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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 30 Jun 2022 at 01:45 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: 2022-06-28

Ogbu TJ, Scales SE, de Almeida MM, et al (2022)

Predictors of exceeding emergency under-five mortality thresholds using small-scale survey data from humanitarian settings (1999 - 2020): considerations for measles vaccination, malnutrition, and displacement status.

Archives of public health = Archives belges de sante publique, 80(1):160.

BACKGROUND: Quantifying the effect of measles containing vaccine (MCV) coverage and the prevalence of global acute malnutrition (GAM) on mortality levels in populations of displaced and crisis-affected resident children is important for intervention programming in humanitarian emergencies.

METHODS: A total of 1597 surveys containing data on under-five death rate, population status (internally displaced, refugee, or crisis-affected resident), measles containing vaccine coverage, and global acute malnutrition were extracted from the Complex Emergency Database (CE-DAT). Under-five mortality rates were dichotomized to those exceeding critical levels or otherwise. A Bayesian multivariable mixed-effect logistic regression model was used to assess the association between an under-five death rate (U5DR) exceeding this threshold and population status (i.e., internally displaced, refugees or residents), GAM prevalence (proxy for food security), and MCV coverage.

RESULTS: The prevalence of GAM, MCV and U5DR were higher in internally displaced children (IDC) with values of 14.6%, 69.9% and 2.07 deaths per 10 000 per day, respectively. Refugee populations had lower average under-five mortality rate (0.89 deaths per 10 000 per day), GAM of 12.0% and the highest measles containing vaccine coverage (80.0%). In crisis-affected residents the prevalence of GAM, MCV and average U5DR are 11.1%, 65.5% and 1.20 deaths per 10 000 per day respectively. In mixed-effect logistic model taking 2 deaths per 10 000 children less than five years old per as emergency threshold (Model III); MCV (AOR = 0.66, 95% Highest Density Interval (HDI): 0.57, 0.78), GAM (AOR = 1.79, 95% HDI: 1.52, 2.12) were associated with a reduction of the odds of U5DR exceeding critical level accounting for country-specific levels of variability. The odds of U5DR exceeding critical level (2/10000/day) in crisis-affected resident children and refugees were 0.36 (95% HDI: 0.22, 0.58) and 0.25(95% HDI: 0.11, 0.55) less than amongst IDP children adjusting for GAM and MCV. In considering country specific yearly median U5DR (model IV) the odds of U5DR exceeding twice the median U5DR were associated with MCV (AOR = 0.72, 95% HDI: 0.64, 0.82), GAM (AOR = 1.53, 95%HDI: 1.34, 1.76). The odds of U5DR exceeding critical level in crisis-affected resident children was 0.30(95% HDI: 0.20, 0.45) less than IDP children, after adjusting for MCV and GAM. We found no difference between the odds of U5DR exceeding twice the country level median U5DR in the refugee population compared to the IDPs.

CONCLUSIONS: In this study vaccination coverage and global acute malnutrition (proxy for food security) were associated with U5DR exceeding critical level. The emergency threshold for IDPs and affected residents is significantly different and consistent across the different outcomes, whereas the result is inconsistent for IDPs and refugees. Continued improvement in measles vaccination coverage and reduction of malnutrition in humanitarian emergencies have the potential to minimize the deterioration of mortality level amongst children in emergency settings. To generate a robust understanding of the critical level of child mortality in displaced and affected resident populations, studies accounting for the impact of the duration of displacement, contextual factors in humanitarian settings, and the level of humanitarian assistance provided are needed.

RevDate: 2022-06-28

Chen S, Yang L, Y Li (2022)

Clinicopathological Features of 166 Cases of Invasive Ductal Breast Carcinoma and Effect of Primary Tumor Location on Prognosis after Modified Radical Mastectomy.

Emergency medicine international, 2022:3158956.

Objective: To investigate the clinicopathological features of 166 cases of invasive ductal carcinoma (IDC) of the breast and to analyze the effect of the location of the primary tumor on the prognosis of modified radical mastectomy.

Materials and Methods: The clinical data of 166 patients with IDC who underwent modified radical mastectomy in our hospital from May 2015 to May 2017 were retrospectively analyzed. The clinicopathological features of IDC patients were recorded. Univariate analysis and the multivariate logistic regression model were used to analyze the relationship between the location of the primary tumor and the prognosis of IDC patients after modified radical surgery. The effect of primary tumor location on the prognosis of modified radical resection was used with Survival curve analysis.

Results: Among the patients in the central region, 13.33% had tumors >5 cm in diameter, which was higher than those in the other four groups. Among the patients in the upper inner quadrant, 59.38% received hormone therapy after operation, which was higher than those in the other four groups (P < 0.05). There were no significant differences in age, menopause, histological grading, molecular typing, lymph node metastasis, vascular invasion, radiation therapy, and chemotherapy among different groups (P > 0.05). Univariate analysis showed that molecular typing, lymph node metastasis, vascular invasion, and location of the primary tumor were all related to the prognosis of IDC patients after modified radical surgery, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that molecular typing, lymph node metastasis, vascular invasion, and primary tumor location were all independent influencing factors for prognosis of IDC patients after modified radical surgery (P < 0.05). As of 31 May 2021, there were 11 patients with recurrence and metastasis and 20 patients with death. The median survival time in the outer upper quadrant group was 80 months, which was higher than that in the outer lower quadrant group by 72 months, the median survival time in the central region group by 71 months, the median survival time in the inner upper quadrant group by 67 months, and the median survival time in the inner lower quadrant group by 61 months. The log-rank test showed all P < 0.001.

Conclusion: Patients with primary tumors located in the central area have larger tumor diameters. Patients located in the central area, upper inner quadrant, and lower inner quadrant are more likely to have lymphatic metastasis, have a more serious condition, and have a shorter prognosis survival time. Unluminal type, multiple lymph node metastases, vascular invasion, and the location of the primary tumor in the inner quadrant are all independent risk factors for prognosis in patients after modified radical surgery for IDC.

RevDate: 2022-06-27

Abou Shousha SA, Hussein B, Shahine Y, et al (2022)

Angiogenic activities of interleukin-8, vascular endothelial growth factor and matrix metalloproteinase-9 in breast cancer.

The Egyptian journal of immunology, 29(3):54-63.

Angiogenesis is a major contributor to tumor growth and metastasis within breast cancer tumor microenvironment in which different proangiogenic factors have been identified and associated with tumor progression, metastasis and poor prognosis. The aim of the current study was to evaluate the angiogenesis among breast cancer patients through ex vivo assessment of the angiogenic factors interleukin 8 (IL-8) and vascular endothelial growth factor (VEGF)-A expressions in excised tumor tissues as well as matrix metalloproteinase 9 (MMP-9) serum levels as well as the prognostic value of MMP-9. Our study included 28 invasive ductal carcinoma female patients who were scheduled for modified radical mastectomy at Medical Research Institute, Alexandria University, Egypt and 10 control subjects. Both IL-8 and VEGF-A expressions were immunohistochemically detected in tumor tissues and serum MMP-9 was determined by ELISA. Although no significant correlations were found between each of IL-8, VEGF-A, MMP-9 levels, and patients' clinicopathological parameters, a significant positive correlation was found between these angiogenic factors each other suggesting their synergistic roles in proceeding angiogenesis. Higher serum MMP-9 level was detected in breast cancer patients compared to the control group, indicating that it can be used as a prognostic biomarker in breast cancer patients.

RevDate: 2022-06-27

Kench JG, Amin MB, Berney DM, et al (2022)

WHO Classification of Tumours 5th Edition: Evolving Issues in Classification, Diagnosis and Prognostication of Prostate Cancer.

Histopathology [Epub ahead of print].

The 5th edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: 1) recognition that PIN-like carcinoma is not synonymous with a pattern of ductal carcinoma but better classified as a subtype of acinar adenocarcinoma; 2) a specific section on treatment-related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; 3) a terminology change of basal cell carcinoma to "adenoid cystic (basal cell) cell carcinoma" given the presence of an underlying MYB::NFIB gene fusion in many cases; 4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and 5) more detailed coverage of intraductal carcinoma of prostate (IDC-P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC-P but containing more atypia than typically seen in high-grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma.

RevDate: 2022-06-27

Ghafil JA, İbrahim BMS, AK Zgair (2022)

Coating indwelling urinary catheters with moxifloxacin prevents biofilm formation by Burkholderia cepacia.

Polimery w medycynie [Epub ahead of print].

BACKGROUND: Burkholderia cepacia adhesion and biofilm formation onto abiotic surfaces is an important feature of clinically relevant isolates. The in vitro biofilm formation of B. cepacia onto coated indwelling urinary catheters (IDCs) with moxifloxacin has not been previously investigated.

OBJECTIVES: To examine the ability of B. cepacia to form biofilms on IDCs and the effect of coating IDCs with moxifloxacin on biofilm formation by B. cepacia in vitro.

MATERIAL AND METHODS: The adhesion of B. cepacia to coated and uncoated IDCs with moxifloxacin was evaluated. Pieces of IDCs were coated with moxifloxacin (adsorption method). The spectrophotometric method was used to check moxifloxacin leaching into tubes. Coated and uncoated tubes were incubated with 107 colony forming units (cfu)/mL of B. cepacia. The viable bacterial count was used to count the number of bacteria adhered to coated and uncoated IDC pieces.

RESULTS: A significant adhesion of B. cepacia to uncoated IDC pieces started 15 min after the incubation in a bacterial suspension (107 cfu/mL). A maximum adhesion was observed at 48 h. The pretreatment of IDCs with 100 μg/mL of moxifloxacin produced the best adsorption of antibiotic onto the IDCs. Coating IDC pieces with moxifloxacin significantly reduced the adhesion and biofilm formation of B. cepacia (p < 0.05) at various time intervals (1 h, 4 h and 24 h).

CONCLUSIONS: The present study has demonstrated for the first time that coated IDCs with moxifloxacin reduce B. cepacia adhesion and biofilm formation. This finding has opened the door to the production of the new generation IDCs that prevent bacteria from attaching and forming biofilms.

RevDate: 2022-06-25

Jeong Y, Jin M, Kim KS, et al (2022)

Biocompatible carbonized iodine-doped dots for contrast-enhanced CT imaging.

Biomaterials research, 26(1):27.

BACKGROUND: Computed tomography (CT) imaging has been widely used for the diagnosis and surveillance of diseases. Although CT is attracting attention due to its reasonable price, short scan time, and excellent diagnostic ability, there are severe drawbacks of conventional CT contrast agents, such as low sensitivity, serious toxicity, and complicated synthesis process. Herein, we describe iodine-doped carbon dots (IDC) for enhancing the abilities of CT contrast agents.

METHOD: IDC was synthesized by one-pot hydrothermal synthesis for 4 h at 180 ℃ and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, NMR, TEM, and DLS. Furthermore, the CT values of IDC were calculated and compared with those of conventional CT contrast agents (Iohexol), and the in vitro and in vivo toxicities of IDC were determined to prove their safety.

RESULTS: IDC showed improved CT contrast enhancement compared to iohexol. The biocompatibility of the IDC was verified via cytotoxicity tests, hemolysis assays, chemical analysis, and histological analysis. The osmotic pressure of IDC was lower than that of iohexol, resulting in no dilution-induced contrast decrease in plasma.

CONCLUSION: Based on these results, the remarkable CT contrast enhancement and biocompatibility of IDC can be used as an effective CT contrast agent for the diagnosis of various diseases compared with conventional CT contrast agents.

RevDate: 2022-06-25

Maimon A, Yizhar O, Buchs G, et al (2022)

A case study in phenomenology of visual experience with retinal prosthesis versus visual-to-auditory sensory substitution.

Neuropsychologia pii:S0028-3932(22)00164-6 [Epub ahead of print].

The phenomenology of the blind has provided an age-old, unparalleled means of exploring the enigmatic link between the brain and mind. This paper delves into the unique phenomenological experience of a man who became blind in adulthood. He subsequently underwent both an Argus II retinal prosthesis implant and training, and extensive training on the EyeMusic visual to auditory sensory substitution device, thereby becoming the first reported case to date of dual proficiency with both devices. He offers a firsthand account into what he considers the great potential of combining sensory substitution devices with visual prostheses as part of a complete visual restoration protocol. While the Argus II retinal prosthesis alone provided him with immediate visual percepts by way of electrically stimulated phosphenes elicited by the device, the EyeMusic SSD requires extensive training from the onset. Yet following the extensive training program with the EyeMusic sensory substitution device, our subject reports that the sensory substitution device allowed him to experience a richer, more complex perceptual experience, that felt more "second nature" to him, while the Argus II prosthesis (which also requires training) did not allow him to achieve the same levels of automaticity and transparency. Following long-term use of the EyeMusic SSD, our subject reported that visual percepts representing mainly, but not limited to, colors portrayed by the EyeMusic SSD are elicited in association with auditory stimuli, indicating the acquisition of a high level of automaticity. Finally, the case study indicates an additive benefit to the combination of both devices on the user's subjective phenomenological visual experience.

RevDate: 2022-06-24

Hardeman AA, Han YJ, Grushko TA, et al (2022)

Subtype-specific expression of MELK is partly due to copy number alterations in breast cancer.

PloS one, 17(6):e0268693 pii:PONE-D-21-40232.

Maternal embryonic leucine-zipper kinase (MELK) regulates cell cycle progression and is highly expressed in many cancers. The molecular mechanism of MELK dysregulation has not been determined in aggressive forms of breast cancer, such as triple negative breast cancer (TNBC). To evaluate molecular markers of MELK aberrations in aggressive breast cancer, we assessed MELK gene amplification and expression in breast tumors. MELK mRNA expression is highly up-regulated in basal-like breast cancer (BLBC), the major molecular subtype of TNBC, compared to luminal or other subtypes of breast tumors. MELK copy number (CN) gains are significantly associated with BLBC, whereas no significant association of CpG site methylation or histone modifications with breast cancer subtypes was observed. Accordingly, the CN gains appear to contribute to an increase in MELK expression, with a significant correlation between mRNA expression and CN in breast tumors and cell lines. Furthermore, immunohistochemistry (IHC) assays revealed that both nuclear and cytoplasmic staining scores of MELK were significantly higher in invasive ductal carcinoma (IDC) tumors compared to ductal carcinoma in situ (DCIS) and normal breast tissues. Our data showed that upregulation of MELK in BLBC may be in part driven by CN gains, rather than epigenetic modifications, indicating a potential for overexpression and CN gains of MELK to be developed as a diagnostic and prognostic marker to identify patients who have more aggressive breast cancer.

RevDate: 2022-06-24

Weis S, Hagel S, Palm J, et al (2022)

Effect of Automated Telephone Infectious Disease Consultations to Nonacademic Hospitals on 30-Day Mortality Among Patients With Staphylococcus aureus Bacteremia: The SUPPORT Cluster Randomized Clinical Trial.

JAMA network open, 5(6):e2218515 pii:2793550.

Importance: Staphylococcus aureus bacteremia (SAB) is a common and potentially severe infectious disease (ID). Retrospective studies and derived meta-analyses suggest that bedside infectious disease consultation (IDC) for SAB is associated with improved survival; however, such IDCs might not always be possible because of the lack of ID specialists, particularly at nonacademic hospitals.

Objectives: To investigate whether unsolicited telephone IDCs (triggered by an automated blood stream infection reporting system) to nonacademic hospitals improved 30-day all-cause mortality in patients with SAB.

This patient-blinded, multicenter, interventional, cluster randomized, controlled, crossover clinical trial was conducted in 21 rural, nonacademic hospitals in Thuringia, Germany. From July 1, 2016, to December 31, 2018, 1029 blood culture reports were assessed for eligibility. A total of 386 patients were enrolled, whereas 643 patients were not enrolled for the following reasons: death before enrollment (n = 59); palliative care (n = 41); recurrence of SAB (n = 9); discharge from the hospital before enrollment (n = 77); age younger than 18 years (n = 5); duplicate report from a single patient (n = 26); late report (n = 17); blood culture reported during the washout phase (n = 48); and no signed informed consent for other or unknown reasons (n = 361).

Interventions: During the ID intervention phase, ID specialists from Jena University Hospital provided unsolicited telephone IDCs to physicians treating patients with SAB. During the control phase, patients were treated according to local standards. Crossover was performed after including 15 patients or, at the latest, 1 year after the first patient was included.

Main Outcomes and Measures: Thirty-day all-cause mortality.

Results: A total of 386 patients (median [IQR] age, 75 [63-82] years; 261 [67.6%] male) were included, with 177 randomized to the IDC group and 209 to the control group. The 30-day all-cause mortality rate did not differ between the IDC and control groups (relative risk reduction [RRR], 0.12; 95% CI, -2.17 to 0.76; P = .81). No evidence was found of a difference in secondary outcomes, including 90-day mortality (RRR, 0.17; 95% CI, -0.59 to 0.57; P = .62), 90-day recurrence (RRR, 0.10; 95% CI, -2.51 to 0.89; P = .89), and hospital readmission (RRR, 0.04; 95% CI, -0.63 to 0.48; P = .90). Exploratory evidence suggested that indicators of quality of care were potentially realized more often in the IDC group than in the control group (relative quality improvement, 0.16; 95% CI, 0.08-0.26; P = .01).

Conclusions and Relevance: In this cluster randomized clinical trial, unsolicited telephone IDC, although potentially enhancing quality of care, did not improve 30-day all-cause mortality in patients with SAB.

Trial Registration: drks.de Identifier: DRKS00010135.

RevDate: 2022-06-24

Ortega MA, Fraile-Martinez O, García-Montero C, et al (2022)

Patients with Invasive Lobular Carcinoma Show a Significant Increase in IRS-4 Expression Compared to Infiltrative Ductal Carcinoma-A Histopathological Study.

Medicina (Kaunas, Lithuania), 58(6): pii:medicina58060722.

Background and Objectives: Breast cancer (BC) is the first diagnosed type of cancer and the second leading cause of cancer-related mortality in women. In addition, despite the improvement in treatment and survival in these patients, the global prevalence and incidence of this cancer are rising, and its mortality may be different according to the histological subtype. Invasive lobular carcinoma (ILC) is less common but entails a poorer prognosis than infiltrative ductal carcinoma (IDC), exhibiting a different clinical and histopathological profile. Deepening study on the molecular profile of both types of cancer may be of great aid to understand the carcinogenesis and progression of BC. In this sense, the aim of the present study was to explore the histological expression of Insulin receptor substrate 4 (IRS-4), cyclooxygenase 2 (COX-2), Cyclin D1 and retinoblastoma protein 1 (Rb1) in patients with ILC and IDC. Patients and Methods: Thus, breast tissue samples from 45 patients with ILC and from 45 subjects with IDC were analyzed in our study. Results: Interestingly, we observed that IRS-4, COX-2, Rb1 and Cyclin D1 were overexpressed in patients with ILC in comparison to IDC. Conclusions: These results may indicate a differential molecular profile between both types of tumors, which may explain the clinical differences among ILC and IDC. Further studies are warranted in order to shed light onto the molecular and translational implications of these components, also aiding to develop a possible targeted therapy to improve the clinical management of these patients.

RevDate: 2022-06-23

Clawson A, Zahir SF, Stewart S, et al (2022)

Characteristics and outcomes of hospitalised inpatients with indwelling urinary catheter-a retrospective study from a large regional hospital in queensland.

Infection, disease & health pii:S2468-0451(22)00026-8 [Epub ahead of print].

BACKGROUND: Indwelling urinary catheters (IDCs) are a common invasive device in hospitalised patients. Their use is associated with increased risks of developing catheter associated urinary tract infections (CAUTI), and blood stream infections (BSI).

