Search results for: cancer surgery
2110 Health Behaviours of Patients Qualified for Bariatric Surgery
Authors: A. Gazdzinska, P. Jagielski, E. Kaniewska, S. P. Gazdzinski, M. Wylezol
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Background: In the multi-factor etiology of obesity, an increasing degree of importance is attributed to behavioral factors. Lifestyle and health-oriented behaviors heavily influence the treatment of multiple diseases, including obesity. However, only a few studies evaluated health-related behaviors exhibited by patients qualified for bariatric surgery. None of them was performed in Polish population. Aim: Assessment of health behaviors of obese patients according to the degree of mood disorders. Method: The study involved 93 patients (66 females) who were qualified for bariatric surgery in the Department of Surgery of the Military Institute of Aviation Medicine in Warsaw. Diagnostic instrument was the Juczynski’s Inventory of Health Behavior (HBI), which evaluates health behavior in four categories, i.e. proper nutrition habits (PNH), preventive behavior (PH), health practices (HP) and positive mental attitude (PMA). The average HBI falls in the range between 24 and 120 points, for each category of health behaviors fall between 1 and 5 (higher score means higher severity declared healthy behaviors). The depressive symptoms in patients were assessed with Beck Depression Inventory (BDI). All analyses were conducted using STATISTICA 12. Results: The average age was 44.2 ± 11.5 years, mean BMI was 44.3 ± 10.5 kg/m2 and 46.8 ± 7.6 kg/m2, in females and males respectively. According to BDI, 32% patients had mild level of depression, 10% moderate and 14% severe depression. BDI scores were not different between females and males. Low results with regard to the health behaviors declared were obtained by 35.5 % of patients, medium by 44.0%, while high ones by only 20.5%. On average, patients gained 3.28 points in PNH, 3.37 points in PH, 3.29 points in HP, while 3.42 in the PMA category, showing average intensity of these behaviors. These health behaviors were practiced significantly more often by women (p = 0.04). The average HBI was 80.2; with average score of 81.5 for females and 76.6 for males, respectively (p = 0.03). Women were better in the PNH category (p = 0.02). A positive correlation was found between age and all categories of health behaviors, in particular PNH (R = 0.38; p = 0.001), PH (R = 0.26; p = 0.01), HP (R = 0.27; p = 0.01) and PMA (R = 0.24; p = 0.02), independent of gender. The severity of depression had a significant impact only on the behaviors associated with proper eating habits, which saw a negative correlation between BDI scores and the PNH (R = -0.21; p = 0.04). Conclusions: Majority of morbidly obese patients qualified for bariatric surgery obtained low to average scores in health behavior questionnaire. However, these results are similar in comparison with the Polish adult population. In accordance to these results, it seems that healthy behaviors, among them eating behaviors, do not appear to be a cause of obesity epidemic or they might be acquired when the disease is already underway. Female gender and age had a positive effect, and depression had a negative effect on the level of health behaviors among patients qualified for bariatric surgery.Keywords: depression, habits, health behaviours, obesity
Procedia PDF Downloads 2862109 Functional Outcome and Quality of Life of Conservative versus Surgical Management of Adult Potts Disease: A Prospective Cohort Study
Authors: Mark Angelo Maranon, David Endriga
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Objective: The aim of the study is to determine the differences in functional outcome and quality of life of adult patients with Potts disease who have undergone surgical versus non-surgical management. Methods: In this prospective cohort study, 45 patients were followed up for 1 year after undergoing pharmacologic treatment alone versus a combination of anti-Kochs and surgery for Potts disease. Oswestry Disability Index (ODI) and Short Form-36 (SF-36) were obtained on initiation of treatment, after three months, six months and one year. Results: ASIA scores from the onset of treatment and after 1 year significantly improved (p<0.001) for both non-surgical and surgical patients. ODI scores significantly improved after 6 months of treatment for both surgical and non-surgical patients. Both surgical and non-surgical patients showed significant improvement in their SF-36 scores, but scores were noted to be higher in patients who underwent surgery. Conclusions: Significant improvement with regards to functional outcome and quality of life was noted from both surgical and non-surgical patients after 1 year of treatment, with earlier improvements and better final scores in SF 36 and ODI in patients who underwent surgery.Keywords: tuberculosis, spinal, potts disease, functional outcome
Procedia PDF Downloads 1482108 Bariatric Surgery Referral as an Alternative to Fundoplication in Obese Patients Presenting with GORD: A Retrospective Hospital-Based Cohort Study
Authors: T. Arkle, D. Pournaras, S. Lam, B. Kumar
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Introduction: Fundoplication is widely recognised as the best surgical option for gastro-oesophageal reflux disease (GORD) in the general population. However, there is controversy surrounding the use of conventional fundoplication in obese patients. Whilst the intra-operative failure of fundoplication, including wrap disruption, is reportedly higher in obese individuals, the more significant issue surrounds symptom recurrence post-surgery. Could a bariatric procedure be considered in obese patients for weight management, to treat the GORD, and to also reduce the risk of recurrence? Roux-en-Y gastric bypass, a widely performed bariatric procedure, has been shown to be highly successful both in controlling GORD symptoms and in weight management in obese patients. Furthermore, NICE has published clear guidelines on eligibility for bariatric surgery, with the main criteria being type 3 obesity or type 2 obesity with the presence of significant co-morbidities that would improve with weight loss. This study aims to identify the proportion of patients who undergo conventional fundoplication for GORD and/or hiatus