Fibroadenoma of the vulva with pseudoangiomatous stromal hyperplasia: A common neoplasm in uncommon site.

Mammary-type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone-sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary-type entities arise from mammary-like anogenital glands, which constitute normal vulvar components. We report a case of a 41-year-old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary-type tissue necessitates excision with clear margins and close monitoring of these patients.

Attenuated adiponectin, omentin, increased interleukin-6 and tumor necrosis factor-alpha levels with altered cognition and depression in non-Hodgkin lymphoma patients: A case-control study.

BACKGROUND AND PURPOSE: Immune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes. METHODS: This case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy. RESULTS: Mean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control. CONCLUSION: Our results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life.

Reducing unwarranted chest x-rays in bronchiolitis: Importance of a robust analysis.

AIM: Bronchiolitis is the commonest reason for hospitalisation amongst infants and is often a target for low-value care (LVC) reduction. We aimed to assess the impact of a multifaceted intervention (clinician education, parent engagement, audit-feedback) on rates of chest x-rays (CXR) in bronchiolitis. METHODS: Longitudinal study of CXRs ordered in infants (1-12 months) diagnosed with bronchiolitis in the Emergency Department (ED) of an Australian paediatric hospital between May 2016 and February 2023. We used logistic regression to measure the impact of the intervention on unwarranted CXR orders, controlling for other potential impacting variables such as time, patient characteristics (age/sex), clinical variables (fever, hypoxia, tachypnoea), seasonal factors (month, day of the week, business hours) and time passed since intervention. RESULTS: Ten thousand one hundred and nine infants were diagnosed with bronchiolitis in the ED over the study period, with 939 (9.3%) receiving a CXR, of which 69% (n = 651) were considered unwarranted. Rates of unwarranted CXRs reduced from 7.9% to 5.4% post-intervention (P < 0.0001). Logistic regression showed the intervention had no significant effect (OR 0.89, 95% CI 0.65-1.23) once other variables and underlying time-based trends were accounted for. CONCLUSIONS: Although pre-post rates appeared significantly improved, a robust analysis demonstrated that our multi-faceted intervention was not effective in reducing CXRs in bronchiolitis. The decision to order CXR was associated with clinical features that overlap with pneumonia suggesting ongoing misconceptions regarding the role of CXR for this indication. Our study highlights the value of large electronic medical record datasets and robust methodology to avoid falsely attributing underlying trends to the LVC intervention.

Sacituzumab Govitecan as a Second-Line Treatment in Relapsed/Refractory Metastatic Triple-Negative Breast Cancer Patients: A Systematic Review and Meta-analysis.

BACKGROUND: Chemotherapy, the only treatment option for metastatic triple-negative breast cancer (mTNBC), showed decreased survival rates. Trophoblast cell surface antigen-2 (Trop-2) could be a possible target for antibody-drug conjugates (ADCs). OBJECTIVE: Sacituzumab govitecan (SG), an anti-Trop-2 ADC for pretreating relapsed/refractory mTNBC patients, was studied to know the efficacy and safety profile of the drug in mTNBC. METHODS: The present review searched MEDLINE (via PubMed), WHO Clinical Trial Registry, Clinical Trials.gov, and Cochrane Central Register of Controlled Trials until December 25, 2022. The studies searched comprised randomized trials and observational studies (retrospective [case-control, cross-sectional] and prospective [cohort designs]). Efficacy assessment was performed in terms of complete response (CR), partial response (PR), objective response rate (ORR), stable disease (SD), progressive disease (PD), and clinical benefit rate (CBR), and safety in terms of adverse events. RESULTS: The overall random-effects pooled prevalence of CR was 4.9 (95% CI: 3.2-7.1), PR was 35.6 (95% CI: 31.5-39.9), ORR was 6.8 (95% CI: 5.9-7.8), SD was 8.0 (95% CI: 6.7-9.4), PD was 5.1 (95% CI: 4.1-6.3), and CBR was 13.4 (95% CI: 11.8-15.1). Adverse events associated with the drug were neutropenia, fatigue, anemia, nausea, and others. CONCLUSION AND RELEVANCE: This is the first meta-analysis conducted in relapsed/refractory mTNBC patients and found that SG is efficacious but associated with some adverse effects that are related to exposure to the drug. The application of these results will allow clinicians to use SG in the management of patients with mTNBC.