AIMS: To examine the characteristics and outcomes of adult inpatients with an IDC inserted in hospital and identify risk factors for developing CAUTI and BSI.

METHODS: We performed a retrospective observational study of 430 patients with IDC admitted to medical and surgical units of a leading (tertiary) hospital between Nov 2019 till April 2020. Multiple logistic regression analysis was performed to determine independent risk factors for developing urinary tract infection and blood stream infection.

RESULTS: The prevalence of CAUTI in our study was 7.4%. Results of multiple logistic regression indicated that with each day of IDC in situ, the likelihood of UTI development increased by 9% (OR 1.09; 95% CI 1.00 to 1.18; p = 0.03). Age, gender, and catheter reinsertion were not associated with UTI development.

CONCLUSIONS: Longer duration of IDC was associated with elevated risk of developing CAUTI. CAUTI rates were higher than some of those previously published. There was no statistical significance in frequency of CAUTI between medical and surgical patients. No statistically significant variables that contributed to the development of BSI were found. Interventions targeted at reducing catheter days should be used to improve CAUTI rates.

RevDate: 2022-06-23

Hammood ZD, Najar KA, Latif S, et al (2022)

Bilateral invasive ductal carcinoma of the breast; a case report with literature review.

Annals of medicine and surgery (2012), 78:103743 pii:S2049-0801(22)00503-9.

Introduction: Carcinoma of breast is a heterogeneous disease. Using their light microscopic appearance, the invasive forms are usually divided into three main types: infiltrating lobular carcinomas, infiltrating ductal carcinomas, and other infiltrating carcinomas. This paper aims to discuss and report a case of bilateral invasive ductal carcinoma of the breast.

Case report: A 48-year-old female presented with bilateral breast masses of 5-month duration. On examination. she had bilateral palpable breast masses, which were hard, mobile, and irregular. On the right side, there was skin tethering and palpable axillary lymph nodes. Ultrasound examination showed a heterogeneous, irregular, ill-defined, mass-like lesion, seen in the upper outer quadrant of the right breast along with a hypoechoic. irregular mass 12*13mm in the upper outer quadrant of the left breast. FNA showed bilateral invasive ductal carcinoma. Right axillary lymph nodes were positive for adenocarcinoma. She received 4 sessions of NACT which was followed by right-side mastectomy with axillary lymph node dissection and left-side mastectomy with sentinel lymph node biopsy.

Discussion: Bilateral breast carcinomas are very rare. They form 2-5% of all breast malignancies. About 2-11% of breast cancer patients develop cancer in the opposite breast in their lifetime with an incidence rate varying from 4 to 8 per 1000 people per year.

Conclusion: Bilateral carcinoma of the breast is very rare. Microscopically, the findings usually reveal infiltrative ductal carcinoma. The treatment of choice is bilateral modified radical mastectomy.

RevDate: 2022-06-20

Gordon O, Peart Akindele N, Schumacher C, et al (2022)

Increasing Pediatric Infectious Diseases Consultation Rates for Staphylococcus aureus Bacteremia.

Pediatric quality & safety, 7(3):e560.

Introduction: Staphylococcus aureus bacteremia (SAB) in children is associated with significant mortality and morbidity, including recurrent bacteremia. Infectious disease consultation (IDC) improves SAB outcomes in adult patients. However, increasing IDC and impact for pediatric patients with SAB is not well described.

Methods: This quality improvement project aimed to increase IDC for SAB events at a quaternary pediatric medical center. First, we evaluated the local practices regarding pediatric SAB and engaged stakeholders (July 2018-August 2020). We added an advisory comment supporting IDC for SAB to all blood culture results in September 2020. Using statistical process control charts, we monitored the number of SAB events with IDC before a SAB event without IDC. Finally, we evaluated SAB recurrences before and after initiating the advisory comment.

Results: In the baseline period, 30 of 49 (61%) SAB events received an IDC with a mean of 1.4 SAB events with IDC before a SAB event without IDC. Postintervention, 22 of 23 (96%) SAB events received IDC with a mean of 14 events with IDC before 1 event without IDC. The SAB recurrence rate was 8%, with 6 events in 4 children; none of the index cases resulting in recurrence received an IDC (P = 0.0002), and all occurred before any intervention.

Conclusions: An electronic advisory comment supporting IDC for SAB significantly increased the rate of pediatric IDC with no further SAB recurrence episodes following intervention. This low-resource intervention may be considered in other pediatric centers to optimize SAB management.

RevDate: 2022-06-20

Enochs C, Filbrun AG, Iwanicki C, et al (2021)

Development of an Interdisciplinary Telehealth Care Model in a Pediatric Cystic Fibrosis Center.

Telemedicine reports, 2(1):224-232 pii:10.1089/tmr.2021.0021.

Background: People with cystic fibrosis (PCF) have unique physical and emotional needs, which are best met through interdisciplinary care (IDC). In the midst of the pandemic, our center aimed to begin a telehealth care model with an objective to increase successful care visits from baseline of 0-95% by June 26, 2020, including meeting cystic fibrosis (CF) care standards of IDC visits that are coproduced through agenda setting with PCF. Methods: Shifting IDC for pediatric CF patients to telehealth was part of a quality improvement initiative. Our team used asynchronous virtual visits (VVs), with the IDC team members' VVs done on different days than the physician's. Multiple plan-do-study-act cycles were completed to address evolving telehealth needs, including IDC team member flow logistics, communication with PCF, and surveying PCF for the patient perspective. Rates of IDC and agenda setting were measured from March 16, 2020 to June 26, 2020. Results: IDC VVs were at 86% in March 2020 with fluctuations until mid-May when we reached 100% and achieved sustainability. Agenda setting was reached at 100% and maintained. With continued effort, an additional 46.3% of PCF registered for the patient portal, totaling 90.6% with access. Our survey revealed 100% of PCF were able to see IDC team members that they needed to, with 87% "extremely satisfied" and 13% "somewhat satisfied" with their telehealth experience. Conclusions: Successful telehealth in pediatric CF IDC can be achieved through continuous communication, optimal utilization of available technologies, and may help foster unique opportunities to help improve health outcomes.

RevDate: 2022-06-21
CmpDate: 2022-06-21

Ssentongo P, Oh JS, Amponsah-Manu F, et al (2022)

Breast Cancer Survival in Eastern Region of Ghana.

Frontiers in public health, 10:880789.

Objective: Five-year overall survival rate of breast cancer in low-income countries (LICs) is significantly lower than in high-resource countries. This study explored clinical and pathological factors influencing mortality in the Eastern region of Ghana.

Methods: We performed a retrospective medical chart review for patients undergoing surgery and chemotherapy for breast cancer at a regional hospital in Ghana from January 2014 to January 2017. Descriptive and survival analysis was done.

Results: One hundred and twenty-nine patients were included in the study. The median age at presentation was 51 years. Sixty percent of patients presented with poorly differential histological grade III. The most common histological type was invasive ductal carcinoma (83%). Based on stage assessment using only tumor size and lymph node status, 60% presented at stage 3. Only 25% were tested for hormone receptor proteins and HER2 status. Of these, 57% had triple-negative breast cancer (TNBC). The 3-year overall survival rate was only 52%.

Conclusion: The cumulative 3-year survival was 52%. Despite success in reducing cancer mortality in northern Africa, survival in sub-Saharan Africa remains poor. A significantly higher percentage of GIII and TNBC is found in breast cancers seen in Ghana. When combined with limited capacity for accurate diagnosis, cancer subtype analysis, adequate therapy, and follow-up, late-stage presentation leads to poor outcomes. Future studies should emphasize the identification of barriers to care and opportunities for cost-effective and sustainable improvements in diagnosing and treating breast cancer in LICs.

RevDate: 2022-06-20

Lu X, Jing L, Liu S, et al (2022)

miR-149-3p Is a Potential Prognosis Biomarker and Correlated with Immune Infiltrates in Uterine Corpus Endometrial Carcinoma.

International journal of endocrinology, 2022:5006123.

Background: Endocrine disruption is an important factor in the development of endometrial cancer. Expression of miR-149-3p is observed in some cancer types, while its role in uterine corpus endometrial carcinoma (UCEC) is unclear.

Methods: The clinical and genomic data and prognostic information on UCEC were obtained for patients from the TCGA database. The Kruskal-Wallis test, Wilcoxon signed-rank test, and logistic regression were used to analyze the relationship between clinical characteristics and miR-149-3p expression. Kaplan-Meier survival curve analysis was used to study the influence of miR-149-3p expression and miR-149-3p target genes on the prognosis of UCEC patients. The TargetScan, PicTar, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine the involvement of miR-149-3p target genes in function. Immune infiltration analysis was used to analyze the functional involvement of miR-149-3p. QRT-PCR was used to validate the expression of miR-149-3p in UCEC cell lines.

Results: High expression of miR-149-3p in UCEC was significantly associated with age (P < 0.001), histological type (P < 0.001), histological grade (P < 0.001), tumor invasion (P=0.014), and radiation therapy (P=0.011). High miR-149-3p expression predicted poorer overall survival (OS) (HR: 2.56; 95% CI: 1.64-4.00; P < 0.001), progression-free interval (PFI) (HR: 1.85; 95% CI: 1.29-2.65; P=0.001), and disease-specific survival (DSS) (HR: 2.33; 95% CI: 1.37-3.99; P=0.002). Low expressions of miR-149-3p target genes, including ADCYAP1R1, CGNL1, CHST3, CYGB, DNAH9, ESR1, HHIP, HIC1, HOXD11, IGF1, INMT, LSP1, MTMR10, NFIC, PLCE1, RARA, SNTN, SPRYD3, and ZBTB7A, were associated with poor OS in UCEC. MiR-149-3p may be involved in the occurrence and development of UCEC via pathways including PI3K-Akt signaling pathway, Ras signaling pathway, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, and MAPK signaling pathway. miR-149-3p may inhibit the function of CD8 T cells, cytotoxic cells, eosinophils, iDC, mast cells, neutrophils, NK CD56bright cells, NK CD56dim cells, pDC, T cells, T helper cells, TFH, Th17 cells, and Treg. miR-149-3p was significantly upregulated in UCEC cell lines compared with endometriotic stromal cells.

Conclusion: High expression of miR-149-3p was significantly associated with poor survival in UCEC patients. It may be a promising biomarker of prognosis and response to immunotherapy for UCEC patients.

RevDate: 2022-06-21

Sakurai M, Weber P, Wolff G, et al (2022)

TSC22D4 promotes TGFβ1-induced activation of hepatic stellate cells.

Biochemical and biophysical research communications, 618:46-53 pii:S0006-291X(22)00823-3 [Epub ahead of print].

Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and liver fibrosis emerge as progressive liver diseases that accompany metabolic syndrome usually characterized by obesity, insulin resistance and type 2 diabetes. Currently no FDA approved treatments exist for the treatment of NASH and liver fibrosis, which requires a better knowledge of the underlying molecular mechanisms. TSC22D4 belongs to the TSC-22 protein family, the members of which are regulated by inflammatory and stress signals. Interestingly, patients with type 2 diabetes, with NAFLD as well as with NASH all have elevated levels of hepatic TSC22D4 expression. Previous studies with targeted deletion of TSC22D4 specifically in hepatocytes showed that TSC22D4 not only acts as a critical controller of diabetic hyperglycemia, but also contributes to NAFLD/NASH progression. To gain better insight into the development of progressive liver diseases, here we studied the function of TSC22D4 in hepatic stellate cells (HSCs), which play a key role in the pathogenesis of liver fibrosis. Our results indicated that TSC22D4 contributes to TGFβ1-mediated activation of HSCs and promotes their proliferation and migration. RNA-Sequencing analysis revealed that TSC22D4 initiates transcriptional events associated with HSC activation. Overall, our findings establish TSC22D4 as a key hub in the development of liver fibrosis, acting across different cellular compartments. Combinatorial TSC22D4 targeting in both hepatocytes and HSC may thus show superior efficacy against progressive liver disease.

RevDate: 2022-06-17

Icht M, Bergerzon-Bitton O, BM Ben-David (2022)

Validation and cross-linguistic adaptation of the Frenchay Dysarthria Assessment (FDA-2) speech intelligibility tests: Hebrew version.

International journal of language & communication disorders [Epub ahead of print].

'Dysarthria' is a group of motor speech disorders resulting from a disturbance in neuromuscular control. Most individuals with dysarthria cope with communicative restrictions due to speech impairments and reduced intelligibility. Thus, language-sensitive measurements of intelligibility are important in dysarthria neurological assessment. The Frenchay Dysarthria Assessment, 2nd edition (FDA-2), is a validated tool for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. The current study conducted a careful culture- and linguistic-sensitive adaption of the two intelligibility subtests of the FDA-2 to Hebrew (words and sentences) and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (acquired dysarthria, n = 15; and developmental dysarthria, n = 19). Analysis indicated that the new subtests were found to be specific and sensitive, valid and reliable, as scores significantly differ between healthy older adults and adults with dysarthria, correlated with other subjective measures of intelligibility, and showed high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers, thus may be an important addition to the speech-language pathologist's toolbox, for clinical work as well as for research purposes. WHAT THIS PAPER ADDS: What is already known on the subject 'Dysarthria' is a group of disorders reflecting impairments in the strength, speed and precision of movements required for adequate control of the various speech subsystems. Reduced speech intelligibility is one of the main consequences of all dysarthria subtypes, irrespective of their underlying cause. Indeed, most individuals with dysarthria cope with communicative restrictions due to speech impairments. Thus, language-sensitive measurements of intelligibility are important in dysarthria assessment. The FDA-2's words and sentences subtests present standardized and validated tools for the identification of the nature and patterns of oro-motor movements associated with different types of dysarthria. What this paper adds to existing knowledge The lack of assessment tools in Hebrew poses challenges to clinical evaluation as well as research purposes. The current study conducted a careful culture- and linguistic-sensitive adaption of the FDA-2 intelligibility subtests to Hebrew and performed a preliminary validation with relevant clinical populations. First, sets of Hebrew words and sentences were constructed, based on the criteria defined in FDA-2, as well as on several other factors that may affect performance: emotional valence, arousal and familiarity. Second, the new subtests were validated in healthy older adults (n = 20), and in two clinical groups (adults with acquired dysarthria, n = 15; and young adults with developmental dysarthria, n = 19). What are the potential or actual clinical implications of this work? Analyses indicated that the new word and sentence subtests are specific, sensitive, valid and reliable. Namely, (1) they successfully differentiate between healthy individuals and individuals with dysarthria; (2) they correlate with other subjective measures of intelligibility; and (3) they show high test-retest reliability. The words and sentences intelligibility subtests can be used to evaluate speech disorders in various populations of Hebrew speakers. Thus, they may be an important addition to the speech-language pathologist's toolbox, for clinical and research purposes. The methods described here can be emulated for the adaptation of speech assessment tools to other languages.

RevDate: 2022-06-20
CmpDate: 2022-06-20

Choi JDW, Hughes TMD, Marx G, et al (2022)

The Utility of the Oncotype DX Test for Breast Cancer Patients in an Australian Multidisciplinary Setting.

The breast journal, 2022:1199245.

Introduction: The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2- breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score.

Methods: We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11-25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4-8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33-77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10-20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%).

Conclusion: This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered.

RevDate: 2022-06-15

Gong AJ, Nguyen DL, Lee EE, et al (2022)

Comparison of Outcomes for One-View Asymmetries Recalled From Digital Breast Tomosynthesis Versus Full-Field Digital Mammography Screening Examinations.

AJR. American journal of roentgenology [Epub ahead of print].

Background: Recall rates are lower for digital breast tomosynthesis (DBT) than full-field digital mammography (FFDM). This difference could have important implications with respect to one-view asymmetries given that missed cancers are often visible on one view. Purpose: To compare outcomes of one-view asymmetries recalled from DBT versus FFDM screening mammography, and to determine predictors of malignancy among recalled asymmetries. Methods: This retrospective study first determined recall rates associated with one-view asymmetries for screening mammograms performed by DBT and FFDM from July 14, 2016 through July 14, 2020. Further analyses included patients recalled for a one-view asymmetry who completed subsequent diagnostic workup and all recommended follow-up. Patient and cancer characteristics were extracted from the electronic health record. Results: Recall rate associated with asymmetries was lower for screening by DBT (3169/128,755 [2.5%]) than FFDM (815/23,898 [3.4%]) (p<.001). Further analyses of patients who completed diagnostic workup and subsequent follow-up included 3119 patients (mean age, 57 years) for DBT and 811 patients (56 years) for FFDM. Distribution of final BI-RADS categories from subsequent diagnostic workup was not different between the two modalities (p>.99). Frequency of malignancy was not different between asymmetries recalled from DBT [54/3119 (1.7%)] and FFDM [(14/811) (1.7%)] (p>.99). Malignant asymmetries identified on FFDM versus DBT were more frequently associated with architectural distortion on diagnostic workup [5/14 (36%) vs 5/54 (9%), p<.001]; and were more commonly invasive ductal carcinoma (93% vs 57%) and less commonly invasive lobular carcinoma (0% vs 24%) (p=.05). In multivariable analysis, independent predictors of malignancy among recalled asymmetries on DBT were age (55-69 years, odds ratio (OR)=2.40, p=.04; ≥70 years, OR=7.93, p<.001; reference: <55 years), and breast density (not dense breasts, OR=2.47, p=.001; reference: dense breasts). Conclusions: Recalled asymmetries were less frequent for DBT than FFDM. Malignancy rate was low for both modalities (1.7%). Age ≥55 and lower breast density predicted malignancy for DBT-recalled asymmetries. Clinical Impact: Our results support use of DBT to reduce unnecessary recalls without altering PPV for asymmetry-associated malignancies. Patient factors should be considered when assessing whether a potential asymmetry on DBT screening represents overlapping fibroglandular tissue or a suspicious finding requiring diagnostic workup.

RevDate: 2022-06-14

Chen YQ, Xu XF, Xu JW, et al (2022)

A high-quality model for predicting the prognosis of breast neuroendocrine carcinoma to help clinicians decide on appropriate treatment methods: A population-based analysis.

Translational oncology, 22:101467 pii:S1936-5233(22)00126-7 [Epub ahead of print].

BACKGROUND: Breast neuroendocrine carcinoma (NEC) is a rare malignancy with unclear treatment options and prognoses. This study aimed to construct a high-quality model to predict overall survival (OS) and breast cancer-specific survival (BCSS) and help clinicians choose appropriate breast NEC treatments.

PATIENTS AND METHODS: A total of 378 patients with breast NEC and 349,736 patients with breast invasive ductal carcinoma (IDC) were enrolled in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Propensity score matching (PSM) was performed to balance the clinical baseline. Prognostic factors determined by multivariate Cox analysis were included in the nomogram. C-index and calibration curves were used to verify the performance of the nomogram.

RESULTS: Nomograms were constructed for the breast NEC and breast IDC groups after PSM. The C-index of the nomograms ranged from 0.834 to 0.880 in the internal validation and 0.818-0.876 in the external validation, indicating that the nomogram had good discrimination. The risk stratification system showed that patients with breast NEC had worse prognoses than those with breast IDC in the low-risk and intermediate-risk groups but had a similar prognosis that those in the high-risk group. Moreover, patients with breast NEC may have a better prognosis when undergoing surgery plus chemotherapy than when undergoing surgery alone or chemotherapy alone.

CONCLUSIONS: We established nomograms with a risk stratification system to predict OS and BCSS in patients with breast NEC. This model could help clinicians evaluate prognosis and provide individualized treatment recommendations for patients with breast NEC.

RevDate: 2022-06-13

Rebbeck CA, Xian J, Bornelöv S, et al (2022)

Gene expression signatures of individual ductal carcinoma in situ lesions identify processes and biomarkers associated with progression towards invasive ductal carcinoma.

