Neoplastic Changes Research Articles

Abstract 3041: ASPSCR1-TFE3 gene fusion in transgenic mouse as a new pediatric kidney cancer model

Abstract A novel genetically engineered mouse (GEM) model for pediatric kidney cancer expressing proximal tubule specific ASPSCR1 :TFE3 fusion gene has been developed. The Rosa26 knock-in ASPSCR1 :TFE3 mouse was crossed with SGLT2-Cre mouse that expresses Cre recombinase in the proximal tubules of the kidney. The ASPSCR1 :TFE3 fusion gene retains the DNA binding and activation domain of TFE3, whereas the N-terminal region of TFE3 is replaced with ASPSCR1 sequences. ASPSCR1 :TFE3 is known to up-regulate the Met receptor tyrosine kinase gene and induce oncogenic phenotypes such as uncontrolled cell proliferation, invasion, and metastasis. However, the molecular roles of ASPSCR1 :TFE3 are poorly understood and no standard of care (SOC) exists for pediatric TFE3 fusion renal cell carcinoma (RCC). Ultrasound (US) and histological analyses of the kidneys of 5, 6 and 7 month old mice revealed bilateral cysts and tumors, while 6-week-old mouse kidney appears normal. At gross inspection, 5-month-old mouse had cysts with a diameter of 1-2 mm while 7-month-old mouse had a polycystic kidney and in the end stage disease. Histopathology revealed neoplastic changes in initial stages in the 5-month-old mouse whereas the neoplasia was predominantly a papillary cystic renal carcinoma; solid tumor formations were observed in the 7-month-old mouse. Neoplastic cells seen in within the blood vessel walls of the 7-month-old mouse indicated future metastasis. This new TFE3 fusion GEM will provide an avenue to understand molecular events of tumorigenesis and progression as well as a model for testing novel therapeutics with survival benefit for a cancer with no current SOC. Citation Format: Aylin Alasonyalilar-Demirer, James L. Miller, Erin E. Miller, Justyna J. Gleba, Han W. Tun, John A. Copland. ASPSCR1-TFE3 gene fusion in transgenic mouse as a new pediatric kidney cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3041.

Germ Line Mutations in the Thyroid Hormone Receptor Alpha Gene Predispose to Cutaneous Tags and Melanocytic Nevi.

Background: Many physiological effects of thyroid hormone (TH) are mediated by its canonical action via nuclear receptors (TH receptor α and β [TRα and TRβ]) to regulate transcription of target genes. Heterozygous dominant negative mutations in human TRα mediate resistance to thyroid hormone alpha (RTHα), characterized by features of hypothyroidism (e.g., skeletal dysplasia, neurodevelopmental retardation, constipation) in specific tissues, but near-normal circulating TH concentrations. Hitherto, 41 RTHα cases have been recorded worldwide.Methods: RTHα cases (n = 10) attending a single center underwent cutaneous assessment, recording skin lesions. Lesions excised from different RTHα patients were analyzed histologically and profiled for cellular markers of proliferation and oncogenic potential. Proliferative characteristics of dermal fibroblasts and inducible pluripotent stem cell (iPSC)-derived keratinocytes from patients and control subjects were analyzed.Results: Multiple skin tags and nevi were recorded in all cases, mainly in the head and neck area with a predilection for flexures. The affected patients had highly deleterious mutations (p.E403X, p.E403K, p.F397fs406X, p.A382PfsX7) involving TRα1 alone or mild/moderate loss-of-function mutations (p.A263V, p.L274P) common to TRα1 and TRα2 isoforms. In four patients, although lesions excised for cosmetic reasons were benign intradermal melanocytic nevi histologically, they significantly overexpressed markers of cell proliferation (K17, cyclin D1) and type 3 deiodinase. In addition, oncogenic markers typical of basal cell carcinoma (Gli-1, Gli-2, Ptch-1, n = 2 cases) and melanoma (c-kit, MAGE, CDK4, n = 1) were markedly upregulated in skin lesions. Cell cycle progression and proliferation of TRα mutation-containing dermal fibroblasts and iPSC-derived keratinocytes from patients were markedly increased.Conclusions: Our observations highlight frequent occurrence of skin tags and benign melanocytic nevi in RTHα, with cutaneous cells from patients being in a hyperproliferative state. Such excess of skin lesions, including nevi expressing oncogenic markers, indicates that dermatologic surveillance of RTHα patients, monitoring lesions for features that are suspicious for neoplastic change, is warranted.

