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Bibliography on: Invasive Ductal Carcinoma

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Robert J. Robbins is a biologist, an educator, a science administrator, a publisher, an information technologist, and an IT leader and manager who specializes in advancing biomedical knowledge and supporting education through the application of information technology. More About:  RJR | OUR TEAM | OUR SERVICES | THIS WEBSITE

RJR: Recommended Bibliography 27 Sep 2020 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®)

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RevDate: 2020-09-25

Yoshida Y, Matsumoto I, Tanaka T, et al (2020)

Pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct leading to pancreatic pleural effusion: a case report.

Surgical case reports, 6(1):222 pii:10.1186/s40792-020-00987-7.

BACKGROUND: Pancreatic pleural effusion and ascites are defined as fluid accumulation in the thoracic and abdominal cavity, respectively, due to direct leakage of the pancreatic juice. They usually occur in patients with acute or chronic pancreatitis but are rarely associated with pancreatic neoplasm. We present here an extremely rare case of pancreatic neuroendocrine tumor with stenosis of the main pancreatic duct, leading to pancreatic pleural effusion.

CASE PRESENTATION: A 51-year-old man complained of dyspnea. Left-sided pleural effusion was detected on the chest X-ray. Pleural puncture was performed, and the pleural fluid indicated a high amylase content (36,854 IU/L). Hence, the patient was diagnosed with pancreatic pleural effusion. Although no tumor was detected, the computed tomography (CT) scan showed a pseudocyst and dilation of the main pancreatic duct in the pancreatic tail. Magnetic resonance cholangiopancreatography showed a fistula from the pseudocyst into the left thoracic cavity. Endoscopic retrograde pancreatic drainage was attempted; however, it failed due to stenosis in the main pancreatic duct in the pancreatic body. Endoscopic ultrasound revealed a hypoechoic mass measuring 15 × 15 mm in the pancreatic body that was not enhanced in the late phase of contrast perfusion and was thus suspected to be an invasive ductal carcinoma. The patient underwent distal pancreatectomy with splenectomy and the postoperative course was uneventful. Histopathological examination confirmed a neuroendocrine tumor of the pancreas (NET G2). The main pancreatic duct was compressed by the tumor. Increased pressure on the distal pancreatic duct by the tumor might have caused formation of the pseudocyst and pleural effusion. To the best of our knowledge, this is the first case report of pancreatic pleural effusion associated with a neuroendocrine tumor.

CONCLUSIONS: Differential diagnosis of a pancreatic neoplasm should be considered, especially when a patient without a history of pancreatitis presents with pleural effusion.

RevDate: 2020-09-25

Alvarado-Cabrero I, Valencia-Cedillo R, R Estevez-Castro (2020)

Preneoplasia of the Breast and Molecular Landscape.

Archives of medical research pii:S0188-4409(20)31756-2 [Epub ahead of print].

The current model of human breast cancer progression proposes a linear multi-step process which initiates as flat epithelial atypia (FEA), progresses to atypical ductal hyperplasia (ADH), evolves into ductal carcinoma in situ (DCIS) and culminates in the potentially lethal stage of invasive ductal carcinoma. FEA commonly coexists with well-developed examples of ADH, low-grade DCIS, lobular neoplasia and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. At the same time, many of the genomic changes of ADH are also shared by common sporadic breast cancer, consistent with a high risk for future development of metachronous breast cancer.

RevDate: 2020-09-24

Mandal S, Bethala MG, Dadeboyina C, et al (2020)

A Rare Presentation of an Invasive Ductal Carcinoma of Ectopic Axillary Breast Tissue.

Cureus, 12(8):e9928.

Ectopic breast tissue (EBT) is a rare entity and can present anywhere along the milk line, including the axilla, inframammary region, thighs, perineum, groin, and vulva. However, the axilla is the most common area of presentation. EBT can present as supernumerary breasts or aberrant breast tissue. Malignancy arising in EBT is rare, but the most common morphological variant is invasive ductal carcinoma. We report a case of a 43-year-old woman, a smoker with a family history of breast cancer, who presented to our clinic with a small mass in the right axillary area. After monitoring it for one year, the mass increased in size, so she returned to the clinic and decided with her care team to excise the mass. Histopathology showed invasive mammary adenocarcinoma arising in EBT and was diagnosed as right accessory stage I breast cancer. This case illustrates the imperative that any mass in the axillary region should be thoroughly assessed to rule out carcinoma in the accessory axillary tissue for timely management.

RevDate: 2020-09-22

Layeequr Rahman R, Puckett Y, Habrawi Z, et al (2020)

A decade of intraoperative ultrasound guided breast conservation for margin negative resection - Radioactive, and magnetic, and Infrared Oh My….

American journal of surgery pii:S0002-9610(20)30575-4 [Epub ahead of print].

BACKGROUND: The oncologic goal of margin-negative breast conservation requires adequate localization of tumor. Intraoperative ultrasound remains most feasible but under-utilized method to localize the tumor and assess margins.

METHODS: A prospectively maintained breast cancer database over a decade was queried for margin status in breast cancer patients undergoing breast conservation. Techniques of tumor localization, margin re-excision and closest margins were analyzed. Rate of conversion to mastectomy was determined.

RESULTS: Of the 945 breast cancer patients treated at a university-based Breast Center of Excellence between January 1, 2009 and December 31, 2018, 149(15.8%) had ductal carcinoma in situ; 712(75.3%) had invasive ductal carcinoma, and 63(6.7%) had invasive lobular carcinoma. Clinical stage distribution was: T1 = 372(39.4%); T2 = 257(27.2%); T3 = 87(9.2%). Five hundred and eighty three (61.7%) patients underwent breast conservation. The median (25th -75th centile) closest margin was 6(2.5, 10.0) mm. Thirty five (6.0%) patients underwent margin re-excision, of which 9(25%) were converted to mastectomy. Tumor localization was achieved with ultrasound in 521(89.4%) patients and with wire localization in 62(10.6%) patients. The median (25th-75th centile) closest margin with wire localization was 5.0(2.0, 8.5) mm versus 5.0 (2.0, 8.0) mm with ultrasound guidance [p = 0.6635]. The re-excision rate with wire localization was 14.5% versus 4.9% with ultrasound guidance [p = 0.0073]. The unadjusted Odds Ratio (95% CI) for margin revision in wire localized group compared with ultrasound was 3.2 (7.14, 1.42) [p = 0.0045]; multivariate adjusted OR (95%) was 4(9.09, 1.7) [p = 0.0013].

CONCLUSIONS: Ultrasound guidance for localization of breast cancer remains the most effective option for margin negative breast conservation.

RevDate: 2020-09-22

Griffin N, Marsland M, Roselli S, et al (2020)

The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer.

Biomolecules, 10(9): pii:biom10091329.

The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours.

RevDate: 2020-09-22

Cheung YC, Chen SC, Ueng SH, et al (2020)

Ductal Carcinoma In Situ Underestimation of Microcalcifications Only by Stereotactic Vacuum-Assisted Breast Biopsy: A New Predictor of Specimens without Microcalcifications.

Journal of clinical medicine, 9(9): pii:jcm9092999.

The mammographic appearance of ductal carcinoma in situ (DCIS) is mostly observed as microcalcifications. Although stereotactic vacuum-assisted breast biopsy (VABB) is a reliable alternative to surgical biopsy for suspicious microcalcifications, underestimation of VABB-proven DCIS is inevitable in clinical practice. We therefore retrospectively analyzed the variables in the prediction of DCIS underestimation manifesting as microcalcifications only proved by stereotactic VABB. In 1147 consecutive VABB on microcalcification-only lesions from 2010 to 2016, patients diagnosed with DCIS were selected to evaluate the underestimation rate. The analyzed variables included clinical characteristics, mammographic features, VABB procedure, and biomarkers. Univariate and multivariate analyses were used, and a p value < 0.05 was considered statistically significant. Of the 131 VABB-proven DCIS, 108 cases were diagnosed with DCIS and 23 were upgraded to invasive ductal carcinoma (IDC) after subsequent surgery. The small extent of microcalcification, grouped microcalcifications distribution, nearly complete microcalcification removal, and non-calcified specimens without DCIS were low for DCIS underestimation. Among them, the results of non-calcified specimens with or without DICS were the only statistically significant variables by multivariate logistic regression. These results indicate that the histology of non-calcified specimens was highly predictive of DCIS underestimation. Specimens without DCIS had a low upgrade rate to IDC.

RevDate: 2020-09-21

Methamem M, Ghadhab I, Hidar S, et al (2020)

Breast cancer in men: a serie of 45 cases and literature review.

The Pan African medical journal, 36:183 pii:PAMJ-36-183.

Immunohistochemical profiling studies carried out on female breast cancer has been extrapolated to breast cancer in males. Although, we do not know if it really reflects the reality of this pathology in males patients since the studies are often retrospective and studying a limited number of patients. The objectives was to describe particualrities of breast cancer in males and analyze the evolutionary characteristics and study the molecular profile of this rare disease in Tunisian men. It is a retrospective, descriptive and analytic study carried out over a period of 15 years in the departments of gynecology-obstetrics, general surgery, medical carcinology and anatomopathology of the Farhat Hached Teaching Hospital in Sousse, Tunisia. Fourty five patients were included.The most common histological type was invasive ductal carcinoma (95% of our patients). Our series was divided into 3 immunohistochemical groups with a majority group: luminal A (68.2%), followed by luminal B (27.3%) and only one patient had a triple negative type tumor (4.5%).The Overall survival rate (OSR) at 5 and 10 years was 83.2% and 76.8% respectively. Recurrence-free survival (RFS) at 5 and 10 years was 64.5% and 58.6%, respectively. The OSR was influenced significantly by age, clinical and histological size of the tumor, the presence of distant metastases and the occurrence of recurrence. Recurrence-free survival (RFS) was influenced by age, clinical and histological size of the tumor, and infiltration of the dermis. Breast cancer in males has similarities with women's breast cancer. However, it remains diagnosed at a later stage.

RevDate: 2020-09-21

Allen A, Mehta N, Younes IE, et al (2020)

Multiorgan metastatic invasive lobular Carcinoma initially presenting as diplopia.

Radiology case reports, 15(11):2229-2236 pii:S1930-0433(20)30419-2.

We present an interesting case of biopsy-proven multiorgan metastatic invasive lobular carcinoma to the orbits and kidney, initially presenting in a 76-year-old woman with diplopia. Invasive lobular carcinoma is a less common subtype of breast cancer and is often difficult to detect on imaging with an unusual metastatic pattern when compared to invasive ductal carcinoma. Metastatic invasive lobular carcinoma most frequently involves the orbits, ovaries, gastrointestinal tract, retroperitoneum and bone. Disease involving these organ systems detected on imaging should raise concern for metastatic disease when appropriate.

RevDate: 2020-09-20

Ohno A, Fujimori N, Miki M, et al (2020)

Collision of a pancreatic ductal adenocarcinoma and a pancreatic neuroendocrine tumor associated with multiple endocrine neoplasm type 1.

Clinical journal of gastroenterology pii:10.1007/s12328-020-01234-0 [Epub ahead of print].

A 54-year-old man with pancreatic head tumor had undergone pancreaticoduodenectomy and was diagnosed with pancreatic neuroendocrine tumor (P-NET) associated with sporadic multiple endocrine neoplasm type 1. Five years after the resection, P-NET recurred and liver metastases were observed. He was treated with a somatostatin analog. Eleven years after the resection, computed tomography revealed a new pancreatic hypodense and hypovascular mass adjacent to the P-NET that was diagnosed as pancreatic adenocarcinoma via endoscopic ultrasound-guided fine-needle aspiration. He underwent a total remnant pancreatectomy. Pathological examination showed that the lesion was constituted by a pancreatic ductal adenocarcinoma (PDAC) and a neuroendocrine tumor. Additionally, the invasive ductal carcinoma collided with the neuroendocrine tumor. Both PDAC and P-NET cells were observed in the collision area. We could observe the onset of PDAC during the treatment of P-NET. Moreover, we are the first to report the case of a collision of pancreatic endocrine and exocrine tumors diagnosed preoperatively.

RevDate: 2020-09-18

Zhang J, Lu CY, Chen CH, et al (2020)

Effect of pathologic stages on postmastectomy radiation therapy in breast cancer receiving neoadjuvant chemotherapy and total mastectomy: A Cancer Database Analysis.

Breast (Edinburgh, Scotland), 54:70-78 pii:S0960-9776(20)30170-3 [Epub ahead of print].

PURPOSE: To use pathologic indicators to determine which patients benefit from postmastectomy radiation therapy (PMRT) for breast cancer after neoadjuvant chemotherapy (NACT) and total mastectomy (TM).

PATIENTS AND METHODS: We enrolled 4236 patients with breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was used to calculate hazard ratios (HRs) and confidence intervals; independent predictors were controlled for or stratified in the analysis.

RESULTS: After multivariate Cox regression analyses, the adjusted HRs derived for PMRT for all-cause mortality were 0.65 (0.52-0.81, P < 0.0001) and 0.58 (0.47-0.71, P < 0.0001) in postchemotherapy pathologic tumor stages T2-4 (ypT3-4) and postchemotherapy pathologic nodal stages N2-3 (ypN2-3), respectively. Moreover, adjusted HRs derived for PMRT with all-cause mortality were 0.51 (0.38-0.69, P < 0.0001), 0.60 (0.40-0.88, P = 0.0096), and 0.64 (0.48-0.86, P = 0.0024) in pathological stages IIIA, IIIB, and IIIC, respectively. Additionally, the PMRT group showed significant locoregional control irrespective of the pathologic response, even ypT0, ypN0, or pathological complete response (pCR), compared with the No-PMRT group. The multivariate analysis showed no statistical differences between the PMRT and No-PMRT groups for distant metastasis-free survival in any pathologic response of ypT0-4, ypN0-3, and pathologic American Joint Committee on Cancer stages pCR to IIIC.

CONCLUSION: For patients with breast cancer ypT3-4, ypN2-3, or pathologic stages IIIA-IIIC receiving NACT and TM, benefit from PMRT if it is associated with OS benefits, regardless of the clinical stage of the disease. Compared with No-PMRT, PMRT improved locoregional recurrence-free survival, even pCR, in patients with breast cancer receiving NACT and TM.

RevDate: 2020-09-19

Sohail SK, Sarfraz R, Imran M, et al (2020)

Estrogen and Progesterone Receptor Expression in Breast Carcinoma and Its Association With Clinicopathological Variables Among the Pakistani Population.

Cureus, 12(8):e9751.

Introduction The prognosis of breast cancer depends on the histological type, size of the tumor, tumor necrosis, skin, nipple and chest wall invasion, lymphovascular invasion, grade, stage, the status of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2), cell proliferation marker (ki-67), and type of therapy. Estrogen receptor and progesterone receptor expression in breast cancer is, so far, the most useful predictive marker. We have undertaken this study to find the expression of ER and PgR in breast carcinoma and its association with other prognostically important clinicopathological variables. Materials and methods In this cross-sectional study, a total of 130 cases of modified radical mastectomy that have been diagnosed as malignant on histopathology were collected from the pathology department of Allama Iqbal Medical College, Lahore, from January 2016 to May 2018. The demographic data and gross and microscopic findings were recorded. Immunohistochemistry (ER, PgR) was applied to suitable tumor sections and their status was evaluated semi-quantitatively by histopathologists using College American Pathologist (CAP) guidelines. Result Most of the breast cancer patients (69; 53.1%) were below 50 years of age. Fifty-nine (45.4%) and 48 (36.9%) cases were positive for ER and PgR, respectively, showing lower hormonal receptor positivity than that reported in the western population where ER expression has been found in 50%-80% of cases and PR expression is found in 60%-70% of cases of invasive ductal carcinoma. The association of the expression of hormone receptors with a clinicopathological variable was demonstrated. ER-/PgR- tumors showed a higher histologic grade, greater tumor size, and more lymph node involvement by metastasis. Conclusion Low hormone receptor positivity is associated with young patients, advanced stage at presentation, and higher grade in our population. The tumor characteristics are different as compared to the western population. This suggests more consideration to the screening, early diagnosis, and molecular or immunohistochemical typing of this cancer in our population.

RevDate: 2020-09-18

Richard F, Majjaj S, Venet D, et al (2020)

Characterization of stromal tumor-infiltrating lymphocytes and genomic alterations in metastatic lobular breast cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research pii:1078-0432.CCR-20-2268 [Epub ahead of print].

PURPOSE: Invasive lobular carcinoma (ILC) represents the second most common histological breast cancer subtype after invasive ductal carcinoma (IDC). While primary ILC has been extensively studied, metastatic ILC has been poorly characterized at the genomic and immune level.

EXPERIMENTAL DESIGN: We retrospectively assembled the multi-centric EuroILC series of matched primary and metastatic samples from 94 patients with estrogen receptor (ER)-positive ILC. Stromal tumor infiltrating lymphocytes (sTIL) were assessed by experienced pathologists. Targeted sequencing and low pass whole genome sequencing were conducted to detect mutations and copy number aberrations (CNAs). We compared the frequencies of the alterations in EuroILC with those from patients with ER-positive metastatic ILC (n=135) and IDC (n=563) from MSK-IMPACT.

RESULTS: Low sTIL levels were observed in ILC metastases, with higher levels in the mixed non-classic histology. Considering ILC metastases from EuroILC and MSK-IMPACT, we observed that >50% of tumors harbor genomic alterations that have previously been associated with endocrine resistance. A matched primary/metastasis comparison in EuroILC revealed mutations (AKT1, ARID1A, ESR1, ERBB2 or NF1) and CNAs (PTEN or NF1 deletion, CYP19A1 amplification) associated with endocrine resistance that were private to the metastasis in 22% (7/32) and 19% (4/21) of patients, respectively. An increase in CDH1, ERBB2, FOXA1 and TBX3 mutations, in CDH1 deletions and a decrease in TP53 mutations was observed in ILC as compared to IDC metastases.

CONCLUSIONS: ILC metastases harbor genomic alterations that may potentially explain endocrine resistance in a large proportion of patients, and present genomic differences as compared to IDC metastases.

RevDate: 2020-09-15

Weinstein SP, Korhonen K, Cirelli C, et al (2020)

Abbreviated Breast Magnetic Resonance Imaging for Supplemental Screening of Women With Dense Breasts and Average Risk.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology [Epub ahead of print].

PURPOSE: Although mammography is the standard of care for breast cancer screening, dense breast tissue decreases mammographic sensitivity. We report the prevalent cancer detection rate (CDR) from the first clinical implementation of abbreviated breast magnetic resonance imaging (AB-MR) as a supplemental screening test in women with dense breasts.

METHODS: The study was approved by the institutional review board and is Health Insurance Portability and Accountability Act complaint. This retrospective review includes women who were imaged between January 1, 2016 and February 28, 2019. On a 1.5 Tesla magnet, the imaging protocol consisted of three sequences: Short-TI Inversion Recovery (STIR), precontrast, and postcontrast. A subtraction sequence and a maximum intensity projection were generated. We report the patient-level CDR and the positive predictive value of AB-MR examinations after negative/benign digital breast tomosynthesis (DBT).