Nature communications, 13(1):3399.

Ductal carcinoma in situ (DCIS) is considered a non-invasive precursor to breast cancer, and although associated with an increased risk of developing invasive disease, many women with DCIS will never progress beyond their in situ diagnosis. The path from normal duct to invasive ductal carcinoma (IDC) is not well understood, and efforts to do so are hampered by the substantial heterogeneity that exists between patients, and even within patients. Here we show gene expression analysis from > 2,000 individually micro-dissected ductal lesions representing 145 patients. Combining all samples into one continuous trajectory we show there is a progressive loss in basal layer integrity heading towards IDC, coupled with two epithelial to mesenchymal transitions, one early and a second coinciding with the convergence of DCIS and IDC expression profiles. We identify early processes and potential biomarkers, including CAMK2N1, MNX1, ADCY5, HOXC11 and ANKRD22, whose reduced expression is associated with the progression of DCIS to invasive breast cancer.

RevDate: 2022-06-13

Gur N, Zimmerman-Brenner S, Fattal-Valevski A, et al (2022)

Group comprehensive behavioral intervention for tics contribution to broader cognitive and emotion regulation in children.

European child & adolescent psychiatry [Epub ahead of print].

There is increasing evidence for the effectiveness of behavioral techniques in managing tics in youth with Tourette syndrome and tics disorders (TDs). One such intervention is Comprehensive Behavioral Intervention for Tics (CBIT), which focuses on reducing tic severity by training control and regulation. In view of the regulation deficits characteristic to TDs, in the current study, we aimed to explore the contribution of CBIT beyond tic control, to a wider expression of regulation abilities-cognitive inhibition and emotion regulation. A total of 55 participants with TDs, aged 8-15, who were randomly assigned to group-CBIT or group-Educational Intervention for Tics, were compared on cognitive inhibition tests and use of emotion-regulation strategies, pre- and post-intervention. Whereas on none of the scales a significant interaction effect was found reflecting superiority of CBIT over EIT, repeated measures ANOVA revealed a significant time effect, with post hoc analyses indicating that cognitive inhibition and cognitive reappraisal significantly increased following CBIT intervention only. Within the group-CBIT, the increase in cognitive reappraisal was associated with higher intellectual ability. These findings may lead to a broader understanding of CBIT contribution to more than tic control, but rather to better cognitive and emotional regulation abilities.

RevDate: 2022-06-13

Agostinetto E, Nader-Marta G, Paesmans M, et al (2022)

ROSALINE: a phase II, neoadjuvant study targeting ROS1 in combination with endocrine therapy in invasive lobular carcinoma of the breast.

Future oncology (London, England) [Epub ahead of print].

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene CDH1, is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in in vivo studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

RevDate: 2022-06-13

Yan Z, Wong A, Ng RP, et al (2022)

Determining the benefit of neoadjuvant chemotherapy in reduction of axillary dissection rates in Z0011 trial cohort with high nodal burden.

Gland surgery, 11(5):788-794.

Background: In breast cancer patients fulfilling the Z0011 trial criteria, axillary lymph node dissection (ALND) is reserved for patients with a high nodal burden of ≥3 metastatic nodes. In this group of patients, to avoid an ALND, neoadjuvant chemotherapy (NACT) could be given instead to achieve nodal pathological complete response (pCR). However, the benefit of NACT in achieving nodal pCR and avoiding ALND in this group of patients is unknown. We aimed to determine the nodal pCR rate in this group of patients who otherwise would have needed an ALND.

Methods: cT1-2N0 breast cancer patients, with histologically proven nodal metastasis, who underwent NACT were identified from a prospectively maintained database. The sonographic criteria of ≥3 abnormal nodes, which has been reported as highly predictive of high nodal burden, was then used to identify the high nodal burden group. Nodal pCR was determined based on the ALND following NACT.

Results: Twenty-four patients with high nodal burden were identified. Mean age was 55.2 years. 91.7% had invasive ductal carcinoma and 29.2% had grade III cancer. 54.2% achieved nodal pCR which was associated with ypT (P=0.006). Nodal pCR was 75%, 70% and 30% in the triple negative, human epidermal growth factor receptor2 (HER2) positive and ER/PR+HER2- tumors, respectively.

Conclusions: In the postulated T1-2 breast cancer patients with high nodal burden, needing an upfront ALND, NACT could result in nodal pCR of 54.2%, with higher pCR in certain subtypes. Hence, to minimize ALND risk, NACT should be offered in this high nodal burden group.

RevDate: 2022-06-10

Silva DJ, Miranda G, A Mesquita (2022)

Clinical relevance of receptor conversion in metastatic breast cancer: Case report.

Medicine, 101(23):e29136 pii:00005792-202206100-00003.

INTRODUCTION: Breast cancer comprises several different pathological entities defined by the presence or absence of hormonal receptors and human epidermal growth factor receptor 2 (HER2). During the disease course, the increase in tumor heterogeneity contributes to the discordant expression of estrogen/progesterone receptors and HER2 status between primary and metastatic lesions. We describe a case that demonstrates the clinical relevance of molecular reassessment during metastatic breast cancer progression.

PATIENT CONCERNS: A 40-year-old Caucasian woman with germline breast cancer gene mutation was referred to a general surgery appointment after breast ultrasound revealed a suspicious nodular lesion in 2012.

DIAGNOSIS: Ultrasound-guided microbiopsy revealed an invasive ductal carcinoma of no special type, hormone receptor-positive, and HER2-negative.

INTERVENTIONS: The patient underwent modified radical left mastectomy, adjuvant radiotherapy, chemotherapy, and endocrine therapy. Four years after the diagnosis, HER2 positive lung progression was documented, and the patient received anti-HER2 targeted systemic therapy for 15 months. New disease progression with a triple-negative profile was found, and palliative systemic treatment was changed to carboplatin for 3 months until new progression. Based on the results of the OlympiAD trial, monotherapy with Olaparib 300 mg twice daily for 28 days was initiated.

OUTCOMES: After seven cycles of treatment, patient showed progressive improvement in quality of life and maintained stable disease without significant adverse events.

CONCLUSION: The clinical relevance of hormone receptor and HER2 status discordance between primary tumors and metastatic lesions has been studied in recent years. This case report illustrates the clinical impact of molecular changes during disease progression and the adaptation of treatment options. This allows for an increase in both survival and quality of life in patients with metastatic breast cancer.

RevDate: 2022-06-10

da Luz FAC, da Costa Marinho E, Nascimento CP, et al (2022)

Prognosis value of lymphovascular invasion in patients with invasive ductal breast carcinoma according to lymph node metastasis status.

Ecancermedicalscience, 16:1364 pii:can-16-1364.

Background: Tumour lymphovascular invasion is not routinely assessed in all pathology services, and whether reporting it quantitatively or qualitatively is the main factor associated with the loss of this prognostic event. This study aimed to analyse the prognostic value of qualitatively reported lymphovascular invasion in patients with invasive breast ductal carcinoma.

Methods: This was a retrospective, single-center study, enrolling a total of 426 patients with invasive ductal carcinoma of the breast with a report of lymphovascular invasion, with a median follow-up of approximately 4.5 years. Kaplan-Meier and Cox regression was performed to obtain the predictive value of lymphovascular invasion. Propensity score matching was performed to reduce bias by standardising factors with significant differential distribution of lymphovascular invasion status.

Results: Lymphovascular invasion was present in 197 (49.2%) patients. Multivariate Cox regression showed that lymphovascular invasion independently increases the risk of death by almost two times (adjusted hazard ratio (HR): 2.045 (1.226-3.406), p = 0.006) and the risk of distant metastasis by more than two times (adjusted HR: 2.373 (1.404-4.010), p = 0.001). Subgroup analysis after matching by propensity score in adjuvant-only patients showed that the lymphovascular invasion is a factor of increased death in N- patients (adjusted HR: 12.597 (1.624-97.728), p = 0.015) and of distant metastasis-free survival in N+ patients (adjusted HR: 4.862 (1.649-14.335), p = 0.004) and almost for N- patients (adjusted HR 7.905 (0.969-64.509), p = 0.004).

Conclusion: The presence of lymphovascular invasion is a predictor of worse prognosis in patients with invasive ductal carcinoma of the breast, even with metastatic lymph node disease (N1-N3).

RevDate: 2022-06-10

Yan R, Ren F, Li J, et al (2022)

Nuclei-Guided Network for Breast Cancer Grading in HE-Stained Pathological Images.

Sensors (Basel, Switzerland), 22(11): pii:s22114061.

Breast cancer grading methods based on hematoxylin-eosin (HE) stained pathological images can be summarized into two categories. The first category is to directly extract the pathological image features for breast cancer grading. However, unlike the coarse-grained problem of breast cancer classification, breast cancer grading is a fine-grained classification problem, so general methods cannot achieve satisfactory results. The second category is to apply the three evaluation criteria of the Nottingham Grading System (NGS) separately, and then integrate the results of the three criteria to obtain the final grading result. However, NGS is only a semiquantitative evaluation method, and there may be far more image features related to breast cancer grading. In this paper, we proposed a Nuclei-Guided Network (NGNet) for breast invasive ductal carcinoma (IDC) grading in pathological images. The proposed nuclei-guided attention module plays the role of nucleus attention, so as to learn more nuclei-related feature representations for breast IDC grading. In addition, the proposed nuclei-guided fusion module in the fusion process of different branches can further enable the network to focus on learning nuclei-related features. Overall, under the guidance of nuclei-related features, the entire NGNet can learn more fine-grained features for breast IDC grading. The experimental results show that the performance of the proposed method is better than that of state-of-the-art method. In addition, we released a well-labeled dataset with 3644 pathological images for breast IDC grading. This dataset is currently the largest publicly available breast IDC grading dataset and can serve as a benchmark to facilitate a broader study of breast IDC grading.

RevDate: 2022-06-09

Russo M, Amboni M, Volzone A, et al (2022)

Interplay between gait and neuropsychiatric symptoms in Parkinson's Disease.

European journal of translational myology [Epub ahead of print].

Parkinson's Disease (PD) is a neurodegenerative disease which involves both motor and non-motor symptoms. Non-motor mental symptoms are very common among patients with PD since the earliest stage. In this context, gait analysis allows to detect quantitative gait variables to distinguish patients affected by non-motor mental symptoms from patients without these symptoms. A cohort of 68 PD subjects (divided in two groups) was acquired through gait analysis (single and double task) and spatial temporal parameters were analysed; first with a statistical analysis and then with a machine learning (ML) approach. Single-task variables showed that 9 out of 16 spatial temporal features were statistically significant for the univariate statistical analysis (p-value< 0.05). Indeed, a statistically significant difference was found in stance phase (p-value=0.032), swing phase (p-value=0.042) and cycle length (p-value=0.03) of the dual task. The ML results confirmed the statistical analysis, in particular, the Decision Tree classifier showed the highest accuracy (80.9%) and also the highest scores in terms of specificity and precision. Our findings indicate that patients with non-motor mental symptoms display a worse gait pattern, mainly dominated by increased slowness and dynamic instability.

RevDate: 2022-06-09

Albogami S (2022)

Comprehensive analysis of gene expression profiles to identify differential prognostic factors of primary and metastatic breast cancer.

Saudi journal of biological sciences, 29(7):103318.

Breast cancer accounts for nearly half of all cancer-related deaths in women worldwide. However, the molecular mechanisms that lead to tumour development and progression remain poorly understood and there is a need to identify candidate genes associated with primary and metastatic breast cancer progression and prognosis. In this study, candidate genes associated with prognosis of primary and metastatic breast cancer were explored through a novel bioinformatics approach. Primary and metastatic breast cancer tissues and adjacent normal breast tissues were evaluated to identify biomarkers characteristic of primary and metastatic breast cancer. The Cancer Genome Atlas-breast invasive carcinoma (TCGA-BRCA) dataset (ID: HS-01619) was downloaded using the mRNASeq platform. Genevestigator 8.3.2 was used to analyse TCGA-BRCA gene expression profiles between the sample groups and identify the differentially-expressed genes (DEGs) in each group. For each group, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to determine the function of DEGs. Networks of protein-protein interactions were constructed to identify the top hub genes with the highest degree of interaction. Additionally, the top hub genes were validated based on overall survival and immunohistochemistry using The Human Protein Atlas. Of the top 20 hub genes identified, four (KRT14, KIT, RAD51, and TTK) were considered as prognostic risk factors based on overall survival. KRT14 and KIT expression levels were upregulated while those of RAD51 and TTK were downregulated in patients with breast cancer. The four proposed candidate hub genes might aid in further understanding the molecular changes that distinguish primary breast tumours from metastatic tumours as well as help in developing novel therapeutics. Furthermore, they may serve as effective prognostic risk markers based on the strong correlation between their expression and patient overall survival.

RevDate: 2022-06-08

Yu Y, Lajkosz K, Finelli A, et al (2022)

Impact of cribriform pattern 4 and intraductal prostatic carcinoma on National Comprehensive Cancer Network (NCCN) and Cancer of Prostate Risk Assessment (CAPRA) patient stratification.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Epub ahead of print].

Pretreatment classification tools are used in prostate cancer to inform patient management. The effect of cribriform pattern 4 (CC) and intraductal carcinoma (IDC) on such nomograms is still underexplored. We analyzed the Cancer of Prostate Risk Assessment (CAPRA) and National Comprehensive Cancer Network (NCCN) risk scores in cases with and without CC/IDC to assess impact on biochemical recurrence (BCR) and metastases/death of prostate cancer (event free survival-EFS) after prostatectomy. A matched biopsy- prostatectomy cohort (2010-2017) was reviewed for CC/IDC. CAPRA and NCCN scores were calculated. CAPRA score 0-2 were deemed "low", 3-5 "intermediate" and 6-10 "high". NCCN scores 1-2 "very low/low", 3 "favorable intermediate", 4 "unfavorable intermediate", 5-6 "high/very high". Cases were stratified by presence of CC/IDC. BCR and EFS probabilities were estimated using the Kaplan-Meier method. Prognostic performance was evaluated using log-rank tests and Harrell's concordance index. 612 patients with mean age 63.1 years were included with mean follow up of 5.3 (range 0-10.8) years. CC/IDC was noted in 159/612 (26%) biopsies. There were 101 (17%) BCR and 36 (6%) events. CAPRA discriminated three distinct risk categories for BCR (p < 0.001) while only high risk separated significantly for EFS (p < 0.001). NCCN distinguished two prognostic groups for BCR (p < 0.0001) and three for EFS (p < 0.0001). Addition of CC/IDC to CAPRA impacted scores 3-5 for BCR and scores 3-5 and 6-10 for EFS and improved the overall concordance index (BCR: 0.66 vs. 0.71; EFS: 0.74 vs. 0.80). Addition of CC/IDC to NCCN impacted scores 4 and 5-6 and also improved the concordance index for BCR (0.62 vs. 0.68). Regarding EFS, NCCN scores 4 and 5-6 demonstrated markedly different outcomes with the addition of CC/IDC. The CAPRA nomogram allows better outcome stratification than NCCN. Addition of CC/IDC status particularly improves patient stratification for CAPRA scores 3-5, 6-10, and for NCCN scores 4 and 5-6.

RevDate: 2022-06-09

Akin-Sari B, Inozu M, Haciomeroglu AB, et al (2022)

Cognitive training using a mobile app as a coping tool against COVID-19 distress: A crossover randomized controlled trial.

Journal of affective disorders, 311:604-613 pii:S0165-0327(22)00644-9 [Epub ahead of print].

BACKGROUND: The COVID-19 pandemic has been suggested to constitute a broad base stressor with severe mental health consequences. mHealth applications are accessible self-help tools that can be used to reduce psychological distress during the pandemic. This randomized controlled trial evaluated the effects of mobile-based cognitive training exercises on COVID-19 related distress and maladaptive cognitions.

METHODS: Following initial screening (n = 924), participants scoring 1 standard deviations above the mean of the COVID-19 Distress Scale were randomized into two groups. Participants in the immediate-app group (iApp; n = 25) started using the application at baseline (T0) for 12 days (from T0 to T1). Participants in the delayed-app group (dApp; n = 22) started using the mobile application at T1 (crossover) and used it for the following 12 days (T1 to T2).

RESULTS: Intention to treat analyses indicated that the iApp group exhibited lower COVID-19 distress, lower depression, fewer intolerance of uncertainty and obsessive beliefs than the dApp group at T1. In addition, using the app for 12 consecutive days was associated with large effect-size reductions (Cohen's d ranging from 0.81 to 2.35) in COVID-19 distress and related maladaptive cognitions in the iApp group (from T0 to T1) and the dApp group (from T1 to T2). Moreover, these reductions were maintained at the follow-up.

LIMITATIONS: This study was a crossover trial with a relatively limited sample size and mainly female participants.

CONCLUSION: Our findings underscore the usefulness of brief, low-intensity, portable interventions in alleviating the negative effects of the pandemic on mental health.

RevDate: 2022-06-08

Fougerat A, Schoiswohl G, Polizzi A, et al (2022)

ATGL-dependent white adipose tissue lipolysis controls hepatocyte PPARα activity.

Cell reports, 39(10):110910.

In hepatocytes, peroxisome proliferator-activated receptor α (PPARα) orchestrates a genomic and metabolic response required for homeostasis during fasting. This includes the biosynthesis of ketone bodies and of fibroblast growth factor 21 (FGF21). Here we show that in the absence of adipose triglyceride lipase (ATGL) in adipocytes, ketone body and FGF21 production is impaired upon fasting. Liver gene expression analysis highlights a set of fasting-induced genes sensitive to both ATGL deletion in adipocytes and PPARα deletion in hepatocytes. Adipose tissue lipolysis induced by activation of the β3-adrenergic receptor also triggers such PPARα-dependent responses not only in the liver but also in brown adipose tissue (BAT). Intact PPARα activity in hepatocytes is required for the cross-talk between adipose tissues and the liver during fat mobilization.

RevDate: 2022-06-08

de Assis ÉG, do Patrocínio ZKG, CN Nobre (2022)

The Use of Convolutional Neural Networks in the Prediction of Invasive Ductal Carcinoma in Histological Images of Breast Cancer.

Studies in health technology and informatics, 290:587-591.

This paper presents a deep learning approach for automatic detection and visual analysis of Invasive Ductal Carcinoma (IDC) tissue regions. The method proposed in this work is a convolutional neural network (CNN) for visual semantic analysis of tumor regions for diagnostic support. Detection of IDC is a time-consuming and challenging task, mainly because a pathologist needs to examine large tissue regions to identify areas of malignancy. Deep Learning approaches are particularly suitable for dealing with this type of problem, especially when many samples are available for training, ensuring high quality of the learned features by the classifier and, consequently, its generalization capacity. A 3-hidden-layer CNN with data balancing reached both accuracy and F1-Score of 0.85 and outperforming other approaches from the literature. Thus, the proposed method in this article can serve as a support tool for the identification of invasive breast cancer.

RevDate: 2022-06-07

Bhaludin BN, Tunariu N, Senthivel N, et al (2022)

Does the addition of whole-body MRI to routine imaging influence real-world treatment decisions in metastatic breast cancer?.

Cancer imaging : the official publication of the International Cancer Imaging Society, 22(1):26.

BACKGROUND: The assessment of metastatic breast cancer (MBC) can be limited with routine imaging such as computed tomography (CT) especially in bone-only or bone-predominant disease. This analysis investigates the effects of the use of WBMRI in addition to the use of routine CT, bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) on influencing systemic anti-cancer treatment (SACT) decisions in patients with known MBC.