Novel NONO::TFE3 fusion and ALK co-expression identified in a subset of cutaneous microcystic/reticular schwannoma.

Microcystic/reticular schwannoma (MRS) is a benign variant of schwannoma with a predilection for the gastrointestinal tract and skin. To date, genetic characterization of this tumor is limited. Prompted by the identification of TFE3::NONO fusion and ALK overexpression in an index case of MRS, a cohort of tumors was collected from institutional and consultation archives of two institutions. Next-generation sequencing (NGS), TFE3 fluorescence in situ hybridization (FISH), and TFE3 and ALK immunohistochemistry were performed, while clinicopathologic variables were documented. Eighteen MRS cases were identified (35 to 85 years) arising in the skin (n=8), gastrointestinal tract (n=5), adrenal gland (n=3), abdominal wall (n=1), and unknown site (n=1). Tumors showed a circumscribed to multinodular to plexiform low-power architecture with variable amounts of microcystic/reticular and solid schwannian components. Mitotic figures were scarce (0-1/10 HPFs), and atypia was absent. S100 protein and/or SOX10 immunoreactivity was noted in the microcystic/reticular and schwannian areas of all cases. NGS performed on two cutaneous tumors yielded NONO exon 12 fusion with TFE3 exon 4, and these lesions also showed HMB45 and ALK expression. Two additional cases showed ALK expression (1 weak), while a third was positive for TFE3, but these cases failed to show ALK or TFE3 rearrangement by FISH/NGS. There were no morphologic variables that correlated with the presence of NONO::TFE3. We identified a subset of microcystic/reticular schwannomas with NONO::TFE3 fusions and ALK co-expression, adding to the cohort of mesenchymal neoplasms that show ALK overexpression without rearrangement of the ALK gene.

Lymphatic vasculature in ovarian cancer.

Ovarian cancer (OVCA) is the second most common gynecological cancer and one of the leading causes of cancer related mortality among women. Recent studies suggest that among ovarian cancer patients at least 70% of the cases experience the involvement of lymph nodes and metastases through lymphatic vascular network. However, the impact of lymphatic system in the growth, spread and the evolution of ovarian cancer, its contribution towards the landscape of ovarian tissue resident immune cells and their metabolic responses is still a major knowledge gap. In this review first we present the epidemiological aspect of the OVCA, the lymphatic architecture of the ovary, we discuss the role of lymphatic circulation in regulation of ovarian tumor microenvironment, metabolic basis of the upregulation of lymphangiogenesis which is often observed during progression of ovarian metastasis and ascites development. Further we describe the implication of several mediators which influence both lymphatic vasculature as well as ovarian tumor microenvironment and conclude with several therapeutic strategies for targeting lymphatic vasculature in ovarian cancer progression in present day.

TNF-α induced extracellular release of keratinocyte high-mobility group box 1 in Stevens-Johnson syndrome/toxic epidermal necrolysis: Biomarker and putative mechanism of pathogenesis.