RESULTS: Out of 511 prevalent rounds of AB-MR examinations, 36 women were excluded. The remaining 475 asymptomatic women with dense breasts had negative/benign DBT examinations before the AB-MR. There were 420 of 475 (88.4%) benign/negative examinations, 13 of 475 (2.7%) follow-up recommendations, and 42 biopsy recommendations. Thirty-nine biopsies were completed, resulting in 12/39 (30.8%) malignancies in 12 women: seven invasive carcinomas and five ductal carcinoma in situ. One additional patient was diagnosed with invasive ductal carcinoma at the time of 6-month follow-up. The CDR was 27.4 per 1,000 (13 of 475; 95% CI, 16.1 to 46.3). The size of invasive carcinomas ranged from 0.6-1.0 cm (mean, 0.5 cm). Of the seven women who underwent surgical evaluation of the axilla, zero of seven patients had positive nodes. There were no interval cancers at 1-year follow-up.

CONCLUSION: Preliminary results from clinical implementation of screening AB-MR resulted in a CDR of 27.4/1,000 at the patient level after DBT in women with dense breasts. Additional evaluation is warranted.

RevDate: 2020-09-15

Taverna C, Baněčková M, Lorenzon M, et al (2020)

MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.

Histopathology [Epub ahead of print].

BACKGROUND: Secretory carcinoma (SC; synonym: mammary analogue SC= MASC) is a low-grade salivary gland tumor which occurs both in major and in minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, that overlaps with several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intraductal carcinoma (IDC) of intercalated type in major, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumors share with SC some morphological features, SOX10 immunoreactivity, and, with the exception of AciCC, they all coexpress S100 and mammaglobin.

METHODS: We compare MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate its potential in differentiating these entities.

RESULTS: Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%) compared to none of IDCs and PACs. On the contrary, mammaglobin is frequently expressed in SC (30 of 36 cases; 83.3%), IDC (24/28; 85.7%) and PAC (7/19; 36.8%). Two of 3 high grade SCs lost MUC4 expression in the high-grade tumor component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK vs. non-ETV6-NTRK).

CONCLUSION: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.

RevDate: 2020-09-16

Cruz C, Vega Carvallo AI, Spodine E, et al (2020)

New Highly Charged Iron(III) Metal-Organic Cube Stabilized by a Bulky Amine.

ACS omega, 5(35):22238-22247.

In this work, we report a new octanuclear cluster based on FeIII and the ligand 1H-imidazole-4,5-dicarboxylic acid, [Et3NH]12[Fe8(IDC)12]·10DMF·13H2O (1), with a metal core containing eight FeIII connected by only one type of organic ligand. A peak at 573 m/z in the mass spectra of the compound suggests the adduct species {[Fe8(IDC)12]+8H}4-. By X-ray photoelectron spectroscopy, the oxidation state of the iron cation was confirmed to be 3+, also identifying the presence of a quaternary nitrogen species, which act as a countercation of the anionic metal core [Fe8(IDC)12]12-. Mössbauer spectra recorded at different temperatures show an isomer shift and quadrupole splitting parameters that confirm the existence of only FeIII-HS in the structure of 1. X-ray analysis reveals that compound 1 crystallizes in the orthorhombic system space group Ibam, confirming a molecular cluster structure with an almost regular cube as geometry, with the FeIII atoms located at the corners of the cube and connected by μ-1κ2N,O:2κ2N',O‴-IDC3- bridges. Additionally, the magnetic measurements reveal a weak antiferromagnetic coupling in the Fe8III coordination cluster (J = -3.8 cm-1). To the best of our knowledge, 1 is the first member of the family of cubes assembled with 1H-imidazole-4,5-dicarboxylic acid and FeIII cation, exhibiting high pH stability over a broad pH range, making it an ideal candidate for the design of supramolecular structures and metal-organic frameworks.

RevDate: 2020-09-16

Xu N, Ke ZB, Chen YH, et al (2020)

Risk Factors for Pathologically Confirmed Lymph Nodes Metastasis in Patients With Clinical T2N0M0 Stage Prostate Cancer.

Frontiers in oncology, 10:1547.

Objective: To explore the risk factors for postoperatively pathological lymph node metastasis in patients with clinical T2N0M0 stage prostate cancer (PCa).

Methods: We retrospectively analyzed clinicopathological data of 316 patients with clinical T2 stage PCa and preoperative negative lymph nodes [LN(-)] indicated by imaging (cT2N0M0) between January 2014 and May 2019. Multivariate logistic regression analysis was performed to determine risk factors for postoperatively pathological pLN(+) in patients with cT2N0M0 stage PCa. Spearman correlation analysis was used to explore the relationship between tumor burden and Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) score.

Results: A total of 45 patients (14.2%) were confirmed by postoperative pathology to have LN metastasis. Univariate analysis indicated that total prostate-specific antigen (tPSA), PI-RADS v2 score, postoperative Gleason grade group (GGG), intraductal carcinoma of the prostate (IDC-P), clinical T2 substaging, and postoperative pathological tumor burden were risk factors for pLN(+) in all patients. Multivariate analysis showed that tPSA and postoperative GGG were risk factors for pLN(+) in all patients. Univariate analysis revealed that tPSA, PIRADS v2 score, clinical T2 substaging, IDC-P, postoperative pathological tumor burden, and postoperative GGG were risk factors for pLN(+) in patients with GGG ≥ 3. Multivariate analysis suggested that tPSA, PI-RADS v2 score, clinical T2 substaging, postoperative pathological tumor burden, and GGG were risk factors for pLN (+) in patients with GGG ≥ 3. Spearman correlation analysis showed that PI-RADS v2 score was positively correlated with clinical T2 substaging and postoperative pathological tumor burden.

Conclusion: There was a high risk of LN metastasis in patients with cT2 PCa if they had high preoperative tPSA or high postoperative GGG. Patients with cT2 PCa and GGG ≥ 3 had a high risk of LN metastasis if they had high PI-RADS v2 score, high preoperative clinical stage or high postoperative pathological tumor burden. PI-RADS v2 score predicted tumor burden well in patients with GGG ≥ 3.

RevDate: 2020-09-13

Bartlett H, Elghobashy M, Deshmukh N, et al (2020)

Radiation-Associated Primary Osteosarcoma of the Breast.

INTRODUCTION: Non-epithelial primary mammary osteosarcomas are extremely rare. The differentials include metaplastic carcinoma and malignant phyllodes tumour. This is the first published case of primary breast osteosarcoma arising after local radiotherapy.

CASE PRESENTATION: A 73-year-old female presented with a right-sided breast lump. The same breast had been irradiated 11 years previously for invasive ductal carcinoma. Diagnostic excision revealed a highly cellular, malignant spindle-cell lesion merged with an osteoid matrix and foci of calcification and bone formation. Immunohistochemistry and molecular studies showed no lines of differentiation. Due to the lack of epithelial/glandular differentiation, in situ carcinoma or leaf-like pattern, the diagnosis of post-irradiation osteosarcoma was made. She underwent mastectomy and is disease-free at 8 months of follow-up.

CONCLUSION: Post-irradiation osteosarcoma should be considered in the differential diagnosis of breast lesions showing malignant osteoid. Extensive sampling and careful search for epithelial differentiation is required to guide management. Complete surgical excision is recommended.

RevDate: 2020-09-13

Aboody D, Siev J, G Doron (2020)

Building resilience to body image triggers using brief cognitive training on a mobile application: A randomized controlled trial.

Behaviour research and therapy, 134:103723 pii:S0005-7967(20)30177-7 [Epub ahead of print].

OBJECTIVE: Body image disturbance (BID) is common among women, characterized by persistent and distressing appearance dissatisfaction, and linked with eating disorders. Although effective, cognitive behavioral therapy (CBT) delivered by trained professionals is not easily accessible. This randomized trial evaluated the effects of a CBT-based mobile application designed to increase resilience to body image triggers and reduce BID symptoms.

METHOD: A non-clinical sample of women (N = 90; Mage = 23.52) was randomized to use the mobile application for approximately 4 min of daily exercises for two weeks or to a control condition. Body image was measured at baseline, immediately after two weeks of mobile application use, and at 1-month follow-up. To examine whether using the application was associated with increased resilience to common BID triggers, participants completed an Instagram exposure resilience task upon completion and at 1-month follow-up.

RESULTS: Relative to those in the control condition, participants who used the application demonstrated increased resiliency and reduced BID symptoms. Theses effects were medium-to-large and were maintained at 1-month follow-up.

CONCLUSION: These results underscore the potential usefulness of brief, low-intensity, portable interventions in reducing BID symptoms and in increasing resilience to thin-ideal body messages often portrayed on social media.

RevDate: 2020-09-15

Ucar EA, Durur-Subasi I, Yilmaz KB, et al (2020)

Quantitative perfusion parameters of benign inflammatory breast pathologies: A descriptive study.

Clinical imaging, 68:249-256 pii:S0899-7071(20)30327-2 [Epub ahead of print].

PURPOSE: With this study, we evaluated the perfusion magnetic resonance imaging (MRI) features of benign inflammatory breast lesions for the first time and compared their Ktrans, Kep, Ve values and contrast kinetic curves to benign masses and invasive ductal carcinoma (IDC).

MATERIALS AND METHODS: Perfusion MRIs of the benign masses (n = 42), inflammatory lesions (n = 25), and IDCs (n = 16) were evaluated retrospectively in terms of Ktrans, Kep, Ve values and contrast kinetic curves and compared by the Kruskal-Wallis, Mann-Whitney U, chi-square tests statistically. Cronbach α test was used to measure intraobserver and interobserver reliability.

RESULTS: Mean Ktrans values were 0.052 for benign masses, 0.086 for inflammatory lesions and 0.101 for IDC (p < 0.001). Mean Kep values were 0.241 for benign masses, 0.435 for inflammatory lesions and 0.530 for IDC (p < 0.001). Mean Ve values were 0.476 for benign masses, 0.318 for inflammatory lesions and 0.310 for IDC (p = 0.067). For inflammatory and IDC lesions, Ktrans and Kep values were found to be higher and Ve values were lower than benign masses (p = 0.001 for Ktrans, p = 0.001 for Kep, p = 0.045 for Ve). There were excellent or good intra-interobserver reliabilities. For the kinetic curve pattern, most of the benign lesions showed progressive (81%), inflammatory lesions progressive (64%) and IDC lesions plateau (75%) patterns (p < 0.001).

CONCLUSIONS: On T1 perfusion MRI, similar to IDC lesions, inflammatory lesions demonstrate higher Ktrans and Kep and lower Ve values than benign masses. Quantitative perfusion parameters are not helpful in differentiating them from IDC lesions.

RevDate: 2020-09-13

Cha YJ, JS Koo (2020)

Expression and Role of Epithelial Membrane Proteins in Tumorigenesis of Hormone Receptor-Positive Breast Cancer.

Journal of breast cancer, 23(4):385-397.

Purpose: Studies on the expression of epithelial membrane proteins (EMPs) in breast cancer have been rare and limited. In the present study, we aimed to evaluate the expression of EMP1, EMP2, and EMP3 in invasive ductal carcinoma (IDC) of the breast, and investigate their clinical implications.

Methods: In total, 418 IDC cases were collected, and specimens were used to construct a tissue microarray. Immunohistochemical staining of EMP1, EMP2, and EMP3 was performed and the results were analyzed in combination with the clinical data.

Results: EMP1 was expressed in > 90% of all IDC subtypes. A decreased expression of EMP2 and EMP3 was observed in triple-negative breast cancer. EMP3 expression was independently associated with human epidermal growth factor receptor 2 (HER2) positivity. HER2-negative cases exhibited a decreased EMP2 expression along with a higher histological grade and an increased proliferative index. No significant difference was found in the overall survival or disease-free survival based on the EMP expression. In HER2-negative breast cancer, EMP2 expression inversely correlated with the histological grade and proliferative index.

Conclusion: EMP2 may be involved in the early stage of tumor development in hormone-positive breast cancer.

RevDate: 2020-09-13

Verma AK, Ahmad I, Yadav P, et al (2020)

Expression and Correlation of Cell-Free cIAP-1 and cIAP-2 mRNA in Breast Cancer Patients: A Study from India.

Journal of oncology, 2020:3634825.

Background: Inhibitors of apoptosis proteins such as cIAP-1 and cIAP-2 have recently emerged as the key mechanism in resistance to apoptosis in various cancers and lead to cell survival. Therefore, the present study aimed to evaluate the cIAP-1 and cIAP-2 expression in breast cancer patients, as well as their association with overall patient survival.

Methods: Histopathologically confirmed 100 invasive ductal carcinoma patients and healthy controls were included in the present study. Total RNA extraction was done from the serum sample of the patients; further, 100 ng of total RNA was used to synthesise cDNA from patients' as well as from healthy controls' serum. Quantitative real-time PCR was performed using the maxima SYBR Green dye to study the expression of cIAP-1 and cIAP-2, and beta-actin was used as the internal control.

Results: The study observed that breast cancer patients had 13.50 mean fold increased cIAP-1 mRNA and 8.76 mean fold increased cIAP-2 mRNA expression compared to the control subjects. Breast cancer patients in the TNM stages I, II, III, and IV showed 9.54, 11.80, 15.19, and 16.83 mean fold increased cIAP-1 mRNA expression (p=0.004). Distant organ metastasis, (p=0.008), PR status of breast cancer patients (p < 0.0001), and HER2 status of breast cancer patients (p < 0.0001) were found to be associated with cIAP-1 mRNA expression. Breast cancer patients with different TNM stages such as stages I, II, III, and IV showed 7.8, 8.09, 7.97, and 12.85 mean fold increased cIAP-2 mRNA expression (p=0.0002). Breast cancer patients with distant organ metastases status were found to be associated with cIAP-2 mRNA expression (p < 0.0001). Breast cancer patients with <13-fold and >13-fold cIAP-1 mRNA expression showed 37.39 months and 34.70 months of overall median survival, and the difference among them was found to be significant (p=0.0001). However, cIAP-2 mRNA expression among <8-fold and >8-fold mRNA expression groups showed 35 months and 27.90 months of overall median survival time (p < 0.0001). Higher cIAP-1 mRNA expression was linked with smoking and alcoholism among the breast cancer patients (p < 0.0001 and p < 0.0001). Significant association of higher cIAP-1 mRNA expression was found with the advancement of the disease, while higher mRNA expression of cIAP-1 was associated with distant organ metastases in ROC curve analysis.

Conclusion: The present study suggested that increased cell-free cIAP-1 and cIAP-2 mRNA expression was correlated with the advancement of disease, progression of disease, and overall reduced patient survival. Cell-free cIAP-1 and cIAP-2 mRNA expression could be the predictive indicator of the disease.

RevDate: 2020-09-17

Israelov H, Ravid O, Atrakchi D, et al (2020)

Caspase-1 has a critical role in blood-brain barrier injury and its inhibition contributes to multifaceted repair.

Journal of neuroinflammation, 17(1):267.

BACKGROUND: Excessive inflammation might activate and injure the blood-brain barrier (BBB), a common feature of many central nervous system (CNS) disorders. We previously developed an in vitro BBB injury model in which the organophosphate paraoxon (PX) affects the BBB endothelium by attenuating junctional protein expression leading to weakened barrier integrity. The objective of this study was to investigate the inflammatory cellular response at the BBB to elucidate critical pathways that might lead to effective treatment in CNS pathologies in which the BBB is compromised. We hypothesized that caspase-1, a core component of the inflammasome complex, might have important role in BBB function since accumulating evidence indicates its involvement in brain inflammation and pathophysiology.

METHODS: An in vitro human BBB model was employed to investigate BBB functions related to inflammation, primarily adhesion and transmigration of peripheral blood mononuclear cells (PBMCs). Caspase-1 pathway was studied by measurements of its activation state and its role in PBMCs adhesion, transmigration, and BBB permeability were investigated using the specific caspase-1 inhibitor, VX-765. Expression level of adhesion and junctional molecules and the secretion of pro-inflammatory cytokines were measured in vitro and in vivo at the BBB endothelium after exposure to PX. The potential repair effect of blocking caspase-1 and downstream molecules was evaluated by immunocytochemistry, ELISA, and Nanostring technology.

RESULTS: PX affected the BBB in vitro by elevating the expression of the adhesion molecules E-selectin and ICAM-1 leading to increased adhesion of PBMCs to endothelial monolayer, followed by elevated transendothelial-migration which was ICAM-1 and LFA-1 dependent. Blocking caspase-8 and 9 rescued the viability of the endothelial cells but not the elevated transmigration of PBMCs. Inhibition of caspase-1, on the other hand, robustly restored all of barrier insults tested including PBMCs adhesion and transmigration, permeability, and VE-cadherin protein levels. The in vitro inflammatory response induced by PX and the role of caspase-1 in BBB injury were corroborated in vivo in isolated blood vessels from hippocampi of mice exposed to PX and treated with VX-765.

CONCLUSIONS: These results shed light on the important role of caspase-1 in BBB insult in general and specifically in the inflamed endothelium, and suggest therapeutic potential for various CNS disorders, by targeting caspase-1 in the injured BBB.

RevDate: 2020-09-10

Alan O, Akin Telli T, Aktas B, et al (2020)

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?.

World journal of surgical oncology, 18(1):242 pii:10.1186/s12957-020-02019-y.

PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment.

METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated.

RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01].

CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

RevDate: 2020-09-12

Kobayashi T, Marra AR, Schweizer ML, et al (2020)

Impact of Infectious Disease Consultation in Patients With Candidemia: A Retrospective Study, Systematic Literature Review, and Meta-analysis.

Open forum infectious diseases, 7(9):ofaa270.

Background: Morbidity and mortality from candidemia remain unacceptably high. While infectious disease consultation (IDC) is known to lower the mortality from Staphylococcus aureus bacteremia, little is known about the impact of IDC in candidemia.

Methods: We conducted a retrospective observational cohort study of candidemia patients at a large tertiary care hospital between 2015 and 2019. The crude mortality rate was compared between those with IDC and without IDC. Then, we systematically searched 5 databases through February 2020 and performed a meta-analysis of the impact of IDC on the mortality of patients with candidemia.

Results: A total of 151 patients met the inclusion criteria, 129 (85%) of whom received IDC. Thirty-day and 90-day mortality rates were significantly lower in the IDC group (18% vs 50%; P = .002; 23% vs 50%; P = .0022, respectively). A systematic literature review returned 216 reports, of which 13 studies including the present report fulfilled the inclusion criteria. Among the 13 studies with a total of 3582 patients, IDC was performed in 50% of patients. Overall mortality was 38.2% with a significant difference in favor of the IDC group (28.4% vs 47.6%), with a pooled relative risk of 0.41 (95% CI, 0.35-0.49). Ophthalmology referral, echocardiogram, and central line removal were performed more frequently among patients receiving IDC.

Conclusions: This study is the first systematic literature review and meta-analysis to evaluate the association between IDC and candidemia mortality. IDC was associated with significantly lower mortality and should be considered in all patients with candidemia.

RevDate: 2020-09-17

Aggius-Vella E, Gori M, Animali S, et al (2020)

Non-spatial skills differ in the front and rear peri-personal space.

Neuropsychologia, 147:107619 pii:S0028-3932(20)30291-8 [Epub ahead of print].

In measuring behavioural and pupillary responses to auditory oddball stimuli delivered in the front and rear peri-personal space, we find that pupils dilate in response to rare stimuli, both target and distracters. Dilation in response to targets is stronger than the response to distracters, implying a task relevance effect on pupil responses. Crucially, pupil dilation in response to targets is also selectively modulated by the location of sound sources: stronger in the front than in the rear peri-personal space, in spite of matching behavioural performance. This supports the concept that even non-spatial skills, such as the ability to alert in response to behaviourally relevant events, are differentially engaged across subregions of the peri-personal space.

