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#32619922   2020/06/20 To Up

Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

There are few comprehensive studies from Asia on clinicopathologic features of mismatch repair (MMR)-deficient endometrial carcinomas, including rarely from our country. One hundred and four cases of endometrial carcinomas were tested for four MMR proteins by immunohistochemistry. Among 50 MMR-deficient (MMRd) tumors(48%), age-range was 27-68 years(median = 53) and tumor size(n = 34) varied from 1.2-10 cm(average = 4.6). Lower uterine segment(LUS) was involved in 21/31 cases(67.7%). Histopathologically, all cases were endometrioid adenocarcinomas(EMACs), of FIGO grade 2(low-grade)(18 cases) and 3(high-grade)(32 cases), displaying de-differentiated, undifferentiated and lymphoepithelioma(LE)-like patterns, in 24 cases(48%). Tumor infiltration ≥ half of myometrium was seen in 30/44 cases (68.1%); lymphovascular emboli in 19/43 cases(44.1%); and lymph node metastasis in 7/22(31.8%) cases. Uncommonly, clear cell component(n = 2) and focal neuroendocrine differentiation (n = 2) were observed. Immunohistochemically, tumor cells showed paired loss of MLH1 and PMS2 in 33(66%) and MSH2 and MSH6 in 14(28%) cases, along with loss of MSH2 and PMS2, in two and a single case, respectively. Nine patients(18%) were treated for another cancer and 9/33(27.2%) disclosed familial history of cancer. MSH2 was the most frequently lost MMR protein in those cases. Additionally, tumor cells displayed ER positivity in 41/50 cases(82%), PR in 38/41cases(92.6%) and wild-type p53 staining in 24/28 cases(85.7%). Tumor with LE-pattern showed PDLI immunoexpression. Certain clinicopathologic features suggestive for MMRd associated ECs, such as relatively large-sized tumors, involving LUS; especially high-grade, infiltrative EMACs, with undifferentiated/de-differentiated, and LE-like patterns; showing deep muscle invasion, frequent PR immunoexpression and invariably, wild-type p53 immunostaining can be useful in screening cases of Lynch syndrome. This constitutes the first report on these tumors from our country.
Bharat Rekhi, Santosh Menon, Kedar K Deodhar, Jaya Ghosh, Supriya Chopra, Amita Maheshwari

1439 related Products with: Clinicopathological features of 50 mismatch repair (MMR)-deficient endometrial carcinomas, tested by immunohistochemistry: A single institutional feasibility study, India.

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#32619809   2020/06/14 To Up

Combined TLR4 and TLR9 agonists induce distinct phenotypic changes in innate immunity in vitro and in vivo.

Toll-like receptor (TLR)4 and TLR9 agonists, MPL and CpG, are used as adjuvants in vaccines and have been investigated for their combined potential. However, how these two combined agonists regulate transcriptional changes in innate immune cells and cells at the site of vaccination has not been thoroughly investigated. Here, we utilized transcriptomics to investigate how CpG, MPL, and CpG + MPL impact gene expression in dendritic cells (DC) in vitro. Principal component analysis of transcriptional changes after single and combined treatment indicated that CpG, MPL, and CpG + MPL caused distinct gene signatures. CpG + MPL induced antiviral gene expression and activated the interferon regulatory factor pathway. In vitro changes were associated with lower in vivo morbidity upon viral challenge, elevated systemic cytokine protein production, local cytokine mRNA expression, and increased migratory monocyte derived DC populations in the draining lymph node following vaccination with CpG + MPL. This report suggests that CpG + MPL enhances transcription of antiviral and inflammatory genes and increases DC migration.
Anna T Lampe, Bhanwar Lal Puniya, Angela K Pannier, Tomás Helikar, Deborah M Brown

1428 related Products with: Combined TLR4 and TLR9 agonists induce distinct phenotypic changes in innate immunity in vitro and in vivo.

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#32619574   2020/06/30 To Up

Bioinformatics analysis of the genes involved in the extension of proCriteriastate cancer to adjacent lymph nodes by supervised and unsupervised machine learning methods: The role of SPAG1 and PLEKHF2.

