Selpercatinib Treatment of RET-Mutated Thyroid Cancers Is Associated With Gastrointestinal Adverse Effects.

CONTEXT: Metastatic medullary thyroid carcinoma (MTC) and radioactive iodine-refractory differentiated thyroid carcinoma (RAI-R DTC) have poor prognosis and limited treatment options. Selpercatinib (LOXO-292), a selective kinase inhibitor targeting the RET gene, has shown a 69% to 79% objective response rate in this cohort with benefits in other tumors including lung cancer harboring the same oncogenic driver. Published reports describe only 17% of patients experiencing gastrointestinal (GI) adverse effects (AEs), which is in contrast to our local experience. OBJECTIVE: Here we characterize the AEs and correlate them with radiological and histopathological findings. METHODS: Sequential patients enrolled in LIBRETTO-001 at Royal North Shore Hospital, Sydney, Australia, with available imaging (n = 22) were recruited. Patients had regular visits with AEs documented and computed tomography (CT) scans every 3 months. CT at screening, at time of GI AE, and at most recent follow-up were reviewed and scored. Endoscopic examination was performed in 5 patients. RESULTS: Of 22 patients in this cohort, the majority had somatic RET alterations (n = 18), most commonly p.Met918Thr (n = 14). Ten patients (50%) developed GI AEs. Dose reduction was required in 8 of the 10 patients, but none discontinued therapy. The majority had stable disease (n = 17). Gastric and small-bowel edema was evident in symptomatic patients after a median time of 67 weeks' treatment. Histological correlation in 5 patients revealed mucosal edema correlating with radiological evidence of congestion and edema. CONCLUSION: GI AEs with selpercatinib may be more common than previously described. Most are self-limiting but often require dose adjustments. Histological evidence of mucosal edema observed in conjunction with the radiological findings of congestion and wall thickening suggest bowel-wall edema is a predominant mechanism of abdominal pain in these patients.

Risk stratification of indeterminate thyroid nodules using ultrasound and machine learning algorithms.

BACKGROUND: Indeterminate thyroid nodules (Bethesda III) are challenging to characterize without diagnostic surgery. Auxiliary strategies including molecular analysis, machine learning models, and ultrasound grading with Thyroid Imaging, Reporting and Data System (TI-RADS) can help to triage accordingly, but further refinement is needed to prevent unnecessary surgeries and increase positive predictive values. DESIGN: Retrospective review of 88 patients with Bethesda III nodules who had diagnostic surgery with final pathological diagnosis. MEASUREMENTS: Each nodule was retrospectively scored through TI-RADS. Two deep learning models were tested, one previously developed and trained on another data set, mainly containing determinate cases and then validated on our data set while the other one trained and tested on our data set (indeterminate cases). RESULTS: The mean TI-RADS score was 3 for benign and 4 for malignant nodules (p = .0022). Radiological high risk (TI-RADS 4,5) and low risk (TI-RADS 2,3) categories were established. The PPV for the high radiological risk category in those with >10 mm nodules was 85% (CI: 70%-93%). The NPV for low radiological risk in patients >60 years (mean age was 100% (CI: 83%-100%). The area under the curve (AUC) value of our novel classifier was 0.75 (CI: 0.62-0.84) and differed significantly from the chance-level (p < .00001). CONCLUSIONS: Novel radiomic and radiologic strategies can be employed to assist with preoperative diagnosis of indeterminate thyroid nodules.

Comprehensive Analysis of a Recalled Modular Total Hip System and Recommendations for Management.

BACKGROUND: Recent total hip arthroplasty designs have introduced modularity at the neck-stem junction. There are reports of failure of this class of designs due to corrosion at the modular junction. The purpose of this study was to evaluate patients implanted with a recently recalled modular total hip arthroplasty system. METHODS: This was a prospective study of 216 total hip arthroplasties in 195 patients performed by a single surgeon. All hips had a titanium-alloy stem, but 199 had a modular cobalt-chromium neck and seventeen were monolithic. The mean patient age was 65.4 years (range, twenty to eighty-eight years); seventy-nine were men and 116 were women. Patients were evaluated for infection and with metal ion assays and MRI (magnetic resonance imaging). Intraoperative tissue samples were graded, and retrieved implants were examined. RESULTS: At a mean follow-up of 19.3 months, eighty (37%) of 216 hips had been revised. An adverse local tissue reaction (ALTR) was the cause for revision in seventy-three of these eighty hips; all had the modular neck design. Assay results for the patients requiring revision showed higher levels of cobalt (mean, 8.6 ng/mL) than chromium (mean, 1.8 ng/mL). MRI showed moderate to severe levels of synovial response in sixty-three of 166 hips. The mean ALVAL (aseptic lymphocyte-dominated vasculitis-associated lesion) score for the revised hips was 8.1. Corrosion was visible on all tapers at the neck-stem junction but not the head-neck junction. CONCLUSIONS: Early failures of modular total hip arthroplasty occur due to fretting and corrosion at the neck-stem junction, resulting in ALTR. Surveillance utilizing metal ion levels and MRI may be indicated for all patients regardless of symptoms, as the early survivorship is poor and the ultimate failure rate may be catastrophically high.