RevDate: 2020-09-14

Okun JG, Conway S, Schmidt KV, et al (2020)

Corrigendum to "Molecular regulation of urea cycle function by the liver glucocorticoid receptor" [Mol Metab 4 (10) (2015 Oct) 732-740].

RevDate: 2020-09-05

Amitai Y, Menes TS, Scaranelo A, et al (2020)

Lobular neoplasia occult on conventional imaging and diagnosed on MRI-guided biopsy: can we estimate upgrade on surgical pathology?.

Breast cancer research and treatment pii:10.1007/s10549-020-05893-y [Epub ahead of print].

PURPOSE: The goal of this study is to evaluate the frequency and imaging features of lobular neoplasia (LN) diagnosed on MRI-guided biopsy, determine the upgrade rate to malignancy, and assess for any features that may be associated with an upgrade on surgical excision.

MATERIALS AND METHODS: Research ethical board approved the review of consecutive patients with MRI-detected LN between January 2009 and December 2018 with differentiation between pure LN and LN with associated other high-risk lesions. The final outcome was determined by final pathology results from surgical excision or 24 months of follow-up. Appropriate statistical tests were used.

RESULTS: Out of 1250 MRI-guided biopsies performed, 76 lesions (6%) fulfilled the inclusion criteria and formed the study cohort. Of the 76 lesions, 54 (71%) were pure LN while the rest had coexistent high-risk lesion. Non-mass enhancement (NME) was the most common lesion type (62, 82%). Fifty-nine lesions (78%) were surgically excised, the other 17 had benign follow-up. Overall, 8 lesions (11%) were upgraded to malignancy on final pathology. Malignant outcome was associated with larger lesion size (5.5 versus 1.9 cm, P < 0.001) and a clumped NME pattern (75% versus 24%, P = 0.006). Lesion size and clumped NME remained significantly associated with upgrade on sub-analysis of the pure LN group.

CONCLUSION: Larger lesion size and clumped NME are imaging findings associated with upgrade of LN diagnosed by MRI-guided biopsy. This may influence patient management in this clinical setting. Additional larger studies are needed to consolidate our results and to potentially detect additional factors associated with upgrade.

RevDate: 2020-09-04

Hirabayashi M, Chambers JK, Sumi A, et al (2020)

Immunophenotyping of Nonneoplastic and Neoplastic Histiocytes in Cats and Characterization of a Novel Cell Line Derived From Feline Progressive Histiocytosis.

Veterinary pathology [Epub ahead of print].

Histiocytic proliferative diseases are rare in cats, and their pathogenesis is poorly understood. In the present study, 25 cases of histiocytic sarcoma (HS) and 6 of feline progressive histiocytosis (FPH) were examined, and survival times were recorded in 19 cases. The immunophenotypes of tumor cells in these cases as well as of nonneoplastic feline histiocytes were characterized using formalin-fixed, paraffin-embedded tissues. An FPH cell line (AS-FPH01) and xenotransplant mouse model of FPH were also established. The median survival time of HS (150 days) was significantly shorter than that of FPH (470 days). Immunohistochemically, nonneoplastic histiocytes were immunopositive for various combinations of Iba-1, HLA-DR, E-cadherin, CD204, CD163, CD208, and MAC387. By immunohistochemistry, dermal interstitial dendritic cells (iDCs) and macrophages were CD204+/E-cadherin-, while epidermal Langerhans cells (LCs) were CD204-/E-cadherin+. Neoplastic cells of 4 FPH and 18 HS were CD204+/E-cadherin- (iDC/macrophage immunophenotype), while 2 FPH and 2 HS were CD204-/E-cadherin+ (LC immunophenotype), and 5 HS were CD204+/E-cadherin+ (LC-like cell immunophenotype). Furthermore, immunohistochemical and western blot analyses of AS-FPH01 cells derived from E-cadherin-negative FPH revealed that cultured cells were immunopositive for both CD204 and E-cadherin in vitro and in vivo. These results indicate that the neoplastic cells of feline HS and FPH were variably positive for iDC/macrophage and LC markers, and their immunophenotype changed in different microenvironments. The novel cell line established in the present study may serve as an experimental model of FPH that will enable further molecular and therapeutic studies on this disease.

RevDate: 2020-09-05

Sharma S, Blaudeau E, S Sharma (2020)

A Case of Asymmetric Nipple Enhancement as an Imaging Precursor to Invasive Ductal Carcinoma.

Cureus, 12(8):e9514.

On multidetector computed tomography (CT), it is important to scrutinize the imaged portions of the breasts. In recent years, the dramatic rise in CT imaging has led to the increased detection of incidental breast lesions. We describe a case of invasive ductal carcinoma that presented as stage IV cancer, and retrospective review of prior imaging study revealed asymmetric nipple enhancement on a trauma protocol CT chest acquired three years earlier. This report highlights the importance of being attentive to breast abnormalities on CT performed for indications other than breast disease and additionally focuses on the approach to address abnormal enhancement of the nipple areolar complex (NAC).

RevDate: 2020-09-05

Ramdas Y, Benn CA, Grubnik A, et al (2020)

Targeted Intraoperative Radiotherapy Is a Safe Approach for Patients with Pacemakers: A Case Study and Literature Review.

Case reports in oncology, 13(2):916-922.

Case reports detailing the effects of targeted intraoperative radiation therapy (IORT) on patients with cardiac pacemakers (PMs) are rare. This growing population sub-group requiring IORT and lack of standardized guidelines necessitate more practical published research. An 81-year-old patient with clinical stage II, T1 N0 grade III, triple-negative invasive ductal carcinoma and an implanted single-lead chamber PM (VVIR mode, model: Biotronik, type Effecta SR) received targeted intraoperative radiotherapy at the time of wide local excision and sentinel lymph node biopsy. It presents the shortest distance between the outer diameter of the PM and IORT applicator in literature. Target IORT was performed utilizing an Intrabeam device (50 kV, Carl Zeiss Surgical, Oberkochen, Germany). This case elucidates the successful use of targeted IORT for breast-conserving surgery in a patient with a single ipsilateral chamber VVIR mode PM. No device failure or malfunction was reported for the PM before, during, or after the procedure. These findings support the use of targeted IORT for patients diagnosed with early-stage breast carcinomas who have a PM implanted. However, further research is needed to understand the safety of other methods and devices for IORT patients with cardiac implantable electronic devices.

RevDate: 2020-09-05

Liu IC, Giap F, Mailhot-Vega RB, et al (2020)

Concomitant Radiation Recall Dermatitis and Organizing Pneumonia following Breast Radiotherapy: A Case Report.

Case reports in oncology, 13(2):875-882.

Purpose: Radiation recall dermatitis (RRD) is a rare complication that occurs after completion of radiation therapy (RT) and initiation of a precipitating agent, most commonly chemotherapeutic medications. Various theories attempt to explain the mechanism, including activation of the body's inflammatory pathways through nonimmune activation. Likewise, radiation-induced organizing pneumonia (RIOP) is an infrequent but potentially life-threatening complication of RT that, while not fully understood, is suspected to be partly an autoimmune reaction.

Patient: We present the case of a 71-year-old female with a history of type 2 diabetes mellitus, hypothyroidism, interstitial cystitis, and osteoarthritis who presented with clinical stage T1N0M0 ER+/PR-/HER2- invasive ductal carcinoma of the lower outer quadrant of the left breast, for which she underwent left segmental mastectomy and sentinel lymph node biopsy followed by completion axillary lymph node dissection. Her final pathologic stage was T1N1M0.

Result: The patient developed RRD and later RIOP following receipt of radiation and chemotherapy, which resolved with steroid administration.

Conclusions: The rarity of both RRD and RIOP occurring in a patient, as in our case, suggests a shared pathophysiology behind these two complications. As both reactions involve some degree of inflammation and respond to corticosteroids, it seems likely that the etiologies of RRD and RIOP lie within the inflammatory pathway. However, further investigation should evaluate the frequency, duration, and triggering of concomitant RRD and RIOP.

RevDate: 2020-09-17

Othong J, Boonmak J, Kielar F, et al (2020)

Dual Function Based on Switchable Colorimetric Luminescence for Water and Temperature Sensing in Two-Dimensional Metal-Organic Framework Nanosheets.

ACS applied materials & interfaces, 12(37):41776-41784.

A simple, rapid, highly selective, and real-time determination of water is urgently required for preventing danger from water contamination in materials. Herein, the excited-state proton transfer (ESPT) concept-based luminescent sensor [Cd2(2,5-tpt)(4,5-idc)(H2O)4] (1) (2,5-tpt = 2,5-dihydroxyterephthalic acid and 4,5-idc = 4,5-imidazoledicarboxylic acid) has been designed for discriminative detection via enol-keto tautomerism. To improve the sensitivity, two-dimensional (2D) nanosheets of 1 have been synthesized by top-down liquid ultrasonic exfoliation technology for sensing water in dimethylformamide, which lead to fast detection (<30 s), high selectivity, broad-range detection (0-50% v/v), and a low detection limit value (0.25% v/v). This sensor can serve dual sensing mechanisms along with a luminescent color change via shifted emission (green→yellow) in low water content and a turn-off method in high water content. For ease of use, the test-strip paper-based 2D nanosheets of 1 have been prepared and applied for water detection with long-term stability, pH stability, and good reusability. On-site water detection in real time can be evaluated using a smartphone color-scanning application for quantitative scanometric assays coupled with test-strip paper-based 2D nanosheets of 1. Also, 1 can be utilized for a colorimetric luminescent thermometer in the ranges of physiological and high temperature with good linearity and recyclability.

RevDate: 2020-09-02

Rohm M, S Herzig (2020)

An Antibody Attack against Body Wasting in Cancer.

Cell metabolism, 32(3):331-333.

Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben et al. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.

RevDate: 2020-09-02

Salim TR, Andrade TM, Klein CH, et al (2020)

Inequalities in Mortality Rates from Malformations of Circulatory System Between Brazilian Macroregions in Individuals Younger Than 20 Years.

Arquivos brasileiros de cardiologia pii:S0066-782X2020005010202 [Epub ahead of print].

Background Deaths from malformations of the circulatory system (MCS) have a major impact on mortality reduction. given that most cases are avoidable with correct diagnosis and treatment. Objectives To describe the distribution of mortality from MCS by sex. age. and macroregion in Brazil. in individuals under the age of 20. between 2000 and 2015. Methods A descriptive study of mortality rates and proportional mortality (PM) from MCS. other congenital malformations (OCM). circulatory system disease (CSD). ill-defined causes (IDC). and external causes (EC) in Brazil. Results There were 1.367.355 deaths from all causes in individuals younger than 20. 55.0% under 1 year of age. A total of 144.057 deaths were caused by congenital malformations. 39% of them by MCS. In both sexes. the annual mortality from MCS was 5.3/100.000. PM from MCS was 4.2%. CSD 2.2%. IDC 6.2% and EC 24.9%. Unspecified MCS showed the highest PM rates in both sexes and age groups. especially in the north and northeast regions (60%). Deaths from malformations occurred 5.7 times more frequently during the first year of life than in other ages (MCS: 5.0; OCM: 6.4). Conclusions MCS was the leading cause of death among all malformations. being twice as important as CSD. mainly under 1 year of age. The frequency of misdiagnosis of MCS as cause of death was high in all ages and both sexes. especially in the north and northeast regions. These findings highlight the need for the development of public health strategies focused on correct diagnosis and early treatment of congenital cardiopathies. leading to a reduction in mortality. (Arq Bras Cardiol. 2020; [online].ahead print. PP.0-0).

RevDate: 2020-09-01

Molocea CE, Tsokanos FF, S Herzig (2020)

Exploiting common aspects of obesity and cancer cachexia for future therapeutic strategies.

Current opinion in pharmacology, 53:101-116 pii:S1471-4892(20)30044-8 [Epub ahead of print].

Obesity and cancer cachexia are diseases at opposite ends of the BMI. However, despite the apparent dichotomy, these pathologies share some common underlying mechanisms that lead to profound metabolic perturbations. Insulin resistance, adipose tissue lipolysis, skeletal muscle atrophy and systemic inflammation are key players in both diseases. Several strategies for pharmacological treatments have been employed in obesity and cancer cachexia but demonstrated only limited effects. Therefore, there is still a need to develop novel, more effective strategies. In this review we summarize existing therapies and discuss potential novel strategies that could arise by bridging common aspects between obesity and cachexia. We discuss the potential role of macrophage manipulation and the modulation of inflammation by targeting Nuclear Receptors (NRs) as potential novel therapeutic strategies.

RevDate: 2020-09-01

Murray AS, Hyland TE, Sala-Hamrick KE, et al (2020)

The cell-surface anchored serine protease TMPRSS13 promotes breast cancer progression and resistance to chemotherapy.

Oncogene pii:10.1038/s41388-020-01436-3 [Epub ahead of print].

Breast cancer progression is accompanied by increased expression of extracellular and cell-surface proteases capable of degrading the extracellular matrix as well as cleaving and activating downstream targets. The type II transmembrane serine proteases (TTSPs) are a family of cell-surface proteases that play critical roles in numerous types of cancers. Therefore, the aim of this study was to identify novel and uncharacterized TTSPs with differential expression in breast cancer and to determine their potential roles in progression. Systematic in silico data analysis followed by immunohistochemical validation identified increased expression of the TTSP family member, TMPRSS13 (transmembrane protease, serine 13), in invasive ductal carcinoma patient tissue samples compared to normal breast tissue. To test whether loss of TMPRSS13 impacts tumor progression, TMPRSS13 was genetically ablated in the oncogene-induced transgenic MMTV-PymT tumor model. TMPRSS13 deficiency resulted in a significant decrease in overall tumor burden and growth rate, as well as a delayed formation of detectable mammary tumors, thus suggesting a causal relationship between TMPRSS13 expression and the progression of breast cancer. Complementary studies using human breast cancer cell culture models revealed that siRNA-mediated silencing of TMPRSS13 expression decreases proliferation, induces apoptosis, and attenuates invasion. Importantly, targeting TMPRSS13 expression renders aggressive triple-negative breast cancer cell lines highly responsive to chemotherapy. At the molecular level, knockdown of TMPRSS13 in breast cancer cells led to increased protein levels of the tumor-suppressive protease prostasin. TMPRSS13/prostasin co-immunoprecipitation and prostasin zymogen activation experiments identified prostasin as a potential novel target for TMPRSS13. Regulation of prostasin levels may be a mechanism that contributes to the pro-oncogenic properties of TMPRSS13 in breast cancer. TMPRSS13 represents a novel candidate for targeted therapy in combination with standard of care chemotherapy agents in patients with hormone receptor-negative breast cancer or in patients with tumors refractory to endocrine therapy.

RevDate: 2020-08-31

Feiss R, Kostrna J, Scruggs JW, et al (2020)

Effects of music tempo on perceived exertion, attention, affect, heart rate, and performance during isometric strength exercise.

Journal of sports sciences [Epub ahead of print].

This study examined the effects of slow and fast music tempi on effort-related thoughts, rating of perceived exertion (RPE), affect, heart rate, and performance during isometric strength exercises. Participants were randomly assigned to one of three conditions (no-music control, fast-tempo music, and slow-tempo music) and performed two isometric strength exercises (wall-sit and plank). RPE, attention allocation, and affect were measured during each exercise task. Participants in both the fast- and slow-tempo music conditions maintained a dissociative state for longer than those in the no-music control condition during the wall-sit exercise; however, this effect did not manifest during the plank exercise. Neither music condition influenced HR, RPE, time to volitional exhaustion, or affect. Within the first few minutes of exercise, participants exhibited an increase in HR and perceived exertion, as well as a corresponding shift towards associative attention and a high arousal state. The results are discussed with reference to potential underlying mechanisms and current theories pertaining to RPE, attention allocation, and affect.

RevDate: 2020-08-31

Miller-Ocuin JL, Howard-McNatt M, Levine EA, et al (2020)

Is Sentinel Lymph Node Biopsy Necessary for Ductal Carcinoma In Situ Patients Undergoing Mastectomy?.

The American surgeon [Epub ahead of print].

BACKGROUND: Current treatment guidelines for ductal carcinoma in situ (DCIS) treated with mastectomy recommend sentinel lymph node biopsy (SLNB). In the modern era, there is a trend toward minimizing invasive staging and treatment of the axilla. In this study, we seek to determine the role of SLNB in patients undergoing mastectomy for the treatment of DCIS.

METHODS: Patients undergoing mastectomy were identified from our institution's SLNB database from 2012 to 2016. Patients were included if core needle biopsy demonstrated DCIS. Patient demographics, tumor characteristics, and pathologic variables were abstracted.

RESULTS: Of 187 patients undergoing mastectomy with SLNB from 2012 to 2016 for DCIS or invasive ductal carcinoma, 39 (21%) were diagnosed with DCIS on core biopsy. Mean age was 57 years. 70% were Caucasian, 18% were African American, 8% were Asian, and the remaining 5% were unknown. One patient (3%) had positive nodes on SLNB and underwent axillary lymph node dissection. Of those with DCIS on core biopsy, 14 (36%) were upstaged to invasive disease on final surgical pathology, including the patient with positive SLNB. Of the remaining 25 (64%) patients with DCIS on final pathology, 0 (0%) had SLNB positivity.

CONCLUSION: Only 3% of patients with DCIS undergoing mastectomy were found to have SLN metastases. However, a significant number of patients (36%) were upstaged due to invasive cancer. Although limited by a small sample size, our results suggest that SLNB should still be recommended to patients undergoing mastectomy for DCIS on core needle biopsy due to the high rate of upstage rate to invasive disease.

RevDate: 2020-08-30

Imamura T, Yamamoto Y, Sugiura T, et al (2020)

Reconsidering the Optimal Regional Lymph Node Station According to Tumor Location for Pancreatic Cancer.

Annals of surgical oncology pii:10.1245/s10434-020-09066-5 [Epub ahead of print].

BACKGROUND: A consensus regarding the optimal extent of lymph node dissection for pancreatic cancer has not yet been achieved. The purpose of this study was to evaluate the efficacy of lymph node dissection according to the location for pancreatic cancer.

METHODS: A total of 495 patients diagnosed with invasive ductal carcinoma of the pancreas who had undergone a pancreatectomy between October 2002 and December 2015 were analyzed. The efficacy index (EI) was calculated for each lymph node station via multiplication of the frequency of metastasis to the station and the 5-year survival rate of the patients with metastasis to that station.

RESULTS: For pancreatic head (Ph) tumors, mesocolon lymph nodes had a high EI, although not regional. For pancreatic body (Pb) tumors, peri-Ph lymph nodes had a high EI, although not regional. For pancreatic tail (Pt) tumors, lymph nodes along the celiac axis and common hepatic artery had a zero EI, although regional. When the Ph was segmented into the pancreatic neck (Ph-neck), uncinate process (Ph-up), and periampullary regions, hepatoduodenal ligament lymph nodes had a zero EI for Ph-up, although regional; the mesojejunum lymph node also had a zero EI, even for Ph-up, regardless of a high incidence of metastasis. Regarding lymph node recurrence after surgery, recurrence was most frequently found at the peri-Ph lymph node (12%) in patients with Pb tumors who had undergone a distal pancreatectomy.

CONCLUSIONS: The optimal extent of lymph node dissection should be estimated in regard to the tumor location.