Decreased epidermal high-mobility group box 1 (HMGB1) expression is an early marker of epidermal injury in Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Etanercept, an anti-tumor necrosis factor therapeutic, is effective in the treatment of SJS/TEN. The objective was to characterize antitumor necrosis factor-alpha (TNF-α)-mediated HMGB1 keratinocyte/epidermal release and etanercept modulation. HMGB1 release from TNF-α treated (± etanercept), or doxycycline-inducible RIPK3 or Bak-expressing human keratinocyte cells (HaCaTs) was determined by western blot/ELISA. Healthy skin explants were treated with TNF-α or serum (1:10 dilution) from immune checkpoint inhibitor-tolerant, lichenoid dermatitis or SJS/TEN patients ± etanercept. Histological and immunohistochemical analysis of HMGB1 was undertaken. TNF-α induced HMGB1 release in vitro via both necroptosis and apoptosis. Exposure of skin explants to TNF-α or SJS/TEN serum resulted in significant epidermal toxicity/detachment with substantial HMGB1 release which was attenuated by etanercept. Whole-slide image analysis of biopsies demonstrated significantly lower epidermal HMGB1 in pre-blistered SJS/TEN versus control (P < 0.05). Keratinocyte HMGB1 release, predominantly caused by necroptosis, can be attenuated by etanercept. Although TNF-α is a key mediator of epidermal HMGB1 release, other cytokines/cytotoxic proteins also contribute. Skin explant models represent a potential model of SJS/TEN that could be utilized for further mechanistic studies and targeted therapy screening.

Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals.

Genome-wide association studies (GWASs) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis that associates serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells strongly impairs choline metabolism due to the inhibition of choline import. Consistently, CRISPR-based genetic screens identified phospholipid synthesis and salvage machinery as synthetic lethal with FLVCR1 loss. Cells and mice lacking FLVCR1 exhibit structural defects in mitochondria and upregulate integrated stress response (ISR) through heme-regulated inhibitor (HRI) kinase. Finally, Flvcr1 knockout mice are embryonic lethal, which is partially rescued by choline supplementation. Altogether, our findings propose FLVCR1 as a major choline transporter in mammals and provide a platform to discover substrates for unknown metabolite transporters.

Therapeutic potential of low dose ionizing radiation against cancer, dementia, and diabetes: evidences from epidemiological, clinical, and preclinical studies.

The growing use of ionizing radiation (IR)-based diagnostic and treatment methods has been linked to increasing chronic diseases among patients and healthcare professionals. However, multiple factors such as IR dose, dose-rate, and duration of exposure influence the IR-induced chronic effects. The predicted links between low-dose ionizing radiation (LDIR) and health risks are controversial due to the non-availability of direct human studies. The studies pertaining to LDIR effects have importance in public health as exposure to background LDIR is routine. It has been anticipated that data from epidemiological and clinical reports and results of preclinical studies can resolve this controversy and help to clarify the notion of LDIR-associated health risks. Accumulating scientific literature shows reduced cancer risk, cancer-related deaths, curtailed neuro-impairments, improved neural functions, and reduced diabetes-related complications after LDIR exposure. In addition, it was found to alter evolutionarily conserved stress response pathways. However, the picture of molecular signaling pathways in LDIR responses is unclear. Besides, there is limited/no information on biomarkers of epidemiological LDIR exposure. Therefore, the present review discusses epidemiological, clinical, and preclinical studies on LDIR-induced positive effects in three chronic diseases (cancer, dementia, and diabetes) and their associated molecular mechanisms. The knowledge of LDIR response mechanisms may help to devise LDIR-based therapeutic modalities to stop disease progression. Modulation of these pathways may be helpful in developing radiation resistance among humans. However, more clinical evidence with additional biochemical, cellular, and molecular data and exploring the side effects of LDIR are the major areas of future research.

Efficacy of Cannabis and its Constituents in Disease Management: Insights from Clinical Studies.

