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18 Aug 2019 at 01:33
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Bibliography on: Invasive Ductal Carcinoma


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RJR: Recommended Bibliography 18 Aug 2019 at 01:33 Created: 

Invasive Ductal Carcinoma

Invasive ductal carcinoma (IDC), also known as infiltrating ductal carcinoma, is cancer that began growing in a milk duct and has invaded the fibrous or fatty tissue of the breast outside of the duct. IDC is the most common form of breast cancer, representing 80 percent of all breast cancer diagnoses.

Created with PubMed® Query: ("invasive ductal carcinoma" OR IDC) NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-08-16

Cohen OBS, Shahar G, A Brunstein Klomek (2019)

Peer Victimization, Coping Strategies, Depression, and Suicidal Ideation Among Young Adolescents.

Crisis [Epub ahead of print].

Background: Victimization by bullying among adolescents is a widespread phenomenon associated with depression and suicidal ideation. Coping with bullying may include aggressive responding and self-blame. Aims: The purpose of this study was to examine the role adolescent self-blame and aggression - representing coping with peer bullying - in depression and suicide ideation. Method: We recruited 97 "pure" victims (41 girls; mean age = 12.69, SD = .80) identified from a sample of 505 adolescents (242 girls; mean age = 12.73, SD = .81) from two Israeli high schools. Self-report questionnaires were used to assess victimization, aggressive responses, self-blame, depression, and suicide ideation. Results: Self-blame in the face of peer bullying was uniquely associated with both depression and suicide ideation. The effect was robust even after controlling for level of victimization. No direct effect of aggressive coping or moderating effects of self-blame or aggression on the association between victimization and depression/suicide ideation were found. Limitations: This study used a cross-sectional design and made exclusive use of self-report measures. Conclusion: Adolescents who blame themselves for being bullied might be at a heightened risk for depression and suicidality compared to adolescents who did not use self-blame.

RevDate: 2019-08-16

Bozkurt H, Karakaya IB, Aktas E, et al (2019)

Coexistence of phylloides tumour and invasive ductal cancer in the breast.

Nigerian journal of clinical practice, 22(8):1169-1171.

Phylloides tumor in the breast is a rare fibroepithelial tumor, which is often seen in young adult women. Phylloides tumor of the breast accounts for about 1% of all breast tumors and approximately 3% of all fibroepithelial tumors. Pre-operative diagnosis is difficult. Since there aren't any specific mammography and ultrasound findings, they cannot be distinguished from fibroadenomas through these imaging methods and are mostly followed up as if they are fibroadenomas. Patients often present with the complaint of a mass that has been present for a long time and had started to grow suddenly. The primary preferred approach for treatment is wide local excision with negative surgical margins. Coexistence of invasive ductal carcinoma with phylloides tumor in the same breast is a very rare occurrence. We present in this article, a 42-year-old female patient with an invasive ductal carcinoma inside a phylloides tumor in the same breast.

RevDate: 2019-08-14

Balbinot EDCA, Pereira MFCC, Skupien JA, et al (2019)

Analysis of transmittance and degree of conversion of composite resins.

Microscopy research and technique [Epub ahead of print].

The objective of this study was to evaluate and correlate light transmittance (T), initial degree of conversion (IDC), and degree of conversion after 24 hr (DC24) for 22 composite resins (CR) for enamel and dentin use. The transmittance (n = 10) was measured with a spectrometer at a wavelength of 468.14 nm. The degree of conversion (DC; n = 5) was measured with Fourier Transform Near-Infrared Spectroscopy before polymerization, immediately after photoactivation, and 24 hr after photoactivation. Both sets of values are provided as percentages. ANOVA and Games-Howell (α = 5%) tests showed that Filtek Supreme Ultra gave the highest T values of all enamel CRs, while Esthet-X HD presented the lowest. Meanwhile, Venus diamond gave the highest values of all dentin CRs, while Esthet-X HD gave the lowest. For IDC and DC24, ANOVA showed differences between individual CRs and the two CR types (p < .0001). Despite the limitations of this study, it can be concluded that there was no correlation between T and either IDC or DC24 (p > .05); however, IDC and DC24 were strongly correlated (p < .05) by Pearson's correlation. That being said, as a higher DC reflects better mechanical properties, certain conclusions can be drawn about overall performance. The best IDC values were observed for the Opallis enamel resin and the Opallis and Premise dentin resins. Meanwhile, the best DC24 values were observed for the Opallis, Charisma, and Premise enamel resins and the Opallis and Premise dentin resins. Degree of conversion and light transmittance showed differences between composite resin types (enamel and dentin) and brands. It is important to know at the moment of composite choice taking into account mechanical and optical properties.

RevDate: 2019-08-14

Walsh L, Haley KE, Moran B, et al (2019)

BET inhibition as a rational therapeutic strategy for invasive lobular breast cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research pii:1078-0432.CCR-19-0713 [Epub ahead of print].

PURPOSE: Invasive lobular carcinoma (ILC) is a subtype of breast cancer accounting for 10% of breast tumors. The majority of patients are treated with endocrine therapy; however, endocrine resistance is common in ER-positive breast cancer and new therapeutic strategies are needed. Bromodomain and extra-terminal inhibitors (BETi) are effective in diverse types of breast cancer but they have not yet been assessed in ILC.

EXPERIMENTAL DESIGN: We assessed whether targeting the BET proteins with JQ1 could serve as an effective therapeutic strategy in ILC in both 2D and 3D models. We used dynamic BH3 profiling and RNA-sequencing to identify transcriptional reprograming enabling resistance to JQ1-induced apoptosis. As part of the RATHER study, we obtained copy number alterations and RNA-seq on 61 ILC patient samples.

RESULTS: Certain ILC cell lines were sensitive to JQ1, while others were intrinsically resistant to JQ1-induced apoptosis. JQ1 treatment led to an enhanced dependence on anti-apoptotic proteins and a transcriptional rewiring inducing Fibroblast Growth Factor Receptor 1 (FGFR1). This increase in FGFR1was also evident in invasive ductal carcinoma (IDC) cell lines. The combination of JQ1 and FGFR1 inhibitor was highly effective at inhibiting growth in both 2D and 3D models of ILC and IDC. Interestingly, we found in the RATHER cohort of 61 ILC patients that 20% hadFGFR1amplification and we showed that high BRD3 mRNA expression was associated with poor survival specifically in ILC.

CONCLUSIONS: We provide evidence that BETi either alone or in combination with FGFR1 inhibitors or BH3 mimetics may be a useful therapeutic strategy for recurrent ILC patients.

RevDate: 2019-08-13

Cernadas Curotto P, Halperin E, Sander D, et al (2019)

Emotions in attacker-defender conflicts.

The Behavioral and brain sciences, 42:e120 pii:S0140525X19000918.

The distinction between attackers and defenders might help refine the understanding of the role of emotions in conflicts. Here, we briefly discuss differences between attackers and defenders in terms of appraisals, action tendencies, emotional preferences, and brain activities. Finally, we outline how attackers and defenders may differ in their response to emotion-based interventions that aim to promote conflict resolution.

RevDate: 2019-08-13

Wan N, Liu D, Lu L, et al (2019)

[Application of pedicled omentum flap in breast reconstruction of breast cancer patients].

Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery, 33(8):1006-1010.

Objective: To explore the clinical application of the pedicled omentum flap in breast reconstruction of breast cancer patients.

Methods: Between May 2013 and October 2017, 205 patients with breast cancer received modified mastectomy. The pedicled omentum flap was used to reconstruct breast at the same time. All patients were female with an average age of 34.9 years (mean, 26-58 years). The tumor located at left breast in 127 cases and right side in 78 cases. The diameter of the tumor was 2-5 cm (mean, 2.9 cm). The 120 cases of breast cancer were at stage Ⅰ and 85 cases were at stage Ⅱ; and 126 cases were invasive ductal carcinoma and 79 cases were invasive lobular carcinoma. The course of disease ranged from 10 to 92 days (mean, 38.5 days). The size of defect after tumor ablation ranged from 9 cm× 6 cm to 18 cm×12 cm; the size of pedicled omentum flap ranged from 18 cm×10 cm to 22 cm×16 cm.

Results: According to the anatomical basis, the omentum was divided into 4 types, including thin type (42 cases, 20.5%), medium type (133 cases, 64.9%), hypertrophy type (24 cases, 11.7%), and absence type (6 cases, 2.9%). All omentum flaps survived successfully and the incisions healed by first intention. All patients were followed up 6-74 months (mean, 24.5 months); 83 cases were followed up more than 5 years. The shape, texture, and elasticity of the reconstructed breast were good and no flap contracture deformation happened. Only linear scar left at the donor sites, and the function of abdomen was not affected. No local recurrence happened.

Conclusion: The pedicled omentum flap can be harvested safely and reliable, which is the one of ideal option for breast reconstruction in breast cancer patients.

RevDate: 2019-08-10

Onuba L, M Perez-Machado (2019)

Pancreas FNA.

Cytopathology : official journal of the British Society for Clinical Cytology [Epub ahead of print].

67-year-old lady diagnosed with right breast invasive ductal carcinoma with axillary node involvement. Staging FDG PET identified a small enhancing 1.2cm 'indeterminate' nodule within pancreatic tail, which CT pancreas with contrast revealed to be hypervascular. This article is protected by copyright. All rights reserved.

RevDate: 2019-08-10

Winer LK, Hinrichs BH, Lu S, et al (2019)

Flat epithelial atypia and the risk of sampling error: Determining the value of excision after image-guided core-needle biopsy.

American journal of surgery pii:S0002-9610(19)30175-8 [Epub ahead of print].

BACKGROUND: We determined the sampling error rate of flat epithelial atypia (FEA) and evaluated current guidelines recommending excisional biopsy.

METHODS: A retrospective review of consecutive excisional biopsies after image-guided core-needle biopsy identified patients with isolated FEA diagnosed between 2014 and 2018. Clinical and pathologic parameters were evaluated.

RESULTS: Twenty-five women with 27 biopsies were included. Based on pathologic review of original core specimens, 44.4% (N = 12) were accurately diagnosed as FEA. Upon excision, lesions were upgraded to ductal carcinoma in situ (N = 2) or invasive ductal carcinoma (N = 1) in 11.1% of cases. Older age, black race, hormone replacement, and calcifications in the image-guided biopsy specimen were associated with the presence of high-risk or malignant lesions in the excisional biopsy (all p ≤ 0.05).

CONCLUSIONS: In this study, FEA was frequently overcalled. However, lesions suspicious for FEA warrant excision due to their association with malignancy or high-risk lesions, which may necessitate further surgical management and/or risk-reducing strategies.

RevDate: 2019-08-08

Tan X, Li Z, Ren S, et al (2019)

Dynamically decreased miR-671-5p expression is associated with oncogenic transformation and radiochemoresistance in breast cancer.

Breast cancer research : BCR, 21(1):89 pii:10.1186/s13058-019-1173-5.

BACKGROUND: Understanding the molecular alterations associated with breast cancer (BC) progression may lead to more effective strategies for both prevention and management. The current model of BC progression suggests a linear, multistep process from normal epithelial to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS), and then invasive ductal carcinoma (IDC). Up to 20% ADH and 40% DCIS lesions progress to invasive BC if left untreated. Deciphering the molecular mechanisms during BC progression is therefore crucial to prevent over- or under-treatment. Our previous work demonstrated that miR-671-5p serves as a tumor suppressor by targeting Forkhead box protein M1 (FOXM1)-mediated epithelial-to-mesenchymal transition (EMT) in BC. Here, we aim to explore the role of miR-671-5p in the progression of BC oncogenic transformation and treatment.

METHODS: The 21T series cell lines, which were originally derived from the same patient with metastatic BC, including normal epithelia (H16N2), ADH (21PT), primary DCIS (21NT), and cells derived from pleural effusion of lung metastasis (21MT), and human BC specimens were used. Microdissection, miRNA transfection, dual-luciferase, radio- and chemosensitivity, and host-cell reactivation (HCR) assays were performed.

RESULTS: Expression of miR-671-5p displays a gradual dynamic decrease from ADH, to DCIS, and to IDC. Interestingly, the decreased expression of miR-671-5p detected in ADH coexisted with advanced lesions, such as DCIS and/or IDC (cADH), but not in simple ADH (sADH). Ectopic transfection of miR-671-5p significantly inhibited cell proliferation in 21NT (DCIS) and 21MT (IDC), but not in H16N2 (normal) and 21PT (ADH) cell lines. At the same time, the effect exhibited in time- and dose-dependent manner. Interestingly, miR-671-5p significantly suppressed invasion in 21PT, 21NT, and 21MT cell lines. Furthermore, miR-671-5p suppressed FOXM1-mediated EMT in all 21T cell lines. In addition, miR-671-5p sensitizes these cell lines to UV and chemotherapeutic exposure by reducing the DNA repair capability.

CONCLUSIONS: miR-671-5p displays a dynamic decrease expression during the oncogenic transition of BC by suppressing FOXM1-mediated EMT and DNA repair. Therefore, miR-671-5p may serve as a novel biomarker for early BC detection as well as a therapeutic target for BC management.

RevDate: 2019-08-07

Goodes LM, King GK, Rea A, et al (2019)

Early urinary tract infection after spinal cord injury: a retrospective inpatient cohort study.

Spinal cord pii:10.1038/s41393-019-0337-6 [Epub ahead of print].

STUDY DESIGN: Retrospective audit.

OBJECTIVES: Examine factors associated with urinary tract infection (UTI), UTI incidence and impact on hospital length of stay (LOS) in new, inpatient adult traumatic spinal cord injury (SCI).

SETTING: Western Australian Hospitals managing SCI patients.

METHODS: Data on UTIs, bladder management and LOS were obtained from hospital databases and medical records over 26 months. Adherence to staff-administered intermittent catheterisation (staff-IC) was determined from fluid balance charts.

RESULTS: Across the cohort (n = 70) UTI rate was 1.1 starts/100 days; UTI by multi-resistant organisms 0.1/100 days. Having ≥1 UTIs compared with none and longer duration of initial urethral indwelling catheterisation (IDC) were associated with longer LOS (p-values < 0.001). For patients with ≥1 UTIs (n = 43/70), longer duration of initial IDC was associated with shorter time to first UTI (1 standard deviation longer [SD, 45.0 days], hazard ratio (HR): 0.7, 95% confidence interval [CI] 0.5-1.0, p-value 0.044). In turn, shorter time to first UTI was associated with higher UTI rate (1 SD shorter [30.7 days], rate ratio (RR): 1.32, 95%CI 1.0-1.7, p-value 0.039). During staff-IC periods (n = 38/70), protocols were followed (85.7% ≤ 6 h apart, 96.1% < 8 h), but 26% of IC volumes exceeded 500 mL; occasional volumes > 800 mL and interruptions requiring temporary IDC were associated with higher UTI rates the following week (odds ratios (ORs): 1.6, 95%CI 1.1-2.3, p-value 0.009; and 3.9, 95%CI 2.6-5.9, p-value < 0.001 respectively).

CONCLUSIONS: Reducing initial IDC duration and limiting staff-IC volumes could be investigated to possibly reduce inpatient UTIs and LOS.


RevDate: 2019-08-06

Forte S, Ritz A, Kubik-Huch R, et al (2019)

Invasive ductal carcinoma detected within a fibroadenolipoma through digital breast tomosynthesis.

Acta radiologica open, 8(7):2058460119865905 pii:10.1177_2058460119865905.

A 52-year-old patient referred to our hospital for a screening mammogram showed a suspicious new architectural distortion. Previously, a fibroadenolipoma within the right breast was diagnosed clinically and radiologically. Further work-up with tomosynthesis, magnetic resonance imaging, and magnetic resonance-guided biopsy showed an invasive ductal carcinoma within the fibroadenolipoma, which are usually benign breast lesions not associated with malignancy. This case report offers a review of the literature and a discussion of signs, which should alert the radiologist.

RevDate: 2019-08-03

Borelli JL, Shai D, Fogel Yaakobi S, et al (2019)

Interpersonal physiological regulation during couple support interactions: Examining the role of respiratory sinus arrhythmia and emotional support.

Psychophysiology [Epub ahead of print].

In times of need, people seek comfort and support from close others. Support provision is an integral component of attachment relationships, one that is linked with physical and psychological well-being. Successful support provision is believed to be grounded in transactions of sensitive, caring behavior between caregivers and support seekers and to serve a profound regulatory function. However, physiological processes underlying support transactions have not been previously studied. We assessed autonomic vagal regulation and coded spontaneous emotional support behaviors in N = 100 heterosexual couples involved in a support interaction. We focused on cardiac vagal activation, operationalized as the increase in respiratory sinus arrhythmia (RSA) from baseline to interaction, as an indicator of regulatory efforts. Analyses revealed a negative association between caregivers' and support seekers' regulatory efforts, which was mediated by emotional support behaviors. We found that caregivers with greater increases in RSA from baseline to interaction provided more emotional support to their partners. Such emotional support was associated with smaller increases in support seekers' RSA and with support seekers' perceptions of their partners as being more sensitive to their needs. Finally, these links were only significant among dyads in which caregivers reported lower levels of attachment anxiety. We interpret these results in the framework of interpersonal regulatory processes, suggesting that provision of support may impose regulatory demands on the side of the caregivers, which in turn could result in attenuated regulatory efforts and positive partner perceptions for the support seekers.

RevDate: 2019-08-02

Levy J, JF Démonet (2019)

MEG data representing a gamma oscillatory response during the hold/release paradigm.

Data in brief, 23:103787 pii:103787.

