Search results for: bladder malignancy

Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

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Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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Authors: Shaik Asha Begum, S. Joshna Rani, Shaik Abdul Rahaman

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INTRODUCTION: Breast cancer is a disease that creates in breast cells. "KAP" study estimates the Knowledge, Attitude, and Practices of a local area. More than 1.5 million ladies (25% of all ladies with malignancy) are determined to have bosom disease consistently all through the world. Understanding the degrees of Knowledge, Attitude and Practice will empower a more effective cycle of mindfulness creation as it will permit the program to be custom-made all the more properly to the necessities of the local area. OBJECTIVES: The objective of this study is to assess the knowledge on signs and symptoms, risk factors, provide awareness on the practicing of the early detection techniques of breast cancer and provide knowledge on the overall breast cancer including preventive techniques. METHODOLOGY: This is an expressive cross-sectional investigation. This investigation of KAP was done in the Nirmala Educational Institutions from January to April 2021. A total of 300 participants are included from women students in pharmacy graduates & lecturers, and also from graduates other than the pharmacy. The examiners are taken from the BCAM (Breast Cancer Awareness Measure), tool compartment (Version 2). RESULT: According to the findings of the study, the majority of the participants were not well informed about breast cancer. A lump in the breast was the most commonly mentioned sign of breast cancer, followed by pain in the breast or nipple. The percentage of knowledge related to the breast cancer risk factors was also very less. The correct answers for breast cancer risk factors were radiation exposure (58.20 percent), a positive family history (47.6 percent), obesity (46.9 percent), a lack of physical activity (43.6 percent), and smoking (43.2 percent). Breast cancer screening, on the other hand, was uncommon (only 30 and 11.3 percent practiced clinical breast examination and mammography respectively). CONCLUSION: In this study, the knowledge on the signs and symptoms, risk factors of breast cancer - pharmacy graduates have more knowledge than the non-pharmacy graduates but in the preventive techniques and early detective tools of breast cancer -had poor knowledge in the pharmacy and non-pharmacy graduate. After the awareness program, pharmacy and non-pharmacy graduates got supportive knowledge on the preventive techniques and also practiced the early detective techniques of breast cancer.

Keywords: breast cancer, mammography, KAP study, early detection

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Authors: Merilin Ivanova Ivanova, Kalin Dimitrov Atanasov, Stefan Petrov Enchev

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Backgroud: Neuromyelitis optica spectrum disorder, also known as Devic’s disease, is a relapsing demyelinating autoimmune inflammatory disorder of the central nervous system associated with anti-aquaporin 4 (AQP4) antibodies that can manifest with devastating secondary neurological deficits. Most commonly affected are the optic nerves and the spinal cord-clinically this is often presented with optic neuritis (loss of vision), transverse myelitis(weakness or paralysis of extremities),lack of bladder and bowel control, numbness. APS is a core clinical entity of NMOSD and adds to the clinical representation the following symptoms: intractable nausea, vomiting and hiccup, it usually occurs isolated at onset, and can lead to a significant delay in the diagnosis. The condition may have features similar to multiple sclerosis (MS) but the episodes are worse in NMO and it is treated differently. It could be relapsing or monophasic. Possible complications are visual field defects and motor impairment, with potential blindness and irreversible motor deficits. In severe cases, myogenic respiratory failure ensues. The incidence of reported cases is approximately 0.3–4.4 per 100,000. Paediatric cases of NMOSD are rare but have been reported occasionally, comprising less than 5% of the reported cases. Objective: The case serves to show the difficulty when it comes to the diagnostic processes regarding a rare autoimmune disease with non- specific symptoms, taking large interval of rimes to reveal as complete clinical manifestation of the aforementioned syndrome, as well as the necessity of multidisciplinary approach in the setting of а general paediatric department in аn emergency hospital. Methods: itpatient's history, clinical presentation, and information from the used diagnostic tools(MRI with contrast of the central nervous system) lead us to the conclusion .This was later on confirmed by the positive results from the anti-aquaporin 4 (AQP4) antibody serology test. Conclusion: APS is a common symptom of NMOSD and is considered a challenge in a differential-diagnostic plan. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing thorough physical examinations are essential if we are to reduce and avoid misdiagnosis.

Keywords: neuromyelitis, devic's disease, hiccup, autoimmune, MRI

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Authors: Kumar Divyendra

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Underwater Sensor Networks (UWSNs) have wide applications in areas such as water quality monitoring, marine wildlife management etc. A typical UWSN system consists of a set of sensors deployed randomly underwater which communicate with each other using acoustic links. RF communication doesn't work underwater, and GPS too isn't available underwater. Additionally Automated Underwater Vehicles (AUVs) are deployed to collect data from some special nodes called Cluster Heads (CHs). These CHs aggregate data from their neighboring nodes and forward them to the AUVs using optical links when an AUV is in range. This helps reduce the number of hops covered by data packets and helps conserve energy. We consider the three-dimensional model of the UWSN. Nodes are initially deployed randomly underwater. They attach themselves to the surface using a rod and can only move upwards or downwards using a pump and bladder mechanism. We use graph theory concepts to maximize the coverage volume while every node maintaining connectivity with at least one surface node. We treat the surface nodes as landmarks and each node finds out its hop distance from every surface node. We treat these hop-distances as coordinates and use them for AUV navigation. An AUV intending to move closer to a node with given coordinates moves hop by hop through nodes that are closest to it in terms of these coordinates. In absence of GPS, multiple different approaches like Inertial Navigation System (INS), Doppler Velocity Log (DVL), computer vision-based navigation, etc., have been proposed. These systems have their own drawbacks. INS accumulates error with time, vision techniques require prior information about the environment. We propose a method that makes use of the earth's magnetic field values for navigation and combines it with other methods that simultaneously increase the coverage volume under the UWSN. The AUVs are fitted with magnetometers that measure the magnetic intensity (I), horizontal inclination (H), and Declination (D). The International Geomagnetic Reference Field (IGRF) is a mathematical model of the earth's magnetic field, which provides the field values for the geographical coordinateson earth. Researchers have developed an inverse deep learning model that takes the magnetic field values and predicts the location coordinates. We make use of this model within our work. We combine this with with the hop-by-hop movement described earlier so that the AUVs move in such a sequence that the deep learning predictor gets trained as quickly and precisely as possible We run simulations in MATLAB to prove the effectiveness of our model with respect to other methods described in the literature.