hernia, which would have been eligible for bariatric surgery referral according to NICE guidelines. Methods: All patients who underwent fundoplication procedures for GORD and/or hiatus hernia repair at a single NHS foundation trust over a 10-year period will be identified using the Trust’s health records database. Pre-operative patient records will be used to find BMI and the presence of significant co-morbidities at the time of consideration for surgery. This information will be compared to NICE guidelines to determine potential eligibility for the bariatric surgical referral at the time of initial surgical intervention. Results: A total of 321 patients underwent fundoplication procedures between January 2011 and December 2020; 133 (41.4%) had available data for BMI or to allow BMI to be estimated. Of those 133, 40 patients (30%) had a BMI greater than 30kg/m², and 7 (5.3%) had BMI >35kg/m². One patient (0.75%) had a BMI >40 and would therefore be automatically eligible according to NICE guidelines. 4 further patients had significant co-morbidities, such as hypertension and osteoarthritis, which likely be improved by weight management surgery and therefore also indicated eligibility for referral. Overall, 3.75% (5/133) of patients undergoing conventional fundoplication procedures would have been eligible for bariatric surgical referral, these patients were all female, and the average age was 60.4 years. Conclusions: Based on this Trust’s experience, around 4% of obese patients undergoing fundoplication would have been eligible for bariatric surgical intervention. Based on current evidence, in class 2/3 obese patients, there is likely to have been a notable proportion with recurrent disease, potentially requiring further intervention. These patient’s may have benefitted more through undergoing bariatric surgery, for example a Roux-en-Y gastric bypass, addressing both their obesity and GORD. Use of patient written notes to obtain BMI data for the 188 patients with missing BMI data and further analysis to determine outcomes following fundoplication in all patients, assessing for incidence of recurrent disease, will be undertaken to strengthen conclusions.Keywords: bariatric surgery, GORD, Nissen fundoplication, nice guidelines
Procedia PDF Downloads 602107 Hypoxia Tolerance, Longevity and Cancer-Resistance in the Mole Rat Spalax – a Liver Transcriptomics Approach
Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln
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The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.Keywords: cancer, hypoxia, longevity, transcriptomics
Procedia PDF Downloads 1572106 Value of Unilateral Spinal Anaesthesia For Hip Fracture Surgery In The Elderly (75 Cases)
Authors: Fedili Benamar, Beloulou Mohamed Lamine, Ouahes Hassane, Ghattas Samir
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Background and aims: While in Western countries, unilateral spinal anesthesia has been widely practiced for a long time, it remains little known in the local anesthesia community, and has not been the object of many studies. However, it is a simple, practical and effective technique. Our objective was to evaluate this practice in emergency anesthesia management in frail patients and to compare it with conventional spinal anesthesia. Methods: This is a prospective, observational, comparative study between hypobaric unilateral and conventional spinal anaesthesia for hip fracture surgery carried out in the operating room of the university military hospital of Staoueli. The work was spread over of 12-month period from 2019 to 2020. The parameters analyzed were hemodynamic variations, vasopressor use, block efficiency, postoperative adverse events, and postoperative morphine consumption. Results: -75 cases (mean age 72±14 years) -Group1= 41 patients (54.6%) divided into (ASA1=14.6% ASA2=60.98% ASA3=24.39%) single shoot spinal anaesthesia -Group2= 34 patients (45.3%) divided into (ASA1=2.9%, ASA2=26.4% ASA3=61.7%, ASA4=8.8%) unilateral hypobaric spinal anesthesia. -Hemodynamic variations were more severe in group 1 (51% hypotension) compared to 30% in group 2 RR=1.69 and odds ratio=2.4 -these variations were more marked in the ASA3 subgroup (group 1=70% hypotension versus group 2=30%) with an RR=2.33 and an odds ratio=5.44 -39% of group 1 required vasoactive drugs (15mg +/- 11) versus 32% of group 2 (8mg+/- 6.49) - no difference in the use of morphine in post-op. Conclusions: Within the limits of the population studied, this work demonstrates the clinical value of unilateral spinal anesthesia in ortho-trauma surgery in the frail patient.Keywords: spinal anaesthesia, vasopressor, morphine, hypobaric unilateral spinal anesthesia, ropivacaine, hip surgery, eldery, hemodynamic
Procedia PDF Downloads 742105 Using Lysosomal Immunogenic Cell Death to Target Breast Cancer via Xanthine Oxidase/Micro-Antibody Fusion Protein
Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel
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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome
Procedia PDF Downloads 1992104 Methotrexate Associated Skin Cancer: A Signal Review of Pharmacovigilance Center
Authors: Abdulaziz Alakeel, Abdulrahman Alomair, Mohammed Fouda
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Introduction: Methotrexate (MTX) is an antimetabolite used to treat multiple conditions, including neoplastic diseases, severe psoriasis, and rheumatoid arthritis. Skin cancer is the out-of-control growth of abnormal cells in the epidermis, the outermost skin layer, caused by unrepaired DNA damage that triggers mutations. These mutations lead the skin cells to multiply rapidly and form malignant tumors. The aim of this review is to evaluate the risk of skin cancer associated with the use of methotrexate and to suggest regulatory recommendations if required. Methodology: Signal Detection team at Saudi Food and Drug Authority (SFDA) performed a safety review using National Pharmacovigilance Center (NPC) database as well as the World Health Organization (WHO) VigiBase, alongside with literature screening to retrieve related information for assessing the causality between skin cancer and methotrexate. The search conducted in July 2020. Results: Four published articles support the association seen while searching in literature, a recent randomized control trial