Search results for: gastric cancer surgery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3076

Search results for: gastric cancer surgery

2056 Stomach Specific Delivery of Andrographolide from Floating in Situ Gelling System

Authors: Pravina Gurjar, Bothiraja Pour, Vijay Kumbhar, Ganesh Dama

Abstract:

Andrographolide (AG), a bioactive phytoconstituent, has a wider range of pharmacological action. However, due to the intestinal degradation, shows low oral bioavailability. The aim of the present work was to develop Floating In-situ gelling Gastro retentive System (FISGS) for AG in order to enhance its site specific absorption and minimize pH dependent hydrolysis in alkaline environment. Further to increase its therapeutic efficacy for peptic ulcer disease caused by H. pyroli. Gellan based floating in situ gelling system of AG were prepared by using sodium citrate and calcium carbonate. The 32 factorial designs was used to study the effect of gellan and calcium carbonate concentration (independent variables) on dependent variable such as viscosity, floating lag time and drug release. Developed system was evaluated for drug content, floating lag time, viscosity, and drug release studies. Drug content, viscosity, and floating lag time was found to be 81-99%, 67-117 Cps, and 3-5 sec, respectively. The obtained system showed good in vitro floating ability for more than 12 h using 0.1 N HCl as dissolution medium with initial burst release followed by the controlled zero order drug release up to 24 hrs. In vivo testing of FISGS of AG to rats demonstrated significant antiulcer activity that were evaluated by various parameters like pH, volume, total acidity, millimole equivalent of H+ ions/30 min, and protein content of gastric content. The densities of all the formulation batches were found to be near about 0.9 and floating duration above 12 hr. It was observed that with the increase in conc. of gellan there was increase in the viscosity of formulation but all formulations were in optimum range. The drug content of optimized batch was found to be 99.23. In histopathology study of stomach, the villi at the mucosal surface, the intercellular junction, the intestinal lumen were intact; no destruction of the epithelium, and submucosal gland in formulation treated and control group animals as compared to pure drug AG and standard ranitidine. Gellan-based in situ gastro retentive floating system could be advantageous in terms of increased bioavailability of AG to maintain an effective drug conc. in gastric fluid as well as in serum for longer period of time.

Keywords: andrographolide, floating drug delivery, in situ gelling system, gastroretentive system

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2055 Phytochemical Content and Bioactive Properties of Wheat Sprouts

Authors: Jasna Čanadanović-Brunet, Lidija Jevrić, Gordana Ćetković, Vesna Tumbas Šaponjac, Jelena Vulić, Slađana Stajčić

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Wheat contains high amount of nutrients such as dietary fiber, resistant starch, vitamins, minerals and microconstituents, which are building blocks of body tissues, but also help in the prevention of diseases such as cardiovascular disease, cancer and diabetes. Sprouting enhances the nutritional value of whole wheat through biosynthesis of tocopherols, polyphenols and other valuable phytochemicals. Since the nutritional and sensory benefits of germination have been extensively documented, using of sprouted grains in food formulations is becoming a trend in healthy foods. The present work addressed the possibility of using freeze-dried sprouted wheat powder, obtained from spelt-wheat cv. ‘Nirvana’ (Triticum spelta L.) and winter wheat cv. ‘Simonida’ (Triticum aestivum L. ssp. vulgare var. lutescens), as a source of phytochemicals, to improve the functional status of the consumer. The phytochemicals' content (total polyphenols, flavonoids, chlorophylls and carotenoids) and biological activities (antioxidant activity on DPPH radicals and antiinflammatory activity) of sprouted wheat powders were assessed spectrophotometrically. The content of flavonoids (216.52 mg RE/100 g), carotenoids (22.84 mg β-carotene/100 g) and chlorophylls (131.23 mg/100 g), as well as antiinflammatory activity (EC50=3.70 mg/ml) was found to be higher in sprouted spelt-wheat powder, while total polyphenols (607.21 mg GAE/100 g) and antioxidant activity on DDPPH radicals (EC50=0.27 mmol TE/100 g) was found to be higher in sprouted winter wheat powders. Simulation of gastro-intestinal digestion of sprouted wheat powders clearly shows that intestinal digestion caused a higher release of polyphenols than gastric digestion for both samples, which indicates their higher bioavailability in the colon. The results of the current study have shown that wheat sprouts can provide a high content of phytochemicals and considerable bioactivities. Moreover, data reported show that they contain a unique pattern of bioactive molecules, which make these cereal sprouts attractive functional foods for a health-promoting diet.