RevDate: 2020-09-17

Picillo M, Amboni M, Bruni A, et al (2020)

Prevalence of heterozygous mutations in Niemann-Pick type C genes in a cohort of progressive supranuclear palsy.

RevDate: 2020-08-31

Chowdhury SS, Khatun M, Khan TH, et al (2020)

Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.

Asian Pacific journal of cancer prevention : APJCP, 21(8):2265-2270.

BACKGROUND: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer.

METHODS: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software.

RESULTS: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study.

CONCLUSIONS: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.

RevDate: 2020-08-28

Weedon-Fekjær H, Li X, S Lee (2020)

Estimating the natural progression of non-invasive ductal carcinoma in situ breast cancer lesions using screening data.

Journal of medical screening [Epub ahead of print].

OBJECTIVES: In addition to invasive breast cancer, mammography screening often detects preinvasive ductal carcinoma in situ (DCIS) lesions. The natural progression of DCIS is largely unknown, leading to uncertainty regarding treatment. The natural history of invasive breast cancer has been studied using screening data. DCIS modeling is more complicated because lesions might progress to clinical DCIS, preclinical invasive cancer, or may also regress to a state undetectable by screening. We have here developed a Markov model for DCIS progression, building on the established invasive breast cancer model.

METHODS: We present formulas for the probability of DCIS detection by time since last screening under a Markov model of DCIS progression. Progression rates were estimated by maximum likelihood estimation using BreastScreen Norway data from 1995-2002 for 336,533 women (including 399 DCIS cases) aged 50-69. As DCIS incidence varies by age, county, and mammography modality (digital vs. analog film), a Poisson regression approach was used to align the input data.

RESULTS: Estimated mean sojourn time in preclinical, screening-detectable DCIS phase was 3.1 years (95% confidence interval: 1.3, 7.6) with a screening sensitivity of 60% (95% confidence interval: 32%, 93%). No DCIS was estimated to be non-progressive.

CONCLUSION: Most preclinical DCIS lesions progress or regress with a moderate sojourn time in the screening-detectable phase. While DCIS mean sojourn time could be deduced from DCIS data, any estimate of preclinical DCIS progressing to invasive breast cancer must include data on invasive cancers to avoid strong, probably unrealistic, assumptions.

RevDate: 2020-08-27

Bakhtari N, Mozdarani H, Salimi M, et al (2020)

Association study of miR-22 and miR-335 expression levels and G2 assay related inherent radiosensitivity in peripheral blood of ductal carcinoma breast cancer patients.

Neoplasma pii:200225N185 [Epub ahead of print].

Identifying patient's cellular radiosensitivity before radiotherapy (RT) in breast cancer (BC) patients allows proper alternations in routinely used treatment programs and reduces the adverse side effects in exposed patients. This study was conducted on blood samples taken from 60 women diagnosed with Invasive Ductal Carcinoma (IDC) BC (mean age: 47 ± 9.93) and 30 healthy women (mean age: 44.43 ± 6.7). The standard G2 assay was performed to predict cellular radiosensitivity. To investigate miR-22 and miR-335 expression levels in peripheral blood mononuclear cells (PBMCs), qPCR was performed. The sensitivity and specificity of the mentioned miRNAs were assessed by plotting the Receiver Operating Characteristic (ROC) curve. Binary logistic regression was performed to identify the miRNA involvement in BC and cellular radiosensitivity (CR) of BC patients. The frequency of spontaneous and radiation-induced chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.05). A cut-off value was determined to differentiate the patients with and without cellular radiosensitivity. miR-22 and miR-335 were significantly downregulated in BC patients. miRNAs expression levels were directly associated with CR. ROC curve assessment identified that both miRNAs had acceptable specificity and sensitivity in the prediction of BC and CR of BC patients. Binary logistic regression showed that both miRNAs could also predict BC successfully. Although only miR-22 was shown potent to predict CR of BC patients, both miR-22 and miR-335 might act as a tumor suppressor miRNAs in BC. miR-22 and miR-335 may be promising potential biomarkers in BC prediction along with other important biomarkers. Moreover, mir-22 might be a potential biomarker for the prediction of CR in BC patients.

RevDate: 2020-09-14
CmpDate: 2020-09-14

Li G, Yao J, Wu T, et al (2020)

Triple metachronous primary cancer of uterus, colon, and breast cancer: A case report and review of the literature.

Medicine, 99(34):e21764.

RATIONALE: Triple or more primary malignancies are rare, with only 23 previous cases including breast cancer reported in the English language studies between January 1990 and December 2019.

PATIENT CONCERNS: The patient was a 67-year-old woman with a mass in her right breast. She had a previous history of uterine and colon cancer. Both ultrasonography and mammography revealed a Breast Imaging Reporting and Data System (BI-RADS) category 3 breast lesion, in which proliferative nodules are more likely. Given her previous history of 2 malignancies, her doctors strongly recommended a biopsy.

DIAGNOSIS AND INTERVENTIONS: The biopsy pathology suggested intraductal breast cancer. Mastectomy and sentinel lymph node biopsy were performed. The postoperative pathological diagnosis was invasive ductal carcinoma, grade II, stage I. The sample was positive for estrogen receptor and progesterone receptor and negative for cerbB-2. No radiotherapy or chemotherapy was administered except for endocrine therapy. A follow-up at 19 months showed no breast recurrence or distant metastases.

OUTCOMES: No recurrence or distant metastasis occurred within the 19-month, 11-year, and 20-year follow-ups for breast, colon, and uterine cancers, respectively.

LESSONS: To our knowledge, this is the first review of triple or more primary malignancies including breast cancer. These malignancies occur predominantly in older female patients. The most prevalent tumors of triple or more primary malignancies including breast cancer occur in the colon, uterus, and lung. A favorable prognosis is associated with early-stage malignancies.

RevDate: 2020-08-26

An JK, Woo JJ, HY Kwak (2020)

The 8-Year Management of an Older Breast Cancer Patient by Non-surgical Primary Therapies and Minimized Surgery: A Case Report.

A 74-year-old woman presented with a palpable lesion in her right breast. At the time of her visit, she was taking medications for diabetes, hypertension, tremors, tinnitus, and lumbago. She was also caring for her husband, who had dementia. Imaging studies revealed another lesion in addition to the palpable mass. A core biopsy of the palpable mass confirmed invasive ductal carcinoma. Surgery was recommended to remove both masses. However, the patient refused the operation due to her comorbidities and her husband's nursing needs. A modified treatment process, including non-surgical primary therapies, minimized surgery, and close follow-up, for 8 years proved successful. This report focuses on the points to consider in the treatment and management of older patients with breast cancer.

RevDate: 2020-08-24

Tuchner T, G Gilboa-Freedman (2020)

Bullshit in a network structure: the two-sided influence of self-generated signals.

Social network analysis and mining, 10(1):65.

In today's social network age, information flowing in networks does not derive solely from external sources; people in the network also independently generate signals. These self-generated signals may not be deliberate lies, but they may not bear any relationship with the truth, either. Following the philosopher Harry G. Frankfurt, we refer to such self-generated signals as bullshit. We present an information diffusion model that allows nodes which hold no value to spread information, capturing the diffusion of bullshit information. The presence of self-generated signals (i.e., bullshit) increases the amount of information available for transmission in the network. However, participants in the spread process respond to the existence of such self-generated information by receiving data from internal sources with caution. These two contradictory forces-the increase in information transmission on the one hand, and in suspicion on the other-result in a two-sided effect of bullshit on the total spread time. We first take a numerical approach, simulating our model on Watts-Strogatz networks and building a decision tree to characterize the effects of bullshit given different network structures. We find that increasing the rate of self-generated information may have either a monotonic or non-monotonic effect on the rumor spread time, depending on the network structure and rate of non-self-generated internal communications. Then, taking an analytical approach, we analyze the spread behavior for cliques, and identify the conditions for monotonic behavior in a 2-clique network.

RevDate: 2020-09-03

Shinden Y, Saho H, Nomoto Y, et al (2020)

Breast cancer with an intraductal component that was proven genetically to be metastasis of contralateral breast cancer: a case report.

Surgical case reports, 6(1):215.

BACKGROUND: When diagnosing patients with bilateral breast cancer, it is challenging to determine the relationship between multiple breast cancer lesions at the individual patient level with certainty.

CASE PRESENTATION: A 35-year-old Japanese woman was diagnosed with a left breast cancer. She was previously diagnosed with right pT3N3M0 stage IIIC breast cancer and underwent chemotherapy with targeted therapy, radiotherapy, and endocrine therapy as adjuvant treatment after mastectomy and axillary lymph node dissection. Approximately 2 years after the first surgery, her left breast cancer was preoperatively diagnosed as a contralateral primary breast cancer, and left mastectomy and axillary lymph node dissection were performed. Histopathologically, the tumor was determined to be invasive ductal carcinoma accompanied with several intraductal components. After a second surgery, mutation analysis of her bilateral breast cancer was performed in a clinical study, which revealed that her metachronous bilateral breast tumors had the same GATA3 and CSMD1 mutations. Thus, mutation analysis strongly supported her latter left breast cancer being a metastatic lesion from the former right breast cancer. Some difficulties in diagnosing bilateral breast cancer exist when determining whether they are double primary cancers or represent contralateral breast metastasis. The existence of intraductal components is a critical piece of information for suspecting primary lesions. However, this case demonstrated that metastatic contralateral breast lesions can have intraductal components.

CONCLUSION: Herein we report a genetically proven contralateral breast metastasis with some intraductal components.

RevDate: 2020-08-26

Kozbial A, Bhandary L, SK Murthy (2019)

Effect of Monocyte Seeding Density on Dendritic Cell Generation in an Automated Perfusion-Based Culture System.

Biochemical engineering journal, 150:.

Dendritic cells (DCs) are increasingly important for research and clinical use but obtaining sufficient numbers of dendritic cells is a growing challenge. We systemically investigated the effect of monocyte (MO) seeding density on the generation of monocyte-derived immature DCs (iDCs) in MicroDEN, a perfusion-based culture system, as well as 6-well plates. Cell surface markers and the ability of the iDCs to induce proliferation of allogeneic T cells were examined. The data shows a strong relationship between iDC phenotype, specifically CD80/83/86 expression, and T cell proliferation. MicroDEN generated iDCs proved better than well plate generated iDCs at inducing T cell proliferation within the 200k-600k MO/cm2 seeding density range studied. We attribute this to perfusion in MicroDEN which supplies fresh differentiation medium continuously to the differentiating MOs while concurrently removing depleted medium and toxic byproducts of cellular respiration. MicroDEN generated fewer iDCs on a normalized basis than the well plates at lower MO seeding densities but generated equivalent numbers of iDCs at 600k MO seeding density. These results demonstrate that MicroDEN is capable of generating greater numbers of iDCs with less manual work than standard well plate culture and the MicroDEN generated iDCs have greater ability to induce T cell proliferation.

RevDate: 2020-08-24

Santos CS, Leite A, Vinhas S, et al (2020)

A combined physiological and biophysical approach to understand the ligand-dependent efficiency of 3-hydroxy-4-pyridinone Fe-chelates.

Plant direct, 4(8):e00256.

Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) class were considered eligible to formulate new Fe fertilizers for Iron Deficiency Chlorosis (IDC). Soybean (Glycine max L.) plants grown in hydroponic conditions and supplemented with Fe-chelate [Fe(mpp)3] were significantly greener, had increased biomass, and were able to translocate more iron from the roots to the shoots than those supplemented with an equal amount of the commercially available chelate [FeEDDHA]. To understand the influence of the structure of 3,4-HPO ligand on the role of the Fe-chelate to improve Fe-uptake, we investigated and report here the effect of Fe-chelates ([Fe(mpp)3], [Fe(dmpp)3], and [Fe(etpp)3]) in addressing IDC. Chlorosis development was assessed by measurement of morphological parameters, quantification of chlorophyll and Fe, and other micronutrient contents, as well as measurement of enzymatic activity (FCR) and gene expression (FRO2, IRT1, and Ferritin). All [Fe(3,4-HPO)3] chelates were able to provide Fe to plants and prevent IDC but with a different efficiency depending on the ligand. We hypothesize that this may be related with the distinct physicochemical characteristics of ligands and complexes, namely, the diverse hydrophilic-lipophilic balance of the three chelates. To test the hypothesis, we performed an EPR biophysical study using liposomes prepared from a soybean (Glycine3 max L.) lipid extract and spin probes. The results showed that the most effective chelate [Fe(mpp)3] shows a preferential location close to the surface while the others prefer the hydrophobic region inside the bilayer.

Significance statement: The 3-hydroxy-4-pyridinone Fe-chelates, [Fe(mpp)3], [Fe(dmpp)3], and [Fe(etpp)3], were all able to provide Fe to plants and prevent IDC. Efficacy is dependent on the structure of the ligand. From an EPR biophysical study using spin probes and liposomes, prepared from a soybean lipid extract, we hypothesize that this may be related with the distinct preferential location close to the surface or on the hydrophobic region of the lipid bilayer. [Fe(mpp)3] provide higher amounts of Fe in the leaves.

RevDate: 2020-09-09
CmpDate: 2020-08-31

Vaidya JS, Bulsara M, Baum M, et al (2020)

Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial.

BMJ (Clinical research ed.), 370:m2836.

OBJECTIVE: To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

DESIGN: Prospective, open label, randomised controlled clinical trial.

SETTING: 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

PARTICIPANTS: 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

INTERVENTIONS: Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).

MAIN OUTCOME MEASURES: Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.

RESULTS: Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).

CONCLUSION: For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.

TRIAL REGISTRATION: ISRCTN34086741, NCT00983684.

RevDate: 2020-08-20

Ceh SM, Annerer-Walcher S, Körner C, et al (2020)

Neurophysiological indicators of internal attention: An electroencephalography-eye-tracking coregistration study.

Brain and behavior [Epub ahead of print].

INTRODUCTION: Many goal-directed and spontaneous everyday activities (e.g., planning, mind wandering) rely on an internal focus of attention. Internally directed cognition (IDC) was shown to differ from externally directed cognition in a range of neurophysiological indicators such as electroencephalogram (EEG) alpha activity and eye behavior.

METHODS: In this EEG-eye-tracking coregistration study, we investigated effects of attention direction on EEG alpha activity and various relevant eye parameters. We used an established paradigm to manipulate internal attention demands in the visual domain within tasks by means of conditional stimulus masking.

RESULTS: Consistent with previous research, IDC involved relatively higher EEG alpha activity (lower alpha desynchronization) at posterior cortical sites. Moreover, IDC was characterized by greater pupil diameter (PD), fewer microsaccades, fixations, and saccades. These findings show that internal versus external cognition is associated with robust differences in several indicators at the neural and perceptual level. In a second line of analysis, we explored the intrinsic temporal covariation between EEG alpha activity and eye parameters during rest. This analysis revealed a positive correlation of EEG alpha power with PD especially in bilateral parieto-occipital regions.

CONCLUSION: Together, these findings suggest that EEG alpha activity and PD represent time-sensitive indicators of internal attention demands, which may be involved in a neurophysiological gating mechanism serving to shield internal cognition from irrelevant sensory information.

RevDate: 2020-09-01

Wong HC, Wang Q, Speller EM, et al (2020)

Photoswitchable Solubility of Fullerene-Doped Polymer Thin Films.

ACS nano [Epub ahead of print].

Controlling polymer film solubility is of fundamental and practical interest and is typically achieved by synthetically modifying the polymer structure to insert reactive groups. Here, we demonstrate that the addition of fullerenes or its derivatives (C60 or phenyl-C61-butyric acid methyl ester, PCBM) to polymers, followed by ultraviolet (UV) illumination can change the film solubility. Contrary to most synthetic polymers, which dissolve in organic solvents but not in water, the fullerene-doped polymer films (such as polystyrene) can dissolve in water yet remain stable in organic solvents. This photoswitchable solubility effect is not observed in either film constituents individually and is derived from a synergy of photochemistries. First, polymer photooxidation generates macroradicals which cross-link with radical-scavenging PCBM, thereby contributing to the films' insolubility in organic solvents. Second, light exposure enhances polymer photooxidation in the presence of PCBM via the singlet oxygen pathway. This results in polymer backbone scission and formation of photooxidized products which can form hydrogen bonds with water, both contributing to water solubility. Nevertheless, the illuminated doped polymer thin films are mechanically robust, exhibiting significantly increased modulus and density compared to their pristine counterpart, such that they can remain intact even upon sonication in conventional organic solvents. We further demonstrate the application of this solubility-switching effect in dual tone photolithography, via a facile, economical, and environmentally benign solution-processing route made possible by the photoactive nature of polymer-PCBM thin films.

RevDate: 2020-08-20

van der Slot MA, Hollemans E, den Bakker MA, et al (2020)

Inter-observer variability of cribriform architecture and percent Gleason pattern 4 in prostate cancer: relation to clinical outcome.

Virchows Archiv : an international journal of pathology pii:10.1007/s00428-020-02902-9 [Epub ahead of print].

The Grade group is an important parameter for clinical decision-making in prostate cancer. Recently, percent Gleason pattern 4 and presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) have been recognized for their independent predictive value for prostate cancer outcome. There is sparse data on the inter-observer agreement for these pathologic features in practice. Our objectives were to investigate inter-observer variability of percent Gleason pattern and CR/IDC and to relate individual tumour scores to clinical outcome. Our cohort included 80 consecutive radical prostatectomies with a median follow-up 87.1 months (interquartile range 43.3-119.2), of which the slide with largest tumour volume was scored by six pathologists for Grade group (four tiers: 1, 2, 3 and 4/5), percent Gleason pattern 4 (four tiers: 0-25%, 26-50%, 51-75% and 76-100%) and presence of CR/IDC (two tiers: absent, present). The individual assignments were related to post-operative biochemical recurrence (20/80). Inter-observer agreement was substantial (Krippendorff's α 0.626) for assessment of Grade group and moderate for CR/IDC (α 0.507) and percent Gleason pattern 4 (α 0.551). For each individual pathologist, biochemical recurrence rates incremented by Grade group and presence of CR/IDC, although such relation was less clear for percent Gleason pattern 4. In conclusion, inter-observer agreement for CR/IDC and percent Gleason pattern 4 is lower than for Grade groups, indicating awareness of these features needs further improvement. Grade group and CR/IDC, but not percent Gleason pattern 4 was related to biochemical recurrence for each pathologist, indicating overall validity of individual grade assignments despite inter-observer variability.

RevDate: 2020-08-19

Zhao H (2020)

The prognosis of invasive ductal carcinoma, lobular carcinoma and mixed ductal and lobular carcinoma according to molecular subtypes of the breast.

Breast cancer (Tokyo, Japan) pii:10.1007/s12282-020-01146-4 [Epub ahead of print].

BACKGROUND: To investigate the prognosis of females with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed invasive ductal and lobular carcinoma (IDLC) according to hormone receptor (HR) and HER2 status.

METHODS: Data of 171,881 patients from the SEER database were analyzed. Propensity score matching was used to balance the covariates. Breast cancer-specific survival (BCSS) and overall survival (OS) of IDC, ILC, and IDLC were investigated.