The article presents magnetoencephalography (MEG) data from healthy participants while undergoing the Hold/Release paradigm. During the paradigm, participants visually perceived a sequence of two letter strings which either assembled into real words (Hold condition) or pseudowords (Release condition). If the first letter string was morphologically valid, they held their attention (and/or held the item in working-memory) to wait for the second string, whereas if it were invalid, they could release it, respectively. We present data on high-frequency neuronal oscillations of the Hold condition compared to the Release condition. Making this information publicly available could allow other researchers to perform analyses and contribute to understanding the cognitive processes such as language, mnemonic or attentional processes.

RevDate: 2019-08-02

Liu J, Zhao J, Zhang M, et al (2019)

The validation of the 2014 International Society of Urological Pathology (ISUP) grading system for patients with high-risk prostate cancer: a single-center retrospective study.

Cancer management and research, 11:6521-6529 pii:196286.

Introduction: Since the new 2014 grading system was recommended by the International Society of Urological Pathology (ISUP), it has been validated in patients with localized prostate cancer (PCa) and it has shown excellent prognostic value. However, its predictive power in high-risk PCa remains unclear.

Methods: A total of 420 patients with high-risk PCa who underwent radical prostatectomy (RP) were included in this study. Biochemical recurrence-free survival (BRFS) was set as the endpoint.

Results: Biochemical recurrence occurred in 84/420 (20.0%) patients at the end of follow-up. Compared to the three-tier grouping system, the five-tier grouping system could more effectively distinguish the BRFS of patients with higher predictive accuracy (C-index: 0.599 vs 0.646). The BRFS of patients with grade group (GG) 1 and GG 2 was similar (P=0.593). Also, the prognosis between those with GG 2 and GG 3 could be clearly distinguished (P=0.001). However, the discrimination capacity between patients with GG 3 and GG 4 was limited (P=0.681). When tertiary Gleason pattern (TGP5) and intraductal carcinoma of the prostate (IDC-P) were excluded, the HR value of the GG 4 group vs the GG 3 group increased from 1.15 (95% CI: 0.59-2.22) to 1.49 (95% CI: 0.72-3.10) and 1.36 (95% CI:0.65-2.83), respectively.

Conclusions: This study is the first to validate the new 2014 ISUP grading system in patients with high-risk PCa who underwent RP. The 2014 system could effectively classify patients into five groups with high predictive accuracy. Notably, the existence of TGP5 and IDC-P needs to be routinely reported in clinical practice, which could help to support the predictive value of the new grading system.

RevDate: 2019-07-31

Can C, H Komek (2019)

Metabolic and volume-based parameters of (18F)FDG PET/CT for primary mass and axillary lymph node metastasis in patients with invasive ductal carcinoma: a retrospective analysis in relation to molecular subtype, axillary lymph node metastasis and immunohistochemistry and inflammatory markers.

Nuclear medicine communications [Epub ahead of print].

OBJECTIVE: To evaluate metabolic and volume-based parameters of 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((F)FDG PET/CT) for primary mass and axillary lymph node (ALN) metastasis in relation to molecular subtype, and immunohistochemistry and inflammatory markers in patients with invasive ductal carcinoma.

METHODS: A total of 129 patients (mean±SD age: 49.2±13.0 years) with invasive ductal breast cancer who had (F)FDG PET/CT imaging prior to chemotherapy or surgery were included in this single-center retrospective study. Data on patient age, molecular subtype, ALN metastasis status, inflammatory markers, immunohistochemistry markers and (F)FDG PET/CT imaging parameters for primary mass and ALN were recorded.

RESULTS: ALN metastasis was evident in 52.7% of patients and associated with significantly higher median diameter (P=0.027), MTV (P<0.001) and TLG (P<0.001). NLR was positively correlated with all primary mass (p ranged from 0.041 to 0.001) and ALN (P ranged from 0.026 to <0.001) PET parameters. PET parameters did not change with respect to molecular subtype or immunohistochemistry markers. Primary mass and ALN metastasis PET parameters showed significant positive correlations for TLG (r=0.274, P=0.001) and SUVmax (r=0.358, P<0.001).

CONCLUSION: In conclusion, our findings in a retrospective cohort of invasive ductal breast cancer patients revealed primary mass PET parameters to significantly differ with respect to ALN metastasis status and NLR levels, but not according to molecular subtype or immunohistochemistry markers. Accordingly, our findings highlight the value of acquisition of preoperative PET/CT imaging and role of both metabolic and volume-based parameters in predicting aggressiveness of the tumor as correlated with presence of ALN metastasis and high NLR.

RevDate: 2019-07-31

Metaxa L, Healy N, SA O'Keeffe (2019)

Breast microcalcifications: The UK RCR 5-point breast imaging system or BI-RADS; which is the better predictor of malignancy?.

The British journal of radiology [Epub ahead of print].

OBJECTIVES: In the UK RCR 5-point breast imaging system (UKS), radiologists grade mammograms from 1 to 5 according to suspicion for malignancy, however unlike BI-RADS, no lexicon of descriptors is published. The aim of this study was to determine whether strict categorisation of microcalcifications (MCC) according to BI-RADS was a better predictor of malignancy than the UKS and whether these descriptors could be used within the UKS.

METHODS: A retrospective review of 241 cases, with MCC on mammography, who underwent biopsy was performed. Morphology, distribution, extent, UKS score, BI-RADS category and pathology were recorded. The positive predicted value (PPV) of each classification system for malignancy was calculated.

RESULTS: 28.6% were diagnosed with DCIS/IDC. The PPV for malignancy using the UKS was 18.9%, 69.4%, 100% for M3-5 respectively (p < 0.001) and using ΒI-RADS morphology was Amorphous: 7.1%, Coarse Heterogeneous: 33.3%, Fine Pleomorphic: 48.1% and Fine linear/Branching: 85.2% (p < 0.001). The PPV based on distribution was Grouped: 14.2%, Regional: 32.3%, Diffuse: 33.3% and Linear/Segmental: 77.8% (p < 0.001). Combining all cases of benign-appearing, amorphous and grouped coarse heterogenous and grouped fine pleomorphic MCC gave a PPV of 12.8%. Combining regional, linear or segmental coarse heterogenous and fine pleomorphic and all fine linear/branching MCC resulted in a PPV of 83.3% for malignancy.

CONCLUSIONS: Combining morphology and distribution of MCC is accurate in malignancy prediction. Use of BI-RADS descriptors could help standardise reporting within the UKS and an algorithm using these within the UKS is proposed. Better prediction would enable more appropriate counselling and help to identify discrepancies.

ADVANCES IN KNOWLEDGE: No guidance exists on scoring of suspicious MCC in the UK breast imaging system. Use of BI-RADS morphologic/distribution descriptors can aid malignancy prediction. Findings other than morphology of MCC are important in malignancy prediction. An algorithm for use by the UK radiologist when evaluating MCC is provided.

RevDate: 2019-07-30

Sinha A, SS Gill (2019)

Cytological Correlates of Axillary Nodal Involvement in Invasive Ductal Carcinoma of Breast.

Journal of cytology, 36(3):142-145.

Context: Fine needle aspiration cytology (FNAC) plays an important role in the diagnosis of breast carcinoma. However, its role as a prognostic tool needs to be explored. This can be achieved by studying its correlation with an established prognostic marker such as axillary nodal metastasis.

Aims: This study was undertaken to correlate the cytological features of invasive ductal carcinoma (IDC) of breast with axillary lymph node status.

Settings and Design: Tertiary care hospital, retrospective analytical study.

Materials and Methods: The study group included 150 cases of IDC of breast diagnosed on FNAC, who had subsequently undergone modified radical mastectomy. Cytologic grades were assigned as per Robinson's grading system. Histopathological sections of axillary lymph nodes were assessed for metastasis.

Statistical Analysis Used: The cytologic grade and each feature of the cytologic grade were correlated with the lymph node metastasis using χ2 test. Values of P < 0.05 were considered significant.

Result: A statistically significant correlation was noted between cytologic grade of tumor and axillary lymph node metastasis (P < 0.05). In addition, a positive correlation was found between two of the individual features of cytologic grade, namely, nuclear size and cell uniformity with axillary lymph node metastasis (P < 0.05).

Conclusion: Robinson's cytologic grade of breast carcinoma correlates well with the presence of axillary lymph node metastasis and hence can be used as a prognostic tool. As there is an increasing trend toward conservative approach to management of breast carcinoma, patients receive preoperative neoadjuvant therapy which may alter the nodal status on the resected specimen. Hence, a high cytological grade of primary tumor, as assessed on FNAC before initiation of therapy, should alert the treating team of the possibility of axillary lymph nodal metastasis.

RevDate: 2019-07-30

Chang CC, Chen CJ, Hsu WL, et al (2019)

Prognostic Significance of Metabolic Parameters and Textural Features on 18F-FDG PET/CT in Invasive Ductal Carcinoma of Breast.

Scientific reports, 9(1):10946 pii:10.1038/s41598-019-46813-5.

To investigate the prognostic significance of metabolic parameters and texture analysis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with breast invasive ductal carcinoma (IDC), from August 2005 to May 2015, IDC patients who had undergone pre-treatment FDG PET/CT were enrolled. The metabolic parameters, including maximal standardized uptake value of breast tumor (SUVbt) and ipsilateral axillary lymph node (SUVln), metabolic tumor volume (MTVbt) and total lesion glycolysis (TLGbt) of breast tumor, whole-body MTV (MTVwb) and whole-body TLG (TLGwb) were recorded. Nine textural features of tumor (four co-occurrence matrices and five SUV-based statistics) were measured. The prognostic significance of above parameters and clinical factors was assessed by univariate and multivariate analyses. Thirty-five patients were enrolled. Patients with low and high MTVwb had 5-year progression-free survival (PFS) of 81.0 and 14.3% (p < 0.0001). The 5-year overall survival for low and high MTVwb was 88.5% and 43.6% (p = 0.0005). Multivariate analyses showed MTVwb was an independent prognostic factor for PFS (HR: 8.29, 95% CI: 2.17-31.64, p = 0.0020). The SUV, TLG and textural features were not independently predictive. Elevated MTVwb was an independent predictor for shorter PFS in patients with breast IDC.

RevDate: 2019-07-30

Li TT, Kang CS, Li HZ, et al (2019)

[Value of shear wave elastrography image classification in the diagnosis of breast masses].

Zhonghua zhong liu za zhi [Chinese journal of oncology], 41(7):540-545.

Objective: To analyze the image features of shear wave elastrography (SWE) in breast masses, and to evaluate their values in the differentiation of benign and malignant breast lesions. Methods: A total of 361 patients with 403 breast lesions who simultaneously underwent conventional ultrasound and SWE examination from February 2015 to January 2018 were selected. Diagnosis in all patients was confirmed by aspiration biopsy or operative pathology. The SWE images were collected and the elastic images were divided into 5 types. The SWE image features of different breast pathological types were summarized, and their values in benign and malignant breast lesion diagnoses were evaluated. Results: The main features of benign breast lesion were type Ⅰ and Ⅱ, the main features of the malignant lesion were type Ⅳ and Ⅴ, and the proportion of which were 43.6% (71/163), 37.4% (61/163), 22.1% (53/240) and 57.9% (139/240), respectively. Type Ⅲ accounted for a certain proportion in both benign and malignant lesions. The SWE image features of benign and malignant lesions were compared and a significant difference was observed (P<0.001). The type Ⅴ features were mainly observed in invasive ductal carcinoma, invasive lobular carcinoma and other types of invasive carcinoma, while the type Ⅳ features were mostly presented in ductal carcinoma in situ and mucinous carcinoma. Fibroadenoma, fibroadenosis accompanied with fibroadenoma, and fibroadenosis were featured with type Ⅰ. Both intraductal papilloma and benign phyllodes tumor were mostly type Ⅱ, while type Ⅲ and Ⅴ were more common in chronic granulomatous mastitis. When type Ⅰ and typeⅡof breast lesions were classified as benign features while type Ⅳ and Ⅴ were malignant features, the sensitivity and specificity of breast malignant lesion diagnosis were 91.2% and 84.7% by application of SWE combined with breast imaging reporting and data system (BI-RADS). The sensitivity of combined diagnosis was slightly lower than that of conventional ultrasound (P>0.05), but the specificity was significantly higher than conventional ultrasound (P<0.01). Conclusion: The SWE is a simple and effective method. Combination of SWE with conventional ultrasound may improve the diagnostic differentiation of benign and malignant breast lesions.

RevDate: 2019-07-29

Arabpour M, Rasolmali R, Talei AR, et al (2019)

Granzyme B production by activated B cells derived from breast cancer-draining lymph nodes.

Molecular immunology, 114:172-178 pii:S0161-5890(19)30137-3 [Epub ahead of print].

B lymphocytes with regulatory or effector functions synthesize granzyme B (GZMB). We investigated the frequency and phenotype of GZMB-producing B cells in breast tumor-draining lymph nodes (TDLNs). Mononuclear cells were isolated from 48 axillary lymph nodes and were stimulated with anti-BCR (B cell receptor), recombinant interleukin (IL)-21 and CD40 L alone or in combination. Flow cytometry was used to evaluate the expression of GZMB in B cells, and in 4 samples the phenotype of GZMB+ B cells was determined. B cells produced GZMB only when stimulated with a combination of IL-21 and anti-BCR for at least 16 h. Adding CD40 L to IL-21 and anti-BCR stimuli resulted in lower GZMB production in B cells. A small fraction of B cells was able to produce perforin in all stimulation conditions, and the majority of GZMB+ B cells were perforin-negative. Both naïve (CD24lowCD27-) and active/memory (CD24hiCD27+) B cells expressed GZMB. In patients with invasive ductal carcinoma, the frequency of GZMB+ B cells was significantly lower in metastatic compared to non-metastatic lymph nodes. The frequency of GZMB+ B cells did not significantly correlate with prognostic factors such as stage, tumor size or Her2 expression. In summary, a subpopulation of both naïve and memory B cells expressed GZMB in breast TDLNs. Our findings underscore the need to investigate the function of GZMB+ B cells in breast tumor immunity.

RevDate: 2019-07-29

Ogunleye AJ, Olanrewaju AJ, Arowosegbe M, et al (2019)

Molecular docking based screening analysis of GSK3B.

Bioinformation, 15(3):201-208 pii:97320630015201.

GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.

RevDate: 2019-07-28

Zacharioudakis K, Kontoulis T, Vella JX, et al (2019)

Can we see what is invisible? The role of MRI in the evaluation and management of patients with pathological nipple discharge.

Breast cancer research and treatment pii:10.1007/s10549-019-05321-w [Epub ahead of print].

INTRODUCTION: The aim of this study was to determine the ability of MRI to identify and assess the extent of disease in patients with pathological nipple discharge (PND) with an occult malignancy not evident on standard pre-operative evaluation with mammography and ultrasound.

METHODS: Patients presenting to the breast unit of Imperial College Healthcare NHS Trust between December 2009 and December 2018 with PND and normal imaging were enrolled in the study. Pre-operative bilateral breast MRI was performed in all patients as part of our protocol and all patients were offered diagnostic microdochectomy.

RESULTS: A total of 82 patients fulfilled our selection criteria and were enrolled in our study. The presence of an intraductal papilloma (IDP) was identified as the cause of PND in 38 patients (46.3%), 14 patients had duct ectasia (DE-17%) and 5 patients had both an IDP and DE. Other benign causes were identified in 11 patients (13.4%). Despite normal mammography and ultrasound a malignancy was identified in 14 patients (17%). Eleven patients had DCIS (13.4%), two had invasive lobular carcinoma and one patient had an invasive ductal carcinoma. The sensitivity of MRI in detecting an occult malignancy was 85.71% and the specificity was 98.53%. The positive predictive value was 92.31% and the negative predictive value was 97.1%.

CONCLUSIONS: Although a negative MRI does not exclude the presence of an occult malignancy the high sensitivity and specificity of this diagnostic modality can guide the surgeon and alter the management of patients with PND.

RevDate: 2019-07-27

Ding Q, Chen H, Lim B, et al (2019)

HER2 somatic mutation analysis in breast cancer: correlation with clinicopathological features.

Human pathology pii:S0046-8177(19)30128-5 [Epub ahead of print].

HER2 mutations have been reported in approximately 2% of breast cancers. Regardless of HER2 overexpression or amplification status, breast cancer with HER2 mutations may respond to HER2-targeted therapy. As HER2 mutation is rare, the clinical and pathological features of HER2-mutated breast cancers, such as hormonal status, histological grade, and metastasis, remain poorly defined. Therefore, the identification of HER2-mutated breast cancer has clinical significance. We retrospectively screened patients with metastatic breast cancer in whom molecular profiling had been performed using next-generation sequencing from 2012 to 2015; we identified 18 patients with HER2 mutation. Mutations were found on next-generation sequencing-based panels, including Ion AmpliSeq Cancer Hotspot, Oncomine, FoundationOne, and Guardant360. HER2 mutations were identified in both the tyrosine kinase (n=14) and extracellular (n=4) domains. Of the 14 cases with tyrosine kinase domain mutations, 13 were estrogen receptor (ER) positive; the 4 cases with extracellular domain mutations were exclusively ER negative. In addition, 11 of 14 patients with tyrosine kinase domain mutations had bone metastasis, whereas no patients with HER2 extracellular domain mutations had bone metastasis. Histologically, 13 patients had invasive ductal carcinoma, 1 had metaplastic carcinoma, and 4 had invasive lobular carcinoma (ILC). All 4 ILCs were high grade and pleomorphic, and not only had an HER2 mutation in the kinase domain but also had an HER2 mutation involving the L755 site. Specific mutation sites may be involved in the pathogenesis of non-classic ILC.

RevDate: 2019-07-27

Lourenco C, Kalkat M, Houlahan KE, et al (2019)

Modelling the MYC-driven normal-to-tumour switch in breast cancer.

Disease models & mechanisms, 12(7): pii:12/7/dmm038083.

