Adnexal lesions detected on CT in postmenopausal females with non-ovarian malignancy: do simple cysts need follow-up?

PURPOSE: To assess whether CT morphology of adnexal lesions in postmenopausal women with history of non-ovarian cancer could be used to discriminate benign and malignant lesions, particularly focusing on applicability of the ACR criteria. MATERIALS AND METHODS: This was an IRB-approved HIPAA-compliant retrospective review of contrast-enhanced CTs of 199 women, 55 years and older. Lesions were classified as simple cystic, complex cystic, solid-cystic, or solid based on CT morphology, and were diagnosed as benign, indeterminate, or malignant on follow-up imaging or pathology. Associated metastatic disease was noted, if present. Findings were analyzed to correlate CT morphology, primary tumor pathology, and metastatic disease pattern with eventual lesion diagnosis. RESULTS: There were 223 adnexal lesions, including 123 (55%) simple cystic, 48 (22%) complex cystic, 40 (18%) solid-cystic, and 12 (5%) solid lesions. 186/223 (83%) lesions were benign, and 37/223 (17%) were malignant. Primary colorectal cancer was significantly associated with an increased likelihood of malignant adnexal lesions (OR 10.2, p < 0.001) compared to patients with other cancers. Adnexal malignancy was significantly associated with the presence of non-ovarian peritoneal metastases (p < 0.001). None of the simple cysts (including 85 cysts between 1-3 cm and 38 cysts > 3 cm) were found to be malignant (malignancy rate: 0.0%, 95% CI 0.0-3.0%). Complex cysts were more likely to be malignant than simple cysts (p = 0.002) and solid-cystic lesions were more likely to be malignant than complex cysts (p < 0.001). CONCLUSION: Simple adnexal lesions on CT in this cohort were unlikely to be malignant, supporting the ACR guidelines. A higher size threshold of 3 cm (vs. 1 cm) may be preferred in all cases of simple cysts for recommending further follow-up. However, more complex-appearing cysts need further evaluation as the risk of malignancy is increased. Peritoneal metastases have a significant correlation with malignant adnexal involvement.

Imaging characterization of adnexal lesions: Do CT findings correlate with US?

OBJECTIVE: To compare contrast-enhanced CT and US agreement in characterizing adnexal lesions in late post-menopausal women. MATERIALS AND METHODS: This was a HIPAA-compliant IRB-approved retrospective review of the contrast-enhanced CTs of 130 late post-menopausal women (> 55 years). The lesions were classified as simple cystic, minimally complex cystic, complex cystic, solid-cystic, or solid based on CT and US morphology. Findings were analyzed to evaluate agreement between CT and US on adnexal lesion characterization. RESULTS: One forty-one adnexal lesions were assessed by both contrast-enhanced CT and US. Overall, there was good agreement between CT and US, which agreed on the lesion morphology in 114 (81%) cases with an unweighted kappa value of 0.68 (95% CI 0.56-0.78). By CT, 83 (59%) were classified as simple cystic, of which 73/83 (88%) were confirmed as simple cystic by US. Of the remaining 10 CT simple cysts, 9 were reclassified by US as minimally complex cystic and one as complex cystic. Eight of these lesions were benign based on pathology or follow-up imaging, while two lesions remained indeterminate. By CT, 27 lesions (19%) were classified as minimally complex, while US reclassified 13 (48%) of the lesions (eight to simple cystic and five as complex or solid-cystic). Among the 31 remaining lesions, there were 4 (13%) discordances between CT and US. CONCLUSION: There is good agreement between CT and US in characterizing adnexal lesion morphology, particularly simple cysts. However, there was significant discordance seen with characterization of minimally complex cysts, indicating that these lesions need US follow-up.

Vascular Endothelial Growth Factor Receptor-1 Is Synthetic Lethal to Aberrant {beta}-Catenin Activation in Colon Cancer.

PURPOSE: The Wnt/beta-catenin (beta-cat) signaling cascade is a key regulator of development, and dysregulation of Wnt/beta-cat contributes to selected cancers, such as colorectal, breast, and hepatocellular carcinoma, through abnormal activation of Wnt target genes. To identify novel modulators of the Wnt/beta-cat pathway that may emerge as therapeutic targets, we did an unbiased high-throughput RNA interference screen. EXPERIMENTAL DESIGN: A synthetic oligonucleotide small interfering RNA library targeting 691 known and predicted human kinases was screened in Wnt3a-stimulated human cells in a live cell luciferase assay for modulation of Wnt/beta-cat-dependent transcription. Follow-up studies of a selected high-confidence "hit" were conducted. RESULTS: A robust quartile-based statistical analysis and secondary screen yielded several kinases worthy of further investigation, including Cdc2L1, Lmtk3, Pank2, ErbB3, and, of note, vascular endothelial growth factor receptor (VEGFR)1/Flt1, a receptor tyrosine kinase (TK) with putative weak kinase activity conventionally believed to be a negative regulator of angiogenesis. A series of loss-of-function, genetic null, and VEGFR TK inhibitor assays further revealed that VEGFR1 is a positive regulator of Wnt signaling that functions in a glycogen synthase kinase-3beta (GSK3beta)-independent manner as a potential synthetic lethal target in Wnt/beta-cat-addicted colon carcinoma cells. CONCLUSIONS: This unanticipated non-endothelial link between VEGFR1 TK activity and Wnt/beta-cat signaling may refine our understanding of aberrant Wnt signaling in colon carcinoma and points to new combinatorial therapeutics targeted to the tumor cell compartment, rather than angiogenesis, in the context of colon cancer. (Clin Cancer Res 2009;15(24):7529-37).