Atypical Ductal Hyperplasia of the Breast on Core Needle Biopsy: Risk of Malignant Upgrade on Surgical Excision.

PURPOSE: This study identified factors predicting malignant upgrade for atypical ductal hyperplasia (ADH) diagnosed on core-needle biopsy (CNB) and developed a nomogram to facilitate evidence-based decision making. METHODS: This retrospective analysis included women diagnosed with ADH at the National Cancer Centre Singapore (NCCS) in 2010-2015. Cox proportional hazards regression was used to identify clinical, radiological, and histological factors associated with malignant upgrade. A nomogram was constructed using variables with the strongest associations in multivariate analysis. Multivariable logistic regression coefficients were used to estimate the predicted probability of upgrade for each factor combination. RESULTS: Between 2010 and 2015, 238,122 women underwent mammographic screening under the National Breast Cancer Screening Program. Among 29,564 women recalled, 5,971 CNBs were performed. Of these, 2,876 underwent CNBs at NCCS, with 88 patients (90 lesions) diagnosed with ADH and 26 lesions upgraded to breast malignancy on excision biopsy. In univariate analysis, factors associated with malignant upgrade were the presence of a mass on ultrasound (p = 0.018) or mammography (p = 0.026), microcalcifications (p = 0.047), diffuse microcalcification distribution (p = 0.034), mammographic parenchymal density (p = 0.008). and ≥ 3 separate ADH foci found on biopsy (p = 0.024). Mammographic parenchymal density (hazard ratio [HR], 0.04; 95% confidence interval [CI], 0.005-0.35; p = 0.014), presence of a mass on ultrasound (HR, 10.50; 95% CI, 9.21-25.2; p = 0.010), and number of ADH foci (HR, 1.877; 95% CI, 1.831-1.920; p = 0.002) remained significant in multivariate analysis and were included in the nomogram. CONCLUSION: Our model provided good discrimination of breast cancer risk prediction (C-statistic of 0.81; 95% CI, 0.74-0.88) and selected for a subset of women at low risk (2.1%) of malignant upgrade, who may avoid surgical excision following a CNB diagnosis of ADH.

Breast metastasis presenting as swelling with calcification - A case report and review of the literature.

Primary breast carcinomas often present as ill-defined, infiltrative lesions which may contain calcifications, whereas metastatic cancers from non-mammary sites are often more well-circumscribed, sharply demarcated from the adjacent breast tissue and are usually not associated with calcifications, although there are exceptions. We report an atypical case of a lady with lung adenocarcinoma with pleural involvement, who presented with diffuse breast swelling with calcifications on imaging from metastatic lung adenocarcinoma, the first of its kind in the literature. We postulate that the pathophysiology of this was due to lymphatic spread of the tumour from the pleura resulting in retrograde lymphovascular congestion of the breast, resulting in swelling and dystrophic calcification.

A Chatbot to Engage Parents of Preterm and Term Infants on Parental Stress, Parental Sleep, and Infant Feeding: Usability and Feasibility Study.

BACKGROUND: Parents commonly experience anxiety, worry, and psychological distress in caring for newborn infants, particularly those born preterm. Web-based therapist services may offer greater accessibility and timely psychological support for parents but are nevertheless labor intensive due to their interactive nature. Chatbots that simulate humanlike conversations show promise for such interactive applications. OBJECTIVE: The aim of this study is to explore the usability and feasibility of chatbot technology for gathering real-life conversation data on stress, sleep, and infant feeding from parents with newborn infants and to investigate differences between the experiences of parents with preterm and term infants. METHODS: Parents aged ≥21 years with infants aged ≤6 months were enrolled from November 2018 to March 2019. Three chatbot scripts (stress, sleep, feeding) were developed to capture conversations with parents via their mobile devices. Parents completed a chatbot usability questionnaire upon study completion. Responses to closed-ended questions and manually coded open-ended responses were summarized descriptively. Open-ended responses were analyzed using the latent Dirichlet allocation method to uncover semantic topics. RESULTS: Of 45 enrolled participants (20 preterm, 25 term), 26 completed the study. Parents rated the chatbot as "easy" to use (mean 4.08, SD 0.74; 1=very difficult, 5=very easy) and were "satisfied" (mean 3.81, SD 0.90; 1=very dissatisfied, 5 very satisfied). Of 45 enrolled parents, those with preterm infants reported emotional stress more frequently than did parents of term infants (33 vs 24 occasions). Parents generally reported satisfactory sleep quality. The preterm group reported feeding problems more frequently than did the term group (8 vs 2 occasions). In stress domain conversations, topics linked to "discomfort" and "tiredness" were more prevalent in preterm group conversations, whereas the topic of "positive feelings" occurred more frequently in the term group conversations. Interestingly, feeding-related topics dominated the content of sleep domain conversations, suggesting that frequent or irregular feeding may affect parents' ability to get adequate sleep or rest. CONCLUSIONS: The chatbot was successfully used to collect real-time conversation data on stress, sleep, and infant feeding from a group of 45 parents. In their chatbot conversations, term group parents frequently expressed positive emotions, whereas preterm group parents frequently expressed physical discomfort and tiredness, as well as emotional stress. Overall, parents who completed the study gave positive feedback on their user experience with the chatbot as a tool to express their thoughts and concerns. TRIAL REGISTRATION: ClinicalTrials.gov NCT03630679; https://clinicaltrials.gov/ct2/show/NCT03630679.