METHODS: MBC patients undergoing SACT who had WBMRI undertaken within 8 weeks of either a routine CT, BS or FDG-PET/CT were reviewed retrospectively. The clinical indications for undertaking the WBMRI examinations were recorded. Data on the extent and distribution of the disease were collected and discordance/concordance of disease status across the imaging modalities were compared. SACT decisions at each time point were also evaluated.

RESULTS: There were 105 MBC patients with 148 WBMRI studies paired with CT, BS or FDG-PET/CT. 50 pairs (33.8%) showed differences in the extent of disease, with 44 pairs due to additional sites (AS) reported on WBMRI alone. 81 patients (Group 1) had one WBMRI paired with routine imaging due to a variety of indications, with clinical symptoms (such as bone pain) being the most common (24.7%). 24 patients (Group 2) had more than one WBMRI study paired with routine imaging comprising 67 pairs. 13/67 pairs (19.4%) showed discordance in assessments. 10/13 pairs had progressive disease (PD) reported on WBMRI alone. SACT change due to AS reported on WBMRI alone occurred in 21/23 pairs (91.3%) in Group 1. SACT change due to PD reported on WBMRI alone in Group 2 occurred in 6/14 pairs (42.9%). SACT change due to AS/PD in both groups occurred in 11/102 pairs (10.8%) with known invasive ductal carcinoma (IDC) and 13/28 pairs (46.4%) with invasive lobular carcinoma (ILC).

CONCLUSIONS: The use of WBMRI in MBC led to earlier recognition of PD and SACT change compared with the other imaging modalities. A higher proportion of discordant response assessments and SACT changes were observed in ILC compared with IDC in our patient group, although larger-scale studies are required to investigate this further.

RevDate: 2022-06-06

Utsunomiya T, Funamizu N, Ozaki E, et al (2022)

A case of radical resection for brain metastases of pancreatic cancer after curative chemotherapy for para-aortic lymph node metastases.

Surgical case reports, 8(1):108.

BACKGROUND: The incidence of brain metastasis of pancreatic cancer has been reported to be approximately 0.3%. The blood-brain barrier of the central nervous system restricts the transfer of substances, including chemotherapeutic agents, from the bloodstream. It is hypothesized that brain metastasis may occur despite successful chemotherapy for the primary tumor. Herein, we report a case of brain metastases of pancreatic cancer that occurred after chemotherapy and discuss relevant literature.

CASE PRESENTATION: A 64-year-old man underwent distal pancreatectomy with D2 lymph node dissection for resectable pancreatic tail cancer. Invasive ductal carcinoma of pancreas, pT3N2M0 pStageIII (TNM Classification of Malignant Tumors, UICC 8th edition) was diagnosed. S-1 adjuvant chemotherapy was initiated. Three months postoperatively, CA19-9 had increased to 619 U/mL. Additionally, contrast-enhanced computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT revealed local recurrence in the para-aortic lymph nodes. Chemotherapy was revised to a combined regimen of gemcitabine and nab-paclitaxel. After 4 cycles, tumor markers were normalized. After 5 cycles, recurrence could not be identified on contrast-enhanced CT; therefore, the patient was adjudged to be in complete remission. However, after 29 cycles of chemotherapy, the patient had symptoms of raised intracranial pressure. Magnetic resonance imaging showed two metastatic lesions of 20 mm and 32 mm in the left frontal lobe and cerebellum, respectively. Quasi-emergency resection of the metastatic brain tumors was performed. Pathological examination revealed that the resected specimens originated from primary pancreatic cancer. The patient was discharged on postoperative day 12, without any complications. Postoperatively, a total of 53 Gy of local brain radiation therapy was added. On postoperative day 30, blood carcinoembryonic antigen level had decreased to 5.4 ng/dl and all other tumor markers were negative. Additionally, tumor markers of the cerebrospinal fluid were markedly reduced and the cytology was negative for tumor cells. These results suggested complete resection of the metastatic brain tumors.

CONCLUSIONS: Aggressive resection and salvage stereotactic radiotherapy for metastatic brain tumors may lead to complete cure and a good long-term prognosis.

RevDate: 2022-06-06

Zhang Y, Luo X, Chen M, et al (2022)

Biomarker profile of invasive lobular carcinoma: pleomorphic versus classic subtypes, clinicopathological characteristics and prognosis analyses.

Breast cancer research and treatment [Epub ahead of print].

PURPOSE: To compare the clinicopathologic features and prognosis of pleomorphic invasive lobular carcinoma (P-ILC) and classic ILC (C-ILC) according to the biomarker profile.

METHODS: A total of 667 C-ILCs and 133 P-ILCs between 2011 and 2021 were included. Clinicopathologic features and stromal tumor-infiltrating lymphocytes (sTILs) status were evaluated. P-ILCs were divided into subtypes based on ER/PR and HER2 expression. The overall survival and disease-free survival (DFS) of patients were compared among matched P-ILCs, C-ILCs, and invasive ductal carcinomas (IDCs) with biomarker subtypes.

RESULTS: Compared to C-ILCs, P-ILCs had greater tumor sizes and stages, fewer ER-positive, more HER2-positive, triple negative (TN), and Ki-67 > 20% tumors (P < 0.05). P-ILCs were subdivided into ER+ (63.1%), HER2+ (21.1%) and TN (15.8%). ER+ P-ILCs were mainly showed trabecular and solid growth patterns. Apocrine and solid features were more strongly associated with HER2+ P-ILCs and TN-P-ILCs, respectively. The prognosis of each biomarker group (ER+, HER2+ and TN) differed by subtype. The P-ILC biomarker subtypes had worse prognosis than the same subtypes in the IDC group, while there was no difference between the P-ILC and the C-ILC counterparts. Solid variants of P-ILC had the worst prognosis. Bone was the most common metastatic site in ER+ P-ILCs and TN-P-ILCs. HER2+ P-ILCs tended to metastasize to the brain and liver. DFS of HER2+ P-ILCs and TN-P-ILCs were worse than that of ER+ P-ILCs. Lacking lobular carcinoma in situ and sTILs ≤ 10% were associated with worse survival of ER+ P-ILCs and TN-P-ILCs, respectively. For HER2+ P-ILCs, Ki-67 > 20% and sTILs ≤ 10% were significant factors for lower DFS.

CONCLUSION: P-ILCs is an aggressive subtype of ILCs. Analyzing the prognostic factors of P-ILCs with heterogeneous morphological and biomarker characteristics is helpful for creating an individualized treatment.

RevDate: 2022-06-06

Elangovan A, Hooda J, Savariau L, et al (2022)

Loss of E-cadherin Induces IGF1R Activation and Reveals a Targetable Pathway in Invasive Lobular Breast Carcinoma.

Molecular cancer research : MCR pii:699382 [Epub ahead of print].

No Special Type breast cancer (NST; commonly known as Invasive Ductal Carcinoma (IDC)) and Invasive Lobular Carcinoma (ILC) are the two major histological subtypes of breast cancer with significant differences in clinicopathological and molecular characteristics. The defining pathognomonic feature of ILC is loss of cellular adhesion protein, E-cadherin (CDH1). We have previously shown that E-cadherin functions as a negative regulator of the Insulin-like Growth Factor 1 Receptor (IGF1R) and propose that E-cadherin loss in ILC sensitizes cells to growth factor signaling which thus alters their sensitivity to growth factor signaling inhibitors and their downstream activators. To investigate this potential therapeutic vulnerability, we generated CRISPR-mediated CDH1 knockout (CDH1 KO) IDC cell lines (MCF7, T47D, ZR75.1) to uncover the mechanism by which loss of E-cadherin results in IGF pathway activation. CDH1 KO cells demonstrated enhanced invasion and migration that was further elevated in response to IGF1, serum and Collagen I. CDH1 KO cells exhibited increased sensitivity to IGF resulting in elevated downstream signaling. Despite minimal differences in membranous IGF1R levels between wildtype (WT) and CDH1 KO cells, significantly higher ligand-receptor interaction was observed in the CDH1 KO cells, potentially conferring enhanced downstream signaling activation. Critically, increased sensitivity to IGF1R, PI3K, Akt and MEK inhibitors was observed in CDH1 KO cells and ILC patient-derived organoids. Implications: Overall, this suggests that these targets require further exploration in ILC treatment and that CDH1 loss may be exploited as a biomarker of response for patient stratification.

RevDate: 2022-06-06

Xu A, Chu X, Zhang S, et al (2022)

Prediction Breast Molecular Typing of Invasive Ductal Carcinoma Based on Dynamic Contrast Enhancement Magnetic Resonance Imaging Radiomics Characteristics: A Feasibility Study.

Frontiers in oncology, 12:799232.

Objective: To investigate the feasibility of radiomics in predicting molecular subtype of breast invasive ductal carcinoma (IDC) based on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI).

Methods: A total of 303 cases with pathologically confirmed IDC from January 2018 to March 2021 were enrolled in this study, including 223 cases from Fudan University Shanghai Cancer Center (training/test set) and 80 cases from Shaoxing Central Hospital (validation set). All the cases were classified as HR+/Luminal, HER2-enriched, and TNBC according to immunohistochemistry. DCE-MRI original images were treated by semi-automated segmentation to initially extract original and wavelet-transformed radiomic features. The extended logistic regression with least absolute shrinkage and selection operator (LASSO) penalty was applied to identify the optimal radiomic features, which were then used to establish predictive models combined with significant clinical risk factors. Receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis were adopted to evaluate the effectiveness and clinical benefit of the models established.

Results: Of the 223 cases from Fudan University Shanghai Cancer Center, HR+/Luminal cancers were diagnosed in 116 cases (52.02%), HER2-enriched in 71 cases (31.84%), and TNBC in 36 cases (16.14%). Based on the training set, 788 radiomic features were extracted in total and 8 optimal features were further identified, including 2 first-order features, 1 gray-level run length matrix (GLRLM), 4 gray-level co-occurrence matrices (GLCM), and 1 3D shape feature. Three multi-class classification models were constructed by extended logistic regression: clinical model (age, menopause, tumor location, Ki-67, histological grade, and lymph node metastasis), radiomic model, and combined model. The macro-average areas under the ROC curve (macro-AUC) for the three models were 0.71, 0.81, and 0.84 in the training set, 0.73, 0.81, and 0.84 in the test set, and 0.76, 0.82, and 0.83 in the validation set, respectively.

Conclusion: The DCE-MRI-based radiomic features are significant biomarkers for distinguishing molecular subtypes of breast cancer noninvasively. Notably, the classification performance could be improved with the fusion analysis of multi-modal features.

RevDate: 2022-06-06

Lone Z, Benidir T, Rainey M, et al (2022)

Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.

European urology focus pii:S2405-4569(22)00125-0 [Epub ahead of print].

BACKGROUND: Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.

OBJECTIVE: The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.

We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).

Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.

RESULTS AND LIMITATIONS: A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p < 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p < 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p < 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).

CONCLUSIONS: This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.

PATIENT SUMMARY: Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

RevDate: 2022-06-06

Sulaj A, Kopf S, von Rauchhaupt E, et al (2022)

Six-Month Periodic Fasting in Patients With Type 2 Diabetes and Diabetic Nephropathy: A Proof-of-Concept Study.

The Journal of clinical endocrinology and metabolism pii:6576281 [Epub ahead of print].

CONTEXT: Novel fasting interventions have gained scientific and public attention. Periodic fasting has emerged as a dietary modification promoting beneficial effects on metabolic syndrome.

OBJECTIVE: Assess whether periodic fasting reduces albuminuria and activates nephropathy-driven pathways.

DESIGN/PARTICIPANTS: Proof-of-concept study where individuals with type 2 diabetes (n = 40) and increased albumin-to-creatinine ratio (ACR) were randomly assigned to receive a monthly fasting-mimicking diet (FMD) or a Mediterranean diet for 6 months with 3-month follow-up.

MAIN OUTCOMES MEASURES: Change in ACR was assessed by analysis of covariance adjusted for age, sex, weight loss, and baseline value. Prespecified subgroup analysis for patients with micro- vs macroalbuminuria at baseline was performed. Change in homeostatic model assessment for insulin resistance (HOMA-IR), circulating markers of dicarbonyl detoxification (methylglyoxal-derived hydroimidazolone 1, glyoxalase-1, and hydroxyacetone), DNA-damage/repair (phosphorylated histone H2AX), lipid oxidation (acylcarnitines), and senescence (soluble urokinase plasminogen activator receptor) were assessed as exploratory endpoints.

RESULTS: FMD was well tolerated with 71% to 95% of the participants reporting no adverse effects. After 6 months, change in ACR was comparable between study groups [110.3 (99.2, 121.5) mg/g; P = 0.45]. FMD led to a reduction of ACR in patients with microalbuminuria levels at baseline [-30.3 (-35.7, -24.9) mg/g; P ≤ 0.05] but not in those with macroalbuminuria [434.0 (404.7, 463.4) mg/g; P = 0.23]. FMD reduced HOMA-IR [-3.8 (-5.6, -2.0); P ≤ 0.05] and soluble urokinase plasminogen activator receptor [-156.6 (-172.9, -140.4) pg/mL; P ≤ 0.05], while no change was observed in markers of dicarbonyl detoxification or DNA-damage/repair. Change in acylcarnitines was related to patient responsiveness to ACR improvement. At follow-up only HOMA-IR reduction [-1.9 (-3.7, -0.1), P ≤ 0.05]) was sustained.

CONCLUSIONS: Improvement of microalbuminuria and of markers of insulin resistance, lipid oxidation, and senescence suggest the potential beneficial effects of periodic fasting in type 2 diabetes.

RevDate: 2022-06-06

Wetzel CL, Gardiner SK, Johnson N, et al (2022)

Variation in adoption of skin and nipple sparing mastectomy: An opportunity to enhance patient outcomes.

American journal of surgery pii:S0002-9610(22)00343-9 [Epub ahead of print].

BACKGROUND: Nipple-sparing mastectomies (NSM) for breast cancer are under-utilized. We sought to investigate NSM utilization.

METHODS: Females with nonmetastatic breast cancer undergoing mastectomy in the Legacy Health System from 2007 to 2020 were identified. Multivariable logistic regression was utilized to evaluate odds of receiving NSM.

RESULTS: Three-thousand-four-hundred-seventeen mastectomies were performed with 772 undergoing NSM. On multivariable analysis, later year (OR 1.22/year, P < 0.001), neoadjuvant chemotherapy (OR 1.33, P = 0.04), HR+ (OR 1.61, P = 0.001) and surgeon volume (OR 1.16/10 yearly mastectomies, P < 0.001) were independently associated with increased odds of receiving a NSM while age (OR 0.94/year, P < 0.001), IDC (OR 0.58, P = 0.01), T3/T4 stage (OR 0.36, P = 0.009), and clinical node positivity (OR 0.63, P = 0.003) were independently associated with decreased odds. Surgeon volume was not associated with odds of receiving a non-NSM with reconstruction (OR 1.01 P = 0.48).

CONCLUSION: NSM is under-utilized by low-volume breast surgeons. Understanding barriers to adoption is an is an opportunity to enhance patient-centered outcomes.

RevDate: 2022-06-01

Tiwari D (2022)

Improving signal-to-noise ratio of magnetic tunnel junction based radio frequency detector via spin-torque ferromagnetic resonance.

The Review of scientific instruments, 93(5):053904.

This article focuses on the spin-torque ferromagnetic resonance (STFMR) technique, which was developed and optimized to investigate spin-transfer effects in magnetic tunnel junctions (MTJ) and spin Hall effect phenomena in ferromagnet/non-magnetic heavy metal bilayer systems. The devices for STFMR are typically fabricated with co-planar waveguides with contact pads for applying radio frequency or direct current, Irf(Idc). The device under investigation was a CoFeB/MgO/CoFeB based MTJ with a resistance-area product of 1.5 Ω (μm)2 having a circular cross section with a diameter of 180 nm and tunneling magneto-resistance in the range of 60%-80%. The development of the STFMR setup and its optimization for achieving higher signal-to-noise ratio (SNR) is discussed using two modulation schemes, namely, radio-frequency modulation and field modulation (FM). The FM-STFMR method reduces frequency-dependent noise and offers a higher SNR of 30 dB compared to other modulation schemes in the literature. In addition, a vector network analyzer based STFMR technique is developed, which provides a simple and fast means for characterizing MTJ devices. Furthermore, to calculate the exact power reaching the MTJ, impedance mismatch is calculated using the de-embedding method. The magnitude of in-plane torkance and out-of-plane torkance with dc bias is measured, and the results are found to be consistent with the results of STFMR techniques. The results show that the magnitude of out-of-plane torkance is substantially smaller than that of in-plane torkance in MTJ.

RevDate: 2022-06-01

Hamed MM, Gouida MS, Abd El-Aziz SR, et al (2022)

Evaluation PD-L1, CD8 and CD20 as early predictor and tracking markers for breast cancer (BC) in Egypt.

Heliyon, 8(5):e09474 pii:S2405-8440(22)00762-9.

Background: Breast cancer (BC) is considered as a common type of cancer threatening women throughout the world. Therefore, development of early predication biomarkers for BC got more concern especially for Egyptian females. This study was aimed to evaluate PD-L1, CD8, and CD20 as early prediction breast cancer biomarkers.

Methods: Flow cytometry (FC), immunohistochemistry (IHC), Western Blot, and q-PCR were used to compare PD-L1, CD20, and CD8 levels in tissues and blood samples of Breast Cancer and controls.

Results: Blood samples showed a significant increase in PD-L1, CD20, and CD8 compared to controls (p˂0.005). A Significant correlation was shown between PD-L1, CD8, and CD20 in tissue and breast cancer subtypes. Whereas, invasive lobular carcinoma (ILC) was characterized by superior PD-L1 and CD20 levels compared to invasive ductal carcinoma (IDC). FC studies on Blood showed 83% and 45.7% PD-L1 expressions for IDC and ILC, respectively. CD20 in ILC and IDC were 78.2% and 62.5%, respectively. Nevertheless, CD8 was 74.2% for IDC and 67.7% for ILC. Whereas, FC studies for PD-L1, CD20, and CD8 in ILC in tissues gave 34.4%, 30.2% and 35.1%, respectively. In addition, IDC tissue samples showed 16%, 12.5, and 13.5% for PD-L1, CD20, and CD8. The moderate stage of adenocarcinoma caused expression of PD-L1 within inflammatory cells, while expression was within neoplastic glandular cells in late stage.

Conclusion: PD-L1, CD8, and CD20 are considered as early predictor and tracking markers for breast cancer.

RevDate: 2022-06-01

Ruan M, Ding Z, Shan Y, et al (2022)

Radiomics Based on DCE-MRI Improved Diagnostic Performance Compared to BI-RADS Analysis in Identifying Sclerosing Adenosis of the Breast.

Frontiers in oncology, 12:888141.

Purpose: Sclerosing adenosis (SA) is a benign lesion that could mimic breast carcinoma and be evaluated as malignancy by Breast Imaging-Reporting and Data System (BI-RADS) analysis. We aimed to construct and validate the performance of radiomic model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) compared to BI-RADS analysis to identify SA.

Methods: Sixty-seven patients with invasive ductal carcinoma (IDC) and 58 patients with SA were included in this retrospective study from two institutions. The 125 patients were divided into a training cohort (n= 88) from institution I and a validation cohort from institution II (n=37). Dynamic contrast-enhanced sequences including one pre-contrast and five dynamic post-contrast series were obtained for all cases with different 3T scanners. Single-phase enhancement, multi-phase enhancement, and dynamic radiomic features were extracted from DCE-MRI. The least absolute shrinkage and selection operator (LASSO) logistic regression and cross-validation was performed to build the radscore of each single-phase enhancement and the final model combined multi-phase and dynamic radiomic features. The diagnostic performance of radiomics was evaluated by receiver operating characteristic (ROC) analysis and compared to the performance of BI-RADS analysis. The classification performance was tested using external validation.