published in 2020 revealed a statistically significant increase in skin cancer among MTX users. Another study mentioned methotrexate increases the risk of non-melanoma skin cancer when used in combination with immunosuppressant and biologic agents. In addition, the incidence of melanoma for methotrexate users was 3-fold more than the general population in a cohort study of rheumatoid arthritis patients. The last article estimated the risk of cutaneous malignant melanoma (CMM) in a cohort study shows a statistically significant risk increase for CMM was observed in MTX exposed patients. The WHO database (VigiBase) searched for individual case safety reports (ICSRs) reported for “Skin Cancer” and 'Methotrexate' use, which yielded 121 ICSRs. The initial review revealed that 106 cases are insufficiently documented for proper medical assessment. However, the remaining fifteen cases have extensively evaluated by applying the WHO criteria of causality assessment. As a result, 30 percent of the cases showed that MTX could possibly cause skin cancer; five cases provide unlikely association and five un-assessable cases due to lack of information. The Saudi NPC database searched to retrieve any reported cases for the combined terms methotrexate/skin cancer; however, no local cases reported up to date. The data mining of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by the WHO Uppsala Monitoring Centre to measure the reporting ratio. Positive IC reflects higher statistical association, while negative values translated as a less statistical association, considering the null value equal to zero. Results showed that a combination of 'Methotrexate' and 'Skin cancer' observed more than expected when compared to other medications in the WHO database (IC value is 1.2). Conclusion: The weighted cumulative pieces of evidence identified from global cases, data mining, and published literature are sufficient to support a causal association between the risk of skin cancer and methotrexate. Therefore, health care professionals should be aware of this possible risk and may consider monitoring any signs or symptoms of skin cancer in patients treated with methotrexate.Keywords: methotrexate, skin cancer, signal detection, pharmacovigilance
Procedia PDF Downloads 1142103 Formulation and Anticancer Evaluation of Beta-Sitosterol in Henna Methanolic Extract Embedded in Controlled Release Nanocomposite
Authors: Sanjukta Badhai, Durga Barik, Bairagi C. Mallick
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In the present study, Beta-Sitosterol in Lawsonia methanolic leaf extract embedded in controlled release nanocomposite was prepared and evaluated for in vivo anticancer efficacy in dimethyl hydrazine (DMH) induced colon cancer. In the present study, colon cancer was induced by s.c injection of DMH (20 mg/kg b.wt) for 15 weeks. The animals were divided into five groups as follows control, DMH alone, DMH and Beta Sitosterol nanocomposite (50mg/kg), DMH and Beta Sitosterol nanocomposite (100 mg/kg) and DMH and Standard Silymarin (100mg/kg) and the treatment was carried out for 15 weeks. At the end of the study period, the blood was withdrawn, and serum was separated for haematological, biochemical analysis and tumor markers. Further, the colonic tissue was removed for the estimation of antioxidants and histopathological analysis. The results of the study displays that DMH intoxication elicits altered haematological parameters (RBC,WBC, and Hb), elevated lipid peroxidation and decreased antioxidants level (SOD, CAT, GPX, GST and GSH), elevated lipid profiles (cholesterol and triglycerides), tumor markers (CEA and AFP) and altered colonic tissue histology. Meanwhile, treatment with Beta Sitosterol nanocomposites significantly restored the altered biochemicals parameters in DMH induced colon cancer mediated by its anticancer efficacy. Further, Beta Sitosterol nanocomposite (100 mg/kg) showed marked efficacy.Keywords: nanocomposites, herbal formulation, henna, beta sitosterol, colon cancer, dimethyl hydrazine, antioxidant, lipid peroxidation
Procedia PDF Downloads 1632102 A Lung Cancer Patients with Septic Shock Nursing Experience
Authors: Syue-Wen Lin
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Objective: This article explores the nursing experience of an 84-year-old male lung cancer patient who underwent a thoracoscopic right lower lobectomy and treatment. The patient has multiple medical histories, including hypertension and diabetes. The nursing process involved cancer treatment, postoperative pain management, as well as wound care and healing. Methods: The nursing period is from February 10 to February 17, 2024. During the nursing process, pain management strategies are implemented, including morphine drugs and non-drug methods, and music therapy, essential oil massage, and extended reception time are used to make patients feel physically and mentally comfortable so as to reduce postoperative pain and encourage active participation in rehabilitation. Strict sterile wound dressing procedures and advanced wound care techniques are used to promote wound healing and prevent infection. Due to septic shock, dialysis is used to relieve worsening symptoms. Taking into account the patient's cancer status, the nursing team provides comprehensive cancer care based on the patient's physical and psychological needs. Given the complexity of the patient's condition, including advanced cancer, palliative care is also incorporated throughout the care process to relieve discomfort and provide psychological support. Results: Through comprehensive health assessment, the nursing team fully understood the patient's condition and developed a personalized care plan based on the patient's condition. The interprofessional critical care team provides respiratory therapy and lung expansion exercises to reduce muscle loss while addressing the patient's psychological status, pain management, and vital sign stabilization needs, resulting in a comprehensive approach to care. Lung expansion exercises and the use of a high-frequency chest wall oscillation vest successfully improved sputum drainage and facilitated weaning from mechanical ventilation. In addition, helping patients stabilize their vital signs and the integration of cancer care, pain management, wound care and palliative care helps the patient be fully supported throughout the recovery process, ultimately improving his quality of life. Conclusion: Lung cancer and septic shock present significant challenges to patients, and the nursing team not only provides critical care but also addresses the unique needs of patients through comprehensive infection control, cancer care, pain management, wound care, and palliative care interventions. These measures effectively improve patients' quality of life, promote recovery, and provide compassionate palliative care for terminally ill patients. Nursing staff work closely with family members to develop a comprehensive care plan to ensure that patients receive high-quality medical care as well as psychological support and a comfortable recovery environment.Keywords: septic shock, lung cancer, palliative care, nursing experience