RESULTS: Patients with ILC were older, had lower tumor grade, higher tumor stage, larger tumor size, more nodal metastasis, higher estrogen receptor(+), lower HER2(-), and less likely to receive partial mastectomy and chemotherapy compared with IDC and IDLC. ILC and IDLC showed better prognosis than IDC after matching by Kaplan-Meier curves. Multivariate Cox regression showed better OS of ILC and IDLC compared with IDC with hazard ratio and a 95% confidence interval of 0.84 (0.77-0.90) and 0.91 (0.83-1.00), respectively. For HR(+)HER2(-) subgroup, ILC showed better OS than IDC; IDC showed worse BCSS and OS than IDLC. For HR(+)HER2(+); ILC showed better OS compared with IDLC; there were no survival differences of IDC, ILC, and IDLC for HER2(+). For HR(-)HER2(-), ILC and IDC showed better BCSS and OS compared with IDLC by multivariate analysis.

CONCLUSIONS: The prognoses of female patients with IDC, ILC or IDLC were associated with the molecular subtypes of breast carcinoma. Management decisions should be based on pathological types and molecular subtypes.

RevDate: 2020-08-25

Chao X, Liu L, Sun P, et al (2020)

Immune parameters associated with survival in metaplastic breast cancer.

Breast cancer research : BCR, 22(1):92.

BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare histological type of breast cancer, which commonly shows resistance to standard therapies and is associated with poor prognosis. The immune microenvironment in MBC and its significance has not been well established due to its low incurrence rate and complex components. We aimed to investigate the diversity of immune parameters including subsets of TILs and PDL1/PD1 expression in MBC, as well as its correlation with prognosis.

METHODS: A total of 60 patients diagnosed with MBC from January 2006 to December 2017 were included in our study. The percentage (%) and quantification (per mm2) of TILs and presence of tertiary lymphoid structures (TLS) were evaluated by hematoxylin and eosin staining (HE). The quantification of CD4+, CD8+ TILs (per mm2), and PD-1/PDL1 expression were evaluated through immunohistochemistry and analyzed in relation to clinicopathological characteristics. A ≥ 1% membranous or cytoplasmatic expression of PD1 and PDL1 was considered a positive expression.

RESULTS: We found squamous cell carcinoma MBC (33/60, 55%) exhibiting most TILs of all the MBC subtypes (p = 0.043). Thirty-three of 60 (50%) of the patients had coexisting invasive ductal carcinoma of no special type (IDC-NST), and the average percentage of TILs in MBC components was lower compared with NST components (p < 0.001). Thirty (50%) patients exhibited positive (≥ 1%) PDL1 expression in their tumor cells, while 36 (60%) had positive (≥ 1%) PDL1 expression in their TILs. Twenty-seven (45%) of all the patients had positive (≥ 1%) PD1 expression in their tumor cells and 33 (55%) had PD1-positive (≥ 1%) stromal TILs. More CD8+ TILs were associated with positive PDL1 expression of tumor cells as well as positive PD1 expression in stromal cells. Greater number of stromal TILS (> 300/mm2, 20%), CD4+ TILs (> 250/mm2), and CD8+ TILs (> 70/mm2) in MBC were found associated with longer disease-free survival. Positive expression of PDL1 in tumor cells (≥ 1%) and PD1 in stromal cells (≥ 1%) were also associated with longer survival.

CONCLUSIONS: The immune characteristics differ in various subtypes as well as components of MBC. Immune parameters are key predictive factors of MBC and provide the clinical significance of applying immune checkpoint therapies in patients with MBC.

RevDate: 2020-09-01

Makary J, Phan K, McClintock G, et al (2020)

Bladder infusion versus standard catheter removal for trial of void: a systematic review and meta-analysis.

World journal of urology pii:10.1007/s00345-020-03408-4 [Epub ahead of print].

PURPOSE: To compare the efficacy and time-to-discharge of two methods of trial of void (TOV): bladder infusion versus standard catheter removal.

METHODS: Electronic searches for randomized controlled trials (RCTs) comparing bladder infusion versus standard catheter removal were performed using multiple electronic databases from dates of inception to June 2020. Participants underwent TOV after acute urinary retention or postoperatively after intraoperative indwelling catheter (IDC) placement. Quality assessment and meta-analyses were performed, with odds ratio and mean time difference used as the outcome measures.

RESULTS: Eight studies, comprising 977 patients, were included in the final analysis. Pooled meta-analysis demonstrated that successful TOV was significantly higher in the bladder infusion group compared to standard TOV (OR 2.41, 95% CI 1.53-3.8, p = 0.0005), without significant heterogeneity (I2=19%). The bladder infusion group had a significantly shorter time-to-decision in comparison to standard TOV (weighted mean difference (WMD)-148.96 min, 95% CI - 242.29, - 55.63, p = 0.002) and shorter time-to-discharge (WMD - 89.68 min, 95% CI - 160.55, - 18.88, p = 0.01). There was no significant difference in complication rates between the two groups.

CONCLUSION: The bladder infusion technique of TOV may be associated with a significantly increased likelihood of successful TOV and reduced time to discharge compared to standard TOV practices.

RevDate: 2020-09-15

Grosset AA, Dallaire F, Nguyen T, et al (2020)

Identification of intraductal carcinoma of the prostate on tissue specimens using Raman micro-spectroscopy: A diagnostic accuracy case-control study with multicohort validation.

PLoS medicine, 17(8):e1003281.

BACKGROUND: Prostate cancer (PC) is the most frequently diagnosed cancer in North American men. Pathologists are in critical need of accurate biomarkers to characterize PC, particularly to confirm the presence of intraductal carcinoma of the prostate (IDC-P), an aggressive histopathological variant for which therapeutic options are now available. Our aim was to identify IDC-P with Raman micro-spectroscopy (RμS) and machine learning technology following a protocol suitable for routine clinical histopathology laboratories.

METHODS AND FINDINGS: We used RμS to differentiate IDC-P from PC, as well as PC and IDC-P from benign tissue on formalin-fixed paraffin-embedded first-line radical prostatectomy specimens (embedded in tissue microarrays [TMAs]) from 483 patients treated in 3 Canadian institutions between 1993 and 2013. The main measures were the presence or absence of IDC-P and of PC, regardless of the clinical outcomes. The median age at radical prostatectomy was 62 years. Most of the specimens from the first cohort (Centre hospitalier de l'Université de Montréal) were of Gleason score 3 + 3 = 6 (51%) while most of the specimens from the 2 other cohorts (University Health Network and Centre hospitalier universitaire de Québec-Université Laval) were of Gleason score 3 + 4 = 7 (51% and 52%, respectively). Most of the 483 patients were pT2 stage (44%-69%), and pT3a (22%-49%) was more frequent than pT3b (9%-12%). To investigate the prostate tissue of each patient, 2 consecutive sections of each TMA block were cut. The first section was transferred onto a glass slide to perform immunohistochemistry with H&E counterstaining for cell identification. The second section was placed on an aluminum slide, dewaxed, and then used to acquire an average of 7 Raman spectra per specimen (between 4 and 24 Raman spectra, 4 acquisitions/TMA core). Raman spectra of each cell type were then analyzed to retrieve tissue-specific molecular information and to generate classification models using machine learning technology. Models were trained and cross-validated using data from 1 institution. Accuracy, sensitivity, and specificity were 87% ± 5%, 86% ± 6%, and 89% ± 8%, respectively, to differentiate PC from benign tissue, and 95% ± 2%, 96% ± 4%, and 94% ± 2%, respectively, to differentiate IDC-P from PC. The trained models were then tested on Raman spectra from 2 independent institutions, reaching accuracies, sensitivities, and specificities of 84% and 86%, 84% and 87%, and 81% and 82%, respectively, to diagnose PC, and of 85% and 91%, 85% and 88%, and 86% and 93%, respectively, for the identification of IDC-P. IDC-P could further be differentiated from high-grade prostatic intraepithelial neoplasia (HGPIN), a pre-malignant intraductal proliferation that can be mistaken as IDC-P, with accuracies, sensitivities, and specificities > 95% in both training and testing cohorts. As we used stringent criteria to diagnose IDC-P, the main limitation of our study is the exclusion of borderline, difficult-to-classify lesions from our datasets.

CONCLUSIONS: In this study, we developed classification models for the analysis of RμS data to differentiate IDC-P, PC, and benign tissue, including HGPIN. RμS could be a next-generation histopathological technique used to reinforce the identification of high-risk PC patients and lead to more precise diagnosis of IDC-P.

RevDate: 2020-09-18

Fleury EFC, K Marcomini (2020)

Impact of radiomics on the breast ultrasound radiologist's clinical practice: From lumpologist to data wrangler.

European journal of radiology, 131:109197 pii:S0720-048X(20)30386-7 [Epub ahead of print].

OBJECTIVE: The study aims to assess the impact of radiomics in the clinical practice of breast ultrasound, to determine which lesions are undetermined by the software, and to discuss the future of the radiologist's role.

METHODS: Consecutive analyses of 207 ultrasound masses from January 2018 to April 2019 referred for percutaneous breast biopsy. Breast masses were classified using dedicated ultrasound software (AI). The AI software automatically classified the masses on a scale of 0-100, where 100 is the most suspicious. We adopt the histology results as the gold standard. The cut-off point of malignancy by radiomics was determined, with ±10 % of margin error according to the Youden's index. We considered these lesions as undetermined masses. The performance of the AI software and the radiologist classification was compared using the area under roc curves (AUROC). We also discuss the impact of radiologist validation of AI results, especially in undetermined lesions.

RESULTS: Of the 207 evaluated masses, 143 were benign, and 64 were malignant. The Youden's index was 0.516, including undetermined masses with a varied range of 10 % (0.464-0.567). Twenty-one (14.58 %) benign and twelve (19.05 %) malignant masses were in this range. The best accuracy performance to classify masses was the combination of the reader and AI (0.829). The most common undetermined masses in AI were fibroadenoma, followed by phyllodes tumor, steatonecrosis as benign. Whereas, low-grade, and high-grade invasive ductal carcinoma represents the malignant lesions.

CONCLUSIONS: Artificial Intelligence has a reliable performance in ultrasound breast masses classification. Radiologist validation is critical to determine the final BI-RADS assessment, especially in undetermined masses to obtain the best classification performance.

RevDate: 2020-08-18

Chikkannaiah P, Thangngeo D, Guruprasad C, et al (2020)

Clinicopathological Study of Mucinous Carcinoma of Breast with Emphasis on Cytological Features: A Study at Tertiary Care Teaching Hospital of South India.

Journal of laboratory physicians, 12(1):68-75.

Introduction Mucinous carcinoma (MC) is a rare form of breast cancer. It accounts for 1 to 7% of the cases and characterized by the presence of extracellular mucin (ECM). Depending on the amount of mucin, it is classified into pure mucinous carcinoma (> 90%, PMC) and mixed mucinous carcinoma (MMC; < 90%). In comparison to most common subtypes, MC is having better prognosis. There exist clinicopathological differences among PMC and MMC and also MC and IDC-NOS. Materials and Methods MCs diagnosed between January 2012 and December 2017 were included. Fine needle aspiration cytology smears were screened for cellularity, ECM, nuclear pleomorphism, signet ring cells (SRC), mucinophages, and myxovascular fragments (MVF). Histopathology slides were screened to confirm the diagnosis. Immunohistochemistry slides were graded as per the standard protocol. Statistical analyses were performed by SPSS software. Results In the present study, MC constituted 3.3%. The mean age of the patients was 50.9 years. ECM, mucinophages, and SRC were the key diagnostic cytological features. The PMC and MMC were clinicopathologically distinct with respect to gross findings and lymph node status. MMCs were highly proliferative. The mean duration of follow-up was 24.5 months. Complications were more common in MMC than PMC. Lymph node involvement is the key prognostic factor and it is independent of other prognostic factors like age, size, and hormonal receptor status. Conclusion PMC are rare subtype of breast cancer. The diagnostic cytological features are ECM, MVF, and SRC. MMC and PMC are clinicopathologically and genetically distinct.

RevDate: 2020-09-11

Rais S, Islam A, Ahmad I, et al (2021)

Preparation of a new magnetic ion-imprinted polymer and optimization using Box-Behnken design for selective removal and determination of Cu(II) in food and wastewater samples.

Food chemistry, 334:127563.

A new magnetic Cu(II) IIP (Fe3O4@IIP-IDC) is synthesized by polymerization of Imidazole-4,5-dicarboxylic acid functionalized Allyl chloride, and significant improvement of its performance has been compared. SPE parameters were optimized using Box-Behnken design to achieve the twin objectives of quantitative determination and removal of Cu(II). FLPSO kinetic model and BS isotherm model fits well with the capacity of 175 mg g-1. Analytical figures of merit includes a linearity range of 10-5,000 µg L-1 (R2 = 0.9986), preconcentration factor of 50 after eluting with 5 mL of 1 M HNO3, LOD of 1.03 µg L-1 and LOQ of 4.5 µg L-1. Accuracy was assessed by analysis of SRM (Standard Reference Material) and recovery experiments after spiking in food samples (Tea, coffee, chocolate, spinach, infant milk substitute) and battery wastewater. Ease of use, reusability (15 cycles), rapid adsorption and high selectivity makes it a promising candidate for efficient and selective removal and trace determination.

RevDate: 2020-08-13

Shuman E, Saguy T, van Zomeren M, et al (2020)

Disrupting the system constructively: Testing the effectiveness of nonnormative nonviolent collective action.

Journal of personality and social psychology pii:2020-59637-001 [Epub ahead of print].

Collective action research tends to focus on motivations of the disadvantaged group, rather than on which tactics are effective at driving the advantaged group to make concessions to the disadvantaged. We focused on the potential of nonnormative nonviolent action as a tactic to generate support for concessions among advantaged group members who are resistant to social change. We propose that this tactic, relative to normative nonviolent and to violent action, is particularly effective because it reflects constructive disruption: a delicate balance between disruption (which can put pressure on the advantaged group to respond) and perceived constructive intentions (which can help ensure that the response to action is a conciliatory one). We test these hypotheses across 4 contexts (total N = 3650). Studies 1-3 demonstrate that nonnormative nonviolent action (compared with inaction, normative nonviolent action, and violent action) is uniquely effective at increasing support for concessions to the disadvantaged among resistant advantaged group members (compared with advantaged group members more open to social change). Study 3 shows that constructive disruption mediates this effect. Study 4 shows that perceiving a real-world ongoing protest as constructively disruptive predicts support for the disadvantaged, whereas Study 5 examines these processes longitudinally over 2 months in the context of an ongoing social movement. Taken together, we show that nonnormative nonviolent action can be an effective tactic for generating support for concessions to the disadvantaged among those who are most resistant because it generates constructive disruption. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

RevDate: 2020-08-13

Wakefield B, Diko S, Gilmer R, et al (2020)

Accuracy of obstetric laceration diagnoses in the electronic medical record.

International urogynecology journal pii:10.1007/s00192-020-04450-x [Epub ahead of print].

INTRODUCTION AND HYPOTHESIS: Patient safety data including rates of obstetric anal sphincter injury (OASI) are often derived from hospital discharge codes. With the transition to electronic medical records (EMRs), we hypothesized that electronic provider-entered delivery data would more accurately document obstetric perineal injury than traditional billing/diagnostic codes.

METHODS: We evaluated the accuracy of perineal laceration diagnoses after singleton vaginal deliveries during one calendar year at an American tertiary academic medical center. We reviewed the entire hospital chart to determine the most likely laceration diagnosis and compared that expert review diagnosis (ExpRD) with documentation in the EMR delivery summary (EDS) and ICD-9 diagnostic codes (IDCs).

RESULTS: We retrospectively selected 354 total delivery records. OASI complicated 56 of those. 303 records (86%) were coded identically by the EDS and IDCs. Diagnoses from the IDCs and the EDS were mostly correct compared with ExpRD (sensitivity = 96%, specificity = 100%). There was no systematic over- or under-diagnosis of OASI for either the EDS (p = 0.070) or the IDCs (p = 0.447). When considering all laceration types the EDS was correct for 21 (5.9%) lacerations that were incorrect according to the IDCs. Overall, the EDS was more accurate (p < 0.05) owing to errors in IDC minor laceration diagnoses.

CONCLUSIONS: Electronic medical record delivery summary data and EMR-derived diagnostic codes similarly characterize OASI. The EDS does not improve OASI reporting, but may be more accurate when considering all perineal lacerations. This assumes that providers have correctly identified and categorized the lacerations that they record in the EMR.

RevDate: 2020-08-22

Cochrane E, Kim S, Kudelka A, et al (2020)

Invasive ductal breast carcinoma metastasis to the cervix: A case review and clinical correlation.

Gynecologic oncology reports, 33:100616.

•Metastatic invasive ductal carcinoma.•IDC metastasis to cervix.•Unusual metastasis to cervix.

RevDate: 2020-09-14

Habrawi Z, Melkus MW, Khan S, et al (2020)

Cryoablation: A promising non-operative therapy for low-risk breast cancer.

American journal of surgery pii:S0002-9610(20)30482-7 [Epub ahead of print].

BACKGROUND: The aim of this study was to evaluate the feasibility of cryoablation for early-stage low-risk breast cancer without tumor resection.

METHODS: Women diagnosed with ER+, PR+, and HER2-infiltrating ductal carcinomas ≤1.5 cm were treated with cryoablation. The non-surgical procedure used a Visica® 2 Treatment System with ultrasound guidance for ablation of the tumor with a 1 cm margin. Patients were monitored at 6-month intervals by MRI, mammogram, and ultrasound.

RESULTS: Twelve patients with unifocal breast cancer were treated with cryoablation for local control without follow-up tumor resection. All patients received adjuvant endocrine therapy, and none had radiation. The median follow-up was 28.5 (range = 4-41) months with 11 patients having at least one six-month follow-up. All imaging modalities showed complete ablation of target zone 11/11 (100%). Four patients (33.3%) have been followed up for ≥ 2 years with no local failure or residual disease.

CONCLUSION: Cryoablation of early-stage low-risk (ER+, PR+, and HER2-) breast cancer is a safe alternative to surgery.

RevDate: 2020-08-18

Yoon GY, Choi WJ, Cha JH, et al (2020)

The role of MRI and clinicopathologic features in predicting the invasive component of biopsy-confirmed ductal carcinoma in situ.

BMC medical imaging, 20(1):95.

BACKGROUND: The upgrade rate of biopsy-confirmed ductal carcinoma in situ (DCIS) to invasive carcinoma is up to 50% on final pathology. We investigated MRI and clinicopathologic predictors of the invasive components of DCIS diagnosed by preoperative biopsy and then compared MRI features between patients with DCIS, microinvasive ductal carcinoma (mIDC), and invasive ductal carcinoma (IDC) diagnosed on final pathology.

METHODS: Two hundred and one patients with 206 biopsy-confirmed DCIS lesions were enrolled. MRI and clinicopathologic features were used to predict either mIDC or IDC via a cumulative logistic regression analysis. For the lesions detected on MRI, morphologic and kinetic analyses were performed using the Chi-square, Fisher's exact, and Kruskal-Wallis tests.

RESULTS: Of all the lesions, 112 (54.4%) were diagnosed as DCIS, 50 (24.3%) were upgraded to mIDC, and 44 (21.4%) to IDC. The detection on MRI as mass (Odds ratio (OR) = 8.84, 95% confidence interval (CI) = 1.05-74.04, P = 0.045) or non-mass enhancement (NME; OR = 11.17, 95% CI = 1.35-92.36, P = 0.025), negative progesterone receptor (PR; OR = 2.40, 95% CI = 1.29-4.44, P = 0.006), and high Ki-67 level (OR = 2.42, 95% CI = 1.30-4.50, P = 0.005) were significant independent predictors of histologic upgrade. On MRI, 87 (42.2%) lesions appeared as mass and 107 (51.9%) as NME. Irregularly shaped, not-circumscribed, heterogeneous, or rim-enhancing masses with intratumoral high signal intensity or peritumoral edema, clumped or clustered ring-enhancing NMEs, and high peak enhancement were significantly associated with histologic upgrade (P < 0.001).