Особенности мазков Папаниколау у женщин репродуктивного периода жизни с папилломавирусом 16, 18

Introduction. According to modern data, cervical diseases do not occur by chance. Precancerous lesions vary from person to person and become invasive over time. The need for specific diagnostic methods for early detection of cervical cancer in women of reproductive age always remains relevant. Over the years, numerous diagnostic, cytological and histological studies have been carried out to identify malignant lesions of the cervix. Human papillomavirus (HPV) is a widespread sexually transmitted infection that affects both women and men around the world and plays an important role in the development of cervical disease. It is the most common sexually transmitted virus in the United States of America. For the first time in 1942, Papanicolaou emphasized the possibility of using smears (PAP smears) from the cervix and from the vagina to diagnose cervical disease. PAP preparations of smears are mainly multilayered flat epithelial cells of the ectocervix and vagina, endocervical cylindrical cells, including mononuclear and polynuclear inflammatory cells that enter the vagina through diapedesis from the surface of the epithelial layer, mixing with the mucoid fluid produced by the endocervical epithelial fluid. Purpose — using objective criteria for cytological examination to identify neoplastic changes in the cervix. Materials and methods. The study included 100 women of reproductive age (18–45 years old) during 2015–2020. Of these, 20 were in the control group (group I — control) and 80 — in the high-risk group for cervical cancer (group II — the main group). Group II women were also divided into 2 subgroups: II A — with pathology of the cervix (n=41), II B — without pathology of the cervix (n=39). The study included patients with a positive result on HPV 16/18 including patients whose PAP smears revealed intracellular damage. Pap smears were included in the study according to the following criteria. The smears contained a sufficient number of squamous epithelial cells and their integrity was preserved. Endocervical cells were monitored in all PAP smears. The examination was carried out with at least 5 cells in each, not completely, and with 2 clusters of endocervical glandular or squamous metaplastic cells. Squamous epithelial cells covered at least 10% of the preparation. Bloody, technically artifactic preparations without clinical data have not been studied. The deficit rate did not exceed 3%, and high interest rates on artifacts were not included in the study. Despite the small number of cells in the presence of abnormal cells, this was unequivocally considered sufficient. Results. Interpretation of PAP smear results identified n=35 ASCUS patients, n=24 LSIL, n=21 HSIL patients in the PAP smear positive reproductive age group. HPV serotypes 16.18 were found in 24 of these patients. In women of the II B subgroup, no pathological changes in the cervix were observed. Conclusions. In women of reproductive age with positive HPV 16, 18, for the diagnosis of precancerous diseases of the cervix, taking pap smears is an integral part of the study. As a result of the study, it was revealed that, despite the absence of a clinical picture, pathological changes at the cell level are detected. Key words: HPV16, 18, ASCUS, LSIL, HSIL, PAP.

Application of artificial intelligence-driven endoscopic screening and diagnosis of gastric cancer.

The landscape of gastrointestinal endoscopy continues to evolve as new technologies and techniques become available. The advent of image-enhanced and magnifying endoscopies has highlighted the step toward perfecting endoscopic screening and diagnosis of gastric lesions. Simultaneously, with the development of convolutional neural network, artificial intelligence (AI) has made unprecedented breakthroughs in medical imaging, including the ongoing trials of computer-aided detection of colorectal polyps and gastrointestinal bleeding. In the past demi-decade, applications of AI systems in gastric cancer have also emerged. With AI’s efficient computational power and learning capacities, endoscopists can improve their diagnostic accuracies and avoid the missing or mischaracterization of gastric neoplastic changes. So far, several AI systems that incorporated both traditional and novel endoscopy technologies have been developed for various purposes, with most systems achieving an accuracy of more than 80%. However, their feasibility, effectiveness, and safety in clinical practice remain to be seen as there have been no clinical trials yet. Nonetheless, AI-assisted endoscopies shed light on more accurate and sensitive ways for early detection, treatment guidance and prognosis prediction of gastric lesions. This review summarizes the current status of various AI applications in gastric cancer and pinpoints directions for future research and clinical practice implementation from a clinical perspective.

