Search results for: benign prostate tumor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1028

Search results for: benign prostate tumor

848 Liver Transplantation after Downstaging with Electrochemotherapy of Large Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis: A Case Report

Authors: Luciano Tarantino, Emanuele Balzano, Aurelio Nasto

Abstract:

S.R. 53 years. January 2009: HCV-related cirrhosis, Child-Pugh A5 class, EGDS no aesophageal Varices. No important comorbidities. Treated with PEG-IFN+Ribavirin (march-november 2009) with subsequent sustained virologic response. HCVRNA absent overtime. October 2016 :CT detected small HCC nodule in the VIII segment (diam.=12 mm). Treated with US guided RF-ablation. November 2016 CT: complete necrosis. Unfortunately, the patient dropped out US and CT follow-up controls.September 2018: asthenia and weight loss. CT showed a large tumor infiltrating V-VII-VI segments and complete PVTT of right portal vein and its branches . Surgical Consultation excluded indication to Liver resection and OLT . 23 october 2018: ECT of a large peri-hilar area of the tumor including the PVTT. 1 and 3 months post-treatment CT showed complete necrosis and retraction of the thrombus and residual viable tumor in the peripheral portion of the right lobe . Therefor, the patient was reevaluated for OLT and considered eligible in waiting list . March 2019: CT showed no perihilar or portal vein recurrence and distant progression in the right lobe . March 2019 : Trans-arterial-Radio-therapy (TARE) of the right lobe. Post-treatment CT demonstrated no perihilar or portal vein recurrence and extensive necrosis of the residual tumor . December 2019: CT demonstrated several recurrences of HCC infiltrating the VI and VII segment . Howewer no recurrence was observed at hepatic hilum and in portal vessels . Therefore, on February 2020 the patient received OLT. At 44 months follow-up, no complication or recurrence or liver disfunction have been observed.

Keywords: hepatocellular carcinoma, portal vein tumor thrombosis, interventional ultrasound, liver tumor ablation, liver transplantation

Procedia PDF Downloads 41
847 Nanomechanical Characterization of Healthy and Tumor Lung Tissues at Cell and Extracellular Matrix Level

Authors: Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo Antonio Netti

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The study of the biophysics of living cells drew attention to the pivotal role of the cytoskeleton in many cell functions, such as mechanics, adhesion, proliferation, migration, differentiation and neoplastic transformation. In particular, during the complex process of malignant transformation and invasion cell cytoskeleton devolves from a rigid and organized structure to a more compliant state, which confers to the cancer cells a great ability to migrate and adapt to the extracellular environment. In order to better understand the malignant transformation process from a mechanical point of view, it is necessary to evaluate the direct crosstalk between the cells and their surrounding extracellular matrix (ECM) in a context which is close to in vivo conditions. In this study, human biopsy tissues of lung adenocarcinoma were analyzed in order to define their mechanical phenotype at cell and ECM level, by using particle tracking microrheology (PTM) technique. Polystyrene beads (500 nm) were introduced into the sample slice. The motion of beads was obtained by tracking their displacements across cell cytoskeleton and ECM structures and mean squared displacements (MSDs) were calculated from bead trajectories. It has been already demonstrated that the amplitude of MSD is inversely related to the mechanical properties of intracellular and extracellular microenvironment. For this reason, MSDs of particles introduced in cytoplasm and ECM of healthy and tumor tissues were compared. PTM analyses showed that cancerous transformation compromises mechanical integrity of cells and extracellular matrix. In particular, the MSD amplitudes in cells of adenocarcinoma were greater as compared to cells of normal tissues. The increased motion is probably associated to a less structured cytoskeleton and consequently to an increase of deformability of cells. Further, cancer transformation is also accompanied by extracellular matrix stiffening, as confirmed by the decrease of MSDs of matrix in tumor tissue, a process that promotes tumor proliferation and invasiveness, by activating typical oncogenic signaling pathways. In addition, a clear correlation between MSDs of cells and tumor grade was found. MSDs increase when tumor grade passes from 2 to 3, indicating that cells undergo to a trans-differentiation process during tumor progression. ECM stiffening is not dependent on tumor grade, but the tumor stage resulted to be strictly correlated with both cells and ECM mechanical properties. In fact, a greater stage is assigned to tumor spread to regional lymph nodes and characterized by an up-regulation of different ECM proteins, such as collagen I fibers. These results indicate that PTM can be used to get nanomechanical characterization at different scale levels in an interpretative and diagnostic context.

Keywords: cytoskeleton, extracellular matrix, mechanical properties, particle tracking microrheology, tumor

Procedia PDF Downloads 249
846 A Study of Permission-Based Malware Detection Using Machine Learning

Authors: Ratun Rahman, Rafid Islam, Akin Ahmed, Kamrul Hasan, Hasan Mahmud

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Malware is becoming more prevalent, and several threat categories have risen dramatically in recent years. This paper provides a bird's-eye view of the world of malware analysis. The efficiency of five different machine learning methods (Naive Bayes, K-Nearest Neighbor, Decision Tree, Random Forest, and TensorFlow Decision Forest) combined with features picked from the retrieval of Android permissions to categorize applications as harmful or benign is investigated in this study. The test set consists of 1,168 samples (among these android applications, 602 are malware and 566 are benign applications), each consisting of 948 features (permissions). Using the permission-based dataset, the machine learning algorithms then produce accuracy rates above 80%, except the Naive Bayes Algorithm with 65% accuracy. Of the considered algorithms TensorFlow Decision Forest performed the best with an accuracy of 90%.

