Quantitative Muscle MRI Depicts Increased Muscle Mass after a Behavioral Change in Myotonic Dystrophy Type 1.

Background Patients with myotonic dystrophy type 1 (DM1) increased their physical activity and exercise capacity following a behavioral intervention. However, it is unknown what is altered in muscles of patients with DM1 as a result of this intervention. The increased exercise capacity suggests that decelerated fat infiltration or increased muscle cross-sectional area (CSA) could be involved. Purpose To assess the effect of this activity-stimulating behavioral intervention on the lower extremity muscles of patients with DM1 with longitudinal quantitative muscle MRI. Materials and Methods In this prospective trial, participants with DM1 were randomized to a behavioral intervention (n = 14) or continued regular care (standard care; n = 13); no age-matched pairing was performed. Participants underwent MRI of the lower extremities at baseline and 10-month follow-up (January 2015 to March 2016). Fat fraction (FF), muscle CSA, and muscle water T2 (T2water) as markers for fat infiltration, muscle mass, and alteration in tissue water distribution (edema), respectively, were assessed with a chemical shift-encoded Dixon sequence and multiecho spin-echo sequence. Longitudinal within-group and between-group changes were assessed with paired-samples t tests and multivariable regression models. Results A total of 27 patients with DM1 (15 men) were evaluated. Patient age was comparable between groups (intervention, 45 years ± 13 [standard deviation]; standard care, 5 years ± 12; P = .96). Muscle CSA increased 5.9 cm2 ± 7.8 in the intervention group during the 10-month follow-up (P = .03) and decreased 3.6 cm2 ± 7.2 in the standard care group (P = .13). After 10 months, the mean difference between the groups was 9.5 cm2 (P = .01). This effect was stronger in muscles with baseline FF below the mean ± standard deviation of unaffected volunteers (-0.4 cm2 ± 0.15; P < .001). FF increased 0.9% ± 1.0 in the intervention group (P = .02) and 1.2% ± 1.2 for standard care (P = .02), with no between-group difference (P = .56). T2water did not change significantly in either group (intervention, P = .08; standard care, P = .88). Conclusion A behavioral intervention targeting physical activity increased lower extremity muscle cross-sectional area in patients with myotonic dystrophy, preferentially in healthy-appearing muscle. © RSNA, 2020 Online supplemental material is available for this article.

Clinicopathologic and molecular features of intracranial desmoplastic small round cell tumors.

Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra-abdominally, and are defined by EWSR1-WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion-positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6-25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma-like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1-WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1-WT1 fusion provides a definitive diagnosis of DSRCT. Genome-wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.

Lower extremity muscle pathology in myotonic dystrophy type 1 assessed by quantitative MRI.

OBJECTIVE: To determine the value of quantitative MRI in providing imaging biomarkers for disease in 20 different upper and lower leg muscles of patients with myotonic dystrophy type 1 (DM1). METHODS: We acquired images covering these muscles in 33 genetically and clinically well-characterized patients with DM1 and 10 unaffected controls. MRIs were recorded with a Dixon method to determine muscle fat fraction, muscle volume, and contractile muscle volume, and a multi-echo spin-echo sequence was used to determine T2 water relaxation time (T2water), reflecting putative edema. RESULTS: Muscles in patients with DM1 had higher fat fractions than muscles of controls (15.6 ± 11.1% vs 3.7 ± 1.5%). In addition, patients had smaller muscle volumes (902 ± 232 vs 1,097 ± 251 cm3), smaller contractile muscle volumes (779 ± 247 vs 1,054 ± 246 cm3), and increased T2water (33.4 ± 1.0 vs 31.9 ± 0.6 milliseconds), indicating atrophy and edema, respectively. Lower leg muscles were affected most frequently, especially the gastrocnemius medialis and soleus. Distribution of fat content per muscle indicated gradual fat infiltration in DM1. Between-patient variation in fat fraction was explained by age (≈45%), and another ≈14% was explained by estimated progenitor CTG repeat length (r 2 = 0.485) and somatic instability (r 2 = 0.590). Fat fraction correlated with the 6-minute walk test (r = -0.553) and muscular impairment rating scale (r = 0.537) and revealed subclinical muscle involvement. CONCLUSION: This cross-sectional quantitative MRI study of 20 different lower extremity muscles in patients with DM1 revealed abnormal values for muscle fat fraction, volume, and T2water, which therefore may serve as objective biomarkers to assess disease state of skeletal muscles in these patients. CLINICALTRIALSGOV IDENTIFIER: NCT02118779.