Chronic gastritis and precancerous diseases of the stomach: Is there a chance of a correct diagnosis?

AIM: The purpose of the study is to investigate the occurrence of the main forms of chronic gastritis, metaplastic and dysplastic changes in the gastric mucosa, the degree of their severity, and to assess their potential risk for the development of gastric cancer.
 MATERIALS AND METHODS: The study involved 2982 patients who underwent esophagogastroduodenoscopy with a standard biopsy of the gastric mucosa for morphological assessment and bacterioscopy. If autoimmune gastritis was suspected, an additional serological diagnosis was performed. When detecting intestinal metaplasia of the gastric mucosa as well as neoplastic changes according to the histological report, the description of this report was analyzed in order to identify possible equivalents in the macroscopic description of the mucous membrane.
 RESULTS: Out of 2982 histological studies of gastric mucosa biopsies, 1273 cases (42.7%) were found to contain H. pylori contamination. In 726 cases (24.3%), intestinal metaplasia. 66 biopsies (2.21%) showed the presence of low-grade intraepithelial neoplasia of the mucosa, 2 biopsies showed indeterminate neoplasia and 4 biopsies showed high-grade neoplasia. In 3 out of the total number of the samples, intravascular gastric adenocarcinoma was detected. In 168 cases (5.6%), gastritis was detected with predominant inflammation of the fundal region characteristic of autoimmune gastritis. In 286 biopsies (10.6%), inflammatory and/or atrophic changes and/or metaplastic changes were preserved, which, as a rule, did not have high activity and pronounced inflammation. In the remaining 1279 cases (42.9%), there was no significant inflammation or atrophic changes. The analysis of endoscopic findings showed that the detectability of intestinal metaplasia of the gastric mucosa without a biopsy study was 13.3%.
 DISCUSSION OF THE RESULTS: According to the results of the conducted research and analysis, it can be stated that at present, the correct diagnosis of chronic gastritis with the establishment of the etiological factor, prognosis and risks of stomach cancer development is practically not feasible within the modern health care system. This not only deprives a doctor of the opportunity to make a correct diagnosis and prescribe adequate treatment to a patient, but also makes almost all cascades of carcinogenesis, including early cancer, invisible.

Effect of Kefir, Yacon (Smallanthus sonchifolius) and the Association Between Yacon and Kefir on Intestinal Physiology in Rats With Colon Cancer

Abstract Objectives To evaluate the effect of consumption of yacon flour, kefir and the association between them on colon cancer induced by 1,2-dimethylhydrazine (DMH) in male Wistar rats, SCFA production, fecal pH and intestinal permeability. Methods The study was conducted with 60 adult Wistar rats divided into 5 groups. For 5 weeks, groups T, Y, K and YK received 1,2-dimethylhydrazine (DMH) to induce colon cancer. After 5 weeks of DMH administration, animals in groups C and T received the standard diet, group Y received a diet with yacon flour with 5% FOS, group K received 1mL /day of kefir and the YK group received a diet with yacon and kefir, for 15 weeks. After euthanasia, intestinal lesions, intraluminal pH, short-chain fatty acids (SCFA) and intestinal permeability were analyzed. Results An increase in macroscopic lesions was observed in groups K (58%) and YK (42%) and a reduction of 5% in group Y, compared to group T. In addition, an increase in neoplastic changes was observed in all groups compared to group T: Y (33%), K (67%) and YK (78%). There was no significant difference in the concentrations of acetate and proprionate, pH, lactulose and mannitol between groups, and butyrate was not found in the samples. Conclusions The consumption of yacon flour, kefir and their association did not influence intestinal physiology and promoted the worsening of the development of colon carcinogenesis in rats. Funding Sources FAPES - Fundação de Amparo à Pesquisa e Inovação do Espírito Santo CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico

