Association Between Breast Arterial Calcifications and Cardiovascular Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Recent studies have shown that breast arterial calcification (BAC) detected on screening mammography is linked to cardiovascular diseases via medial calcification. However, its effect on cardiovascular outcomes remains unclear. Therefore, we conducted a meta-analysis to determine the effect of BAC on cardiovascular outcomes in patients. METHODS: Three electronic databases (Pubmed, Embase, and Scopus) were searched on May 1, 2022, for studies examining the relationship between BAC and cardiovascular outcomes including cardiac death, acute myocardial infarction, ischemic heart disease, stroke, peripheral artery disease, and heart failure. A random-effects meta-analysis model was used to summarise the studies. RESULTS: A total of 5 longitudinal studies were included with a combined cohort of 87,865 patients. Significantly, the pooled risk ratio (RR) of the association between BAC and cardiac death was 2.06 (P < 0.00001). BAC was associated with a significantly increased risk of developing other cardiovascular diseases, such as ischemic/hemorrhagic stroke (RR 1.51; P = 0.003), ischemic stroke (RR 1.82; P < 0.00001), peripheral vascular disease (RR 1.24; P = 0.003), and heart failure (RR 1.84; P < 0.00001). There was no significant relationship for developing myocardial infarction or for total cardiovascular diseases. CONCLUSIONS: Our findings suggest that BAC was associated with an increased risk of cardiovascular mortality, and certain cardiovascular outcomes. There is thus a potential to use BAC as a sex-specific cardiovascular risk assessment tool. Furthermore, there is a need for more widespread reporting of BAC to better understand the pathophysiologic mechanisms behind its correlation with cardiovascular disease and to apply it in clinical practice.

Vascular anatomy of the breast and its implications in the breast-sharing reconstruction technique.

The most frequently described breast-sharing procedure consists in a pedicled technique where the transferred lower breast pole is based on the lower perforators of the internal mammary (IM) artery. The current article investigates the vascular supply of the breast and its surgical implications in breast-sharing reconstruction. Contrast-enhanced magnetic resonance images of 55 patients (110 breasts) were retrospectively examined. A total of 473 branches of the IM, lateral thoracic (LT) and anterior intercostal (AI) arteries with a diameter greater than 0.5 mm were traced throughout their course in the breast. Distinct connections between the vessels were equally recorded. Although any vessel could vascularise any quadrant in the individual patient, blood supply to the lower quadrants came fundamentally from the AI arteries (76.2% of all the perforators). Lower IM branches (4th-5th) were seen to reach both lower quadrants in only 6.4% of the breasts, whereas LT branches did in 15.5%. In 86.4% of the breasts, at least a distinct AI perforator was seen to perfuse both lower quadrants. Well-defined connections between the IM and the LT arteries were observed in 41.8% of the breasts, always at or above the nipple-areola level. Other connections were far less common. Our study strongly indicates that the breast-sharing technique based on 4th-5th contralateral branches of the IM or LT arteries is unreliable in most patients. Given the unpredictable vascularization pattern in the lower breast pole, a preoperative imaging study is mandatory when the use of the contralateral breast is considered. Due to its accuracy, availability, and anatomical reliability, contrast-enhanced magnetic resonance is the best technique in the preoperative evaluation of the breast-sharing reconstruction.

Invisible Surgery Concept and Scenario Strategy: How to Get the Best Aesthetic Results in Oncoplastic Breast-Conserving Surgery.

SUMMARY: The authors believe that oncoplastic breast surgery has to achieve the best possible aesthetic results. In this article, they propose the concept of "invisible surgery." This is a combination of certain oncoplastic techniques that allows for restoration of the original appearance of the breast without obvious scars on the breast. Further, the authors classify the techniques as follows: the "level 1 technique," with contour approach; the "from inside" technique; the lateral parenchymal flap; the axillary subcutaneous adipofascial flap; the rotational lateral thoracic flap; regional island perforator flaps (lateral intercostal artery perforator, lateral thoracic artery perforator, anterior intercostal artery perforator, and medial intercostal artery perforator flaps); and the nipple-sparing mastectomy with immediate expander reconstruction. These techniques were combined by internal logic-one can move from one to another according to the preoperative planning and margins status during the operation. They call their approach the "scenario strategy." The authors have performed 138 operations in 137 patients using this approach. Most of them involved the "from inside" technique and perforator flaps. The average tumor size was 2.4 cm, and the average specimen weight was 43.2 g. The total rate of complications was 14.6 percent. According to this concept, the surgery should be performed in such way that breast appearance will not change. It should be planned as one would plan a staged procedure, taking into account possible changes in the scenario during the operation to achieve the best possible aesthetic result.

