Pushing the envelope in breast conserving surgery - is multiple-wire localization (3 or more wires) associated with increased risk of compromised margins and long-term recurrence?

INTRODUCTION: In the last two decades there has been a paradigm shift with breast conserving surgery (BCS) being applied to larger and more extensive breast malignancies. The aim of this study is to examine the success of BCS being performed in patients with extensive breast malignancies requiring at least 3 wires for localization, and to assess possible risk factors for failure. MATERIALS AND METHODS: We performed a retrospective single center review of 232 patients who underwent BCS between 2010 and 2020 requiring at least 3 wires for localization, thus comprising the multi-wire group (MWG). The cohort included a control group of 232 single-wire BCS patients (SWG) chronologically matched with the MWG. Patients with either invasive malignancy or ductal carcinoma in situ (DCIS) were included in the study. Clinical, radiological, and pathological data was collected. Proportions of positive surgical margins, re-lumpectomies and conversion to mastectomy were calculated. Survival analysis for locoregional and distant recurrence was performed. RESULTS: Women in the MWG were younger (mean age 57 vs. 63.1, P < 0.001), had larger tumor size (mean size 5.1 cm vs. 1.3 cm, p < 0.001), a higher prevalence of calcifications on mammograms (72 % vs. 17 %, P < 0.001), a higher proportion of positive lymph nodes (75 % vs. 45 %, P = 0.019), and an elevated incidence of a ductal carcinoma in situ (DCIS) component (72 % vs. 38 %, P < 0.001). Positive surgical margins were higher in the MWG (13 % vs 7 %, P = 0.03), which lead to higher proportions of re-lumpectomies or conversion to mastectomies (7 % vs 4 %, P = 0.17). On multivariate analysis of the entire cohort, patients with positive margins were more likely to have a DCIS component (77 % vs 53 %, P = 0.001), an infiltrating lobular carcinoma (ILC) component (15 % vs 9 %, P = 0.013), and positive ER hormonal status (94 % vs 85 %, p = 0.05). The number of wires was not an independent predictor of positive margins. On long-term analysis, the locoregional disease-free survival was similar between the SWG and MWG (P = 0.1). However, the MWG showed higher rates of distant metastasis (12 % vs 4 %, P = 0.006). CONCLUSIONS: BCS requiring 3 or more wires is associated with a slightly higher proportion of positive margins. The increased risk of positive margins appears to be related to the type of tumor (DCIS component, ILC component and ER status) rather than to the number of wires. The number of wires does not significantly impact locoregional disease-free survival.

The diagnostic performance of ultrafast MRI to differentiate benign from malignant breast lesions: a systematic review and meta-analysis.

OBJECTIVES: To assess the diagnostic performance of ultrafast magnetic resonance imaging (UF-DCE MRI) in differentiating benign from malignant breast lesions. MATERIALS AND METHODS: A comprehensive search was conducted until September 1, 2023, in Medline, Embase, and Cochrane databases. Clinical studies evaluating the diagnostic performance of UF-DCE MRI in breast lesion stratification were screened and included in the meta-analysis. Pooled summary estimates for sensitivity, specificity, diagnostic odds ratio (DOR), and hierarchic summary operating characteristics (SROC) curves were pooled under the random-effects model. Publication bias and heterogeneity between studies were calculated. RESULTS: A final set of 16 studies analyzing 2090 lesions met the inclusion criteria and were incorporated into the meta-analysis. Using UF-DCE MRI kinetic parameters, the pooled sensitivity, specificity, DOR, and area under the curve (AUC) for differentiating benign from malignant breast lesions were 83% (95% CI 79-88%), 77% (95% CI 72-83%), 18.9 (95% CI 13.7-26.2), and 0.876 (95% CI 0.83-0.887), respectively. We found no significant difference in diagnostic accuracy between the two main UF-DCE MRI kinetic parameters, maximum slope (MS) and time to enhancement (TTE). DOR and SROC exhibited low heterogeneity across the included studies. No evidence of publication bias was identified (p = 0.585). CONCLUSIONS: UF-DCE MRI as a stand-alone technique has high accuracy in discriminating benign from malignant breast lesions. CLINICAL RELEVANCE STATEMENT: UF-DCE MRI has the potential to obtain kinetic information and stratify breast lesions accurately while decreasing scan times, which may offer significant benefit to patients. KEY POINTS: • Ultrafast breast MRI is a novel technique which captures kinetic information with very high temporal resolution. • The kinetic parameters of ultrafast breast MRI demonstrate a high level of accuracy in distinguishing between benign and malignant breast lesions. • There is no significant difference in accuracy between maximum slope and time to enhancement kinetic parameters.

Vitamin D and S-farnesylthiosalicylic acid have a synergistic effect on hepatic stellate cells proliferation.

BACKGROUND: Hepatic stellate cells (HSCs) have a key role in the formation of hepatic fibrosis. The active form of vitamin D, 1,25(OH)2D3, has been found to have antiproliferative and antifibrotic effects in various tissues including liver. Farnesylthiosalicylic acid (FTS), a novel Ras antagonist, was also found to inhibit hepatic fibrosis. AIMS: The purpose of this study was to examine the antiproliferative and antifibrotic effects of the combined treatment of 1,25(OH)2D3 and FTS on primary cultured HSCs. METHODS: Primary HSCs, isolated from rat's livers, were treated with 1,25(OH)2D3, FTS or a combination of both. Proliferation was assessed by bromodeoxyuridine. Expression of p-ERK, ERK, Ras-GTP, total-Ras, CyclinD1 and fibrotic markers was measured by western blotting analysis and real-time PCR. Cytotoxicity was assessed by lactate dehydrogenase method. RESULTS: The combined treatment inhibited HSCs proliferation by threefold. The effect was synergistic and non-cytotoxic. In concordance, the combined treatment suppressed CyclinD1 expression by ~2-fold, whereas 1,25(OH)2D3 or FTS alone showed a significantly lower inhibitory effect. The effect of the combined treatment on CyclinD1 expression was mediated via Ras-GTP and p-ERK signal transduction pathway. The effect on fibrotic markers showed that 1,25(OH)2D3 decreased collagen Iα1 expression by ~40%, FTS by ~50% and the combined treatment by ~60%. 1,25(OH)2D3 inhibited tissue inhibitor of metalloproteinases-1 (TIMP-1) expression by 20%. FTS alone or 1,25(OH)2D3 + FTS inhibited TIMP-1 expression by 60%. FTS inhibited transforming growth factor-ß (TGF-ß) expression by 25%, while 1,25(OH)2D3 had no effect. CONCLUSION: Although the combination of 1,25(OH)2D3 and FTS did not demonstrate an additive antifibrotic effect, it showed a synergistic antiproliferative effect on primary HSCs. Therefore, the combined treatment may have a potential therapeutic value in the initiation of fibrotic process.