755-P: A 26-Week Carcinogenicity Study with the Novel Glucagon Analog Dasiglucagon in CByB6F1-Tg(HRAS)2Jic Mice

Carcinogenicity testing is a regulatory requirement for new pharmaceuticals indicated for chronic diseases. Historically, carcinogenicity testing has been done in 2-year “lifelong” studies in rats and mice. The challenges with these studies in terms of a high false-positive rate and a high background tumor incidence in control animals have led to the development of an alternative transgenic mouse model. The rasH2 mouse is a hemizygous transgenic mouse carrying the human c-Ha-ras gene with its own promoter/enhancer elements, which induces high enhancer activity. The advantages offered by rasH2 mice are the low rate of spontaneous background findings and a lower false-positive rate with a comparable ability to predict known human carcinogens as the 2-year bioassays. We undertook the current carcinogenicity study to assess the novel glucagon analog, dasiglucagon, in the rasH2 mouse model. Four groups of 25 male and female CByB6F1-g(HRAS)2Jic mice received once-daily subcutaneous administration of the vehicle (25 mM sodium phosphate buffer, 17 mg/mL propylene glycol, pH 6.5) or dasiglucagon at 1, 5, and 20 mg/kg. The high dose was selected to result in exposure at least 25 times higher than the relevant clinical exposure. A positive control group received a single intraperitoneal injection of N-methyl-N-nitrosourea. Dasiglucagon at doses up to 20 mg/kg/day to transgenic CByB6F1-Tg(HRAS)2Jic mice for 26 weeks did not result in any neoplastic changes to demonstrate that dasiglucagon was not carcinogenic in the transgenic CByB6F1-Tg(HRAS)2Jic mouse model. Neoplastic findings in stomach of positive control animals demonstrated the functionality of the transgene and the suitability of the batch of transgenic animals. The data provide additional confidence that dasiglucagon has an acceptable profile for use in the treatment of humans. Disclosure M. Elander: None. A. Froud: None.

Pathological Nipple discharge: a comparison between breast ultrasound and mammography

Background:Nipple discharge is a relatively common complaint of females in reproductive age and after menopause.
 Objectives: The aim of this stud was to compare the radiological findings of mammography and ultrasound in women with pathological nipple discharge of different pathology.
 Methods: mammography and ultrasound was done for a total of 50 patients attending the National center of Early detection of Breast cancer with pathological nipple discharge. Ultrasound guided FNA was performed for all cases, and histopathology was available for eleven case.
 Results: ultrasound was able to provide clue of possible underlying cause for all pathological nipple discharge whereas mammography was negative in 54%. Ultrasound was more sensitive in diagnosing malignant breast lesions associated with pathological nipple discharge (85.7%) but less specific (88.3%) as compared with mammography which had (71.4%) sensitivity and (90.6%) specificity. Negative predictive value of ultrasound was 97.4% , mammography was 95.1% and of non-bloody nipple discharge was 94%.
 Conclusion: Ultrasound is essential to complete pathological nipple discharge workup, particularly when mammography is normal, to rule out the possibility of neoplastic changes and to provide clues for nonneoplastic etiology that may guide the management.

Survey on Reporting of Endometrial Biopsies From Women on Progestogen Therapy for Endometrial Atypical Hyperplasia/Endometrioid Carcinoma.

Histologic assessment of response to progestogen therapy is a cornerstone of nonsurgical management of atypical hyperplasia/low-grade endometrioid carcinoma. Pathologists are required to assess whether there is ongoing preneoplastic or neoplastic change in the biopsies (often multiple) taken during therapy. There have been few studies documenting the specific histologic changes induced by therapeutic progestogens and currently there are no guidelines on terminology used in this scenario. Given the need for uniformity in reporting and the lack of guidance in the current literature, we initiated an online survey (including questions, categories of reporting, and scanned slides for assessment) which was sent to all members of British Association of Gynaecological Pathologists (BAGP) and the International Society of Gynecological Pathologists (ISGyP) with the aim to assess the variability among pathologists in reporting these specimens and to come up with a consensus-based terminology for reporting of endometrial biopsies from women on progestogen therapy for endometrial atypical hyperplasia/endometrioid carcinoma. In total, 95 pathologists participated in this survey. This manuscript elaborates on the results of the survey with recommendations aimed at promoting uniform terminology in reporting these biopsies.