Comparing Incision Choices in Immediate Microvascular Breast Reconstruction after Nipple-Sparing Mastectomy: Unique Considerations to Optimize Outcomes.

BACKGROUND: Incision planning is a critical factor in nipple-sparing mastectomy outcomes. Evidence on optimal incision patterns in patients undergoing nipple-sparing mastectomy and immediate microvascular breast reconstruction is lacking in the literature. METHODS: A single-institution retrospective review was performed of consecutive patients undergoing nipple-sparing mastectomy and immediate microvascular autologous reconstruction from 2007 to 2019. Outcomes-including major mastectomy flap necrosis, full nipple-areola complex necrosis, and any major ischemic complication of the skin envelope-were compared among incision types. Multivariable logistic regression identified factors associated with major ischemic complication. RESULTS: Two hundred seventy-nine reconstructions (163 patients) were identified, primarily using internal mammary recipient vessels (98.9 percent). Vertical incisions were used in 139 cases; inframammary, in 53; lateral radial, in 51; and inverted-T, in 35. Thirty-two cases (11.5 percent) had major mastectomy flap necrosis, 11 (3.9 percent) had full nipple-areola complex necrosis, and 38 (13.6 percent) had any major ischemic complication. Inframammary incisions had higher rates of major ischemic complication (25 percent) than vertical (5.8 percent; p < 0.001) and lateral radial (7.8 percent; p = 0.032) incisions. Inverted-T incisions also had higher rates of major ischemic complication (36.1 percent) than both vertical (p < 0.001) and lateral radial (p = 0.002) incisions. Inframammary incisions (OR, 4.382; p = 0.002), inverted-T incisions (OR, 3.952; p = 0.011), and mastectomy weight (OR, 1.003; p < 0.001) were independently associated with an increased risk of major ischemic complication. Inframammary incisions with major ischemic complication demonstrated significantly higher body mass index, mastectomy weight, and flap weight compared to those without. CONCLUSIONS: Inframammary and inverted-T incisions are associated with a higher risk of major ischemic skin envelope complications after nipple-sparing mastectomy and immediate microvascular breast reconstruction. Radial incisions can be considered to optimize recipient vessel exposure without compromising perfusion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Diagnostic accuracy of ultrasound shear wave elastography combined with superb microvascular imaging for breast tumors: A protocol for systematic review and meta-analysis.

BACKGROUND: Shear wave elastography (SWE) is a new ultrasonic elastography technique for evaluating the hardness of living tissue by measuring the propagation velocity of shear wave in tissue, which is characterized by real-time, non-invasive and quantitative. The SWE technique can be used to diagnose the lesions of different tissues and organs, and the quantitative measurement of SWE is considered as more objective information about breast masses. Superb microvascular imaging (SMI) is a new noninvasive Doppler ultrasound imaging method, which can display blood flow information with high spatial resolution and high frame rate, while keeping the minimum low-speed blood flow components. Therefore, SMI can diagnose diseases closely related to angiogenesis at a relatively early stage. However, the results of these studies have been contradictory. The present meta-analysis aimed at determining the accuracy of SWE combined with SMI in the differential diagnosis between benign and malignant breast lesions. METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the April 18, 2021, without language restrictions. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14. 0 software will be used for data analysis. RESULTS: This systematic review will determine the accuracy of shear wave elastography combined with superb microvascular imaging in the differential diagnosis between benign and malignant breast tumors. CONCLUSION: Its findings will provide helpful evidence for the accuracy of shear wave elastography combined with superb microvascular imaging in the differential diagnosis between benign and malignant breast tumors. SYSTEMATIC REVIEW REGISTRATION: INPLASY202150075.

Assessment of breast arteries and lymph nodes by 3D MR angiography enhancement imaging: feasibility and pilot clinical results.

BACKGROUND: Conventional dynamic contrast enhanced (DCE) magnetic resonance (MR) hardly achieves a good imaging performance of arteries and lymph nodes in the breast area. Therefore, a new imaging method is needed for the assessment of breast arteries and lymph nodes. METHODS: We performed prospective research. The research included 52 patients aged from 25 to 64 between June 2019 and April 2020. The isotropic e-THRIVE sequence scanned in the coronal direction after DCE-THRIVE. Reconstructed images obtained by DCE-THRIVE and the coronal e-THRIVE were compared mainly in terms of the completeness of the lateral thoracic artery, thoracodorsal artery, and lymph nodes. We proposed a criterion for evaluating image quality. According to the criterion, images were assigned a score from 1 to 5 according to the grade from low to high. Two board-certified doctors evaluated images individually, and their average score was taken as the final result. The chi-square test was used to assess the difference. RESULTS: The coronal e-THRIVE score is 4.60, which is higher than the DCE-THRIVE score of 3.48, there are significant differences between the images obtained by two sequences (P = 1.2712e-8). According to the score of images, 44 patients (84.61%) had high-quality images on the bilateral breast. Only 3 patients' (5.77%) images were not ideal on both sides. The improved method is effective for most patients to get better images. CONCLUSIONS: The proposed coronal e-THRIVE scan can get higher quality reconstruction images than the conventional method to visualize the course of arteries and the distribution of lymph nodes in most patients, which will be helpful for the clinical follow-up treatment.