Keywords: clustering, deep learning, network backbone, parallel computing

Procedia PDF Downloads 63

Authors: Miceska Simona, Škof Erik, Frković Grazio Snježana, Jeričević Anja, Smrkolj Špela, Cvjetićanin Branko, Novaković Srdjan, Grčar Kuzmanov Biljana, Kloboves-Prevodnik Veronika

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Objectives: High-grade serous ovarian cancer (HGSOC) is characterized by the dissemination of the tumor cells (TC) in the peritoneal cavity forming malignant ascites at the time of diagnosis or recurrence. Still, cytology itself has been underutilized as a modality for the diagnosis of HGSOC from ascites, and histological examination from the tumor tissue is yet the only validated method used. The objective of this study was to evaluate the reliability of cytology in the diagnosis of HGSOC in relation to the histopathological examination. Methods: The study included 42 patients with histologically confirmed HGSOC, accompanied by malignant ascites. To confirm the malignancy of the TC in the ascites and to define their immunophenotype, immunohistochemical reaction (IHC) of the following antigens: Calretinin, MOC, WT1, PAX8, p53, p16 & Ki-67 was evaluated on ascites cytospins and tissue blocks. For complete cytological determination of HGSOC, BRCA 1/2 gene mutation was determined from ascites, tissue block, and blood. BRCA1/2 mutation from blood was performed to define the type of mutation, somatic vs germline. Results: Among 42 patients, the immunophenotype of HGSOC from ascites was confirmed in 36 cases (86%). For more profound analysis, the patients were divided in 3 groups regarding the number of TC present in the ascites: patients with less than 10% TC, 10% TC, and more than 10% TC. From all included patients, in the group with less than 10% TC, there were 10 cases, and only 5 of them(50%) showed HGSOC phenotype; 12 cases had equally 10% of TC, and 11 cases (92%) showed HGSOC phenotype; 20 cases had more than 10% TC and all of them (100%) confirmed the HGSOC immunophenotype from ascites. Only 33 patients were eligible for further BRCA1/2 analysis. Eleven BRCA1/2 mutations were detected from thetissue block: 6 germline and 5 somatic. In 2 cases with less than 10% TC, BRCA1/2 mutation was not detected; 4 cases had 10% TC, and 2 of them (50%) confirmed the mutation; 4 cases had more than 10% TC, and all showed 100% reliability with the tumor tissue. Conclusions: Cytology is a highly reliable method for determining the immunophenotype of HGSOC and BRCA1/2 mutation if more than 10% of tumor cells are present in the ascites. This may present an additional non-invasive clinical approach for fast and effective diagnose in the future, especially in inoperable conditions or relapses.

Keywords: cytology, ascites, high-grade serous ovarian cancer, immunophenotype, BRCA1/2

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Authors: Salina Yahya Saddick

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Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Priyal Chikhaliwala, Sudeshna Chandra

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Liver cancer is one of the most common malignant tumors with poor prognosis. This is because liver cancer does not exhibit any symptoms in early stage of disease. Increased serum level of AFP is clinically considered as a diagnostic marker for liver malignancy. The present diagnostic modalities include various types of immunoassays, radiological studies, and biopsy. However, these tests undergo slow response times, require significant sample volumes, achieve limited sensitivity and ultimately become expensive and burdensome to patients. Considering all these aspects, electrochemical biosensors based on dendrimer-magnetic nanoparticles (MNPs) was designed. Dendrimers are novel nano-sized, three-dimensional molecules with monodispersed structures. Poly-amidoamine (PAMAM) dendrimers with eight –NH₂ groups using ethylenediamine as a core molecule were synthesized using Michael addition reaction. Dendrimers provide added the advantage of not only stabilizing Fe₃O₄ NPs but also displays capability of performing multiple electron redox events and binding multiple biological ligands to its dendritic end-surface. Fe₃O₄ NPs due to its superparamagnetic behavior can be exploited for magneto-separation process. Fe₃O₄ NPs were stabilized with PAMAM dendrimer by in situ co-precipitation method. The surface coating was examined by FT-IR, XRD, VSM, and TGA analysis. Electrochemical behavior and kinetic studies were evaluated using CV which revealed that the dendrimer-Fe₃O₄ NPs can be looked upon as electrochemically active materials. Electrochemical immunosensor was designed by immobilizing anti-AFP onto dendrimer-MNPs by gluteraldehyde conjugation reaction. The bioconjugates were then incubated with AFP antigen. The immunosensor was characterized electrochemically indicating successful immuno-binding events. The binding events were also further studied using magnetic particle imaging (MPI) which is a novel imaging modality in which Fe₃O₄ NPs are used as tracer molecules with positive contrast. Multicolor MPI was able to clearly localize AFP antigen and antibody and its binding successfully. Results demonstrate immense potential in terms of biosensing and enabling MPI of AFP in clinical diagnosis.

Keywords: alpha-fetoprotein, dendrimers, electrochemical biosensors, magnetic nanoparticles

Procedia PDF Downloads 117

Authors: J. A. Marañón, L. Lozano C. De Los Santos, L. Martínez-Campesino, E. Caballero-Garrido, F. Galán-Estella