Procedia PDF Downloads 222101 Spatial Variability of Soil Metal Contamination to Detect Cancer Risk Zones in Coimbatore Region of India
Authors: Aarthi Mariappan, Janani Selvaraj, P. B. Harathi, M. Prashanthi Devi
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Anthropogenic modification of the urban environment has largely increased in the recent years in order to sustain the growing human population. Intense industrial activity, permanent and high traffic on the roads, a developed subterranean infrastructure network, land use patterns are just some specific characteristics. Every day, the urban environment is polluted by more or less toxic emissions, organic or metals wastes discharged from specific activities such as industrial, commercial, municipal. When these eventually deposit into the soil, the physical and chemical properties of the surrounding soil is changed, transforming it into a human exposure indicator. Metals are non-degradable and occur cumulative in soil due to regular deposits are a result of permanent human activity. Due to this, metals are a contaminant factor for soil when persistent over a long period of time and a possible danger for inhabitant’s health on prolonged exposure. Metals accumulated in contaminated soil may be transferred to humans directly, by inhaling the dust raised from top soil, or by ingesting, or by dermal contact and indirectly, through plants and animals grown on contaminated soil and used for food. Some metals, like Cu, Mn, Zn, are beneficial for human’s health and represent a danger only if their concentration is above permissible levels, but other metals, like Pb, As, Cd, Hg, are toxic even at trace level causing gastrointestinal and lung cancers. In urban areas, metals can be emitted from a wide variety of sources like industrial, residential, commercial activities. Our study interrogates the spatial distribution of heavy metals in soil in relation to their permissible levels and their association with the health risk to the urban population in Coimbatore, India. Coimbatore region is a high cancer risk zone and case records of gastro intestinal and respiratory cancer patients were collected from hospitals and geocoded in ArcGIS10.1. The data of patients pertaining to the urban limits were retained and checked for their diseases history based on their diagnosis and treatment. A disease map of cancer was prepared to show the disease distribution. It has been observed that in our study area Cr, Pb, As, Fe and Mg exceeded their permissible levels in the soil. Using spatial overlay analysis a relationship between environmental exposure to these potentially toxic elements in soil and cancer distribution in Coimbatore district was established to show areas of cancer risk. Through this, our study throws light on the impact of prolonged exposure to soil contamination in soil in the urban zones, thereby exploring the possibility to detect cancer risk zones and to create awareness among the exposed groups on cancer risk.Keywords: soil contamination, cancer risk, spatial analysis, India
Procedia PDF Downloads 4032100 Immunomodulatory Role of Heat Killed Mycobacterium indicus pranii against Cervical Cancer
Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay
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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.Keywords: cancer, mycobacterium, immunity, immunotherapy.
Procedia PDF Downloads 2492099 The Osteocutaneous Distal Tibia Turn-over Fillet Flap: A Novel Spare-parts Orthoplastic Surgery Option for Functional Below-knee Amputation
Authors: Harry Burton, Alexios Dimitrios Iliadis, Neil Jones, Aaron Saini, Nicola Bystrzonowski, Alexandros Vris, Georgios Pafitanis
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This article portrays the authors’ experience with a complex lower limb bone and soft tissue defect, following chronic osteomyelitis and pathological fracture, which was managed by the multidisciplinary orthoplastic team. The decision for functional amputation versus limb salvage was deemed necessary, enhanced by the principles of “spares parts” in reconstructive microsurgery. This case describes a successful use of the osteocutaneous distal tibia turn-over fillet flap that allowed ‘lowering the level of the amputation’ from a through knee to the conventional level of a below-knee amputation to preserve the knee joint function. This case demonstrates the value of ‘spare-parts’ surgery principles and how these concepts refine complex orthoplastic approaches when limb salvage is not possible to enhance function. The osteocutaneous distal tibia turn-over fillet flap is a robust technique for modified BKA reconstructions that provides sufficient bone length to achieve a tough, sensate stump and functional knee joint.Keywords: osteocutaneous flap, fillet flap, spare-parts surgery, Below knee amputation
Procedia PDF Downloads 1662098 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer
Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan
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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer
Procedia PDF Downloads 942097 Spatio-Temporal Risk Analysis of Cancer to Assessed Environmental Exposures in Coimbatore, India
Authors: Janani Selvaraj, M. Prashanthi Devi, P. B. Harathi