Results: In the training cohort, the AUCs of BI-RADS analysis were 0.71 (95%CI [0.60, 0.80]), 0.78 (95%CI [0.67, 0.86]), and 0.80 (95%CI [0.70, 0.88]), respectively. In single-phase analysis, the second enhanced phase radiomic signature achieved the highest AUC of 0.88 (95%CI [0.79, 0.94]) in distinguishing SA from IDC. Nine multi-phase radiomic features and two dynamic radiomic features showed the best predictive ability for final model building. The final model improved the AUC to 0.92 (95%CI [0.84, 0.97]), and showed statistically significant differences with BI-RADS analysis (p<0.05 for all). In the validation cohort, the AUC of the final model was 0.90 (95%CI [0.75, 0.97]), which was higher than all BI-RADS analyses and showed statistically significant differences with one of the BI-RADS analysis observers (p = 0.03).

Conclusions: Radiomics based on DCE-MRI could show better diagnostic performance compared to BI-RADS analysis in differentiating SA from IDC, which may contribute to clinical diagnosis and treatment.

RevDate: 2022-06-01

Engelhard CA, Huang C, Khani S, et al (2022)

Comprehensive Transcriptional Profiling and Mouse Phenotyping Reveals Dispensable Role for Adipose Tissue Selective Long Noncoding RNA Gm15551.

Non-coding RNA, 8(3): pii:ncrna8030032.

Cold and nutrient-activated brown adipose tissue (BAT) is capable of increasing systemic energy expenditure via the uncoupled respiration and secretion of endocrine factors, thereby protecting mice against diet-induced obesity and improving insulin response and glucose tolerance in men. Long non-coding RNAs (lncRNAs) have recently been identified as fine-tuning regulators of cellular function. While certain lncRNAs have been functionally characterised in adipose tissue, their overall contribution in the activation of BAT remains elusive. We identified lncRNAs correlating to interscapular brown adipose tissue (iBAT) function in a high fat diet (HFD) and cold stressed mice. We focused on Gm15551, which has an adipose tissue specific expression profile, is highly upregulated during adipogenesis, and downregulated by β-adrenergic activation in mature adipocytes. Although we performed comprehensive transcriptional and adipocyte physiology profiling in vitro and in vivo, we could not detect an effect of gain or loss of function of Gm15551.

RevDate: 2022-05-31

Schwartz-Lifshitz M, Hertz-Palmor N, Dekel I, et al (2022)

Loneliness and Social Media Use Among Adolescents with Psychiatric Disorders.

Cyberpsychology, behavior and social networking [Epub ahead of print].

Studies have demonstrated that a prolonged feeling of loneliness is a major risk factor for psychopathology among children and adolescents. The purpose of this study was to evaluate the association between patterns of social media use with loneliness and psychopathology among 65 adolescents who were diagnosed with psychiatric disorders and treated at a psychiatric outpatient clinic in Israel. Social capital (online and offline) was negatively associated with loneliness. There was no association between loneliness and patterns of social media use, age, gender, psychiatric diagnosis, or disease severity. Our findings indicate that both online and offline social capital are associated with loneliness, and highlight the importance of studying the effect of peer online social support in alleviating loneliness.

RevDate: 2022-05-31

Groheux D (2022)

FDG-PET/CT for Primary Staging and Detection of Recurrence of Breast Cancer.

Seminars in nuclear medicine pii:S0001-2998(22)00051-4 [Epub ahead of print].

Breast cancer is the most frequent cancer diagnosed in women worldwide. Accurate baseline staging is necessary to plan optimal breast cancer management. Early detection and staging of recurrence are also essential for optimal therapeutic management. Hybrid FDG-PET/CT imaging offers high sensitivity in detecting extra axillary lymph nodes and distant metastases. Although FDG-PET/CT has some limitations for low proliferative tumors, low-grade tumors and for well-differentiated luminal breast cancer, PET/CT is useful for the initial staging of breast cancer, regardless of tumor phenotype (luminal, triple negative, or HER2+) and of tumor grade. Although FDG-PET/CT performs better for invasive ductal carcinoma (invasive carcinoma of no specific subtype), it is also helpful for staging invasive lobular carcinomas. At initial staging, FDG-PET/CT becomes very useful for staging from clinical stage IIB (T2N1 or T3N0). FDG-PET/CT could be useful in patients with clinical stage IIA (T1N1 or T2N0), but there is not enough strong evidence to recommend routine use in this subgroup. For clinical stage I (T1N0) patients, FDG-PET/CT offers no added value. In patients with recurrent breast cancer, FDG-PET/CT is more effective than conventional imaging in detecting locoregional or distant recurrence, whether suspected by clinical examination, conventional imaging, or elevation of a tumor marker (CA 15.3 or CEA). PET/CT is effective even in the presence of normal tumor markers. PET/CT is also a powerful imaging modality for performing a whole-body workup of a known recurrence and for determining whether or not the recurrence is isolated.

RevDate: 2022-05-31

Willemsen N, Arigoni I, Studencka-Turski M, et al (2022)

Proteasome dysfunction disrupts adipogenesis and induces inflammation via ATF3.

Molecular metabolism pii:S2212-8778(22)00087-4 [Epub ahead of print].

OBJECTIVE: Regulation of proteasomal activity is an essential component of cellular proteostasis and function. This is evident in patients with mutations in proteasome subunits and associated regulators, who suffer from proteasome-associated autoinflammatory syndromes (PRAAS). These patients display lipodystrophy and fevers, which may be partly related to adipocyte malfunction and abnormal thermogenesis in adipose tissue. However, the cell-intrinsic pathways that could underlie these symptoms are unclear. Here, we investigate the impact of two proteasome subunits implicated in PRAAS, Psmb4 and Psmb8, on differentiation, function and proteostasis of brown adipocytes.

METHODS: In immortalized mouse brown pre-adipocytes, levels of Psmb4, Psmb8, and downstream effectors genes were downregulated through reverse transfection with siRNA. Adipocytes were differentiated and analyzed with various assays of adipogenesis, lipogenesis, lipolysis, inflammation, and respiration.

RESULTS: Loss of Psmb4, but not Psmb8, disrupted proteostasis and adipogenesis. Proteasome function was reduced upon Psmb4 loss, but partly recovered by the activation of Nuclear factor, erythroid-2, like-1 (Nfe2l1). In addition, cells displayed higher levels of surrogate inflammation and stress markers, including Activating transcription factor-3 (Atf3). Simultaneous silencing of Psmb4 and Atf3 lowered inflammation and restored adipogenesis.

CONCLUSIONS: Our study shows that Psmb4 is required for adipocyte development and function in cultured adipocytes. These results imply that in humans with PSMB4 mutations, PRAAS-associated lipodystrophy is partly caused by disturbed adipogenesis. While we uncover a role for Nfe2l1 in the maintenance of proteostasis under these conditions, Atf3 is a key effector of inflammation and blocking adipogenesis. In conclusion, our work highlights how proteasome dysfunction is sensed and mitigated by the integrated stress response in adipocytes with potential relevance for PRAAS patients and beyond.

RevDate: 2022-05-28

Yu JM, Chen LY, Pan MC, et al (2022)

In Vivo Validation of Diffuse Optical Imaging with a Dual-Direction Measuring Module of Parallel-Plate Architecture for Breast Tumor Detection.

Biomedicines, 10(5): pii:biomedicines10051040.

We demonstrate a working prototype of an optical breast imaging system involving parallel-plate architecture and a dual-direction scanning scheme designed in combination with a mammography machine; this system was validated in a pilot study to demonstrate its application in imaging healthy and malignant breasts in a clinical environment. The components and modules of the self-developed imaging system are demonstrated and explained, including its measuring architecture, scanning mechanism, and system calibration, and the reconstruction algorithm is presented. Additionally, the evaluation of feature indices that succinctly demonstrate the corresponding transmission measurements may provide insight into the existence of malignant tissue. Moreover, five cases are presented including one subject without disease (a control measure), one benign case, one suspected case, one invasive ductal carcinoma, and one positive case without follow-up treatment. A region-of-interest analysis demonstrated significant differences in absorption between healthy and malignant breasts, revealing the average contrast between the abnormalities and background tissue to exceed 1.4. Except for ringing artifacts, the average scattering property of the structure densities was 0.65-0.85 mm-1.

RevDate: 2022-05-27

Cho YA, Ko SY, Suh YJ, et al (2022)

PIK3CA Mutation as Potential Poor Prognostic Marker in Asian Female Breast Cancer Patients Who Received Adjuvant Chemotherapy.

Current oncology (Toronto, Ont.), 29(5):2895-2908 pii:curroncol29050236.

BACKGROUND: The prognostic relevance of the PIK3CA mutation together with PD-L1, c-Met, and mismatch repair deficiency (dMMR) have not been fully investigated in Asian women with breast cancer (BC) who have undergone postoperative adjuvant chemotherapy.

METHODS: We analyzed PIK3CA mutations via peptide nucleic acid (PNA)-mediated real-time PCR assay, PD-L1/c-Met expression via immunohistochemistry (IHC), and microsatellite instability (MSI) status using PCR and IHC, in 191 resected BCs from 2008 to 2011. The Cancer Genome Atlas (TCGA) dataset for the involvement of the PIK3CA mutation with PD-L1/c-Met/MMR was explored.

RESULTS: The PNA clamp-mediated assay was able to detect the PIK3CA mutation in 1% of the mutant population in the cell line validation. Using this method, the PIK3CA mutation was found in 78 (49.4%) of 158 samples. c-Met and PD-L1 positivity were identified in 31.4 and 21.8% of samples, respectively, which commonly correlated with high histologic grade and triple-negative subtype. MSI/dMMR was observed in 8.4% of patients, with inconsistency between MMR IHC and the MSI PCR. The PIK3CA mutation exhibited a poor prognostic association regarding recurrence-free survival (RFS) in both overall and triple-negative BCs. In subgroup analyses, the PIK3CA-mutated tumors showed poorer RFS than the PIK3CA-wildtype within the c-Met-positive, MSS, triple-negative, or age onset <50 years subgroups, which showed a similar trend of association in TCGA data.

CONCLUSIONS: PIK3CA mutation together with c-Met or dMMR/MSI status might be relevant to poor prognosis in BC subsets, especially in Asian women.

RevDate: 2022-05-27

Wang X, Mathews A, Erickson A, et al (2022)

Single Center Oncoplastic Experience and Patient Satisfaction Reported via Patient Reported Outcomes.

Plastic and reconstructive surgery. Global open, 10(5):e4336.

Oncoplastic breast surgery (OPS) is gaining in popularity compared with traditional breast conserving surgery due to wider resections and better satisfaction with cosmetic outcomes. This study analyzed OPS versus traditional breast conserving surgery outcomes: wound complications, reoperations for margins or fat necrosis, and ipsilateral recurrence.

Methods: This retrospective review compared 191 OPS and traditional breast conserving surgery patients on patient-related factors, primary outcomes, and patient reported outcome measures results. A propensity score method analysis using 1:1 to nearest neighbor was also performed.

Results: OPS patients were younger, less likely to be smokers, more likely to be ER+ and PR+, and had larger specimen volumes than did traditional breast conserving surgery patients (P < 0.05). There were also differences in distribution of invasive ductal carcinoma and noninvasive disease (P < 0.05). After the propensity score method, the differences observed between the cohorts disappeared. No differences were observed between groups for wound complication, reoperation for positive margins or fat necrosis, or ipsilateral recurrence. Results of patient reported outcome measures showed greater satisfaction with breast surgery in OPS patients (P < 0.01).

Conclusions: We showed that OPS is a noninferior technique that should be discussed with appropriate patients. Operative planning should involve patient preferences in optimizing long-term cosmetic outcomes.

RevDate: 2022-05-27

Belzer A, McNiff JM, JS Leventhal (2022)

Skin eruption involving bilateral breasts following radiation therapy for invasive ductal carcinoma of the left breast.

International journal of women's dermatology, 8(2):e016.

RevDate: 2022-05-26

Zhang ML, Wang X, Xing ZY, et al (2022)

[Young mammary Paget's disease patients with underlying breast invasive ductal carcinoma: clinicopathological features and prognosis].

Zhonghua zhong liu za zhi [Chinese journal of oncology], 44(5):425-429.

Objective: To investigate the clinicopathological factors and prognostic status of young Mammary Paget's disease (MPD) patients with invasive ductal carcinoma (IDC). Methods: In this study, we defined the age at diagnosis below 40 years old as young patients, and retrospectively analyzed data from 123 MPD-IDC patients who were admitted at the Cancer Hospital Chinese Academy of Medical Sciences from June 2002 to February 2019. Patients were divided into the young group (≤40 years old, 15 cases) and the old group (>40 years old, 108 cases) according to the age of onset, and the clinicopathological characteristics and prognosis of the two groups were compared. Cox regression model analysis was used to analyze the prognosis influencing factors. Results: The proportions of patients in the young group with non-menopausal, axillary lymph node metastasis, and Ki-67 index ≥15% were 93.3% (14/15), 73.3% (11/15), and 86.7% (13/15), respectively, which were higher than those in the old group [45.4% (49/108), 39.8%(43/108), and 60.2% (65/108), respectively] , with statistically significant differences (P<0.05). At an average follow-up of 63.2 months, patients in the young group had a significantly shorter disease-free survival (DFS) compared with that of the old group (P=0.012), while the difference in overall survival (OS) between the two groups was not statistically significant (P=0.161). Multifactorial Cox regression analysis showed that axillary lymph node status was an independent influencing factor on OS (HR=3.339, 95% CI: 1.121-9.943) in patients with MPD-IDC, while age was not. Conclusion: Compared with the old group, young patients with MPD-IDC have a higher incidence of axillary lymph node metastasis, high Ki-67 expression, and a shorter DFS, but age is not an independent influencing factor on DFS or OS in patients with MPD-IDC.

RevDate: 2022-05-24

Artati A, Prehn C, Lutter D, et al (2022)

Untargeted and Targeted Circadian Metabolomics Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Flow Injection-Electrospray Ionization-Tandem Mass Spectrometry (FIA-ESI-MS/MS).

Methods in molecular biology (Clifton, N.J.), 2482:311-327.

A diverse array of 24-h oscillating hormones and metabolites direct and reflect circadian clock function. Circadian metabolomics uses advanced high-throughput analytical chemistry techniques to comprehensively profile these small molecules (<1.5 kDa) across 24 h in cells, media, body fluids, breath, tissues, and subcellular compartments. The goals of circadian metabolomics experiments are often multifaceted. These include identifying and tracking rhythmic metabolic inputs and outputs of central and peripheral circadian clocks, quantifying endogenous free-running period, monitoring relative phase alignment between clocks, and mapping pathophysiological consequences of clock disruption or misalignment. Depending on the particular experimental question, samples are collected under free-running or entrained conditions. Here we describe both untargeted and targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) and flow injection-electrospray ionization-tandem mass spectrometry (FIA-ESI-MS/MS) based assays we have used for circadian metabolomics studies. We discuss tissue homogenization, chemical derivatization, measurement, and tips for data processing, normalization, scaling, how to handle outliers, and imputation of missing values.

RevDate: 2022-05-23

Shah RB, Palsgrove DN, Desai NB, et al (2022)

Enrichment of "Cribriform" morphologies (intraductal and cribriform adenocarcinoma) and genomic alterations in radiorecurrent prostate cancer.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc pii:10.1038/s41379-022-01093-9 [Epub ahead of print].

Locally relapsed prostate cancer (PCa) after radiation therapy (RT) is associated with substantial morbidity and mortality. Morphological and molecular consequences that may contribute to RT resistance and local recurrence remain poorly understood. Locally recurrent PCa tissue from 53 patients with clinically localized PCa who failed with primary RT and subsequently underwent salvage radical prostatectomy (RP) was analyzed for tumor focality, clinicopathological, molecular, and genomic characteristics. Targeted next-generation sequencing with full exon coverage of 1,425 cancer-related genes was performed on 10 representative radiorecurrent PCas exhibiting no RT effect with matched adjacent benign prostate tissue. At RP, 37 (70%) of PCas had no RT effect with the following characteristics: grade group (GG) ≥ 3 (70%), unifocal tumor (75%), extraprostatic disease (78%), lymph node metastasis (8%), and "cribriform" morphologies (84%) [cribriform PCa (78%) or intraductal carcinoma (IDC-P) (61%)] at a median percentage of approximately 80% of tumor volume. In the setting of multifocal tumors (25%) at RP, the cribriform morphologies were restricted to index tumors. Of 32 patients with available pre-RT biopsy information, 16 had GG1 PCa, none had cribriform morphologies at baseline but 81% demonstrated cribriform morphologies at RP. Notable alterations detected in the sequenced tumors included: defects in DNA damage response and repair (DDR) genes (70%) (TP53, BRCA2, PALB2, ATR, POLQ), PTEN loss (50%), loss of 8p (80%), and gain of MYC (70%). The median tumor mutational burden was 4.18 mutations/Mb with a range of 2.16 to 31.86. Our findings suggest that most radiorecurrent PCas are enriched in cribriform morphologies with potentially targetable genomic alterations. Understanding this phenotypic and genotypic diversity of radiorecurrent PCa is critically important to facilitate optimal patient management.

RevDate: 2022-05-23

de Faria Castro Fleury E, Castro C, do Amaral MSC, et al (2022)

Management of Non-Mass Enhancement at Breast Magnetic Resonance in Screening Settings Referred for Magnetic Resonance-Guided Biopsy.

Breast cancer : basic and clinical research, 16:11782234221095897 pii:10.1177_11782234221095897.

Rationale and Objectives: According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions.

Materials and Methods: We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions.

Results: From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns.

Conclusion: We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values.

RevDate: 2022-05-22

Iyengar AS, Ein-Dor T, Zhang EX, et al (2022)

Increased traumatic childbirth and postpartum depression and lack of exclusive breastfeeding in Black and Latinx individuals.

International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics [Epub ahead of print].

RevDate: 2022-05-20

Lafcı O, Celepli P, Seher Öztekin P, et al (2022)

DCE-MRI Radiomics Analysis in Differentiating Luminal A and Luminal B Breast Cancer Molecular Subtypes.

Academic radiology pii:S1076-6332(22)00251-3 [Epub ahead of print].

RATIONALE AND OBJECTIVES: The aim of the present study was to investigate the association between Luminal A and Luminal B molecular subtypes and radiomic features of dynamic contrast‑enhanced magnetic resonance imaging in patients with invasive breast cancer.

MATERIALS AND METHODS: Seventy-three patients with histopathologically proven invasive ductal cancer (IDC) were selected. Tumors were classified into molecular subtypes: Luminal A (estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive, human epidermal growth factor receptor type 2 (HER2) -negative, proliferation marker Ki-67<20) and Luminal B (ER-positive and/or PR-positive, HER2-positive or HER2-negative with high Ki-67 ≥20). A total of 81 tumoral lesions were evaluated on T1-weighted fat-suppressed sagittal post-contrast late-phase MRI images after the required "pre-process" steps and 3D segmentations were made. Forty-three radiomic features including: 1 conventional, 4 shape, 6 histogram, 7 Grey-Level Co-occurrence Matrix (GLCM), 11 Grey-Level Run-Length Matrix (GLRLM), 3 Neighborhood Grey-Level Difference Matrix (NGLDM), 11 Grey-Level Zone-Length Matrix (GLZLM) were extracted by using the software LIFEX.