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Urinary incontinence (UI) is a significant health problem with considerable social and economic impact. An estimated 30% of women aged 30 to 60 years old have urinary incontinence (UI), while more than 50% of community-dwelling older women have the condition. Stress urinary incontinence and overactive bladder are the common types of incontinence The prevalence of stress and mixed (stress and urge) incontinence is higher than urge incontinence, but the latter is more likely to require treatment. In women, moderate and severe have a prevalence ranging from about 12% to 17% The objectives of this study was to examine the effect of the supplementation of tablets containing Dropsordry in women with urge urinary incontinence (UUI). Dropsordry is a novel active containing phytoestrogens from SOLGEN, the high genistin soy bean extract and pyrogallol plus polyphenols from standarized pumpkin seed extract,. The study was a single-center, not randomiized open prospective, study. 28 women with urinary incontinence ≥45 years were enrolled in this study (45-62 y. old age . Mean 52 y old). Items related to UI symptoms, were previously collected (T0) and these ítems were reviewed at the final of the study – 8 weeks. (T2). The presence of UI was previously diagnosed using the International Continence Society standards (ICS). Relationships between presence of UI and potential related factors as diabetes were also explored. Daily urinary test control was performed during the 8 weeks of treatment. Daily dosage was 1 g/ day (500 mg twice per day) from 0 to 4 week (T1), following a 500 mg/day daily intake from 4 to 8 week (T2). After eight weeks of treatment, the urgency grade score was reduced a 24,7%. The total urge episodes was reduced a 46%. Surprisingly there was no a significant change in daytime urinations (< 5%), however nocturia was reduced a 69,35%. Strenght Urinary Incontinence (SUI) was also tested showing a remarkably 52,17% reduction. Moreover the use of daily pantyliners was reduced a 66,25%. In addition, it was performed a panel test survey with quests when subjects of the study were enrolled (T0) and the same quests was performed after 8 weeks of supplementation (T2). 100% of the enrolled women fullfilled the ICIQ-SF quest (Spanish versión) and they were also questioned about the effects they noticed in response to taking the supplement and the change in quality of life. Interestingly no side effects were reported. There was a 96,2% of subjective satisfaction and a 85,8% objective score in the improvement of quality of life. CONCLUSION: the combination of High genistin isoflavones and pumpkin seed pyrogallol in Dropsordry tablets seems to be a safe and highly effective supplementation for the relieve of the urinary incontinence symptoms and a better quality of life in perimenopause women .

Keywords: isoflavones, pumpkin, menopause, incontinence, genistin

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Authors: Joshua Russell, Omar Zubair, Reuben Ndegwa

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Introduction: Mesenteric ischemia is an uncommon condition that can be challenging to diagnose in the acute setting, with the potential for significant morbidity and mortality. Very rarely has acute acalculous cholecystitis been described in the setting of mesenteric ischemia. Case: This was the case in a 78-year-old male, who initially presented with clinical and radiological evidence of small bowel obstruction, thought likely secondary to malignancy. The patient had a 6-week history of anorexia, worsening lower abdominal pain, and ~30kg of unintentional weight loss over a 12-month period and a CT- scan demonstrated a transition point in the distal ileum. The patient became increasingly hemodynamically unstable and peritonitic, and an emergency laparotomy was performed. Intra-operatively, however, no obvious transition point was identified, and instead, the gallbladder was markedly gangrenous and oedematous, consistent with acalculous cholecystitis. An open total cholecystectomy was subsequently performed. The patient was admitted to the Intensive Care Unit post-operatively and continued to deteriorate over the proceeding 48 hours, with two re-look laparotomies demonstrating progressively worsening bowel ischemia, initially in the distribution of the superior mesenteric artery and then the coeliac trunk. On review, the patient was found to have an aberrant right hepatic artery arising from the superior mesenteric artery. The extent of ischemia was considered non-survivable, and the patient was palliated. Discussion: Multiple theories currently exist for the underlying pathophysiology of acalculous cholecystitis, including biliary stasis, sepsis, and ischemia. This case lends further support to ischemia as the underlying etiology of acalculous cholecystitis. This is particularly the case when considered in the context of the patient’s aberrant right hepatic artery arising from the superior mesenteric artery, which occurs in 11-14% of patients. Conclusion: This case report adds further insight to the debate surrounding the pathophysiology of acalculous cholecystitis. It also presents acalculous cholecystitis as a complication of mesenteric ischemia that should always be considered, especially in the elderly patient and in the context of relatively common anatomical variations. Furthermore, the case brings to attention the importance of maintaining dynamic working diagnoses in the setting of evolving pathophysiology and clinical presentations.

Keywords: acalculous cholecystitis, anatomical variation, general surgery, mesenteric ischemia

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Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

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After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

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Authors: Bridgette Merriman, Wen Fan

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Background: Existing cancer survivorship literature explores varying physical, psychosocial, and psychological late effects experienced by survivors of childhood cancer. However, adolescent and young adult (AYA) survivors of childhood cancer are understudied compared to their adult and pediatric cancer counterparts. Furthermore, existing quality of life (QoL) research fails to account for how cancer survivorship affects survivors across the lifespan. Given that prior research suggests positive cognitive appraisals of adverse events - such as cancer - mitigate detrimental psychosocial symptomologies later in life; it is crucial to understand cancer’s impacts on AYA survivors of childhood malignancies across the life course in order to best support these individuals and prevent maladaptive psychosocial outcomes. Methods: This qualitative study adopted the life-course perspective to investigate the experiences of AYA survivors of childhood malignancies. Eligible patients included AYA 21-30 years old who were diagnosed with cancer <18 years old and off active treatment for >2 years. Participants were recruited through social media posts. Study fulfillment included taking part in one semi-structured video interview to explore areas of survivorship previously identified as being specific to AYA survivors. Interviews were transcribed, coded, and analyzed in accordance with narrative analysis and life-course theory. This study was approved by the Boston College Institutional Review Board. Results: Of 28 individuals who met inclusion criteria and expressed interest in the study, nineteen participants (12 women, 7 men, mean age 25.4 years old) completed the study. Life course theory analysis revealed that events relating to childhood cancer are interconnected throughout the life course rather than isolated events. This “trail of survivorship” includes age at diagnosis, transitioning to life after cancer, and relationships with other childhood survivors. Despite variability in objective characteristics surrounding these events, participants recalled positive experiences regarding at least one checkpoint, ultimately finding positive meaning from their cancer experience. Conclusions: These findings suggest that favorable subjective experiences at these checkpoints are critical in fostering positive conceptions of childhood malignancy for AYA survivors of childhood cancer. Ultimately, healthcare professionals and communities may use these findings to guide support resources and interventions for childhood cancer patients and AYA survivors, therein minimizing detrimental psychosocial effects and maximizing resiliency.