Keywords: android malware detection, machine learning, malware, malware analysis

Procedia PDF Downloads 127
845 Using Multiomic Plasma Profiling From Liquid Biopsies to Identify Potential Signatures for Disease Diagnostics in Late-Stage Non-small Cell Lung Cancer (NSCLC) in Trinidad and Tobago

Authors: Nicole Ramlachan, Samuel Mark West

Abstract:

Lung cancer is the leading cause of cancer-associated deaths in North America, with the vast majority being non-small cell lung cancer (NSCLC), with a five-year survival rate of only 24%. Non-invasive discovery of biomarkers associated with early-diagnosis of NSCLC can enable precision oncology efforts using liquid biopsy-based multiomics profiling of plasma. Although tissue biopsies are currently the gold standard for tumor profiling, this method presents many limitations since these are invasive, risky, and sometimes hard to obtain as well as only giving a limited tumor profile. Blood-based tests provides a less-invasive, more robust approach to interrogate both tumor- and non-tumor-derived signals. We intend to examine 30 stage III-IV NSCLC patients pre-surgery and collect plasma samples.Cell-free DNA (cfDNA) will be extracted from plasma, and next-generation sequencing (NGS) performed. Through the analysis of tumor-specific alterations, including single nucleotide variants (SNVs), insertions, deletions, copy number variations (CNVs), and methylation alterations, we intend to identify tumor-derived DNA—ctDNA among the total pool of cfDNA. This would generate data to be used as an accurate form of cancer genotyping for diagnostic purposes. Using liquid biopsies offer opportunities to improve the surveillance of cancer patients during treatment and would supplement current diagnosis and tumor profiling strategies previously not readily available in Trinidad and Tobago. It would be useful and advantageous to use this in diagnosis and tumour profiling as well as to monitor cancer patients, providing early information regarding disease evolution and treatment efficacy, and reorient treatment strategies in, timethereby improving clinical oncology outcomes.

Keywords: genomics, multiomics, clinical genetics, genotyping, oncology, diagnostics

Procedia PDF Downloads 120
844 Epulis in Cat's Lips: Understanding the Causes, Symptoms, and Treatment Options

Authors: Sadaf Salek

Abstract:

Introduction: Cats are susceptible to various health conditions, and one such ailment that can affect their oral health is epulis in their lips. Epulis refers to a benign tumor or growth that can develop in different areas of a cat's mouth, including the lips. While epulis is not life-threatening, it can still cause discomfort and affect a cat's overall quality of life. This essay aims to delve into the causes, symptoms, and treatment options for epulis in cat's lips, shedding light on this lesser-known oral condition. Causes: Epulis in a cat's lips can have several causes. Firstly, genetic predisposition plays a significant role, with certain breeds being more prone to developing these growths. Secondly, chronic irritation to the mouth, such as from dental diseases or foreign objects, can also contribute to the development of epulis. Lastly, hormonal imbalances, specifically an excess of estrogen, have been associated with the occurrence of these tumors in cats. Understanding these causes can help cat owners take preventive measures to reduce the risk of epulis in their feline companions. Symptoms: Identifying the symptoms of epulis in a cat's lips is vital for early intervention and effective treatment. The most common symptoms include swelling, redness, and the presence of a visible growth or lump on the lip. Cats with epulis may also exhibit drooling, difficulty eating, and a reluctance to groom themselves. Any change in eating habits or oral behavior should not be overlooked and prompt a visit to the veterinarian for a thorough examination. Treatment ptions: When it comes to treating epulis in a cat's lips, various options are available, depending on the size, location, and characteristics of the growth. The primary treatment involves surgical removal of the tumor. This procedure should be performed by a qualified veterinarian, ensuring complete excision of the mass while preserving as much healthy tissue as possible. In some cases, radiation therapy may be necessary, especially if the tumor is large or aggressive. Additionally, a veterinarian may recommend oral hygiene care and regular dental cleaning to prevent further growths and maintain the cat's oral health. Prevention and Care: Preventing epulis in a cat's lips is not always possible, especially if genetic factors are involved. However, certain preventive measures can minimize the risk of these growths. Maintaining good oral hygiene through regular brushing and the use of appropriate dental products can help prevent chronic irritation and dental diseases. Routine veterinary check-ups should also include thorough oral examinations to detect any abnormal growths or changes in the mouth at an early stage. Pet owners should be observant and seek veterinary care promptly for any signs of discomfort or changes in eating habits. Conclusion: Epulis in a cat's lips is a condition that requires attention and proper treatment. Understanding the causes, identifying symptoms, and exploring treatment options are of utmost importance to help improve a cat's oral health and overall well-being.