RESULTS: A statistically significant difference was found in radiomic features including; a) Histogram: "skewness", b) Shape: "volume-ml, volume-voxel," c) GLCM: "entropy.log10, entropy.log2, energy", d) GLRLM: "GLNU, RLNU, HGRE," e) NGLDM: "busyness," f) GLZLM: "GLNU, HGZE, ZLNU, SZE" between two different molecular subtypes. The model combining Shape-volume (ml) and GLZLM-HGZE yielded 0.746 area under the curve (AUC), 0.744 sensitivity, 0.643 specificity and 0.694 accuracy.

CONCLUSION: Radiomic properties that may distinguish Luminal A and Luminal B molecular subtypes of IDC were identified. The radiomic features were thought to reflect the intratumoral heterogeneity in molecular subtypes. This study demonstrated that the characterization of Luminal A and Luminal B tumors could be made non-invasively by radiomics analysis.

RevDate: 2022-05-20

Koori N, Miyati T, Ohno N, et al (2022)

Sigmoid model analysis of breast dynamic contrast-enhanced MRI: Distinguishing between benign and malignant breast masses and breast cancer subtype prediction.

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

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE-MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype. A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1-min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann-Whitney U-test was used for the statistical analysis. The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A-like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05). The sigmoid model analysis of breast DCE-MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A-like breast cancer.

RevDate: 2022-05-20

Fernandez-Pacheco M, Ortmann O, Ignatov A, et al (2022)

Does cavity margin shaving reduce residual tumor and re-excision rates? A systematic review.

PURPOSE: Cavity shaving (CS) is a surgical technique used in the treatment of breast cancer (BC). It may reduce margin positivity in histologic assessment and consequently reduces re- excision rates in breast conserving surgery (BCS). The evidence for this assumption is described in the present review.

METHODS: A systematic review of relevant literature in English from January 1999 to April 2019 was conducted. The analysis included studies on CS and its effects on re-excision rates and margin positivity. We searched PubMed databases for relevant publications. In total, 22 studies were included in the present review.

RESULTS: The benefit from CS on re-excision rates and histologic margin positivity was variable. Out of 22 studies, 17 reported a reduction in both re-excision rates and histologic margin positivity in margin shaved patients. Four studies could not find a significant reduction of second surgeries and residual tumor rates. One study suggested that CS after BCS was superior to single BCS only in subgroup analysis in IDC tumors.

CONCLUSION: CS is a surgical technique that was shown to reduce re-excision and margin positivity rates in most of the studies. Furthermore, it can be a useful tool to assess specimen margins and detect multifocality.

RevDate: 2022-05-20

Vincenzi P, Stronati M, Isidori P, et al (2022)

Opioid-Free Segmental Thoracic Spinal Anesthesia with Intrathecal Sedation for Breast and Axillary Surgery: Report of Four Cases.

Local and regional anesthesia, 15:23-29 pii:358157.

Purpose: Few studies have described segmental thoracic spinal anesthesia (STSA) as primary anesthesiologic method in breast and axillary surgery, documenting the association of intrathecal local anesthetics and opioids. This case series reports an opioid-free scheme of STSA in four elderly patients undergoing major breast and axillary oncological surgery.

Patients and Methods: STSA was performed in three female patients undergoing unilateral mastectomy ± axillary lymph node dissection (ALND) or sentinel lymph node biopsy for invasive ductal carcinoma and in one male patient undergoing ALND for melanoma metastases. The level of needle insertion was included between T6-8, via a median or paramedian approach. Midazolam (2 mg) and ketamine (20 mg) were used as adjuvants for intrathecal sedation, followed by the administration of hypobaric ropivacaine 0.25% at a dose of 8 mg. The level of sensory blockade achieved was comprised between C2-3 and T11-12. Postoperative analgesia was maintained through continuous intravenous administration of Ketorolac by an elastomeric pump (90 mg over 24 hrs.).

Results: Spinal anesthesia was completed without complications in all patients. Conversion to general anesthesia (GA) and perioperative intravenous sedation were not required. No major postoperative complications and no episodes of postoperative nausea and vomiting (PONV) were reported. No rescue analgesic was administered. All patients were discharged in postoperative day 2 and are alive at 30, 29, 27 and 13 months after surgery, respectively. High grade of satisfaction on the anesthesiologic method was expressed by all cases.

Conclusion: STSA with local anesthetic plus midazolam and ketamine might be considered a safe and effective alternative to GA, even in surgeries involving the breast and axillary region, particularly in elderly and frail patients. Larger prospective studies are required to validate these findings.

RevDate: 2022-05-19

Bean GR, Najjar S, Shin SJ, et al (2022)

Genetic and immunohistochemical profiling of small cell and large cell neuroendocrine carcinomas of the breast.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc pii:10.1038/s41379-022-01090-y [Epub ahead of print].

Neuroendocrine carcinomas (NEC) of the breast are exceedingly rare tumors, which are classified in the WHO system as small cell (SCNEC) and large cell (LCNEC) carcinoma based on indistinguishable features from their lung counterparts. In contrast to lung and enteropancreatic NEC, the genomics of breast NEC have not been well-characterized. In this study, we examined the clinicopathologic, immunohistochemical, and genetic features of 13 breast NEC (7 SCNEC, 4 LCNEC, 2 NEC with ambiguous small versus large cell morphology [ANEC]). Co-alterations of TP53 and RB1 were identified in 86% (6/7) SCNEC, 100% (2/2) ANEC, and 50% (2/4) LCNEC. The one SCNEC without TP53/RB1 alteration had other p53 pathway aberrations (MDM2 and MDM4 amplification) and was immunohistochemically RB negative. PIK3CA/PTEN pathway alterations and ZNF703 amplifications were each identified in 46% (6/13) NEC. Two tumors (1 SCNEC, 1 LCNEC) were CDH1 mutated. By immunohistochemistry, 100% SCNEC (6/6) and ANEC (2/2) and 50% (2/4) LCNEC (83% NEC) showed RB loss, compared to 0% (0/8) grade 3 neuroendocrine tumors (NET) (p < 0.001) and 38% (36/95) grade 3 invasive ductal carcinomas of no special type (IDC-NST) (p = 0.004). NEC were also more often p53 aberrant (60% vs 0%, p = 0.013), ER negative (69% vs 0%, p = 0.005), and GATA3 negative (67% vs 0%, p = 0.013) than grade 3 NET. Two mixed NEC had IDC-NST components, and 69% (9/13) of tumors were associated with carcinoma in situ (6 neuroendocrine DCIS, 2 non-neuroendocrine DCIS, 1 non-neuroendocrine LCIS). NEC and IDC-NST components of mixed tumors were clonally related and immunophenotypically distinct, lacking ER and GATA3 expression in NEC relative to IDC-NST, with RB loss only in NEC of one ANEC. The findings provide insight into the pathogenesis of breast NEC, underscore their classification as a distinct tumor type, and highlight genetic similarities to extramammary NEC, including highly prevalent p53/RB pathway aberrations in SCNEC.

RevDate: 2022-05-19

Albon D, Thomas L, Hoberg L, et al (2022)

Cystic fibrosis learning network telehealth innovation lab during the COVID-19 pandemic: a success QI story for interdisciplinary care and agenda setting.

BMJ open quality, 11(2):.

INTRODUCTION: The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH.

AIM: The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020.

METHODS: The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan-do-study-act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform.

RESULTS: Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS.

CONCLUSION: Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.

RevDate: 2022-05-19

Elisha E, Guetzkow J, Shir-Raz Y, et al (2022)

Suppressing Scientific Discourse on Vaccines? Self-perceptions of researchers and practitioners.

HEC forum : an interdisciplinary journal on hospitals' ethical and legal issues [Epub ahead of print].

The controversy over vaccines has recently intensified in the wake of the global COVID-19 pandemic, with calls from politicians, health professionals, journalists, and citizens to take harsh measures against so-called "anti-vaxxers," while accusing them of spreading "fake news" and as such, of endangering public health. However, the issue of suppression of vaccine dissenters has rarely been studied from the point of view of those who raise concerns about vaccine safety. The purpose of the present study was to examine the subjective perceptions of professionals (physicians, nurses, researchers) involved with vaccines through practice and/or research and who take a critical view on vaccines, about what they perceive as the suppression of dissent in the field of vaccines, their response to it, and its potential implications on science and medicine. Respondents reported being subjected to a variety of censorship and suppression tactics, including the retraction of papers pointing to vaccine safety problems, negative publicity, difficulty in obtaining research funding, calls for dismissal, summonses to official hearings, suspension of medical licenses, and self-censorship. Respondents also reported on what has been termed a "backfire effect" - a counter-reaction that draws more attention to the opponents' position. Suppression of dissent impairs scientific discourse and research practice while creating the false impression of scientific consensus.

RevDate: 2022-05-19

Leong-Škorničková J, Böhmová A, HĐ Trần (2022)

A new species and new combination in basally flowering Vietnam Costaceae.

PhytoKeys, 190:103-111 pii:76494.

Cheilocostuscandidus sp. nov. (Costaceae), a basally flowering spiral ginger with cream white flowers from southern Vietnam, is described and illustrated here. A new combination, Cheilocostustonkinensis (Gagnep.) Škorničk., is proposed here and the lectotype is designated. A key to Cheilocostus in Vietnam is included.

RevDate: 2022-05-18

Oride Y, Koi Y, Sasada T, et al (2022)

Endobronchial ultrasound-guided transbronchial needle aspiration facilitating diagnosis of sarcoidosis in a breast cancer patient with multiple lymphadenopathy: a case report.

Journal of medical case reports, 16(1):194.

BACKGROUND: Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology. Cell-mediated immunity disorder is often found in sarcoidosis patients, and an association between malignant tumors and sarcoidosis has been suggested. Sarcoidosis and malignant disease can occur simultaneously or sequentially, leading to misdiagnosis and mistreatment. Sarcoidosis is diagnosed clinically, radiologically, and histologically. We report herein a case of sarcoidosis diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration from the mediastinal lymph nodes of a breast cancer patient.

CASE PRESENTATION: The patient was a 70-year-old Asian woman who presented with right breast tumor. A 20-mm movable mass was identified in the inferolateral quadrant of the right breast, and mammography revealed a spiculated mass with calcification. Ultrasonography revealed a mass with internal hypoechogenicity, and biopsy revealed estrogen receptor-positive, human epidermal growth factor receptor 2-positive invasive ductal carcinoma. Positron emission tomography/computed tomography showed multiple lymphadenopathy including mediastinal lymph nodes, with fluorodeoxyglucose accumulation in those nodes suggesting breast cancer metastases. Endobronchial ultrasound-guided transbronchial needle aspiration of a mediastinal lymph node revealed noncaseous epithelioid granuloma. Due to a history of uveitis and elevated soluble interleukin 2 receptor, lymphadenopathy due to sarcoidosis and stage IIA breast cancer were diagnosed. Right partial mastectomy and axillary lymph node dissection were performed after preoperative chemotherapy. No exacerbation of sarcoidosis symptoms has been observed during treatment.

CONCLUSION: We report a case of breast cancer in which sarcoidosis could be diagnosed based on endobronchial ultrasound-guided transbronchial needle aspiration, a history of uveitis, and elevated soluble interleukin 2 receptor despite fluorodeoxyglucose positron emission tomography/computed tomography suggesting multiple lymph node metastases. This report emphasizes the importance of differential diagnosis of lymph node involvements in cancer patients.

RevDate: 2022-05-18

Ban K, Tsunoda H, Togashi S, et al (2022)

Comparative study of the usefulness of adjunctive tomosynthesis in breast cancer screening by mammography and ultrasound in Japan.

Breast cancer (Tokyo, Japan) [Epub ahead of print].

INTRODUCTION: There are few studies have conducted digital breast tomosynthesis (DBT) in addition to digital mammography (2DDM) and ultrasound (US) for screening. The purpose of this study is to determine the possibility of synergistic effects of DBT and US screening for Japanese.

METHODS: 5023 examinations of the opportunistic screening using 2DDM and US (2D group: 2581) or 2DDM and US plus DBT (3 group: 2442) were performed at our facility from May 1, 2017 to March 31, 2019. This study was not RCT, and the backgrounds of the two groups were different.

RESULTS: The recall rate was 3.1% in the 2D group and 2.6% for the 3D group (p = 0.27). The number of detected cancer cases was 6 (0.23%) in the 2D group and 12 (0.49%) in the 3D group (p = 0.16). The positive predictive value (PPV) was 7.4% for the 2D group and 19.0% for the 3D group (p = 0.045). There was one invasive ductal carcinoma case which had no findings in 2DDM and US, but had a slight distortion in the images of DBT.

CONCLUSION: We examined and reported whether DBT was useful for breast cancer screening combined with mammography and US. Compared to the 2D group, the 3D group showed better results of PPV with significant difference. However, due to the non-randomized design and difference between the two groups, the results should be interpreted in caution. Adding DBT in 2DDM and US screening would be acceptable only if the benefits and disadvantages are explained to the women undergoing the screening.

RevDate: 2022-05-17

Higashi T, Ozawa K, Takei S, et al (2022)

[A Case of Postoperative Pulmonary Metastasis of Breast Cancer with Complete Response by Abemaciclib plus Fulvestrant Therapy].

Gan to kagaku ryoho. Cancer & chemotherapy, 49(5):581-583.

A 66-year-old woman underwent total mastectomy with level Ⅰ and Ⅱ axillary lymph node dissection for right breast cancer in July 2007. The pathology results indicated the presence of T2N0M0 invasive ductal carcinoma(tubule forming type), that was estrogen receptor-positive and human epidermal growth factor 2-negative. She received postoperative adjuvant therapy with oral anastrozole(ANA)for 5 years. Eleven years after surgery, at the age of 77 years, a chest X-ray examination during a routine health checkup identified a mass shadow in the right lung. Further investigation revealed bilateral multiple lung metastases due to breast cancer recurrence. Histological examination of a tissue obtained by computed tomography(CT)-guided lung biopsy confirmed that the histological type and subtype were identical to those found in the initial surgery. Hence, endocrine therapy with ANA plus CDK4/6 inhibitor was started in November 2018. However, the first CDK4/6 inhibitor, palbociclib, caused severe myelosuppression even when the dose was reduced by 2 levels. Therefore in January 2019, the patient was switched to abemaciclib, with the dose reduced by 1 level initially and then reduced by 2 levels from August 2019. In June 2019, new multiple lung metastases appeared, and the patient was switched from ANA to fulvestrant, after which complete response was achieved in 6 months. CT in June 2021 showed no recurrence, and the patient(now 80-year-old)continues to take abemaciclib plus fulvestrant therapy.

RevDate: 2022-05-17

Aladag Kurt S, V Celik (2022)

Dramatic increase in volume versus length of invasive ductal carcinoma mimicking intramammary lymph node in a small nodular lesion.

Bulletin of the National Research Centre, 46(1):136.

Background: The tumor growth pattern in breast cancer appears to be variable and unpredictable. A minor increase in size in a pre-existing lesion, especially under 1 cm, corresponds to a more pronounced increase in volume.

Case presentation: We report a 63-year-old woman with a nodular density mimicking intramammary lymph node, diagnosed as invasive carcinoma of luminal B subtype. The lesion increased size and density over time in following mammograms until having indistinct margins. While the tumor volume was 12.7 mm3 at the first observation on mammography, it has increased approximately 6.7 times to reach 85.7 mm3 in four years. Finally, the patient diagnosed with early-stage breast cancer (T1N0M0) was treated with breast-conserving surgery.

Conclusions: Minor changes in size, density, and margin status of a lesion on serial mammograms are warning for breast cancer. Withal, a slight increase in lesion size in two dimensions can result in significant differences in volume. Therefore, comparative evaluation with previous mammograms and observing any difference in morphological features by screening are crucial for early diagnosis and optimal management of the disease.

RevDate: 2022-05-16

He S, Jia Q, Zhou L, et al (2022)

SIRT5 is involved in the proliferation and metastasis of breast cancer by promoting aerobic glycolysis.

Pathology, research and practice, 235:153943 pii:S0344-0338(22)00187-X [Epub ahead of print].

OBJECTIVE: Breast cancer (BC) is the most commonly diagnosed cancer among females and has a poor prognosis, breast invasive ductal carcinoma is the most common histological type. The occurrence and development of BC is closely related to aberrant glucose metabolism. In the hyperglycemic environment caused by abnormal glucose metabolism, hypoxia-inducible factor-1 alpha (HIF-1α) enables tumor cells to absorb large amounts of glucose and enhance glycolysis by inducing the expression of glucose transporter type1 (GLUT1) and glycolysis genes, thus promoting tumor cell proliferation and metastasis. Mitochondrial Sirtuin5 (SIRT5) plays a role in the rewiring of glucose metabolism during the progression of cancers. Thus, we aimed to elucidate whether SIRT5 promotes BC proliferation and metastasis by facilitating aerobic glycolysis in BC.

METHODS: The expression of SIRT5 in breast carcinoma tissue and cells was evaluated using immunohistochemical staining, western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis to confirm the biological role of SIRT5 in breast carcinoma. We established a stable cell line with SIRT5 knockdown using lentiviral transduction in T47D cells to reduce SIRT5 expression and then evaluated the effect of SIRT5 on cells cultured in the presence of high glucose (4500 mg/L) and normal glucose (2000 mg/L) concentrations. Cell proliferation was detected using the CCK-8 assay, the cell cycle and cell apoptosis were measured using flow cytometry and Annexin V staining, and cell migration was tested by performing Celigo scratch and Transwell assays. The expression of PKM2, HK2, mTOR and HIF-1α, which play roles in aerobic glycolysis, was investigated using western blot.

RESULTS: SIRT5 was overexpressed in BC tissues compared with paired normal tissues. Prognostic and OS analyses showed that the SIRT5 expression level was an individual prognostic factor for patients with BC. SIRT5 knockdown inhibited proliferation and metastasis and slightly increased apoptosis in T47D cells under high-glucose conditions. Furthermore, the downregulation of HK2 and HIF-1α caused by SIRT5 knockdown was a high glucose-dependent process, while the downregulation of PKM2 was mediated by a high glucose-independent process.

CONCLUSIONS: SIRT5 is an independent prognostic factor for BC and contributes to cell proliferation and metastasis in a high glucose-dependent manner to some degree, which might be mediated by promoting aerobic glycolysis.

RevDate: 2022-05-16

Bergman YS, Palgi Y, Ben-David B, et al (2022)

COVID-19 Vaccinations and Anxiety in Middle-Aged and Older Jews and Arabs in Israel: The Moderating Roles of Ethnicity and Subjective Age.

Journal of applied gerontology : the official journal of the Southern Gerontological Society [Epub ahead of print].

Subjective age (i.e., feeling younger/older than one's chronological age) plays a significant role in older minority group members' psychological well-being. In light of the importance of vaccinations for fighting COVID-19, it is unclear whether ethnicity and subjective age moderate the connection between receiving COVID-19 vaccinations and anxiety in Israel. Jewish (n = 198) and Arab older adults (n = 84) provided information regarding COVID-19 vaccinations, subjective age, and anxiety symptoms, as well as additional socio-demographic and COVID-19-related health factors (age range= 40-100, M = 62.5, SD = 12.34). Results demonstrated that feeling older was associated with increased anxiety (p < .001) and that vaccinations were linked to increased anxiety among Jews (p < .05). Moreover, the association between COVID-19 vaccinations and anxiety was significant only among Jewish participants with an older subjective age (p < .05). We stress the importance of examining cultural diversities regarding the contribution of subjective age in the context of COVID-19 and psychological well-being.

RevDate: 2022-05-14

Wilson GM, Dinh P, Pathmanathan N, et al (2022)

Ductal Carcinoma in Situ: Molecular Changes Accompanying Disease Progression.

Journal of mammary gland biology and neoplasia [Epub ahead of print].