Molecular Landscape of the Epithelial–Mesenchymal Transition in Endometrioid Endometrial Cancer

Modern diagnostics are based on molecular analysis and have been focused on searching for new molecular markers to use in diagnostics. Included in this has been the search for the correlation between gene expression in tissue samples and liquid biological materials. The aim of this study was to evaluate the differences in the expression profile of messenger RNA (mRNA) and micro-RNA (miRNA) related to the epithelial–mesenchymal transition (EMT) in different grades of endometrial cancer (G1–G3), in order to select the most promising molecular markers. The study material consisted of tissue samples and whole blood collected from 30 patients with endometrial cancer (study group; G1 = 15; G2 = 8; G3 = 7) and 30 without neoplastic changes (control group). The molecular analysis included the use of the microarray technique and RTqPCR. Microarray analysis indicated the following number of mRNA differentiating the endometrial cancer samples from the control (tissue/blood): G1 vs. C = 21/18 mRNAs, G2 vs. C = 19/14 mRNAs, and G3 vs. C = 10/9 mRNAs. The common genes for the tissue and blood samples (Fold Change; FC > 3.0) were G1 vs. C: TGFB1, WNT5A, TGFB2, and NOTCH1; G2 vs. C: BCL2L, SOX9, BAMBI, and SMAD4; G3 vs. C STAT1 and TGFB1. In addition, mRNA TGFB1, NOTCH1, and BCL2L are common for all grades of endometrial cancer. The analysis showed that miR-144, miR-106a, and miR-30d are most strongly associated with EMT, making them potential diagnostic markers.

Features of the Manifestation of Marek's Disease in Poultry Farms of the Rostov Region, Russian Federation

The authors carried out monitoring studies to examine the epizootic process features and the manifestation of clinical signs and pathological changes in Marek’s disease in various poultry farms in the Rostov region. The disease was most often in chickens aged 1.5 to 6 months. Two forms of the disease were registered: classical (nervous) - 63.3% of cases, and tumor (visceral) - 36.7% of cases. There was an unequal manifestation of symptoms of the disease, because of the different state of natural resistance and immunological reactivity of sick birds. The main clinical signs of Marek’s disease in chickens included: oppression; loss of appetite; development of paresis and paralysis; violation of movement coordination; cachexia; anemic crest, earrings and visible mucous membranes; change in the shape and constriction of the pupil; depigmentation of the iris of the eyes; partial or complete loss of vision; lameness; damage to the feather follicles; and the formation of tumors on the skin. The mortality rate of birds with nervous lesions was 70%. The surviving birds died within 1–2 months from the development of neoplastic changes in the internal organs. The main pathological changes in Marek’s disease were thickening and destructive changes in nerve fibers; and neoplastic changes in the parenchymal organs, lungs, intestinal mesentery, gastrointestinal tract, muscle tissue and skin. Most often, the disease was registered in the personal subsidiary plots of citizens. It manifested itself in massive epizootic outbreaks, usually in a nervous form with a high morbidity and mortality. In poultry farms, the disease was recorded extremely rarely. As a rule, it manifested itself in a tumor-like form, in isolated cases among a small percentage of poultry.
 Keywords: poultry, chickens, Marek’s disease, clinical signs, pathological changes

The cytological component of cervical cancer screening: causes of false negative and false positive results, and ways to avoid them