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Epidemiologic studies conducted over several decades have provided evidence to suggest that long-term exposure to elevated ambient levels of particulate air pollution is associated with increased mortality. Air quality risk management is significant in developing countries and it highlights the need to understand the role of ecologic covariates in the association between air pollution and mortality. Several new methods show promise in exploring the geographical distribution of disease and the identification of high risk areas using epidemiological maps. However, the addition of the temporal attribute would further give us an in depth idea of the disease burden with respect to forecasting measures. In recent years, new methods developed in the reanalysis were useful for exploring the spatial structure of the data and the impact of spatial autocorrelation on estimates of risk associated with exposure to air pollution. Based on this, our present study aims to explore the spatial and temporal distribution of the lung cancer cases in the Coimbatore district of Tamil Nadu in relation to air pollution risk areas. A spatio temporal moving average method was computed using the CrimeStat software and visualized in ArcGIS 10.1 to document the spatio temporal movement of the disease in the study region. The random walk analysis performed showed the progress of the peak cancer incidences in the intersection regions of the Coimbatore North and South taluks that include major commercial and residential regions like Gandhipuram, Peelamedu, Ganapathy, etc. Our study shows evidence that daily exposure to high air pollutant concentration zones may lead to the risk of lung cancer. The observations from the present study will be useful in delineating high risk zones of environmental exposure that contribute to the increase of cancer among daily commuters. Through our study we suggest that spatially resolved exposure models in relevant time frames will produce higher risks zones rather than solely on statistical theory about the impact of measurement error and the empirical findings.Keywords: air pollution, cancer, spatio-temporal analysis, India
Procedia PDF Downloads 5132096 Measurement of Sarcopenia Associated with the Extent of Gastrointestinal Oncological Disease
Authors: Adrian Hang Yue Siu, Matthew Holyland, Sharon Carey, Daniel Steffens, Nabila Ansari, Cherry E. Koh
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Introduction: Peritoneal malignancies are challenging cancers to manage. While cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) may offer a cure, it’s considered radical and morbid. Pre-emptive identification of deconditioned patients for optimization may mitigate the risks of surgery. However, the difficulty lies in the scarcity of validated predictive tools to identify high-risk patients. In recent times, there has been growing interest in sarcopenia, which can occur as a result of malnutrition and malignancies. Therefore, the purpose of this study was to assess the utility of sarcopenia in predicting post-operative outcomes. Methods: A single quaternary-center retrospective study of CRS and HIPEC patients between 2017-2020 was conducted to determine the association between pre-operative sarcopenia and post-operative outcomes. Lumbar CT images were analyzed using Slice-o-matic® to measure sarcopenia. Results : Cohort (n=94) analysis found that 40% had sarcopenia, with a majority being female (53.2%) and a mean age of 55 years. Sarcopenia was statistically associated with decreased weight compared to non-sarcopenia patients, 72.7kg vs. 82.2kg (p=0.014) and shorter overall survival, 1.4 years vs. 2.1 years (p=0.032). Post-operatively, patients with sarcopenia experienced more post-operative complications (p=0.001). Conclusion: Complex procedures often require optimization to prevent complications and improve survival. While patient biomarkers – BMI and weight – are used for optimization, this research advocates for the identification of sarcopenia status for pre-operative planning. Sarcopenia may be an indicator of advanced disease requiring further treatment and is an emerging area of research. Larger studies are required to confirm these findings and to assess the reversibility of sarcopenia after surgery.Keywords: sarcopaenia, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, surgical oncology
Procedia PDF Downloads 852095 Sider Bee Honey: Antitumor Effect in Some Experimental Tumor Cell Lines
Authors: Aliaa M. Issa, Mahmoud N. ElRouby, Sahar A. S. Ahmad, Mahmoud M. El-Merzabani
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Sider honey is a type of honey produced by bees feeding on the nectar of Sider tree, Ziziphus spina-christi (L) Desf . Honey is an effective agent for preventing, inhibiting and treating the growth of human and animal cancer cell lines in vitro and in vivo. The aim of the present study was to evaluate the impact of different dilutions from crude Sider honey and different duration times of exposure on the growth of six tumor cell lines (human cervical cancer cell line, HeLa; human hepatocellular carcinoma cell line, HepG-2; human larynx carcinoma cell line, Hep-2; brain tumor cell line, U251) as well as one animal cancerous cell line (Ehrlich ascites carcinoma cells line, EAC) and one normal cell line, Homo sapiens, human, (WISH) CCL-25. Different concentrations and treatment durations with Sider honey were tested on the growth of several cancer cell lines types. Histopathological changes in the tumor masses, animal survival, apoptosis and necrosis of the used cancer cell lines (using flow cytometry) were evaluated. Sider honey was administers either to the tumor mass itself by intratumoral injection or via drinking water. One-way ANOVA test was used for the analysis of (the means + standard error) of the optical density obtained from the Elisa reader and flow cytometry. The study revealed that different concentrations of Sider honey affected the growth patterns of all the studied cancer cell lines as well as their histopathological changes, and it depended on the cell line nature and the concentration of honey used. It is obvious that the relative animal survival percentage (bearing Ehrlich ascites carcinoma, EAC cells) was proportionally increased with the increase in the used honey concentrations. The study of apoptosis and necrosis using the flow cytometry technique emphasized the viability results. In conclusion, Sider honey was effective as antitumor agent, in the used concentrations.Keywords: antitumor, honey, sider, tumor cell lines
