13 post-surgical wound infections. Higher VAT and SAT attenuation were associated with post-surgical wound infections ( P < 0.04); however, VAT attenuation lost significance after adjustment for covariates. Conclusion Abdominal adipose tissue and psoas muscle attenuation assessed on non-contrast CT may predict tumor recurrence and post-surgical infections in patients with extremity soft tissue sarcomas.

BACKGROUND:We assessed whether there was a difference in attenuation measurements (in Hounsfield units - HU) and geometric distribution of HU between femora with metastatic lesions that fracture, and metastatic lesions that did not fracture nor underwent prophylactic fixation. METHODS:Nine patients with femoral metastases who underwent CT and developed a pathological fracture were matched to controls. All femora were delineated in axial CT slices using a region of interest (ROI) tool; the HU within these ROIs were used to calculate: (1) the cumulative HU of the affected over the nonaffected side per slice and presented as a percentage, and (2) the cumulative HU accounting for geometric distribution (polar moment of HU). We repeated the analyses including cortical bone only (HU of 600 and above). RESULTS:CT-based calculations did not differ between patients with a lesion that fractured and those that did not fracture nor underwent prophylactic fixation when analyzing all tissue. However, when including cortical bone only, the pathological fracture group had a lower cumulative HU value compared to the no fracture and no fixation group for the weakest cross-sectional CT image (pathological fracture group, mean: 71, SD: 23 and no fracture and no prophylactic fixation group, mean: 85, SD: 18, p = 0.042) and the complete lesion analysis (pathological fracture group, mean: 78, SD: 21 and no fracture and no prophylactic fixation group, mean: 92, SD: 15, p = 0.032). CONCLUSION/CONCLUSIONS:The demonstrated CT-based algorithms can be useful for predicting pathological fractures in metastatic lesions.

This paper summarizes the highlights of the Special Scientific Sessions of the 44th Annual Scientific Meeting of the International Skeletal Society (ISS), which was hosted in New York, NY, in August 2017.