There is a long history of informal use of Cannabis sativa (commonly called cannabis) for many purposes, including treating various ailments worldwide. However, the legalization of cannabis in multiple countries, specifically for medical purposes, has grabbed the researchers' attention to discover the scientific evidence regarding cannabis's beneficial effects. Among over 500 identified compounds (cannabinoids), Δ9-Tetrahydrocannabinol (THC) and cannabidiol (CBD) are two major active cannabinoids derived from cannabis. Cannabinoids exert their effects through cannabinoid receptors (CB1R and CB2R). In the recent past, clinical trials have shown the efficacy of cannabis and cannabinoids for various human ailments, such as cancer, neurological disorders, inflammatory bowel disease, chronic pain, and metabolic disorders. The commonly used constituents and derivatives of cannabis include CBD, THC, THCV, dronabinol, nabilone, and nabiximol. The cannabis constituents have also been used in combination with other agents, such as megestrol acetate, in some clinical trials. The common routes for the administration of cannabis are oral, sublingual, or topical. Cannabis has also been consumed through smoking, inhalation, or with food and tea. A maximum of 572 patients and a minimum of nine patients have participated in a single clinical trial. Cannabis is legalized in some countries with restrictions, such as Belize, Canada, Colombia, Costa Rica, The Czech Republic, Jamaica, Netherlands, South Africa, Spain, and Uruguay. This article provides a compilation of published studies focusing on clinal trials on the therapeutic effects of cannabis. The adverse effects of cannabis and its constituents are also discussed.

TNF-α‒Mediated Keratinocyte Expression and Release of Matrix Metalloproteinase 9: Putative Mechanism of Pathogenesis in Stevens‒Johnson Syndrome/Toxic Epidermal Necrolysis.

Stevens‒Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions characterized by widespread keratinocyte cell death and epidermal detachment. At present, there is little understanding of how the detachment occurs or how it is abrogated by the TNF-α inhibitor etanercept, an effective SJS/TEN treatment. RNA sequencing was used to identify upregulated transcripts in formalin-fixed paraffin-embedded SJS/TEN skin biopsies. Epidermal matrix metalloproteinase 9 (MMP9) expression was assessed by immunohistochemistry in skin biopsies and cultured human skin explants exposed to serum from patients with cutaneous adverse drug reactions. TNF-α‒induced MMP9 expression and activity and its abrogation by etanercept were determined using the HaCaT immortalized keratinocyte cell line. Epidermal MMP9 expression was significantly higher in SJS/TEN skin (70.6%) than in healthy control skin (0%) (P = 0.0098) and nonbullous skin reactions (10.7%) (P = 0.0002). SJS/TEN serum induced significant MMP9 expression and collagenase activity in healthy skin explants, which was reduced by etanercept. Etanercept was also able to negate the TNF-α‒induced MMP9 expression in the HaCaT cell line. Data suggest that elevated epidermal MMP9 expression and collagenase activity are a putative pathogenic mechanism in SJS/TEN, which is limited by etanercept. Modulation of MMP9 expression and activity represents, to our knowledge, a previously unreported therapeutic target for the treatment of SJS/TEN.

Fuzzy inference system (FIS) - long short-term memory (LSTM) network for electromyography (EMG) signal analysis.

A wide range of application domains,s such as remote robotic control, rehabilitation, and remote surgery, require capturing neuromuscular activities. The reliability of the application is highly dependent on an ability to decode intentions accurately based on captured neuromuscular signals. Physiological signals such as Electromyography (EMG) and Electroencephalography (EEG) generated by neuromuscular activities contain intrinsic patterns for users' particular actions. Such actions can generally be classified as motor states, such as Forward, Reverse, Hand-Grip, and Hand-Release. To classify these motor states truthfully, the signals must be captured and decoded correctly. This paper proposes a novel classification technique using a Fuzzy Inference System (FIS) and a Long Short-Term Memory (LSTM) network to classify the motor states based on EMG signals. Existing EMG signal classification techniques generally rely on features derived from data captured at a specific time instance. This typical approach does not consider the temporal correlation of the signal in the entire window. This paper proposes an LSTM with a Fuzzy Logic method to classify four major hand movements: forward, reverse, raise, and lower. Features associated with the pattern generated throughout the motor state movement were extracted by exploring published data within a given time window. The classification results can achieve a 91.3% accuracy for the 4-way action (Forward/Reverse/GripUp/RelDown) and 95.1% (Forward/Reverse Action) and 96.7% (GripUp/RelDown action) for 2-way actions. The proposed mechanism demonstrates high-level, human-interpretable results that can be employed in rehabilitation or medical-device industries.