CONCLUSION: MRI detection, negative PR, and high Ki-67 levels are associated with a histologic upgrade in patients with biopsy-confirmed DCIS. Suspicious MRI features are more frequent in such patients.

RevDate: 2020-08-13

Souza TO, Souza ER, LW Pinto (2020)

Analysis of the correlation of socioeconomic, sanitary, and demographic factors with homicide deaths - Bahia, Brazil, 2013-2015.

Revista brasileira de enfermagem, 73(6):e20190346.

OBJECTIVE: To analyze the correlation of socioeconomic, sanitary, and demographic factors with homicides in Bahia, from 2013 to 2015.

METHODS: Ecological study, using data from the Information System on Mortality and from the Superintendence of Economic and Social Studies. The depending variable is the corrected homicide rate. Explanatory variables were categorized in four axes. Simple and multiple negative binomial regression models were used.

RESULTS: Positive associations were found between homicides and the Index of Economy and Finances (IEF), the Human Development Index, the Gini Index, population density, and legal intervention death rates (LIDR). The variables Index of Education Levels (IEL), rates of death with undetermined intentions (RDUI), and the proportion of ill-defined causes (IDC) presented a negative association with the homicide rates.

CONCLUSION: The specific features of the context of each community, in addition to broader socioeconomic municipal factors, directly interfere in life conditions and increase the risk of dying by homicide.

RevDate: 2020-09-07

Domínguez-de-la-Cruz E, Muñoz ML, Pérez-Muñoz A, et al (2020)

Reduced mitochondrial DNA copy number is associated with the haplogroup, and some clinical features of breast cancer in Mexican patients.

Gene, 761:145047.

Mitochondrial DNA (mtDNA) copy number and mitochondrial DNA haplogroups have been associated with different types of cancer, including breast cancer, because they alter cellular energy metabolism. However, whether mtDNA copy number or haplogroups are predictors of oxidative stress-related risks in human breast cancer tissue in Mexican patients remains to be determined. Using quantitative real-time PCR assays and sequencing of the mtDNA hypervariable region, analysis of mtDNA copy numbers in 82 breast cancer tissues (BCT) and matched normal adjacent tissues (NAT) was performed to determine if copy number correlated with clinical features and Amerindian haplogroups (A2, B2, B4, C1 and D1) . The results showed that the mtDNA copy number was significantly decreased in BCT compared with NAT (p = 0.010); it was significantly decreased in BCT and NAT in women > 50 years of age, compared with NAT in women < 50 years of age (p = 0.032 and p = 0.037, respectively); it was significantly decreased in NAT and BCT in the postmenopausal group and in BCT in the premenopausal group compared with NAT in the premenopausal group (p = 0.011, p = 0.010 and, p = 0.018; respectively); and it was also significantly decrease in members of the BCT group classified as having invasive ductal carcinoma I-III (IDC-I, IDC-II and IDC-III) and IDC-II for NAT compared to IDC-I of NAT (p = 0.025, p = 0.022 and p = 0.031 and p = 0.020; respectively). The mtDNA copy number for BCT from patients with haplogroup B2 was decreased compared to patients with haplogroup D1 (p = 0.01); for BCT from patients with haplogroup C1 was also decreased compare with their NAT counterpart (p = 0.006) and with BCT patients belonging to haplogroups A2 and D1 (p = 0.01 and p = 0.03; respectively). In addition, the mtDNA copy number was decrease in the sequences with three deletions relative to the rCRS at nucleotide positions A249del, A290del and A291del, or C16327T polymorphism with the same p = 0.019 for all four variants. Contrary, the copy number increased in sequences containing C16111T, G16319A or T16362C polymorphisms (p = 0.021, =0.048, and = 0.001; respectively). In conclusion, a decrease in the copy number of mtDNA in BCT compared with NAT was shown by the results, which suggests an imbalance in oxidative phosphorylation (OXPHOS) that can affect the apoptosis pathway and cancer progression. It was also observed an increase of the copy number in samples with specific polymorphisms, which may be a good sign of favourable prognosis.

RevDate: 2020-08-14

Chen ML, Ma ZS, Cao FL, et al (2020)

Retroperitoneal metastasis synchronous with brain and mediastinal lymph nodes metastasis from breast invasive ductal carcinoma as the first site of distant metastasis: a case report and review of literature.

International journal of clinical and experimental pathology, 13(7):1693-1697.

Breast carcinoma retroperitoneal metastasis is rare. The clinical symptoms of this disease are always non-specific. Laboratory tests are not always helpful for diagnosis and evaluation. We reported a case of a 52 year old Chinese patient who was diagnosed with retroperitoneal metastasis from breast invasive ductal carcinoma as the first site of distant metastasis synchronous with brain and mediastinal lymph nodes metastasis 4 years after modified radical mastectomy. Second-line chemotherapy of docetaxel and capecitabine was recommended. The response evaluation every two to three months was good. Unfortunately, the metastasis in the brain advanced. The patient was transferred to a radiotherapy department to receive radiotherapy and died 10 months later. We also review the related literature.

RevDate: 2020-08-14

Zhao J, Liu J, Wu N, et al (2020)

ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer.

Oncology letters, 20(3):2499-2505.

The aim of the present study was to analyze the expression levels of angiopoietin-like 4 (ANGPTL4) in breast cancer to investigate the association between ANGPTL4 and breast cancer. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tissues, including 205 invasive ductal carcinoma (IDC) of no special type, 40 normal breast, 40 atypical ductal hyperplasia (ADH) and 40 ductal carcinomas in situ (DCIS) tissues. The non-parametric Kruskal-Wallis test was used to evaluate the differential expression of ANGPTL4 and clinicopathological parameters in breast cancer. Kaplan-Meier analysis and Cox regression analysis were used to evaluate the association between the expression levels of ANGPTL4 and the prognosis of breast cancer. The results revealed that ANGPTL4 expression was higher in IDC (63.4%; 130/205) compared with in normal breast tissues (17.5%; 7/40), ADH (30%; 12/40) and DCIS (37.5%; 15/40). The clinical significance of ANGPTL4 expression was analyzed in a total of 205 IDC tissues, and high expression levels of ANGPTL4 were positively associated with pathological stage (P<0.001), tumor size (P<0.001), histological grade (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P<0.001) and local recurrence (P<0.001). Kaplan-Meier analysis revealed that patients with high ANGPTL4 expression had a shorter overall survival (OS; P<0.001) and disease-free survival (DFS; P<0.001) compared with patients with low ANGPTL4 expression. Multivariate Cox regression analysis revealed that ANGPTL4 was an independent prognostic factor for breast cancer OS (P=0.034) and DFS (P=0.011). The results of the present study demonstrated that ANGPLT4 was associated with malignant progression and poor prognosis of breast cancer, suggesting that ANGPLT4 may be a novel therapeutic target for breast cancer.

RevDate: 2020-08-22

Kurozumi S, Alsaleem M, Monteiro CJ, et al (2020)

Targetable ERBB2 mutation status is an independent marker of adverse prognosis in estrogen receptor positive, ERBB2 non-amplified primary lobular breast carcinoma: a retrospective in silico analysis of public datasets.

Breast cancer research : BCR, 22(1):85.

BACKGROUND: Invasive lobular carcinoma (ILC) accounts for 10-15% of primary breast cancers and is typically estrogen receptor alpha positive (ER+) and ERBB2 non-amplified. Somatic mutations in ERBB2/3 are emerging as a tractable mechanism underlying enhanced human epidermal growth factor 2 (HER2) activity. We tested the hypothesis that therapeutically targetable ERBB2/3 mutations in primary ILC of the breast associate with poor survival outcome in large public datasets.

METHODS: We performed in silico comparison of ERBB2 non-amplified cases of ER+ stage I-III primary ILC (N = 279) and invasive ductal carcinoma (IDC, N = 1301) using METABRIC, TCGA, and MSK-IMPACT information. Activating mutations amenable to HER2-directed therapy with neratinib were identified using existing functional data from in vitro cell line and xenograft experiments. Multivariate analysis of 10-year overall survival (OS) with tumor size, grade, and lymph node status was performed using a Cox regression model. Differential gene expression analyses by ERBB2 mutation and amplification status was performed using weighted average differences and an in silico model of response to neratinib derived from breast cancer cell lines.

RESULTS: ILC tumors comprised 17.7% of all cases in the dataset but accounted for 47.1% of ERBB2-mutated cases. Mutations in ERBB2 were enriched in ILC vs. IDC cases (5.7%, N = 16 vs. 1.4%, N = 18, p < 0.0001) and clustered in the tyrosine kinase domain of HER2. ERBB3 mutations were not enriched in ILC (1.1%, N = 3 vs. 1.8%, N = 23; p = 0.604). Median OS for patients with ERBB2-mutant ILC tumors was 66 months vs. 211 months for ERBB2 wild-type (p = 0.0001), and 159 vs. 166 months (p = 0.733) for IDC tumors. Targetable ERBB2 mutational status was an independent prognostic marker of 10-year OS-but only in ILC (hazard ratio, HR = 3.7, 95% CI 1.2-11.0; p = 0.021). Findings were validated using a novel ERBB2 mutation gene enrichment score (HR for 10-year OS in ILC = 2.3, 95% CI 1.04-5.05; p = 0.040).

CONCLUSIONS: Targetable ERBB2 mutations are enriched in primary ILC and their detection represents an actionable strategy with the potential to improve patient outcomes. Biomarker-led clinical trials of adjuvant HER-targeted therapy are warranted for patients with ERBB2-mutated primary ILC.

RevDate: 2020-09-20

Lu K, Wang X, Zhang W, et al (2020)

Clinicopathological and genomic features of breast mucinous carcinoma.

Breast (Edinburgh, Scotland), 53:130-137.

INTRODUCTION: Mucinous carcinoma (MC) of the breast is a special histological type of breast cancer. Clinicopathological characteristics and genomic features of MC is not fully understood.

MATERIALS AND METHODS: 186,497 primary breast cancer patients from SEER database diagnosed with invasive ductal carcinoma (IDC) or MC were included. 801 primary IDC or MC patients from TCGA cohort were included for transcriptomic and genomic analysis.

RESULTS: MC patients were older, had lower tumor grade and T and N stage, higher hormone receptor positive proportions and lower HER2 positive proportions than IDC patients. Kaplan-Meier plots showed that the breast cancer-specific survival (BCSS) of MC patients was significantly better than IDC patients (P < 0.001). However, after adjusting for clinicopathological factors, survival advantage of MC disappeared. In terms of genomic features of MC, representative upregulated genes of MC in transcriptomic level were MUC2, TFF1 and CARTPT. Upregulated pathways of MC included neurotransmitter-related pathways. Moreover, MC was featured by the amplification of 6p25.2, 6q12 and 11q12.3.

CONCLUSION: MC is a distinct histological subtype compared with IDC in terms of clinicopathological characteristics and genomic features. Further investigation need to be conducted to explore the formation of this specific histological subtype.

RevDate: 2020-09-15

Chi W, Qiao Q, Wang C, et al (2020)

Descriptor ΔGC-O Enables the Quantitative Design of Spontaneously Blinking Rhodamines for Live-Cell Super-Resolution Imaging.

Angewandte Chemie (International ed. in English) [Epub ahead of print].

Herein, we reported a simple, fast, and quantitative theoretical descriptor ΔGC-O that allows accurate predictions of a wide range of spontaneously blinking rhodamines. ΔGC-O denotes the Gibbs free energy differences between the closed and open forms of rhodamines and has a good linear relationship with experimental pKcycl values. This correlation affords an effective guide for the quantitative designs of spontaneously blinking rhodamines and eliminates trial-and-error. We have validated the predictive power of ΔGC-O via the development of two spontaneously blinking rhodamines of different colors and enhanced brightness. We also demonstrated their super-resolution imaging utilities in dynamic live-cell imaging. We expect that ΔGC-O will greatly facilitate the efficient creations of spontaneously blinking fluorophores and aid the advancements of super-resolution bioimaging techniques.

RevDate: 2020-08-10

Takahara T, Satou A, Sugie M, et al (2020)

Prognostic significance of p16 expression in high-grade prostate adenocarcinoma.

Pathology international [Epub ahead of print].

Management of advanced hormone-naïve prostate cancer (HNPC) is a critical public health issue. Useful prognostic markers are thus needed to select patients who will benefit from recently introduced upfront therapies. p16 expression is an adverse prognostic marker in prostate cancer. The present study aimed to determine whether p16 expression would serve as an adverse prognostic marker in advanced HNPC. A total of 79 patients diagnosed by needle biopsy with adenocarcinoma Gleason score ≥8 between 2010 and 2013 at Aichi Medical University were included in this study. The median patient age was 73 (range 52-87) years. The median follow-up was 62 months (range 2-98). Fourteen patients had p16-positive samples. Fifteen patients died from prostate cancer, 10 of whom were in the p16-positive group. p16 positivity was associated with clinical T stage (P < 0.001), presence of IDC-P (P < 0.001), distant metastasis (P < 0.001) and lymph node metastasis (P < 0.001). These results indicate that p16 expression is associated with adverse prognostic factor of prostate cancer and suggest that p16 expression may provide useful information for treatment planning and identifying suitable candidates for upfront chemotherapy or androgen receptor axis-targeted therapy.

RevDate: 2020-08-10

Wang H, Hu Y, Li H, et al (2020)

Preliminary study on identification of estrogen receptor-positive breast cancer subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) texture analysis.

Gland surgery, 9(3):622-628.

Background: Currently, breast cancer is divided into Luminal A, Luminal B, HER-2 overexpression (HER-2) and basal cell at genetic level. However, the differential diagnosis of estrogen receptor (ER)-positive breast cancer subtypes is rare. Therefore, we aimed to investigate the feasibility of identifying the ER-positive breast cancer subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) texture analysis.

Methods: A retrospective analysis was performed for clinical data of 51 patients with ER-positive breast invasive ductal carcinoma confirmed by surgery and pathology from January 20 to October 2018. FireVoxel texture analysis software was used to delineate the tumor boundary layer by layer. The differences in the above characteristics between Luminal A and Luminal B breast cancer were compared, and the diagnostic efficacy of statistically significant texture parameters for ER-positive breast cancer subtypes was analyzed.

Results: There were no significant differences in mean, standard deviation (SD), skewness and tumor size between Luminal A and Luminal B groups (P>0.05). The kurtosis, inhomogeneity and entropy could effectively distinguish between the two groups with statistically significant difference (P=0.001, P=0.000, and P=0.000). The area under the receiver operating characteristic (ROC) curve (AUC) of kurtosis, inhomogeneity and entropy diagnosed with malignant mass were 0.832, 0.859 and 0.891, respectively (P<0.01). In addition, the entropy was the best among the three indicators. When the entropy was ≤4.22, the sensitivity of the diagnosis Luminal B was 90.62% and the specificity was 78.95%.

Conclusions: The texture analysis features based on DCE-MRI can help to identify ER-positive breast cancer subtypes. Entropy can be the best single texture indicator.

RevDate: 2020-08-10

Zhang JQ, Lu CY, Qin L, et al (2020)

Outcome of post-mastectomy radiotherapy after primary systemic treatment in patients with different clinical tumor and nodal stages of breast cancer: a cohort study.

American journal of cancer research, 10(7):2185-2198.

To evaluate the effect of post-mastectomy radiation therapy (PMRT) stratified by clinical tumor (T) or nodal (N) staging and determine predictors of overall survival (OS), locoregional recurrence (LRR), distant metastasis, and disease-free survival (DFS) in patients with breast cancer who received neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we enrolled patients who received a diagnosis of breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was employed to calculate hazard ratios (HRs) and confidence intervals (CIs). Univariate and multivariate Cox regression analyses indicated that non-PMRT, Charlson comorbidity index ≥ 2, advanced clinical T or N stage, pathologic partial response, pathologic stationary disease, or pathologic progression disease were poor prognostic factors for OS. Well-differentiated tumor grade, pathologic complete response, and positive hormone receptors were better independent prognostic factors for OS. Adjusted HRs derived from PMRT for breast cancer after NACT and TM were 0.69 (0.53-0.89) and 0.74 (0.59-0.93) in clinical T3 and T4, respectively. aHRs derived from PMRT for breast cancer after NACT and TM were 0.67 (0.45-0.99), 0.75 (0.62-0.92), and 0.77 (0.60-0.98) in clinical N0, N1, N2-3, respectively. The aHRs (95% CI) of the PMRT group to the non-PMRT group for LRR-free survival and DFS were improved significantly. Our study indicated that PMRT significantly improved OS in clinical T3N0-T4N3 and for LRR-free survival and DFS in clinical T2N0-T4N3 from those of non-PMRT patients regardless of pathologic response and other predictors.

RevDate: 2020-08-10

Geha RC, Taback B, Cadena L, et al (2020)

A Single institution's randomized double-armed prospective study of lumpectomy margins with adjunctive use of the MarginProbe in nonpalpable breast cancers.

The breast journal [Epub ahead of print].

Breast conservation surgery (BCS) aims to excise all cancerous tissue while minimizing the amount of healthy breast tissue removed. Up to 30% of patients undergoing BCS require a second operation for re-excision to obtain negative margins. Previous studies reported a lower re-excision rate with intraoperative use of the MarginProbe device (Dune Medical Devices). This device utilizes radiofrequency spectroscopy to detect differences between cancerous and normal tissue. From July 2009 to January 2010, our institution enrolled 46 patients electing for BCS in a prospective double-arm randomized controlled trial and had a significantly lower re-excision rate than that reported in the multicenter trial. Intraoperatively, after performing conventional lumpectomy with excision of any additional shavings deemed necessary based on palpation and visual inspection alone, patients were then randomized. In the device arm, the surgeon used the MarginProbe to interrogate the lumpectomy specimen, taking additional shavings from the cavity surfaces corresponding to the parts of the specimen read as positive by the device. In the control arm, only standard intraoperative assessments were performed. All specimens were evaluated by pathologists who were blinded to the study arm. In this population, 72% had invasive ductal carcinoma (IDC), 20% had ductal carcinoma in situ (DCIS), and 8% had invasive lobular carcinoma (ILC). Average age was 64 years old. The average size of the specimen was 5.6 cm, the average volume was 37.8 cm3 , and the average weight was 32.7 g. The mean size of DCIS was 1.4 cm. For invasive specimens, 32 were T1 and 7 were T2. Prior to randomization, 43 patients were thought to have positive or close margins and therefore underwent additional shavings. Twenty-three patients were randomized to the device arm and 23 to the control arm. In the device arm, 14 (60%) patients had IDC, 7 (30%) had DCIS, and 2 (8%) had ILC, vs the control arm where 19 (82%) patients had IDC, 2 (8%) had DCIS, and 2 (8%) had ILC. Eight (35%) patients in the control group vs 1 (4%) in the device group underwent re-excision for margin involvement (P < .05). The use of the MarginProbe device at our institution significantly improved the ability of our surgeons to obtain clear margins during initial BCS. Our results show a lower re-excision rate (4%) than those published in the multicenter trial (19.8%). We postulate that in the face of more patients having DCIS in our device group (30%), our surgeons responded by taking thicker shavings when the MarginProbe device reported margin involvement during the initial lumpectomy, resulting in greater success achieving clear final margins on the shaved tissue and a significantly lower re-excision rate than previously reported with the MarginProbe device.

