Search results for: portal vein tumor thrombosis

Authors: Guoqiang Yu, Mehrana Mohtasebi, Jinghong Sun, Thomas Pittman

Abstract:

Malignant glioma (MG) is the most common type of primary malignant brain tumor. Surgical resection of MG remains the cornerstone of therapy, and the extent of resection correlates with patient survival. A limiting factor for resection, however, is the difficulty in differentiating the tumor from normal tissue during surgery. Fluorescence imaging is an emerging technique for real-time intraoperative visualization of MGs and their boundaries. However, most clinical-grade neurosurgical operative microscopes with fluorescence imaging ability are hampered by low adoption rates due to high cost, limited portability, limited operation flexibility, and lack of skilled professionals with technical knowledge. To overcome the limitations, we innovatively integrated miniaturized light sources, flippable filters, and a recording camera to the surgical eye loupes to generate a wearable fluorescence eye loupe (FLoupe) device for intraoperative imaging of fluorescent MGs. Two FLoupe prototypes were constructed for imaging of Fluorescein and 5-aminolevulinic acid (5-ALA), respectively. The wearable FLoupe devices were tested on tumor-simulating phantoms and patients with MGs. Comparable results were observed against the standard neurosurgical operative microscope (PENTERO® 900) with fluorescence kits. The affordable and wearable FLoupe devices enable visualization of both color and fluorescence images with the same quality as the large and expensive stationary operative microscopes. The wearable FLoupe device allows for a greater range of movement, less obstruction, and faster/easier operation. Thus, it reduces surgery time and is more easily adapted to the surgical environment than unwieldy neurosurgical operative microscopes.

Keywords: fluorescence guided surgery, malignant glioma, neurosurgical operative microscope, wearable fluorescence imaging device

Procedia PDF Downloads 31

Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

Abstract:

In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

Procedia PDF Downloads 123

Authors: Tugce Caliskan

Abstract:

The gentrification literature in Turkey provided important insights regarding the analysis of the socio-spatial change in İstanbul mostly through the existing gentrification theories which were produced in Anglo-American literature. Yet early researches focused on the classical gentrification while failing to notice other place-specific forms of the phenomena. It was only after the mid-2000s that scholarly attention shifted to the recent discussions in the mainstream such as the neoliberal urban policies, government involvement, and resistance. Although these studies have considerable potential to contribute to the geography of gentrification, it seems that copying the linear timeline of Anglo-American conceptualization limited the space to introduce contextually nuanced way of process in Turkey. More specifically, the gentrification literature in Turkey acknowledged the linear timeline of the process drawing on the mainstream studies, and, made the spontaneous classical gentrification as the starting point in İstanbul at the expense of contextually specific forms of the phenomenon that took place in the same years. This paper is an attempt to understand place-specific forms of gentrification through the abandonment of the linear understanding of time. In this vein, this paper approaches the process as moving both linear and cyclical rather than the waves succeeded each other. Maintaining a dialectical relationship between the cyclical and the linear time, this paper investigates how the components of gentrification have been taken place in the cyclical timeline while becoming bolder in the linear timeline. This paper argues that taking the (re)investment in the secondary circuit of capital and class transformation as the core characteristics of gentrification, and accordingly, searching for these components beyond the linear timeline provide strategic value to decenter the perspectives, not merely for Turkish studies. In this vein, this strategy revealed that Western experience of gentrification did not travel, adopted or copied in Turkey but gentrification -as an abstract and general concept- has emerged as a product of different contextual, historical and temporal forces which must be considered within the framework of state-led urbanization as early as 1980 differing from the Global North trajectories.