Keywords: fibroma, cat, lip, epulis

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843 An Integrative Computational Pipeline for Detection of Tumor Epitopes in Cancer Patients

Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

Abstract:

Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

Procedia PDF Downloads 230
842 The Role of Surgery to Remove the Primary Tumor in Patients with Metastatic Breast Cancer

Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

Abstract:

Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

Procedia PDF Downloads 390
841 DOG1 Expression Is in Common Human Tumors: A Tissue Microarray Study on More than 15,000 Tissue Samples

Authors: Kristina Jansen, Maximilian Lennartz, Patrick Lebok, Guido Sauter, Ronald Simon, David Dum, Stefan Steurer

Abstract:

DOG1 (Discovered on GIST1) is a voltage-gated calcium-activated chloride and bicarbonate channel that is highly expressed in interstitial cells of Cajal and in gastrointestinal stromal tumors (GIST) derived from Cajal cells. To systematically determine in what tumor entities and normal tissue types DOG1 may be further expressed, a tissue microarray (TMA) containing 15,965 samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. DOG1 immunostaining was found in 67 tumor types, including GIST (95.7%), esophageal squamous cell carcinoma (31.9%), pancreatic ductal adenocarcinoma (33.6%), adenocarcinoma of the Papilla Vateri (20%), squamous cell carcinoma of the vulva (15.8%) and the oral cavity (15.3%), mucinous ovarian cancer (15.3%), esophageal adenocarcinoma (12.5%), endometrioid endometrial cancer (12.1%), neuroendocrine carcinoma of the colon (11.1%) and diffuse gastric adenocarcinoma (11%). Low level-DOG1 immunostaining was seen in 17 additional tumor entities. DOG1 expression was unrelated to histopathological parameters of tumor aggressiveness and/or patient prognosis in cancers of the breast (n=1,002), urinary bladder (975), ovary (469), endometrium (173), stomach (233), and thyroid gland (512). High DOG1 expression was linked to estrogen receptor expression in breast cancer (p<0.0001) and the absence of HPV infection in squamous cell carcinomas (p=0.0008). In conclusion, our data identify several tumor entities that can show DOG1 expression levels at similar levels as in GIST. Although DOG1 is tightly linked to a diagnosis of GIST in spindle cell tumors, the differential diagnosis is much broader in DOG1 positive epithelioid neoplasms.

Keywords: biomarker, DOG1, immunohistochemistry, tissue microarray

Procedia PDF Downloads 183
840 A Dose Distribution Approach Using Monte Carlo Simulation in Dosimetric Accuracy Calculation for Treating the Lung Tumor

Authors: Md Abdullah Al Mashud, M. Tariquzzaman, M. Jahangir Alam, Tapan Kumar Godder, M. Mahbubur Rahman

Abstract:

This paper presents a Monte Carlo (MC) method-based dose distributions on lung tumor for 6 MV photon beam to improve the dosimetric accuracy for cancer treatment. The polystyrene which is tissue equivalent material to the lung tumor density is used in this research. In the empirical calculations, TRS-398 formalism of IAEA has been used, and the setup was made according to the ICRU recommendations. The research outcomes were compared with the state-of-the-art experimental results. From the experimental results, it is observed that the proposed based approach provides more accurate results and improves the accuracy than the existing approaches. The average %variation between measured and TPS simulated values was obtained 1.337±0.531, which shows a substantial improvement comparing with the state-of-the-art technology.

Keywords: lung tumour, Monte Carlo, polystyrene, Elekta synergy, Monaco planning system

Procedia PDF Downloads 414
839 Membrane-Localized Mutations as Predictors of Checkpoint Blockade Efficacy in Cancer

Authors: Zoe Goldberger, Priscilla S. Briquez, Jeffrey A. Hubbell

Abstract:

Tumor cells have mutations resulting from genetic instability that the immune system can actively recognize. Immune checkpoint immunotherapy (ICI) is commonly used in the clinic to re-activate immune reactions against mutated proteins, called neoantigens, resulting in tumor remission in cancer patients. However, only around 20% of patients show durable response to ICI. While tumor mutational burden (TMB) has been approved by the Food and Drug Administration (FDA) as a criterion for ICI therapy, the relevance of the subcellular localizations of the mutated proteins within the tumor cell has not been investigated. Here, we hypothesized that localization of mutations impacts the effect of immune responsiveness to ICI. We analyzed publicly available tumor mutation sequencing data of ICI treated patients from 3 independent datasets. We extracted the subcellular localization from the UniProtKB/Swiss-Prot database and quantified the proportion of membrane, cytoplasmic, nuclear, or secreted mutations per patient. We analyzed this information in relation to response to ICI treatment and overall survival of patients showing with 1722 ICI-treated patients that high mutational burden localized at the membrane (mTMB), correlate with ICI responsiveness, and improved overall survival in multiple cancer types. We anticipate that our results will ameliorate predictability of cancer patient response to ICI with potential implications in clinical guidelines to tailor ICI treatment. This would not only increase patient survival for those receiving ICI, but also patients’ quality of life by reducing the number of patients enduring non-effective ICI treatments.