Blood supply of the male breast nipple-areola complex evaluated by CTA.

PURPOSE: In addition to women, men also undergo breast surgeries, and early studies on the blood supply of breasts are nearly all conducted in female subjects. The vasculature of the male breast is seldom studied. Understanding the male-specific blood supply of the breast is important for pre-operative planning and reducing complications. The purpose of this retrospective study is to fill the gap in the literature by describing the main blood supply and its orientation in the male breast. METHODS: We retrospectively evaluated thoracic computed tomographic angiography (CTA) data from January 1, 2017 to July 30, 2019. Single or multiple dominant arteries and their origins were traced, and the artery route and orientation related to the nipple-areola complex (NAC) were revealed through data analysis of the images. RESULTS: Totally, 284 breasts were included. Most breasts were supplied by a single dominant artery (196, 69%), among which the lateral thoracic artery (LTA; 119, 41.9%; type I) and internal thoracic artery (ITA; 63, 22.2%; type II) were the most common arteries. A minority of breasts were supplied by vascular anastomoses formed by dual arteries (17, 6.0%; type III), and in 25.0% of breasts, no specific dominant artery was found (type IV). The predominant artery distribution was evaluated. CONCLUSION: This study cohort of male thoracic CTA provided and analysed the elaborate vascular anatomy of the NAC region. Our results favour inferior periareolar incision in regard to diminished vascular-related complications in male surgeries without pre-operative vascular evaluation. This study also suggests that super-lateral or lower-lateral-based pedicles can reserve more vasculature.

Managing breast gangrene during the COVID-19 pandemic.

At the onset of the COVID-19 crisis, a 63-year-old woman with multiple life-limiting comorbidities was referred with a necrotic infected left breast mass on a background of breast cancer treated with conservation surgery and radiotherapy 22 years previously. The clinical diagnosis was locally advanced breast cancer, but four separate biopsies were non-diagnostic. Deteriorating renal function and incipient sepsis and endocarditis resulted in urgent salvage mastectomy during the peak of the COVID19 pandemic. The final diagnosis was infected ischaemic/infarcted breast (wet gangrene) secondary to vascular insufficiency related to diabetes, cardiac revascularisation surgery and breast radiotherapy.

18F-Fluorodeoxyglucose positron emission tomography computed tomography detection of single organ vasculitis of the breast: A case report.

RATIONALE: Although single organ vasculitis (SOV) is a rare occurrence and it is difficult to diagnose, its possibility as a cause of fever of unknown origin (FUO) must be considered. Recently, the usefulness of 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET/CT) in the diagnosis of unknown fevers due to vasculitis, especially in cases of small and medium-sized vasculitis, has begun to be pointed out. PATIENT CONCERNS: We report the case of an 84-year-old woman with persisting fever for more than 2 weeks. She had no accompanying symptoms, other than fever, and the physical examination, echocardiography, and contrast-enhanced CT did not reveal any diagnostic clue. DIAGNOSES: The FDG PET/CT revealed positive uptakes of FDG in the left breast, with a standardized uptake value (SUV) of 2.9. The biopsy specimen of the left breast lesion revealed rupture of the elastic plate and evidence of fibrinoid necrosis of arteries, leading to the diagnosis of polyarteritis (PAN). Further angiographic examination and additional imaging did not reveal the presence of other lesions. Therefore, the diagnosis was established as a PAN-SOV of the left breast. INTERVENTIONS: This patient has improved with follow-up only. OUTCOMES: There has been no evidence of a relapse of PAN over a 5-year follow-up period. LESSONS: SOV presenting with unspecific local symptoms is difficult to diagnose based on the medical history and clinical examination. Our findings show that early "Combination of PET-CT and biopsy" can be a powerful diagnostic tool in patients with FUO for whom diagnosis of the underlying cause is difficult despite appropriate clinical examination.

High-speed three-dimensional photoacoustic computed tomography for preclinical research and clinical translation.

Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.