Keywords: comparative urbanism, geography of gentrification, linear and cyclical timeline, state-led gentrification

Procedia PDF Downloads 84

Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

Abstract:

The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

Procedia PDF Downloads 193

Authors: Eun-Joong Kim, Sankarprasad Bhuniya, Hyunseung Lee, Hyun Min Kim, Chaejoon Cheong, Su-khendu Maiti, Kwan Soo Hong, Jong Seung Kim

Abstract:

Metastatic cancers have historically been difficult to treat. However, metastatic tumors have been found to have high levels of reactive oxygen species such as hydrogen peroxide (H2O2), supporting the hypothesis that a prodrug could be activated by intracellular H2O2 and lead to a potential anti-metastatic therapy. In this study, prodrug 7 was designed to be activated by H2O2-mediated boronate oxidation, resulting in activation of the fluorophore for detection and release of the therapeutic agent, SN-38. Drug release from prodrug 7 was investigated by monitoring fluorescence after addition of H2O2 to the cancer cells. Prodrug 7 activated by H2O2 selectively inhibited tumor cell growth. Furthermore, intratracheally administered prodrug 7 showed effective anti-tumor activity in a mouse model of metastatic lung disease. Thus, this H2O2-responsive prodrug has therapeutic potential as a novel treatment for metastatic cancer via cellular imaging with fluorescence as well as selective release of the anti-cancer drug, SN-38.

Keywords: hydrogen peroxide, prodrug, metastatic tumors, fluorescence

Procedia PDF Downloads 428

Authors: Mateusz Bilski, Jakub Klas, Emilia Kowalczyk, Sylwia Koziej, Katarzyna Kulszo, Ludmiła Grzybowska- Szatkowska

Abstract:

Background: Liver metastases are a common complication of primary solid tumors and sig-nificantly reduce patient survival. In the era of increasing diagnosis of oligometastatic disease and oligoprogression, methods of local treatment of metastases, i.e. MDT, are becoming more important. Implementation of such treatment can be considered for liver metastases, which are a common complication of primary solid tumors and significantly reduce patient survival. To date, the mainstay of treatment for oligometastatic disease has been surgical resection, but not all patients qualify for the procedure. As an alternative to surgical resection, radiotherapy techniques have become available, including stereotactic body radiation therapy (SBRT) or high-dose interstitial brachytherapy (iBT). iBT is an invasive method that emits very high doses of radiation from the inside of the tumor to the outside. This technique provides better tumor coverage than SBRT while having little impact on surrounding healthy tissue and elim-inates some concerns involving respiratory motion. Methods: We conducted a systematic re-view of the scientific literature on the use of brachytherapy in the treatment of liver metasta-ses from 2018 - 2023 using PubMed and ResearchGate browsers according to PRISMA rules. Results: From 111 articles, 18 publications containing information on 729 patients with liver metastases were selected. iBT has been shown to provide high rates of tumor control. Among 14 patients with 54 unresectable RCC liver metastases, after iBT LTC was 92.6% during a median follow-up of 10.2 months, PFS was 3.4 months. In analysis of 167 patients after treatment with a single fractional dose of 15-25 Gy with brachytherapy at 6- and 12-month follow-up, LRFS rates of 88,4-88.7% and 70.7 - 71,5%, PFS of 78.1 and 53.8%, and OS of 92.3 - 96.7% and 76,3% - 79.6%, respectively, were achieved. No serious complications were observed in all patients. Distant intrahepatic progression occurred later in patients with unre-sectable liver metastases after brachytherapy (PFS: 19.80 months) than in HCC patients (PFS: 13.50 months). A significant difference in LRFS between CRC patients (84.1% vs. 50.6%) and other histologies (92.4% vs. 92.4%) was noted, suggesting a higher treatment dose is necessary for CRC patients. The average target dose for metastatic colorectal cancer was 40 - 60 Gy (compared to 100 - 250 Gy for HCC). To better assess sensitivity to therapy and pre-dict side effects, it has been suggested that humoral mediators be evaluated. It was also shown that baseline levels of TNF-α, MCP-1 and VEGF, as well as NGF and CX3CL corre-lated with both tumor volume and radiation-induced liver damage, one of the most serious complications of iBT, indicating their potential role as biomarkers of therapy outcome. Con-clusions: The use of brachytherapy methods in the treatment of liver metastases of various cancers appears to be an interesting and relatively safe therapeutic method alternative to sur-gery. An important challenge remains the selection of an appropriate brachytherapy method and radiation dose for the corresponding initial tumor type from which the metastasis origi-nated.