Keywords: wheat, sprouts, phytochemicals, bioactivity

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2054 In silico Repopulation Model of Various Tumour Cells during Treatment Breaks in Head and Neck Cancer Radiotherapy

Authors: Loredana G. Marcu, David Marcu, Sanda M. Filip

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Advanced head and neck cancers are aggressive tumours, which require aggressive treatment. Treatment efficiency is often hindered by cancer cell repopulation during radiotherapy, which is due to various mechanisms triggered by the loss of tumour cells and involves both stem and differentiated cells. The aim of the current paper is to present in silico simulations of radiotherapy schedules on a virtual head and neck tumour grown with biologically realistic kinetic parameters. Using the linear quadratic formalism of cell survival after radiotherapy, altered fractionation schedules employing various treatment breaks for normal tissue recovery are simulated and repopulation mechanism implemented in order to evaluate the impact of various cancer cell contribution on tumour behaviour during irradiation. The model has shown that the timing of treatment breaks is an important factor influencing tumour control in rapidly proliferating tissues such as squamous cell carcinomas of the head and neck. Furthermore, not only stem cells but also differentiated cells, via the mechanism of abortive division, can contribute to malignant cell repopulation during treatment.

Keywords: radiation, tumour repopulation, squamous cell carcinoma, stem cell

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2053 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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2052 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),

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2051 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

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2050 Pegylated Liposomes of Trans Resveratrol, an Anticancer Agent, for Enhancing Therapeutic Efficacy and Long Circulation

Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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2049 A Study on the Application of Machine Learning and Deep Learning Techniques for Skin Cancer Detection

Authors: Hritwik Ghosh, Irfan Sadiq Rahat, Sachi Nandan Mohanty, J. V. R. Ravindra

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In the rapidly evolving landscape of medical diagnostics, the early detection and accurate classification of skin cancer remain paramount for effective treatment outcomes. This research delves into the transformative potential of Artificial Intelligence (AI), specifically Deep Learning (DL), as a tool for discerning and categorizing various skin conditions. Utilizing a diverse dataset of 3,000 images representing nine distinct skin conditions, we confront the inherent challenge of class imbalance. This imbalance, where conditions like melanomas are over-represented, is addressed by incorporating class weights during the model training phase, ensuring an equitable representation of all conditions in the learning process. Our pioneering approach introduces a hybrid model, amalgamating the strengths of two renowned Convolutional Neural Networks (CNNs), VGG16 and ResNet50. These networks, pre-trained on the ImageNet dataset, are adept at extracting intricate features from images. By synergizing these models, our research aims to capture a holistic set of features, thereby bolstering classification performance. Preliminary findings underscore the hybrid model's superiority over individual models, showcasing its prowess in feature extraction and classification. Moreover, the research emphasizes the significance of rigorous data pre-processing, including image resizing, color normalization, and segmentation, in ensuring data quality and model reliability. In essence, this study illuminates the promising role of AI and DL in revolutionizing skin cancer diagnostics, offering insights into its potential applications in broader medical domains.