The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CAH1047R) led to the development of organised acinar structures in mice. Expressing both PIK3CAH1047R and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulation of MYC expression in this setting creates a MYC-dependent normal-to-tumour switch that can be measured in vivo These MYC-driven tumours exhibit classic hallmarks of human breast cancer at both the pathological and molecular level. Moreover, tumour growth is dependent upon sustained deregulated MYC expression, further demonstrating addiction to this potent oncogene and regulator of gene transcription. We therefore provide a MYC-dependent model of breast cancer, which can be used to assay invivo tumour signalling pathways, proliferation and transformation from normal breast acini to invasive breast carcinoma. We anticipate that this novel MYC-driven transformation model will be a useful research tool to better understand the oncogenic function of MYC and for the identification of therapeutic vulnerabilities.

RevDate: 2019-07-25

Champion CD, Ren Y, Thomas SM, et al (2019)

DCIS with Microinvasion: Is It In Situ or Invasive Disease?.

Annals of surgical oncology pii:10.1245/s10434-019-07556-9 [Epub ahead of print].

BACKGROUND: Ductal carcinoma in situ (DCIS) with microinvasion (DCISM) can be challenging in balancing the risks of overtreatment versus undertreatment. We compared DCISM, pure DCIS, and small volume (T1a) invasive ductal carcinoma (IDC) as related to histopathology, treatment patterns, and survival outcomes.

METHODS: Women ages 18-90 years who underwent breast surgery for DCIS, DCISM, or T1a IDC were selected from the SEER Database (2004-2015). Multivariate logistic regression and Cox proportional hazards models were used to estimate the association of diagnosis with treatment and survival, respectively.

RESULTS: A total of 134,569 women were identified: 3.2% DCISM, 70.9% DCIS, and 25.9% with T1a IDC. Compared with invasive disease, DCISM was less likely to be ER+ or PR+ and more likely to be HER2+. After adjustment, DCIS and invasive patients were less likely to undergo mastectomy than DCISM patients (DCIS: OR 0.53, 95% CI 0.49-0.56; invasive: OR 0.86, CI 0.81-0.92). For those undergoing lumpectomy, the likelihood of receiving radiation was similar for DCISM and invasive patients but lower for DCIS patients (OR 0.57, CI 0.52-0.63). After adjustment, breast-cancer-specific survival was significantly different between DCISM and the other two groups (DCIS: HR 0.59, CI 0.43-0.8; invasive: HR 1.43, CI 1.04-1.96). However, overall survival was not significantly different between DCISM and invasive disease, whereas patients with DCIS had improved OS (HR 0.83, CI 0.75-0.93).

CONCLUSIONS: Although DCISM is a distinct entity, current treatment patterns and prognosis are comparable to those with small volume IDC. These findings may help providers counsel patients and determine appropriate treatment plans.

RevDate: 2019-07-25

Mamtani A, Zabor EC, Stempel M, et al (2019)

Lobular Histology Does Not Predict the Need for Axillary Dissection Among ACOSOG Z0011-Eligible Breast Cancers.

Annals of surgical oncology pii:10.1245/s10434-019-07536-z [Epub ahead of print].

BACKGROUND: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that axillary lymph node dissection (ALND) may be omitted for women with two or fewer positive sentinel nodes (SLNs) undergoing breast-conservation therapy (BCT). Lobular histology comprises a minority of patients, and applicability to these discohesive cancers has been questioned.

METHODS: From August 2010 to March 2017, patients undergoing BCT for cT1-2N0 cancer with positive SLNs were prospectively managed with ALND for three or more positive SLNs or gross extracapsular extension (ECE). In this study, clinicopathologic characteristics and nodal burden were compared between pure/mixed invasive lobular cancer (ILC) and invasive ductal cancer (IDC) patients.

RESULTS: Among 813 consecutive patients, 104 (12.8%) had ILC and 709 (87.2%) had IDC. ILC was more often multifocal and low grade, and less frequently had lymphovascular invasion (all p < 0.001). ILC more often had SLN macrometastases (81.7% ILC vs. 69.4% IDC; p = 0.01) and more than 2 mm of ECE (30.8% ILC vs. 19.5% IDC; p = 0.03), but the proportions of cases with three or more positive SLNs were similar in the two groups (14.4% ILC vs. 9.9% IDC; p = 0.2). The ALND procedure was performed for 20 ILC patients (19.2%) compared with 97 IDC patients (13.7%) (p = 0.2). Additional positive nodes were found in 80% of the ILC patients versus 56.7% of the IDC patients (p = 0.09). The ALND and nodal burden rates were similar in the estrogen receptor-positive (ER+) subset analysis. In the multivariable analysis, lobular histology (p = 0.03) and larger tumors (p = 0.03) were associated with additional positive nodes. During a median follow-up period of 42 months, there were no isolated axillary recurrences.

CONCLUSIONS: Despite a higher proportion of SLN macrometastases and association with more positive nodes at ALND, lobular histology does not predict the need for ALND. ALND is not indicated on the basis of histology among patients otherwise meeting Z0011 criteria.

RevDate: 2019-07-25

Oluogun WA, Adedokun KA, Oyenike MA, et al (2019)

Histological classification, grading, staging, and prognostic indexing of female breast cancer in an African population: A 10-year retrospective study.

International journal of health sciences, 13(4):3-9.

Background: Breast cancer (BC) is a heterogeneous disease characterized with diverse genetic and ethnic/racial variations that may influence tumor characteristics and prognosis. We studied different histological types of BC and their prognostic indicators in part of Southwestern Nigeria.

Materials and Methods: A 10-year retrospective study of archival tissue-paraffin blocks and records of surgical cases (documented as BCs) between January 2005 and December 2014 was done. Tumor classification was made after the World Health Organization guidelines. Modified Bloom-Richardson score and TNM staging system were used in grading and staging the tumors. Nottingham prognostic index was employed in scoring the prognosis.

Results: The mean age was 49.7 years (20-89 years). The age group from 50 to 59 years was most affected. Out of 343 total cases, the most common histological type was invasive ductal carcinoma of no special type (88.9%). The majority (51.9%) had tumor sizes ranging 2-5 cm (pT2) and some (39.1%) with >5 cm (pT3) were all at palpable stages. The tumors were mostly Grades II and III types. Observation for lymph node metastasis confirmed that 261 (76.1%) were pN0 (negative), 77 (22.4%) were pN1, and 5 (1.5%) were pN2. Prediction of a chance of survival showed moderate prognosis in the majority (48.7%) of the cases.

Conclusion: Although early detection of BC in this region was considerably poor, there was a better outcome compared with some other black populations. Clinical presentation, histological type, and prognostic indices varied from existing reports in many ethnic/racial groups. Indexing of BC pattern on a regional standpoint may serve a new direction toward better management considering the associated geographic disparity.

RevDate: 2019-07-24

Lurie I, Nakash O, Gerber Y, et al (2019)


Harefuah, 158(7):432-436.

INTRODUCTION: In 2012, 183,896 work migrants and 47,704 asylum-seekers and work-migrants arrived in Israel. These populations are at high-risk for depression, anxiety and posttraumatic stress disorder (PTSD). The Open Clinic of Physicians for Human Rights (PHR) delivers free medical and mental health services to these individuals.

AIMS: To evaluate exposure to traumatic events, and compare the prevalence and risk for PTSD, depression and anxiety symptoms between work-migrants and asylum-seekers.

METHODS: An analytical cross-sectional study of adults visiting the Open Clinic was conducted. Participants completed self-report questionnaires including information on demographics and exposure to traumas, depression, anxiety and PTSD. Statistical models were constructed to predict outcome variables of PTSD, depression and anxiety as dichotomist variables using a logistic regression, and association odds ratio (OR) and confidence interval (CI) on 95% level.

RESULTS: There were 241 participants; 165 asylum-seekers, 76 work-migrants. Work-migrants were exposed to more traumatic events. A total of 17-31% met PTSD criteria. Significantly more asylum-seekers met PTSD criteria. A total of 43%-50% met criteria for depression and/or anxiety, with no between-group differences. Significant association was found between immigration status and PTSD risk. Exposure to traumatic events was significantly associated with the prediction of PTSD, depression and anxiety.

DISCUSSION: Exposure to traumatic events was high among the Open Clinic service users, specifically work-migrants. Prevalence and risk for post-traumatic symptoms were significantly higher among asylum-seekers. It is important to conduct further research, in order to characterize risk and resilience factors in this excluded population, and to plan language and culture-competent mental health services.

RevDate: 2019-07-24

Rodriguez J, Schulz S, Giraldo BF, et al (2019)

Risk Stratification in Idiopathic Dilated Cardiomyopathy Patients Using Cardiovascular Coupling Analysis.

Frontiers in physiology, 10:841.

Cardiovascular diseases are one of the most common causes of death; however, the early detection of patients at high risk of sudden cardiac death (SCD) remains an issue. The aim of this study was to analyze the cardio-vascular couplings based on heart rate variability (HRV) and blood pressure variability (BPV) analyses in order to introduce new indices for noninvasive risk stratification in idiopathic dilated cardiomyopathy patients (IDC). High-resolution electrocardiogram (ECG) and continuous noninvasive blood pressure (BP) signals were recorded in 91 IDC patients and 49 healthy subjects (CON). The patients were stratified by their SCD risk as high risk (IDCHR) when after two years the subject either died or suffered life-threatening complications, and as low risk (IDCLR) when the subject remained stable during this period. Values were extracted from ECG and BP signals, the beat-to-beat interval, and systolic and diastolic blood pressure, and analyzed using the segmented Poincaré plot analysis (SPPA), the high-resolution joint symbolic dynamics (HRJSD) and the normalized short time partial directed coherence methods. Support vector machine (SVM) models were built to classify these patients according to SCD risk. IDCHR patients presented lowered HRV and increased BPV compared to both IDCLR patients and the control subjects, suggesting a decrease in their vagal activity and a compensation of sympathetic activity. Both, the cardio -systolic and -diastolic coupling strength was stronger in high-risk patients when comparing with low-risk patients. The cardio-systolic coupling analysis revealed that the systolic influence on heart rate gets weaker as the risk increases. The SVM IDCLR vs. IDCHR model achieved 98.9% accuracy with an area under the curve (AUC) of 0.96. The IDC and the CON groups obtained 93.6% and 0.94 accuracy and AUC, respectively. To simulate a circumstance in which the original status of the subject is unknown, a cascade model was built fusing the aforementioned models, and achieved 94.4% accuracy. In conclusion, this study introduced a novel method for SCD risk stratification for IDC patients based on new indices from coupling analysis and non-linear HRV and BPV. We have uncovered some of the complex interactions within the autonomic regulation in this type of patient.

RevDate: 2019-07-23

Machado J, Silveira WA, Gonçalves DA, et al (2019)

α-Calcitonin gene-related peptide inhibits autophagy and calpain systems and maintains the stability of neuromuscular junction in denervated muscles.

Molecular metabolism pii:S2212-8778(19)30254-6 [Epub ahead of print].

OBJECTIVE: Although it is well established that a-calcitonin gene-related peptide (CGRP) stabilizes muscle-type cholinergic receptors nicotinic subunits (AChR), the underlying mechanism by which this neuropeptide regulates muscle protein metabolism and neuromuscular junction (NMJ) morphology is unclear.

METHODS: To elucidate the mechanisms how CGRP controls NMJ stability in denervated mice skeletal muscles, we carried out physiological, pharmacological, and molecular analyses of atrophic muscles induced by sciatic nerve transection.

RESULTS: Here, we report that CGRP treatment in vivo abrogated the deleterious effects on NMJ upon denervation (DEN), an effect that was associated with suppression of skeletal muscle proteolysis, but not stimulation of protein synthesis. CGRP also blocked the DEN-induced increase in endocytic AChR vesicles and the elevation of autophagosomes per NMJ area. The treatment of denervated animals with rapamycin blocked the stimulatory effects of CGRP on mTORC1 and its inhibitory actions on autophagic flux and NMJ degeneration. Furthermore, CGRP inhibited the DEN-induced hyperactivation of Ca2+-dependent proteolysis, a degradative system that has been shown to destabilize NMJ. Consistently, calpain was found to be activated by cholinergic stimulation in myotubes leading to the dispersal of AChR clusters, an effect that was abolished by CGRP.

CONCLUSION: Taken together, these data suggest that the inhibitory effect of CGRP on autophagy and calpain may represent an important mechanism for the preservation of synapse morphology when degradative machinery is exacerbated upon denervation conditions.

RevDate: 2019-07-20

Mojahed D, Ha RS, Chang P, et al (2019)

Fully Automated Postlumpectomy Breast Margin Assessment Utilizing Convolutional Neural Network Based Optical Coherence Tomography Image Classification Method.

Academic radiology pii:S1076-6332(19)30324-1 [Epub ahead of print].

BACKGROUND: The purpose of this study was to develop a deep learning classification approach to distinguish cancerous from noncancerous regions within optical coherence tomography (OCT) images of breast tissue for potential use in an intraoperative setting for margin assessment.

METHODS: A custom ultrahigh-resolution OCT (UHR-OCT) system with an axial resolution of 2.7 μm and a lateral resolution of 5.5 μm was used in this study. The algorithm used an A-scan-based classification scheme and the convolutional neural network (CNN) was implemented using an 11-layer architecture consisting of serial 3 × 3 convolution kernels. Four tissue types were classified, including adipose, stroma, ductal carcinoma in situ, and invasive ductal carcinoma.

RESULTS: The binary classification of cancer versus noncancer with the proposed CNN achieved 94% accuracy, 96% sensitivity, and 92% specificity. The mean five-fold validation F1 score was highest for invasive ductal carcinoma (mean standard deviation, 0.89 ± 0.09) and adipose (0.79 ± 0.17), followed by stroma (0.74 ± 0.18), and ductal carcinoma in situ (0.65 ± 0.15).

CONCLUSION: It is feasible to use CNN based algorithm to accurately distinguish cancerous regions in OCT images. This fully automated method can overcome limitations of manual interpretation including interobserver variability and speed of interpretation and may enable real-time intraoperative margin assessment.

RevDate: 2019-07-19

Yamba K, Kalinowski MB, O Sanogo (2019)

On the usability of event zero time determinations using radioxenon isotopic activity ratios given the real atmospheric background observations.

Journal of environmental radioactivity, 208-209:106014 pii:S0265-931X(19)30283-8 [Epub ahead of print].

This work focuses on the usability of event zero time determination using xenon isotopic activity ratios. Two data sets from Nevada underground nuclear test and Fukushima accident debris were used to calculate the age of radioxenon release by considering three kinds of radioactivity release radionuclide sources: nuclear explosion scenarios, nuclear power reactor release and medical isotopes production facilities release. Typical nuclear power reactor releases were characterized and reference values are proposed for six isotopic activity ratios, which data can be considered as reference point of nuclear reactor effluents at the time of their release obtained from real observations. The same reference values of isotopic activity ratio are given for medical isotopes production facilities releases. The purpose of this study is to evaluate the use of zero-time calculation for source characterization under the assumption that a hypothesis about the event time is made. The event time information may come from a seismo-acoustic event of interest or an inverse atmospheric transport simulation or other context information. For both data sets used in this study, the age precisions are calculated and the time precision difference is evaluated and used as a parameter for the characterization of each radionuclide event. Almost all radioxenon isotopic activity ratios are found to correctly identifying the source type of the radionuclide events studied in this work. The results from this radionuclide events characterization study may be helpful for event screening activities of the Comprehensive Nuclear Test Ban Treaty Organization (CTBTO).

RevDate: 2019-07-19

Lewis GD, Xing Y, Haque W, et al (2019)

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast.

The breast journal [Epub ahead of print].

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)-positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow-up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2- disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR-HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African-American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.

RevDate: 2019-07-19

Borlinhas F, Conceição RC, HA Ferreira (2019)

Optimal b-values for diffusion kurtosis imaging in invasive ductal carcinoma versus ductal carcinoma in situ breast lesions.

Australasian physical & engineering sciences in medicine pii:10.1007/s13246-019-00773-2 [Epub ahead of print].

Diffusion kurtosis imaging (DKI) is a diffusion-weighted MRI technique that probes the non-Gaussian diffusion of water molecules within biological tissues. The purpose of this study was to investigate the DKI model optimal b-values combinations in invasive ductal carcinoma (IDC) versus ductal carcinoma in situ (DCIS) breast lesions. The study included 114 malignant breast lesions (64 IDC and 50 DCIS). Patients underwent a breast MRI examination which included a diffusion-weighted sequence (b = 0-3000 s/mm2). For each lesion, the b-values were combined among each other (109 combinations) and each mean kurtosis (MK) parameter was obtained. Differences between the lesion groups and b-values combinations were assessed. Also, the diagnostic performance of the combinations was determined through receiver operating characteristic (ROC) curve analysis, and compared. Root mean square error (RMSE) was also obtained. All the b-values combinations showed significant differences between the lesion groups (p < 0.05). The combination 0, 50, 200, 750, 1000, 2000 s/mm2 showed the best performance (AUC = 0.930, sensitivity = 95.3%, specificity = 82.0%, accuracy = 89.5%), with a RMSE of 17.65. The b-values combinations with the worst performance were composed of only high or ultra-high b-values, or with b = 1000 s/mm2 as the maximum b-value. Better results were obtained when zero b-value was included in the DKI model fitting with at least one b-value below 1000 s/mm2 and one b-value above 1000 s/mm2 (conserving b = 1000 s/mm2). Six was the optimal number of b-values, nonetheless other combinations with less b-values may be considered, but with a consequent diagnostic performance loss.

RevDate: 2019-07-19

Mukhtar RA, Holland M, Sieber DA, et al (2019)

Synchronous Breast Implant-associated Anaplastic Large Cell Lymphoma and Invasive Carcinoma: Genomic Profiling and Management Implications.