Telereporting in Breast Imaging Involving More Than 1 Country Requires Careful Consideration.

PURPOSE: To examine the effect that a test set from 1 region of the world has on the performance of expert breast radiologists from that region and from a distant region. METHODS: Forty-seven Australian and 15 Singaporean breast radiologists interpreted the same test set (ie, 60 mammograms of Australian women consisting of 40 typical and 20 atypical cases) in their respective locations. The radiologists assigned each case a confidence score of 1 to 5, where 1 was typical, 2 was benign, and 3 to 5 indicated identifiable cancer. Localization-response operating characteristic area under the curve (AUC), receiver operating characteristic AUC, location sensitivity, case sensitivity, and specificity were calculated for each radiologist and compared between Australian and Singaporean readers using nonparametric 2-tailed Mann-Whitney U tests. RESULTS: Australian readers performed better than did their Singaporean counterparts with respect to localization-response operating characteristic AUC (.738 vs .642, P = .0395) and location sensitivity (.775 vs .660, P = .0185). DISCUSSION: Technological advancement has made possible telereporting, in which radiologists report on mammograms originating from other countries. However, those readers' levels of performance might be affected by interpreting images from populations that are different from those with which they are familiar. CONCLUSION: Radiologist performance differed between the groups when localization of lesions was taken into account. This difference might be because of the Australians' reading mammograms from populations with which they were familiar, in contrast to the Singaporeans.

Machine Learning Supports Automated Digital Image Scoring of Stool Consistency in Diapers.

BACKGROUND/AIMS: Accurate stool consistency classification of non-toilet-trained children remains challenging. This study evaluated the feasibility of automated classification of stool consistencies from diaper photos using machine learning (ML). METHODS: In total, 2687 usable smartphone photos of diapers with stool from 96 children younger than 24 months were obtained after independent ethical study approval. Stool consistency was assessed from each photo according to the original 7 types of the Brussels Infant and Toddler Stool Scale independently by study participants and 2 researchers. A health care professional assigned a final score in case of scoring disagreement between the researchers. A proof-of-concept ML model was built upon this collected photo database, using transfer learning to re-train the classification layer of a pretrained deep convolutional neural network model. The model was built on random training (n = 2478) and test (n = 209) subsets. RESULTS: Agreements between study participants and both researchers were 58.0% and 48.5%, respectively, and between researchers 77.5% (assessable n = 2366). The model classified 60.3% of the test photos in exact agreement with the final score. With respect to the 4-class grouping of the 7 Brussels Infant and Toddler Stool Scale types, the agreement between model-based and researcher classification was 77.0%. CONCLUSION: The automated and objective scoring of stool consistency from diaper photos by the ML model shows robust agreement with human raters and overcomes limitations of other methods relying on caregiver reporting. Integrated with a smartphone application, this new framework for photo database construction and ML classification has numerous potential applications in clinical studies and home assessment.

Behaviour and characteristics of low-grade ductal carcinoma in situ of the breast: literature review and single-centre retrospective series.

AIMS: Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease that has risen to prominence and more recently controversy, with the advent of screening mammography. Debate concerning the true biological potential of low nuclear grade DCIS continues to challenge therapeutic considerations. In this study, we carried out a comprehensive literature review of the behaviour, outcomes and current management trials of low-grade DCIS, as well as a retrospective study of a large single institutional series of low-grade DCIS diagnosed at our hospital. METHODS AND RESULTS: The study cohort comprised 195 cases of low-grade DCIS diagnosed at the Singapore General Hospital from 1994 to 2010. Clinicopathological parameters and follow-up data were retrieved and compared between screen-detected and symptomatic low-grade DCIS. Immunohistochemistry was performed for ER, PR and HER2. Among 195 cases, 123 (63.1%) were screen-detected, while 72 (36.9%) were symptomatic. Screen-detected cases had frequent calcifications (P < 0.001) and were smaller (P = 0.018) than symptomatic cases. All cases were ER-positive and rate of PR expression was high. No HER2 overexpression was observed. Mean and median follow-up periods were 107.8 and 109.6 months, respectively. Six patients recurred ipsilaterally, and one patient developed direct distant metastasis. One breast cancer-related death was recorded. Positive surgical margins (P = 0.023) were significantly associated with a higher risk of ipsilateral recurrences, as well as poorer disease-free survivals (P = 0.010). CONCLUSION: Our data indicate that low-grade DCIS may be followed by invasive recurrences and even metastatic disease, requiring more study before being regarded as innocuous and indolent.