Keywords: medical sociology, pediatric oncology, survivorship, qualitative, life course perspective

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Ilija Kelepurovski, Stefan Lazorovski, Pece Petkovski, Marian Anakievski, Svetlana Petkovska

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Introduction: Benign prostatic hyperplasia (BPH) is a common condition that affects men over the age of 50 and is characterized by an enlarged prostate gland that can cause lower urinary tract symptoms (LUTS). Uroflowmetry and cystoscopy are two commonly used diagnostic tests to evaluate LUTS and diagnose BPH. While both tests can be useful, there is a risk of overusing cystoscopy and underusing uroflowmetry in the evaluation of LUTS. The aim of this study was to compare the use of uroflowmetry and cystoscopy in a prospective cohort of 100 patients with suspected BPH or other urinary tract conditions and to assess the diagnostic yield of each test. Materials and Methods: This was a prospective study of 100 male patients over the age of 50 with suspected BPH or other urinary tract conditions who underwent uroflowmetry and cystoscopy for the evaluation of LUTS at a single tertiary care center. Inclusion criteria included male patients over the age of 50 with suspected BPH or other urinary tract conditions, while exclusion criteria included previous urethral or bladder surgery, active urinary tract infection, and significant comorbidities. The primary outcome of the study was the frequency of cystoscopy in the evaluation of LUTS, and the secondary outcome was the diagnostic yield of each test. Results: Of the 100 patients included in the study, 86 (86%) were diagnosed with BPH and 14 (14%) had other urinary tract conditions. The mean age of the study population was 67 years. Uroflowmetry was performed on all 100 patients, while cystoscopy was performed on 70 (70%) of the patients. The diagnostic yield of uroflowmetry was high, with a clear diagnosis made in 92 (92%) of the patients. The diagnostic yield of cystoscopy was also high, with a clear diagnosis made in 63 (90%) of the patients who underwent the procedure. There was no statistically significant difference in the diagnostic yield of uroflowmetry and cystoscopy (p = 0.20). Discussion: Our study found that uroflowmetry is an effective and well-tolerated diagnostic tool for evaluating LUTS and diagnosing BPH, with a high diagnostic yield and low risk of complications. Cystoscopy is also a useful diagnostic tool, but it is more invasive and carries a small risk of complications such as bleeding or urinary tract infection. Both tests had a high diagnostic yield, suggesting that either test can provide useful information in the evaluation of LUTS. However, the fact that 70% of the study population underwent cystoscopy raises concerns about the potential overuse of this test in the evaluation of LUTS. This is especially relevant given the focus on patient-centered care and the need to minimize unnecessary or invasive procedures. Our findings underscore the importance of considering the clinical context and using evidence-based guidelines. Conclusion: In this prospective study of 100 patients with suspected BPH or other urinary tract conditions, we found that uroflowmetry and cystoscopy were both valuable diagnostic tools for the evaluation of LUTS. However, the potential overuse of cystoscopy in this population warrants further investigation and highlights the need for careful consideration of the optimal use of diagnostic tests in the evaluation of LUTS and the diagnosis of BPH. Further research is needed to better understand the relative roles of uroflowmetry and cystoscopy in the diagnostic workup of patients with LUTS, and to develop evidence-based guidelines for their appropriate use.

Keywords: uroflowmetry, cystoscopy, LUTS, BPH

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Authors: Muhammad Qasim, Dolors Puigjaner, Josep Maria López, Joan Herrero, Carme Olivé, Gerard Fortuny

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Computational modeling of the human pelvis using the finite element (FE) method has become extremely important to understand the mechanics of prostate motion and deformation when transrectal ultrasound (TRUS) guided biopsy is performed. The number of reliable and validated hyperelastic constitutive FE models of the male pelvis region is limited, and given models did not precisely describe the anatomical behavior of pelvis organs, mainly of the prostate and its neoplasms location. The motion and deformation of the prostate during TRUS-guided biopsy makes it difficult to know the location of potential lesions in advance. When using this procedure, practitioners can only provide roughly estimations for the lesions locations. Consequently, multiple biopsy samples are required to target one single lesion. In this study, the whole pelvis model (comprised of the rectum, bladder, pelvic muscles, prostate transitional zone (TZ), and peripheral zone (PZ)) is used for the simulation results. An isotropic hyperelastic approach (Signorini model) was used for all the soft tissues except the vesical muscles. The vesical muscles are assumed to have a linear elastic behavior due to the lack of experimental data to determine the constants involved in hyperelastic models. The tissues and organ geometry is taken from the existing literature for 3D meshes. Then the biomechanical parameters were obtained under different testing techniques described in the literature. The acquired parametric values for uniaxial stress/strain data are used in the Signorini model to see the anatomical behavior of the pelvis model. The five mesh nodes in terms of small prostate lesions are selected prior to biopsy and each lesion’s final position is targeted when TRUS probe force of 30 N is applied at the inside rectum wall. Code_Aster open-source software is used for numerical simulations. Moreover, the overall effects of pelvis organ deformation were demonstrated when TRUS–guided biopsy is induced. The deformation of the prostate and neoplasms displacement showed that the appropriate material properties to organs altered the resulting lesion's migration parametrically. As a result, the distance traveled by these lesions ranged between 3.77 and 9.42 mm. The lesion displacement and organ deformation are compared and analyzed with our previous study in which we used linear elastic properties for all pelvic organs. Furthermore, the visual comparison of axial and sagittal slices are also compared, which is taken for Magnetic Resource Imaging (MRI) and TRUS images with our preliminary study.

Keywords: code-aster, magnetic resonance imaging, neoplasms, transrectal ultrasound, TRUS-guided biopsy

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Authors: D. Pradhan, G. Tripathy, S. Pradhan

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Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

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Authors: Liane J. Ioannou, Jonathan Serpell, Joanne Dean, Cino Bendinelli, Jenny Gough, Dean Lisewski, Julie Miller, Win Meyer-Rochow, Stan Sidhu, Duncan Topliss, David Walters, John Zalcberg, Susannah Ahern