Keywords: artificial intelligence, machine learning, deep learning, skin cancer, dermatology, convolutional neural networks, image classification, computer vision, healthcare technology, cancer detection, medical imaging

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2048 Evaluating the Effectiveness of Combined Psychiatric and Psychotherapeutic Care versus Psychotherapy Alone in the Treatment of Depression and Anxiety in Cancer Patients

Authors: Nathen A. Spitz, Dennis Martin Kivlighan III, Arwa Aburizik

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Background and Purpose: Presently, there is a paucity of naturalistic studies that directly compare the effectiveness of psychotherapy versus concurrent psychotherapy and psychiatric care for the treatment of depression and anxiety in cancer patients. Informed by previous clinical trials examining the efficacy of concurrent approaches, this study sought to test the hypothesis that a combined approach would result in the greatest reduction of depression and anxiety symptoms. Methods: Data for this study consisted of 433 adult cancer patients, with 252 receiving only psychotherapy and 181 receiving concurrent psychotherapy and psychiatric care at the University of Iowa Hospitals and Clinics. Longitudinal PHQ9 and GAD7 data were analyzed between both groups using latent growth curve analyses. Results: After controlling for treatment length and provider effects, results indicated that concurrent care was more effective than psychotherapy alone for depressive symptoms (γ₁₂ = -0.12, p = .037). Specifically, the simple slope for concurrent care was -0.25 (p = .022), and the simple slope for psychotherapy alone was -0.13 (p = .006), suggesting that patients receiving concurrent care experienced a greater reduction in depressive symptoms compared to patients receiving psychotherapy alone. In contrast, there were no significant differences between psychotherapy alone and concurrent psychotherapy and psychiatric care in the reduction of anxious symptoms. Conclusions: Overall, as both psychotherapy and psychiatric care may address unique aspects of mental health conditions, in addition to potentially providing synergetic support to each other, a combinatorial approach to mental healthcare for cancer patients may improve outcomes.

Keywords: psychiatry, psychology, psycho-oncology, combined care, psychotherapy, behavioral psychology

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2047 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

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Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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2046 Cost-Conscious Treatment of Basal Cell Carcinoma

Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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2045 Methodology for Diagnosing Architecture Improvements in a Cancer Hospital in Brasilia

Authors: Mariana Sabino, Janes Cleiton de Oliveira, Carlos Luna de Melo

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This paper presents a discussion about the importance and influence of the environment in the patient’s recovery process. Some users (employees and patients) were submitted to a questionnaire that helps to diagnoses the major problems of the hospital, specially related to comfort (aesthetic, thermal, acoustic, light, ergonomic), well-being, how does the flow of patients and employees works in the hospital and wayfinding as well. After a short literature review presenting the topic, the hospital will be characterized, showing photos, the projects available and describing the hospital as well (how many rooms, functions of each one, receptions, waiting rooms, between other things.), than the questionnaire will be applied to patients and to the employees. Lastly the results of the answers given will be analyzed in graphics, and it will help to identify which are the major improvements needed immediately. This paper has the intention to propose a methodology to diagnose architecture problems in a cancer hospital in Brasilia, Brazil, besides to open a space to hear the people that use the building to tell about their discomforts and perceptions of the environment, it also will give an opportunity to apply the possible improvements. It is important to tell that it will be considered if the hospital has a healing environment, and it will also be considered the ergonomic issues about comfort and the way the system of this particular hospital works in general.

Keywords: cancer hospital, comfort, diagnose, healing environment

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2044 Analysis of Relative Gene Expression Data of GATA3-AS1 Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients of Luminal B Subtype

Authors: X. Cervantes-López, C. Arriaga-Canon, L. Contreras Espinosa

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The goal of this study is to validate the overexpression of the lncRNA GATA3-AS1 associated with resistance to neoadjuvant chemotherapy of female patients with locally advanced mammary adenocarcinoma of luminal B subtype This study involved a cohort of one hundred thirty-seven samples for which total RNA was isolated from formalin fixed paraffin embedded (FFPE) tissue. Samples were cut using a Microtome Hyrax M25 Zeiss and RNA was isolated using the RNeasy FFPE kit and a deparaffinization solution, the next step consisted in the analysis of RNA concentration and quality, then 18 µg of RNA was treated with DNase I, and cDNA was synthesized from 50 ng total RNA, finally real-time PCR was performed with SYBR Green/ROX qPCR Master Mix in order to determined relative gene expression using RPS28 as a housekeeping gene to normalize in a fold calculation ΔCt. As a result, we validated by real-time PCR that the overexpression of the lncRNA GATA3-AS1 is associated with resistance to neoadjuvant chemotherapy in locally advanced breast cancer patients of luminal B subtype.