MR Imaging of Knee Arthroplasty Implants.

Primary total knee arthroplasty is a highly effective treatment that relieves pain and improves joint function in a large percentage of patients. Despite an initially satisfactory surgical outcome, pain, dysfunction, and implant failure can occur over time. Identifying the etiology of complications is vital for appropriate management and proper timing of revision. Due to the increasing number of knee arthroplasties performed and decreasing patient age at implantation, there is a demand for accurate diagnosis to determine appropriate treatment of symptomatic joints following knee arthroplasty, and for monitoring of patients at risk. Magnetic resonance (MR) imaging allows for comprehensive imaging evaluation of the tissues surrounding knee arthroplasty implants with metallic components, including the polyethylene components. Optimized conventional and advanced pulse sequences can result in substantial metallic artifact reduction and afford improved visualization of bone, implant-tissue interfaces, and periprosthetic soft tissue for the diagnosis of arthroplasty-related complications. In this review article, we discuss strategies for MR imaging around knee arthroplasty implants and illustrate the imaging appearances of common modes of failure, including aseptic loosening, polyethylene wear-induced synovitis and osteolysis, periprosthetic joint infections, fracture, patellar clunk syndrome, recurrent hemarthrosis, arthrofibrosis, component malalignment, extensor mechanism injury, and instability. A systematic approach is provided for evaluation of MR imaging of knee implants. MR imaging with optimized conventional pulse sequences and advanced metal artifact reduction techniques can contribute important information for diagnosis, prognosis, risk stratification, and surgical planning.

MR Imaging of Adverse Local Tissue Reactions around Rejuvenate Modular Dual-Taper Stems.

PURPOSE: To describe the magnetic resonance (MR) imaging characteristics associated with adverse local tissue reactions and tissue damage around hip arthroplasties in which the recalled Rejuvenate modular dual-taper stem was used. MATERIALS AND METHODS: The institutional review board of the Hospital for Special Surgery approved the study. All study patients provided informed consent. MR imaging studies were retrospectively reviewed in a cohort of 58 patients with 66 hip arthroplasties with Rejuvenate stems who had presented for imaging evaluation because of recall of the implant. Multiple regression analysis was used to examine MR imaging features, biomechanical factors, and metal ion levels as predictors of aseptic lymphocytic vasculitis-associated lesion (ALVAL) score at histologic assessment while adjusting for age and sex for 54 revised hips. RESULTS: Revision surgery was performed in 54 hips on the basis of clinical or imaging findings (24% of hips were completely asymptomatic). The median ALVAL score among the revised hips was 9 (range, 1-10). Imaging characteristics observed with high frequency in patients with ALVAL included synovitis, mixed- or solid-type synovitis, synovial thickening, and capsular dehiscence. CONCLUSION: MR imaging provides an effective noninvasive method for assessing the presence and severity of adverse local tissue reaction, as well as the degree of pre-existing tissue damage, thereby facilitating early and accurate identification of candidates for revision surgery.

All-inside, physeal-sparing anterior cruciate ligament reconstruction does not significantly compromise the physis in skeletally immature athletes: a postoperative physeal magnetic resonance imaging analysis.

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction in skeletally immature patients can result in growth disturbance due to iatrogenic physeal injury. Multiple physeal-sparing ACL reconstruction techniques have been described; however, few combine the benefits of anatomic reconstruction using sockets without violation of the femoral or tibial physis. PURPOSE: To utilize physeal-specific magnetic resonance imaging (MRI) to quantify the zone of physeal injury after all-inside ACL reconstruction in skeletally immature athletes. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Twenty-three skeletally immature patients (mean chronologic age 12.6 years; range, 10-15 years) were prospectively evaluated after all-inside ACL reconstruction. The mean bone age was 13.2 years. There were 8 females and 15 males. Fifteen patients underwent an all-epiphyseal (AE) ACL reconstruction and 8 patients had a partial transphyseal (PTP) ACL reconstruction, which spared the femoral physis but crossed the tibial physis. At 6 and 12 months postoperatively, MRI using 3-dimensional fat-suppressed spoiled gradient recalled echo sequences and full-length standing radiographs were performed to assess graft survival, growth arrest, physeal violation, angular deformity, and leg length discrepancy. RESULTS: The mean follow-up for this cohort was 18.5 months (range, 12-39 months). Minimal tibial physeal violation was seen in 10 of 15 patients in the AE group and, by definition, all patients in the PTP group. The mean area of tibial physeal disturbance (±SD) was 57.8 ± 52.2 mm(2) (mean 2.1% of total physeal area) in the AE group compared with 145.1 ± 100.6 mm(2) (mean 5.4% of total physeal area) in the PTP group (P = .003). Minimal compromise of the femoral physis (1.5%) was observed in 1 case in the PTP group and no cases in the AE group. No cases of growth arrest, articular surface violation, or avascular necrosis were noted on MRI. No postoperative angular deformities or significant leg length discrepancies were observed. CONCLUSION: The study data suggest that all-inside ACL reconstruction is a safe technique for skeletally immature athletes at short-term follow-up. Physeal-specific MRI reveals minimal growth plate compromise that is significantly lower than published thresholds for growth arrest.