Keywords: cancer, immunotherapy, membrane neoantigens, efficacy prediction, biomarkers

Procedia PDF Downloads 86
838 Tumor Detection of Cerebral MRI by Multifractal Analysis

Authors: S. Oudjemia, F. Alim, S. Seddiki

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This paper shows the application of multifractal analysis for additional help in cancer diagnosis. The medical image processing is a very important discipline in which many existing methods are in search of solutions to real problems of medicine. In this work, we present results of multifractal analysis of brain MRI images. The purpose of this analysis was to separate between healthy and cancerous tissue of the brain. A nonlinear method based on multifractal detrending moving average (MFDMA) which is a generalization of the detrending fluctuations analysis (DFA) is used for the detection of abnormalities in these images. The proposed method could make separation of the two types of brain tissue with success. It is very important to note that the choice of this non-linear method is due to the complexity and irregularity of tumor tissue that linear and classical nonlinear methods seem difficult to characterize completely. In order to show the performance of this method, we compared its results with those of the conventional method box-counting.

Keywords: irregularity, nonlinearity, MRI brain images, multifractal analysis, brain tumor

Procedia PDF Downloads 421
837 Drastic Improvement in Vision Following Surgical Excision of Juvenile Nasopharyngeal Angiofibroma with Compressive Optic Neuropathy

Authors: Sweta Das

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This case report is a 15-year-old male who presented with painless unilateral vision loss from left optic nerve compression due to juvenile nasopharyngeal angiofibroma. JNA is a rare, benign neoplasm that causes intracranial and intraorbital bone destruction and extends aggressively into surrounding soft tissues. It accounts for <1% of all head and neck tumors, is predominantly found in pediatric males and tends to affect indigenous population disproportionately. The most common presenting symptom for JNA is epistaxis and nasal obstruction. However, it can invade orbit, chiasm and pituitary gland, causing loss of vision and field. Visual acuity and function near normalized following surgical excision. Optometry plays an important role in the diagnosis and co-management of JNA with optic nerve compression by closely monitoring afferent optic nerve function and structure, and extraocular motility. Visual function and acuity in patients with short-term compressive neuropathy may drastically improve following surgical resection as this case demonstrates.

Keywords: orbital mass, painless monocular vision loss, compressive optic neuropathy, pediatric tumor

Procedia PDF Downloads 35
836 Effects of α-IFN –SingleWalled Carbon NanoTube and α-IFN-PLGA Encapsulated on Breast Cancer in Rats Induced by DMBA by Using CA15-3 Tumor Marker

Authors: Anoosh Eghdami

Abstract:

Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

Procedia PDF Downloads 299
835 Management of Renal Malignancies with IVC Thrombus: Our Experience

Authors: Sujeet Poudyal

Abstract:

Introduction: Renal cell carcinoma is the most common malignancy associated with Inferior vena cava (IVC) thrombosis. Radical nephrectomy with tumor thrombectomy provides durable cancer-free survival. Other renal malignancies like Wilms’ tumors are also associated with IVC thrombus. We describe our experience with the management of renal malignancies associated with IVC thrombus. Methods: This prospective study included 28 patients undergoing surgery for renal malignancies associated with IVC thrombus from February 2017 to March 2023. Demographics of patients, types of renal malignancy, level of IVC thrombus, intraoperative details, need for venovenous bypass, cardiopulmonary bypass and postoperative outcomes were all documented. Results: Out of a total of 28 patients, 24 patients had clear cell Renal Cell Carcinoma,1 had renal osteosarcoma and 3 patients had Wilms tumor. The levels. of thrombus were II in eight, III in seven, and IV in six patients. The mean age of RCC was 62.81±10.2 years, renal osteosarcoma was 26 years and Wilms tumor was 23 years. There was a need for venovenous bypass in four patients and cardiopulmonary bypass in four patients, and the Postoperative period was uneventful in most cases except for two mortalities, one in Level III due to pneumonia and one in Level IV due to sepsis. All cases followed up till now have no local recurrence and metastasis except one case of RCC with Level IV IVC thrombus, which presented with paraaortic nodal recurrence and is currently managed with sunitinib. Conclusion: The complexity in the management of renal malignancy with IVC thrombus increases with the level of IVC thrombus. As radical nephrectomy with tumor thrombectomy provides durable cancer-free survival in most cases, the surgery should be undertaken in an expert and experienced setup with a strong cardiovascular backup to minimize morbidity and mortality associated with the procedure.