Keywords: breast cancer, biomarkers, genomics, neoadjuvant chemotherapy, lncRNAS

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2043 Literature Review of Empirical Studies on the Psychological Processes of End-of-Life Cancer Patients

Authors: Kimiyo Shimomai, Mihoko Harada

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This study is a literature review of the psychological reactions that occur in end-of-life cancer patients who are nearing death. It searched electronic databases and selected literature related to psychological studies of end-of-life patients. There was no limit on the search period, and the search was conducted until the second week of December 2021. The keywords were specified as “death and dying”, “terminal illness”, “end-of-life”, “palliative care”, “psycho-oncology” and “research”. These literatures referred to Holly (2017): Comprehensive Systematic Review for Advanced Practice Nursing, P268 Figure 10.3 to ensure quality. These literatures were selected with a dissertation score of 4 or 5. The review was conducted in two stages with reference to the procedure of George (2002). First, these references were searched for keywords in the database, and then relevant references were selected from the psychology and nursing studies of end-of-life patients. The number of literatures analyzed was 76 for overseas and 17 for domestic. As for the independent variables, "physical variable" was the most common in 36 literatures (66.7%), followed by "psychological variable" in 35 literatures (64.8%), "spiritual variable" in 21 literatures (38%), and "social variable" in 17 literatures. (31.5%), "Variables related to medical care / treatment" were 16 literatures (29.6%). To summarize the relationship between these independent variables and the dependent variable, when the dependent variable is "psychological variable", the independent variables are "psychological variable", "social variable", and "physical variable". Among the independent variables, the physical variables were the most common. The psychological responses that occur in end-stage cancer patients who are nearing death are mutually influenced by psychological, social, and physical variables. Therefore, it supported the "total pain" advocated by Cicely Saunders.

Keywords: cancer patient, end-of-life, literature review, psychological process

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2042 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

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2041 Mammographic Multi-View Cancer Identification Using Siamese Neural Networks

Authors: Alisher Ibragimov, Sofya Senotrusova, Aleksandra Beliaeva, Egor Ushakov, Yuri Markin

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Mammography plays a critical role in screening for breast cancer in women, and artificial intelligence has enabled the automatic detection of diseases in medical images. Many of the current techniques used for mammogram analysis focus on a single view (mediolateral or craniocaudal view), while in clinical practice, radiologists consider multiple views of mammograms from both breasts to make a correct decision. Consequently, computer-aided diagnosis (CAD) systems could benefit from incorporating information gathered from multiple views. In this study, the introduce a method based on a Siamese neural network (SNN) model that simultaneously analyzes mammographic images from tri-view: bilateral and ipsilateral. In this way, when a decision is made on a single image of one breast, attention is also paid to two other images – a view of the same breast in a different projection and an image of the other breast as well. Consequently, the algorithm closely mimics the radiologist's practice of paying attention to the entire examination of a patient rather than to a single image. Additionally, to the best of our knowledge, this research represents the first experiments conducted using the recently released Vietnamese dataset of digital mammography (VinDr-Mammo). On an independent test set of images from this dataset, the best model achieved an AUC of 0.87 per image. Therefore, this suggests that there is a valuable automated second opinion in the interpretation of mammograms and breast cancer diagnosis, which in the future may help to alleviate the burden on radiologists and serve as an additional layer of verification.

Keywords: breast cancer, computer-aided diagnosis, deep learning, multi-view mammogram, siamese neural network

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2040 An Audit of Restaging Transurethral Resection of Bladder Tumor (Re-TURBT) Quality in a District General Hospital

Authors: Rizwan Iqbal

Abstract:

Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.