The present study aimed to identify the genes associated with the involvement of adjunct lymph nodes of patients with prostate cancer (PCa) and to provide valuable information for the identification of potential diagnostic biomarkers and pathological genes in PCa metastasis. The most important candidate genes were identified through several machine learning approaches including K-means clustering, neural network, Naïve Bayesian classifications and PCA with or without downsampling. In total, 21 genes associated with lymph nodes involvement were identified. Among them, nine genes have been identified in metastatic prostate cancer, six have been found in the other metastatic cancers and four in other local cancers. The amplification of the candidate genes was evaluated in the other PCa datasets. Besides, we identified a validated set of genes involved in the PCa metastasis. The amplification of SPAG1 and PLEKHF2 genes were associated with decreased survival in patients with PCa.
Elham Shamsara, Jamal Shamsara

2553 related Products with: Bioinformatics analysis of the genes involved in the extension of proCriteriastate cancer to adjacent lymph nodes by supervised and unsupervised machine learning methods: The role of SPAG1 and PLEKHF2.



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#32619439   2020/06/30 To Up

Immunophenotypic and Pathologic Heterogeneity of Unclassified Renal Cell Carcinoma: A Study of 300 Cases.

Renal cell carcinoma, unclassified (RCC-U), is a heterogenous group of tumors that do not fit in any recognized histologic types. Immunohistochemical studies are frequently used to characterize these tumors. Herein, we sought to investigate the immunophenotypes of 300 cases of RCC-U. The cases were morphologically classified into three groups: oncocytoma/chromophobe renal cell carcinoma-like -Group 1; clear cell renal cell carcinoma-like - Group 2; and others (i.e., papillary renal cell carcinoma-like/collecting duct-like/pure sarcomatoid) - Group 3. Male-to-female ratio was 1.4. Most cases (168, 66%) were Group 1. Group 3 was associated with larger tumor size, advanced stage, and frequent lymph node metastases. The most commonly used immunohistochemical stains were CK7 (n=270; 89.5%), vimentin (n=186, 82%), CD10 (n=181; 59.9%), and AMACR (n=162; 54%). Pancytokeratin (79/101; 78.2%) and PAX8 (54/61; 88.5%) were diffusely positive in most cases, followed by AMACR (69/117; 59%). CD117 was positive in 53/118 cases (45%). RCC-U is a morphologically and immunophenotypically heterogenous group of tumors, comprehensive work-up is needed before rendering the diagnosis.
Mahmut Akgul, Liang Cheng

1721 related Products with: Immunophenotypic and Pathologic Heterogeneity of Unclassified Renal Cell Carcinoma: A Study of 300 Cases.



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#32619381   2020/07/03 To Up

Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?

The purpose of this study was to estimate the additional risk of side effects attributed to internal mammary node irradiation (IMNI) as part of regional lymph node irradiation (RNI) in breast cancer patients and to compare it with estimated overall survival (OS) benefit from IMNI. Treatment plans ( = 80) with volumetric modulated arc therapy (VMAT) were calculated for 20 patients (4 plans per patient) with left-sided breast cancer from the prospective GATTUM trial in free breathing (FB) and in deep inspiration breath hold (DIBH). We assessed doses to organs at risk ((OARs) lung, contralateral breast and heart) during RNI with and without additional IMNI. Based on the OAR doses, the additional absolute risks of 10-year cardiac mortality, pneumonitis, and secondary lung and breast cancer were estimated using normal tissue complication probability (NTCP) and risk models assuming different age and risk levels. IMNI notably increased the mean OAR doses. The mean heart dose increased upon IMNI by 0.2-3.4 Gy (median: 1.9 Gy) in FB and 0.0-1.5 Gy (median 0.4 Gy) in DIBH. However, the estimated absolute additional 10-year cardiac mortality caused by IMNI was <0.5% for all patients studied except 70-year-old high risk patients (0.2-2.4% in FB and 0.0-1.1% in DIBH). In comparison to this, the published oncological benefit of IMNI ranges between 3.3% and 4.7%. The estimated additional 10-year risk of secondary cancer of the lung or contralateral breast ranged from 0-1.5% and 0-2.8%, respectively, depending on age and risk levels. IMNI increased the pneumonitis risk in all groups (0-2.2%). According to our analyses, the published oncological benefit of IMNI outweighs the estimated risk of cardiac mortality even in case of (e.g., cardiac) risk factors during VMAT. The estimated risk of secondary cancer or pneumonitis attributed to IMNI is low. DIBH reduces the estimated additional risk of IMNI even further and should be strongly considered especially in patients with a high baseline risk.
Kai Joachim Borm, Cristoforo Simonetto, Pavel Kundrát, Markus Eidemüller, Markus Oechsner, Mathias Düsberg, Stephanie Elisabeth Combs

1659 related Products with: Toxicity of internal mammary irradiation in breast cancer. Are concerns still justified in times of modern treatment techniques?