Cervical cancer (CC) screening is a major component of secondary prevention of CC and involves screening all women at risk of developing this disease, most of whom are asymptomatic. Cytology remains an important component of CC screening in the era of primary screening by genotyping the human papillomavirus. Papanikolaou staining is the method of choice for CC screening. This review highlights the causes of false negative results for various methods of Pap tests and how they can be prevented. A detailed analysis of conditions accompanied by a high probability of false positive abnormal results of the Pap test, an explanation of the pathophysiological basis of this phenomenon, clinical and cytological criteria for differential diagnosis is also presented.Pap test is a screening test. The aim of the cytological examination in CC screening is to assign the patient to a group with absent neoplastic changes in the cervical epithelium, a group with neoplastic changes in the cervical epithelium present, or a group when it is impossible to make an accurate differential diagnosis between benign reactive changes and neoplasia. The Bethesda Cytology Reporting System is used to unify and standardize these categories in most countries of the world. Benign conditions are a common cause of false positive reports of cellular atypia on cervical screening, as evidenced by a large number of studies. This fact should be taken into account both in the interpretation of the results and, if possible, in the planning of cervical screening. The most common conditions that are accompanied by reactive changes in the cervical epithelium, which can be incorrectly assessed as atypia, are: reactive and reparative inflammatory changes, atrophy, metaplasia, reactive changes caused by intrauterine devices. In this regard, when working with the cytological component of cervical screening, it is important for the clinician to understand the basic principles of assessing the cervical epithelium, which will allow using the descriptive part of the report to determine tactics if a false negative or false positive screening result is suspected.Thus, understanding the impact of common benign conditions on the cervical epithelium makes it possible to rationally plan cytological cervical screening and correctly interpret its results in order to achieve the best clinical results that are not limited to the detection of precancerous conditions.

A murine model of tuberculosis/type 2 diabetes comorbidity for investigating the microbiome, metabolome and associated immune parameters.

Tuberculosis (TB) is one of the deadliest infectious diseases in the world. The metabolic disease type 2 diabetes (T2D) significantly increases the risk of developing active TB. Effective new TB vaccine candidates and novel therapeutic interventions are required to meet the challenges of global TB eradication. Recent evidence suggests that the microbiota plays a significant role in how the host responds to infection, injury and neoplastic changes. Animal models that closely reflect human physiology are crucial in assessing new treatments and to decipher the underlying immunological defects responsible for increased TB susceptibility in comorbid patients. In this study, using a diet‐induced murine T2D model that reflects the etiopathogenesis of clinical T2D and increased TB susceptibility, we investigated how the intestinal microbiota may impact the development of T2D, and how the gut microbial composition changes following a very low‐dose aerosol infection with Mycobacterium tuberculosis (Mtb). Our data revealed a substantial intestinal microbiota dysbiosis in T2D mice compared to non‐diabetic animals. The observed differences were comparable to previous clinical reports in TB patients, in which it was shown that Mtb infection causes rapid loss of microbial diversity. Furthermore, diversity index and principle component analyses demonstrated distinct clustering of Mtb‐infected non‐diabetic mice vs. Mtb‐infected T2D mice. Our findings support a broad applicability of T2D mice as a tractable small animal model for studying distinct immune parameters, microbiota and the immune‐metabolome of TB/T2D comorbidity. This model may also enable answers to be found to critical outstanding questions about targeted interventions of the gut microbiota and the gut‐lung axis.

Flipside of the Coin: Iron Deficiency and Colorectal Cancer.

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.

Adaptive two-way sweeping method to 3D kidney reconstruction

ObjectiveThis article presents a novel method of automatic kidney contour detection in computed tomography angiography images. This technique allows to read as input the entire set of CTA images. It allows to read an entire set of kidney CTA images as input and then automatically generates binary images of the detected kidney outlines for each scan separately. Its additional feature is a real-time 3D kidney model reconstruction. MethodsThe main idea is based on an innovative two-way scanning technique. To adapt an algorithm, a CT is analyzed on the basis of a previous slice. The final kidney contour recognition uses the following digital image processing techniques: mathematical morphology, region growth, colorization. Resultsto assess the quality of our technique, we consulted the results with a pathology department. The F1-score of the researched method is 88 % compared to human specialist’s verification. We also conducted a comparative study of computation time, system reliability, and recognition accuracy using three recent alternative methods. ConclusionIn comparison to machine learning algorithms, the presented method is very precise thanks to the application of the adaptive sweeping technique. This solution can be successfully applied in CTA image analyzing, visualization, and neoplastic changes detection. Significancecomputer-aided medical diagnostic is currently one of the greatest challenges for biomedical engineers. The technique can find a real-life application in medical centers and medical-pathology departments.