Plastic and reconstructive surgery. Global open, 7(4):e2188.

A 59-year-old woman with a history of cosmetic implants developed ipsilateral synchronous breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and invasive ductal carcinoma in the left breast. Each tumor was subjected to next-generation sequencing, and separate analyses revealed mutually exclusive aberrations: an activating STAT3 mutation in the lymphoma and a PIK3CA in-frame deletion in the carcinoma. The patient was treated with removal of implants, capsulectomy, partial mastectomy, sentinel node biopsy, radiotherapy, and endocrine therapy with no evidence of recurrence for 1 year. This case illustrates the importance of obtaining thorough evaluation for concomitant malignancies in the breast at the time of diagnosis of BIA-ALCL. Herein, we review the current recommendations for evaluation and management of BIA-ALCL.

RevDate: 2019-07-19

Kitahara M, Hozumi Y, Nakamura A, et al (2019)

HER2-Positive Conversion in a Metastatic Liver Focus in Late Recurrent Breast Cancer.

Case reports in oncology, 12(2):473-479 pii:cro-0012-0473.

Late recurrence of estrogen receptor (ER) positive breast cancer is common. When tissues from a recurrent or metastatic focus are available, re-evaluation of ER, progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status is recommended for treatment selection. This case report describes a 59-year-old woman who underwent surgery for left breast cancer, with a histopathological diagnosis of invasive ductal carcinoma (pathological stage T2N1aM0 Stage IIB, ER positive, PgR positive and HER2 negative). A health check-up 16 years after surgery revealed multiple hepatic mass lesions, and the patient was referred to our hospital for tests. Based on computed tomography, intrahepatic bile duct cancer or metastatic hepatic tumors were suspected, and a liver biopsy was performed. The histopathological diagnosis was a poorly differentiated adenocarcinoma (ER negative, PgR negative and HER2 positive), and the distinction from poorly differentiated intrahepatic bile duct cancer was difficult. Fluorodeoxyglucose (FDG)-positron emission tomography revealed FDG accumulation in the patient's bones and soft tissues, in addition to the hepatic tumors. The patterns and finding of metastasis were compatible with breast cancer recurrence, and the patient was diagnosed with postoperative recurrence of left breast cancer. Pertuzumab, trastuzumab, and docetaxel were started, and the therapeutic effect was assessed as a partial response. It was evident that in this case, the expression of hormone receptors and HER2 differed between the primary focus and the recurrence foci, and this contributed to the treatment strategy. Whenever possible, a biopsy should be performed for lesions that are suspected to be distal metastases.

RevDate: 2019-07-19

Fang A, Dong J, R Zhang (2019)

Simulation of Heavy Metals Migration in Soil-Wheat System of Mining Area.

International journal of environmental research and public health, 16(14): pii:ijerph16142550.

Heavy metals in the soil of mining areas have become a primary source of pollution, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. A long-term field experiment under natural conditions was carried out to explore the distribution characteristic and migration law of heavy metals in a soil-wheat system of a mining area in Xuzhou. According to the second level standard of environmental quality standards for soils of China (GB 15618-1995), 30.8 g of CrCl3·6H2O, 8.3 g of Pb(CH3COO)2·3H2O, and 16.5 g of ZnSO4·7H2O were added into the soil of three experimental sites, respectively. The other experimental site with no additional compounds was used as the control site. The Cr, Pb, and Zn concentrations in the soil-wheat system were counted and their corresponding migration models were constructed. From 2014 to 2017, the mean concentrations of Cr (49.09 mg·kg-1), Pb (20.08 mg·kg-1), and Zn (39.11 mg·kg-1) in the soil of the addition sites were higher than that of the control site. The mean concentrations of Cr, Pb, and Zn in wheat of the addition sites were greater than that of the control site with the values of 3.29, 0.06, and 29 mg·kg-1. In comparison, the Cr, Pb, and Zn concentrations in the soil of all experimental sites were lower than the second level standard of environmental quality standards for soils of China (GB 15618-1995), whereas the Cr concentration exceeded its corresponding soil background value of Xuzhou in 2017. The Pb concentration in soil of the addition site was greater than its corresponding background value from 2014 to 2016. The Pb and Zn concentrations in wheat of all experimental sites were lower than the national hygienic standard for grains of China (GB2715-2005) and the national guidelines for cereals of China (NY 861-2004), but the Cr concentration significantly exceeded the national guidelines for cereals of China (NY 861-2004). By constructing the Identical-Discrepant-Contrary (IDC) gray connection models, the result showed that there was a non-linear relationship of Cr, Pb, and Zn concentrations in the soil-wheat system, and the absolute values of most correlation coefficients r were lower than 0.5 and the values of greyness f G (r) were more than 0.5. The curvilinear regression models could not reflect the relationship of Cr, Pb, and Zn concentrations in the soil-wheat system with the regression coefficient r 2 values far less than 1. Due to the values of regression coefficient r 2 being close to 1, this study suggested that the allocation estimation models could be used for simulating the Cr, Pb, and Zn migration in the soil-wheat system of a mining area in Xuzhou.

RevDate: 2019-07-17

Durhan G, Azizova A, Önder Ö, et al (2019)

Imaging Findings and Clinicopathological Correlation of Breast Cancer in Women under 40 Years Old.

European journal of breast health, 15(3):147-152 pii:ejbh-15-3-147.

Objective: The aim of this study was to evaluate the clinical, imaging and histopathological features of breast cancer in patients aged under 40 years of age. The relationship between radiological characteristics and histopathological features was also investigated.

Materials and Methods: The study included 131 patients aged under 40 years, diagnosed pathologically with breast cancer. A retrospective evaluation was made of the imaging and clinicopathological findings and the relationship between pathological and imaging findings was investigated.

Results: Most of the cancers were detected from clinical symptoms, especially a palpable mass (76.3%). The most common histological type of tumor was invasive ductal carcinoma and 64.8% of the tumors were high grade tumors. The predominant features were irregular borders (92.4%), microlobulated-angulated contours (43.5%), hypo-homogeneous internal echogenicity (80.9%) on ultrasonography, and the presence of a mass (41.2%) and suspicious microcalcifications (40.2%) on mammography. Magnetic resonance imaging commonly showed mass enhancement (66.7%) with type 2 or 3 dynamic curve (92.6%). High-grade tumors were associated with posterior acoustic enhancement (p: 0.03) while low-grade tumors presented with spiculated margins more than high grade tumors (p: 0.04).

Conclusion: Breast cancer in women aged under 40 years usually presents with a self-detected palpable mass and can show different imaging findings according to the histological grade. Ultrasonography is the main modality for the diagnosis of breast cancer in young women, but mammography and magnetic resonance imaging can help in both diagnosis and evaluation of the extent of disease.

RevDate: 2019-07-17

Traoré B, Koulibaly M, Diallo A, et al (2019)

Molecular profile of breast cancers in Guinean oncological settings.

The Pan African medical journal, 33:22 pii:PAMJ-33-22.

Breast cancer is a complex disease characterized by the accumulation of multiple molecular alterations giving each tumor phenotype and an own evolutionary potential. This study aimed to describe the distribution of the profile and molecular subtypes of breast cancers followed at Surgical Oncology Unit of Donka National Hospital. This was retrospective and descriptive study on cases of breast cancer in which the hormone receptor status and expression of the Her2 oncogene have been performed from 2007 to 2016. We recorded 58 cases including 56 (96.6%) women and 2 (3.4%) men. The average age was 48.2 ± 10.9. Invasive ductal carcinoma accounted for 50 (86.2%) cases. The SBR grade was II in 31(53.4%) cases, III in 21 (36.2%) cases and I in 6 (10.3%) cases. The tumor was classified as T4 in 36 (62.1%) cases; it was metastatic in 11(19.0%) cases. Estrogen receptors were positive in 29 (50.0%) cases, progesterone receptors positive in 25 (43.1%) cases, the Her2 oncogene was positive in 22 (39.3%) cases. The distribution of molecular sub-types was: 20 (34.5%) luminal A, 15 (25.9%) triple negative, 13 (22.4%) Her2 overexpressed, 8 (13.8%) luminal B and 2 (3.2%) undetermined. This preliminary study showed the poor accessibility of immunohistochemistry for the molecular diagnosis of breast cancer in our country. Luminal A subtypes and triple negatives were more common. The determination of molecular subtypes is a rational basis for hormone therapy and targeted therapy, thus personalizing the treatment of breast cancer.

RevDate: 2019-07-16

Sorriso A, Sorrentino P, Rucco R, et al (2019)

An automated magnetoencephalographic data cleaning algorithm.

Computer methods in biomechanics and biomedical engineering [Epub ahead of print].

The problem of cleaning magnetoencephalographic data is addressed in this manuscript. At present, several denoising procedures have been proposed in the literature, nevertheless their adoption is limited due to the difficulty in implementing and properly tuning the algorithms. Therefore, as of today, the gold standard remains manual cleaning. We propose an approach developed with the aim of automating each step of the manual cleaning. Its peculiarities are the ease of implementation and using and the remarkable reproducibility of the results. Interestingly, the algorithm has been designed to imitate the reasoning behind the manual procedure, carried out by trained experts. Our statistical analysis shows that no significant differences can be found between the two approaches.

RevDate: 2019-07-16

Malik SS, Baig M, Khan MB, et al (2019)

Survival analysis of breast cancer patients with different treatments: a multicentric clinicopathological study.

JPMA. The Journal of the Pakistan Medical Association, 69(7):976-980.

OBJECTIVE: To explore and better understand clinic pathological details of breast cancer patients and analyse their survival rate among different treatment groups.

Methods: The prospective cohort, multi-centric study was conducted from September, 2014, to February, 2018, at five hospitals in Rawalpindi and Islamabad, Pakistan, and comprised histo-pathologically confirmed breast cancer cases. Patient characteristics and medical history were collected using a detailed questionnaire. All the subjects were followed up, and information regarding their current health and treatment status was collected. Data was analysed using SPSS 24.

RESULTS: There were 347 subjects with a mean age of 44.3±12.2 years and body mass index of 27.9±4.0 kg/m2. Younger age, increased body mass index, consanguinity and family history were major contributing factors in breast cancer development (p<0.05). Overall, 267(77%) had invasive ductal carcinoma and Grade II tumour 234(67%) was more frequent. A total of 221(64%) cases had positive lymph nodes and 97(28%) had metastasis to different body organs. Overall survival analysis showed statistically significant role (p<0.0001) of all treatment options.

CONCLUSIONS: Combination of different treatments can provide more promising health outcomes in breast cancer cases.

RevDate: 2019-07-16

Bae MS, Bernard-Davila B, Sung JS, et al (2019)

Preoperative breast MRI features associated with positive or close margins in breast-conserving surgery.

European journal of radiology, 117:171-177.

PURPOSE: To determine preoperative magnetic resonance imaging (MRI) features associated with positive or close margins in patients with breast cancer who underwent breast-conserving surgery (BCS).

MATERIALS AND METHODS: A retrospective review identified 249 patients with invasive ductal carcinoma (IDC) who underwent preoperative MRI and BCS as a primary procedure between 2008 and 2010. The MR images were reviewed for descriptions of findings with no new interpretations made. Margins were defined as positive (tumor touching the inked specimen margin), close (<2 mm tumor-free margin), or negative (≥2 mm tumor-free margin). Multivariate logistic regression analysis was performed to evaluate imaging and clinical factors predictive of positive or close margins.

RESULTS: Of the 249 patients, 83 (33.3%) had positive or close margins and 166 (66.7%) had negative margins on the initial BCS specimen. Multivariate analysis showed that multifocal disease (odds ratio, 4.8; 95% CI, 1.9-12.2; p = 0.001), nonmass enhancement lesion (odds ratio, 3.0; 95% CI, 1.5-6.2, p = 0.003), greater background parenchymal enhancement (odds ratio, 2.5; 95% CI, 1.1-5.6; p = 0.023), larger lesion size (odds ratio, 1.3; 95% CI, 1.0-1.7, p = 0.032), and presence of ductal carcinoma in situ on needle biopsy (odds ratio, 2.4; 95% CI, 1.3-4.6; p = 0.008) were independent predictors of positive or close margins.

CONCLUSIONS: Multifocal disease, nonmass enhancement lesion, or greater background parenchymal enhancement on preoperative breast MRI were significantly associated with positive or close margins. Identifying these MRI features before surgery can be helpful to reduce the reoperation rate in BCS.

RevDate: 2019-07-15

Carvalho MET, Oliveira WF, Cunha CRA, et al (2019)

Evaluating the glycophenotype on breast cancer tissues with quantum dots-Cramoll lectin conjugates.

International journal of biological macromolecules pii:S0141-8130(19)33651-7 [Epub ahead of print].

During carcinogenesis, modifications in the glycosylation can occur on cell surfaces causing changes in biological processes such as adhesion and immunological recognition. Thus, the interest in exploring and understanding the roles of carbohydrates as cancer biomarkers has been increasing. Lectins are macromolecules that, specifically, recognize carbohydrates and have been applied as useful tools in glycobiology, especially when associated with fluorescent reporters. Therefore, to take advantage of the physicochemical properties of quantum dots (QDs), herein, we conjugated Cramoll, a lectin that recognizes glucose/mannose residues, with those nanoparticles. We applied the conjugates to investigate the glycocode of human normal, fibroadenoma (FB), and invasive ductal carcinoma (IDC) breast tissues. Additionally, we proposed a method to quantitatively evaluate the tissue labeling intensity by a fluorescence microplate assay (FMA). Conjugates showed intense fluorescence, specificity, and functional activity, as demonstrated by optical characterizations, hemagglutinating assay, and Candida albicans cell labeling. Moreover, fluorescence images showed that ductal cells of normal mammary and FB tissues were preferentially labeled by conjugates, whereas both cells and stroma were strongly labeled in IDC tissues. The FMA showed in a quantitative, practical, and sensitive way that the level of exposed glucose/mannose residues increased accordingly to the sample malignancy degree. In conclusion, QDs-Cramoll conjugates can be considered effective, specific, and versatile probes able to be applied to evaluate glycan profiles in normal and transformed tissues, by fluorescence microscopy as well as FMA quantification. Furthermore, FMA showed to be a potential method that can be applied with other fluorescent conjugates.

RevDate: 2019-07-15

Vaziri Fard E, Ali Y, Wang XI, et al (2019)

Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma.

American journal of clinical pathology pii:5532251 [Epub ahead of print].

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer.

METHODS: We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups.

RESULTS: TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance.

CONCLUSIONS: Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.

RevDate: 2019-07-13

Son MJ, Kim S, Jung HK, et al (2019)

Can Ultrasonographic Vascular and Elastographic Features of Invasive Ductal Breast Carcinoma Predict Histologic Aggressiveness?.

Academic radiology pii:S1076-6332(19)30313-7 [Epub ahead of print].

RATIONALE AND OBJECTIVES: To investigate if preoperative ultrasonographic vascular and shear-wave elastographic examinations can predict histologic aggressiveness.

MATERIALS AND METHODS: Preoperative ultrasonographic vascular features and shear-wave elasticities were retrospectively evaluated for 147 invasive ductal carcinomas. Vascular feature was assessed using four-tier vascularity score. Mean and maximum elasticities (Emean and Emax), and the lesion-to-fat ratio (Eratio) were documented. Histologic parameters were reviewed for tumor size, multiplicity, axillary lymph node status, lymphovascular invasion, histologic grade, estrogen receptor, progesterone receptor, human epidermal growth factor receptor2 (HER2), Ki-67, p53, and histologic subtype. Vascularity score and elasticities were correlated with histologic parameters and histologic parameters were compared between the group with low vascularity score and elasticities and the group with high vascularity score and elasticities using ANOVA, chi-squared test, and regression analysis.

RESULTS: Vascularity score was independently associated with tumor size (p = 0.010) and HER2 (p = 0.007). Emean and Emax were associated with tumor size, histologic grade, and lymphovascular invasion, and Eratio was associated with tumor size, histologic grade, estrogen receptor, progesterone receptor, Ki-67, and histologic subtype (p < 0.05). Emean and Emax were independently associated with tumor size (p < 0.001). The group with high vascularity score and Eratio showed large tumor size (p < 0.001) and HER2 positivity (p = 0.039) in comparison to the group with low vascularity score and Eratio.

CONCLUSION: Ultrasonographic vascular features were associated with tumor size and HER2. SWE elasticities were associated with tumor size, histologic grade, hormonal receptor, and histologic subtype. Therefore, preoperative vascular and elastographic examinations could predict histologic aggressiveness of invasive ductal breast carcinoma.

RevDate: 2019-07-13

Mendoza Arnau I, Sánchez Sánchez R, Culiáñez Casas M, et al (2019)

Surgical clips vs. iodine-125 (125I) seeds for marking the location of nonpalpable malignant breast lesions: preliminary results.

Radiologia pii:S0033-8338(19)30068-2 [Epub ahead of print].

OBJECTIVES: To assess the usefulness of iodine-125 (125I) seeds as an alternative to surgical clips for marking the location of nonpalpable malignant breast lesions for surgery.

MATERIAL AND METHODS: We included patients with histologically confirmed nonpalpable malignant lesions treated by surgery in 2015 or 2016. Patients were randomly assigned to presurgical marking with metallic clips (Group A) or with 125I seeds (Group B). In both groups, marking was guided by ultrasound and/or mammography depending on the radiologic characteristics of the lesion. During surgery, a gamma probe was used and afterward the presence of seeds in the surgical specimen was checked radiologically. In the histological analysis, the absence of tumor in the stain was considered free margins. We analyzed the following variables: age, lesion characteristics (laterality, mean size on MRI and in the surgical specimen, radiological type), and presence/absence of free margins.

