Prevalence of Malignancy in Adrenal Nodules With Heterogeneous Microscopic Fat on Chemical-Shift MRI: A Multiinstitutional Study.

BACKGROUND. Homogeneous microscopic fat within adrenal nodules on chemical-shift MRI (CS-MRI) is diagnostic of benign adrenal adenoma, but the clinical relevance of heterogeneous microscopic fat is not well established. OBJECTIVE. This study sought to determine the prevalence of malignancy in adrenal nodules with heterogeneous microscopic fat on dual-echo T1-weighted CS-MRI. METHODS. We performed a retrospective study of adult patients with adrenal nodules detected on MRI performed between August 2007 and November 2020 at seven institutions. Eligible nodules had a short-axis diameter of 10 mm or larger with heterogeneous microscopic fat (defined by an area of signal loss of < 80% on opposed-phase CS-MRI). Two radiologists from each center, blinded to reference standard results, determined the signal loss pattern (diffuse, two distinct parts, speckling pattern, central loss, or peripheral loss) within the nodules. The reference standard used was available for 283 nodules (pathology for 21 nodules, ≥ 1 year of imaging follow-up for 245, and ≥ 5 years of clinical follow-up for 17) in 282 patients (171 women and 111 men; mean age, 60 ± 12 [SD] years); 30% (86/282) patients had prior malignancy. RESULTS. The mean long-axis diameter was 18.7 ± 7.9 mm (range, 10-80 mm). No malignant nodules were found in patients without prior cancer (0/197; 95% CI, 0-1.5%). Four of the 86 patients with prior malignancy (hepatocellular carcinoma [HCC], renal cell carcinoma [RCC], lung cancer, or both colon cancer and RCC) (4.7%; 95% CI, 1.3-11.5%) had metastatic nodules. Detected patterns were diffuse heterogeneous signal loss (40% [114/283]), speckling (28% [80/283]), two distinct parts (18% [51/283]), central loss (9% [26/283]), and peripheral loss (4% [12/283]). Two metastases from HCC and RCC showed diffuse heterogeneous signal loss. Lung cancer metastasis manifested as two distinct parts, and the metastasis in the patient with both colon cancer and RCC showed peripheral signal loss. CONCLUSION. Presence of heterogeneous microscopic fat in adrenal nodules on CS-MRI indicates a high likelihood of benignancy, particularly in patients without prior cancer. This finding is also commonly benign in patients with cancer; however, caution is warranted when primary malignancies may contain fat or if the morphologic pattern of signal loss may indicate a collision tumor. CLINICAL IMPACT. In the absence of prior cancer, adrenal nodules with heterogeneous microscopic fat do not require additional imaging evaluation.

SLC26A9 is selected for endoplasmic reticulum associated degradation (ERAD) via Hsp70-dependent targeting of the soluble STAS domain.

SLC26A9, a member of the solute carrier protein family, transports chloride ions across various epithelia. SLC26A9 also associates with other ion channels and transporters linked to human health, and in some cases these heterotypic interactions are essential to support the biogenesis of both proteins. Therefore, understanding how this complex membrane protein is initially folded might provide new therapeutic strategies to overcome deficits in the function of SLC26A9 partners, one of which is associated with Cystic Fibrosis. To this end, we developed a novel yeast expression system for SLC26A9. This facile system has been used extensively with other ion channels and transporters to screen for factors that oversee protein folding checkpoints. As commonly observed for other channels and transporters, we first noted that a substantial fraction of SLC26A9 is targeted for endoplasmic reticulum associated degradation (ERAD), which destroys folding-compromised proteins in the early secretory pathway. We next discovered that ERAD selection requires the Hsp70 chaperone, which can play a vital role in ERAD substrate selection. We then created SLC26A9 mutants and found that the transmembrane-rich domain of SLC26A9 was quite stable, whereas the soluble cytosolic STAS domain was responsible for Hsp70-dependent ERAD. To support data obtained in the yeast model, we were able to recapitulate Hsp70-facilitated ERAD of the STAS domain in human tissue culture cells. These results indicate that a critical barrier to nascent membrane protein folding can reside within a specific soluble domain, one that is monitored by components associated with the ERAD machinery.

Impact of magnetic resonance imaging on functional integrity of non-conditional cardiovascular implantable electronic devices.

BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) have historically restricted the use of magnetic resonance imaging (MRI) due to the potential clinical and configurational risks associated with electromagnetic interference. In this study, the authors investigated the impact of MRI on the functional integrity of non-conditional CIEDs and their clinical correlates. METHODS: In this prospective, observational single-center study, we enrolled patients undergoing MRI over a 5-year period. Prior to assessing the impact of MRI on CIEDs, we performed interrogations in sequential duplication to assess the intrinsic variability of devices. Subsequently, we performed interrogations immediately after MRI, and monitored changes in device parameters and clinical events. RESULTS: We completed 492 MRI studies, 58% in patients with permanent pacemakers (PPMs) and 42% with implantable cardioverter defibrillators (ICDs). Subsequent MRI exposures occurred in 15% encounters. Accounting for intrinsic variability in CIED leads, there were no significant changes in RA, RV, or LV parameters after MRI, regardless of the region imaged (thoracic vs. non-thoracic), type of CIED (PPMs vs. ICDs) and among those with serial MRIs. When ranked for % change pre- to post-MRI, the majority of RA, RV, and LV metrics for thresholds, sensing, and impedance conformed to ≤20% change from baseline. No significant clinical adverse cardiac events or effect on device microcircuitry occurred during the study. CONCLUSION: Incorporating a novel reproducibility tactic, there were neither clinically meaningful device parameter changes nor adverse clinical events during or following MRIs, suggesting the effects of MRI on non-conditional CIED integrity are far less than previously perceived.

Staging and Restaging of Rectal Cancer with MRI: A Pictorial Review.

MRI plays an integral role in the initial local staging of rectal cancer and assessment of treatment response, with the goal of treatment to minimize local recurrence. Standard treatment of rectal cancer includes surgical excision with the addition of neoadjuvant chemoradiation therapy for locally advanced disease. MRI is ideally suited for both surgical planning and risk stratification, allowing for accurate evaluation of tumor location and characteristics, T and N staging, and other MRI-specific features. The role of MRI in risk stratification continues to expand with the emergence of novel organ-sparing management options including active surveillance, minimally invasive surgery, and alternative neoadjuvant therapies. Thus, optimal MRI interpretation requires precise evaluation of the primary tumor and its relationship to surrounding structures with a familiarity of the concepts important in risk stratification and treatment management. Additionally, recognition of the imaging modality's current challenges and limitations can prevent interpretive errors and optimize its diagnostic utility. This pictorial review discusses key concepts of MRI in the initial staging of rectal cancer, assessment of treatment response, and active surveillance of disease, including a focus and discussion on current interpretive challenges and opportunities for advancement.