Procedia PDF Downloads 5372094 Inhibitory Effect of P2Y1R Agonist 1-Indolinoalkyl 2-Phenolic Derivative on Prostate Cancer Cell Proliferation via the MAPK Signalling
Authors: Hien Thi Thu Le, Nuno Rafael Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu
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Purinergic receptor 1 (P2Y1R) is the potential therapeutic target for inducing prostate cancer (PCa) cell death. Recently, 1-indolinoalkyl 2-phenolic derivative, HIC, was identified as a P2Y1R agonist that increases apoptosis and inhibits cell proliferation of PCa. However, the biological effects of HIC have not been extensively studied at the molecular level. In the present study, we have investigated the anticancer effects of HIC and the molecular mechanisms underlying in PCa cells. Half maximal inhibitory concentration (IC₅₀) of HIC was measured as 15.98 μM and 15.64 μM for DU145 and PC3 cells, respectively. In addition, we found that HIC inhibited cell growth and metastasis of PC3 and DU145 cells colonies, spheroid areas, and migrated cells. RNA seq analysis revealed significant changes of over 3000 genes (p value < 0.05) upon HIC treatment in PC3 and DU145 cells. Genes involved in DNA damage, apoptosis, cell cycle arrest at G1/S phase were modulated by HIC treatment. MAPK and NF-κB protein array revealed the increased expression of ERK1/2, JNK1/2, p53 phosphorylation, and p53 protein. ERK1/2 and JNK1/2 activations are known to increase the stabilization of p53, a tumor suppressor protein, which is required to arrest the cell cycle at G1/S phase and cause cell death of PCa cells. Overall, our results suggest that HIC can serve as a multi-dimensional chemotherapeutic agent possessing strong cytotoxic, anti-cancer, and anti-metastasis against PCa growth.Keywords: prostate cancer, P2Y1 receptor, apoptosis, metastasis
Procedia PDF Downloads 1332093 Muslim Husbands’ Participation in Women’s Health and Illness: A Descriptive Exploratory Study Applied to Muslim Women in Indonesia
Authors: Restuning Widiasih, Katherine Nelson, Joan Skinner
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Muslim husbands have significant roles in the family including their roles in women’s health and illness. However, studies that explore Muslim husbands’ participation in women’s health is limited. The objective of this study was to uncover Muslim husbands’ participation in women’ health and illness including cancer prevention and screening. A descriptive exploratory approach was used involving 20 Muslim women from urban and rural areas of West Java Province, Indonesia. Muslim women shared experience related to their husbands support and activities in women’s health and illness. The data from the interviews were analyzed using the Comparative Analysis for Interview (CAI). Women perceived that husbands fully supported their health by providing opportunities for activities, and reminding them about healthy food, their workloads, and family planning. Husbands actively involved when women faced health issues including sharing knowledge and experience, discussing any health problems, advising for medical check-ups, and accompanying them for treatments. The analysis also found that husbands were less active and offered less advice regarding prevention and early detection of cancer. This study highlights the significant involvement of Muslim husbands in women’s health and illness, yet a lack of support from husbands related to screening and cancer prevention. This condition could be a burden for Muslim women to participate in health programs related to cancer prevention and early detection. Health education programs to improve Muslim husbands’ understanding of women’s health is needed.Keywords: descriptive exploratory study, Muslim husbands, Muslim women, women's health and illness
Procedia PDF Downloads 5132092 Post-Anesthetic Recovery: The Best Moment to Apply Positive Pressure in Airway in Postoperative Bariatric Surgery
Authors: Eli Maria Pazzianotto-Forti, Patrícia Brigatto, Letícia Baltieri, Carolina Moraes Da Costa, Maura Rigoldi Simoes Da Rocha, Irineu Rasera Jr
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The application of positive pressure in airway can contribute to the restoration of lung volumes, capacities and prevent respiratory complications. The aim was to investigate the use of Bilevel Positive Airway Pressure (BIPAP) in morbidly obese in two moments in postoperative bariatric surgery: In the post-anesthetic recovery (PAR) and on the 1st postoperative day (1stPO). Twenty morbidly obese, aged between 25 and 55 years, underwent pulmonary function test and chest X-ray preoperatively and on the day of discharge (2nd day after surgery). They were randomly allocated in groups. GPAR: received BIPAP treatment in PAR, for an hour and G1stPO: received BIPAP for one hour, on the 1stPO. There were significant reductions in slow vital capacity (SVC) (p=0.0007), inspiratory reserve volume (IRV) (p=0.0016) and forced vital capacity (FVC) (p=0.0013) in the postoperative in GPAR and the expiratory reserve volume (ERV) remained (p=0.4446). In the G1stPO, there were significant reductions for: SVC p=<0.0001, ERV p=0.0191, IRV p= 0.0026 and FVC p=<0.0001. Comparing between groups, the SVC (p=0.0027) and FVC (p=0.0028) showed significant difference between the treatments. However, the GPAR showed fewer declines of these capacities. To the ERV (p= 0.1646) and IRV (p=0.3973) there was no significant difference between groups. The atelectasis prevalence was 10% for the GPAR and 30% for G1stPO, with significant difference between the proportions (p = 0.0027). The lowest reduction in SVC and FVC happens when positive pressure is applied in PAR. Thus, the use of BIPAP in the PAR can promote a restoration of ERV and contribute to the reduction of atelectasis. FAPESP 2013/06334-8.Keywords: atelectasis, bariatric surgery, physiotherapy, pulmonary function, positive pressure
Procedia PDF Downloads 4042091 Glyco-Biosensing as a Novel Tool for Prostate Cancer Early-Stage Diagnosis
Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik
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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.Keywords: biomarker, glycosylation, lectin, prostate cancer