Computed tomography - indications and the course of the examination

AdmissionComputed tomography, abbreviated CT or CK (computed tomography) is an imaging diagnostic method that uses the action of X-rays. The test allows you to obtain sections of the examined organs, as well as their 3D visualization, which greatly improves the diagnostic process. A tomograph is used to perform a CT scan, and the image obtained with it is called a tomogram. Computed tomography was first performed for diagnostic purposes in the early 1970s in the United States.The computer tomograph consists of three basic elements: the table, the operator's console and the scanner. During the examination, the scanner performs rotations around the patient's body, making a series of x-rays. Then the obtained image is transferred to a computer equipped with specialized software. The image is visible in 2D or 3D technology.AimThe aim of the study is to analyze the indications and the course of computed tomography examination. Material and methodReview of the available literature on the subject.ResultsComputed tomography is always performed based on a medical referral. It is the specialist who determines whether computed tomography will be more suitable than other imaging tests. Usually, computed tomography of the head and sinuses, chest and abdominal cavity are performed. The most common indications for head tomography are recurring headaches and dizziness, previous craniocerebral and sinus injuries, cerebral ischemia and strokes, as well as suspected neoplastic changes in the head. CT is also performed on people who struggle with neurodegenerative diseases, such as Alzheimer's disease. We can receive a referral for this examination froma neurologistan oncologist ophthalmologist, whether ENT specialist. Chest tomography shows the structure of the heart, coronary vessels and the entire respiratory system. Usually it is recommended in the diagnosis of cancers of the respiratory and cardiovascular systems and in the assessment of the stage of coronary artery disease. He can refer us to this research cardiologist, pulmonologist or internal medicine doctor. Abdominal tomography is performed in order to detect possible inflammations (pancreas, large intestine, appendix, kidneys), gastrointestinal obstruction or bleeding, as well as kidney stones or thrombosis of the liver veins. In this case, a referral can be obtained from a gastroenterologist, urologist, whether gynecologist.ConclusionsComputed tomography examination is completely painless and completely non-invasive for patients. It does not last long and allows you to quickly detect changes taking place inside the body. If the test was performed with a contrast agent, the patient may or may not experience some side effects, such as dizziness, a metallic taste in the mouth, nausea and vomiting, and palpitations.

Diagnostic accuracy of clinical visualization and light-based tests in precancerous and cancerous lesions of the oral cavity and oropharynx: a systematic review and meta-analysis.

Evaluate and compare the performance of autofluorescence, chemiluminescence, and clinical visual examination in the detection of oral potentially malignant disorders (OPMD), oral cancer (OC), and oropharyngeal cancer (OPC). A systematic review with meta-analysis based on diagnostic test studies. A literature search was carried out in the MEDLINE and EMBASE databases through August 30, 2020. For this review, the quality assessment tool of diagnostic precision studies (QUADAS-2) was used. Hierarchical regression models were used to estimate pooled diagnostic precision values in a random effects model. A total of 40 studies were identified for this review according to each test evaluated: 5.562 samples for autofluorescence, 1.353 samples for chemiluminescence, and 1.892 samples for clinical examination. The summary measures sensitivity and specificity of the clinical examination were 63% and 78%, respectively, AUC = 0.78 95% CI (0.74-0.81). In the autofluorescence test, these were 86% and 72%, respectively, AUC = 0.86 95% CI (0.83-0.89); and the chemiluminescent test were 67% and 48%, respectively, AUC = 0.59 95% CI (0.54-0.63) CONCLUSIONS: Autofluorescence devices displayed superior accuracy levels in the identification of premalignant lesions and early neoplastic changes compared to clinical examination and chemiluminescent test. Overall, biopsy remains the gold standard for the definitive diagnosis of OPMD, OC, and OPC. Light-based clinical methods such as autofluorescence and chemiluminescence techniques have been used in clinical diagnosis for the differentiation of OPMD and malignant and benign lesions; although detailed visual examination appears to be effective in identifying, previous systematic reviews have not evaluated a relevant number of studies and they did not evaluate the accuracy of the clinical examination.