Keywords: urology, bladder cancer, turbt, cancer

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2039 Modulation of Tamoxifen-Induced Cytotoxicity in Breast Cancer Cell Lines by 3-Bromopyruvate

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

Abstract:

Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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2038 Comparison of Intraocular Pressure Measurement Prior and Following Full Intracorneal Ring Implantation in Patient with Keratoconus by Three Different Instruments

Authors: Seyed Aliasghar Mosavi, Mostafa Naderi, Khosrow Jadidi, Amir Hashem Mohammadi

Abstract:

To study the measurement of intraocular pressure (IOP) before and after implantation of intrastromal corneal ring (MyoRing) in patients with keratoconus. Setting: Baqiyatallah University of Medical Sciences, Tehran, Iran. Methods: We compared the IOP of 13 eyes which underwent MyoRing implantation prior and six months post operation using Goldman applanation (as gold standard), Icare, and Corvis ST (uncorrected, corrected and corrected with cornea biomechanics). Results: The resulting intraocular pressure measurements prior to surgery, Icare, Corvis (corrected with cornea biomechanics) overestimated the IOP, however measurements by Corvis uncorrected underestimate the IOP. The resulting intraocular pressure measurements after surgery, Icare, Corvis (corrected with cornea biomechanics) overestimated the IOP but measurements by Corvis uncorrected underestimate the IOP. Conclusion: Consistent intraocular pressure measurements on eyes with Myoring in keratoconus can be obtained with the Goldman applanation tonometer as the gold standard measurement. We were not able to obtain consistent results when we measured the IOP by Icare and Corvis prior and after surgery.

Keywords: intraocular pressure, MyoRing, Keratoconus, Goldmann applanation, Icare, Corvis ST

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2037 Caspase-11 and AIM2 Inflammasome are Involved in Smoking-Induced COPD and Lung Adenocarcinoma

Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

Abstract:

Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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2036 Sparse Modelling of Cancer Patients’ Survival Based on Genomic Copy Number Alterations

Authors: Khaled M. Alqahtani

Abstract:

Copy number alterations (CNA) are variations in the structure of the genome, where certain regions deviate from the typical two chromosomal copies. These alterations are pivotal in understanding tumor progression and are indicative of patients' survival outcomes. However, effectively modeling patients' survival based on their genomic CNA profiles while identifying relevant genomic regions remains a statistical challenge. Various methods, such as the Cox proportional hazard (PH) model with ridge, lasso, or elastic net penalties, have been proposed but often overlook the inherent dependencies between genomic regions, leading to results that are hard to interpret. In this study, we enhance the elastic net penalty by incorporating an additional penalty that accounts for these dependencies. This approach yields smooth parameter estimates and facilitates variable selection, resulting in a sparse solution. Our findings demonstrate that this method outperforms other models in predicting survival outcomes, as evidenced by our simulation study. Moreover, it allows for a more meaningful interpretation of genomic regions associated with patients' survival. We demonstrate the efficacy of our approach using both real data from a lung cancer cohort and simulated datasets.

Keywords: copy number alterations, cox proportional hazard, lung cancer, regression, sparse solution

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2035 Impact of Massive Weight Loss Body Contouring Surgery in the Patient’s Quality of Life

Authors: Maria Albuquerque, Miguel Matias, Ângelo Sá, Juliana Sousa, Maria Manuel Mouzinho

Abstract:

Obesity is a frequent disease in Portugal. The surgical treatment is very effective and has an indication when there is a failure of the medical treatment. Although massive weight loss is associated with considerable health gains, these patients are characterized by a variable degree of dermolipodistrophy. In some cases, there is even the development of physical symptoms such as intertriginous, and some degree of psychological distress is present. In almost all cases, a desire for a better body contour, which inhibits some aspects of social life, is a fact. A prospective study was made to access the impact of body contouring surgery in the quality of life of patients who underwent a massive weight lost correction surgical procedure at Centro Hospitalar de Lisboa Central between January 2020 and December 2021. The patients were submitted to the Body Q subjective questionnaire adapted for the Portuguese language and accessed for the following categories: Anguish with Appearance, Contempt with Body Image, Satisfaction with the Abdomen, and Overall Satisfaction with the Body. The questionnaire was repeated at the 6 months mark. A total of 80 patients were sampled. The sex distribution was 79 female and 1 male. The median BMI index before surgery was inferior to 28%. The pre operatory questionnaire showed high scores for Anguish with Appearance and low scores for the body image self-evaluation. Overall, there was an improvement of at least 50% in all the evaluated scores. Additionally, a correlation was found between abdominoplasty and the contempt with body image and satisfaction with the abdomen (p-value <0.05). Massive weight loss is associated with important body deformities that have a significant impact on the patient’s personal and social life. Body contouring surgery is then vital for these patients as it implicates major aesthetic and functional benefits.

