Aberrant crypt foci (ACF) are collections of abnormal colonic crypts with heterogeneous molecular and pathologic characteristics. Large and dysplastic ACF are putative precursors of colon cancer with neoplastic risk related to increased proliferation. In this study, we examined the role of epidermal growth factor receptor (EGFR) signaling in regulating ACF proliferation. Using magnification chromoendoscopy, we collected large ACF with endoscopic features of dysplasia and separately biopsied adjacent mucosa. Transcript levels were measured by real-time PCR, proteins were assessed by Western blotting, and levels were expressed as fold changes of adjacent mucosa. K-ras and B-Raf mutations were assessed by PCR and Ras activation by the ratio Ras-GTP / (Ras-GTP + Ras-GDP). At the RNA level, 38% of ACF were hyperproliferative, with proliferating cell nuclear antigen (PCNA) mRNA z2-fold of adjacent mucosa. Hyperproliferative ACF had significantly increased mRNA levels of EGFR (6.0 F 1.7-fold), transforming growth factor-A (14.4 F 5.0-fold), heparin-binding EGF-like growth factor (4.5 F 1.4-fold), cyclin D1 (4.6 F 0.7-fold), and cyclooxygenase-2 (COX-2; 9.3 F 4.2-fold; P < 0.05). At the protein level, 46% of ACF were hyperproliferative (PCNA, 3.2 F 1.2-fold). In hyperproliferative ACF, 44% possessed significant increases in four EGFR signaling components: EGFR (9.5 F 1.3-fold), phosphoactive ErbB2 (2.6 F 0.4-fold), phosphoactive extracellular signal-regulated kinase (3.7 F 1.1-fold), and cyclin D1 (3.4 F 0.8-fold; P < 0.05). Ras was activated in 46% of ACF (3.2 F 0.4-fold; P < 0.05), but K-ras mutations were present in only 7% of ACF. In contrast to COX-2 mRNA, the protein was not increased in hyperproliferative ACF. In summary, we have shown that ACF with up-regulated PCNA possess increased EGFR signaling components that likely contribute to the enhanced proliferative state of
Mesenteric ischemia is an uncommon condition resulting from decreased blood flow to the small or large bowel in an acute or chronic setting. Acute ischemia is associated with high rates of morbidity and mortality; however, it is difficult to diagnose clinically. Therefore, a high degree of suspicion and prompt imaging evaluation are necessary. Chronic mesenteric ischemia is less common and typically caused by atherosclerotic occlusion or severe stenosis of at least two of the main mesenteric vessels. While several imaging examination options are available for the initial evaluation of both acute and chronic mesenteric ischemia, CTA of the abdomen and pelvis is overall the most appropriate choice for both conditions.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
We prospectively evaluated the use of combined 18 F-NaF/ 18 F-FDG PET/CT in patients with breast and prostate cancer and compared the results with those for 99m Tc-MDP bone scintigraphy and whole-body MRI. Methods: Thirty patients (15 women with breast cancer and 15 men with prostate cancer) referred for standard-ofcare bone scintigraphy were prospectively enrolled in this study. 18 F-NaF/ 18 F-FDG PET/CT and whole-body MRI were performed after bone scintigraphy. The whole-body MRI protocol consisted of both unenhanced and contrast-enhanced sequences. Lesions detected with each test were tabulated, and the results were compared. Results: For extraskeletal lesions, 18 F-NaF/ 18 F-FDG PET/CT and whole-body MRI had no statistically significant differences in sensitivity (92.9% vs. 92.9%, P 5 1.00), positive predictive value (81.3% vs. 86.7%, P 5 0.68), or accuracy (76.5% vs. 82.4%, P 5 0.56). However, 18 F-NaF/ 18 F-FDG PET/CT showed significantly higher sensitivity and accuracy than whole-body MRI (96.2% vs. 81.4%, P , 0.001, 89.8% vs. 74.7%, P 5 0.01) and bone scintigraphy (96.2% vs. 64.6%, P , 0.001, 89.8% vs. 65.9%, P , 0.001) for the detection of skeletal lesions. Overall, 18 F-NaF/ 18 F-FDG PET/CT showed higher sensitivity and accuracy than whole-body MRI (95.7% vs. 83.3%, P , 0.002, 87.6% vs. 76.0%, P , 0.02) but not statistically significantly so when compared with a combination of whole-body MRI and bone scintigraphy (95.7% vs. 91.6%, P 5 0.17, 87.6% vs. 83.0%, P 5 0.53). 18 F-NaF/ 18 F-FDG PET/CT showed no significant difference from a combination of 18 F-NaF/ 18 F-FDG PET/ CT and whole-body MRI. No statistically significant differences in positive predictive value were noted among the 3 examinations. Conclusion: 18 F-NaF/ 18 F-FDG PET/CT is superior to whole-body MRI and 99m Tc-MDP scintigraphy for evaluation of skeletal disease extent. Further, 18 F-NaF/ 18 F-FDG PET/CT and whole-body MRI detected extraskeletal disease that may change the management of these patients. 18 F-NaF/ 18 F-FDG PET/CT provides diagnostic ability similar to that of a combination of whole-body MRI and bone scintigraphy in patients with breast and prostate cancer. Larger cohorts are needed to confirm these preliminary findings, ideally using the newly introduced simultaneous PET/MRI scanners.
MR enterography is playing an evolving role in the evaluation of small bowel Crohn's disease (CD). Standard MR enterography includes a combination of rapidly acquired T2 sequence, balanced steady-state acquisition, and contrast enhanced T1-weighted gradient echo sequence. The diagnostic performance of these sequences has been shown to be comparable, and in some respects superior, to other small bowel imaging modalities. The findings of CD on MR enterography have been well described in the literature. New and emerging techniques such as diffusion-weighted imaging (DWI), dynamic contrast enhanced MRI (DCE-MRI), cinematography, and magnetization transfer, may lead to improved accuracy in characterizing the disease. These advanced techniques can provide quantitative parameters that may prove to be useful in assessing disease activity, severity, and response to treatment. In the future, MR enterography may play an increasing role in management decisions for patients with small bowel CD; however, larger studies are needed to validate these emerging MRI parameters as imaging biomarkers.
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