Keywords: renal malignancy, IVC thrombus, radical nephrectomy with tumor thrombectomy, renal cell carcinoma

Procedia PDF Downloads 46
834 Mammotome Vacuum-Assisted Breast Biopsy versus Conventional Open Surgery: A Meta-Analysis

Authors: Dylan Shiting Lu, Samson Okello, Anita Chunyan Wei, Daniel Xiao Li

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Mammotome vacuum-assisted breast biopsy (MVB) introduced in 1995 can be used for the removal of benign breast lesions. Whether or not MVB is a better option compared to conventional open surgery is inconclusive. We aim to compare the clinical and patient-related outcomes between MVB and open surgery to remove benign breast tumors less than 5 cm in women. We searched English and Chinese electronic databases with the keywords of Mammotome, clinical trial (CT), vacuum-assisted breast biopsy for studies comparing MVB and open surgery until May 2021. We performed a systematic review and random-effects meta-analysis to compare incision size, operation time, intraoperative blood loss, healing time, scar length, patient satisfaction, postoperative hematoma rate, wound infection rate, postoperative ecchymosis, and postoperative sunken skin among those who have Mammotome and those who have surgery. Our analysis included nine randomized CTs with 1155 total patients (575 Mammotome, 580 surgery) and mean age 40.32 years (standard deviation 3.69). We found statistically significant favorable outcomes for Mammotome including blood loss (ml) [standardized mean difference SMD -5.03, 95%CI (-7.30, -2.76)], incision size (cm) [SMD -12.22, 95%CI (-17.40, -7.04)], operation time (min) [SMD -6.66, 95%CI (-9.01, -4.31)], scar length (cm) [SMD -7.06, 95%CI (-10.76, -3.36)], healing time (days) [SMD -6.57, 95%CI (-10.18, -2.95)], and patient satisfaction [relative risk RR 0.38, 95%CI (0.13, 1.08)]. In conclusion, Mammotome vacuum-assisted breast biopsy compared to open surgery shows better clinical and patient-related outcomes. Further studies should be done on whether or not MVB is a better option for benign breast tumors excision.

Keywords: clinical and patient outcomes, open surgery, Mammotome vacuum-assisted breast biopsy, meta-analysis

Procedia PDF Downloads 178
833 Differential Infection of Primary Human B-Cells and EBV Positive B-Lymphoma Cell Lines by Recombinant AAV Serotypes

Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

Abstract:

B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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832 Functionalized SPIO Conjugated with Doxorubicin for Tumor Diagnosis and Chemotherapy Enhanced by Applying Magnetic Fields

Authors: Po-Chin Liang, Yung-Chu Chen, Chi-Feng Chiang, Yun-Ping Lin, Wen-Yuan Hsieh, Win-Li Lin

Abstract:

The aim of this study was to develop super paramagnetic iron oxide (SPIO) nano-particles comprised of a magnetic Fe3O4 core and a shell of aqueous stable self-doped polyethylene glycol (PEG) with a high loading of doxorubicin (SPIO-PEG-D) for tumor theranostics. The in-vivo MRI study showed that there was a stronger T2-weighted signal enhancement for the group under a magnetic field, and hence it indicated that this group had a better accumulation of SPIO-PEG than the group without a magnetic field. In the anticancer evaluation of SPIO-PEG-D, the group with a magnetic field displayed a significantly smaller tumor size than the group without. The overall results show that SPIO-PEG-D nanoparticles have the potential for the application of MRI/monitoring chemotherapy and the therapy can be locally enhanced by applying an external magnetic field.

Keywords: super paramagnetic iron oxide nano particles, doxorubicin, chemotherapy, MRI, magnetic fields

Procedia PDF Downloads 579
831 PD-L1 Expression in Papillary Thyroid Carcinoma Arising Denovo or on Top of Autoimmune Thyroiditis

Authors: Dalia M. Abouelfadl, Noha N. Yassen, Marwa E. Shabana

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Background: The evolution of immune therapy motivated many to study the relation between immune response and progression of cancer. Little is known about expression of PD-L1 (a newly evolving immunotherapeutic drug) in papillary thyroid carcinoma (PTC) arising de-novo and PTC arising on top of autoimmune thyroiditis (Hashimoto's (HT) and lymphocytic thyroiditis (LT)). The aim of this work is to study the alteration of expression of PD-L1 in PTCs arising from de-novo or on top of HT OR LT using immunohistochemistry and image analyser system. Method: 100 paraffin blocks for PTC cases were collected retrospectively for staining using PD-L1 rabbit monoclonal antibody (BIOCARE-ACI 3171 A, C). The antibody expression is measured digitally using Image Analyzer Leica Qwin 3000, and the membranous and cytoplasmic expression of PD-L1 in tumor cells was considered positive. The results were correlated with tumor grade, size, and LN status. Results: The study samples consisted of 41 cases of PTC arising De novo, 36 cases on top of HT, and 23 on top of LT. Expression of PD-L1 was highest among the PTC-HL group (25 case-69%) followed by PTC-TL group (14 case-60.8%) then de-novo PTC (19 case-46%) with P Value < 0.05. PD-L1 expression correlated with nodal metastasis and was not relevant to tumor size or grade. Conclusion: The severity of the immune response in tumor microenvironment directly influences PTC prognosis. The anti PD-L1 Ab can be a very successful therapeutic agent for PTC arising on top of HT.