RevDate: 2020-08-10

Silveira WA, Gonçalves DA, Machado J, et al (2020)

cAMP-dependent protein kinase inhibits FoxO activity and regulates skeletal muscle plasticity in mice.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

Although we have shown that catecholamines suppress the activity of the Ubiquitin-Proteasome System (UPS) and atrophy-related genes expression through a cAMP-dependent manner in skeletal muscle from rodents, the underlying mechanisms remain unclear. Here, we report that a single injection of norepinephrine (NE; 1 mg kg-1 ; s.c) attenuated the fasting-induced up-regulation of FoxO-target genes in tibialis anterior (TA) muscles by the stimulation of PKA/CREB and Akt/FoxO1 signaling pathways. In addition, muscle-specific activation of PKA by the overexpression of PKA catalytic subunit (PKAcat) suppressed FoxO reporter activity induced by (1) a wild-type; (2) a non-phosphorylatable; (3) a non-phosphorylatable and non-acetylatable forms of FoxO1 and FoxO3; (4) downregulation of FoxO protein content, and probably by (5) PGC-1α up-regulation. Consistently, the overexpression of the PKAcat inhibitor (PKI) up-regulated FoxO activity and the content of Atrogin-1 and MuRF1, as well as induced muscle fiber atrophy, the latter effect being prevented by the overexpression of a dominant negative (d. n.) form of FoxO (d.n.FoxO). The sustained overexpression of PKAcat induced fiber-type transition toward a smaller, slower, and more oxidative phenotype and improved muscle resistance to fatigue. Taken together, our data provide the first evidence that endogenous PKA activity is required to restrain the basal activity of FoxO and physiologically important to maintain skeletal muscle mass.

RevDate: 2020-08-14

Kimura M, Narui K, Shima H, et al (2020)

Development of an invasive ductal carcinoma in a contralateral composite nipple graft after an autologous breast reconstruction: a case report.

Surgical case reports, 6(1):203.

BACKGROUND: Nipple-areola complex (NAC) reconstruction is a technique used in breast reconstructive surgery, which is performed during the final stage of breast reconstruction after total mastectomy of primary breast cancer. Composite nipple grafts utilizing the contralateral NAC are common; however, to our knowledge, there are no reports of new primary invasive ductal carcinoma development within the graft. Here, we describe one such case for the first time.

CASE PRESENTATION: A 54-year-old woman was referred to us by the Department of Plastic and Reconstructive Surgery in our medical center for further evaluation of right nipple erosion. She had undergone total mastectomy of the right breast following a breast cancer diagnosis 15 years ago, at which time tumor biological profiling revealed the following: estrogen receptor (ER), positive; progesterone receptor (PgR), negative; and human epidermal growth factor receptor 2 (HER2), undetermined. She received adjuvant chemotherapy and endocrine therapy. She defaulted endocrine therapy for a few years, and 7 years after surgery, she underwent autologous breast reconstruction with a deep inferior epigastric perforator (DIEP) flap. In the following year, NAC reconstruction was performed using a composite graft technique. Seven years after the NAC reconstruction, erosion appeared on the nipple grafted from its contralateral counterpart; scrape cytology revealed malignancy. The skin on the right side of her chest around the NAC and subcutaneous fat tissue consisted of transferred tissue from the abdomen, as the DIEP flap and grafted nipple were located on the graft skin. The right nipple carcinoma arose from the tissue taken from the left nipple. Magnetic resonance imaging (MRI) or computed tomography showed no malignant findings in the left breast. As the malignant lesion seemed limited to the area around the grafted right nipple on MRI, surgical resection with sufficient lateral and deep margins was performed around the right nipple. Pathological findings revealed invasive ductal carcinoma with comedo ductal components infiltrating the graft skin and underlying adipose tissue. Immunohistochemistry revealed positive for ER, PgR, and HER2.

CONCLUSIONS: To our knowledge, this is the first case involving the development of invasive ductal carcinoma in a nipple graft constructed on the skin of a DIEP flap, with the origin from the contralateral breast's nipple.

RevDate: 2020-08-14

Tsutsumi C, Abe T, Sawatsubashi Y, et al (2020)

Synchronous solid pseudopapillary neoplasm and invasive ductal carcinoma of the pancreas: a case report.

Surgical case reports, 6(1):202.

BACKGROUND: Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare neoplasm with a favorable prognosis. On the other hand, pancreatic invasive ductal carcinoma (IDC) is known to be an aggressive malignancy. To the best of our knowledge, there is no report of SPN combined with IDC of the pancreas.

CASE PRESENTATION: A 66-year-old woman presented with abnormal genital bleeding and was diagnosed with inoperable cervical cancer. During computed tomography for cancer staging, the patient was incidentally diagnosed with pancreatic cancer. After radiation therapy for the cervical cancer, distal pancreatectomy with D2 lymph node dissection was performed. A postoperative pathological examination revealed SPN with ossification and well-differentiated IDC in the pancreatic body. On immunohistochemical staining, SPN tumor cells showed positive β-catenin and CD10 staining, whereas IDC cells were negative for both. The tumor boundaries were clear. Accordingly, the final pathological diagnosis was synchronous SPN and IDC of the pancreas. Moreover, pathological findings such as the ossification and small number of SPN cells suggested that SPN may have existed long before IDC initiation.

CONCLUSIONS: Here, we report the first case of SPN combined with IDC of the pancreas. They may occur independently, and the long-term presence of SPN may lead to the development of IDC.

RevDate: 2020-08-11

Nguyen QD, Tavana A, Saenz Rios F, et al (2020)

A Case of Male Breast Cancer Patient with CHEK2*1100delC Mutation.

Cureus, 12(7):e8972.

Male breast cancer (MBC) is a rare disease that accounts for less than one percent of all breast cancers. The association between BRCA1 and BRCA2 mutations and MBC has been well-established; recent data suggest that CHEK2 1100delC heterozygosity is also associated with an increased risk of MBC. Herein, we present the case of a 47-year-old male who was initially diagnosed with bilateral symmetric gynecomastia on a diagnostic mammogram performed for right breast palpable lump. Sixteen months after his diagnosis of gynecomastia, he presented with enlarging right breast palpable lumps and underwent a diagnostic mammogram and breast ultrasound. Ultrasound-guided biopsies were performed on the right breast mass and axillary lymphadenopathy. Pathology revealed right breast invasive ductal carcinoma (IDC) and right axillary metastatic lymphadenopathy. Subsequent genetic testing found CHEK2*1100delC mutation. This case report focuses on the presentation, diagnosis, and management of breast cancer, as well as long-term cancer screening in the setting of CHEK2 mutation in a relatively young male patient.

RevDate: 2020-08-08

Keisari S, Feniger-Schaal R, Palgi Y, et al (2020)

Synchrony in Old Age: Playing the Mirror Game Improves Cognitive Performance.

Clinical gerontologist [Epub ahead of print].

OBJECTIVE: Studies have shown that synchronized motion between people positively affects a range of emotional and social functions. The mirror-game is a synchrony-based paradigm, common to theater, performance arts, and therapy, which includes dyadic synchronized motion, playfulness, and spontaneity. The goal of the current study is to examine the effects of the mirror-game on subjective and cognitive indices in late life.

METHOD: Thirty-four older adults (aged 71-98) participated in a within-group study design. Participants conducted two sessions of 9-minute movement activities: the mirror-game and the control condition - a physical exercise class. Several measures were taken before and after experimental sessions to assess socio-emotional and attentional functions.

RESULTS: The mirror-game enhanced performance on the attention sub-scale and led to faster detections of spoken words in noise. Further, it enhanced perceived partner responsiveness and led to an increase in positive reported experience.

CONCLUSIONS: Our preliminary findings suggest that the mirror-game, rather than the exercise class, may have an immediate impact on mood and some attentional functions.

CLINICAL IMPLICATIONS: The mirror-game is a novel intervention, with potential benefits of social-emotional and cognitive functioning, which can be easily implemented into the daily routine care of older adults. Future studies should explore the effect of the mirror-game on additional cognitive and socio-emotional aspects.

RevDate: 2020-08-09

Falicov C, Nakash O, M Alegría (2020)

Centering the Voice of the Client: On Becoming a Collaborative Practitioner with Low-Income Individuals and Families.

Family process [Epub ahead of print].

Despite current interest in collaborative practices, few investigations document the ways practitioners can facilitate collaboration during in-session interactions. This investigation explores verbatim psychotherapy transcripts to describe and illustrate therapist's communications that facilitate or hinder centering client's voice in work with socioeconomically disadvantaged populations. Four exemplar cases were selected from a large intervention trial aimed at improving shared decision making (SDM) skills of psychotherapists working with low-income clients. The exemplar cases were selected because they showed therapist's different degrees of success in facilitating SDM. Therapist's verbalizations were grouped into five distinct communicative practices that centered or de-centered the voice of clients. Communication practices were examined through the lens of collaborative approaches in family therapy. The analysis suggests that cross-fertilization between SDM and family-oriented collaborative and critical approaches shows promise to illuminate and enhance the challenging road from clinician-led to client-led interactions. This paper also stresses the importance of incorporating relational intersectionality with individuals and families who may not feel entitled to express their expectations or raise questions when interacting with authority figures.

RevDate: 2020-09-18

Sechrist H, Glasgow A, Bomeisl P, et al (2020)

Concordance of breast cancer biomarker status between routine immunohistochemistry/in situ hybridization and Oncotype DX qRT-PCR with investigation of discordance, a study of 591 cases.

Human pathology, 104:54-65 pii:S0046-8177(20)30146-5 [Epub ahead of print].

Patients with estrogen receptor (ER)+/human epidermal growth factor receptor (HER)2-, lymph node- breast cancer with high recurrence risk benefit from adjuvant chemotherapy in addition to hormonal therapy. This study compares ER, progesterone receptor (PR), and HER2 status between routine immunohistochemistry (IHC)/in situ hybridization (ISH) and Oncotype DX (ODX) in 591 cases. ODX recurrence score (RS) and clinicopathologic features were compared between ER/PR-concordant and discordant cases. Hematoxylin and eosin (H&E) slides from ER discordant cases were reexamined. Concordance was high between ODX and IHC for ER status (580/591, 98.1%) and moderate for PR status (512/591, 86.6%). All 11 ER discordant cases were ER+ by IHC but ER- by ODX and high risk by ODX. Histologically, all of these cases were grade III invasive ductal carcinoma (IDC), except one case diagnosed as IDC with apocrine features. Although this case was grade I and ER/PR+ by IHC, this patient received chemotherapy because of high RS. Of 79 PR discordant cases, 60 were PR+ by IHC but PR- by ODX. Five hundred eighty-four cases had available HER2 data, with high negative agreement (580/582, 99.7%). However, both HER2+ cases by ISH were HER2- by ODX. Mean RS was higher for ER discordant than concordant cases (48.0 versus 17.1, P < 0.0001) and for PR discordant (IHC+/ODX-) than concordant cases (27.2 versus 16.7, P < 0.0001) with no significant differences in recurrence or metastasis. Overall, detection was more sensitive by IHC, and high RS of discordant cases suggests possible risk overestimation. Therapeutic decisions for discordant cases should continue to be based on clinicopathologic correlation and not oncotype alone.

RevDate: 2020-08-18
CmpDate: 2020-08-18

Lee J, Yang JD, Lee JW, et al (2020)

Acellular dermal matrix combined with oxidized regenerated cellulose for partial breast reconstruction: Two case reports.

Medicine, 99(31):e21217.

RATIONALE: Filling materials for partial defect of the breast have rarely been developed because of safety and durability.

PATIENT CONCERNS: Two female patients (ages, 53 and 50 years) with breast cancer underwent partial mastectomy with sentinel lymph node biopsy.

DIAGNOSIS: Core needle biopsy revealed an invasive ductal carcinoma in both patients. Breast ultrasound showed hypoechoic nodules with irregular margins. Breast magnetic resonance imaging showed an irregularly shaped enhancing mass with duct extension in Patient 1 and irregularly shaped multifocal, enhancing masses with non-mass enhancement in Patient 2.

INTERVENTION: A combination method using acellular dermal matrix and oxidized regenerated cellulose was used for partial breast reconstruction. The safety and cosmetic outcomes were evaluated for both patients.

OUTCOMES: There were no significant complications, and the breast shape and volume were well maintained, even 2 years after surgery. There was no postoperative tumor recurrence.

CONCLUSION: The combination of acellular dermal matrix and oxidized regenerated cellulose for partial breast reconstruction can be a good option based on oncological safety and cosmetic outcome.

RevDate: 2020-09-03

Keshavarzi B, Tabatabaei M, Zarnani AH, et al (2020)

The effect of human amniotic epithelial cell on dendritic cell differentiation of peripheral blood monocytes: An experimental study.

International journal of reproductive biomedicine, 18(6):449-464.

Background: The amniotic membrane plays an important role in maintaining a healthy pregnancy. The main population cells from amniotic membrane include human amnion epithelial cells (hAECs) which have been shown to possess immunomodulatory properties.

Objective: The proximity of hAECs with monocyte leads to the generation of tollerogenic dendritic cells.

Materials and Methods: hAECs were obtained from normal pregnancy. Peripheral blood monocytes were isolated by anti-CD14 MACS method. Co-cultures of monocytes and hAECs were established in Transwell chambers supplemented with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in the absence and presence of lipopolysaccharide (LPS) to produce immature and mature DCs, respectively. Immunophenotyping of the obtained DCs was done through flow cytometry and the production of cytokines was measured by ELISA. Mixed leukocyte Reaction (MLR) was also performed for the functional assessment of DCs.

Results: Immunophenotyping of [hAECs - Immature DC (iDC)] and [hAECs - iDC] + LPS cells revealed that the expression of CD1a, CD80, CD86, CD40, HLA-DR, and CD83 markers showed no significant difference as compared with the control group (iDCs and mDCs alone). In the [hAECs-iDCs] + LPS cells, the percentage of CD14 cells at the ratio of 1:2.5 showed significant differences compared to the control group. The production of IL-10 and IL-12 showed no significant difference in any of the cultures as compared to the control groups. Also, co-cultured DCs did not inhibit proliferation of lymphocyte.

Conclusion: Our findings show that factors secreted from cultured hAECs are unable to generate of tollerogenic dendritic cells. To achieve a better understanding of other mechanisms more investigations are needed.

RevDate: 2020-08-06

Hashemi Bahremani M, Ebrahimi A, M Fallahi (2020)

Predicting Effects of Clinicopathological Variables on Her2 Gene Amplification by Chromogenic in situ Hybridization (CISH) in IHC Her2 (2+) Breast Cancer Patients; A Study from Iran.

Iranian journal of pathology, 15(3):217-224.

Background & Objective: The her2 amplification plays an important role in breast cancer management. Therefore, there is a need for using supplementary molecular methods in IHC equivocal cases. Present study has been conducted to determine the effects of clinicopathological variables on her2 gene amplification by chromogenic in situ hybridization (CISH) in IHC Her2 (2+) breast cancer individuals.

Methods: A cross-sectional study was conducted in Zaferanyeh Laboratory collaborated with Shahid Beheshti University of Medical Sciences (Tehran-Iran; 2015-2018). All pathological data related invasive breast cancer patients with equivocal IHC results were included. CISH method was performed as a supplementary technique. The associations between histopathologic variables, status of Ki-67 index, progesterone and estrogen receptors (PR & ER) with her2 amplification by CISH were investigated and analyzed. The level of significance was considered as P-value < 0.05.

Results: Totally, 239 patients with mean age of 53.2 years were studied. CISH identified her2 gene amplification in 51 subjects (21.3%). The type of tumor (invasive ductal carcinoma), the tumor grade, and the value of Ki-67 index were directly correlated with her2 amplification. Significant negative associations were also observed between CISH results and ER and PR expression.

Conclusion: As her2 gene amplification was identified in 21.3% of invasive breast cancer patients with equivocal IHC results, it is supposed that applying CISH method may consider as a potentially valuable supplementary method. Results have also shown that higher grades of tumor, invasive ductal carcinoma, absences of hormone receptors and high Ki-67 index significantly correlated with the her2 amplification.

RevDate: 2020-08-08

Choridah L, Sari WK, Dwianingsih EK, et al (2020)

Advanced lesions of synchronous bilateral mammary Paget's disease: a case report.

Journal of medical case reports, 14(1):119.

BACKGROUND: Mammary Paget's disease is an eczematous eruption on the nipple and areola with underlying breast malignancy. It is often misinterpreted as chronic dermatitis or psoriasis causing a delayed diagnosis. Synchronous bilateral mammary Paget's disease is exceptionally rare and an advanced case with underlying invasive carcinoma might require long-term treatment and follow-up that could affect a patient's physical, psychological, and social aspects of well-being.

CASE PRESENTATION: A 54-year-old Javanese woman presented in our clinic with a 2-year history of itching and chronic eczema in both areolae. Bilateral nipple retraction and retro-areolar palpable lumps were observed during the first presentation. Breast ultrasound revealed hypoechoic lesions in her left and right breasts. Mammograms showed an irregular hyperdense lesion and multiple microcalcifications. Histopathology from biopsy and bilateral mastectomy demonstrated infiltration of large Paget's cells in the epidermis of the areola with underlying lesions of invasive ductal carcinoma, diagnosed solid type with high nuclear grade and negative expression of estrogen receptor and progesterone receptor, with positive expression of human epidermal growth receptor-2(HER2) and Ki-67 (45%).

CONCLUSIONS: In a patient with suspicious chronic inflammation of the nipple and areolae, prompt biopsy should be performed to avoid a delayed diagnosis of any malignant breast lesion.

RevDate: 2020-08-04

Gatek J, Petru V, Kosac P, et al (2020)

Targeted axillary dissection with preoperative tattooing of biopsied positive axillary lymph nodes in breast cancer.

Neoplasma pii:191228N1344 [Epub ahead of print].

Sentinel lymph node biopsy (SLNB) has emerged as an alternative to axillary lymph node dissection during breast cancer surgery during the last 2 decades. However, there are several controversies regarding the indication of the sentinel node biopsy after neoadjuvant chemotherapy which can convert positive lymph nodes to negative. The false negative rate after neoadjuvant chemotherapy is unacceptably high. This high false negative rate can be decreased by marking of the positive lymph nodes and removal during sentinel lymph node biopsy procedure in addition to the sentinel lymph nodes. The aim of this study was to investigate the possibility of carbon tattooing of the positive sentinel lymph nodes before neoadjuvant chemotherapy. In 2016, a prospective protocol was launched investigating the black carbon tattooing procedure of the suspective and positive axillary lymph nodes by injecting 0.1-0.5 carbon ink in normal saline under ultrasound guidance. All patients underwent black carbon tattooing of the suspected or positive axillary lymph nodes before the chemotherapy or one week before the primary surgery when chemotherapy was not indicated in the neoadjuvant setting. Sentinel lymph nodes together with lymph nodes marked by the black carbon ink were removed and histologically evaluated. So far 27 patients were treated under this protocol. Breast saving surgery was performed in 22 cases and mastectomy in 5 cases. All patients had invasive ductal carcinoma. In 20 patients neoadjuvant chemotherapy was indicated and in 7 patients primary surgery was performed. All lymph nodes marked by black carbon ink were successfully identified and removed. Sentinel lymph node biopsy was performed in 8 cases and sentinel lymph node biopsy followed by axillary dissection in 15 cases. Axillary dissection alone was performed in 4 cases. In 19 cases the black carbon ink was present in the sentinel lymph node at the same time and in 4 cases carbon dye was present in other lymph nodes than lymph node identified during SLNB, which corresponds to 17.4%. In the group of patients undergoing primary surgery, in one case from six, the sentinel lymph node was negative and the lymph node marked with carbon ink positive which represents false negative lymph node and failure of the SLNB procedure. After neoadjuvant chemotherapy, there was no false negative lymph node identified, but the conversion of the positive lymph nodes to negative was present in 10 cases (50%). There were no complications attributed to carbon ink tattooing. The results of positive sentinel lymph nodes tattooing have confirmed that this method is safe and allows a decrease in the false negativity rate during the sentinel node biopsy procedure.