MR imaging of hip arthroplasty implants.

Hip arthroplasty has become the standard treatment for end-stage hip disease, allowing pain relief and restoration of mobility in large numbers of patients; however, pain after hip arthroplasty occurs in as many as 40% of cases, and despite improved longevity, all implants eventually fail with time. Owing to the increasing numbers of hip arthroplasty procedures performed, the demographic factors, and the metal-on-metal arthroplasty systems with their associated risk for the development of adverse local tissue reactions to metal products, there is a growing demand for an accurate diagnosis of symptoms related to hip arthroplasty implants and for a way to monitor patients at risk. Magnetic resonance (MR) imaging has evolved into a powerful diagnostic tool for the evaluation of hip arthroplasty implants. Optimized conventional pulse sequences and metal artifact reduction techniques afford improved depiction of bone, implant-tissue interfaces, and periprosthetic soft tissue for the diagnosis of arthroplasty-related complications. Strategies for MR imaging of hip arthroplasty implants are presented, as well as the imaging appearances of common causes of painful and dysfunctional hip arthroplasty systems, including stress reactions and fractures; bone resorption and aseptic loosening; polyethylene wear-induced synovitis and osteolysis; adverse local tissue reactions to metal products; infection; heterotopic ossification; tendinopathy; neuropathy; and periprosthetic neoplasms. A checklist is provided for systematic evaluation of MR images of hip arthroplasty implants. MR imaging with optimized conventional pulse sequences and metal artifact reduction techniques is a comprehensive imaging modality for the evaluation of the hip after arthroplasty, contributing important information for diagnosis, prognosis, risk stratification, and surgical planning.

Is the iliolumbar ligament a reliable identifier of the L5 vertebra in lumbosacral transitional anomalies?

OBJECTIVE: Sufficiently sized studies to determine the value of the iliolumbar ligament (ILL) as an identifier of the L5 vertebra in cases of a lumbosacral transitional vertebra (LSTV) are lacking. METHODS: Seventy-one of 770 patients with LSTV (case group) and 62 of 611 subjects without LSTV with confirmed L5 level were included. Two independent radiologists using coronal MR images documented the level(s) of origin of the ILL. The interobserver agreement was analysed using weighted kappa/kappa (wκ/κ) and a Fischer's exact test to assess the value of the ILL as an identifier of the L5 vertebra. RESULTS: The ILL identified the L5 vertebra by originating solely from L5 in 95 % of the controls; additional origins were observed in 5 %. In the case group, the ILL was able to identify the L5 vertebra by originating solely from L5 in 25-38 %. Partial origin from L5, including origins from other vertebra was observed in 39-59 % and no origin from L5 at all in 15-23 % (wκ = 0.69). Both readers agreed that an ILL was always present and its origin always involved the last lumbar vertebra. CONCLUSION: The level of the origin of the ILL is unreliable for identification of the L5 vertebra in the setting of an LSTV or segmentation anomalies. KEY POINTS: • The origin of the ILL is evaluated in subjects with an LSTV. • The origin of the ILL is anatomically highly variable in LSTV. • The ILL is not a reliable landmark of the L5 vertebra in LSTV.

Three-dimensional magnetic resonance imaging of physeal injury: reliability and clinical utility.