RESULTS: In Group A (n=53), the most common histologic subtypes were infiltrating ductal carcinoma (IDC, 84.9%) and luminal A (LA, 49.1%); the mean size of the lesions was 1.8cm. In Group B (n=45), the most common histologic subtypes were IDC (82.2%) and LA (46.5%); the mean size of the lesions was 1.5cm. In Group A, 13.2% had involved margins and 13.2% underwent a second surgical intervention. In Group, B 11.4% had involved margins and 7.5% underwent a second surgical intervention. The differences between groups were not significant (p=0.7 for involved margins and p=0.5 for reintervention). The volume of the surgical specimens was significantly lower in Group B than in Group A (128.68cm3 vs. 189.37cm3; p<0.05).

CONCLUSIONS: Using 125I seeds was feasible and enabled significantly smaller surgical specimens than using metallic clips.

RevDate: 2019-07-12

Soldevilla-Gallardo I, Villaseñor-Navarro Y, Medina-Ornelas SS, et al (2018)

Positron emission mammography in the evaluation of interim response to neoadjuvant chemotherapy in patients with locally advanced breast cancer.

Cancer treatment and research communications, 16:24-31.

Neoadjuvant chemotherapy (NAC) has an important role in patients with locally advanced cancers, treating distant micrometastases, downstaging tumors, improving operability, and sometimes allowing breast-conserving surgery to take place. We studied the association between two Positron Emission Mammography with 18F-FDG (18F-FDG-PEM) semi-quantitative parameters in 108 patients and correlated with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers.

AIM: Examine the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of NAC with pathologic response in each breast cancer subtype.

METHODS: 108 patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with 18F-FDG-PEM scans baseline and after end of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG).

RESULTS: After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ± 0.26 vs. 1.9 ± 0.18; p < 0.001) and LTB exhibited a significant decay after the first course of NACT (15.8 ± 1.36 vs. 5.5 ± 0.49; p < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (p = 0.52), but if a correlation was found between the response rate by MPG and both semiquantitative parameters (p = 0.05).

CONCLUSION: 2 PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.

RevDate: 2019-07-11

Eras N, Daloglu FT, Çolak T, et al (2019)

The Correlation between IL-1β-C31T Gene Polymorphism and Susceptibility to Breast Cancer.

Journal of breast cancer, 22(2):210-218.

Purpose: Interleukin-1 beta (IL-1β), a pro-inflammatory cytokine, has been shown to influence breast cancer susceptibility. The relationship between its risk of breast cancer and IL-1β-C31T polymorphism has been demonstrated, but the results remain controversial. Therefore, our study aimed to investigate the correlation between the IL-1β-C31T gene polymorphism and susceptibility to breast cancer.

Methods: The genotype frequencies of IL-1β-C31T polymorphism were compared between 204 breast cancer cases and 210 controls using polymerase chain reaction and restriction fragment length polymorphism techinques. Further multivariate binary logistic regression analyses were used to assess the association between IL-1β-C31T polymorphism and breast cancer risk.

Results: The frequency of the T allele of IL-1β-C31T polymorphism in breast cancer cases was significantly higher than that in the controls (56.1% vs. 47.9%). The frequencies of genotypes CC, CT, and TT in the cases were 22.1%, 43.6%, and 34.3%, respectively, while in the control group they were 24.3%, 55.7%, and 20.0%, respectively. There was a significant difference between the prevalence of TT genotype in the 2 groups (adjusted odds ratio [OR], 2.06; 95% confidence interval [CI], 1.16-3.66; p = 0.014). Breast cancer risk increased in women with TT genotype, body mass index (BMI) ≥ 25 kg/m2 (OR, 2.19; 95% CI, 1.09-4.36), late age at first birth (OR, 2.43; 95% CI, 1.29-4.56), postmenopausal status (OR, 3.15; 95% CI, 1.39-7.16), and negative smoking history (OR, 2.52; 95% CI, 1.32-4.82). Furthermore, increase in breast cancer risk among women diagnosed with invasive ductal carcinoma was associated with CT/TT genotypes (OR, 2.82; 95% CI, 1.38-5.76).

Conclusion: The IL-1β-C31T polymorphism affects breast cancer susceptibility, especially in women with late age at first birth, high BMI, postmenopausal status, negative smoking history, and invasive ductal carcinoma. Our study adds to the evidence about the importance of IL-1β-C31T polymorphism in breast cancer susceptibility.

RevDate: 2019-07-12

Molina J, Noguer M, Lepe JA, et al (2019)

Clinical impact of an educational antimicrobial stewardship program associated with Infectious Diseases consultation targeting patients with cancer: results of a 9-year quasi-experimental study with an interrupted time-series analysis.

The Journal of infection pii:S0163-4453(19)30197-5 [Epub ahead of print].

OBJECTIVES: Antibiotic stewardship programs (ASP) have already demonstrated clinical benefits. However, their effectiveness or safety in immunocompromised hosts needs to be proved.

METHODS: An ecologic quasi-experimental study was performed from January 2009 to June 2017 in the Oncology department of a tertiary-care hospital. A stable program of Infectious Diseases consultation (IDC) already existed at this unit, and an educational ASP was added in 2011. Its main intervention consisted of face-to-face educational interviews. Antibiotic consumption was assessed through quarterly Defined Daily Doses (DDD) per 100 occupied bed-days. Mortality was evaluated in patients with bloodstream infections through the quarterly incidence density per 1,000 admissions, and the annual mortality rates at 7 and 30-days. Time-trends were analysed through segmented-regression analysis, and the impact of the ASP was assessed through before-after interrupted time-series analysis.

RESULTS: Mortality significantly decreased throughout the study period (-13.3% annual reduction for 7-day mortality rate, p<0.01; -8.1% annual reduction for 30-day mortality, p=0.03), parallel to a reduction in antibiotic consumption (quarterly reduction -0.4%, p=0.01), especially for broader-spectrum antibiotics. The before-after study settled a significant inflexion point on the ASP implementation for the reduction of antibiotic consumption (change in level 0.95 DDD, p=0.71; change in slope -1.98 DDD per quarter, p<0.01). The decreasing trend for mortality before the ASP also continued after its implementation.

CONCLUSIONS: The combination of an ASP with IDC improved antibiotic use among patients with cancer, and was accompanied by a reduction of mortality of bacteraemic infections. Implementation of the ASP was necessary to effectively change antibiotic use.

RevDate: 2019-07-11

Xu Q, Shao Y, Zhang J, et al (2019)

Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response.

Cancer research and treatment : official journal of Korean Cancer Association pii:crt.2019.217 [Epub ahead of print].

Purpose: Anterior gradient 3(AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression.

Materials and Methods: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability and chemotherapeutic drug sensitivity of breast cancer cells were also detected.

Results: AGR3was up-regulated in luminal subtype of histological grade Ⅰ-Ⅱ of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines.

Conclusion: AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade Ⅰ-Ⅱ. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.

RevDate: 2019-07-10

Kole AJ, Park HS, Johnson SB, et al (2019)

Overall survival is improved when DCIS accompanies invasive breast cancer.

Scientific reports, 9(1):9934 pii:10.1038/s41598-019-46309-2.

Invasive ductal carcinoma (IDC) often presents alone or with a co-existing ductal carcinoma in situ component (IDC + DCIS). Studies have suggested that pure IDC may exhibit different biological behavior than IDC + DCIS, but whether this translates to a difference in outcomes is unclear. Here, utilizing the National Cancer Database we identified 494,801 stage I-III breast cancer patients diagnosed with either IDC alone or IDC + DCIS. We found that IDC + DCIS was associated with significantly better overall survival (OS) compared to IDC alone (5-year OS, 89.3% vs. 85.5%, p < 0.001), and this finding persisted on multivariable Cox modeling adjusting for demographic, clinical, and treatment-related variables. The significantly superior OS observed for IDC + DCIS was limited to patients with invasive tumor size < 4 cm or with node negative disease. A greater improvement in OS was observed for tumors containing ≥25% DCIS component. We also found IDC + DCIS to be associated with lower T/N stage, low/intermediate grade, ER/PR positivity, and receipt of mastectomy. Thus, the presence of a DCIS component in patients with IDC is associated with favorable clinical characteristics and independently predicts improved OS. IDC + DCIS could be a useful prognostic factor for patients with breast cancer, particularly if treatment de-escalation is being considered for small or node negative tumors.

RevDate: 2019-07-09

Shelef L, Klomek AB, Fruchter E, et al (2019)

Suicide ideation severity is associated with severe suicide attempts in a military setting.

European psychiatry : the journal of the Association of European Psychiatrists, 61:49-55 pii:S0924-9338(19)30103-8 [Epub ahead of print].

BACKGROUND: There is an ongoing debate on the effectiveness of suicidal behavior prevention measures in the military. The association of three widely used tools with severe suicide attempts was assessed in this setting.

METHODS: Thirty-nine Israeli soldiers (59% males), mean age 19 yrs., who attempted suicide during military service were divided into two groups: severe (n = 14; 35.9%) and moderate suicide attempts, and were assessed using the Scale for Suicide Ideation (SSI), Suicide Intent Scale (SIS) and the Columbia Suicide Severity Rating Scale (C-SSRS).

RESULTS: Seven items from the SSI (p = 0.008), two items from SIS and one item from C-SSRS were associated with severe suicide attempts. Kendall's tau-b correlation with bootstrap demonstrated stability of these correlations.

CONCLUSION: Greater severity of suicidal ideation was associated with more severe suicide attempts. The combination of male gender, available firearms and current severe suicide ideation is high-risk danger sign in a military setting, even when reported intent to die is low.

RevDate: 2019-07-08

Liu S, Wei H, Li Y, et al (2019)

Characterization of Dendritic Cell(DC)10 in recurrent miscarriage and recurrent implantation failure.

Reproduction (Cambridge, England) pii:REP-19-0172.R1 [Epub ahead of print].

During pregnancy, the maternal immune system must tolerate the persistence of semi-allogeneic fetus in the maternal tissue. Inadequate recognition of fetal antigens may lead to pregnancy complications, such as recurrent miscarriage (RM) and recurrent implantation failure (RIF). Dendritic cells (DCs) are key regulators of protective immune responses and the development and maintenance of tolerance. Regarding that DCs are important in the establishment of immune tolerance in human pregnancy, it would be important to study the microenvironment in which DCs reside or are activated may affect their functions towards tolerance rather than active immune response. IL-10 play a critical role in the maintenance of normal pregnancy, and the increased production of IL-10 is associated with successful pregnancy. In this study, we provide an in-depth comparison of the phenotype and cytokine production by DC-10 and other DC subsets, such as iDC and mDC. CD14+ monocyte-derived DCs were differentiated in the presence of IL-10 (DC-10) in vitro from 10 normal fertile controls, 6 RM women and 7 RIF women, and characterized for relevant markers. DC-10 was characterized by relatively low expression of costimulatory molecule CD86, as well as MHC class II molecule HLA-DR, high expression of tolerance molecules HLA-G, ILT2, ILT4 and immunosuppressive cytokine IL-10, but produced little or no proinflammatory cytokines, such as TNF-α, IL-6 and IL-12p70. Our study provides a better understanding of the phenotypical properties of DC-10, which may participate in the complex orchestration that leads to maternal immune tolerance and homeostatic environment in human pregnancy.

RevDate: 2019-07-08

Klepac K, Georgiadi A, Tschöp M, et al (2019)

The role of brown and beige adipose tissue in glycaemic control.

Molecular aspects of medicine pii:S0098-2997(19)30022-6 [Epub ahead of print].

For the past decade, brown adipose tissue (BAT) has been extensively studied as potential therapy for obesity and metabolic diseases due to its thermogenic and glucose-consuming properties. It is now clear that function of BAT goes beyond heat production, as it also plays an important endocrine role by secreting the so-called batokines to communicate with other metabolic tissues and regulate systemic energy homeostasis. However, despite numerous studies showing the benefits of BAT in rodents, it is still not clear whether recruitment of BAT can be utilized to treat human patients. Here, we review the advances on understanding the role of BAT in metabolism and its benefits on glucose and lipid homeostasis in both humans and rodent. Moreover, we discuss the latest methodological approaches to assess the contribution of BAT to human metabolism as well as the possibility to target BAT, pharmacologically or by lifestyle adaptations, to treat metabolic disorders.

RevDate: 2019-07-08

Qiu R, Zhao W, Yang J, et al (2019)

Comparative Analysis of Outcomes and Clinicopathological Characteristics of Synchronous and Metachronous Contralateral Breast Cancer: A Study of the SEER Database.

Journal of breast cancer, 22(2):297-310.

Purpose: Numerous previous studies have reported inconsistent results about the differences between synchronous contralateral breast cancer (sCBC) and metachronous contralateral breast cancer (mCBC). This study aimed to compare the clinical characteristics and outcomes between sCBC and mCBC and determine predictive factors for the survival of sCBC and mCBC patients.

Methods: Using the Surveillance, Epidemiology, and End Results Program database, we identified sCBC or mCBC patients from 2000 to 2010. The Kaplan-Meier method and Cox proportional hazards regression analysis were used to analyze overall survival and breast cancer-specific survival (BCSS) rates of sCBCs and mCBCs, respectively.

Results: Overall, 14,057 sCBC (n = 8,139, 57.9%) and mCBC (n = 5,918, 42.1%) patients were included. The first tumors of sCBC were more likely to have higher stage and more lymph and distant metastases, whereas those of mCBC were more often infiltrating ductal carcinoma (IDC), had localized stage, were estrogen receptor (ER) and progesterone receptor (PR) negative, and had less axillary nodal involvement. The second tumors of mCBC tended to be IDC and have higher grade, adverse stage, ER and PR-negativity; and more axillary nodal involvement, compared to the second tumors of sCBC. mCBC patients had significantly favorable 5-year BCSS but worse long-term BCSS compared with sCBC patients. Moreover, subgroup analysis revealed no significant difference of BCSS between sCBC and mCBC among patients aged 18-60 years. Multivariate analysis indicated that age, grade, and stage of 2 tumors; surgery for second tumor; and ER status of the second tumor were independent prognostic factors for BCSS of contralateral breast cancer (CBC).

Conclusion: The characteristics and outcomes of sCBCs and mCBCs were substantially different. sCBC and mCBC patients may have different prognosis, and the prognosis of CBC depends on the first and second tumors.

RevDate: 2019-07-05

Simeunovic D, Odanovic N, Pljesa-Ercegovac M, et al (2019)

Glutathione Transferase P1 Polymorphism Might Be a Risk Determinant in Heart Failure.

Disease markers, 2019:6984845.

Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.

RevDate: 2019-07-02

Levine KM, Priedigkeit N, Basudan A, et al (2019)

FGFR4 overexpression and hotspot mutations in metastatic ER+ breast cancer are enriched in the lobular subtype.

NPJ breast cancer, 5:19 pii:114.

Invasive lobular carcinoma (ILC) is an understudied subtype of breast cancer that requires novel therapies in the advanced setting. To study acquired resistance to endocrine therapy in ILC, we have recently performed RNA-Sequencing on long-term estrogen deprived cell lines and identified FGFR4 overexpression as a top druggable target. Here, we show that FGFR4 expression also increases dramatically in endocrine-treated distant metastases, with an average fold change of 4.8 relative to the paired primary breast tumor for ILC, and 2.4-fold for invasive ductal carcinoma (IDC). In addition, we now report that FGFR4 hotspot mutations are enriched in metastatic breast cancer, with an additional enrichment for ILC, suggesting a multimodal selection of FGFR4 activation. These data collectively support the notion that FGFR4 is an important mediator of endocrine resistance in ILC, warranting future mechanistic studies on downstream signaling of overexpressed wild-type and mutant FGFR4.

RevDate: 2019-07-01

Xie T, Wang Z, Zhao Q, et al (2019)

Machine Learning-Based Analysis of MR Multiparametric Radiomics for the Subtype Classification of Breast Cancer.

Frontiers in oncology, 9:505.

Objective: To investigate whether machine learning analysis of multiparametric MR radiomics can help classify immunohistochemical (IHC) subtypes of breast cancer. Study design: One hundred and thirty-four consecutive patients with pathologically-proven invasive ductal carcinoma were retrospectively analyzed. A total of 2,498 features were extracted from the DCE and DWI images, together with the new calculated images, including DCE images changing over six time points (DCEsequential) and DWI images changing over three b-values (DWIsequential). We proposed a novel two-stage feature selection method combining traditional statistics and machine learning-based methods. The accuracies of the 4-IHC classification and triple negative (TN) vs. non-TN cancers were assessed. Results: For the 4-IHC classification task, the best accuracy of 72.4% was achieved based on linear discriminant analysis (LDA) or subspace discrimination of assembled learning in conjunction with 20 selected features, and only small dependent emphasis of Kendall-tau-b for sequential features, based on the DWIsequential with the LDA model, yielding an accuracy of 53.7%. The linear support vector machine (SVM) and medium k-nearest neighbor using eight features yielded the highest accuracy of 91.0% for comparing TN to non-TN cancers, and the maximum variance for DWIsequential alone, together with a linear SVM model, achieved an accuracy of 83.6%. Conclusions: Whole-tumor radiomics on MR multiparametric images, DCE images changing over time points, and DWI images changing over different b-values provide a non-invasive analytical approach for breast cancer subtype classification and TN cancer identification.

RevDate: 2019-07-01

Huang L, Ji H, Yin L, et al (2019)

High Expression of Plakoglobin Promotes Metastasis in Invasive Micropapillary Carcinoma of the Breast via Tumor Cluster Formation.

Journal of Cancer, 10(12):2800-2810 pii:jcav10p2800.