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Background: The occurrence of thyroid cancer is increasing throughout the developed world, including Australia and New Zealand, and since the 1990s has become the fastest increasing malignancy. Following the success of a number of institutional databases that monitor outcomes after thyroid surgery, the Australian and New Zealand Endocrine Surgeons (ANZES) agreed to auspice the development of a bi-national thyroid cancer registry. Objectives: To establish a bi-national population-based clinical quality registry with the aim of monitoring and improving the quality of care provided to patients diagnosed with thyroid cancer in Australia and New Zealand. Patients and Methods: The Australian and New Zealand Thyroid Cancer Registry (ANZTCR) captures clinical data for all patients, over the age of 18 years, diagnosed with thyroid cancer, confirmed by histopathology report, that have been diagnosed, assessed or treated at a contributing hospital. Data is collected by endocrine surgeons using a web-based interface, REDCap, primarily via direct data entry. Results: A multi-disciplinary Steering Committee was formed, and with operational support from Monash University the ANZTCR was established in early 2017. The pilot phase of the registry is currently operating in Victoria, New South Wales, Queensland, Western Australia and South Australia, with over 30 sites expected to come on board across Australia and New Zealand in 2018. A modified-Delphi process was undertaken to determine the key quality indicators to be reported by the registry, and a minimum dataset was developed comprising information regarding thyroid cancer diagnosis, pathology, surgery, and 30-day follow up. Conclusion: There are very few established thyroid cancer registries internationally, yet clinical quality registries have shown valuable outcomes and patient benefits in other cancers. The establishment of the ANZTCR provides the opportunity for Australia and New Zealand to further understand the current practice in the treatment of thyroid cancer and reasons for variation in outcomes. The engagement of endocrine surgeons in supporting this initiative is crucial. While the pilot registry has a focus on early clinical outcomes, it is anticipated that future collection of longer-term outcome data particularly for patients with the poor prognostic disease will add significant further value to the registry.

Keywords: thyroid cancer, clinical registry, population health, quality improvement

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Authors: Hacer Kobya Bulut, Ilknur Kahriman, Birsel C. Demirbag

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Introduction and Purpose: The lives of children with cancer are affected by long term hospitalizations in a negative way due to complications arising from diagnosis or treatment. However, the children's parents are known to have difficulties in meeting their children’s needs and providing home care after cancer treatment or during remission process. Supporting these children and their parents by giving a planned discharge training starting from the hospital and home care leads to reducing hospital applications, hospitalizations, hospital costs, shortening the length of hospital stay and increasing the satisfaction of the children with cancer and their families. This study was conducted to investigate the status of children and their parents' unplanned application to hospital and re-hospitalization. Methods: The study was carried out with 65 children with hematological malignancy in 0-17 age group and their families in a hematology clinic and polyclinic of a university hospital in Trabzon. Data were collected with survey methodology between August-November, 2015 through face to face interview using numbers, percentage and chi-square test in the evaluation. Findings: Most of the children were leukemia (90.8%) and 49.2% had been ill over 13 months. Few of the parents (32.3%) stated that they had received discharge and home care training (24.6%) but most of them (69.2%) found themselves enough in providing home care. Very few parents (6.2%) received home care training after their children being discharged and the majority of parents (61.5%) faced difficulties in home care and had no one to call around them. The parents expressed that in providing care to their children with hematological malignance, they faced difficulty in feeding them (74.6%), explaining their disease (50.0%), giving their oral medication (47.5%), providing hygiene (43.5%) and providing oral care (39.3%). The question ‘What are the emergency situations in which you have to bring your children to a doctor immediately?' was replied as fever (89.2%), severe nausea and vomiting (87.7%), hemorrhage (86.2%) and pain (81.5%). The study showed that 50.8% of the children had unplanned applications to hospitals and 33.8% of them identified as unplanned hospitalization and the first causes of this were fever and pain. The study showed that the frequency of applications (%78.8) and hospitalizations (%81.8) was higher for boys and a statistically significant difference was found between gender and unplanned applications (X=4.779; p=0.02). Applications (48.5%) and hospitalizations (40.9%) were found lower for the parents who had received hospital discharge training, and a significant difference was determined between receiving training and unplanned hospitalizations (X=8.021; p=0.00). Similarly, applications (30.3%) and hospitalizations (40.9%) was found lower for the ones who had received home care training, and a significant difference was determined between receiving home care training and unplanned hospitalizations (X=4.758; p=0.02). Conclusion: It was found out that caregivers of children with cancer did not receive training related to home care and complications about treatment after discharging from hospital, so they faced difficulties in providing home care and this led to an increase in unplanned hospital applications and hospitalizations.

Keywords: cancer, children, unplanned application, unplanned hospitalization

Procedia PDF Downloads 241

Authors: S. Pradhan, D. Pradhan, G. Tripathy

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

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Authors: Mohammed Khalil Ur Rahman, Mohammed Alsharon, Arshad Muktar, Zahid Shaik

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Any ailment can go into terminal stages, cancer being one such disease which is many times detected in latent stages. Cancer is often characterized by constitutional symptoms which are agonizing in nature which disturbs patients and their family as well. In order to relieve such intolerable symptoms treatment modality employed is known to be ‘Palliative Care’. The goal of palliative care is to enhance patient’s quality of life by relieving or rather reducing the distressing symptoms of patients such as pain, nausea/ vomiting, anorexia/loss of appetite, excessive salivation, mouth ulcers, weight loss, constipation, oral thrush, emaciation etc. which are due to the effect of disease or due to the undergoing treatment such as chemotherapy, radiation etc. Ayurveda and Unani as well as other traditional medicines is getting more and more international attention in recent years and Ayurveda and Unani holistic perspective of the disease, it seems that there are many herbs and herbomineral preparation which can be employed in the treatment of malignancy and also in palliative care. Though many of them have yet to be scientifically proved as anti-cancerous but there is definitely a positive lead that some of these medications relieve the agonising symptoms thereby making life of the patient easy. Health is viewed in Islam in a holistic way. One of the names of the Quran is al-shifa' meaning ‘that which heals’ or ‘the restorer of health’ to refer to spiritual, intellectual, psychological, and physical health. The general aim of medical science, according to Islam, is to secure and adopt suitable measures which, with Allah’s permission, help to preserve or restore the health of the human body. Islam motivates the Physician to view the patient as one organism. The patient has physical, social, psychological, and spiritual dimensions that must be considered in synthesis with an integrated, holistic approach. Aims & Objectives: - To suggest herbs which are mentioned in Ayurveda Unani with potential palliative activity in case of Cancer patients. - Most of tibb nabawi [Prophetic Medicine] is preventive medicine and must have been divinely inspired. - Spiritual Aspects of Healing: Prayer, dua, recitation of the Quran - Remembrance of Allah play a central role.Materials & Method: Literary review of the herbs supported with experiential evidence will be discussed. Discussion: On the basis of collected data subject will be discussed in length. Conclusion: Will be presented in paper.