Reprogramming of glycolysis by chemical carcinogens during tumor development.

Indiscriminate usage and mismanagement of chemicals in the agricultural and industrial sectors have contaminated different environmental compartments. Exposure to these persistent and hazardous pollutants like heavy metals, endocrine disruptors, aromatic hydrocarbons, and pesticides can result in various health adversities, including cancer. Chemical carcinogens follow a similar pattern of carcinogenesis, like oxidative stress, chromosomal aberration, DNA double-strand break, mismatch repair, and misregulation of oncogenic and/or tumor suppressors. Out of several cancer-associated endpoints, cellular metabolic homeostasis is the commonest to be deregulated upon chemical exposure. Chemical carcinogens hamper glycolytic reprogramming to fuel the malignant transformation of the cells and/or promote cancer progression. Several regulators like Akt, ERK, Ras, c-Myc, HIF-1α, and p53 regulate glycolysis in chemical-induced carcinogenesis. However, the deregulation of the anabolic biochemistry of glucose during chemical-induced carcinogenesis remains to be uncovered. This review comprehensively covers the environmental chemical-induced glycolytic shift during carcinogenesis and its mechanism. The focus is also to fill the major gaps associated with understanding the fairy tale between environmental carcinogens and metabolic reprogramming. Although evidence from studies regarding glycolytic reprogramming in chemical carcinogenesis provides valuable insights into cancer therapy, exposure to a mixture of toxicants and their mechanism of inducing carcinogenesis still needs to be studied.

ROS-directed activation of Toll/NF-κB in the hematopoietic niche triggers benzene-induced emergency hematopoiesis.

Hematopoietic stem cells/progenitor cells (HSC/HPCs) orchestrate the hematopoietic process, effectively regulated by the hematopoietic niche under normal and stressed conditions. The hematopoietic niche provides various soluble factors which influence the differentiation and self-renewal of HSC/HSPs. Unceasing differentiation/proliferation/high metabolic activity of HSC/HPCs makes them susceptible to damage by environmental toxicants like benzene. Oxidative stress, epigenetic modifications, and DNA damage in the HSC/HPCs are the key factors of benzene-induced hematopoietic injury. However, the role of the hematopoietic niche in benzene-induced hematopoietic injury/response is still void. Therefore, the current study aims to unravel the role of the hematopoietic niche in benzene-induced hematotoxicity using a genetically tractable model, Drosophila melanogaster. The lymph gland is a dedicated hematopoietic organ in Drosophila larvae. A group of 30-45 cells called the posterior signaling center (PSC) in the lymph gland acts as a niche that regulates Drosophila HSC/HPCs maintenance. Benzene exposure to Drosophila larvae (48 h) resulted in aberrant hemocyte production, especially hyper-differentiation of lamellocytes followed by premature lymph gland dispersal and reduced adult emergence upon developmental exposure. Subsequent genetic experiments revealed that benzene-induced lamellocyte production and premature lymph gland dispersal were PSC mediated. The genetic experiments further showed that benzene generates Dual oxidase (Duox)-dependent Reactive Oxygen Species (ROS) in the PSC, activating Toll/NF-κB signaling, which is essential for the aberrant hemocyte production, lymph gland dispersal, and larval survival. Together, the study establishes a functional perspective of the hematopoietic niche in a benzene-induced hematopoietic emergency in a genetic model, Drosophila, which might be relevant to higher organisms.

PD-L1 expression in muscle invasive urothelial carcinoma: Comparison of SP142 and SP263 assay.