Enhanced neoplasia detection in chronic ulcerative colitis: the ENDCaP-C diagnostic accuracy study

Background Chronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection. Objectives To establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme. Design Module 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later. Setting Thirty-one UK hospitals. Participants Patients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis. Interventions An optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy. Main outcome Identifying ulcerative colitis patients with neoplasia. Results Module 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interval 0.79 to 0.88). Precancerous neoplasia showed a higher area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.84 to 0.92). Background mucosa had poorer discrimination (optimism-adjusted area under the receiver operating characteristic curve was 0.68, 95% confidence interval 0.62 to 0.73). Module 2 was unable to develop a robust next-generation sequencing assay because of the low amplification rates across all genes. In module 3, 818 patients underwent a baseline colonoscopy. The methylation assay (testing non-neoplastic mucosa) was compared with pathology assessments for neoplasia and showed a diagnostic odds ratio of 2.37 (95% confidence interval 1.46 to 3.82; p = 0.0002). The probability of dysplasia increased from 11.1% before testing to 17.7% after testing (95% confidence interval 13.0% to 23.2%), with a positive methylation result suggesting added value in neoplasia detection. To determine added value above colonoscopy alone, a second (reference) colonoscopy was performed in 193 patients without neoplasia. Although the test showed an increased number of patients with neoplasia associated with primary methylation changes, this failed to reach statistical significance (diagnostic odds ratio 3.93; 95% confidence interval 0.82 to 24.75; p = 0.09). Limitations Since the inception of ENDCaP-C, technology has advanced to allow whole-genome or methylome testing to be performed. Conclusions Methylation testing for chronic ulcerative colitis patients cannot be recommended based on this study. However, following up this cohort will reveal further neoplastic changes, indicating whether or not this test may be identifying a population at risk of future neoplasia and informing future surveillance programmes. Trial registration Current Controlled Trials ISRCTN81826545. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 1. See the NIHR Journals Library website for further project information.

ARSENIC: IT’S TOXICITY AND IMPACT ON HUMAN HEALTH

Water pollution is a major problem in modern life. Almost all the heavy metals are toxic at higher concentrations and some are lethal at very low concentration. Arsenic is a naturally occurring element present in water, food and soil, but now-a-days this element is one of the rapidly emerging serious environmental pollutants; released into the environment through industrial and agricultural usage. In many parts of India, the ground water is contaminated with arsenic. The genesis of arsenic pollution is not understood fully, yet it is thought that natural geological weathering is mostly responsible for the dissolved arsenic in ground water. Arsenic exposure to human causes degenerative, inflammatory and neoplastic changes in skin, respiratory system, blood, lymphatic system, nervous system and reproductive system. There is no particular remedial action for chronic arsenic poisoning. Nearly 100 million people are to be affected by arsenic diseases like spots on the skin, high blood pressure, diabetes, skin cancer, cancer of urinary bladder, kidney and lungs. Low socio-economic status and malnutrition may increase the risk of chronic toxicity. There is a strong relationship between chronic ingestion of arsenic and deleterious human health effects. Safe drinking water and well-nourished food is essential for the prevention of chronic arsenic toxicity. Balance nutritious-supplements play a major role in the prevention of chronic arsenic poisoning. In this review article, authors tried to provide an overview of some of the major effects documented in the scientific literature.

A Benign Intraoral Swelling – Case Report

Salivary gland tumors are rarer compared to other tumors of head and neck region. The major salivary glands like parotid, submandibular ad sublingual glands are more likely to undergo neoplastic changes than the minor salivary glands. Pleomorphic adenoma is the most common tumor of the major salivary glands and the prevalence of its involvement of theminor salivary glands are rare. Intraorally the palate is more vulnerable for pleomorphic adenoma followed by other areas.