Keywords: palliative care, holistic, Ayurvedic and Unani traditional system of medicine, Quran, hadith

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Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

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Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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Authors: Abdulkadir Sarauta

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Almost every type of industrial process involves the release of trace quantity of toxic organic and inorganic compound that up in receiving water bodies, this study was aimed at assessing the Persistent Organic Pollutant Level in Challawa River Basin of Kano State, Nigeria. And the research formed the basis of identifying the presence of PCBs and PAHs in receiving water bodies in the study area, assessing the PCBs and PAHs concentration in receiving water body of Challawa system, evaluate the concentration level of PCBs and PAHs in fishes in the study area, determine the concentration level of PCBs and PAHs in crops irrigated in the study area as well as compare the concentration of PCBs and PAHs with the acceptable limit set by Nigerian, EU, U.S and WHO standard. Data were collected using reconnaissance survey, site inspection, field survey, laboratory experiment as well as secondary data source. A total of 78 samples were collected through stratified systematic random sampling (i.e., 26 samples for each of water, crops and fish) three sampling points were chosen and designated A, B and C along the stretch of the river (i.e. up, middle, and downstream) from Yan Danko Bridge to Tambirawa bridge. The result shows that the Polychlorinated biphenyls (PCBs) was not detected while, polycyclic aromatic hydrocarbons (PAHs) was detected in the whole samples analysed at the trench of Challawa River basin in order to assess the contribution of human activities to global environmental pollution. The total concentrations of ΣPAH and ΣPCB ranges between 0.001 to 0.087mg/l and 0.00 to 0.00mg/l of water samples While, crops samples ranges between 2.0ppb to 8.1ppb and fish samples ranges from 2.0 to 6.7ppb.The whole samples are polluted because most of the parameters analyzed exceed the threshold limits set by WHO, Nigerian, U.S and EU standard. The analytical results revealed that some chemicals are present in water, crops and fishes are significantly very high at Zamawa village which is very close to Challawa industrial estate and also is main effluent discharge point and drinking water around study area is not potable for consumption. Analysis of Variance was obtained by Bartlett’s test performance. There is only significant difference in water because the P < 0.05 level of significant, But there is no difference in crops concentration they have the same performance, likes wise in the fishes. It is said to be of concern to health hazard which will increase incidence of tumor related diseases such as skin, lungs, bladder, gastrointestinal cancer, this show there is high failure of pollution abatement measures in the area. In conclusion, it can be said that industrial activities and effluent has impact on Challawa River basin and its environs especially those that are living in the immediate surroundings. Arising from the findings of this research some recommendations were made the industries should treat their liquid properly by installing modern treatment plants.

Keywords: Challawa River Basin, organic, persistent, pollutant

Procedia PDF Downloads 554

Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

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Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

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Authors: Chee Wai Ku, Pui See Chin

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As an emerging alternative to hysterectomy, uterine artery embolization (UAE) has been widely used in the management of fibroids and in controlling postpartum hemorrhage (PPH) unresponsive to other therapies. Research has shown UAE to be a safe, minimally invasive procedure with few complications and minimal effects on future fertility. We present two cases highlighting the use of UAE in preventing PPH in a patient with a large fibroid at the time of cesarean section and in the treatment of secondary PPH refractory to other therapies in another patient. We present a 36-year primiparous woman who booked at 18+6 weeks gestation with a 13.7 cm subserosal fibroid at the lower anterior wall of the uterus near the cervix and a 10.8 cm subserosal fibroid in the left wall. Prophylactic internal iliac artery occlusion balloons were placed prior to the planned classical midline cesarean section. The balloons were inflated once the baby was delivered. Bilateral uterine arteries were embolized subsequently. The estimated blood loss (EBL) was 400 mls and hemoglobin (Hb) remained stable at 10 g/DL. Ultrasound scan 2 years postnatally showed stable uterine fibroids 10.4 and 7.1 cm, which was significantly smaller than before. We present the second case of a 40-year-old G2P1 with a previous cesarean section for failure to progress. There were no antenatal problems, and the placenta was not previa. She presented with term labour and underwent an emergency cesarean section for failed vaginal birth after cesarean. Intraoperatively extensive adhesions were noted with bladder drawn high, and EBL was 300 mls. Postpartum recovery was uneventful. She presented with secondary PPH 3 weeks later complicated by hypovolemic shock. She underwent an emergency examination under anesthesia and evacuation of the uterus, with EBL 2500mls. Histology showed decidua with chronic inflammation. She was discharged well with no further PPH. She subsequently returned one week later for secondary PPH. Bedside ultrasound showed that the endometrium was thin with no evidence of retained products of conception. Uterotonics were administered, and examination under anesthesia was performed, with uterine Bakri balloon and vaginal pack insertion after. EBL was 1000 mls. There was no definite cause of PPH with no uterine atony or products of conception. To evaluate a potential cause, pelvic angiogram and super selective left uterine arteriogram was performed which showed profuse contrast extravasation and acute bleeding from the left uterine artery. Superselective embolization of the left uterine artery was performed. No gross contrast extravasation from the right uterine artery was seen. These two cases demonstrated the superior efficacy of UAE. Firstly, the prophylactic use of intra-arterial balloon catheters in pregnant patients with large fibroids, and secondly, in the diagnosis and management of secondary PPH refractory to uterotonics and uterine tamponade. In both cases, the need for laparotomy hysterectomy was avoided, resulting in the preservation of future fertility. UAE should be a consideration for hemodynamically stable patients in centres with access to interventional radiology.

Keywords: fertility preservation, secondary postpartum hemorrhage, uterine embolization, uterine fibroids

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Authors: Harmeet Pal Singh Dhooria, Deepinder Chinna, UPS Sidhu, Alok Jain

