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Objective: To evaluate the utility of digital mammography in detecting asymptomatic malignancy in autologous flap reconstructions after mastectomy., Methods: A retrospective database review identified all mammograms performed on asymptomatic patients with flap reconstructions over a 9-year period (1/1/2009 to 12/31/2017). A negative examination was defined as BI-RADS 1 or 2 and a positive examination was defined as BI-RADS 0, 4, or 5 assigned to the mastectomy side. Malignant outcomes were determined by pathology results. Interval cancers, or false negatives, were defined as locoregional malignant diagnosis within one year of a negative mammogram. Sensitivity, specificity, predictive values, abnormal interpretation rate, and cancer detection rate were calculated., Results: 626 mammograms of asymptomatic flap reconstructions were performed in 183 patients. The most common flap type was TRAM (83.5 %, 523/626) and DIEP (13.4 %, 84/626). Most exams (98.2 %, 615/626) were negative, assessed as BI-RADS 1 or 2, with no interval cancers at follow-up. Eleven exams (1.8 %, 11/626) were positive, assessed as BI-RADS 0, 4, or 5. After diagnostic work-up of all BI-RADS 0 exams, 9 cases had a final recommendation for biopsy of which 3 were malignant. Mammography yielded a cancer detection rate of 0.5 % (3/626), abnormal interpretation rate of 1.8 % (11/626), NPV of 100 % (615/615), overall PPV of 27.3 % (3/11), PPV2 (positive predictive value of a biopsy recommendation) of 33.3 % (3/9), sensitivity of 100 % (3/3), and specificity of 98.7 % (615/623)., Conclusion: Digital mammography of asymptomatic autologous flap reconstructions after mastectomy demonstrated high sensitivity and low abnormal interpretation rate. Cancer detection rate was comparable to current national benchmarks for mammographic screening in the general U.S. population without mastectomy., Competing Interests: Declaration of competing interest The authors report no relevant disclosures or conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: As radiology continues to grow in low- and middle-income countries (LMICs), radiation exposure and risk to patients and staff will concurrently increase. This study aims to assess the knowledge of radiation safety among medical staff in Tanzania., Methods: A survey was distributed to 350 staff members at a national referral hospital in Tanzania over a 7-month period (February-August 2021). This consisted of a structured questionnaire evaluating participants' knowledge and awareness ionizing radiation and radiation safety. Chi-square and Fisher's exact tests were used to determine the association between independent and dependent categorical variables., Results: A total of 300 surveys were completed (86% response rate). Mean age was 31 and 53% of participants were female. The majority (89%) were clinical staff employed in direct patient care. Most reported having heard of radiation protection (85%) but only 61% reported receiving training in radiation protection. Regarding radiation knowledge, 73% correctly answered how to protect oneself from radiation and 74% knew which medical staff were at greater risk of radiation exposure. However, only 32% correctly answered which imaging tests emit more radiation and only 53% correctly answered which age group was at greatest risk of radiation effects. Non-clinical staff had a significantly lower radiation awareness than clinical staff, with 69.7% reporting having heard about radiation protection, compared to 88.3% of clinical staff (p = 0.004). Female participants were more knowledgeable of radiation risks in pregnancy (p = 0.002). More early career staff reported receiving radiation protection training (64.5%) compared to those with >5 years work experience (53.9%), though this difference was not statistically significant (p = 0.09). When stratifying radiation knowledge by high (score of 80-100%), moderate (60-79.9%) and low (<60%), 20% of participants scored high, 47% moderate, and 33% low., Conclusion: Most staff had low to moderate knowledge on radiation safety. Our findings highlight the importance of education on ionizing radiation as medical imaging continues to rise in Africa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: There are currently various conflicting recommendations for breast cancer screening with mammography in women between ages 40-49. There are no specific guidelines for breast cancer screening in women of this age group prior to assisted reproductive technology (ART) for the treatment of infertility. The purpose of our study was to evaluate outcomes of screening mammography, specifically ordered for the purpose of pre-fertility treatment clearance in women aged 40-49 years old., Materials and Methods: This was an IRB approved retrospective study of women aged 40-49 presenting for screening mammography prior to ART between January 2010 and October 2018. Clinical history, imaging, and pathology results were gathered from the electronic medical record. Descriptive statistics were performed., Results: Our study cohort consisted of 118 women with a mean age of 42 years (range 40-49). Sixteen of 118 (14%) women were recalled from screening for additional diagnostic work-up. Five of the 16 (31%) were recommended for biopsy (BI-RADS 4 or 5). One of 5 biopsies yielded a malignant result (PPV 20%). Overall cancer detection rate was 0.85% or 8.5 women per 1000 women screened. The single cancer in this cohort was an ER+ PR+ HER2- invasive ductal carcinoma., Conclusion: Screening mammography in women 40-49 performed prior to initiation of ART may identify asymptomatic breast malignancy. In accordance with ACR and SBI guidelines to screen women of this age group, women of this age group