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#32619179   2020/07/03 To Up

Serum Carboxypeptidase N 1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer.

The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3.
Ranliang Cui, Chaomin Wang, Qi Zhao, Yichao Wang, Yueguo Li

2120 related Products with: Serum Carboxypeptidase N 1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer.

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#32618845   2020/06/28 To Up

Recent developments in head and neck melanoma.

To provide an overview of recently published articles covering melanoma management of the head and neck region.
Neal Deot, Amar Suryadevara

1251 related Products with: Recent developments in head and neck melanoma.



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#32618680   2020/07/01 To Up

Managing Lymphedema in Fracture Care: Current Concepts and Treatment Principles.

Lymphatic flow plays a notable role in the regulation of bone formation and remodeling. Chronic accumulation of the lymph fluid within tissues may lead to issues with proper bone healing after fractures, emphasizing the importance of proper management of lymphedema after trauma. Many associated risk factors place patients at risk for lymphedema, including previous surgery with nodal dissection, radiation therapy, infection, malignancy, family history of congenital lymphedema, and trauma. The benchmark imaging technique for the diagnosis of lymphedema is lymphoscintigraphy. Other modalities include duplex ultrasonography, CT, and MRI. First-line conservative treatment of lymphedema is compression. Complete decongestive therapy or complex physical therapy, also known as decongestive lymphatic therapy (DLT), has shown positive results in reducing lymphedema. Surgical interventions aim to either reconstruct and restore function of the lymphatic system or debulk and reduce tissues and fluids. Understanding the significance of lymphedema on bone healing and techniques available to recognize it are important factors in preventing delay in diagnosis and ensuring proper management of lymphedema after trauma.
Christopher Thomas, Jessica T Le, Emily Benson

2463 related Products with: Managing Lymphedema in Fracture Care: Current Concepts and Treatment Principles.

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#32618338   2020/07/03 To Up

A theoretic approach to the mode of gut microbiome translocation in SIV-infected Asian macaques.

Human gut microbiome could translocate to other tissues, and the relocation triggered by HIV/SIV infection has received increasing attention. However, the underlying mode of this translocation, whether it is deterministic or random (passive) process, is not clear, not to mention quantitative estimation of the relocation probability and rates. Using multi-tissue microbiome datasets collected from SIV-infected macaques, originally reported by Klase et al. (2015), we apply Hubbell's unified neutral theory of biodiversity (UNTB) implemented by Harris et al. (2015) in the form of multi-site neutral (MSN) model to explore the translocation mode and rates of the gut microbiome. We found that (i) The translocation from gastrointestinal tract to tissues was driven by stochastic (neutral) forces as revealed by 100% neutrality-passing rates with MSN testing; (ii) The translocation probability from gastrointestinal tract to tissues is significantly larger than the baseline dispersal rates occurring within gastrointestinal tract (0.234 vs. 0.006 at the phylum level, p<0.001). (iii) Approximately 23% of phyla and 55% of genera were migrated from gastrointestinal tract to the tissues (liver and mesenteric lymph nodes). Our findings offer the first interpretation of the microbial translocation mode from gastrointestinal tract to tissues, and the first estimates of the translocation probability and level.
Wendy Li, Zhanshan Sam Ma

2443 related Products with: A theoretic approach to the mode of gut microbiome translocation in SIV-infected Asian macaques.

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#32618211   // To Up

Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.

Sarcoidosis is a multisystem granulomatous disease commonly involving the lungs and mediastinal lymph nodes with the exact etiology being unclear. The simultaneous presence of malignant disease such as breast cancer and sarcoidosis has been reported. Sarcoidosis preceding a diagnosis of malignancy and that occurring years after treatment of malignant disease has been noted in the past. The presence of sarcoidosis in the setting of malignant disease carries a high risk of misdiagnosis. In this article, we report the case of a 45-year-old female with stage IA invasive ductal carcinoma of left breast that was in remission for 2 years; however, radiological imaging including magnetic resonance imaging of thoracic spine and positron emission tomography-computed tomography scanning were highly suspicious for malignant disease metastasis versus lymphoma with the widespread lymphadenopathy. Multiple tissue biopsies with histopathological evaluation allowed us to definitively exclude malignant disease metastasis and to correctly diagnose her atypical presentation of sarcoidosis.
Pradnya Brijmohan Bhattad, Vinay Jain

2325 related Products with: Diffuse Sarcoidosis Masquerading as Widespread Malignant Disease: A Rare Case Report and Literature Review.



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