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Serious infections caused by gram-negative bacteria are a significant cause of mortality and morbidity in the hospital setting. In acute care facilities like in intensive care units (ICUs), the intensity of antimicrobial use together with a population highly susceptible to infection, creates an environment, which facilitates both emergence and transmission of Extended Spectrum -lactamase (ESBL) producing Enterobacteriaceae species. The study was conducted in the Medical Intensive Care Unit (MICU) and the Pulmonary Critical Care Unit (PCCU) of the Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab, India. Out of a total of 1108 samples of urine, blood and respiratory tract secretions received for culture and sensitivity analysis from Medical Intensive Care Unit and Pulmonary Critical Care Unit, a total of 170 isolates of Enterobacteriaceae species were obtained which were then included in our study. Out of these 170 isolates, confirmed ESBL production was seen in 116 (68.24%) cases. E.coli was the most common species isolated (56.47%) followed by Klebsiella (32.94%), Enterobacter (5.88%), Citrobacter (3.53%), Enterobacter (0.59%) and Morganella (0.59%) among the total isolates. The rate of ESBL production was more in Klebsiella (78.57%) as compared to E.coli (60.42%). ESBL producers were found to be significantly more common in patients with prior history of hospitalization, antibiotic use, and prolonged ICU stay. Also significantly increased the prevalence of ESBL related infections was observed in patients with a history of catheterization or central line insertion but not in patients with the history of intubation. Patients who had an underlying malignancy had significantly higher prevalence of ESBL related infections as compared to other co-morbid illnesses. A slightly significant difference in the rate of mortality/LAMA was observed in the ESBL producer versus the non-ESBL producer group. The rate of mortality/LAMA was significantly higher in the ESBL related UTI but not in the ESBL related respiratory tract and bloodstream infections. ESBL producing isolates had significantly higher rates of resistance to Cefepime and Piperacillin/Tazobactum, and to non β-lactum antibiotics like Amikacin and Ciprofloxacin. The level of resistance to Imipenem was lower as compared to other antibiotics. However, it was noted that ESBL producing isolates had higher levels of resistance to Imipenem as compared to non-ESBL producing isolates. Conclusion- The prevalence of ESBL producing organisms was found to be very high (68.24%) among Enterobacteriaceae isolates in our ICU setting as among other ICU care settings around the world.

Keywords: enterobacteriaceae, extended spectrum B-lactamase (ESBL), ICU, antibiotic resistance

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Authors: Skyler Kim

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An early diagnosis of leukemia has always been a challenge to doctors and hematologists. On a worldwide basis, it was reported that there were approximately 350,000 new cases in 2012, and diagnosing leukemia was time-consuming and inefficient because of an endemic shortage of flow cytometry equipment in current clinical practice. As the number of medical diagnosis tools increased and a large volume of high-quality data was produced, there was an urgent need for more advanced data analysis methods. One of these methods was the AI approach. This approach has become a major trend in recent years, and several research groups have been working on developing these diagnostic models. However, designing and implementing a leukemia diagnostic system in real clinical environments based on a deep learning approach with larger sets remains complex. Leukemia is a major hematological malignancy that results in mortality and morbidity throughout different ages. We decided to select acute lymphocytic leukemia to develop our diagnostic system since acute lymphocytic leukemia is the most common type of leukemia, accounting for 74% of all children diagnosed with leukemia. The results from this development work can be applied to all other types of leukemia. To develop our model, the Kaggle dataset was used, which consists of 15135 total images, 8491 of these are images of abnormal cells, and 5398 images are normal. In this paper, we design and implement a leukemia diagnostic system in a real clinical environment based on deep learning approaches with larger sets. The proposed diagnostic system has the function of detecting and classifying leukemia. Different from other AI approaches, we explore hybrid architectures to improve the current performance. First, we developed two independent convolutional neural network models: VGG19 and ResNet50. Then, using both VGG19 and ResNet50, we developed a hybrid deep learning architecture employing transfer learning techniques to extract features from each input image. In our approach, fusing the features from specific abstraction layers can be deemed as auxiliary features and lead to further improvement of the classification accuracy. In this approach, features extracted from the lower levels are combined into higher dimension feature maps to help improve the discriminative capability of intermediate features and also overcome the problem of network gradient vanishing or exploding. By comparing VGG19 and ResNet50 and the proposed hybrid model, we concluded that the hybrid model had a significant advantage in accuracy. The detailed results of each model’s performance and their pros and cons will be presented in the conference.

Keywords: acute lymphoblastic leukemia, hybrid model, leukemia diagnostic system, machine learning

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Authors: Jaci Mastrandrea

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening is directly correlated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project is to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline from March 15th, 2022, to April 29th, 2022. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated and evidence-based PC referral criteria. The tool was initially implemented using paper forms and later was integrated into the Epic-Beacon EHR system. Patients were screened by registered nurses on the SLCTC treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher were considered to be a positive screen. Scores of five or higher triggered a PC referral order in the patient’s EHR for the oncologist to review and approve. All patients with a positive screen received an educational handout on the topic of PC, and the EHR was flagged for follow-up. Results: Prior to implementation of the PSCNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the first 100 patient screenings completed within the eight-week data collection period. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting the criteria were flagged in the EHR for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative care, symptom management, symptom screening, ambulatory oncology, cancer, supportive care

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Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel

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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.

Keywords: myelofibrosis, arthritis, arthralgia, malignancy

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Authors: Jaspinder Kaur, Jatinder Pal Singh

Abstract:

Introduction- Delusional parasitosis is a rare psychotic illness characterized by a fixed belief of manifesting a parasite in a body when in reality, it was not. Also known as Ekbom syndrome or delusional infestations, or acarophobia. Although the patient has no primary skin pathology, but all skin findings were secondary to skin manipulation by the patient itself, which is why up to 90% of patients first seek consultation from a dermatologist. Most commonly, it was seen in older people with female to male ratio is 2:1. For treatment, the patient first need to be investigated to rule all other possible causes, as Delusional parasitosis can be caused by Vitamin B12 deficiency, pellagra, hepatic and renal disease, diabetes mellitus, multiple sclerosis, and leprosy. When all possible causes ruled out, psychiatric referral to be done. Rule out other psychiatric comorbidities, and treatment should be done accordingly. Patient with delusional parasitosis responds well to second generation antipsychotics and need to continuous medication over years, and relapse is likely if treatment is stopped. Case Presentation- A 79-year-old female, belonging to lower socio-economic status, presented with complaints of itching sensation with erythematous patches over the scalp and multiple scratch excoriations lesion over the scalp, face and neck from the past 7-8 months. She had a feeling of small insect crawling under her skin and scalp area. To reduce the itching and kill the insect, she would scratch and squeeze her skin repeatedly. When the family tried to give her explanation that there was no insect in her body, she would not get convinced, rather got angry and abuse family members for not believing her. Gradually, her sleep would remain disturbed, she would be seen awake at night, seen to be scratching her skin, pull her scalp hair, even squeeze out her healed lesions. She collected her skin debris, scalp hairs and look out for insect. Because of her continuous illness, the patient started to remain sad and had crying spells. Her appetite decreased. She became socially isolated and stopped doing her activities of daily living. Family member’s first consulted dermatologist, investigated thoroughly with routine investigations, autoimmune and malignancy workup. As all investigations were normal, following which patient was referred for psychiatric evaluation. The patient was started on Tablet Olanzapine 2.5 mg, gradually increased to 7.5 mg. Over 1 month, there was reduction in itching, skin pricking. Lesions were gradually healed, and the patient continued to take other dermatological medications and ointment and was in regular follow up with psychiatric liaison from past 2 months with 70-80 % improvement in her symptoms. Conclusion- Delusional parasitosis is a psychiatric disorder of insidious onset, seen commonly in middle and old age people. Both psychiatric and dermatology consultation liaison will help the patient for an early diagnosis and adequate treatment. If a primary psychiatric diagnosis, the patient respond well to second generation antipsychotics but always require a further evaluation and treatment management if it is secondary to some physical or other psychiatric comorbidity.