Introduction: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). Methods: We evaluated Ventana PD-L1 "SP263 and SP142" qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. Results: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. Conclusion: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

Primary extraskeletal myxoid chondrosarcoma of the breast: report of a case and literature review.

Primary extraskeletal myxoid chondrosarcoma (pEMC) of the breast is rare and only a few cases have been reported to date. Herein, we report a case of primary EMC of the breast in a 45-year-old female. The patient presented with a left breast mass for 1 month. Mammogram revealed a fairly circumscribed mass with spicules of calcifications. The core biopsy and resection specimen showed a myxoid soft tissue neoplasm with histologic features of a myxoid chondrosarcoma. Necrosis, hemorrhage, and brisk mitotic activity were present. No malignant epithelial element was identified even after extensive sampling. The tumor cells exhibited immunoreactivity for vimentin, S100, neuron specific enolase, CD99, and synaptophysin, while the epithelial, myoepithelial, and mammary lineage-associated markers were negative. As up to 81% of EMC cases harbor t(9;22)(q22;q12), this results in a fusion of EWS RNA-binding protein 1 gene (EWSR1) at 22q12 to the nuclear receptor subfamily 4, group A, member 3 gene at 9q22. A rearrangement involving the EWSR1 locus was detected in our case. Whole body PET-CT did not reveal any other mass. A diagnosis of pEMC was rendered. The patient received six cycles of 5-Fluorouracil, Cyclophosphamide, and Adriamycin. The patient was in clinical and radiologic remission at the last follow-up (18 months post surgery). PET-CT and brain MRI were negative. In conclusion, surgical pathologists should include EMC in their differential while dealing with a myxoid soft tissue lesion of the breast, particularly in the core needle biopsies. An expeditious diagnosis of EMC of the breast would allow the surgeon to carry out conservative breast surgery instead of more radical approaches taken in cases of other primary malignant mammary neoplasms.

Expression of glucose transporter 1 (SLC2A1) - Clinicopathological associations and survival in an Indian cohort of colorectal cancer patients.

Background: Glucose transporter 1 (GLUT1) facilitates the uptake of glucose in malignant cells. We investigated GLUT1 transcript expression in colorectal cancer (CRC) tumors and explored its relationship to clinicopathological features, diabetes condition, and patient survival. Materials and Methods: The expression of GLUT1 was determined using fluorescent probe-based quantitative real-time polymerase chain reaction assay of tumor tissue and corresponding normal mucosa from 180 archived formalin-fixed, paraffin-embedded tissue blocks of ninety upfront surgically resected colorectal adenocarcinoma cases. Clinical information was collected from the hospital medical records and statistical analyses were performed. Results: Compared to normal mucosa tissue, the GLUT1 expression was significantly elevated in CRC tumor tissue (0.024 ± 0.056 vs. 0.004 ± 0.005; P < 0.0001). The expression was significantly more in poorly differentiated tumors than well/moderately differentiated tumors (P = 0.024) and in patients with liver metastasis (P = 0.013). The high GLUT1 expression correlated with advanced tumor stage (P = 0.003), liver metastasis (P = 0.003), poor tumor differentiation (P = 0.02), and death (P = 0.001). In univariate Cox regression analysis for survival, high GLUT1 expression, presence of any comorbidity, diabetic condition, advanced or metastatic stage, and liver metastasis were significant risk factors for death. CRC patients with high GLUT1 expression showed worse survival outcomes than those with low GLUT1 expression (P = 0.001). Furthermore, the high GLUT1/diabetes (+) patients had an inferior survival outcome than the patients with low GLUT1/diabetes (+) condition. Conclusions: GLUT1 is significantly upregulated in colorectal adenocarcinoma. The expression correlated with poor tumor histology, higher stage, hepatic metastases, and adverse survival in the study cohort.

Co-relation of SARS-CoV-2 related 30-d mortality with HRCT score and RT-PCR Ct value-based viral load in patients with solid malignancy.