Invasive micropapillary carcinoma of the breast (IMPC) is a rare subtype of breast cancer that has a high frequency of lymph node (LN) involvement and metastasis to distant organs. IMPC is characterized by distinct histomorphology and unfavorable prognosis when compared with invasive ductal carcinoma no special type (IDC-NST). However, the underlying molecular mechanisms remain unclear. We reported here that plakoglobin, as a key component in cell adhesion, can promote collective metastasis through facilitating IMPC clusters formation. In comparing the clinicopathological features of 451 IMPC patients and 282 IDC-NST patients, our results showed that tumor emboli were significantly higher in IMPC patients and were associated with a high frequency of metastasis. Both in vitro and in vivo data showed overexpression of plakoglobin in both the cell membrane and the cytoplasm of IMPC clusters. When plakoglobin was knocked down in IMPC cell models, the tumor cell clusters were depolymerized. Using mouse models, we validated the metastatic potential of tumor clusters was higher than single cells in vivo. Further analysis showed that higher expression of plakoglobin was able to promote activation of the PI3K/Akt/Bcl-2 pathway, which might protect the clusters from anoikis. Our data indicate that plakoglobin promotes tumor cluster formation in IMPC and downregulates apoptosis in the cell clusters through activation of PI3K/Akt/Bcl-2 signaling. These results provide a convincing rationale for the high metastatic propensity seen in IMPC.

RevDate: 2019-06-30

D'Iorio A, Maggi G, Vitale C, et al (2019)

Prospective memory in Parkinson's disease: the role of the motor subtypes.

Journal of neurology pii:10.1007/s00415-019-09448-0 [Epub ahead of print].

BACKGROUND: Prospective memory (PM) is defined as memory for future intentions and it is typically divided into time-based and event-based PM. Deficit of PM has been reported in patients with Parkinson's disease (PD) but no study has yet explored the association between motor subtypes (tremor dominant and rigidity/bradykinesia dominant) and performance on PM tasks. The aim of the study was to explore the role of motor subtypes in the defect of PM.

METHODS: Consecutive outpatients with tremor dominant (TD-PD) or rigidity/bradykinesia dominant (PIGD-PD) PD and healthy subjects (HCs) were enrolled and underwent a neuropsychological battery assessing PM, verbal memory and executive functions and questionnaires assessing apathy, functional autonomy, and perceived memory disturbances.

RESULTS: We enrolled 28 patients with TD-PD, 28 patients with PIGD-PD and 50 HCs. The three groups did not differ on demographic and cognitive variables. Patients with TD-PD performed worse on time-based PM tasks than patients with PIGD-PD and HCs; no significant difference was found among the three groups on event-based PM tasks. Executive dysfunctions contributed to reduced time-based PM scores in TD-PD. Moreover, severe deficit of time-based and more frequency of perceived failures of PM contributed to reduced functional autonomy in TD-PD.

CONCLUSION: The finding of a poorer performance of patients with TD-PD than ones with PIGD-PD and HCs suggests a selective deficit of time-based PM abilities in TD-PD group; therefore, deficit of time-based PM might be considered as a distinctive non-motor symptom of TD-PD and it might affect the functional autonomy in this subtype of PD.

RevDate: 2019-06-28

Albrecht W, Kappenberg F, Brecklinghaus T, et al (2019)

Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations.

Archives of toxicology pii:10.1007/s00204-019-02492-9 [Epub ahead of print].

Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity.

RevDate: 2019-06-27

Ghaderi F, Mehdipour F, Hosseini A, et al (2019)

Establishment and Characterization of a New Triple Negative Breast Cancer Cell Line from an Iranian Breast Cancer Tissue.

Asian Pacific journal of cancer prevention : APJCP, 20(6):1683-1689.

Breast cancer is the most common malignancy and the leading cause of cancer-related death among women
worldwide. The underlying mechanisms for breast cancer development, especially in young women, are not completely
understood. Although there are several experimental models to understand the biology of breast cancer such as
immortalized cell lines, many of these cell lines have been in culture for decades and most of them have been derived
from Caucasians or African-Americans. So, it is required to establish a new cell line derived from primary tumors and
Asian women. In this study Pari-Institute for Cancer Research (Pari-ICR) was derived from the primary breast tumor
of a 36-years old patient with invasive ductal carcinoma. We characterized the cell line by examining morphology,
expression of different markers, and functional profile. Immunocytochemistry showed that this cell line does not express
estrogen and progesterone receptors as well as human epidermal growth factor receptor 2 (HER2). Pari-ICR cell line
expresses high levels of Vimentin, Ezrin, and S100 but does not express EpCAM, Cytokeratin19, Pan-cytokeratin,
Nestin, and Desmin. Its doubling time of Pari-ICR was about 22h and was able to grow as colonies in soft agar. It
displayed a higher ability of migration and invasion in comparison with MCF-7 cell line. This breast cancer cell line
can serve as a model for understanding the molecular mechanisms of breast carcinogenesis. Moreover, it can be used
as an appropriate resource to find novel biomarkers or assess new drugs.

RevDate: 2019-06-27

Zwarts I, van Zutphen T, Kruit JK, et al (2019)

Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR.

Scientific reports, 9(1):9299 pii:10.1038/s41598-019-45803-x.

Fructose has become a major constituent of our modern diet and is implicated as an underlying cause in the development of metabolic diseases. The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human GLUT5 promoter we identified a strong and specific regulation by liver X receptor α (LXRα, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human GLUT5 promoter, located at -385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the in vivo relevance of its regulation by LXR. Together, our findings show that LXRα regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXRα might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.

RevDate: 2019-06-26

Shenkman G, Pardo Aviv L, Hain D, et al (2019)

The moderation of attachment in the association between depressive symptoms and self-harm among a clinical sample.

Journal of mental health (Abingdon, England) [Epub ahead of print].

Background: Self-harm is a severe health problem worldwide and in particular in clinical settings. The association of depression and self-harm has been extensively studied alongside various variables that have been examined as moderating this association. However, no previous study has examined the moderating role of attachment in this association. Aim: We explored the role of attachment orientation in moderating the association between depressive symptoms and self-harm among a sample of patients in a community mental health clinic. Method: This study was a de-identified archival study of patients' medical charts, and used a convenience sample of 199 patients, which completed self-report measures following the initial intake appointment as part of clinic procedures. Results: Findings showed that both attachment anxiety and avoidance moderated the association between depressive symptoms and self-harm, such that depressive symptoms were positively associated with self-harm only when attachment anxiety scores were high, and attachment avoidance scores were high or average. Conclusions: Attachment anxiety and avoidance should be assessed in the initial intake of patients as it has a contribution to understanding self-harm vulnerability among new patients. Future studies should explore this moderation longitudinally so causality could be inferred.

RevDate: 2019-06-26

Thomas M, Kelly ED, Abraham J, et al (2019)

Invasive lobular breast cancer: A review of pathogenesis, diagnosis, management, and future directions of early stage disease.

Seminars in oncology pii:S0093-7754(19)30044-2 [Epub ahead of print].

Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer after invasive ductal carcinoma (IDC). Invasive lobular carcinoma has unique clinical, pathologic, and radiographic features which suggest that it is a distinct clinical entity; however, it is treated with the same treatment paradigms as IDC. Information regarding the specific treatment of ILC, including response to standard therapy, is sparse. Neoadjuvant treatment considerations are of great importance in this space as ILC is often found at a locally advanced stage. In this review, we summarize the classic features of ILC and the available data regarding efficacy of both endocrine therapy and chemotherapy in curative treatment of breast cancer.

RevDate: 2019-06-26

Farsang A, Bódi I, Fölker O, et al (2019)

Avian coronavirus infection induces mannose-binding lectin production in dendritic cell precursors of chicken lymphoid organs.

Acta veterinaria Hungarica, 67(2):183-196.

The aim of this immunocytochemical study was to compare mannose-binding lectin (MBL) production induced by avian coronavirus in the spleen and caecal tonsil (CT). One-day-old specific-pathogen-free (SPF) chickens were experimentally infected with six QX field isolates and the H120 vaccine strain. In the negative control birds, the spleen was MBL negative, while the CT showed scattered MBL-positive cells in close proximity and within the surface epithelium and germinal centre (GC)-like cell clusters. MBL was detectable in the ellipsoid-associated cells (EACs) and cell clusters in the periarterial lymphoid sheath (PALS) by 7 days post infection (dpi). In both organs, the MBL-positive cells occupy antigen-exposed areas, indicating that GC formation depends on resident precursors of dendritic cells. The majority of MBL-positive EACs express the CD83 antigen, providing evidence that coronavirus infection facilitated the maturation of dendritic cell precursors. Surprisingly, co-localisation of MBL and CD83 was not detectable in the CT. In the spleen (associated with circulation), the EACs producing MBL and expressing CD83 are a common precursor of both follicular (FDC) and interdigitating dendritic cells (IDC). In the CT (gut-associated lymphoid tissue, GALT) the precursors of FDC and IDC are MBL-producing cells and CD83-positive cells, respectively. In the CT the two separate precursors of lymphoid dendritic cells provide some 'autonomy' for the GALT.

RevDate: 2019-06-20

Lodd E, Wiggenhauser LM, Morgenstern J, et al (2019)

The combination of loss of glyoxalase1 and obesity results in hyperglycemia.

JCI insight, 4(12): pii:126154.

The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1-/- zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced-obesity zebrafish model was used to analyze glo1-/- zebrafish under high nutrient intake. Glo1-/- zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1-/- zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1-/- zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.

RevDate: 2019-06-18

Saleh Gargari S, Taheri M, Kholghi Oskooei V, et al (2019)

Transcription Levels of nicotinamide nucleotide transhydrogenase and Its Antisense in Breast Cancer Samples.

Cell journal, 21(3):331-336.

Objective: To evaluate association of patients' clinicopathological data with expression of nicotinamide nucleotide transhydrogenase (NNT) and naturally occurring antisense RNA of the same gene locus (NNT-AS1) in breast cancer samples.

Materials and Methods: In the current case-control study, mean expressions of NNT and NNT-AS1 were assessed in 108 breast tissue samples including 54 invasive ductal carcinoma samples and 54 adjacent non-cancerous tissues (ANCTs) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results: NNT expression was not significantly different between tumor tissues and ANCTs. However, NNT-AS1 expression was significantly down-regulated in tumor tissues compared to ANCTs (expression ratio=0.51, P=0.01). NNT-AS1 expression was significantly higher in estrogen receptor (ER) negative samples, in comparison with ER positives (P=0.01). No considerable difference was found in the gene expressions between other subcategories of patients. Considerable correlations were detected between expression levels of these two genetic loci in both tumor tissues and ANCTs.

Conclusion: In the current study, for the first time we simultaneously assessed expression of NNT and NNT-AS1 in breast cancer tissues. This study highlights association of ER status with dysregulation of NNT-AS1 in breast cancer tissues. Future researches are necessary to explore the function of this long non-coding RNA (lncRNA) in the pathogenesis of breast cancer.

RevDate: 2019-06-17

Blanc-Durand P, Milliner M, Huchet V, et al (2019)

18F-FDG Whole-body PET/MRI of a 30-Week Pregnant Woman With Breast Cancer Revealed Interesting Fetal Findings.

Clinical nuclear medicine [Epub ahead of print].

A 35-year-old 30-week pregnant woman was referred to our institution for initial staging of a triple negative invasive ductal carcinoma of the left breast. To avoid fetal radiation exposure from CT, a whole-body F-FDG PET/MRI was performed. Simultaneous acquisition of PET, T1-, T2-, and diffusion-weighted sequences revealed left axillary node extension and no distant metastases. Fetal radiation dose was estimated at 1.9 mGy. Interestingly, low fetal brain uptake and high symmetrical myocardial metabolism in both ventricles were found. Delivery was induced at 37 weeks of amenorrhea, and the patient underwent 4 cycles of neoadjuvant chemotherapy.

RevDate: 2019-06-16

Raetz AG, SS David (2019)

When you're strange: Unusual features of the MUTYH glycosylase and implications in cancer.

DNA repair, 80:16-25 pii:S1568-7864(19)30098-9 [Epub ahead of print].

MUTYH is a base-excision repair glycosylase that removes adenine opposite 8-oxoguanine (OG). Variants of MUTYH defective in functional activity lead to MUTYH-associated polyposis (MAP), which progresses to cancer with very high penetrance. Whole genome and whole exome sequencing studies have found MUTYH deficiencies in an increasing number of cancer types. While the canonical OG:A repair activity of MUTYH is well characterized and similar to bacterial MutY, here we review more recent evidence that MUTYH has activities independent of OG:A repair and appear centered on the interdomain connector (IDC) region of MUTYH. We summarize evidence that MUTYH is involved in rapid DNA damage response (DDR) signaling, including PARP activation, 9-1-1 and ATR signaling, and SIRT6 activity. MUTYH alters survival and DDR to a wide variety of DNA damaging agents in a time course that is not consistent with the formation of OG:A mispairs. Studies that suggest MUTYH inhibits the repair of alkyl-DNA damage and cyclopyrimidine dimers (CPDs) is reviewed, and evidence of a synthetic lethal interaction with mismatch repair (MMR) is summarized. Based on these studies we suggest that MUTYH has evolved from an OG:A mispair glycosylase to a multifunctional scaffold for DNA damage response signaling.

RevDate: 2019-06-15

Jeyapala R, Savio AJ, Olkhov-Mitsel E, et al (2019)

GBX2 Methylation Is a Novel Prognostic Biomarker and Improves Prediction of Biochemical Recurrence Among Patients with Prostate Cancer Negative for Intraductal Carcinoma and Cribriform Architecture.

European urology oncology, 2(3):231-238.

BACKGROUND: Tumor intraductal carcinoma/cribriform architecture (IDC/C) is associated with an unfavorable prognosis and biochemical recurrence (BCR) in prostate cancer (PCa). Up to 70% of PCa patients are IDC/C-negative, but it is estimated that 20% of these cases still experience BCR. Thus, biomarkers for better detection of aggressive disease in IDC/C-negative patients are required.

OBJECTIVE: To investigate tumor-specific methylation of the transcription factor GBX2 as a novel prognosticator and predictor of BCR in PCa patients stratified by histopathologic features including IDC/C.

Using genome-wide methylome profiling, we identified higher GBX2 methylation in grade group (GG) 4 tumors compared to GG1 (discovery cohort). The prognostic nature of GBX2 methylation was validated in silico using The Cancer Genome Atlas data (n=478) and a quantitative methylation assay for radical prostatectomy samples (n=254). Regulation of GBX2 methylation was investigated in prostate cells using methyl-CpG-binding domain sequencing and methylation analysis in functional knockouts of TET2, a key epigenetic player in prostate carcinogenesis.

The association of GBX2 methylation with Gleason score (GS), pathologic stage (pT), IDC/C, and BCR was analyzed using Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression analyses were used to predict BCR.

RESULTS: GBX2 methylation was associated with GS (p<0.05), pT (p<0.01), and BCR (p<0.05). GBX2 methylation (p=0.004), GS (p<0.001), pT (p=0.012), and prostate-specific antigen (p=0.005) were independent predictors of BCR. Among IDC/C-negative patients, GBX2 methylation improved prediction of BCR (p=0.002). Loss of TET2 in prostate cells resulted in greater GBX2 methylation.

CONCLUSIONS: We identified GBX2 methylation as a novel prognostic factor in PCa and an independent predictor of BCR. We demonstrated the additive value of GBX2 methylation in predicting BCR among IDC/C-negative patients and elucidated a novel TET2-mediated upstream epigenetic regulatory mechanism of GBX2.

PATIENT SUMMARY: We identified GBX2 methylation as a promising prognostic biomarker that could improve the identification of prostate cancer patients at higher risk of biochemical recurrence.

RevDate: 2019-06-14

Tan QT, AG Mihir (2019)

A case of invasive ductal carcinoma presenting as an exophytic nipple mass.

The breast journal [Epub ahead of print].

RevDate: 2019-06-14

Sherbuk JE, McManus D, Topal JE, et al (2019)

Improved mortality in Staphylococcus aureus bacteremia with the involvement of antimicrobial stewardship team and infectious disease consultation.

Infection control and hospital epidemiology pii:S0899823X19001363 [Epub ahead of print].

A retrospective study was conducted to evaluate the value of the antimicrobial stewardship team (AST) combined with infectious diseases consultation (IDC) on management and outcomes of Staphylococcus aureus bacteremia (SAB) in a tertiary-care academic center. Involvement of AST or IDC was associated with reduced mortality of SAB.

RevDate: 2019-06-13

Erel H, Ronen T, Freedman G, et al (2019)

Preserved left and upper visual field advantages in older adults' orienting of attention.

Experimental gerontology pii:S0531-5565(19)30097-X [Epub ahead of print].

Lateralization of the distribution of attentional function in the brain is asserted to lead to asymmetry in attentional allocation. This is expressed in the phenomenon of pseudoneglect, in which line and object bisection judgments indicate left visual field (and presumably right hemisphere) dominance. Several studies indicate that this asymmetry is not found in old age, which is taken as an indication of decline in attentional function with aging. We examined this assertion using a more comprehensive assay of attentional asymmetry. We contrasted the spatial distribution of older and younger adults' visual attention using the Starry Night Task, a speeded visual search task in which targets must be located across a wide spatial distribution against a dynamic background of distracters. As expected, compared to younger adults, older adults' response times were longer overall. However, we found that older adults exhibited a graded left visual field advantage, even more distinctly than did younger adults. Additionally, older adults exhibited a graded upper visual field advantage equivalent to that of younger adults. These results indicate that aging may not necessarily compromise basic patterns of distribution of spatial attention. They do not support claims of aging-related loss of attentional lateralization.

RevDate: 2019-06-13

Horimoto Y, Terao T, Tsutsumi Y, et al (2019)

Estrogen Receptor-positive Ductal Carcinoma In Situ Frequently Overexpresses HER2 Protein Without Gene Amplification.

The American journal of surgical pathology [Epub ahead of print].