RevDate: 2020-08-04

Kato M, Hirakawa A, Kobayashi Y, et al (2020)

Effect of core needle biopsy number on intraductal carcinoma of the prostate (IDC-P) diagnosis in patients with metastatic hormone-sensitive prostate cancer.

International journal of clinical oncology pii:10.1007/s10147-020-01756-0 [Epub ahead of print].

BACKGROUND: The number of core needle biopsies in metastatic prostate cancer cases are sometimes reduced to avoid various complications. We analyzed whether core needle biopsy number influence IDC-P detection rate in patients with metastatic castration-sensitive prostate cancer (mHSPC).

METHODS: We retrospectively evaluated data from 150 patients diagnosed with mHSPC. Subjects were allocated to three groups according to the number of core biopsies performed: ≤ 5, 6-9, and ≥ 10. The study endpoints were the cancer-specific survival (CSS) and overall survival (OS) rates.

RESULTS: For patients who underwent ≥ 10 core biopsies, a significant difference on CSS was detected between with or without IDC-P (P = 0.016). On the other hand, the difference decreased as the number of core biopsies became smaller (6-9; P = 0.322 and ≤ 5; P = 0.815). A similar trend was identified for the OS outcome. A significant difference on OS was also found between with or without IDC-P in patients who underwent ≥ 10 and 6-9 core needle biopsies (P = 0.0002 and 0.017, respectively), but not in those who underwent ≤ 5 core biopsies (P = 0.341). IDC-P served as a stronger prognostic marker for CSS and OS than did the other factors included in the multivariate analysis for patients had ≥ 10 core biopsies (P = 0.016, and P = 0.0014, respectively).

CONCLUSIONS: Given the IDC-P detection and its value as a prognostic marker, we propose the performance of ≥ 10 core biopsy procedures in patients diagnosed with mHSPC to minimize the sampling error of the IDC-P.

RevDate: 2020-09-20

Altinoz A, Al Ameri M, Qureshi W, et al (2020)

Clinicopathological characteristics of gene-positive breast cancer in the United Arab Emirates.

Breast (Edinburgh, Scotland), 53:119-124.

INTRODUCTION: Breast cancer is the most prevalent cancer in the United Arab Emirates (UAE). This is the first study to provide data on predisposition of breast cancer susceptibility genes with associated clinical and pathological aspects in the UAE.

MATERIAL & METHODS: A retrospective chart review for breast cancer patients undergoing genetic testing from 2016 to 2018. According to National Comprehensive Cancer Network (NCCN) guidelines genetic testing was offered. The analyzed data included; age, ethnicity, family cancer history, pathogenic variant, histopathology, stage, molecular subtype and proliferation.

RESULTS: 309 patients underwent genetic testing with a positive result in 130 patients (11.9%) over a period of 36 months. In 34.6% pathogenic and likely pathogenic variants were identified. BRCA2 was the most common gene identified. The mean age was 42.9 years (±9.01). Positive family history was identified in 66 patients (50.7%). Majority had stage 1 or 2 disease (66.2%), invasive ductal carcinoma (81.5%) and hormone receptor positive cancer (45.3%).

CONCLUSIONS: This is the first study in the UAE to describe the clinical and pathological characteristics of hereditary breast cancer in a mixed ethnic group with dominant Arabic population. Further genetic studies will be required in the UAE population, as the prevalence of breast cancer continues to rise.

RevDate: 2020-08-02

Gao W, Zeng Y, Fei X, et al (2020)

Axillary lymph node and non-sentinel lymph node metastasis among the ACOSOG Z0011 eligible breast cancer patients with invasive ductal, invasive lobular, or other histological special types: a multi-institutional retrospective analysis.

Breast cancer research and treatment pii:10.1007/s10549-020-05842-9 [Epub ahead of print].

PURPOSE: Given the histological special types (HST) of breast carcinoma accounted for minority of the Z0011 study population, this study aimed to assess the rates of axillary lymph node (ALN) involvement and non-sentinel lymph node (SLN) metastasis in patients with invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), or other HST.

METHODS: Patients with cT1-2N0M0 breast cancer treated between 2009 and 2018 were retrospectively included from a multi-institutional database. Rates of nodal involvement were analyzed among different histological subgroups. The impact of ALN dissection (ALND) on adjuvant treatment decisions and prognosis were also analyzed among patients with 1-2 + SLNs.

RESULTS: A total of 8294 patients were included: 6854 (82.6%), 257 (3.1%), and 1183 (14.3%) patients with IDC, ILC, and other HST, respectively. IDC patients had a significantly higher rate of ALN metastasis compared with ILC or other HST (31.9% vs. 22.6% vs. 16.4%, P < 0.001). However, in patients with 1-2 + SLNs, rates of non-SLN metastasis were similar among three groups (IDC: n = 182, 28.6% vs. ILC: n = 5, 31.2% vs. other HST: n = 29, 34.9%, P = 0.481). For patients with 1-2 + SLNs, rates of adjuvant chemotherapy and the estimated 3-year recurrence-free survival were similar between the SLN biopsy and ALND arms, regardless of the histological types.

CONCLUSION: Among patients with 1-2 + SLNs, ILC or other HST had similar rates of non-SLN metastasis compared with IDC. Omission of ALND may not influence adjuvant chemotherapy usage or disease outcome regardless of histological types.

RevDate: 2020-09-10

Granek L, O Nakash (2020)

Prevalence and risk factors for suicidality in cancer patients and oncology healthcare professionals strategies in identifying suicide risk in cancer patients.

Current opinion in supportive and palliative care, 14(3):239-246.

PURPOSE OF REVIEW: The aim of this study was to summarize the literature on prevalence and risk factors for suicidality in cancer patients and to document the research on oncology healthcare professionals' strategies in identifying this risk.

RECENT FINDINGS: Cancer patients exhibit increased risk of suicidality compared with the general population. Various risk factors have been identified including sociodemographic factors such as poverty, being male and elderly as well as disease-related attributes such as cancer type and stage. The literature on how healthcare professionals identify suicide risk is sparse. Ten articles were found that focused on two main themes. These included information on systematic strategies in identifying suicide risk and factors that affect healthcare professionals' ability to identify risk in their patients.

SUMMARY: Although there is an immense amount of literature documenting the problem of suicidality among patients, the research on how healthcare professionals identify and respond to these indications in patients is nearly nonexistent. Cancer centres should implement standardized and systematic screening of cancer patients for suicidality and research on this patient population should collect and report these data. Ongoing training and education for healthcare professionals who work in the oncology setting on how to identify and respond to suicide risk among cancer patients is urgently needed.

RevDate: 2020-09-02

Cerea S, Ghisi M, Bottesi G, et al (2020)

Reaching reliable change using short, daily, cognitive training exercises delivered on a mobile application: The case of Relationship Obsessive Compulsive Disorder (ROCD) symptoms and cognitions in a subclinical cohort.

Journal of affective disorders, 276:775-787.

BACKGROUND: Relationship Obsessive Compulsive Disorder (ROCD) is a presentation of OCD centering on interpersonal relationships. The aim of this Randomized Control Trial (RCT) was to assess the efficacy of short, game like, daily cognitive interventions delivered via mobile application in reducing subclinical ROCD symptoms and associated phenomena.

METHODS: Fifty university students identified as having subclinical levels of ROCD symptoms (using the Structured Clinical Interview for DSM-5 Clinical Version) were randomized into: immediate-use group (iApp group; n = 25) and delayed-use group (dApp group; n = 25). The iApp group started using the evaluated cognitive-behavioral training application at baseline for 15 days (T0 to T1). The dApp group commenced using the application at T1 for 15 days (T1 to T2). All participants completed questionnaires at baseline (T0), 15 days from baseline (T1), and 30 days from baseline (T2).

RESULTS: Repeated measure MANOVAs showed significant Group (iApp vs. dApp) × Time (T0 vs. T1) interactions. These interactions indicated greater decrease in ROCD symptoms, OCD beliefs and social anxiety symptoms, as well as a greater increase in self-esteem in the iApp group compared to dApp group at T1. Moreover, the Reliable Change Index (RCI) indicated reliable change on ROCD symptoms for a significant portion of participants (42-52%).

LIMITATIONS: Sample size and the use of self-report measures limits the generalizability of the results.

CONCLUSIONS: Short, daily cognitive training interventions delivered via mobile applications may be useful in reducing subclinical ROCD symptoms and associated features. Further testing is needed for clinical populations.

RevDate: 2020-09-07

Lilly AJ, Johnson M, Kuzmiak CM, et al (2020)

MRI-guided core needle biopsy of the breast: Radiology-pathology correlation and impact on clinical management.

Annals of diagnostic pathology, 48:151563 pii:S1092-9134(20)30106-4 [Epub ahead of print].

OBJECTIVE: Breast MRI is used to screen high-risk patients and determine extent of disease in breast cancer (BC) patients. The goal of this study was to determine the pathologic correlates of breast MRI abnormalities biopsied under MRI guidance.

METHODS: We retrospectively identified 101 MRI-guided core needle biopsies (CNB) of the breast from 79 women over a 4-year period. MRI-detected lesions biopsied with ultrasound or stereotactic guidance were excluded. MRI studies and pathology were reviewed by breast radiologists and pathologists.

RESULTS: Of the 79 patients, 72 (91%) had a history of prior (n = 13) or concurrent (n = 59) BC. There were 101 MRI abnormalities: 60 (59%) with non-mass enhancement (NME) and 41 (41%) with mass enhancement. Pathology was benign in 83/101 (82%), including in the majority of NME lesions (43/60, 72%). The most common benign findings were: fibrocystic changes (FCC) (49%), sclerosing lesions (13%), and fibroadenoma (FA) (9%). There were 18 (18%) malignant diagnoses: 8 (44%) invasive lobular carcinoma (ILC), 7 (39%) ductal carcinoma in situ (DCIS), and 3 (17%) invasive ductal carcinoma (IDC). Of the 18 malignant diagnoses, 16 (89%) occurred in 14 unique patients with concurrent BC. Based on the malignant MRI-guided CNB, 6 (46%) of these patients had additional (sentinel lymph node biopsy or contralateral breast surgery) or more extensive (wider lumpectomy) surgery.

CONCLUSION: In this series, most MRI-guided CNB of the breast were benign. The vast majority of malignant diagnoses occurred in patients with concurrent BC and frequently resulted in changes in clinical management.

RevDate: 2020-09-12

Camacho Londoño JE, Kuryshev V, Zorn M, et al (2020)

Transcriptional signatures regulated by TRPC1/C4-mediated Background Ca2+ entry after pressure-overload induced cardiac remodelling.

Progress in biophysics and molecular biology pii:S0079-6107(20)30071-7 [Epub ahead of print].

AIMS: After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca2+ entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling.

METHODS AND RESULTS: Mn2+-quench analysis in cardiomyocytes from several Trpc-deficient mice revealed that both TRPC1 and TRPC4 are required for BGCE. Electrically-evoked cell shortening of cardiomyocytes from TRPC1/C4-DKO mice was reduced, whereas parameters of cardiac contractility and relaxation assessed in vivo were unaltered. As pathological cardiac remodelling in mice depends on their genetic background, and the development of cardiac remodelling was found to be reduced in TRPC1/C4-DKO mice on a mixed genetic background, we studied TRPC1/C4-DKO mice on a C57BL6/N genetic background. Cardiac hypertrophy was reduced in those mice after chronic isoproterenol infusion (-51.4%) or after one week of transverse aortic constriction (TAC; -73.0%). This last manoeuvre was preceded by changes in the pressure overload induced transcriptional program as analysed by RNA sequencing. Genes encoding specific collagens, the Mef2 target myomaxin and the gene encoding the mechanosensitive channel Piezo2 were up-regulated after TAC in wild type but not in TRPC1/C4-DKO hearts.

CONCLUSIONS: Deletion of the TRPC1 and TRPC4 channel proteins protects against development of pathological cardiac hypertrophy independently of the genetic background. To determine if the TRPC1/C4-dependent changes in the pressure overload induced alterations in the transcriptional program causally contribute to cardio-protection needs to be elaborated in future studies.

RevDate: 2020-08-01

Sergio L, Teresita BM, Emanuel C, et al (2020)

Working together for the family: determination of HER oncogene co-amplifications in breast cancer.

Oncotarget, 11(28):2774-2792.

HER2 is a well-studied tyrosine kinase (TK) membrane receptor which functions as a therapeutic target in invasive ductal breast carcinomas (IDC). The standard of care for the treatment of HER2-positive breast is the antibody trastuzumab. Despite specific treatment unfortunately, 20% of primary and 70% of metastatic HER2 tumors develop resistance. HER2 belongs to a gene family, with four members (HER1-4) and these members could be involved in resistance to anti-HER2 therapies. In this study we designed a probemix to detect the amplification of the four HER oncogenes in a single reaction. In addition, we developed a protocol based on the combination of MLPA with ddPCR to detect the tumor proportion of co-amplified HERs. On 111 IDC, the HER2 MLPA results were validated by FISH (Adjusted r2 = 0,91, p < 0,0001), CISH (Adjusted r2 = 0,938, p < 0,0001) and IHC (Adjusted r2 = 0,31, p < 0,0001). HER1-4 MLPA results were validated by RT-qPCR assays (Spearman Rank test p < 0,05). Of the 111 samples, 26% presented at least one HER amplified, of which 23% showed co-amplifications with other HERs. The percentage of cells with HER2 co-amplified varied among the tumors (from 2-72,6%). Independent in-silico findings show that the outcome of HER2+ patients is conditioned by the status of HER3 and HER4. Our results encourage further studies to investigate the relationship with patient's response to single or combined treatment. The approach could serve as proof of principle for other tumors in which the HER oncogenes are involved.

RevDate: 2020-08-01

Murali P, Johnson BP, Lu Z, et al (2020)

Novel role for the Golgi membrane protein TMEM165 in control of migration and invasion for breast carcinoma.

Oncotarget, 11(28):2747-2762.

The TMEM165 gene encodes for a multiple pass membrane protein localized in the Golgi that has been linked to congenital disorders of glycosylation. The TMEM165 protein is a putative ion transporter that regulates H+/Ca++/Mn++ homeostasis and pH in the Golgi. Previously, we identified TMEM165 as a potential biomarker for breast carcinoma in a glycoproteomic study using late stage invasive ductal carcinoma tissues with patient- matched adjacent normal tissues. The TMEM165 protein was not detected in non-malignant matched breast tissues and was detected in invasive ductal breast carcinoma tissues by mass spectrometry. Our hypothesis is that the TMEM165 protein confers a growth advantage to breast cancer. In this preliminary study we have investigated the expression of TMEM165 in earlier stage invasive ductal carcinoma and ductal carcinoma in situ cases. We created a CRISPR/Cas9 knockout of TMEM165 in the human invasive breast cancer cell line MDAMB231. Our results indicate that removal of TMEM165 in these cells results in a significant reduction of cell migration, tumor growth, and tumor vascularization in vivo. Furthermore, we find that TMEM165 expression alters the glycosylation of breast cancer cells and these changes promote the invasion and growth of breast cancer by altering the expression levels of key glycoproteins involved in regulation of the epithelial to mesenchymal transition such as E-cadherin. These studies illustrate new potential functions for this Golgi membrane protein in the control of breast cancer growth and invasion.

RevDate: 2020-07-30

Botty Van den Bruele A, ML Gemignani (2020)

Management of ipsilateral supernumerary nipple at time of breast cancer diagnosis.

Supernumerary breast components occur predominantly between the breast and umbilicus. Carcinoma of this ectopic, or accessory breast tissue (ABT), is exceedingly rare, accounting for <1% of breast cancer cases. Historically, ectopic breast carcinoma was considered aggressive with poor outcome. In 1995, Evans et al reported 90 cases spanning from 1929 to 1993 with a 9.4% survival beyond 4 years. More contemporary studies reveal improvement in both treatment and survival. There is currently no consensus on whether prophylactic excision of an ipsilateral supernumerary nipple at the time of initial breast cancer diagnosis is necessary. The following describes a patient with an ipsilateral tumor uniquely located within her supernumerary nipple 5 years after mastectomy.

RevDate: 2020-08-29

Mutlu EC, Kaya Ö, Wood M, et al (2020)

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial.

Materials (Basel, Switzerland), 13(15):.

Immature dendritic cells (IDc), 'dexosomes', are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 ± 0.33 ng/106 cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 µg/mL, dExoII, 1.2 µg/mL, and dExoI, 0.6 µg/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naïve) were obtained by CellMaskTM membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 °C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between -15 to -20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the "BioNanoMaterial" after DOX loading via ultrasonication technique.

RevDate: 2020-07-29

Findlay-Shirras LJ, Lima I, Smith G, et al (2020)

Population Trends in Lobular Carcinoma of the Breast: The Ontario Experience.

Annals of surgical oncology pii:10.1245/s10434-020-08895-8 [Epub ahead of print].

BACKGROUND: Invasive lobular carcinoma (ILC) is less common that invasive ductal carcinoma (IDC), and more challenging to diagnose by examination and screening mammography. This study evaluated current trends in ILC incidence, and described the 5-, 10-, and 15-year survival probabilities for women diagnosed with ILC in Ontario, Canada.

METHODS: This retrospective cohort analysis included all women aged 18 years and older diagnosed with breast cancer between 1991 and 2015. Health administrative data from the Institute of Clinical Evaluative Sciences and the Ontario Cancer Registry were used to identify breast cancer cases. Age-adjusted incidence was plotted by year. Crude proportions were plotted by year of diagnosis for stage and hormone receptor status. Kaplan-Meier curves were generated to determine the 5-, 10-, and 15-year survival probabilities for ILC and IDC.

RESULTS: From 1991 to 2015, there were 194,065 cases of breast cancer in Ontario, 14.7% of which were ILC. The age-adjusted incidence of breast cancer increased 1.04-fold, while ILC rates increased 1.53-fold. All bilateral breast cancers were of lobular origin. The proportion of stage 1 ILC decreased, while the proportion of stage 2-4 ILC increased. The 5-, 10-, and 15-year overall survival probabilities for women diagnosed with ILC were 82.7%, 65.3%, and 50.2%, respectively.

CONCLUSIONS: This study contains the largest population dataset of ILC evaluated to date. While total breast cancer incidence rates in Ontario are largely unchanged, ILC incidence rates are steadily increasing and there is a trend towards diagnosis of ILC at a later stage. These trends highlight the ongoing diagnostic and treatment challenge ILC presents for patients and clinicians.

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RJR Experience and Expertise

Researcher

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.

Educator

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.

Administrator

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.

Technologist

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.

Publisher

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.

Speaker

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.

Facilitator

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.

Designer

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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