MicroRNA 34a-AXL Axis Regulates Vasculogenic Mimicry Formation in Breast Cancer Cells.

Targeting the tumor vasculature is an attractive strategy for cancer treatment. However, the tumor vasculature is heterogeneous, and the mechanisms involved in the neovascularization of tumors are highly complex. Vasculogenic mimicry (VM) refers to the formation of vessel-like structures by tumor cells, which can contribute to tumor neovascularization, and is closely related to metastasis and a poor prognosis. Here, we report a novel function of AXL receptor tyrosine kinase (AXL) in the regulation of VM formation in breast cancer cells. MDA-MB-231 cells exhibited VM formation on Matrigel cultures, whereas MCF-7 cells did not. Moreover, AXL expression was positively correlated with VM formation. Pharmacological inhibition or AXL knockdown strongly suppressed VM formation in MDA-MB-231 cells, whereas the overexpression of AXL in MCF-7 cells promoted VM formation. In addition, AXL knockdown regulated epithelial-mesenchymal transition (EMT) features, increasing cell invasion and migration in MDA-MB-231 cells. Finally, the overexpression of microRNA-34a (miR-34a), which is a well-described EMT-inhibiting miRNA and targets AXL, inhibited VM formation, migration, and invasion in MDA-MB 231 cells. These results identify a miR-34a-AXL axis that is critical for the regulation of VM formation and may serve as a therapeutic target to inhibit tumor neovascularization.

Recent Advances in Experimental Models of Breast Cancer Exosome Secretion, Characterization and Function.

Breast cancer (BC) is responsible for 15% of all the cancer deaths among women in the USA. The tumor microenvironment (TME) has the potential to act as a driver of breast cancer progression and metastasis. The TME is composed of stromal cells within an extracellular matrix and soluble cytokines, chemokines and extracellular vesicles and nanoparticles that actively influence cell behavior. Extracellular vesicles include exosomes, microvesicles and large oncosomes that orchestrate fundamental processes during tumor progression through direct interaction with target cells. Long before tumor cell spread to future metastatic sites, tumor-secreted exosomes enter the circulation and establish distant pre-metastatic niches, hospitable and permissive milieus for metastatic colonization. Emerging evidence suggests that breast cancer exosomes promote tumor progression and metastasis by inducing vascular leakiness, angiogenesis, invasion, immunomodulation and chemoresistance. Exosomes are found in almost all physiological fluids including plasma, urine, saliva, and breast milk, providing a valuable resource for the development of non-invasive cancer biomarkers. Here, we review work on the role of exosomes in breast cancer progression and metastasis, and describe the most recent advances in models of exosome secretion, isolation, characterization and functional analysis. We highlight the potential applications of plasma-derived exosomes as predictive biomarkers for breast cancer diagnosis, prognosis and therapy monitoring. We finally describe the therapeutic approaches of exosomes in breast cancer.

Role of Superb Microvascular Imaging in Differentiating Between Malignant and Benign Solid Breast Masses.

INTRODUCTION: The purpose of this study was to evaluate the diagnostic performance of superb microvascular imaging (SMI) in breast lesions. MATERIALS AND METHODS: Eighty-five solid breast lesions were studied with color Doppler flow imaging (CDFI), power Doppler imaging (PDI), monochromatic SMI (mSMI), and contrast-enhanced ultrasonography (CEUS). The penetrating vessels (PVs) and microvascular morphologic and distribution features of the breast tumors were evaluated for each modality. RESULTS: The diagnostic accuracies of CDFI, PDI, mSMI, and CEUS were calculated and compared. Surgical pathologic analysis showed 47 benign and 38 malignant lesions. Compared with CDFI and PDI, mSMI and CEUS detected more PVs in breast lesions. The microvascular architecture showed significant differences between benign and malignant lesions. Benign lesions mainly displayed avascular, line-like, and branch-like patterns, and malignant lesions tended to display root hair-like and crab claw-like patterns. mSMI and CEUS identified more root hair-like and crab claw-like patterns in malignant lesions than CDFI and PDI. The sensitivity, negative predictive value, and accuracy of mSMI findings in diagnosing malignancy based on PVs and vascular patterns were both higher than those of CDFI and PDI. CONCLUSIONS: mSMI is equal to CEUS and superior to CDFI and PDI in identifying microvascular and discriminating malignant and benign breast masses.

Diagnostic accuracy of ultrasound superb microvascular imaging for breast tumor: a meta-analysis.