Keywords: liver metastases, brachytherapy, CT-HDRBT, iBT

Procedia PDF Downloads 84

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

Abstract:

One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

Procedia PDF Downloads 195

Authors: Steven Robinson, Adriana Dager, Param Patel

Abstract:

Wandering spleen is a rare variant where there is abnormal development of the ligamentous peritoneal attachments of the spleen which normally anchor it in the left upper quadrant of the abdomen. Ligamentous abnormalities can be congenital, or acquired through pregnancy, injury, or iatrogenic causes. Absence or laxity of these ligaments allows migration of the spleen into ectopic portions of the abdomen, which is also associated with an elongated vascular pedicle. Incidence of wandering spleen is reported at less than 0.25% with a female to male ratio of approximately 6:1. The most common complication of a wandering spleen is torsion around its vascular pedicle which can lead to thrombosis and infarction. Torsion of a wandering spleen is a rare but important cause of an acute abdomen. Imaging, and specifically CT or ultrasound, is crucial in the diagnosis. We present a case of a torsed wandering spleen which was treated with splenectomy.

Keywords: Wandering Spleen, Torsion, Splenic Torsion, Spleen

Procedia PDF Downloads 54

Authors: Yaya Gao, Jifeng Liu, Yafeng Liu

Abstract:

Objectives: This study aimed to improve clinicians' understanding and diagnosis of the Mammary analogue secretory carcinoma of the salivary gland（MASC）. Methods: The clinical features of a MASC patient who was admitted to WestChina Hospital of Sichuan University in July 2020 were reviewed and analyzed. A 49-year-old woman with left upper neck pain for three months was admitted to the hospital. She underwent adenoma resection of the left submandibular gland 14 years ago and mucoepidermoid carcinoma resection surgery five years ago. Three months before admission, the patient developed pain in the left mandibular angle after "fatigue" and gradually developed radiation pain in the left ear, which could be relieved after rest. A mass of 1cm could be touched at the mandibular, with tenderness, poor mobility, and hard texture. No swelling, heat, pain, rupture, or pus was found on the surrounding skin. Color doppler ultrasonography of the salivary gland indicated a weak echo mass of 23*14*17mm in the left parotid gland. Results: Surgical excision was completed. Immunohistochemistry of the tumor samples after operation showed that P63（a few，+）, CK7（+）, S100（+）, DOG1（-）, Ki67（MIB-1）（+，5%），pan-TRK（+）, PAS(+) . ETV-6 gene translocation was detected in FISH in postoperative pathology, which indicated MASC. After this diagnosis, the patient sent the postoperative specimen of the second submandibular tumor to our hospital for consultation. The morphology of the two was similar. FISH detected ETV-6 gene translocation, so the second pathological diagnosis was revised to MASC. Conclusion: MASC of the salivary gland is a rare salivary gland tumor whose diagnosis depends on the result of the ETV6-NTRK3 fusion gene.

Keywords: mammary analogue secretory carcinoma, ETV6-NTRK3, salivary gland, misdiagnosed

Procedia PDF Downloads 46

Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

Abstract:

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

Procedia PDF Downloads 39

Authors: Sara S. Fouad, Omneya Messallam

Abstract:

In 1818, a seventy-five kilometer long canal was dug (called the Mahmoudiyah canal) connecting between Alexandria city in Egypt and the western branch of the Nile. It was a productive resource and vital to its environment, context, transportation, and recreation. It played a significant role in people’s lives and Alexandria city’s shape. The canal, which was the main vein of goods’ transporting from Alexandria’s seaport to the different parts of Egypt, was still in use today as a major source of clear water in the city. But nowadays, Mahmoudiyah canal is converting into ‘dead waterway’. The canal became sources of pollution as a result of solid and industrial waste thus causing many diseases, destroying communities and biodiversity, with urban invasion, the loss of community aesthetic value and healthy environment. Therefore, this paper aims to propose an urban strategy, as a solution to revive the forgotten canal, through recreating a cultural promenade on its shore. The main aim of this research is to formulate decent quality of life, unpolluted space, an area gathering the city space for nature, tourism and investments. As a case study, this paper investigates Mahmoudiyah canal through urban and ecological analyses, aiming to design an urban strategy for reviving it by creating a cultural promenade enriched with public spaces and green areas, which can most probably enhance the quality of life, city re-living and development. Community participation is also considered as vital and intrinsic implementation stage. The empirical research involved using several data assembly methods such as interviews, mental mapping, structural observations and questionnaires. The paper ends with a set of conclusions leading to proposals for the Mahmoudiyah canal revitalization considering the complex challenges and processes of sustainable regeneration focusing on city’s rehabilitation and lost identity.