Keywords: carcinoma, Hashimoto's, lymphocytic, papillary, PD-L1, thyroiditis

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830 Correlation Between Different Radiological Findings and Histopathological diagnosis of Breast Diseases: Retrospective Review Conducted Over Sixth Years in King Fahad University Hospital in Eastern Province, Saudi Arabia

Authors: Sadeem Aljamaan, Reem Hariri, Rahaf Alghamdi, Batool Alotaibi, Batool Alsenan, Lama Althunayyan, Areej Alnemer

Abstract:

The aim of this study is to correlate between radiological findings and histopathological results in regard to the breast imaging-reporting and data system scores, size of breast masses, molecular subtypes and suspicious radiological features, as well as to assess the concordance rate in histological grade between core biopsy and surgical excision among breast cancer patients, followed by analyzing the change of concordance rate in relation to neoadjuvant chemotherapy in a Saudi population. A retrospective review was conducted over 6-year period (2017-2022) on all breast core biopsies of women preceded by radiological investigation. Chi-squared test (χ2) was performed on qualitative data, the Mann-Whitney test for quantitative non-parametric variables, and the Kappa test for grade agreement. A total of 641 cases were included. Ultrasound, mammography, and magnetic resonance imaging demonstrated diagnostic accuracies of 85%, 77.9% and 86.9%; respectively. magnetic resonance imaging manifested the highest sensitivity (72.2%), and the lowest was for ultrasound (61%). Concordance in tumor size with final excisions was best in magnetic resonance imaging, while mammography demonstrated a higher tendency of overestimation (41.9%), and ultrasound showed the highest underestimation (67.7%). The association between basal-like molecular subtypes and the breast imaging-reporting and data system score 5 classifications was statistically significant only for magnetic resonance imaging (p=0.04). Luminal subtypes demonstrated a significantly higher percentage of speculation in mammography. Breast imaging-reporting and data system score 4 manifested a substantial number of benign pathologies in all the 3 modalities. A fair concordance rate (k= 0.212 & 0.379) was demonstrated between excision and the preceding core biopsy grading with and without neoadjuvant therapy, respectively. The results demonstrated a down-grading in cases post-neoadjuvant therapy. In cases who did not receive neoadjuvant therapy, underestimation of tumor grade in biopsy was evident. In summary, magnetic resonance imaging had the highest sensitivity, specificity, positive predictive value and accuracy of both diagnosis and estimation of tumor size. Mammography demonstrated better sensitivity than ultrasound and had the highest negative predictive value, but ultrasound had better specificity, positive predictive value and accuracy. Therefore, the combination of different modalities is advantageous. The concordance rate of core biopsy grading with excision was not impacted by neoadjuvant therapy.

Keywords: breast cancer, mammography, MRI, neoadjuvant, pathology, US

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829 Ancelim: Health System Restoration Protocol for Cancer Patients

Authors: Mark Berry

Abstract:

A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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828 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

Abstract:

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

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827 Phantom and Clinical Evaluation of Block Sequential Regularized Expectation Maximization Reconstruction Algorithm in Ga-PSMA PET/CT Studies Using Various Relative Difference Penalties and Acquisition Durations

Authors: Fatemeh Sadeghi, Peyman Sheikhzadeh

Abstract:

Introduction: Block Sequential Regularized Expectation Maximization (BSREM) reconstruction algorithm was recently developed to suppress excessive noise by applying a relative difference penalty. The aim of this study was to investigate the effect of various strengths of noise penalization factor in the BSREM algorithm under different acquisition duration and lesion sizes in order to determine an optimum penalty factor by considering both quantitative and qualitative image evaluation parameters in clinical uses. Materials and Methods: The NEMA IQ phantom and 15 clinical whole-body patients with prostate cancer were evaluated. Phantom and patients were injected withGallium-68 Prostate-Specific Membrane Antigen(68 Ga-PSMA)and scanned on a non-time-of-flight Discovery IQ Positron Emission Tomography/Computed Tomography(PET/CT) scanner with BGO crystals. The data were reconstructed using BSREM with a β-value of 100-500 at an interval of 100. These reconstructions were compared to OSEM as a widely used reconstruction algorithm. Following the standard NEMA measurement procedure, background variability (BV), recovery coefficient (RC), contrast recovery (CR) and residual lung error (LE) from phantom data and signal-to-noise ratio (SNR), signal-to-background ratio (SBR) and tumor SUV from clinical data were measured. Qualitative features of clinical images visually were ranked by one nuclear medicine expert. Results: The β-value acts as a noise suppression factor, so BSREM showed a decreasing image noise with an increasing β-value. BSREM, with a β-value of 400 at a decreased acquisition duration (2 min/ bp), made an approximately equal noise level with OSEM at an increased acquisition duration (5 min/ bp). For the β-value of 400 at 2 min/bp duration, SNR increased by 43.7%, and LE decreased by 62%, compared with OSEM at a 5 min/bp duration. In both phantom and clinical data, an increase in the β-value is translated into a decrease in SUV. The lowest level of SUV and noise were reached with the highest β-value (β=500), resulting in the highest SNR and lowest SBR due to the greater noise reduction than SUV reduction at the highest β-value. In compression of BSREM with different β-values, the relative difference in the quantitative parameters was generally larger for smaller lesions. As the β-value decreased from 500 to 100, the increase in CR was 160.2% for the smallest sphere (10mm) and 12.6% for the largest sphere (37mm), and the trend was similar for SNR (-58.4% and -20.5%, respectively). BSREM visually was ranked more than OSEM in all Qualitative features. Conclusions: The BSREM algorithm using more iteration numbers leads to more quantitative accuracy without excessive noise, which translates into higher overall image quality and lesion detectability. This improvement can be used to shorter acquisition time.