Procedia PDF Downloads 4062090 Comparison the Effectiveness of Pain Cognitive- Behavioral Therapy and Its Computerized Version on Reduction of Pain Intensity, Depression, Anger and Anxiety in Children with Cancer: A Randomized Controlled Trial
Authors: Najmeh Hamid, Vajiheh Hamedy , Zahra Rostamianasl
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Background: Cancer is one of the medical problems that have been associated with pain. Moreover, the pain is combined with negative emotions such as anxiety, depression and anger. Poor pain management causes negative effects on the quality of life, which results in negative effects that continue a long time after the painful experiences. Objectives: The aim of this research was to compare the effectiveness of Common Cognitive Behavioral Therapy for Pain and its computerized version on the reduction of pain intensity, depression, anger and anxiety in children with cancer. Methods: The research method of this “Randomized Controlled Clinical Trial” was a pre, post-test and follow-up with a control group. In this research, we have examined the effectiveness of Common Cognitive Behavioral Therapy for Pain and its computerized version on the reduction of pain intensity, anxiety, depression and anger in children with cancer in Ahvaz. Two psychological interventions (cognitive behavioral therapy for pain and the computerized version) were compared with the control group. The sample consisted of 60 children aged 8 to 12 years old with different types of cancer at Shafa hospital in Ahwaz. According to the including and excluding criteria such as age, socioeconomic status, clinical diagnostic interview and other criteria, 60 subjects were selected. Then, randomly, 45 subjects were selected. The subjects were randomly divided into three groups of 15 (two experimental and one control group). The research instruments included Spielberger Anxiety Inventory (STAY-2) and International Pain Measurement Scale. The first experimental group received 6 sessions of cognitive-behavioral therapy for 6 weeks, and the second group was subjected to a computerized version of cognitive-behavioral therapy for 6 weeks, but the control group did not receive any interventions. For ethical considerations, a version of computerized cognitive-behavioral therapy was provided to them. After 6 weeks, all three groups were evaluated as post-test and eventually after a one-month follow-up. Results: The findings of this study indicated that both interventions could reduce the negative emotions (pain, anger, anxiety, depression) associated with cancer in children in comparison with a control group (p<0.0001). In addition, there were no significant differences between the two interventions (p<0.01). It means both interventions are useful for reducing the negative effects of pain and enhancing adjustment. Conclusion: we can use CBT in situations in which there is no access to psychologists and psychological services. In addition, it can be a useful alternative to conventional psychological interventions.Keywords: pain, children, psychological intervention, cancer, anger, anxiety, depression
Procedia PDF Downloads 802089 Synthesis and Biological Activity Evaluation of U Complexes
Authors: Mohammad Kazem Mohammadi
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The use of anticancer agents forms an important part of the treatment of cancer of various types. Uranyl Complexes with DPHMP ligand have been used for the prevention and treatment of cancers. U(IV) metal complexes prepared by reaction of uranyl salt UO2 (NO3)2.6H2O with DPHMP in dry acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT-IR, 1H NMR, 13C NMR and UV–Visible spectroscopy. These new complex showed excellent antitumor activity against two kinds of cancer cells that that are HT29:Haman colon adenocarcinoma cell line and T47D:human breast adenocarcinoma cell line.Keywords: uranyl complexes, DPHMP ligand, antitumor activity, HT29, T47D
Procedia PDF Downloads 4702088 Craniopharyngiomas: Surgical Techniques: The Combined Interhemispheric Sub-Commissural Translaminaterminalis Approach to Tumors in and Around the Third Ventricle: Neurological and Functional Outcome
Authors: Pietro Mortini, Marco Losa
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Objective: Resection of large lesions growing into the third ventricle remains a demanding surgery, sometimes at risk of severe post-operative complications. Transcallosal and transcortical routes were considered as approaches of choice to access the third ventricle, however neurological consequences like memory loss have been reported. We report clinical results of the previously described combined interhemispheric sub-commissural translaminaterminalis approach (CISTA) for the resection of large lesions located in the third ventricle. Methods: Authors conducted a retrospective analysis on 10 patients, who were operated through the CISTA, for the resection of lesions growing into the third ventricle. Results: Total resection was achieved in all cases. Cognitive worsening occurred only in one case. No perioperative deaths were recorded and, at last follow-up, all patients were alive. One year after surgery 80% of patients had an excellent outcome with a KPS 100 and Glasgow Outcome score (GOS) Conclusion: The CISTA represents a safe and effective alternative to transcallosal and transcortical routes to resect lesions growing into the third ventricle. It allows for a multiangle trajectory to access the third ventricle with a wide working area free from critical neurovascular structures, without any section of the corpus callosum, the anterior commissure and the fornix.Keywords: craniopharingioma, surgery, sub-commissural translaminaterminalis approach (CISTA),
Procedia PDF Downloads 2932087 A Development of Practice Guidelines for Surgical Safety Management to Reduce Undesirable Incidents from Surgical Services in the Operating Room of Songkhla Hospital, Thailand
Authors: Thitima Plejai