Keywords: delusional parasitosis, delusional infestations, rare, primary psychiatric diagnosis, antipsychotic agents

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Authors: Mustafa Cam, Nedim Ongun, Ufuk Kutluana

Abstract:

Introduction: Restless LegsSyndrome (RLS) is a common, under-recognized disorder disrupts sleep and diminishes quality of life (1). The most common conditions highly associated with RLS include renalfailure, iron and folic acid deficiency, peripheral neuropathy, pregnancy, celiacdisease, Crohn’sdiseaseandrarelymalignancy (2).Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficientanemic populations is unknown (2). We report here a case of RLS due to iron deficiency in the setting of neuroendocrinetumor. Report of Case: A 35 year-old man was referred to our clinic with general weakness, weight loss (10 kg in 2 months)and 2-month history of uncomfortable sensations in his legs with urge to move, partially relieved by movement. The symptoms were presented very day, worsening in the evening; the discomfort forced the patient to getup and walk around at night. RLS was severe, with a score of 22 at the International RLS ratingscale. The patient had no past medical history. The patient underwent a complete set of blood analyses and the following ab normal values were found (normal limitswithinbrackets): hemoglobin 9.9 g/dl (14-18), MCV 70 fL (80-94), ferritin 3,5 ng/mL (13-150). Brain and spinemagnetic resonance imaging was normal. The patient consultated with gastroenterology clinic and gastointestinal systemendoscopy was performed for theetiology of the iron deficiency anemia. After the gastricbiopsy, results allowed us to reach the diagnosis of neuroen docrine tumor and the patient referred to oncology clinic. Discussion: The first important consideration from this case report is that the patient was referred to our clinic because of his severe RLS symptoms dramatically reducing his quality of life. However, our clinical study clearly demonstrated that RLS was not the primary disease. Considering the information available for this patient, we believe that the most likely possibility is that RLS was secondary to iron deficiency, a very well-known and established cause of RLS in theliterature (3,4). Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation that most commonly originate in the lungs and gastrointestinal tract (5). NETs vary widely in their clinical presentation; symptoms are often nonspecific and can be mistaken for those of other more common conditions (6). 50% of patients with reported disease stage have either regional or distant metastases at diagnosis (7). Accurate and earlier NET diagnosis is the first step in shortening the time to optimal care and improved outcomes for patients (8). The most important message from this case report is that RLS symptoms can sometimes be thesign of a life-threatening condition. Conclusion: Careful and complete collection of clinical and laboratory data should be carried out in RLS patients. Inparticular, if RLS onset coincides with weight loss and iron deficieny anemia, gastricendos copy should be performed. It is known about that malignancy is a rare etiology in RLS patients and to our knowledge; it is the first case with neuro endocrine tumor presenting with RLS.

Keywords: neurology, neuroendocrine tumor, restless legs syndrome, sleep

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Authors: Beverly Wang

Abstract:

Background: Rosai-Dorfman disease (RDD), aka sinus histiocytosis with massive lymphadenopathy, is a rare, idiopathic histiocytic proliferative disorder. Although RDD can be seen involving the head and neck lymph nodes, rarely it can affect other extranodal sites. It present 3 unique cases of RDD affecting the nasal cavity, paranasal sinuses, and ear canal. The initial clinical presentation on two cases mimicked a malignant neoplasm. The 3rd case of RDD co-existed with a cholesteatoma of the ear canal. The clinical presentation, histology and immunohistochemical stains, and radiographic findings are discussed. Design: An overview of 3 cases of RDD affected sinonasal cavity and ear canal from UCI Medical Center was conducted. Case 1: A 61 year old male complaining of breathing difficulty presented with bilateral polypoid sinonasal masses and severe nasal obstruction. The masses elevated the nasal floor, and involved the anterior nasal septum to lateral wall. It was endoscopically excised. At intraoperative consultation, frozen section reported a pleomorphic spindle cell neoplasm with scattered large atypical spindle cells, resembling a high grade sarcoma. Case 2: A 46 year old male presented with recurrent bilateral maxillary chronic sinusitis with mass formation, clinically suspicious for malignant lymphoma. Excisional tissue sample showed large irregular spindled histiocytes with abundant granular and vacuolated cytoplasm. Case 3: A 36 year old female with a history of asthma initially presented with left-sided chronic otalgia, occasional nausea, vertigo, and fluctuating pain exacerbated by head movement and temperature changes. CT scan revealed an external auditory canal mass extending to the middle ear, coexisting with a small cholesteatoma. Results: The morphology of all cases revealed large atypical spindled histiocytes resembling fibrohistiocytic or myofibroblastic proliferative neoplasms. Scattered emperipolesis was seen. All 3 cases were confirmed as extranodal sinus RDD, confirmed by immunohistochemistry. The large atypical cells were positive for S100, CD68, and CD163. No evidence for malignancy was identified. Case 3 showed concurrent RDD co-existing with a cholesteatoma. Conclusion: Due to its rarity and variable clinical presentations, the diagnosis of RDD is seldom clinically considered. Extranodal sinus RDD morphologically can be pitfall as mimicker of spindly neoplasm, especially at intraoperative consultation. It can create diagnostic and therapeutic challenges. Correlation of radiological findings with histologic features will help to reach the diagnosis.

Keywords: head and neck, extranodal, rosai-dorfman disease, mimicker, immunohistochemistry

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