BACKGROUND: Coronavirus disease 2019 (COVID-19) patients with malignancy are published worldwide but are lacking in data from India. AIM: To characterize COVID-19 related mortality outcomes within 30 d of diagnosis with HRCT score and RT-PCR Ct value-based viral load in various solid malignancies. METHODS: Patients included in this study were with an active or previous malignancy and with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the institute database. We collected data on demographic details, baseline clinical conditions, medications, cancer diagnosis, treatment and the COVID-19 disease course. The primary endpoint was the association between the mortality outcome and the potential prognostic variables, specially, HRCT score, RT-PCR Ct value-based viral load, etc. using logistic regression analyses treatment received in 30 d. RESULTS: Out of 131 patients, 123 met inclusion criteria for our analysis. The median age was 57 years (interquartile range = 19-82) while 7 (5.7%) were aged 75 years or older. The most prevalent malignancies were of GUT origin 49 (39.8%), hepatopancreatobiliary (HPB) 40 (32.5%). 109 (88.6%) patients were on active anticancer treatment, 115 (93.5%) had active (measurable) cancer. At analysis on May 20, 2021, 26 (21.1%) patients had died. In logistic regression analysis, independent factors associated with an increased 30-d mortality were in patients with the symptomatic presentation. Chemotherapy in the last 4 wk, number of comorbidities (≥ 2 vs none: 3.43, 1.08-8.56). The univariate analysis showed that the risk of death was significantly associated with the HRCT score: for moderate (8-15) [odds ratio (OR): 3.44; 95% confidence interval (CI): 1.3-9.12; P = 0.0132], severe (> 15) (OR: 7.44; 95%CI: 1.58-35.1; P = 0.0112). CONCLUSION: To the best of our knowledge, this is the first study from India reporting the association of HRCT score and RT-PCR Ct value-based 30-d mortality outcomes in SARS-CoV-2 infected cancer patients.

Dosimetric Influence of Acuros XB Dose-to-Medium and Dose-to-Water Reporting Modes on Carcinoma Cervix Using Intensity-Modulated Radiation Therapy and Volumetric RapidArc Technique.

Aim: We aimed to evaluate the dosimetric influence of Acuros XB (AXB) dose-to-medium (Dm) and dose-to-water (Dw) reporting mode on carcinoma cervix using intensity-modulated radiation therapy (IMRT) and RapidArc (RA) technique. Materials and Methods: A cohort of thirty patients cared for carcinoma cervix was retrospectively selected for the study. Plans were computed using analytical anisotropic algorithm (AAA), AXB-Dm, and AXB-Dw algorithms for dosimetric comparison. A paired t-test and Pitman-Morgan dispersion test were executed to appraise the difference in mean values and the inter-patient variability of the differences. Results: The dose-volume parameters were higher for AXB-Dw in contrast to AAA for IMRT and RA plans, excluding D98%, minimum dose to planning target volume (PTV) and rectum mean dose (RA). There was no systematic trend observed in dose-volume parameters for PTV and organs at risk (OARs) between AXB-Dm and AXB-Dw for IMRT and RA plans. The dose-volume parameters for target were higher for AXB-Dm in comparison to AAA in IMRT and RA plans, except D98% and minimum dose to PTV. Analysis envisaged less inter-patient variability while switching from AAA to AXB-Dm in comparison to those switching from AAA to AXB-Dw. Conclusions: The present study reveals the important difference between AAA, AXB-Dm, and AXB-Dw computations for cervix carcinoma using IMRT and RA techniques. The inter-patient variability and systematic difference in dose-volume parameters computed using AAA, AXB-Dm, and AXB-Dw algorithms present the possible impact on the dose prescription to PTV and their relative constraints to OARs for IMRT and RA techniques. This may help in the decision-making in clinic while switching from AAA to AXB (Dm or Dw) algorithm for cervix carcinoma using IMRT and RA techniques.