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive ductal carcinoma (IDC), whereby if left untreated, approximately 12% of patients develop invasive disease. The current standard of care is surgical removal of the lesion, to prevent potential progression, and radiotherapy to reduce risk of recurrence. There is substantial overtreatment of DCIS patients, considering not all DCIS lesions progress to invasive disease. Hence, there is a critical imperative to better predict which DCIS lesions are destined for poor outcome and which are not, allowing for tailored treatment. Active surveillance is currently being trialed as an alternative management practice, but this approach relies on accurately identifying cases that are at low risk of progression to invasive disease. Two DCIS-specific genomic profiling assays that attempt to distinguish low and high-risk patients have emerged, but imperfections in risk stratification coupled with a high price tag warrant the continued search for more robust and accessible prognostic biomarkers. This search has largely turned researchers toward the tumor microenvironment. Recent evidence suggests that a spectrum of cell types within the DCIS microenvironment are genetically and phenotypically altered compared to normal tissue and play critical roles in disease progression. Uncovering the molecular mechanisms contributing to DCIS progression has provided optimism for the search for well-validated prognostic biomarkers that can accurately predict the risk for a patient developing IDC. The discovery of such markers would modernize DCIS management and allow tailored treatment plans. This review will summarize the current literature regarding DCIS diagnosis, treatment, and pathology.

RevDate: 2022-05-13

Shenkman G (2022)

Winds of change: Will current amendments to Israeli laws discriminating against LGBTQ+ individuals positively affect their mental health?.

RevDate: 2022-05-13

Smith PD, Bhenderu LS, Kommuri S, et al (2022)

Treatment of Leptomeningeal Carcinomatosis Following Treatment of Cerebellar Metastasis of HER2+ (Human Epidermal Growth Factor Receptor 2 Positive) Breast Cancer: Case Report and Review of Literature.

Cureus, 14(4):e24008.

Leptomeningeal carcinomatosis (LC) after metastasis of breast cancer is a rare occurrence with potentially devastating complications. Treatment options are limited, and there is a lack of literature on this topic. We report the case of a 38-year-old woman with estrogen/progesterone receptor negative (ER/PR-), human epidermal growth factor receptor 2 positive (HER2+) invasive ductal carcinoma of the left breast who underwent bilateral mastectomies with axillary lymph node dissection and chemotherapy treatment. The patient returned 11 months later with persistent headaches. Imaging and resection found cerebellar metastasis of the breast carcinoma. The brain metastasis was treated with further chemotherapy and stereotactic radiosurgery. Follow-up imaging showed the development of small lesions outside the radiation site. Metabolic studies were performed to determine if the new lesions were due to tumor recurrence or radiation necrosis, but the studies were inconclusive as to the etiology of these lesions. The patient later developed LC that was successfully treated with full resolution of the disease using intrathecal trastuzumab. There are currently no consensuses on treatment guidelines for treating LC. Here, we demonstrate successful treatment of LC from an ER/PR-, HER2+ breast carcinoma with intrathecal trastuzumab.

RevDate: 2022-05-13

Dor YI, Algom D, Shakuf V, et al (2022)

Age-Related Changes in the Perception of Emotions in Speech: Assessing Thresholds of Prosody and Semantics Recognition in Noise for Young and Older Adults.

Frontiers in neuroscience, 16:846117.

Older adults process emotions in speech differently than do young adults. However, it is unclear whether these age-related changes impact all speech channels to the same extent, and whether they originate from a sensory or a cognitive source. The current study adopted a psychophysical approach to directly compare young and older adults' sensory thresholds for emotion recognition in two channels of spoken-emotions: prosody (tone) and semantics (words). A total of 29 young adults and 26 older adults listened to 50 spoken sentences presenting different combinations of emotions across prosody and semantics. They were asked to recognize the prosodic or semantic emotion, in separate tasks. Sentences were presented on the background of speech-spectrum noise ranging from SNR of -15 dB (difficult) to +5 dB (easy). Individual recognition thresholds were calculated (by fitting psychometric functions) separately for prosodic and semantic recognition. Results indicated that: (1). recognition thresholds were better for young over older adults, suggesting an age-related general decrease across channels; (2). recognition thresholds were better for prosody over semantics, suggesting a prosodic advantage; (3). importantly, the prosodic advantage in thresholds did not differ between age groups (thus a sensory source for age-related differences in spoken-emotions processing was not supported); and (4). larger failures of selective attention were found for older adults than for young adults, indicating that older adults experienced larger difficulties in inhibiting irrelevant information. Taken together, results do not support a sole sensory source, but rather an interplay of cognitive and sensory sources for age-related differences in spoken-emotions processing.

RevDate: 2022-05-11

Taunk K, Taware R, More TH, et al (2018)

A non-invasive approach to explore the discriminatory potential of the urinary volatilome of invasive ductal carcinoma of the breast.

RSC advances, 8(44):25040-25050 pii:c8ra02083c.

Worldwide, breast invasive ductal carcinoma (IDC) accounts for the majority of the reported cases of this form of cancer. IDC effective management, as for any form of cancer, would greatly benefit from early diagnosis. This, however, due to various socio-economic reasons, is very far for the reality in developing countries like India, where cancer diagnosis is often carried out at late stages when disease management is troublesome. With the present work, we aim to evaluate a simple analytical methodology to identify a set of volatile organic compounds (VOCs) in urine samples, as a biosignature for IDC. Using solid-phase microextraction followed by gas chromatography/mass spectrometry, a panel of 14 urinary VOCs was found to discriminate IDC (n = 65) from a healthy control (HC) group (n = 70) through multivariate statistical treatments. Furthermore, metabolic pathway analysis revealed various dysregulated pathways involved in IDC patients hinting that their detailed investigations could lead to novel mechanistic insights into the disease pathophysiology. In addition, we validated the expression pattern of five of these VOCs namely 2-ethyl-1-hexanol, isolongifolenone, furan, dodecanoic acid, 2-methoxy-phenol in another external cohort of 59 urinary samples (IDC = 32 and HC = 27) and found their expression pattern to be consistent with the primary sample set. To our knowledge, this is the first study exploring breast IDC volatome alterations in Indian patients.

RevDate: 2022-05-11

Irshad M, Mujahid A, Afzal A, et al (2018)

A miniaturized electronic sensor for instant monitoring of ethanol in gasohol fuel blends.

RSC advances, 8(41):22952-22962 pii:c8ra02170h.

Gasoline-ethanol (gasohol) fuel blends have gained considerable attention in the petroleum and energy sectors as relatively cheaper and greener high-octane alternative fuels with gasoline-comparable efficiency in modern transportation vehicles. However, due to different combustion rates the relative concentration of ethanol in gasohol fuel blends may vary over time. Furthermore, there is a need to monitor ethanol concentration in fuel blends for quality control applications. This article reports a miniaturized electronic sensor based on an interdigital capacitor (IDC) as the transducer and a dual-imprinted titania-polyaniline composite film as the receptor. The device has an active surface area of 0.9 cm2 and is easy to fabricate. The receptor material is synthesized by imprinting ethanol in both titania sol (EITS, the matrix) and polyaniline nanoparticles (EIPani, the filler), and subsequently mixing them to obtain a dual-imprinted EITS-EIPani composite. The structural and morphological characteristics of the receptor layers are determined with Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM), respectively. The IDC devices are fabricated with pristine EITS and dual-imprinted EITS-EIPani composite to test their metrological sensor characteristics in standard ethanol solutions and real-time gasohol fuel blends. The instant shift in capacitance is measured upon exposure to different concentrations of ethanol. These devices show excellent sensitivity and selectivity patterns and demonstrate reliable sensor response toward ethanol in different gasohol fuel blends with 1-10 vol% ethanol. The results of this study reveal that these miniaturized ethanol sensors are potentially useful for rapid analysis of ethanol in gasohol and may be optimized for onboard fuel quality control applications.

RevDate: 2022-05-10

D'Iorio A, Baiano C, Maraucci G, et al (2022)

A longitudinal study on the effects of COVID-19 pandemic on non-motor symptoms in Parkinson's disease.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology [Epub ahead of print].

INTRODUCTION: The COVID-19 pandemic led to psychological consequences on people's mental health, representing a condition of increased vulnerability for the weakest sections of population, including elderly patients with Parkinson's disease (PD). This longitudinal study aimed at exploring the impact of the most frequent non-motor symptoms and their contribute on health-related quality of life of PD patients after the COVID-19 outbreak, in comparison with the pre-pandemic status.

METHODS: Forty-two non-demented PD patients underwent a first assessment between December 2018 and January 2020 (T0). Then, between March and May 2021 (T1), they were contacted again and asked to complete the second assessment. Levels of global functioning, several non-motor symptoms (i.e. depression, apathy, anxiety, anhedonia) and health-related quality of life were investigated.

RESULTS: Results of the the paired Wilcoxon signed-rank test showed that at T1, PD patients scored lower on the emotional subscale of the DAS, Z = - 2.49; p = 0.013; Cohen dz = 0.691. Higher scores of the TEPS total score, Z = - 2.38; p = 0.025; Cohen dz = 0.621, and LEDD, Z = - 2.63; p = 0.008; Cohen dz = 0.731, were also reported at T1.

CONCLUSION: The present study suggested that self-isolation at home might lead to a reduction of apathy and anhedonia in PD patients due to the increase in social support provided by families during COVID-19 restrictions. This evidence brings out the need of a consistent and persistent social support which might be represented by caregivers or/and social assistive robotics.

RevDate: 2022-05-10

Simond AM, Bui T, Zuo D, et al (2022)

Physiological expression of PI3K H1047R mutation reveals its anti-metastatic potential in ErbB2-driven breast cancer.

Oncogene [Epub ahead of print].

p110α is a catalytic subunit of phosphoinositide 3-kinase (PI3K), a major downstream effector of receptor tyrosine kinase ErbB2, that is amplified and overexpressed in 20-30% of breast cancers, 40% of which have an activating mutation in p110α. Despite the high frequency of PIK3CA gain-of-function mutations, their prognostic value is controversial. Here, we employ a knock-in transgenic strategy to restrict the expression of an activated form of ErbB2 and p110α kinase domain mutation (p110αHR) in the mammary epithelium. Physiological levels of transgene expression under the control of their endogenous promoters did not result in a major synergistic effect. However, tumors arising in ErbB2/p110αHR bi-genic strain metastasized to the lung with significantly reduced capacity compared to tumors expressing ErbB2 alone. The reduced metastasis was further associated with retention of the myoepithelial layer reminiscent of ductal carcinoma in situ (DCIS), a non-invasive stage of human breast cancer. Molecular and biochemical analyses revealed that these poorly metastatic tumors exhibited a significant decrease in phospho-myosin light chain 2 (MLC2) associated with cellular contractility and migration. Examination of human samples for MLC2 activity revealed a progressive increase in cellular contractility between non-invasive DCIS and invasive ductal carcinoma. Collectively, these data argue that p110αHR mutation attenuates metastatic behavior in the context of ErbB2-driven breast cancer.

RevDate: 2022-05-10

Garg S, P Singh (2022)

Transfer Learning Based Lightweight Ensemble Model for Imbalanced Breast Cancer Classification.

IEEE/ACM transactions on computational biology and bioinformatics, PP: [Epub ahead of print].

Automated classification of breast cancer can often save lives, as manual detection is usually time-consuming & expensive. Since the last decade, deep learning techniques have been most widely used for the automatic classification of breast cancer using histopathology images. This paper has performed the binary and multi-class classification of breast cancer using a transfer learning-based ensemble model. To analyze the correctness and reliability of the proposed model, we have used an imbalance IDC dataset, an imbalance BreakHis dataset in the binary class scenario, and a balanced BACH dataset for the multi-class classification. A lightweight shallow CNN model with batch normalization technology to accelerate convergence is aggregated with lightweight MobileNetV2 to improve learning and adaptability. The aggregation output is fed into a multilayer perceptron to complete the final classification task. The experimental study on all three datasets was performed and compared with the recent works. We have fine-tuned three different pre-trained models (ResNet50, InceptionV4, and MobilNetV2) and compared it with the proposed lightweight ensemble model in terms of execution time, number of parameters, model size, etc. In both the evaluation phases, it is seen that our model outperforms in all three datasets.

RevDate: 2022-05-09

Chen WM, Fu M, Zhang CJ, et al (2022)

Deep Learning-Based Universal Expert-Level Recognizing Pathological Images of Hepatocellular Carcinoma and Beyond.

Frontiers in medicine, 9:853261.

Background and Aims: We aim to develop a diagnostic tool for pathological-image classification using transfer learning that can be applied to diverse tumor types.

Methods: Microscopic images of liver tissue with and without hepatocellular carcinoma (HCC) were used to train and validate the classification framework based on a convolutional neural network. To evaluate the universal classification performance of the artificial intelligence (AI) framework, histological images from colorectal tissue and the breast were collected. Images for the training and validation sets were obtained from the Xiamen Hospital of Traditional Chinese Medicine, and those for the test set were collected from Zhongshan Hospital Xiamen University. The accuracy, sensitivity, and specificity values for the proposed framework were reported and compared with those of human image interpretation.

Results: In the human-machine comparisons, the sensitivity, and specificity for the AI algorithm were 98.0, and 99.0%, whereas for the human experts, the sensitivity ranged between 86.0 and 97.0%, while the specificity ranged between 91.0 and 100%. Based on transfer learning, the accuracies of the AI framework in classifying colorectal carcinoma and breast invasive ductal carcinoma were 96.8 and 96.0%, respectively.

Conclusion: The performance of the proposed AI framework in classifying histological images with HCC was comparable to the classification performance achieved by human experts, indicating that extending the proposed AI's application to diagnoses and treatment recommendations is a promising area for future investigation.

RevDate: 2022-05-07

Weiler G, Bartovic J, Ebbesen BB, et al (2022)

Improving health in immigration detention and promoting alternatives to detention.

Lancet (London, England) pii:S0140-6736(22)00742-5 [Epub ahead of print].

RevDate: 2022-05-06

Butcher MR, White MJ, Rooper LM, et al (2022)

MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.

The American journal of surgical pathology pii:00000478-990000000-00021 [Epub ahead of print].

Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.

RevDate: 2022-05-06

Kryvenko ON, Punnen S, Udayakumar TS, et al (2022)

Experimental Support for the Possibility of Retrograde Genesis of Intraductal Carcinoma of the Prostate.

International journal of surgical pathology [Epub ahead of print].

Background. Historically, intraductal carcinoma of the prostate (IDC-P) was postulated to be a retrograde spread of high-grade invasive prostate cancer. There is evidence that IDC-P can primary originate in the prostatic ducts. The retrograde genesis has never been experimentally or clinically confirmed before. Methods. Biopsy proven intermediate or high-risk prostate cancer was orthotopically grafted in the prostate of severe combined immunodeficiency gamma mice. Cancer growth was monitored by serum PSA levels. The animals were sacrificed and grafted areas were histological examined. Results. Twenty-one of 23 mice survived and demonstrated rising serum PSA. In 10 of 21 animals, human prostate cancer was identified orthotopically. Except for one case where the human biopsy showed a Grade Group 2 prostate cancer and mouse graft was Grade Group 5, other 9 specimens showed comparable grades. One of the specimens demonstrated a cribriform invasive prostate cancer and adjacent IDC-P. Conclusion. These experimental data offer some evidence that invasive prostate cancer can demonstrate a retrograde spread in the prostatic ducts as IDC-P. Its ability to primarily arise in the ducts has been demonstrated in other studies. However, the issue which remains unresolved is in its most common presentation of IDC-P intermixed with high-grade invasive cancer if it is the former or the latter which came first. Possibly resolving this dilemma will shed some light on the existing controversies if IDC-P should or should not be graded when invasive cancer is present.

RevDate: 2022-05-06

Lee CP, Karyappa R, M Hashimoto (2020)

3D printing of milk-based product.

RSC advances, 10(50):29821-29828 pii:d0ra05035k.

We developed a method to perform direct ink writing (DIW) three-dimensional (3D) printing of milk products at room temperature by changing the rheological properties of the printing ink. 3D printing of food products has been demonstrated by different methods such as selective laser sintering (SLS) and hot-melt extrusion. Methods requiring high temperatures are, however, not suitable to creating 3D models consisting of temperature-sensitive nutrients. Milk is an example of such foods rich in nutrients such as calcium and protein that would be temperature sensitive. Cold-extrusion is an alternative method of 3D printing, but it requires the addition of rheology modifiers and the optimization of the multiple components. To address this limitation, we demonstrated DIW 3D printing of milk by cold-extrusion with a simple formulation of the milk ink. Our method relies on only one milk product (powdered milk). We formulated 70 w/w% milk ink and successfully fabricated complex 3D structures. Extending our method, we demonstrated multi-material printing and created food with various edible materials. Given the versatility of the demonstrated method, we envision that cold extrusion of food inks will be applied in creating nutritious and visually appealing food, with potential applications in formulating foods with various needs for nutrition and materials properties, where food inks could be extruded at room temperature without compromising the nutrients that would be degraded at elevated temperatures.

RevDate: 2022-05-06

Aizawa R, Tsuzuki T, Haga H, et al (2022)

Clinical significance of IDC-P as predictive factor after intensity-modulated radiation therapy.

Cancer science [Epub ahead of print].

The clinical significance of intraductal carcinoma of the prostate (IDC-P) in men with nonmetastatic prostate cancer (PCa) treated with high-dose external-beam radiation therapy remains unclear. The aim of this study was to evaluate the impact of IDC-P in men who received intensity-modulated radiation therapy (IMRT) for nonmetastatic PCa. All patients with high-risk (HR) and very high-risk (VHR) PCa who received IMRT between September 2000 and December 2013 at our institution were analyzed retrospectively. We re-reviewed biopsy cores for the presence of IDC-P. Treatment consisted of IMRT (median: 78 Gy at 2 Gy per fraction) plus 6-month neoadjuvant hormonal therapy (HT). In total, 154 consecutive patients with HR and VHR PCa were analyzed. IDC-P was present in 27.9% (n=43). The median follow-up period was 8.4 years. The 10-year PCa-specific survival, biochemical failure (BF), clinical failure, and castration-resistant PCa rates were 90.0, 47.8, 27.5, and 24.5% in patients with IDC-P, and 96.6, 32.6, 10.8, and 7.0% in those without IDC-P, respectively (p=0.12, 0.04, 0.0031, and 0.012, respectively). In multivariable analysis, IDC-P was not identified as an independent predictive factor for BF (p=0.26). The presence of IDC-P was correlated with a significantly higher incidence of disease progression in men with HR and VHR PCa who received IMRT, although it was not identified as an independent predictive factor for BF. Further investigations are needed to determine the significance of IDC-P as an independent predictive factor for survival outcomes.

RevDate: 2022-05-05

Bruce MK, Joseph WJ, Grunwaldt L, et al (2022)

Transgender Mastectomy: Incidence of High-Risk Pathologic Findings and the Need for Postoperative Cancer Surveillance.

Annals of plastic surgery, 88(3 Suppl 3):S148-S151.

BACKGROUND: Chest masculinization surgeries are one of the most common gender-affirming procedures performed. There is a need for better understanding of the risk of breast cancer and postsurgical screening in female to male (FtM) individuals. This study aimed to evaluate the incidence of high-risk pathologic findings in FtM transgender patients undergoing gender-affirming chest reconstructive surgery.

METHODS: Medical records were reviewed from all FtM patients undergoing gender-affirming chest reconstructive surgery from January 2010 to February 2021 by 3 plastic surgeons at the University of Pittsburgh Medical Center. Relative risk of malignant progression was used to stratify pathologic data. Subsequent management of atypical, in situ, and invasive pathology were recorded.