Overexpression of human epidermal growth factor receptor 2 (HER2) protein is well known to be more frequent in ductal carcinoma in situ (DCIS) than in invasive ductal carcinoma (IDC). However, the reasons for this difference are poorly understood. On the basis of the high frequency of estrogen receptor-positive (ER+) and HER2-positive (HER2+) DCIS, we hypothesized that this tumor type overexpresses HER2 protein without gene amplification and retrospectively investigated the HER2/neu gene status of 71 ER(+)HER2(+) DCIS, surgically removed during the 2007 to 2017 period, employing fluorescence in situ hybridization (FISH). To compare HER2 protein expressions between in situ and invasive components of individual tumors, 86 pT1mi/1a IDC with predominantly in situ disease were also examined. Furthermore, for comparison of FISH status between in situ and coexisting invasive components, another patient cohort, 78 FISH-positive IDC cases, were employed. To elucidate biological differences among DCIS with various combinations of ER and HER2 protein expressions, we also analyzed public microarray data of mRNA. HER2 gene amplification was observed in 35% of ER(+) and HER2 protein-overexpressing specimens, significantly lower than the 94% in ER-negative (ER-) and HER2 protein-overexpressing specimens (P<0.001). HER2 protein expression was decreased in the invasive component as compared with coexisting in situ portions in 40% of individual tumors, whereas the FISH status of these 2 components was well preserved. Moreover, ER(+) and HER2 protein-overexpressing DCIS showed significantly higher hypoxia-inducible factor-1α protein expression than the ER(+) and HER2 protein-nonoverexpressing tumors (P=0.016). We revealed that ER(+) and HER2 protein-overexpressing DCIS, especially ER-high tumors, frequently overexpress HER2 protein without gene amplification. Our data may provide novel insights for understanding the biology of DCIS.

RevDate: 2019-06-13

Zhang J, Zhao B, F Jin (2019)

The assessment of 8th edition AJCC prognostic staging system and a simplified staging system for breast cancer: The analytic results from the SEER database.

The breast journal [Epub ahead of print].

The prognostic value of the prognostic staging system that incorporated estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor-2 (Her-2), and histological grade has been validated in breast cancer (BC) patients, but the staging system seems to be somewhat complex. Recently, an updated bioscore system based on these tumor biological factors was proposed. The purpose of this study was to compare the prognostic stratification between prognostic staging system of American Joint Commission on Cancer (AJCC) and a simplified staging system based on the bioscore system and anatomic TNM staging for BC patients. A total of 44 593 patients with invasive ductal carcinoma who underwent radical resection between 2010 and 2011 were reviewed using the SEER database. The patients were reclassified into different groups according to the anatomic staging system, prognostic staging system, risk bioscore system, and simplified staging system, respectively. The prognostic differences between different groups were compared and clinicopathologic features were analyzed. The anatomic TNM staging failed to clearly distinguish the prognostic difference between stage IIIB and stage IIIC. Therefore, we proposed an adjusted anatomic staging, in which T1N3 and T2N3 were downstaged from stage IIIC to stage IIIB, and T4N2 was upstaged from stage IIIB to stage IIIC. Histological grade III, ER(-), PR(-), and Her-2(-) were identified as independent prognostic factors in the multivariate analysis, and these factors were separately marked as 1 point. There were significant survival differences among different risk points except for the comparison between 0 and 1 point. The higher the risk points, the poorer the prognosis of BC patients. In addition, the curve distance between stage IIA and stage IIB was not significantly broaden according to the prognostic staging system. However, the prognostic stratification for BC patients could be significantly improved by the simplified staging system incorporated the bioscore system and adjusted anatomic staging. Several drawbacks may still exist in the prognostic staging system of AJCC. A simplified staging system that incorporated risk score system and the anatomic staging could provide more accurate prognostic information for BC patients.

RevDate: 2019-06-12

Zhu L, Ma N, Wang B, et al (2019)

Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer.

Oncology letters, 17(6):5469-5480.

The 21-gene recurrence score (RS) predicts the prognosis of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer and the effectiveness of adding adjuvant chemotherapy on the basis of endocrine therapy to avoid excessive chemotherapy. The present study aimed to analyze clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS in hormone receptor-positive early-stage breast cancer in China. The prognostic value of chemotherapeutic efficacy-related target genes was also examined. In addition, this study investigated the postoperative adjuvant therapeutic decision-oriented role of 21-gene RS in hormone receptor-positive and lymph node-negative early-stage breast cancer. In the present retrospective study, 110 ER+/HER2- early-stage breast cancer patients were tested with the 21-gene RS. The analyses of clinicopathological characteristics and chemotherapeutic efficacy-related target genes with the 21-gene RS were performed using the χ2 test, the Wilcoxon rank-sum test and binary logistic regression. Kaplan-Meier survival plots were drawn in www.kmplot.com. Furthermore, the McNemar χ2 test was used to compare the changes of treatment decisions before and after the 21-gene test. The median RS of 110 patients was 16 (range, 2-47), and patients were categorized as low (59.1%), intermediate (34.5%) or high risk (6.4%). The results revealed that higher body mass index, invasive ductal carcinoma type, higher histological grade, luminal B molecular type and higher thymidylate synthetase (TYMS) and DNA topoisomerase IIα (TOP2A) gene expression levels were more likely to have a higher RS. Kaplan-Meier plots suggested that expression of TYMS, tubulin β3 class III (TUBB3) and TOP2A genes was significantly associated with relapse-free survival for ER+ breast cancer. Additionally, prior to 21-gene RS testing, 61 patients (55%) were recommended adjuvant chemotherapy and endocrine therapy; however, following 21-gene test, 32 patients (29%) were treated with only adjuvant endocrine therapy. TYMS, TUBB3 and TOP2A gene expression may have prognostic value for ER+ breast cancer. In addition, 21-gene RS testing may aid to avoid excessive postoperative adjuvant chemotherapy.

RevDate: 2019-06-12

Cuesta Cuesta AB, Martín Ríos MD, Noguero Meseguer MR, et al (2019)

Accuracy of tumor size measurements performed by magnetic resonance, ultrasound and mammography, and their correlation with pathological size in primary breast cancer.

Cirugia espanola pii:S0009-739X(19)30145-9 [Epub ahead of print].

INTRODUCTION: The objective of this study was to determine which image test used to measure the size of pre-operative primary breast cancer (mammography, ultrasound or magnetic resonance imaging [MRI]) correlated best with the size of the tumor in the postoperative surgical specimen.

METHODS: A retrospective analysis was conducted of women diagnosed with breast cancer for which primary surgical treatment was indicated and who underwent surgical intervention between January 2014 and December 2016. Sociodemographic, imaging and histological variables were collected. The results are presented by age group, tumor size and histological type.

RESULTS: In the 224 women studied, mammography and MRI tumor sizes were compared with pathology study tumor measurements, revealing no significant differences, both overall and based on histologic type or age. However, both significantly underestimated large tumors and significantly overestimated small tumors. Ultrasound significantly underestimated tumor size, especially in large tumors, older patients and in infiltrating ductal carcinoma (IDC) and infiltrating ductal carcinoma with associated ductal carcinoma in situ (IDC+DCIS). MRI correlated best with histological tumor size, although with no statistically significant differences.

CONCLUSIONS: MRI is the best predictor of tumor size in breast cancer. Histologic type and tumor size are key parameters when estimating tumor size and should be taken into account when planning surgery. Patient age does not interfere with the interpretation of imaging tests.

RevDate: 2019-06-11

Troisi J, Landolfi A, Vitale C, et al (2019)

A metabolomic signature of treated and drug-naïve patients with Parkinson's disease: a pilot study.

Metabolomics : Official journal of the Metabolomic Society, 15(6):90 pii:10.1007/s11306-019-1554-x.

INTRODUCTION: About 90% of cases of Parkinson's disease (PD) are idiopathic and attempts to understand pathogenesis typically assume a multifactorial origin. Multifactorial diseases can be studied using metabolomics, since the cellular metabolome reflects the interplay between genes and environment.

OBJECTIVE: The aim of our case-control study is to compare metabolomic profiles of whole blood obtained from treated PD patients, de-novo PD patients and controls, and to study the perturbations correlated with disease duration, disease stage and motor impairment.

METHODS: We collected blood samples from 16 drug naïve parkinsonian patients, 84 treated parkinsonian patients, and 42 age matched healthy controls. Metabolomic profiles have been obtained using gas chromatography coupled to mass spectrometry. Multivariate statistical analysis has been performed using supervised models; partial least square discriminant analysis and partial least square regression.

RESULTS: This approach allowed separation between discrete classes and stratification of treated patients according to continuous variables (disease duration, disease stage, motor score). Analysis of single metabolites and their related metabolic pathways revealed unexpected possible perturbations related to PD and underscored existing mechanisms that correlated with disease onset, stage, duration, motor score and pharmacological treatment.

CONCLUSION: Metabolomics can be useful in pathogenetic studies and biomarker discovery. The latter needs large-scale validation and comparison with other neurodegenerative conditions.

RevDate: 2019-06-11

Bao Y, Wang L, Shi L, et al (2019)

Transcriptome profiling revealed multiple genes and ECM-receptor interaction pathways that may be associated with breast cancer.

Cellular & molecular biology letters, 24:38 pii:162.

Background: Exploration of the genes with abnormal expression during the development of breast cancer is essential to provide a deeper understanding of the mechanisms involved. Transcriptome sequencing and bioinformatics analysis of invasive ductal carcinoma and paracancerous tissues from the same patient were performed to identify the key genes and signaling pathways related to breast cancer development.

Methods: Samples of breast tumor tissue and paracancerous breast tissue were obtained from 6 patients. Sequencing used the Illumina HiSeq platform. All. Only perfectly matched clean reads were mapped to the reference genome database, further analyzed and annotated based on the reference genome information. Differentially expressed genes (DEGs) were identified using the DESeq R package (1.10.1) and DEGSeq R package (1.12.0). Using KOBAS software to execute the KEGG bioinformatics analyses, enriched signaling pathways of DEGs involved in the occurrence of breast cancer were determined. Subsequently, quantitative real time PCR was used to verify the accuracy of the expression profile of key DEGs from the RNA-seq result and to explore the expression patterns of novel cancer-related genes on 8 different clinical individuals.

Results: The transcriptomic sequencing results showed 937 DEGs, including 487 upregulated and 450 downregulated genes in the breast cancer specimens. Further quantitative gene expression analysis was performed and captured 252 DEGs (201 downregulated and 51 upregulated) that showed the same differential expression pattern in all libraries. Finally, 6 upregulated DEGs (CST2, DRP2, CLEC5A, SCD, KIAA1211, DTL) and 6 downregulated DEGs (STAC2, BTNL9, CA4, CD300LG, GPIHBP1 and PIGR), were confirmed in a quantitative real time PCR comparison of breast cancer and paracancerous breast tissues from 8 clinical specimens. KEGG analysis revealed various pathway changes, including 20 upregulated and 21 downregulated gene enrichment pathways. The extracellular matrix-receptor (ECM-receptor) interaction pathway was the most enriched pathway: all genes in this pathway were DEGs, including the THBS family, collagen and fibronectin. These DEGs and the ECM-receptor interaction pathway may perform important roles in breast cancer.

Conclusion: Several potential breast cancer-related genes and pathways were captured, including 7 novel upregulated genes and 76 novel downregulated genes that were not found in other studies. These genes are related to cell proliferation, movement and adhesion. They may be important for research into breast cancer mechanisms, particularly CST2 and CA4. A key signaling pathway, the ECM-receptor interaction signal pathway, was also identified as possibly involved in the development of breast cancer.

RevDate: 2019-06-11

Arabpour M, Ghods A, Shariat M, et al (2019)

Correlation of 4-1BBL+ B Cells in Tumor Draining Lymph Nodes with Pathological Characteristics of Breast Cancer.

Iranian journal of immunology : IJI, 16(2):108-116.

BACKGROUND: B cells can increase the expression of granzyme B in CD8+ T cells through 4-1BBL/4-1BB interaction and promote anti-tumor immunity.

OBJECTIVE: To investigate the expression of 4-1BBL on B cells in the breast tumor draining lymph nodes (TDLNs) and its association with disease parameters.

METHODS: Using Ficoll-Hypaque gradient centrifugation, mononuclear cells were isolated from axillary lymph nodes of 42 patients. Cells received 4 hours of PMA/Ionomycin stimulation, in vitro. Both unstimulated and stimulated cells were stained with anti‒CD19 and anti‒4-1BBL antibodies and subjected to flow cytometry.

RESULTS: 4-1BBL expression was detected on 2.8 ± 1.7% of unstimulated B cells, while 27.4 ± 11.9% of B cells expressed this co-stimulatory molecule following stimulation. In steady state, the percentage of 4-1BBL+ B cells was not associated with cancer characteristics. However, in patients with invasive ductal carcinoma, the percentage of 4-1BBL expressing B cells in stimulated condition had a decreasing trend in grade III, compared to grade II+I. In addition, significantly higher frequency of 4-1BBL+ B cells was seen in the TDLNs of ER+ or PR+ compared with ER‒ or PR‒ patients (p=0.021 and p=0.015, respectively). No significant associations were observed between the frequency of 4-1BBL+ B cells and the number of involved LNs, Her2 expression or disease stage.

CONCLUSIONS: The frequency of 4-1BBL+ B cells significantly increased following a short time activation, and showed relative and significant associations with tumor grade and estrogen receptor status, respectively. More investigations are required to evaluate the potential of 4-1BBL+ B cells for use in immunotherapy.

RevDate: 2019-06-09

Gilleron J, Gerdes JM, A Zeigerer (2019)

Metabolic regulation through the endosomal system.

Traffic (Copenhagen, Denmark) [Epub ahead of print].

The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type-2 diabetes, hypercholesterolemia and non-alcoholic fatty liver disease. By taking insights from in vitro studies of endocytosis and exploring their effects on metabolism, we can begin to connect the fields of endosomal transport and metabolic homeostasis. In this review, we explore current understanding of how the endosomal system influences the systemic regulation of glucose and lipid metabolism in mice and humans. We highlight exciting new insights that help translate findings from single cells to a wider physiological level and open up new directions for endosomal research. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-09

Downes MR, Xu B, TH van der Kwast (2019)

Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome.

Histopathology [Epub ahead of print].

BACKGROUND: Lymph node metastases at the time of prostatectomy are an infrequent finding. The correlation of the pattern of nodal metastases with patient outcome has yet to be explored.

METHODS: Lymph node positive prostatectomies were retrospectively reviewed. The presence of cribriform carcinoma (CC), intraductal carcinoma (IDC) and ISUP grade (G) were documented. The largest nodal metastasis was assessed for morphologic patterns present. G was assigned to the metastasis based on percentage morphologic patterns present. Statistical analysis used SPSS to assess disease specific survival (DSS), disease free survival (DFS) and distant metastasis free survival (DMFS).

RESULTS: 110 cases were identified: G5 (n=52), G4 (n=8), G 3 (n=34), G2 (n=10), no G (n=6; treatment effect). IDC or CC was present in 103 (94%) specimens. >1 positive node correlated with worse DFS (p=0.012, hazard ratio HR=1.951, 95% confidence interval 1.142-3.331) and DMFS (p=0.009, HR=2.647, 95% CI 1.239-5.651). G in the prostate and nodal metastasis were poorly correlated (kappa= 0.073, p=0.195). The presence of pattern 5 was seen in 33 nodes (30%) and correlated with DFS (p=0.020, HR=1.903, 95% CI 1.091-3.320), DSS (p=0.021, HR=5.937, 95% CI 1.084-32.533) and DMFS (p=0.007, HR=2.695, 95% CI 1.269-5.726). Nodal cribriform pattern showed no prognostic correlation and pattern 3 metastasis showed a significant trend towards better outcome (DMFS p=0.033, HR=0.431, 95% CI 0.194-0.958).

CONCLUSIONS: IDC or CC is identified in 94% of node positive prostate cancers. Although G in the largest nodal metastasis has prognostic significance, its G does not reflect that of the primary prostatic adenocarcinoma. This article is protected by copyright. All rights reserved.

RevDate: 2019-06-10

Stohl S, Sprung CL, Lippert A, et al (2019)

Impact of triage-to-admission time on patient outcome in European intensive care units: A prospective, multi-national study.

Journal of critical care, 53:11-17 pii:S0883-9441(19)30306-5 [Epub ahead of print].

PURPOSE: Ubiquitous bed shortages lead to delays in intensive care unit (ICU) admissions worldwide. Assessing the impact of delayed admission must account for illness severity. This study examined both the relationship between triage-to-admission time and 28-day mortality and the impact of controlling for Simplified Acute Physiology Score (SAPS) II scores on that relationship.

METHODS: Prospective cross-sectional analysis of referrals to eleven ICUs in seven European countries between 2003 and 2005. Outcomes among patients admitted within versus after 4 h were compared using a Chi-square test. Triage-to-admission time was also analyzed as a continuous variable; outcomes were assessed using a non-parametric Kruskal-Wallis test.

RESULTS: Among 3175 patients analyzed, triage-to-admission time was 2.1 ± 3.9 h. Patients admitted within 4 h had higher SAPS II scores (33.6 versus 30.6, Pearson correlation coefficient -0.07, p < 0.0001). 28-day mortality was surprisingly higher among patients admitted earlier (29.6 vs 25.2%, OR 1.25, 95% CI 0.99-1.58, p = 0.06). Even after adjusting for SAPS II scores, delayed admission was not associated with higher mortality (OR 1.08, CI 0.83-1.41, p = 0.58).

CONCLUSIONS: Even after accounting for quantifiable parameters of illness severity, delayed admission did not negatively impact outcome. Triage practices likely influence outcomes. Severity scores may not fully reflect illness acuity or trajectory.