Keywords: abdominoplasty, cruroplasty, obesity, massive weight loss

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2034 Autophagy Suppresses Tumorigenesis through Upregulation of MiR-449a in Colorectal Cancer

Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

Abstract:

Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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2033 Anti-proliferative Activity and HER2 Receptor Expression Analysis of MCF-7 (Breast Cancer Cell) Cells by Plant Extract Coleus Barbatus (Andrew)

Authors: Anupalli Roja Rani, Pavithra Dasari

Abstract:

Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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2032 Effects on Inflammatory Biomarkers and Respiratory Mechanics in Laparoscopic Bariatric Surgery: Desflurane vs. Total Intravenous Anaesthesia with Propofol

Authors: L. Kashyap, S. Jha, D. Shende, V. K. Mohan, P. Khanna, A. Aravindan, S. Kashyap, L. Singh, S. Aggarwal

Abstract:

Obesity is associated with a chronic inflammatory state. During surgery, there is an interplay between anaesthetic and surgical stress vis-a-vis the already present complex immune state. Moreover, the postoperative period is dictated by inflammation, which is crucial for wound healing and regeneration. An excess of inflammatory response might hamper recovery besides increasing the risk for infection and complications. There is definite evidence of the immunosuppressive role of inhaled anaesthetic agents. This immune modulation may be brought into effect directly by influencing the innate and adaptive immunity cells. The effects of propofol on immune mechanisms in has been widely elucidated because of its popularity. It reduces superoxide generation, elastase release, and chemotaxis. However, there is no unequivocal proof of one’s superiority over the other. Hence, an anaesthetic regimen with lesser inflammatory potential and specific to the obese patient is needed. OBESITA trial protocol (2019) by Sousa and co-workers in progress aims to test the hypothesis that anaesthesia with sevoflurane results in a weaker proinflammatory response compared to propofol, as evidenced by lower IL-6 and other biomarkers and an increased macrophage differentiation into M2 phenotype in adipose tissue. IL-6 was used as the objective parameter to evaluate inflammation as it is regulated by both surgery and anesthesia. It is the most sensitive marker of the inflammatory response to tissue damage since it is released within minutes by blood leukocytes. We hypothesized that maintenance of anaesthesia with propofol would lead to less inflammation than that with desflurane. Aims: The effect of two anaesthetic techniques, total intravenous anaesthesia (TIVA) with propofol and desflurane, on surgical stress response was evaluated. The primary objective was to compare serum interleukin-6 (IL-6) levels before and after surgery. Methods: In this prospective single-blinded randomized controlled trial undertaken, 30 obese patients (BMI>30 kg/m2) undergoing laparoscopic bariatric surgery under general anaesthesia were recruited. Patients were randomized to receive desflurane or TIVA using a target-controlled infusion for maintenance of anaesthesia. As a marker of inflammation, pre-and post-surgery IL-6 levels were compared. Results: After surgery, IL-6 levels increased significantly in both groups. The rise in IL-6 was less with TIVA than with desflurane; however, it did not reach significance. IL-6 rise post-surgery correlated positively with the complexity of procedure and duration of surgery and anaesthesia, rather than anaesthetic technique. Both groups did not differ in terms of intra-operative hemodynamic and respiratory variables, time to awakening, postoperative pulmonary complications, and duration of hospital stay. The incidence of nausea was significantly higher with desflurane than with TIVA. Conclusion: Inflammatory response did not differ as a function of anaesthetic technique when propofol and desflurane were compared. Also, patient and surgical variables dictated post-operative inflammation more than the anaesthetic factors. Further, larger sample size is needed to confirm or refute these findings.