AIM: This meta-analysis aimed to identify the accuracy of ultrasound superb microvascular imaging (SMI) for the diagnosis of a breast tumor. MATERIAL AND METHOD: We searched PubMed, Web of Science, Google Scholar, Cochrane Library, EBSCO, and CBM databases from January 1st, 2013 until February 1st, 2020 without language restrictions. Meta-analysis was conducted using STATA version 14.0 and Meta-Disc version 1.4 software. We calculated the summary statistics for sensitivity (Sen), specificity (Spe), positive and negative likelihood ratio (LR+/LR-), diagnostic odds ratio (DOR) and receiver operating characteristic (SROC) curve. RESULTS: Fifteen studies that met all inclusion criteria were included in this meta-analysis. A total of 955 breast neoplasm patients and 1116 patients with benign breast tumors were assessed. All breast lesions were histologically confirmed after SMI. The pooled Sen was 0.81 (95%CI=0.78-0.83); the pooled Spe was 0.71 (95%CI=0.68-0.73) The pooled LR+ was 3.24 (95%CI=2.27-4.64); the pooled negative LR-was 0.25 (95%CI=0.18-0.34) The pooled DOR of SMI in the diagnosis of breast tumor was 46.97 (95 % CI=16.72∼131.97). The area under the SROC curve was 0.87 (95%CI=0.84- 0.90). We found no evidence for publication bias (t=-0.84, p=0.42). CONCLUSION: Our meta-analysis indicates that SMI may have a high diagnostic accuracy in differential diagnosis between benign and malignant breast tumors. Thus, SMI may be a good tool for the diagnosis of breast tumors.

Intravenous Tranexamic Acid in Implant-Based Breast Reconstruction Safely Reduces Hematoma without Thromboembolic Events.

BACKGROUND: Antifibrinolytic medications, such as tranexamic acid, have recently garnered increased attention. Despite its ability to mitigate intraoperative blood loss and need for blood transfusion, there remains a paucity of research in breast reconstruction. The authors investigate whether intravenous tranexamic acid safely reduces the risk of hematoma following implant-based breast reconstruction. METHODS: A single-center retrospective cohort study was performed to analyze all consecutive patients undergoing immediate two-stage implant-based breast reconstruction following mastectomy between 2015 and 2016. The incidence of postoperative hematomas and thromboembolic events among all patients was reviewed. The patients in the intervention group received 1000 mg of intravenous tranexamic acid before mastectomy incision and 1000 mg at the conclusion of the procedure. Fisher's exact test and the Mann-Whitney-Wilcoxon test were used. Multivariate logistic regression models were performed to study the impact of intravenous tranexamic acid after adjusting for possible confounders. RESULTS: A total of 868 consecutive breast reconstructions (499 women) were reviewed. Overall, 116 patients (217 breasts) received intravenous tranexamic acid, whereas 383 patients (651 breasts) did not. Patient characteristics and comorbidities were similar between the two the groups. Patients who received tranexamic acid were less likely to develop hematomas [n = 1 (0.46 percent)] than patients who did not [n = 19 (2.9 percent)] after controlling for age, hypertension, and type of reconstruction (prepectoral and subpectoral) (p = 0.018). Adverse effects of intravenous tranexamic acid, including thromboembolic phenomena were not observed. Multivariate analysis demonstrated that age and hypertension independently increase risk for hematoma. CONCLUSIONS: Intravenous tranexamic acid safely reduces risk of hematoma in implant-based breast reconstruction. Further prospective randomized studies are warranted to further corroborate these findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Evaluating the Image Quality of Monoenergetic Images From Dual-Energy Computed Tomography With Low-Concentration and Low-Flow-Rate Contrast Media for the Arterials Supply to the Nipple-Areola Complex in Breast Cancer Compared With Conventional Computed Tomography Angiography.

OBJECTIVE: The objective of this study was to evaluate the image quality of monoenergetic images (MEIs (+)) acquired from dual-energy computed tomography with low-concentration and low-flow-rate contrast media for the arterial supply to the nipple-areola complex (NAC) in breast cancer compared with conventional computed tomography angiography (CTA). METHODS: We enrolled 25 patients (MEI (+)300 group, 300 mg/mL and 2.5 mL/s of contrast media) and 23 patients (CTA370 group, 370 mg/mL and 3.5 mL/s of contrast media) for assessing NAC blood supply angiography. The image quality of the 2 groups was evaluated objectively and subjectively. RESULTS: The 40 keV MEI (+)300 demonstrated higher attenuation and contrast-to-noise ratio than CTA370 group (P < 0.001). The subjective image quality and visualization of the arteries were comparable between 2 groups. CONCLUSIONS: The 40 keV MEI (+)300 acquired from dual-energy computed tomography can achieve comparable image quality of arterial supply to NAC with low-concentration and low-flow-rate contrast media in breast cancer compared with CTA370.