RESULTS: A total of 318 patients were included in this study; the average age at surgery was 24.6 ± 8.1 years. Eighty-six patients (27%) had a family history of breast and/or ovarian cancer. Overall, 21 patients (6.6%) had some increased risk of breast cancer: 17 (5.3%) had proliferative lesions, mean age 38.2 ± 12.4 years; 2 had atypical ductal hyperplasia, ages 33.4 and 38.3 years; and 2 had invasive ductal carcinoma, ages 35.4 and 40.6 years.

CONCLUSIONS: In this study, we found that 6.6% of FtM transgender patients undergoing top surgery had an elevated risk of breast cancer, with 1.2% of patients having a greater than 2 times risk of breast cancer. These results highlight the importance of appropriate preoperative screening as well as pathological analysis of surgical specimens to help guide clinical care. The authors advocate for a thorough breast cancer risk assessment before surgery for all patients, as well as using pathologic findings to guide postoperative cancer screening and follow-up.

RevDate: 2022-05-05

Tao Q, Li X, Zhu T, et al (2022)

Lactate Transporter SLC16A3 (MCT4) as an Onco-Immunological Biomarker Associating Tumor Microenvironment and Immune Responses in Lung Cancer.

International journal of general medicine, 15:4465-4474 pii:353592.

Purpose: Lactate, a marker of tumor metabolic reprogramming, maintains the acidic microenvironment and also affects the metabolism and function of immune cells. SLC16A3 is responsible for the extracellular transport of lactate, which is a key component of glycolysis. However, the role of SLC16A3 in immune infiltration and immunosuppression of lung cancer is largely unknown. Our study explored the therapeutic and prognostic value of SLC16A3 in predicting immune infiltration and immune checkpoint efficacy of lung cancer.

Methods: SLC16A3 expression was evaluated with TCGA database. Kaplan-Meier analysis was performed for survival rates. GO and KEEG enrichment was conducted to determine predictive signaling pathways. We utilized TIMER and CIBERSORT to analyze the correlation between SLC16A3 and immunocyte infiltration as well as immune checkpoint. Interleukin and HIF-1a expression was measured with ELISA kit and flow cytometry separately.

Results: In comparison with normal tissues, SLC16A3 expression was significantly upregulated in both lung adenocarcinoma (LUAD) and squamous carcinoma (LUSC), which was closely related to poor prognosis. GO analysis indicated that SLC16A3 involved in different signal pathways in LUAD and LUSC and linked to HIF-1 signaling in LUAD. High SLC16A3 was correlated with immunosuppressive cells (Treg, Th2 and iDC), immune checkpoint (PD1, PD-L1, PVR, Tim-3, ITGAM) and immunosuppressive factors (foxp3, TGF-β) in LUAD not LUSC. Furthermore, SLC16A3 was identified to tightly interact with IL-8 which may induce microenvironment immune tolerance. Based on the clinical prediction, we performed experiments with LUAD A549 cells and showed reduced IL-8 and HIF-1a when treated with SLC16A3 knockdown. HIF-1a stimulation by dimethyloxalylglycine (DMOG) could restore IL-8 secretion in SLC16A3 downregulated cells.

Conclusion: Taken together, our results suggest that SLC16A3 contributes to a worse prognosis in lung cancer and may play an important role in immune microenvironment and evasion through HIF-1a-IL8 axis, which could be a novel therapeutic target for immunotherapy in lung cancer.

RevDate: 2022-05-04

Icht M, Zukerman G, Ben-Itzchak E, et al (2022)

Response to McKenzie et al. 2021: Keep It Simple; Young Adults With Autism Spectrum Disorder Without Intellectual Disability Can Process Basic Emotions.

We recently read the interesting and informative paper entitled "Empathic accuracy and cognitive and affective empathy in young adults with and without autism spectrum disorder" (McKenzie et al. in Journal of Autism and Developmental Disorders 52: 1-15, 2021). This paper expands recent findings from our lab (Ben-David in Journal of Autism and Developmental Disorders 50: 741-756, 2020a; International Journal of Audiology 60: 319-321, 2020b) and a recent theoretical framework (Icht et al. in Autism Research 14: 1948-1964, 2021) that may suggest a new purview for McKenzie et al.'s results. Namely, these papers suggest that young adults with autism spectrum disorder without intellectual disability can successfully recruit their cognitive abilities to distinguish between different simple spoken emotions, but may still face difficulties processing complex, subtle emotions. McKenzie et al. (Journal of Autism and Developmental Disorders 52: 1-15, 2021) extended these findings to the processing of emotions in video clips, with both visual and auditory information.

RevDate: 2022-05-04

Latif S, Perveen S, Iqbal M, et al (2022)

Epidemiology of Carcinoma Breast in Young Adolescence Women.

Cureus, 14(3):e23683.

Introduction The aim of this study was to compare epidemiological characteristics of breast cancer in young adolescent women (YAW) versus older women (OW). Methods This was a cross-sectional prospective observational study, conducted in Ward 3, Jinnah Postgraduate Medical Center, Karachi, Pakistan, from September 2021 to February 2022. A total of 120 female patients were recruited in this study from the Outpatient Department of Jinnah Postgraduate Medical Center, out of which 22 patients were below the age of 40 years and 98 were above 40 years. For breast cancer diagnosis, we used the triple assessment method involving clinical examination, radiology, and histopathology. Diagnosed patients were further evaluated for hormonal status and metastatic workup. Results were noted on a performa, and differences between both age groups were analyzed. Results Out of 120 patients, 22 were younger than 40 years and 98 were older than 40 years. YAW used to present late after the appearance of symptoms. Patients of both age groups mostly presented with breast lumps (68.18% in YAW and 81.6% in OW). YAW presented with larger sizes of lumps and with more nodal involvement as compared to OW. BI-RADS IV (Breast Imaging Reporting and Data System Category IV) was the most commonly observed (27.27% in YAW and 48.97% in OW) mammographic finding in both age groups. Invasive ductal carcinoma was the most common histological type in both age groups (72.73% in YAW and 76.53% in OW). The triple-negative disease was more commonly found in YAW than OW (40.91% in YAW vs 21.43% in OW). We found that usually YAW presented at advanced stages (stages III and IV, 54.55%) and higher grades (grade III, 63.63%). Conclusion Breast cancer in young patients is rare but more aggressive with higher grades, advanced stages, and poor prognostic features. Heredity is mainly the risk factor in young breast cancer patients. There should be proper screening programs for high-risk group for early diagnosis and prompt treatment. Other age-specific concerns such as psychological impact of disease should be addressed as well.

RevDate: 2022-05-02

Grove J, Komforti MK, Craig-Owens L, et al (2022)

A Collision Tumor in the Breast Consisting of Invasive Ductal Carcinoma and Malignant Melanoma.

Cureus, 14(3):e23588.

Collision tumors are rare neoplasms that consist of at least two different cell lineages at the same site. Given the many possible combinations that can occur, collision tumors, while rare, have been reported in multiple locations such as the stomach, bladder, and thyroid. Collision tumors are rarely found in breast tissue, with only a few cases reported in the literature. We herein report a unique case of a 79-year-old woman with a history of melanoma who presented with a left breast mass that was subsequently found to have invasive ductal carcinoma (IDC) and metastatic melanoma in the breast tissue. This is one of the first reported combinations of these two malignancies.

RevDate: 2022-05-02

Kim DH, Webster TK, Bartolacci JG, et al (2022)

Use of Needle Localization in the Surgical Management of Non-seroma, Mass-forming BIA-ALCL.

Plastic and reconstructive surgery. Global open, 10(4):e4286.

Outcomes related to the treatment of breast implant-associated anaplastic large cell lymphoma, a rare extranodal T-cell lymphoma associated with textured breast implants, are largely dependent on the successful resection to negative margins via en bloc capsulectomy and resection of any associated masses. To date, the use of needle localization, a common technique used in breast surgery, to assist in the complete removal of breast implant-associated anaplastic large cell lymphoma has not been described. We present the case report of a 66-year-old woman, with a previous medical history of left-sided invasive ductal carcinoma, who presented 7 years after textured breast implant placement with a left-sided mass without peri-implant seroma. Biopsy demonstrated breast implant-associated anaplastic large cell lymphoma and the associated breast mass extended beyond the capsule borders. The present report describes the novel use of needle localization in this patient to facilitate the complete removal of the malignancy-associated mass with maximal preservation of the overlying soft tissue envelope.

RevDate: 2022-05-02

Sazawal S, Das S, Ryckman KK, et al (2022)

Machine learning prediction of gestational age from metabolic screening markers resistant to ambient temperature transportation: Facilitating use of this technology in low resource settings of South Asia and East Africa.

Journal of global health, 12:04021 pii:jogh-12-04021.

Background: Knowledge of gestational age is critical for guiding preterm neonatal care. In the last decade, metabolic gestational dating approaches emerged in response to a global health need; because in most of the developing world, accurate antenatal gestational age estimates are not feasible. These methods initially developed in North America have now been externally validated in two studies in developing countries, however, require shipment of samples at sub-zero temperature.

Methods: A subset of 330 pairs of heel prick dried blood spot samples were shipped on dry ice and in ambient temperature from field sites in Tanzania, Bangladesh and Pakistan to laboratory in Iowa (USA). We evaluated impact on recovery of analytes of shipment temperature, developed and evaluated models for predicting gestational age using a limited set of metabolic screening analytes after excluding 17 analytes that were impacted by shipment conditions of a total of 44 analytes.

Results: With the machine learning model using all the analytes, samples shipped in dry ice yielded a Root Mean Square Error (RMSE) of 1.19 weeks compared to 1.58 weeks for samples shipped in ambient temperature. Out of the 44 screening analytes, recovery of 17 analytes was significantly different between the two shipment methods and these were excluded from further machine learning model development. The final model, restricted to stable analytes provided a RMSE of 1.24 (95% confidence interval (CI) = 1.10-1.37) weeks for samples shipped on dry ice and RMSE of 1.28 (95% CI = 1.15-1.39) for samples shipped at ambient temperature. Analysis for discriminating preterm births (gestational age <37 weeks), yielded an area under curve (AUC) of 0.76 (95% CI = 0.71-0.81) for samples shipped on dry ice and AUC of 0.73 (95% CI = 0.67-0.78) for samples shipped in ambient temperature.

Conclusions: In this study, we demonstrate that machine learning algorithms developed using a sub-set of newborn screening analytes which are not sensitive to shipment at ambient temperature, can accurately provide estimates of gestational age comparable to those from published regression models from North America using all analytes. If validated in larger samples especially with more newborns <34 weeks, this technology could substantially facilitate implementation in LMICs.

RevDate: 2022-04-30

Chung Y, Kim S, Kim HS, et al (2022)

High Receptor-interacting Serine/Threonine-protein Kinase 3 (RIP3) Expression Serves as an Independent Poor Prognostic Factor for Triple-negative Breast Carcinoma.

Anticancer research, 42(5):2753-2761.

BACKGROUND/AIM: Receptor-interacting serine/threonine-protein kinase 3 (RIP3) is a key component related to tumor necrosis factor-dependent necroptosis. RIP3 has been known to be a predictive biomarker in many types of carcinomas. We aimed to investigate whether RIP3 expression is correlated with clinicopathological characteristics and the outcomes of patients with breast carcinoma.

PATIENTS AND METHODS: We performed immunostaining for RIP3 and analyzed the association of RIP3 expression status with the clinicopathological characteristics and survival of 203 patients with invasive ductal carcinoma of the breast.

RESULTS: High RIP3 expression was significantly correlated with lymph node metastasis and human epidermal growth factor receptor 2 positivity. In patients with triple-negative breast carcinoma (TNBC), high RIP3 expression was an independent prognostic factor for disease-free survival (DFS). RIP3-high TNBC showed the lowest DFS rate.

CONCLUSION: High RIP3 expression is associated with aggressive clinical behavior of breast carcinoma. Our data suggest that RIP3 serves as an independent prognostic factor in TNBC.

RevDate: 2022-04-28

Nitsan G, Banai K, BM Ben-David (2022)

One Size Does Not Fit All: Examining the Effects of Working Memory Capacity on Spoken Word Recognition in Older Adults Using Eye Tracking.

Frontiers in psychology, 13:841466.

Difficulties understanding speech form one of the most prevalent complaints among older adults. Successful speech perception depends on top-down linguistic and cognitive processes that interact with the bottom-up sensory processing of the incoming acoustic information. The relative roles of these processes in age-related difficulties in speech perception, especially when listening conditions are not ideal, are still unclear. In the current study, we asked whether older adults with a larger working memory capacity process speech more efficiently than peers with lower capacity when speech is presented in noise, with another task performed in tandem. Using the Eye-tracking of Word Identification in Noise Under Memory Increased Load (E-WINDMIL) an adapted version of the "visual world" paradigm, 36 older listeners were asked to follow spoken instructions presented in background noise, while retaining digits for later recall under low (single-digit) or high (four-digits) memory load. In critical trials, instructions (e.g., "point at the candle") directed listeners' gaze to pictures of objects whose names shared onset or offset sounds with the name of a competitor that was displayed on the screen at the same time (e.g., candy or sandal). We compared listeners with different memory capacities on the time course for spoken word recognition under the two memory loads by testing eye-fixations on a named object, relative to fixations on an object whose name shared phonology with the named object. Results indicated two trends. (1) For older adults with lower working memory capacity, increased memory load did not affect online speech processing, however, it impaired offline word recognition accuracy. (2) The reverse pattern was observed for older adults with higher working memory capacity: increased task difficulty significantly decreases online speech processing efficiency but had no effect on offline word recognition accuracy. Results suggest that in older adults, adaptation to adverse listening conditions is at least partially supported by cognitive reserve. Therefore, additional cognitive capacity may lead to greater resilience of older listeners to adverse listening conditions. The differential effects documented by eye movements and accuracy highlight the importance of using both online and offline measures of speech processing to explore age-related changes in speech perception.

RevDate: 2022-04-28

Xu M, Li F, Yu S, et al (2022)

Value of Histogram of Gray-Scale Ultrasound Image in Differential Diagnosis of Small Triple Negative Breast Invasive Ductal Carcinoma and Fibroadenoma.

Cancer management and research, 14:1515-1524 pii:359986.

Objective: To investigate the value of gray-scale ultrasound (US) image histogram in the differential diagnosis between small (≤2.00 cm), oval, or round triple negative breast invasive ductal carcinoma (TN-IDC) and fibroadenoma (FA).

Methods: Fifty-five cases of triple negative breast invasive ductal carcinoma (TN-IDC group) and 57 cases of breast fibroadenoma (FA group) confirmed by pathology in Hubei cancer hospital from September 2017 to September 2021 were analyzed retrospectively. The gray-scale US images were analyzed by histogram analysis method, from which some parameters (including mean, variance, skewness, kurtosis and 1st, 10th, 50th, 90th and 99th percentile) can be obtained. Intraclass correlation coefficient (ICC) was used to evaluate the inter observer reliability of histogram parameters. Histogram parameters between the TN-IDC and FA groups were compared using independent Student's t-test or Mann-Whitney U-test, respectively. In addition, the receiver operating characteristic (ROC) curve analysis was used for the significant parameters to calculate the differential diagnosis efficiency.

Results: All the histogram parameters showed excellent inter-reader consistency, with the ICC values ranged from 0.883 to 0.999. The mean value, 1st, 10th, 50th, 90th and 99th percentiles of TN-IDC group were significantly lower than those of FA group (P < 0.05). The area under ROC curve (AUC) values of mean and n percentiles were from 0.807 to 0.848. However, there were no significant differences in variance, skewness and kurtosis between the two groups (P > 0.05).

Conclusion: Histogram analysis of gray-scale US images can well distinguish small, oval, or round TN-IDC from FA.

RevDate: 2022-04-28

Salih MM, Higgo AA, Khalifa AS, et al (2022)

Incidence of Epstein-Barr Virus Among Women With Breast Cancer Using Monoclonal Antibodies for Latent Membrane Protein 1 (LMP1).

In vivo (Athens, Greece), 36(3):1513-1518.

BACKGROUND/AIM: Breast cancer is a common type of cancer in Sudan. Numerous studies propose viral oncogenesis as an etiological factor for breast cancer. The aim of the study was to analyze the presence of the Epstein-Barr virus (EBV) using monoclonal antibodies against latent membrane protein 1 (LAMP1) and determine the correlation between the presence of EBV and clinicopathological characteristics.

PATIENTS AND METHODS: This study used immunohistochemistry to analyze the presence of EBV in 202 samples from Sudanese women diagnosed with breast cancer. Clinicopathological data were collected from patient records from the Radiation and Isotopes Centre in Khartoum State, Republic of Sudan.

RESULTS: This study included 202 patients 168 (83.2%), 16 (7.9%), and 18 (8.9%), diagnosed with invasive ductal carcinoma, invasive lobular carcinoma, and papillary carcinoma, respectively. Axillary lymph node metastasis was present in 57 (28.2%) of cases, while 11 patients (5.4%) tested positive for EBV. The mean age of patients was 48.14±14.4 years. EBV infection was more frequently detected in invasive ductal carcinoma cases, and EBV positivity was not associated with cancer type, grade, progesterone levels, and HER2 expression. On the other hand, a statistically significant association was found between EBV presence and lymph node involvement, estrogen receptor status, and age group.

CONCLUSION: EBV may not play a vital role in the pathogenesis of breast carcinoma in Sudanese women.

RevDate: 2022-04-28

Shah NR, Pfost SS, Mao RD, et al (2022)

Oncoplastic reconstruction of a large chest wall defect using dual fasciocutaneous flaps: A case report.

International journal of surgery case reports, 93:107010.

INTRODUCTION AND IMPORTANCE: Large chest wall defects in the context of breast cancer or its sequelae can be challenging to address. Oncoplastic techniques have been demonstrated to be safe and feasible options for immediate reconstruction. We describe the use of dual fasciocutaneous flaps for coverage following resection of a large chest wall mass in an area with a remote history of radiation therapy.

CASE PRESENTATION: A 67-year-old woman with a distant history of bilateral mastectomies and adjuvant chemoradiation for Stage IIB triple negative invasive ductal carcinoma presented with an enlarging left chest wall mass and chronic wound. The mass was excised with adequate margins, and the resulting defect was reconstructed with two locoregional fasciocutaneous flaps. Pathology returned negative for malignancy and follow-up demonstrated viable flaps that were healing well.

CLINICAL DISCUSSION: Fasciocutaneous flaps are one of many techniques for breast reconstruction and offer advantages of a relatively superficial dissection, shorter operative time, and decreased risk of functional impairment. They are consequently an attractive option for patients with multiple comorbidities and high risk of perioperative complications. Historically used for immediate reconstruction at the time of oncologic resection, we present its successful use decades after the index cancer operation to manage a chest wall defect secondary to radiation injury.

CONCLUSIONS: Oncoplastic reconstruction with dual fasciocutaneous flaps is a feasible option for a large chest wall defect in the setting of previous radiation.

RevDate: 2022-04-27

Cole NA, Copeland-Halperin LR, Shank N, et al (2022)

BRCA2-associated Breast Cancer in Transgender Women: Reconstructive Challenges and Literature Review.

Plastic and reconstructive surgery. Global open, 10(4):e4059.

Breast cancer in trans women is rare. Only 21 cases have been reported worldwide. Multidisciplinary teams must balance oncologic treatment with patient goals. Here we describe a case of invasive ductal carcinoma in a transgender woman who was found to have a BRCA2 gene mutation. A shared decision-making process led to the patient undergoing bilateral nipple-sparing mastectomy with immediate tissue expander placement. Later findings prompted discussions about adjuvant chemotherapy and radiation. Additionally, we discuss the complexities associated with reconstructing a transfeminine chest.

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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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