Keywords: bariatric, biomarkers, inflammation, laparoscopy

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2031 Predictive Value of ¹⁸F-Fdg Accumulation in Visceral Fat Activity to Detect Colorectal Cancer Metastases

Authors: Amil Suleimanov, Aigul Saduakassova, Denis Vinnikov

Abstract:

Objective: To assess functional visceral fat (VAT) activity evaluated by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictor of metastases in colorectal cancer (CRC). Materials and methods: We assessed 60 patients with histologically confirmed CRC who underwent 18F-FDG PET/CT after a surgical treatment and courses of chemotherapy. Age, histology, stage, and tumor grade were recorded. Functional VAT activity was measured by maximum standardized uptake value (SUVmax) using ¹⁸F-FDG PET/CT and tested as a predictor of later metastases in eight abdominal locations (RE – Epigastric Region, RLH – Left Hypochondriac Region, RRL – Right Lumbar Region, RU – Umbilical Region, RLL – Left Lumbar Region, RRI – Right Inguinal Region, RP – Hypogastric (Pubic) Region, RLI – Left Inguinal Region) and pelvic cavity (P) in the adjusted regression models. We also report the best areas under the curve (AUC) for SUVmax with the corresponding sensitivity (Se) and specificity (Sp). Results: In both adjusted for age regression models and ROC analysis, 18F-FDG accumulation in RLH (cutoff SUVmax 0.74; Se 75%; Sp 61%; AUC 0.668; p = 0.049), RU (cutoff SUVmax 0.78; Se 69%; Sp 61%; AUC 0.679; p = 0.035), RRL (cutoff SUVmax 1.05; Se 69%; Sp 77%; AUC 0.682; p = 0.032) and RRI (cutoff SUVmax 0.85; Se 63%; Sp 61%; AUC 0.672; p = 0.043) could predict later metastases in CRC patients, as opposed to age, sex, primary tumor location, tumor grade and histology. Conclusions: VAT SUVmax is significantly associated with later metastases in CRC patients and can be used as their predictor.

Keywords: ¹⁸F-FDG, PET/CT, colorectal cancer, predictive value

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2030 Synthesis of Porphyrin-Functionalized Beads for Flow Cytometry

Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

Abstract:

Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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2029 New Quinazoline Derivative Exhibit Cytotoxic Effect agaisnt MCF-7 Human Breast Cancer Cell

Authors: Maryam Zahedifard, Fadhil Lafta Faraj, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

Abstract:

The new quinazoline Schiff bases have been synthesized through condensation reaction of 2-aminobenzhydrazide with 5-bromosalicylaldehyde and 3-methoxy-5-bromosalicylaldehyde. The compound was investigated for anticancer activity against MCF-7 human breast cancer cell line. It demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41±0.34, after 72 hours of treatment. Most apoptosis morphological features in treated MCF-7 cells were observed by AO/PI staining. The results of cell cycle analysis indicate that compounds did not induce S and M phase arrest in cell after 24 hours of treatment. Furthermore, MCF-7 cells treated with compound subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome C release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity results demonstrated the nontoxic nature of the compounds in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potential candidate for further in vivo and clinical breast cancer studies.

Keywords: quinazoline Schiff base, apoptosis, MCF-7, caspase, cell cycle, acute toxicity

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2028 The Efficacy of Preoperative Thermal Pulsation Treatment in Reducing Post Cataract Surgery Dry Eye Disease: A Systematic Review and Meta-analysis

Authors: Lugean K. Alomari, Rahaf K. Sharif, Basil K. Alomari, Hind M. Aljabri, Faisal F. Aljahdali, Amal A. Alomari, Saeed A. Alghamdi

Abstract:

Background: The thermal pulsation system is a therapy that uses heat and massage to treat dry eye disease; thus, some trials have been published to compare it with the conventional treatment. The aim of this study is to conduct a systematic review and meta-analysis comparing the efficacy of thermal pulsation systems with conventional treatment in patients undergoing cataract surgery. Methods: Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for eligible trials. We included three randomized controlled trials (RCTs) that compared the thermal pulsation system with the conventional treatment in patients undergoing cataract surgery. A table of characteristics was plotted, and the Quality of the studies was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB 2). Forest plots were plotted using the Random-effect Inverse Variance method. χ2 test and the Higgins-I-squared (I2) model were used to assess heterogeneity. A total of 201 cataract surgery patients were included, with 105 undergoing preoperative pulsation therapy and 96 receiving conventional treatment. Demographic analysis revealed comparable distributions across groups. Results: All the studies in our analysis are of good quality with a low risk of bias. A total of 201 patients were included in the analysis, out of which 105 underwent pulsation therapy, and 95 were in the control group. Tear Break-up Time (TBUT) analysis revealed no significant baseline differences, except pulsation therapy being better at 1 month. (SMD 0.42 [95%CI 0.14 - 0.70] p=0.004). This positive trend continued at three months (SMD 0.52 [95% CI (0.20 – 0.84)] p=0.002). Corneal fluorescein staining scores and Meibomian gland-yielding secretion scores showed no significant differences at baseline. However, at one month, pulsation therapy significantly improved Meibomian gland function (SMD -0.86 [95% CI (-1.20 - -0.53)] p<0.00001), indicating a reduced risk of dry eye syndrome. Conclusion: Preoperative pulsation therapy appears to enhance post-cataract surgery outcomes, particularly in terms of tear film stability and Meibomian gland secretory function. The sustained positive effects observed at one and three months post-surgery suggest the potential for long-term benefits.

Keywords: lipiflow, cataract, thermal pulsation, dry eye

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2027 The Effect of Surgical Intervention on Pediatric and Adolescent Obstructive Sleep Apnea Syndrome

Authors: Ching-Yi Yiu, Hui-Chen Hsu

Abstract:

Objectives: Obstructive sleep apnea syndrome (OSAS) is a popular problem in the modern society. It usually leads to sleep disorder, excessive daytime sleepiness and associated with cardiovascular diseases, cognitive dysfunction and even death. The nonsurgical therapies include continuous positive airway pressure (CPAP), diet and oral appliances. The surgical approaches have nasal surgery, tonsillectomy, adenoidectomy, uvulopalatopharyngoplasty (UPPP) and transoral robotic surgery (TORS).We compare the impact of surgical treatments on these kinds of patients. Methods: Between January 2018 to September 2022, We have enrolled 125 OSAS patients including 82 male and 43 female in Chi Mei Medical Center, Liouying, Taiwan. The age distribution from 6 to 71 years old (y/o) with mean age 36.1 y/o. The averaged body mass index (BMI) is 25 kg/m2 in male and 25.5 kg/m2 in female. In this cohort, we evaluated their upper airway obstruction sites with nasopharyngoscopy and scheduled a planned surgery. Some of cases received polysomnography (PSG) preoperatively, the averaged apnea-hypopnea index (AHI) is 37.7 events/hour. We have 68 patients received tonsillectomy, 9 received UPPP, 42 received UPPP and septomeatoplasty (SMP) and 6 received adenoidectomy and tonsillectomy (A and T). The subjective daytime sleepiness was evaluated with the Epworth sleepiness scale (ESS). Results: In the 68 tonsillectomy group, the averaged BMI is 24.9 kg/m2. In the UPPP group, the averaged BMI is 28.9 kg/m2. In UPPP and SMP group, the averaged BMI is 27.9 kg/m2. In the A and T group, the averaged BMI is 17.2 kg/m2. The reduction of AHI less than 20 is 58% postoperatively. The ESS reduced from 10.9 to 4.9 after surgery. Conclusion: Obstructive sleep apnea syndrome is a common upper airway disturbance in the general population. The prevalence rate is ranging high depending on different regions, age, sex and race. It leads to severe morbidity and mortality including car accident, stroke, nocturnal desaand sudden death and should be considered to be a major public health problem. The CPAP is effective to improve daytime sleepiness but the long-term compliance is low. The surgical treatment with different modalities can produce 50% decrease in AHI and ESS after surgery in the 6 to 12 months short-term period.

Keywords: apnea-hypopnea index, obstructive sleep apnea syndrome, polysomnography, uvulopalatopharyngoplasty

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