RevDate: 2019-06-07

Hamzah JL, Ong KW, BY Tan (2019)

Isolated invasive ductal carcinoma of the nipple-areolar complex: A rare occurrence yet to be reported in current literature.

Invasive ductal carcinoma of the nipple-areolar complex is exceedingly rare. Patients who present with bloody nipple discharge with or without the presence of Paget's disease constitute one-third of all symptomatic in situ patients. Only rarely does an invasive cancer cause nipple discharge in the absence of a clinical mass. Even more obscure is the case of the invasive cancer involving solely the nipple-areolar complex. Sir James Paget first described 'an eczematous change in the skin of the nipple preceding an underlying mammary cancer' in 1874, which is now known as Paget's disease, considered to be ductal carcinoma in situ of the nipple-areolar region. There are two competing theories as to the pathogenesis of Paget's disease of the breast-one suggests that Pagetoid cells are keratinocytes that have undergone malignant transformation. According to this theory, Paget's disease of the breast represents an in situ carcinoma of the skin-and that overlying skin changes and underlying malignancy are discontinuous. The second theory suggests that cells migrate along basement membranes and enter the epidermis and dermis of the nipple-areola complex. Pagetoid cells and underlying carcinomas demonstrate similar immunohistochemical staining patterns.

RevDate: 2019-06-07

Chavez DE, Gronau I, Hains T, et al (2019)

Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus).

Scientific reports, 9(1):8329 pii:10.1038/s41598-019-44772-5.

Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.

RevDate: 2019-06-11

Haythorne E, Rohm M, van de Bunt M, et al (2019)

Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells.

Nature communications, 10(1):2474 pii:10.1038/s41467-019-10189-x.

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.

RevDate: 2019-06-07

Kim SJ, JY Kim (2019)

An Unusual Cutaneous Recurrence of Carcinoma in the Mastectomy Bed and Its Imaging Features: A Case Report.

The American journal of case reports, 20:800-805 pii:916609.

BACKGROUND Chest wall recurrences of carcinoma after mastectomy usually involve subcutaneous tissue or the deep muscular layer. Recurrences arising in the skin are rare, and there are few reports of the associated radiologic features. This report presents an unusual case of cutaneous recurrence in the mastectomy bed and demonstrates its radiologic features using sonography and magnetic resonance imaging (MRI). CASE REPORT A 44-year-old woman presented with a palpable lump in the inferomedial area of the right chest wall. Six years ago, she had undergone total mastectomy for ductal carcinoma in situ in her right breast. Sonography showed an indistinct, oval, heterogeneous echoic mass measuring 0.9 cm, confined within the skin layer, corresponding to the palpable lump. A color Doppler sonogram showed minimal, spotted vascularity in and around the mass. Sonography-guided fine-needle aspiration biopsy was performed, revealing multiple clusters of atypical cells, suggestive of ductal carcinoma. On subsequent breast MRI, the mass, measuring 1.3 cm, was again localized to the skin; dynamic contrast-enhanced scans showed a circumscribed margin, oval shape, and rim enhancement (morphology) and slow initial enhancement and persistent delayed enhancement (kinetics). The mass was surgically excised and the pathological examination confirmed the diagnosis as recurrent invasive ductal carcinoma in the dermis. CONCLUSIONS Cutaneous recurrence in the mastectomy bed can manifest as a mass with suspicious radiologic features: indistinct margin on the sonogram and rim enhancement on the MRI. Awareness of such radiologic features may aid in differentiating between the various cutaneous manifestations encountered after mastectomy.

RevDate: 2019-06-06

Yamashita H, Kurita A, Azuma S, et al (2019)

Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer.

Diagnostic cytopathology [Epub ahead of print].

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51-year-old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound-fine-needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.

RevDate: 2019-06-05

Suzuki Y, Sakurai K, Adachi K, et al (2019)

[Usefulness of Automated Breast Ultrasound for Deciding on a Surgical Approach in a Patient with Breast Cancer- A Case Report].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(4):778-780.

Since breast reconstruction has been covered by health insurance, we can choose a procedure that combines the cosmetic satisfaction of patients with curability. We report about a patient with breast cancer that who underwent nipple-sparing mastectomy after evaluating the intraductal spread by automated breast ultrasound system(ABUS), while hand held ultrasound(HHUS)showed only limited information on the intraductal spread of the lesion. A 52-year old woman with an abnormal screening finding was referred to our hospital. HHUS showed an irregular and poorly defined hypoechoic mass lesion with a lactiferous duct extending to directly under the nipple. A core needle biopsy revealed invasive ductal carcinoma. We performed ABUS to assess the intraductal spread in the lesion because the patient requested breast reconstruction. The coronal section of the breast in the ABUS did not showintraductal spread. We, therefore, decided to perform a nipple-sparing mastectomy and sentinel lymph node biopsy. Intraoperative evaluation by frozen and permanent sections showed negative margins. The ABUS findings helped in the evaluation of the intraductal spread of the lesion and in the choice of the optimal procedure for the patient.

RevDate: 2019-06-05

Yamamoto K, Hayashi K, Waraya M, et al (2019)

[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].

Gan to kagaku ryoho. Cancer & chemotherapy, 46(4):757-759.

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

RevDate: 2019-06-10

Khan RN, Parvaiz MA, Khan AI, et al (2019)

Invasive carcinoma in accessory axillary breast tissue: A case report.

International journal of surgery case reports, 59:152-155 pii:S2210-2612(19)30284-6 [Epub ahead of print].

INTRODUCTION: Accessory or ectopic breast tissue is an aberration of normal breast development. It is known to be a rare entity present anywhere along the embryologic mammary streak or milk line but more common in axilla.

PRESENTATION OF CASE: We report a case of 36 year old female with accessory breast carcinoma who presented with a progressive lump in her left axilla for 1 year. On examination a 2 cm solitary mass was palpable in axilla. Ultrasound confirmed a 19 mm mass with no other lesion in breast and axilla. Core biopsy showed invasive ductal carcinoma. She was discussed in multidisciplinary board meeting and was offered upfront surgery with excision of accessory breast tissue and sentinel lymph node biopsy. Axillary lymph node dissection was omitted following ACOSG Z0011 criteria. She was offered adjuvant chemotherapy and radiation post operatively along with endocrine treatment as she was hormone receptor positive.

DISCUSSION: Accessory breast development is hormone dependent just like normal breast. Breast cancer in accessory breast tissue is very rare. The incidence is around 6%. Most common pathology is invasive ductal carcinoma (50-75%). The most common location is axilla (60-70%) although it can present in other less common locations like infra-mammary region (5-10%) and rarely in thighs, perineum, groin, and vulva.

CONCLUSION: Since accessory axillary breast tissue is out of the image of screening breast examination, it is necessary for the oncologists to be aware of this entity and associated pathologies. Their preventive excision in high risk women can also be considered.

RevDate: 2019-06-02

Zhu B, RT Farouki (2019)

A general framework for solving inverse dynamics problems in multi-axis motion control.

ISA transactions pii:S0019-0578(19)30234-4 [Epub ahead of print].

An inverse dynamics compensation (IDC) scheme for the execution of curvilinear paths by multi-axis motion controllers is proposed. For a path specified by a parametric curve r(ξ), the IDC scheme computes a real-time path correction Δr(ξ) that (theoretically) eliminates path deviations incurred by the inertia and damping of the machine axes. To exploit the linear time-invariant nature of the dynamic equations, the correction term is computed as a function of elapsed time t, and the corresponding curve parameter values ξ are only determined as the final step of the IDC scheme, through a real-time interpolator algorithm. It is shown that, in general, the correction term for P, PI, and PID controllers consists of derivative, natural, and integral terms (the integrand of the latter involving only the path r(ξ), and not its derivatives). The use of lead segments to minimize transient effects associated with the initial conditions is also discussed, and the performance of the method is illustrated by simulation results. The IDC scheme is expressed in terms of a linear differential operator formalism to provide a clear, general, and systematic development, amenable to further adaptations and extensions.

RevDate: 2019-05-30

Zhu J, Sun K, Xu X, et al (2019)

A preliminary attempt of non-intervention in the treatment of patients with intervertebral disc calcification combined with ossification of the posterior longitudinal ligament.

World neurosurgery pii:S1878-8750(19)31446-9 [Epub ahead of print].

BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, contrary remains in terms of the best way to treat this condition.

CASE DESCRIPTION: An eight-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurological dysfunction. CT and MRI revealed the calcified intervertebral disc and OPLL at C5/6 level and the spinal cord compression. We performed a non-intervention strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and CT revealed the complete resorption of ossified lesion. MRI also showed no sign of compression on the spinal cord and nerve root at the involved segment.

CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and gender-specific, further research is necessary. Ladder therapy, as described in the text, may be an acceptable treatment for IDC combined with OPLL.

RevDate: 2019-06-10

Piasecka D, Braun M, Kitowska K, et al (2019)

FGFs/FGFRs-dependent signalling in regulation of steroid hormone receptors - implications for therapy of luminal breast cancer.

Journal of experimental & clinical cancer research : CR, 38(1):230 pii:10.1186/s13046-019-1236-6.

Stromal stimuli mediated by growth factor receptors, leading to ligand-independent activation of steroid hormone receptors, have long been implicated in development of breast cancer resistance to endocrine therapy. Mutations in fibroblast growth factor receptor (FGFR) genes have been associated with a higher incidence and progression of breast cancer. Increasing evidence suggests that FGFR-mediated interaction between luminal invasive ductal breast carcinoma (IDC) and its microenvironment contributes to the progression to hormone-independence. Therapeutic strategies based on FGFR inhibitors hold promise for overcoming resistance to the ER-targeting treatment. A series of excellent reviews discuss a potential role of FGFR in development of IDC. Here, we provide a concise updated summary of existing literature on FGFR-mediated signalling with an emphasis on an interaction between FGFR and estrogen/progesterone receptors (ER/PR) in IDC. Focusing on the regulatory role of tumour microenvironment in the activity of steroid hormone receptors, we compile the available functional data on FGFRs-mediated signalling, as a fundamental mechanism of luminal IDC progression and failure of anti-ER treatment. We also highlight the translational value of the presented findings and summarize ongoing oncologic clinical trials investigating FGFRs inhibition in interventional studies in breast cancer.

RevDate: 2019-05-30

Zhao JG, Nie L, Chen XQ, et al (2019)

[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].

Zhonghua wai ke za zhi [Chinese journal of surgery], 57(6):422-427.

Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 μg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.

RevDate: 2019-05-28

Chen S, Chen H, Yi Y, et al (2019)

Comparative study of breast cancer with or without concomitant Paget disease: An analysis of the SEER database.

Cancer medicine [Epub ahead of print].

BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone.

METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD.

RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS.

CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.

RevDate: 2019-06-01

Yokoi T, Morimoto R, Oishi H, et al (2019)

Left Ventricular Relaxation Half-Time as a Predictor of Cardiac Events in Idiopathic Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy With Left Ventricular Systolic and/or Diastolic Dysfunction.

The American journal of cardiology pii:S0002-9149(19)30505-3 [Epub ahead of print].

PURPOSE: Diastolic dysfunction preceding systolic dysfunction is considered an important interaction in cardiomyopathy with poor prognosis. The aim of this study was to compare left ventricular (LV) isovolumic relaxation with the other parameters as a potential prognostic marker for patients with idiopathic dilated cardiomyopathy (IDC) and hypertrophic cardiomyopathy (HC).

METHODS: A total of 145 patients with IDC and 116 with HC were evaluated for hemodynamic parameters; LV pressure was directly measured by a micromanometer catheter, and relaxation half-time (T1/2) was used to determine LV isovolumic relaxation. The median follow-up period was 4.7 years.

RESULTS: The mean ages of the patients with IDC and HC were 52.0 ± 12.0 and 57.1 ± 12.4 years, respectively. Each patient group was further divided into 2 groups based on the median value of T1/2: (1) <41.0 ms (D-L group) and ≥41.0 ms (D-H group) (2) <38.5 ms (H-L group) and ≥38.5 ms (H-H group). Kaplan-Meier analysis showed a significantly higher probability of cardiac events in the D-H group than in the D-L group (p = 0.001) and in the H-H group than in the H-L group (p = 0.028). Further, Cox proportional hazard regression analysis revealed that T1/2 was an independent predictor of cardiac events for patients with IDC (hazard ratio 1.109; p = 0.007) and HC (hazard ratio 1.062; p = 0.041). In conclusion, regardless of the type of cardiomyopathy, T1/2 as a measure of LV isovolumic relaxation function was found to be associated with the occurrence of cardiac events.

RevDate: 2019-05-27

Li JP, Zhang XM, Zhang YS, et al (2019)

The prognostic value of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in triple-negative breast cancer.

Neoplasma pii:190107N26 [Epub ahead of print].

The American Joint Committee on Cancer (AJCC) released its 8th edition of cancer staging which is to be implemented in early 2018. This study aims to compare anatomic staging (AS) with prognostic staging (PS) based on the updated AJCC 8th edition staging manual. A retrospective single-center analysis of 313 triple-negative breast invasive ductal carcinoma patients who received surgery at department of breast surgery in the Fourth Hospital of Hebei Medical University from 2010-01 to 2012-12 was performed. All cases were restaged using the AJCC 8th edition AS and PS system. The 7-year DFS and the 7-year OS rates were 76.30% and 78.27%, respectively. Applying the PS system, 277 (88.5%) patients of the AS groups were up-staged to the PS groups, 31 cases with IIIC and 5 cases with IV unchanged (11.5%), and no cases down-staged. Both 7-year DFS and 7-year OS were significantly different in the different AS and PS groups (all, P<0.001). The PS system was found to provide better prognostic information in patients with AS group IIB. A total of 43 patients with AS group IIB were up-staged by PS system, in which 30 patients were +2 up-staged to PS IIIB, and 13 patients were +3 up-staged to PS IIIC. PS IIIB and IIIC from AS IIB had significant differences in 7‑year DFS (χ2 = 5.628, P = 0.014) and 7‑year OS (χ2 = 6.037, P = 0.018). Both AS and PS systems proposed in the 8th edition of the AJCC breast cancer staging manual had prognostic value in TNBC. Moreover, the PS system predicts clinical outcomes of TNBC patients more accurately than the traditional AS system.

RevDate: 2019-05-24

Tao WJ, Zhang HX, Zhang LM, et al (2019)

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

Journal of applied clinical medical physics [Epub ahead of print].

PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS.

METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters Ktrans , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares.

RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans , Kep , D and the combined indicator of Ktrans , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016).

CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.


RJR Experience and Expertise


Robbins holds BS, MS, and PhD degrees in the life sciences. He served as a tenured faculty member in the Zoology and Biological Science departments at Michigan State University. He is currently exploring the intersection between genomics, microbial ecology, and biodiversity — an area that promises to transform our understanding of the biosphere.


Robbins has extensive experience in college-level education: At MSU he taught introductory biology, genetics, and population genetics. At JHU, he was an instructor for a special course on biological database design. At FHCRC, he team-taught a graduate-level course on the history of genetics. At Bellevue College he taught medical informatics.


Robbins has been involved in science administration at both the federal and the institutional levels. At NSF he was a program officer for database activities in the life sciences, at DOE he was a program officer for information infrastructure in the human genome project. At the Fred Hutchinson Cancer Research Center, he served as a vice president for fifteen years.


Robbins has been involved with information technology since writing his first Fortran program as a college student. At NSF he was the first program officer for database activities in the life sciences. At JHU he held an appointment in the CS department and served as director of the informatics core for the Genome Data Base. At the FHCRC he was VP for Information Technology.


While still at Michigan State, Robbins started his first publishing venture, founding a small company that addressed the short-run publishing needs of instructors in very large undergraduate classes. For more than 20 years, Robbins has been operating The Electronic Scholarly Publishing Project, a web site dedicated to the digital publishing of critical works in science, especially classical genetics.


Robbins is well-known for his speaking abilities and is often called upon to provide keynote or plenary addresses at international meetings. For example, in July, 2012, he gave a well-received keynote address at the Global Biodiversity Informatics Congress, sponsored by GBIF and held in Copenhagen. The slides from that talk can be seen HERE.


Robbins is a skilled meeting facilitator. He prefers a participatory approach, with part of the meeting involving dynamic breakout groups, created by the participants in real time: (1) individuals propose breakout groups; (2) everyone signs up for one (or more) groups; (3) the groups with the most interested parties then meet, with reports from each group presented and discussed in a subsequent plenary session.


Robbins has been engaged with photography and design since the 1960s, when he worked for a professional photography laboratory. He now prefers digital photography and tools for their precision and reproducibility. He designed his first web site more than 20 years ago and he personally designed and implemented this web site. He engages in graphic design as a hobby.

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Cancer is the generic name for more than 100 diseases in which cells begin to grow and divide in an uncontrolled manner. Usually, when cells get too old or damaged, they die and new cells take their place. Cancer begins when genetic changes impair this orderly process so that some cells start to grow uncontrollably. The Emperor of All Maladies is a "biography" of cancer — from its first documented appearances thousands of years ago through the epic battles in the twentieth century to cure, control, and conquer it to a radical new understanding of its essence. This is a must read book for anyone with an interest in cancer. R. Robbins

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Collection of publications by R J Robbins

Reprints and preprints of publications, slide presentations, instructional materials, and data compilations written or prepared by Robert Robbins. Most papers deal with computational biology, genome informatics, using information technology to support biomedical research, and related matters.

Research Gate page for R J Robbins

ResearchGate is a social networking site for scientists and researchers to share papers, ask and answer questions, and find collaborators. According to a study by Nature and an article in Times Higher Education , it is the largest academic social network in terms of active users.

Curriculum Vitae for R J Robbins

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Curriculum Vitae for R J Robbins

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RJR Picks from Around the Web (updated 11 MAY 2018 )