Autophagy Governs Protumorigenic Effects of Mitotic Slippage-induced Senescence.

The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment.Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625-40. ©2018 AACR.

Metastases to the breast: great radiological mimicker of primary breast carcinoma and a forgotten entity. A case series of three patients and a review of the literature.

Metastases to breast accounts for 0.5-1.3% of all breast malignancies, with the exclusion of leukaemia and lymphoma. These have a wide range of clinical and radiological manifestations and their diagnosis is difficult. There is a need to distinguish them from primary breast carcinoma to prevent unnecessary mastectomy. Imaging and immunohistological correlation plays a vital role in distinguishing this. Our case series review describes the clinical presentation, radiological and histopathological appearances of three patients who presented to our institution.

Characteristics and behaviour of screen-detected ductal carcinoma in situ of the breast: comparison with symptomatic patients.

Breast cancer is the most common malignancy in Singapore women. Ductal carcinoma in situ (DCIS) is the putative, non-obligate precursor of the majority of invasive breast cancers. The efficacy of the Singapore breast-screening pilot project in detecting early stage breast cancer led to the launch of a national breast-screening programme, BreastScreen Singapore (BSS), in January 2002. In this study, we compared clinicopathological and immunohistochemical characteristics, as well as clinical outcomes, between screen-detected and symptomatic DCIS. The study cohort comprised 1202 cases of DCIS diagnosed at Singapore General Hospital from 1994 to 2010. Comparison of clinicopathological parameters, immunohistochemical results of ER, PR, HER2, CK14, EGFR, and 34ßE12, and clinical outcomes was carried out between the 2 groups. Amongst 1202 cases, 610 (50.7%) were screen-detected and 592 (49.3%) were symptomatic DCIS. Screen-detected cases were smaller in size (P < 0.001), of lower nuclear grade (P = 0.004), and more frequently expressed ER (P < 0.001). Luminal A phenotype was more frequently observed in screen-detected DCIS, while triple-negative and HER2 phenotypes were more common in symptomatic DCIS (P < 0.001). The basal-like phenotype was also more frequent in symptomatic DCIS (P = 0.041). Mean and median follow-up was 99.7 and 97.8 months, respectively, with a maximum follow-up of 246.0 months. More symptomatic patients developed invasive recurrences compared to screen-detected patients (P = 0.001). A trend for better disease-free survival was observed in screen-detected patients (P = 0.076). Patients who were screen-detected experienced better overall survival than those with symptomatic DCIS (P = 0.007). Our data indicate a more favourable outcome of screen-detected DCIS patients confirming the role of BSS in early identification of this curable disease.

Papillary lesions of the breast: imaging findings and diagnostic challenges.

Papillary breast lesions encompass a wide spectrum of pathologies ranging from benign lesions, such as solitary intraductal papilloma, to the uncommon papillary carcinoma. These lesions have various clinical presentations and diverse radiological features. Differentiating benign and malignant papillary lesions based on imaging features may often be difficult. Other benign and malignant pathologies can also mimic papillary lesions on imaging, and tissue diagnosis is essential. Imaging plays an important role in lesion identification, assessment of extent, tissue sampling, and follow-up. Surgical excision has been recommended for all papillary lesions due to an increased incidence of high-risk lesions and neoplasia even with percutaneous, biopsy-proven benign papillomas. This review looks at papillary breast lesions from the radiologists' standpoint and discusses the clinical, imaging, and pathological features of these lesions, as well as the role of imaging in their evaluation.

Mammographic and sonographic findings of steatocystoma multiplex presenting as breast lumps.

Steatocystoma multiplex (SM) is an uncommon cutaneous disorder characterised by multiple intradermal cysts distributed over the trunk and proximal extremities. This condition affects both genders and is often inherited as an autosomal dominant trait, although sporadic cases have been described. This report describes the mammographic and sonographic features of the cysts, which presented as breast lumps, for evaluation. The cysts appeared as numerous well-circumscribed, radiolucent nodules with thin radiodense rims on mammography. On sonography, the cysts could be hypoechoic, isoechoic or demonstrate mixed echoes containing debris-fluid levels, depending on the amount of clear oily liquid and keratinous material. SM can be diagnosed based on a clinical setting of multiple asymptomatic small intradermal nodules over the trunk and proximal extremities, positive family history and imaging findings.