Magnetic-resonance-imaging-based three-dimensional muscle reconstruction of hip abductor muscle volume in a person with a transfemoral bone-anchored prosthesis: A feasibility study.

BACKGROUND: Persons with transfemoral amputation typically have severe muscle atrophy of the residual limb. The effect of bone-anchored prosthesis use on existing muscle atrophy is unknown. A potentially feasible method to evaluate this is magnetic resonance imaging (MRI)-based three-dimensional (3D) muscle reconstruction. We aimed to (1) examine the feasibility of MRI-based 3D muscle reconstruction technique in a person with a cobalt-chrome-molybdenum transfemoral bone-anchored prosthesis; and (2) describe the change of hip abductor muscle volume over time. METHODS: In this single case, 1-year follow-up study we reconstructed the 3D hip abductor muscle volumes semiautomatically from MRI scans at baseline, 6- and 12-month follow-up. The number of adverse events, difficulties in data analysis, time investment and participants' burden determined the level of feasibility. RESULTS: We included a man (70 years) with a transfemoral amputation who received a bone-anchored prosthesis after 52 years of socket prosthesis use. No adverse events occurred. The accuracy of the 3D reconstruction was potentially reduced by severe adipose tissue interposition. Data analysis was time-intensive (115 h). Participants' burden was limited to 3-h time investment. Compared to baseline, the total hip abductor volume of both the residual limb (6 month: 5.5%; 12 month: 7.4%) and sound limb (6 month: 7.8%; 12 month: 5.5%) increased. CONCLUSION: The presented technique appears feasible to follow muscle volume changes over time in a person with a cobalt-chrome-molybdenum transfemoral bone-anchored prosthesis in an experimental setting. Future research should focus on analysis of muscle tissue composition and the feasibility in bone-anchored prostheses of other alloys.

Subclinical enthesitis in nail psoriasis patients: a case-control study.

BACKGROUND: Patients with nail psoriasis have a higher prevalence of psoriatic arthritis; however, the pathogenetic relationship between these two disorders is as yet unclear. Entheses have been suggested as disease epicenter, which might explain the pathogenesis on an anatomical level. OBJECTIVE: To contribute to the elucidation of the hypothesis as regards the anatomical link between nail psoriasis and psoriatic arthritis, with the extensor enthesis of the distal interphalangeal joint as the epicenter. METHODS: We conducted a cross-sectional cohort study, visualizing the distal interphalangeal (DIP) joints entheses of patients with fingernail psoriasis (n = 54), psoriasis patients without nail involvement (n = 32), and healthy controls (n = 32) using three-dimensional ultrasound. Patients with nail psoriasis underwent repeat imaging studies after one year. RESULTS: Individuals with nail psoriasis had significantly thicker radial entheses than psoriasis patients without nail involvement. However, there were no significant differences in entheseal thickness between adjacent nails that were affected and those that were not (1.297 mm vs. 1.253 mm, p = 0.13). Follow-up after one year showed no significant differences in entheseal thickness in correlation with nail psoriasis activity. CONCLUSIONS: The present study provides evidence for subclinical enthesitis at the level of the DIP joint in patients with nail psoriasis. However, an anatomical correlation between nail psoriasis and psoriatic arthritis could not be confirmed.

Myxoid liposarcoma of the foot: a study of 8 cases.

INTRODUCTION: Myxoid liposarcoma is the only translocation-associated liposarcoma subtype. It classically originates in the deep soft tissues of the thigh. At distal sites of the extremities, this tumor is exceedingly rare. We present a series of 8 cases occurring in the foot/ankle. RESULTS: Two female and 6 male patients, aged between 32 and 77 years (mean, 54.3 years), were identified. Tumor size ranged from 1.1 to 10 cm (mean, 6.8 cm). Two lesions eroded bone. All tumors were treated by excision and 7 by (neo)adjuvant radiotherapy. R0 status was reached in 2 cases with 1 case followed by metastasis in the groin. All other cases were documented with R1 (n=2) or R2 (n=4) resection status. In 1 patient, the follow-up status was unknown. All other patients were alive 15-135 (mean, 55.8) months after initial diagnosis. We conclude that myxoid liposarcoma at acral sites are exceedingly rare, and in this series, prognosis was good irrespective of resection status. Clinicians and pathologists have to be aware because this sarcoma type shows a peculiar clinical behavior with high radio- and chemosensitivity and metastatic spread to extrapulmonary sites.