Keywords: Mahmoudiyah canal, community aesthetic value, city re-living, cultural promenade

Procedia PDF Downloads 101

Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

Abstract:

Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

Procedia PDF Downloads 316

Authors: Jasminka Mujic, Karin Milde-Langosch, Volkmar Mueller, Mirza Suljagic, Tea Becirevic, Jozo Coric, Daria Ler

Abstract:

MACC1 (metastasis associated in colon cancer-1) is a prognostic biomarker for tumor progression, metastasis, and survival of a variety of solid cancers. MACC1 also causes tumor growth in xenograft models and acts as a master regulator of the HGF/MET signaling pathway. In breast cancer, the expression of MACC1 determined by immunohistochemistry was significantly associated with positive lymph node status and advanced clinical stage. The aim of the present study was to further investigate the prognostic or predictive value of MACC1 expression in breast cancer using western blot analysis and immunohistochemistry. The results of our study have shown that high MACC1 expression in breast cancer is associated with shorter disease-free survival, especially in node-negative tumors. The MACC1 might be a suitable biomarker to select patients with a higher probability of recurrence which might benefit from adjuvant chemotherapy. Our results support a biologic role and potentially open the perspective for the use of MACC1 as predictive biomarker for treatment decision in breast cancer patients.

Keywords: breast cancer, biomarker, HGF/MET, MACC1

Procedia PDF Downloads 203

Authors: Parveen Kundu, Zile Singh, Kunika Kundu, Swaran Kaur

Abstract:

Context: Tuberculous osteomyelitis is a relatively uncommon condition that can present with various clinical and radiological features, often mimicking bone tumors or tumor-like lesions. In endemic countries like India, tuberculosis should be considered as a potential differential diagnosis for lytic bone lesions. This study aimed to highlight the different presentations of tuberculosis that can mimic tumors or tumor-like lesions in bone and emphasize the successful outcome of antitubercular therapy (ATT) in treating these cases. Research Aim: The main objective of this research was to explore the varied presentations of tuberculosis that mimic bone tumors or tumor-like lesions both clinically and radiologically, focusing on different bones. The study aimed to raise awareness among clinicians about this possibility and highlight the importance of histopathological confirmation before initiating treatment for lytic bone lesions. Methodology: This study utilized a retrospective review of 22 patients with suspected lytic bone lesions, who were subsequently diagnosed with tuberculous osteomyelitis through histopathological examination. The cases were collected over a period of ten years. Eleven cases required curettage for extensive lesions with sequestrations, while all 22 patients received 12 months of antitubercular therapy. Findings: The study included 14 male and 8 female patients, ranging in age from 3 to 61 years, with an average age of 22.05. The clinical and radiological presentations varied, with examples including bone cysts in the metaphyseal area of long bones, lesions resembling chondroblastomas, giant cell tumors, and osteoid osteoma, as well as multifocal lytic lesions resembling metastasis or multiple myeloma. One patient had lesions in both the clavicle and hand. Lesions mimicking chondromas were also observed in the phalanges of the hand and foot metatarsal. All patients showed resolution of the lesions and no residual disability following ATT. Theoretical Importance: This study highlights the importance of considering tuberculosis as a potential differential diagnosis for lytic bone lesions, particularly in endemic regions. It emphasizes the need for histopathological confirmation to accurately diagnose tuberculous osteomyelitis, as this is considered the gold standard. Data Collection and Analysis Procedures: Data for this study were collected retrospectively from medical records and radiological images of the 22 patients. The cases were analyzed based on clinical presentation, radiological findings, and histopathological confirmation. The outcomes of antitubercular therapy were also assessed. The data were summarized and presented descriptively. Question Addressed: This study aimed to address the question of how tuberculosis can mimic different bone tumors and tumor-like lesions clinically and radiologically. It also aimed to assess the successful outcome of antitubercular therapy in treating these cases. Conclusion: Tuberculous osteomyelitis can present with varied clinical and radiological features, often mimicking bone tumors or tumor-like lesions. Clinicians should consider tuberculosis as a potential diagnosis for lytic bone lesions, especially in endemic areas. Histopathological confirmation is essential for accurate diagnosis. Antitubercular therapy is an effective treatment for tuberculous osteomyelitis, leading to the resolution of the lesions with no residual disability.