Keywords: BSREM reconstruction, PET/CT imaging, noise penalization, quantification accuracy

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826 Brain Tumor Segmentation Based on Minimum Spanning Tree

Authors: Simeon Mayala, Ida Herdlevær, Jonas Bull Haugsøen, Shamundeeswari Anandan, Sonia Gavasso, Morten Brun

Abstract:

In this paper, we propose a minimum spanning tree-based method for segmenting brain tumors. The proposed method performs interactive segmentation based on the minimum spanning tree without tuning parameters. The steps involve preprocessing, making a graph, constructing a minimum spanning tree, and a newly implemented way of interactively segmenting the region of interest. In the preprocessing step, a Gaussian filter is applied to 2D images to remove the noise. Then, the pixel neighbor graph is weighted by intensity differences and the corresponding minimum spanning tree is constructed. The image is loaded in an interactive window for segmenting the tumor. The region of interest and the background are selected by clicking to split the minimum spanning tree into two trees. One of these trees represents the region of interest and the other represents the background. Finally, the segmentation given by the two trees is visualized. The proposed method was tested by segmenting two different 2D brain T1-weighted magnetic resonance image data sets. The comparison between our results and the standard gold segmentation confirmed the validity of the minimum spanning tree approach. The proposed method is simple to implement and the results indicate that it is accurate and efficient.

Keywords: brain tumor, brain tumor segmentation, minimum spanning tree, segmentation, image processing

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825 Novel Liposomal Nanocarriers For Long-term Tumor Imaging

Authors: Mohamad Ahrari, Kayvan Sadri, Mahmoud Reza Jafari

Abstract:

PEGylated liposomes have a smaller volume of distribution and decreased clearance, consequently, due to their more prolonged presence in bloodstream and maintaining their stability during this period, these liposomes can be applied for imaging tumoral sites. The purpose of this study is to develop an appropriate radiopharmaceutical agent in long-term imaging for improved diagnosis and evaluation of tumors. In this study, liposomal formulations encapsulating albumin is synthesized by solvent evaporation method along with homogenization, and their characteristics were assessed. Then these liposomes labeled by Philips method and the rate of stability of labeled liposomes in serum, and ultimately the rate of biodistribution and gamma scintigraphy in C26-colon carcinoma tumor-bearing mice, were studied. The result of the study of liposomal characteristics displayed that capable of accumulating in tumor sites based of EPR phenomenon. these liposomes also have high stability for maintaining encapsulated albumin in a long time. In the study of biodistribution of these liposomes in mice, they accumulated more in the kidney, liver, spleen, and tumor sites, which, even after clearing formulations in the bloodstream, they existed in high levels in these organs up to 96 hours. In gamma scintigraphy also, organs with high activity accumulation from early hours up to 96 hours were visible in the form of hot spots. concluded that PEGylated liposomal formulation encapsulating albumin can be labeled with In-Oxine, and obtained stabilized formulation for long-term imaging, that have more favorable conditions for the evaluation of tumors and it will cause early diagnosis of tumors.

Keywords: nano liposome, 111In-oxine, imaging, biodistribution, tumor

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824 Targeted Photodynamic Therapy for Intraperitoneal Ovarian Cancer, A Way to Stimulate Anti-Tumoral Immune Response

Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

Abstract:

Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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823 The Effect of Size and Tumor Depth on Histological Clearance Margins of Basal Cell Carcinomas

Authors: Martin Van, Mohammed Javed, Sarah Hemington-Gorse

Abstract:

Aim: Our aim was to determine the effect of size and tumor depth of basal cell carcinomas (BCCs) on surgical margin clearance. Methods: A retrospective study was conducted at the Welsh Centre for Burns and Plastic Surgery (WCBPS), Morriston Hospital between 1 Jan 2016 – 31 July 2016. Only patients with confirmed BCC on histopathological analysis were included. Patient data including anatomical region treated, lesion size, histopathological clearance margins and histological sub-types were recorded. An independent T-test was performed determine statistical significance. Results: A total of 228 BCCs were excised in 160 patients. Eleven lesions (4.8%) were incompletely excised. The nose area had the highest rate of incomplete excision. The mean diameter of incompletely excised lesions was 11.4mm vs 11.5mm in completely excised lesions (p=0.959) and the mean histological depth of incompletely excised lesions was 4.1mm vs. 2.5mm for completely excised BCCs (p < 0.05). Conclusions: BCC tumor depth of > 4.1 mm was associated with high rate of incomplete margin clearance. Hence, in prospective patients, a BCC tumor depth (>4 mm) on tissue biopsy should alert the surgeon of potentially higher risk of incomplete excision of lesion.