Mucin extravasation in breast core biopsies--clinical significance and outcome correlation.

AIMS: To document the spectrum of lesions associated with mucin extravasation (ME) in breast core biopsy specimens, and to correlate with open surgical excisions. METHODS AND RESULTS: Thirty-nine lesions in 37 women with ME on core biopsies constituted the study group. Fibrocystic change (FC), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were found in 21 (53.8%), 13 (33.3%) and four (10.3%) core biopsy specimens, respectively, with one (2.6%) consisting only of mucin pools. Except for the latter, all disclosed mucocoele-like lesions (MLL) accompanying ME. Columnar cell lesions (CCL) were frequently observed (84.6%). On open biopsy, three cases underdiagnosed on core biopsy included FC that later disclosed ADH; one ADH lesion on core later upgraded to DCIS; and a case of mucin pools that revealed mucinous carcinoma on excision. The extent of CCL on core biopsy appeared to predict sinister lesions on open excision. For calcified lesions that were completely removed on core biopsy, there were no malignant lesions discovered on open excision that had not already been diagnosed preoperatively. CONCLUSIONS: ME and MLL on core biopsy warrant close radiological-pathological correlation. When the entire radiological abnormality has been removed with large core mammotome biopsy specimens, surgery may potentially be avoided in histologically benign lesions, although such an approach requires further validation.

Early detection of breast cancer through population-based mammographic screening in Asian women: a comparison study between screen-detected and symptomatic breast cancers.

The first nation-wide mammographic screening program in Asia, BreastScreen Singapore (BSS), was launched in Singapore in January 2002. This study compared the presentation and results of screen-detected breast cancers with symptomatic breast cancers in two affiliated high-volume institutions, one of which was an assessment centre for BSS. The medical records of patients diagnosed with primary breast cancer at the Department of General Surgery, Singapore General Hospital and the Department of Surgical Oncology, National Cancer Centre, Singapore, during the period January 2002 to December 2003 were reviewed. Clinical and pathological comparisons were made between screen-detected lesions and symptomatic lesions. Of a total of 767 cases, 640 (83.4%) were invasive carcinomas and 127 (16.6%) were ductal carcinoma in-situ (DCIS) lesions. Only 13.4% of them were screen-detected. Compared to symptomatic cancers, screen-detected lesions were of smaller size (median size 18 versus 23 mm), a lower stage (stages 0-2, 95 versus 83.2%) and histologic grade (grade 1-2, 71 versus 60%), with a higher incidence of DCIS (31.0 versus 14.3%) and had higher rates of breast conservation (45.6 versus 28.2%) (all p-values <0.05). By multivariate analysis, tumor palpability, tumor size >20 mm, nodal involvement, cerbB2 overexpression, and advanced disease stage were independent poor prognostic factors for disease-free survival, whereas nodal involvement, advanced disease, and recurrence predicted poor cancer-specific survival. However, there was no statistically significant difference in disease-free survival or cancer-specific survival between the two groups at a median follow-up of 38 months. Screening mammography has allowed the detection of smaller and hence oncologically more favorable lesions in Asian women. Although no significant survival benefit was demonstrated in our study, a longer period of follow-up is essential before the benefit of mortality reduction, as a result of mammography screening becomes evident in our population.

Underestimation of malignancy of atypical ductal hyperplasia diagnosed on 11-gauge stereotactically guided Mammotome breast biopsy: an Asian breast screen experience.

The incidence of malignancy in excision biopsies performed for atypical ductal hyperplasia (ADH) diagnosed on needle biopsies has decreased since the advent of larger tissue sampling and improved accuracy using vacuum-assisted Mammotome biopsy. We undertook a retrospective study to identify predictive factors for understaging of ADH diagnosed on 11-gauge Mammotome biopsy, to determine whether it was possible to avoid surgical excision in women where mammographically visible calcifications had been completely removed. Sixty-one biopsy diagnosed ADH lesions were correlated with surgical excision findings that revealed DCIS in 14 (23%). The mammographic and biopsy features were statistically analyzed using Fisher's exact test. There was no association between morphology, extent of calcifications, number of cores sampled with underestimation of malignancy (P=0.503, 0.709, 0.551 respectively). In the absence of residual calcifications, the frequency of underestimation of carcinoma still occurred in 17%.

Apoptosis and traumatic brain injury.

Traumatic brain injury is a cause of high mortality and morbidity and is an area of intense research. Apoptosis plays a crucial role in the pathogenesis of head injury, and the inhibition of apoptosis can potentially reverse the deleterious effects and lead to better functional outcome. Elucidation of the apoptotic pathway and its role in traumatic brain injury will provide potential targets for therapeutic intervention. This article aims to review the current wealth of literature on apoptosis and traumatic head injury and explores the current status of therapeutic strategies available.