Prediction of incomplete primary debulking surgery in patients with advanced ovarian cancer: An external validation study of three models using computed tomography.

OBJECTIVE: To test the ability of three prospectively developed computed tomography (CT) models to predict incomplete primary debulking surgery in patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer. METHODS: Three prediction models to predict incomplete surgery (any tumor residual >1cm in diameter) previously published by Ferrandina (models A and B) and by Gerestein were applied to a validation cohort consisting of 151 patients with advanced epithelial ovarian cancer. All patients were treated with primary debulking surgery in the Eastern part of the Netherlands between 2000 and 2009 and data were retrospectively collected. Three individual readers evaluated the radiographic parameters and gave a subjective assessment. Using the predicted probabilities from the models, the area under the curve (AUC) was calculated which represents the discriminative ability of the model. RESULTS: The AUC of the Ferrandina models was 0.56, 0.59 and 0.59 in model A, and 0.55, 0.60 and 0.59 in model B for readers 1, 2 and 3, respectively. The AUC of Gerestein's model was 0.69, 0.61 and 0.69 for readers 1, 2 and 3, respectively. AUC values of 0.69 and 0.63 for reader 1 and 3 were found for subjective assessment. CONCLUSIONS: Models to predict incomplete surgery in advanced ovarian cancer have limited predictive ability and their reproducibility is questionable. Subjective assessment seems as successful as applying predictive models. Present prediction models are not reliable enough to be used in clinical decision-making and should be interpreted with caution.

Is etoricoxib effective in preventing heterotopic ossification after primary total hip arthroplasty?

PURPOSE: Heterotopic ossification is a common complication after total hip arthroplasty. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to prevent heterotopic ossifications effectively, however gastrointestinal complaints are reported frequently. In this study, we investigated whether etoricoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor that produces fewer gastrointestinal side effects, is an effective alternative for the prevention of heterotopic ossification. METHODS: We investigated the effectiveness of oral etoricoxib 90 mg for seven days in a prospective two-stage study design for phase-2 clinical trials in a small sample of patients (n = 42). A cemented primary total hip arthroplasty was implanted for osteoarthritis. Six months after surgery, heterotopic ossification was determined on anteroposterior pelvic radiographs using the Brooker classification. RESULTS: No heterotopic ossification was found in 62 % of the patients that took etoricoxib; 31 % of the patients had Brooker grade 1 and 7 % Brooker grade 2 ossification. CONCLUSIONS: Etoricoxib seems effective in preventing heterotopic ossification after total hip arthroplasty. This finding further supports the use of COX-2 inhibitors for the prevention of heterotopic ossification following total hip arthroplasty.

Fatal pericardial tamponade after superior vena cava stenting.

We discuss a fatal complication of percutaneous superior vena cava (SVC) self-expandable stent placement in a patient with superior vena cava syndrome (SVCS). The SVCS was caused by a malignant mediastinal mass with total occlusion of the SVC. Twenty-four hours after the procedure, the patient died of a hemopericardial tamponade. In the literature, only seven cases have been described with this life-threatening complication. Patients with a necrotic tumor mass are more likely to develop this complication. Knowledge of this complication may increase patient survival.

Angiosarcoma with malignant peripheral nerve sheath tumour developing in a patient with klippel-trénaunay-weber syndrome.

PURPOSE: We discuss the coexistence of Klippel-Trénaunay-Weber syndrome with various malignancies, the possible histogenetic pathways and therapeutic implications. PATIENT: We report on a 46-year-old man presenting with increasing pain and swelling of his right lower leg after fracturing his fibula. Since birth he was known as having the uncommon syndrome of Klippel-Trénaunay-Weber of his right lower leg. METHODS: Our patient underwent an above-knee amputation for biopsy-proven malignant vascular tumour, first thought to be a composite hemangio-endothelioma and/or angiosarcoma with lung metastases. RESULTS: In the amputated extremity, a vascular malformation was found with tumour showing various components with foci of angiosarcoma adjacent to diffuse neurofibroma and areas with high-grade malignant peripheral nerve sheath tumour. Amputation and palliative chemotherapy were indicated, but he died of pulmonary and cerebral metastases 2 months postoperatively. DISCUSSION: This case describes an angiosarcoma with malignant peripheral nerve sheath tumour developing in a patient with Klippel-Trénaunay-Weber syndrome. A case never described before in literature and probably, as in our case, difficult to diagnose at first biopsy.