Keywords: basal cell carcinoma, excision margins, plastic surgery, treatment

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822 Connecting MRI Physics to Glioma Microenvironment: Comparing Simulated T2-Weighted MRI Models of Fixed and Expanding Extracellular Space

Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

Abstract:

Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

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821 Computer-Aided Diagnosis System Based on Multiple Quantitative Magnetic Resonance Imaging Features in the Classification of Brain Tumor

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

Abstract:

Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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820 Deep Learning Approach for Colorectal Cancer’s Automatic Tumor Grading on Whole Slide Images

Authors: Shenlun Chen, Leonard Wee

Abstract:

Tumor grading is an essential reference for colorectal cancer (CRC) staging and survival prognostication. The widely used World Health Organization (WHO) grading system defines histological grade of CRC adenocarcinoma based on the density of glandular formation on whole slide images (WSI). Tumors are classified as well-, moderately-, poorly- or un-differentiated depending on the percentage of the tumor that is gland forming; >95%, 50-95%, 5-50% and <5%, respectively. However, manually grading WSIs is a time-consuming process and can cause observer error due to subjective judgment and unnoticed regions. Furthermore, pathologists’ grading is usually coarse while a finer and continuous differentiation grade may help to stratifying CRC patients better. In this study, a deep learning based automatic differentiation grading algorithm was developed and evaluated by survival analysis. Firstly, a gland segmentation model was developed for segmenting gland structures. Gland regions of WSIs were delineated and used for differentiation annotating. Tumor regions were annotated by experienced pathologists into high-, medium-, low-differentiation and normal tissue, which correspond to tumor with clear-, unclear-, no-gland structure and non-tumor, respectively. Then a differentiation prediction model was developed on these human annotations. Finally, all enrolled WSIs were processed by gland segmentation model and differentiation prediction model. The differentiation grade can be calculated by deep learning models’ prediction of tumor regions and tumor differentiation status according to WHO’s defines. If multiple WSIs were possessed by a patient, the highest differentiation grade was chosen. Additionally, the differentiation grade was normalized into scale between 0 to 1. The Cancer Genome Atlas, project COAD (TCGA-COAD) project was enrolled into this study. For the gland segmentation model, receiver operating characteristic (ROC) reached 0.981 and accuracy reached 0.932 in validation set. For the differentiation prediction model, ROC reached 0.983, 0.963, 0.963, 0.981 and accuracy reached 0.880, 0.923, 0.668, 0.881 for groups of low-, medium-, high-differentiation and normal tissue in validation set. Four hundred and one patients were selected after removing WSIs without gland regions and patients without follow up data. The concordance index reached to 0.609. Optimized cut off point of 51% was found by “Maxstat” method which was almost the same as WHO system’s cut off point of 50%. Both WHO system’s cut off point and optimized cut off point performed impressively in Kaplan-Meier curves and both p value of logrank test were below 0.005. In this study, gland structure of WSIs and differentiation status of tumor regions were proven to be predictable through deep leaning method. A finer and continuous differentiation grade can also be automatically calculated through above models. The differentiation grade was proven to stratify CAC patients well in survival analysis, whose optimized cut off point was almost the same as WHO tumor grading system. The tool of automatically calculating differentiation grade may show potential in field of therapy decision making and personalized treatment.

Keywords: colorectal cancer, differentiation, survival analysis, tumor grading

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819 Identifying the True Extend of Glioblastoma Based on Preoperative FLAIR Images

Authors: B. Shukir, L. Szivos, D. Kis, P. Barzo

Abstract:

Glioblastoma is the most malignant brain tumor. In general, the survival rate varies between (14-18) months. Glioblastoma consists a solid and infiltrative part. The standard therapeutic management of glioblastoma is maximum safe resection followed by chemo-radiotherapy. It’s hypothesized that the pretumoral hyperintense region in fluid attenuated inversion recovery (FLAIR) images includes both vasogenic edema and infiltrated tumor cells. In our study, we aimed to define the sensitivity and specificity of hyperintense FLAIR images preoperatively to examine how well it can define the true extent of glioblastoma. (16) glioblastoma patients included in this study. Hyperintense FLAIR region were delineated preoperatively as tumor mask. The infiltrative part of glioblastoma considered the regions where the tumor recurred on the follow up MRI. The recurrence on the CE-T1 images was marked as the recurrence masks. According to (AAL3) and (JHU white matter labels) atlas, the brain divided into cortical and subcortical regions respectively. For calculating specificity and sensitivity, the FLAIR and the recurrence masks overlapped counting how many regions affected by both . The average sensitivity and specificity was 83% and 85% respectively. Individually, the sensitivity and specificity varied between (31-100)%, and (100-58)% respectively. These results suggest that despite FLAIR being as an effective radiologic imaging tool its prognostic value remains controversial and probabilistic tractography remain more reliable available method for identifying the true extent of glioblastoma.

Keywords: brain tumors, glioblastoma, MRI, FLAIR

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