Purpose Patients with anaplastic lymphoma kinase (ALK) gene rearrangements often manifest dramatic responses to crizotinib, a small molecule ALK inhibitor. Unfortunately, not every patient responds and acquired drug resistance inevitably develops in those that do respond. This study aimed to define molecular mechanisms of resistance to crizotinib in ALK+ non-small cell lung cancer (NSCLC) patients. Experimental Design We analyzed tissue obtained from 14 ALK+ NSCLC patients demonstrating evidence of radiologic progression while on crizotinib in order to define mechanisms of intrinsic and acquired resistance to crizotinib. Results Eleven patients had material evaluable for molecular analysis. Four patients (36%) developed secondary mutations in the tyrosine kinase domain of ALK. A novel mutation in the ALK kinase domain, encoding a G1269A amino acid substitution that confers resistance to crizotinib in vitro, was identified in two of these cases. Two patients, one with a resistance mutation, exhibited new onset ALK copy number gain (CNG). One patient demonstrated outgrowth of EGFR mutant NSCLC without evidence of a persistent ALK gene rearrangement. Two patients exhibited a KRAS mutation, one of which occurred without evidence of a persisting ALK gene rearrangement. One patient demonstrated the emergence of an ALK gene fusion negative tumor compared to the baseline sample, but with no identifiable alternate driver. Two patients retained ALK positivity with no identifiable resistance mechanism. Conclusions Crizotinib resistance in ALK+ NSCLC occurs through somatic kinase domain mutations, ALK gene fusion CNG, and emergence of separate oncogenic drivers.

Sclerotherapy is the therapeutic use of sclerosants in the controlled destruction of undesired target tissues. Sclerosants have been used in vascular and nonvascular settings, both as primary and adjunctive therapy. Effective sclerotherapy requires a conceptual understanding of key questions about the process being treated, including the method of delivery, the presence of flow, and the required contact time to initiate sclerosis. However, beyond technique and delivery, practical and safe application of sclerotherapy requires an understanding of the uses, limitations, dosing, and side effects of sclerosants used during interventional radiology procedures. Agents discussed here include detergents and surfactants [ethanol, Sotradecol 1 (Bioniche Pharma, Pointe Claire, Quebec and Angiodynamics, Latham, NY), ethanolamine oleate], hypertonics (saline, glucose), and a review of several other types that are used less frequently.

The ACR Task Force on Medical Student Education in Radiology, in partnership with the Alliance of Medical Student Educators in Radiology, investigated the current status of how and to what extent medical imaging was being taught in medical schools. The task force executed a 3-part survey of medical school deans, radiology department chairs, and intern physicians. The results provided an updated understanding of the status of radiology education in medical schools in the United States. This summary includes recommendations about how individual radiology departments and ACR members can assist in advancing the specialty of diagnostic radiology through medical student education.

Context In an era in which testing of patient tumor material for molecular and other ancillary studies is of increasing clinical importance for selection of therapy, the ability to test on small samplings becomes critical. Often, small samplings are rapidly depleted in the diagnostic workup or are insufficient for multiple ancillary testing approaches. Objective To describe technical methodologies that can be implemented to preserve and maximize tissue for molecular and other ancillary testing. Data Sources Retrospective analysis of a case cohort from the University of Colorado, description of techniques used at the University of Colorado, and published literature. Conclusions Numerous techniques can be deployed to maximize molecular and other ancillary testing, even when specimens are from small samplings. A dedicated process for molecular prioritization has a high success rate, but also increases workload, which must be factored into establishing such a process. Additionally, establishing high-fidelity communication strings is critical for success of dedicated molecular prioritization of samples. Numerous approaches can be deployed for alternative specimen types, and several technical approaches can also aid in maximizing small specimens.

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Percutaneous renal biopsy is widely used for diagnosis, prognosis, and management of nephropathies. Complications may arise after renal biopsy, most commonly in the form of bleeding. Efforts should be taken to optimize modifiable risk factors such as hypertension, thrombocytopenia, and coagulopathy prior to the procedure. Unmodifiable risk factors such as poor renal function, gender, and underlying histologic diagnosis may be used to identify high-risk patients. Delayed presentation of bleeding complications is common, and close clinical follow-up is crucial.

Vertebral fractures account for $27% of all osteoporotic fractures in both men and women. The economic burden is substantial and growing: osteoporosis is expected to affect 14 million people by the year 2020. There is substantial morbidity associated with osteoporotic vertebral compression fractures (VCFs) including decreased quality of life, reduced pulmonary function, and increased mortality. Relatively recent additions to the treatment armamentarium include vertebral augmentation using vertebroplasty and kyphoplasty. Numerous retrospective and case studies demonstrate short-term efficacy and low complication rates of vertebroplasty and kyphoplasty in the treatment of osteoporotic VCFs, but controlled trials are needed for validation. The pathophysiology, risk factors, consequences, characteristics, and imaging of osteoporotic VCFs are presented in detail along with a discussion of treatment options and patient selection. Vertebral augmentation is comprehensively reviewed, including the technical aspects of the procedures, contraindications, complications, and clinical outcomes.

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