should undergo screening mammography prior to ART., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Localization of metastatic axillary lymph nodes in breast cancer patients is an increasingly common procedure performed by radiologists. In 2014, the National Comprehensive Cancer Network guidelines stated that "clinically positive axillary lymph node (s) should be sampled by FNA or core biopsy and clipped with image-detectable marker; clipped lymph nodes must be removed if FNA or core biopsy was positive prior to neoadjuvant therapy". Since then, multiple studies have further supported targeted axillary surgery after neoadjuvant chemotherapy (NAC), with excision of the clipped metastatic axillary node in addition to the sentinel node (s). Requests for image guided localization of clipped axillary nodes will continue to increase and likely become the standard of care. However, when lymph nodes have decreased in size after NAC, or when small deep lymph nodes are sampled, the clipped node can be difficult to identify under ultrasound at the time of localization. When the target node is questionable, we have found it valuable to place an intermediary clip, and use an axillary mammographic view to confirm this intermediary clip co-localizes with the intended target. With this confirmation, safe, accurate localization can then be performed. We describe 3 cases of intermediary clip placement facilitating successful localization of previously clipped axillary lymph nodes., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To assess the use and outcomes of ultrasound for the evaluation of breast signs and symptoms in pediatric females., Methods: A retrospective database review identified all patients ≤18-years-old who underwent breast ultrasound at an academic institution over a 20-year period. Each symptomatic site was designated a case and analyses were performed on each case. Imaging findings were obtained from the radiology reports. Clinical and pathology data were obtained from the medical records. Descriptive statistics were performed., Results: The final cohort comprised 124 cases in 101 patients. Mean age was 15 years (range 1-18). The most common indication for ultrasound was a palpable lump (71%). Thirty-seven cases (30%) demonstrated no sonographic correlate to the symptom; 36 (29%) had a benign correlate. The most common benign correlates were abscess/phlegmon and cyst. All cases of abscess/phlegmon had infectious symptoms. Fifty-one cases (41%) demonstrated a sonographic mass that was not characteristically benign. Of these indeterminate masses, 27 were recommended for biopsy, 13 for short-interval follow-up, and 6 had no recommendation. Of 27 biopsied masses, 63% were fibroadenomas. No symptoms were due to malignancy. Therefore, the NPV of ultrasound was 100% and the PPV 0%., Conclusion: In this cohort of pediatric and adolescent patients, malignancy was never the cause of breast symptoms. Imaging yielded false positives with a biopsy recommendation in 22% of cases. Ultrasound provided value in evaluating infectious symptoms. Given the extreme rarity of breast cancer in this population, surveillance may be a safe alternative for most indeterminate lesions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To compare the characteristics, outcomes, and performance metrics in women undergoing initial breast MRI screening versus subsequent screening., Methods: A retrospective database search identified screening MRIs performed at an academic practice from 2013 to 2015. MRIs were divided into two groups: (1) initial screens and (2) subsequent screens (interpreted with at least one prior MRI for comparison). Benignity was confirmed with pathology or >1-year follow-up. Malignancy was confirmed by pathology. Performance metrics were calculated. Comparisons were made using Binomial and Fisher's exact tests., Results: We observed a higher rate of abnormal interpretations (52% vs. 19%; p < 0.001) and rate of biopsy (49% vs. 15%; p < 0.001) in the initial versus subsequent screen group. The positive predictive value of biopsy was slightly lower at initial versus subsequent screen (17% vs. 19%, p = 0.99). However, the cancer detection rate was higher at initial than at subsequent screen (85 vs. 29/1000, p = 0.08). Sensitivity was higher at initial (100%) versus subsequent (88%) screen. However, the specificity at initial screen was low (55%) compared to subsequent screen (83%)., Conclusions: The higher rate of abnormal interpretations in the initial versus subsequent screen group in part reflects a prevalence screening. Although we observed more abnormal interpretations in the initial screen, this was likely justified by the significantly higher cancer detection. This evidence may be used to counsel patients and referring providers on the expected higher likelihood of recall from an initial screening MRI balanced with higher detection of malignancies. Findings also highlight the importance of having comparison MRIs to decrease false positives., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: There are currently no evidence-based guidelines regarding breast cancer screening in women under 40 prior to initiating assisted reproductive technology (ART). The prevalence of abnormal findings on screening mammography in this population is unknown. The purpose of this study was to describe screening mammography outcomes in women less than 40 years old, referred for the indication of pre-ART., Materials, Methods, Procedures: This is a retrospective review of women less than 40 years old presenting for screening mammography prior to ART between January 2010 and March 2017. Clinical history, breast cancer risk factors, imaging and pathology results were gathered from the electronic medical record., Results: The study included 80 women. Mean patient age was 37 years (range 34-39 years). Sixty-seven (84%) had negative or benign screening (BI-RADS 1 or 2) and 13 (16%) were recalled for diagnostic imaging (BI-RADS 0). Four of 13 (31%) recalled women were given BI-RADS 1 or 2 at diagnostic work-up, 4 (31%) were given a BI-RADS 3, and 5 (38%) were recommended for biopsy (BI-RADS 4). At patient request, 2 of 4 (50%) BI-RADS 3 cases underwent biopsy, for 7 total biopsies. Six (86%) biopsies yielded benign results and 1 (14%) yielded DCIS. Overall cancer yield was 1.3%., Conclusion: In women under 40 who plan to undergo ART, screening mammography may identify breast malignancies. This may be of particular importance given many breast cancers are hormone sensitive, and thus fertility treatments may affect tumor growth. Future, larger studies are needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tuberculosis mastitis can be a challenging diagnosis, often presenting with clinical and imaging findings that are suspicious for malignancy. We present a case of a 49-year-old female with a breast mass initially diagnosed as idiopathic granulomatous mastitis. Failure to respond to standard treatments, development of new breast masses, and discovery of a concurrent ulcerating thigh rash with similar histologic findings as the breast masses prompted further investigation, which ultimately lead to the diagnosis of tuberculosis mastitis. There was rapid resolution of both breast and skin symptoms after initiation of empiric drug therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To review the use of diagnostic breast imaging and outcomes for symptomatic male patients., Methods: We retrospectively evaluated 122 males who underwent diagnostic imaging for breast symptoms at our academic center., Results: The majority (94%) of cases had negative or benign imaging, with gynecomastia being the most common diagnosis (78%). There were two malignancies, both of which had positive imaging. Fifteen patients underwent percutaneous biopsy, and over half (53%) were palpation-guided biopsies initiated by the referring clinician despite negative imaging. Diagnostic imaging demonstrated 100% sensitivity and 96% specificity for identifying cancer., Conclusions: Malignancy is rarely a cause of male breast symptoms. Diagnostic breast imaging is useful to establish benignity and avert unnecessary biopsies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Dickkopf-1 (Dkk-1) is a secreted protein that acts as a potent inhibitor of the Wnt signal transduction pathway. It is thought that the antagonistic effect of Dkk-1 is specific to the canonical (Wnt/beta-catenin) pathway. In this study, we demonstrate that restoration of Dkk-1 expression suppresses cell growth and induces apoptotic cell death in beta-catenin-deficient mesothelioma cell lines H28 and MS-1. Furthermore, we found that a small-molecule inhibitor of JNK inhibited the apoptosis induced by Dkk-1 overexpression in these cells. Together, our data suggest that Dkk-1 may be able to antagonize Wnt signaling and exert its tumor suppressive effects through beta-catenin-independent non-canonical pathways (i.e., the Wnt/JNK pathway).

Wnt inhibitory factor-1 (WIF-1) is a secreted antagonist of Wnt signaling and functions by directly binding to Wnt ligands in the extracellular space. Here we report the identification of the 5' promoter region (approximately 1.5 kb) of the human WIF-1 gene. Functional analysis of this region shows that a whole fragment displays high basal promoter activity in different cell lines, while the truncated forms do not, indicating that integrity of the WIF-1 promoter region may be important for WIF-1 activity. Moreover, we found that the expression level of beta-catenin in cancer cell lines correlates with the WIF-1 promoter activity, suggesting that the WIF-1 promoter may be regulated by the Wnt/beta-catenin pathway and may function in a negative feedback manner. Our results also suggest that a methylated CpG island, which we observed recently in human lung cancer, lies within the functional WIF-1 promoter region and therefore bears the importance of the methylation-status of this CpG island as an important key in Wnt activation in human cancer., (Copyright 2004 Elsevier Inc.)

The Janus kinase (JAKs)/signal transducers and activators of transcription (STAT) signaling pathway is controlled by a classical feedback loop through suppressors of cytokine signaling (SOCS/JAB/SSI). Suppressors of cytokine signaling proteins are induced rapidly by activated STATs upon phosphorylation and act to block the cytokine signal. Abnormalities of the JAK/STAT pathway are associated with cancer. Recently, we cloned the functional 5' promoter region of the human SOCS-3 gene and showed that this region is highly conserved in murine and rat SOCS-3 promoters. In addition, we found that the wild type SOCS-3 promoter construct has significantly greater activity in human non-small-cell lung cancer (NSCLC) cell lines than in normal cells in accordance with STAT3 deregulation in these cells. Furthermore, we have confirmed that frequent hypermethylation of the functional SOCS-3 promoter correlates with its transcription silencing in NSCLC cell lines and primary lung cancer tissue samples. Restoration of SOCS-3 in lung cancer cells in which SOCS-3 has been methylation-silenced induces apoptosis and suppresses growth. Therefore, methylation silencing of SOCS-3 may be used as a marker for early detection of NSCLC. Suppressor of cytokine signaling-3 therapy may be useful for the treatment of lung cancer.

Aberrant activation of the Wingless-type (Wnt)/beta-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi) were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.