BACKGROUND: Injuries to the physis are common in children with a subset resulting in an osseous bar and potential growth disturbance. Magnetic resonance imaging allows for detailed assessment of the physis with the ability to generate 3-dimensional physeal models from volumetric data. The purpose of this study was to assess the interrater reliability of physeal bar area measurements generated using a validated semiautomated segmentation technique and to highlight the clinical utility of quantitative 3-dimensional (3D) physeal mapping in pediatric orthopaedic practice. METHODS: The Radiology Information System/Picture Archiving Communication System (PACS) at our institution was searched to find consecutive patients who were imaged for the purpose of assessing a physeal bar or growth disturbance between December 2006 and October 2011. Physeal segmentation was retrospectively performed by 2 independent operators using semiautomated software to generate physeal maps and bar area measurements from 3-dimensional spoiled gradient recalled echo sequences. Inter-reliability was statistically analyzed. Subsequent surgical management for each patient was recorded from the patient notes and surgical records. RESULTS: We analyzed 24 patients (12M/12F) with a mean age of 11.4 years (range, 5-year to 15-year olds) and 25 physeal bars. Of the physeal bars: 9 (36%) were located in the distal tibia; 8 (32%) in the proximal tibia; 5 (20%) in the distal femur; 1 (4%) in the proximal femur; 1 (4%) in the proximal humerus; and 1 (4%) in the distal radius. The independent operator measurements of physeal bar area were highly correlated with a Pearson correlation coefficient (r) of 0.96 and an intraclass correlation coefficient for average measures of 0.99 (95% confidence interval, 0.97-0.99). Four patients underwent resection of the identified physeal bars, 9 patients were treated with epiphysiodesis, and 1 patient underwent bilateral tibial osteotomies. CONCLUSIONS: Semiautomated segmentation of the physis is a reproducible technique for generating physeal maps and accurately measuring physeal bars, providing quantitative and anatomic information that may inform surgical management and prognosis in patients with physeal injury. LEVEL OF EVIDENCE: Level IV.

Interreader and intermodality reliability of standard anteroposterior radiograph and magnetic resonance imaging in detection and classification of lumbosacral transitional vertebra.

BACKGROUND CONTEXT: Different types of lumbosacral transitional vertebra (LSTV) are classified based on the relationship of the transverse process of the last lumbar vertebra to the sacrum. The Ferguson view (30° angled anteroposterior [AP] radiograph) is supposed to have a sufficient interreader reliability in classification of LSTV, but is not routinely available. Standard AP radiographs and magnetic resonance imaging (MRI) are often available, but their reliability in detection and classification of LSTV is unknown. PURPOSE: The purpose of this study was to evaluate the interreader reliability of detection and classification of LSTV with standard AP radiographs and report its accuracy by use of intermodality statistics compared with MRI as the gold standard. STUDY DESIGN/SETTING: Retrospective case control study. PATIENT SAMPLE: A total of 155 subjects (93 cases: LSTV type 2 or higher; 62 controls). OUTCOME MEASURES: Interreader reliability in detection and classification of LSTV using standard AP radiographs and coronal MRI as well as accuracy of radiographs compared with MRI. METHODS: After institutional review board approval, coronal MRI scans and conventional AP radiographs of 155 subjects (93 LSTV type 2 or higher and 62 controls) were retrospectively reviewed by two independent, blinded readers and classified according to the Castellvi classification. Interreader reliability was assessed using kappa statistics for detection of an LSTV and identification of all subtypes (six variants; 1: no LSTV or type I, 2: LSTV type 2a, 3: LSTV type 2b, 4: LSTV type 3a, 5: LSTV type 3b, 6: LSTV type 4) for MRI scans and standard AP radiographs. Further, accuracy and positive and negative predictive values were calculated for standard AP radiographs to detect and classify LSTV using MRI as the gold standard. RESULTS: The interreader reliability was at most moderate for the detection (k=0.53) and fair for classification (wk=0.39) of LSTV in standard AP radiograph. However, the interreader reliability was very good for detection (k=0.93) and classification (wk=0.83) of LSTV in MRI. The accuracy and positive and negative predictive values of standard AP radiograph were 76% to 84%, 72% to 86%, and 79% to 81% for the detection and 53% to 58%, 51% to 76%, and 49% to 55% for the classification of LSTV, respectively. CONCLUSION: Standard AP radiographs are insufficient to detect or classify LSTV. Coronal MRI scans, however, are highly reliable for classification of LSTV.

Imaging of hip arthroplasty.

Imaging studies are central to the evaluation of persistent or recurrent symptoms after hip arthroplasty. The evaluation starts with radiographs and may be followed by arthrography, aspiration, scintigraphy, sonography, computed tomography, and MR imaging. Common etiologies of a painful or dysfunctional hip arthroplasty are mechanical loosening, polyethylene wear-induced osteolysis, adverse local tissue reaction to metal wear products, infection, fractures, heterotopic ossification, tendinopathy, and nerve injury. MR imaging with optimized protocols and dedicated techniques for metal artifact reduction is the most comprehensive imaging modality. In this article, we discuss and illustrate the imaging appearances of these conditions with a focus on the MR imaging evaluation.