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The practice in the operating room has been continually performed according to standards of services; however, undesirable incidents from surgical services are found such as surgical complications in the operating room. This participation action research aimed to develop practice guidelines for surgical safety management to reduce undesirable incidents from surgical services in the operating room of Songkhla Hospital. The target population was all 84 members of the multidisciplinary team who were involved in surgical services in the operating room consisting of 28 surgeons from five branches of surgery, 27 anesthetists and nurse anesthetists, and 29 surgical nurses. The data were collected through in-depth interviews, and non-participatory observations. The research instrument was tested by three experts, and the steps of the development consisted of four cycles, each consisting of assessment, planning, practice, practice reflection, and improvement until every step is practicable. The data were validated through triangulation research method, analyzed through content analysis and statistical analysis with number and percentage. The results of the development of practice guidelines surgical safety management to reduce undesirable incidents from surgical services could be concluded as follows. 1) The multidisciplinary team in surgery participated in the needs assessment for development of practice guidelines for surgical patient safety, and agreed on adapting the WHO Surgical Safety Checklists for use. 2) The WHO Surgical Safety Checklists was implemented, and meetings were held for the multidisciplinary team in surgery and the organizational risk committee to improve the practice guidelines to make them more practicable. 3) The multidisciplinary team consisting of surgeons from five branches of surgery, anesthetists, nurse anesthetists, surgical nurses, and the organizational risk committee announced policy on safety for surgical patients; the organizational risk committee designated the Surgical Safety Checklist as an instrument for surgical patient safety. The results of the safety management found that the surgical team members who could follow 100 percent of the guidelines were: professional nurses who checked patient identity and information before taking the patient to the operating room and kept complete records of data on the patients; surgical nurses who checked readiness of the patient before surgery; nurse anesthetists who assessed readiness before administering anesthetic drugs, and confirmed correctness of the patient; and circulating perioperative nurses who gave confirmation to the surgical team after completion of the surgery. The rates of undesirable incidents (surgical complications rates) before and after the implementation of the surgical safety management were 1.60 percent and 0.66 percent, respectively. The satisfaction of the surgery-related teams towards the use of the guidelines was 89 percent. The practice guidelines for surgical safety management to reduce undesirable incidents were taken as guidelines for surgical safety that the multidisciplinary team involved in the surgical process implemented correctly and in the same direction and clearly reduced undesirable incidents in surgical patients.Keywords: practice guidelines, surgical safety management, reduce undesirable incidents, operating Room
Procedia PDF Downloads 2972086 Managing Incomplete PSA Observations in Prostate Cancer Data: Key Strategies and Best Practices for Handling Loss to Follow-Up and Missing Data
Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal
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Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer
Procedia PDF Downloads 892085 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity
Authors: Nigatu Tadesse, Li Juan, Liuhong Ming
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Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase
Procedia PDF Downloads 482084 Engineering a Tumor Extracellular Matrix Towards an in vivo Mimicking 3D Tumor Microenvironment
Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang
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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.Keywords: cancer, extracellular matrix, hydrogel, microfluidic
Procedia PDF Downloads 912083 Comparative Study of Outcome of Patients with Wilms Tumor Treated with Upfront Chemotherapy and Upfront Surgery in Alexandria University Hospitals
Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly
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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery
Procedia PDF Downloads 3172082 Anti-Cancerous Activity of Sargassum siliquastrum in Cervical Cancer: Choreographing the Fly's Danse Macabre
Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan
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Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation
Procedia PDF Downloads 6322081 The Role of Micro-Ribonucleic Acid-182 and Micro-Ribonucleic Acid-214 in Cisplatin Resistance of Triple-Negative Breast Cancer Cells
Authors: Bahadir Batar, Elif Serdal, Berna Erdal, Hasan Ogul
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Micro-ribonucleic acids (miRNAs) are small short non-coding ribonucleic acid molecules about 22 nucleotides long. miRNAs play a key role in response to chemotherapeutic agents. WW domain-containing oxidoreductase (WWOX) gene encodes a tumor suppressor protein. Loss or reduction of Wwox protein is observed in many breast cancer cases. WWOX protein deficiency is increased in triple-negative breast cancer (TNBC). TNBC is a heterogeneous, highly aggressive, and difficult to treat tumor type. WWOX loss contributes to resistance to cisplatin therapy in patients with TNBC. Here, the aim of the study was to investigate the potential role of miRNAs in cisplatin therapy resistance of WWOX-deficient TNBC cells. This was a cell culture study. miRNA expression profiling was analyzed by LightCycler 480 system. miRNA Set Enrichment Analysis tool was used to integrate experimental data with literature-based biological knowledge to infer a new hypothesis. Increased miR-182 and decreased miR-214 were significantly correlated with cisplatin resistance in WWOX-deficient TNBC cells. miR-182 and miR-214 may involve in cisplatin resistance of WWOX-deficient TNBC cells by deregulating the DNA repair, apoptosis, or protein kinase B signaling pathways. These data highlight the mechanism by which WWOX regulates cisplatin resistance of TNBC and the potential use of WWOX as a predictor biomarker for cisplatin resistance.Keywords: cisplatin, microRNA, triple-negative breast cancer, WWOX
Procedia PDF Downloads 131