Keywords: tuberculosis, tumor, curettage, bone

Procedia PDF Downloads 58

Authors: Spira A., Marabelle A., Kientop D., Moser E., Mumm J.

Abstract:

Background: Both interleukin-2 (IL-2) and interleukin-10 (IL-10) have been extensively studied for their stimulatory function on T cells and their potential to obtain sustainable tumor control in RCC, melanoma, lung, and pancreatic cancer as monotherapy, as well as combination with PD-1 blockers, radiation, and chemotherapy. While approved, IL-2 retains significant toxicity, preventing its widespread use. The significant efforts undertaken to uncouple IL-2 toxicity from its anti-tumor function have been unsuccessful, and early phase clinical safety observed with PEGylated IL-10 was not met in a blinded Phase 3 trial. Deka Biosciences has engineered a novel molecule coupling wild-type IL-2 to a high affinity variant of Epstein Barr Viral (EBV) IL-10 via a scaffold (scFv) that binds to epidermal growth factor receptors (EGFR). This patented molecule, termed DK210 (EGFR), is retained at high levels within the tumor microenvironment for days after dosing. In addition to overlapping and non-redundant anti-tumor function, IL-10 reduces IL-2 mediated cytokine release syndrome risks and inhibits IL-2 mediated T regulatory cell proliferation. Methods: DK210 (EGFR) is being evaluated in an open-label, dose-escalation (Phase 1) study with 5 (0.025-0.3 mg/kg) monotherapy dose levels and (expansion cohorts) in combination with PD-1 blockers, or radiation or chemotherapy in patients with advanced solid tumors overexpressing EGFR. Key eligibility criteria include 1) confirmed progressive disease on at least one line of systemic treatment, 2) EGFR overexpression or amplification documented in histology reports, 3) at least a 4 week or 5 half-lives window since last treatment, and 4) excluding subjects with long QT syndrome, multiple myeloma, multiple sclerosis, myasthenia gravis or uncontrolled infectious, psychiatric, neurologic, or cancer disease. Plasma and tissue samples will be investigated for pharmacodynamic and predictive biomarkers and genetic signatures associated with IFN-gamma secretion, aiming to select subjects for treatment in Phase 2. Conclusion: Through successful coupling of wild-type IL-2 with a high affinity IL-10 and targeting directly to the tumor microenvironment, DK210 (EGFR) has the potential to harness IL-2 and IL-10’s known anti-cancer promise while reducing immunogenicity and toxicity risks enabling safe concomitant cytokine treatment with other anti-cancer modalities.

Keywords: cytokine, EGFR over expression, interleukine-2, interleukine-10, clinical trial

Procedia PDF Downloads 58

Authors: Elisangela Sobreira, Denise Teixeira

Abstract:

Visceral leishmaniasis is a public health problem in Brazil, it is the main reservoir dog. In the period 2012-2016 78 diagnoses were performed in dogs suspected. Blood samples were collected from the cephalic vein obtaining serum used for the indirect immunofluorescence test and enzyme-linked immunosorbent assay, while it collected a drop of blood for the rapid chromatographic immunoassay. Obtained in 32 dogs positive. The test is important for the control of this disease and is used routinely in the Zoonoses Control Center.

Keywords: Brazil, dogs, Leismaniasis, Zoonoses center

Procedia PDF Downloads 230

Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

Procedia PDF Downloads 116

Authors: Taleb Lotfi, Benarbia Maheidine, Allam Hamza, Boutira Fatima, Boukerche Abdelbaki

Abstract:

Introduction and purpose of the study: This is a retrospective single-center study with an analytical aim to determine the prognostic factors for relapse in patients treated with radiotherapy after total laryngectomy with lymph node dissection for laryngeal cancer at the Emir Abdelkader cancer center in Oran (Algeria). Material and methods: During the study period from January 2014 to December 2018, eighty-nine patients (n=89) with squamous cell carcinoma of the larynx were treated with postoperative radiotherapy. Relapse-free survival was studied in the univariate analysis according to pre-treatment criteria using Kaplan-Meier survival curves. We performed a univariate analysis to identify relapse factors. Statistically significant factors have been studied in the multifactorial analysis according to the Cox model. Results and statistical analysis: The average age was 62.7 years (40-86 years). It was a squamous cell carcinoma in all cases. Postoperatively, the tumor was classified as pT3 and pT4 in 93.3% of patients. Histological lymph node involvement was found in 36 cases (40.4%), with capsule rupture in 39% of cases, while the limits of surgical excision were microscopically infiltrated in 11 patients (12.3%). Chemotherapy concomitant with radiotherapy was used in 67.4% of patients. With a median follow-up of 57 months (23 to 104 months), the probabilities of relapse-free survival and five-year overall survival are 71.2% and 72.4%, respectively. The factors correlated with a high risk of relapse were locally advanced tumor stage pT4 (p=0.001), tumor site in case of subglottic extension (p=0.0003), infiltrated surgical limits R1 (p=0.001), l lymph node involvement (p=0.002), particularly in the event of lymph node capsular rupture (p=0.0003) as well as the time between surgery and adjuvant radiotherapy (p=0.001). However, in the subgroup analysis, the major prognostic factors for disease-free survival were subglottic tumor extension (p=0.001) and time from surgery to adjuvant radiotherapy (p=0.005). Conclusion: Combined surgery and postoperative radiation therapy are effective treatment modalities in the management of laryngeal cancer. Close cooperation of the entire cervicofacial oncology team is essential, expressed during a multidisciplinary consultation meeting, with the need to respect the time between surgery and radiotherapy.

Keywords: laryngeal cancer, laryngectomy, postoperative radiotherapy, survival

Procedia PDF Downloads 78

Authors: George Zhou, Yunchan Chen, Candace Chien

Abstract:

Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

Procedia PDF Downloads 58

Authors: Abder-Rahman Ali, Antoine Vacavant, Manuel Grand-Brochier, Adélaïde Albouy-Kissi, Jean-Yves Boire

Abstract:

In this paper, we present a new segmentation approach for liver lesions in regions of interest within MRI (Magnetic Resonance Imaging). This approach, based on a two-cluster Fuzzy C-Means methodology, considers the parameter variable compactness to handle uncertainty. Fine boundaries are detected by a local recursive merging of ambiguous pixels with a sequential forward floating selection with Zernike moments. The method has been tested on both synthetic and real images. When applied on synthetic images, the proposed approach provides good performance, segmentations obtained are accurate, their shape is consistent with the ground truth, and the extracted information is reliable. The results obtained on MR images confirm such observations. Our approach allows, even for difficult cases of MR images, to extract a segmentation with good performance in terms of accuracy and shape, which implies that the geometry of the tumor is preserved for further clinical activities (such as automatic extraction of pharmaco-kinetics properties, lesion characterization, etc).

Keywords: defuzzification, floating search, fuzzy clustering, Zernike moments

Procedia PDF Downloads 425

Authors: Temesgen Oljira, Olugbenga Akindeji Okunlola, Akinade Shadrach Olatunji, Dereje Ayalew, Bekele A. Bedada, Tasin Godlove Bafon

Abstract:

The Megele area gold-bearing Neoproterozoic rocks in the Western Ethiopian Shield has been under exploration for the last few decades. The geochemical and ore petrological characterization of the gold-bearing granite gneiss and associated quartz vein is crucial in understanding the gold's genesis. The present study concerns the ore petrological, geochemical, and stable O2 and S characterization of the gold-bearing granite gneiss and associated quartz vein. This area is known for its long history of placer gold mining. The presence of quartz veins of different generations and orientations, visible sulfide mineralization, and oxidation suggests that the Megele area is geologically fertile for mineralization. The Au and base metals analysis also indicate that Megele area rocks are characterized by Cu (2-22 ppm av. 7.83 ppm), Zn (2-53 ppm av. 29.33 ppm), Co (1-27 ppm av. 13.33 ppm), Ni (2-16 ppm av. 10 ppm), Pb (5-10 ppm av. 8.33 ppm), Au (1-5 ppb av. 2.11 ppb), Ag (0.5 ppm), As (5-12 ppm av. 7.83 ppm), Cd (0.5ppm), Li (0.5 ppm), Mo (1-4 ppm av. 1.6 ppm), Sc (5-13 ppm av. 9.3 ppm), and Tl (10 ppm). The oxygen isotope (δ18O) values of gold-bearing granite gneiss and associated quartz veins range from +8.6 to +11.5 ‰, suggesting the mixing of metamorphic water with magmatic water within the ore-forming fluid. The Sulfur isotope (δ34S) values of gold-bearing granite gneiss range from -1.92 to -0.45 ‰ (mean value of -1.13 ‰) indicating the narrow range of value. This suggests that the sulfides have been precipitated from the fluid system originating from a single source of the magmatic component under sulfur isotopic fractionation equilibrium condition. The tectonic setting of the host rocks, the occurrence of ore bodies, mineral assemblages of the host rocks and proposed ore-forming fluids of the Megele area gold prospects have similarities with features of orogenic gold deposit. The δ18O and δ34S isotopic values also suggested a metamorphic origin with the magmatic components. Thus, the Megele gold prospect could be related to an orogenic gold deposit related to metamorphism and associated intrusions.

Keywords: fluid source, gold mineralization, oxygen isotope, stable isotope, sulfur isotope

Procedia PDF Downloads 53

Authors: A. Y. Tsidulko, T. M. Pankova, E. V. Grigorieva

Abstract:

High-grade gliomas are the most frequent and most aggressive brain tumors which are characterized by active invasion of tumor cells into the surrounding brain tissue, where the extracellular matrix (ECM) plays a crucial role. Disruption of ECM can be involved in anticancer drugs effectiveness, side-effects and also in tumor relapses. The anti-inflammatory agent dexamethasone is a common drug used during high-grade glioma treatment for alleviating cerebral edema. Although dexamethasone is widely used in the clinic, its effects on normal brain tissue ECM remain poorly investigated. It is known that proteoglycans (PGs) are a major component of the extracellular matrix in the central nervous system. In our work, we studied the effects of dexamethasone on the ECM proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, NG2, decorin, biglican, lumican) using RT-PCR in the experimental animal model. It was shown that proteoglycans in rat brain have age-specific expression patterns. In early post-natal rat brain (8 days old rat pups) overall PGs expression was quite high and mainly expressed PGs were biglycan, decorin, and syndecan-1. The overall transcriptional activity of PGs in adult rat brain is 1.5-fold decreased compared to post-natal brain. The expression pattern was changed as well with biglycan, decorin, syndecan-1, glypican-1 and brevican becoming almost equally expressed. PGs expression patterns create a specific tissue microenvironment that differs in developing and adult brain. Dexamethasone regimen close to the one used in the clinic during high-grade glioma treatment significantly affects proteoglycans expression. It was shown that overall PGs transcription activity is 1.5-2-folds increased after dexamethasone treatment. The most up-regulated PGs were biglycan, decorin, and lumican. The PGs expression pattern in adult brain changed after treatment becoming quite close to the expression pattern in developing brain. It is known that microenvironment in developing tissues promotes cells proliferation while in adult tissues proliferation is usually suppressed. The changes occurring in the adult brain after dexamethasone treatment may lead to re-activation of cell proliferation due to signals from changed microenvironment. Taken together obtained data show that dexamethasone treatment significantly affects the normal brain ECM, creating the appropriate microenvironment for tumor cells proliferation and thus can reduce the effectiveness of anticancer treatment and promote tumor relapses. This work has been supported by a Russian Science Foundation (RSF Grant 16-15-10243)

Keywords: dexamthasone, extracellular matrix, glioma, proteoglycan

Procedia PDF Downloads 168

Authors: Balasooriya B. M. C. M., Sujeeva N., Thowfeek Z., Siddiqa Omo, Liyanagunawardana J. E., Jayawardana Saiu, Manathunga S. S., Katulanda G. W.

Abstract:

Introduction and objectives: Adrenal venous sampling (AVS) is the gold standard to discriminate unilateral primary aldosteronism (UPA) from bilateral disease (BPA). AVS is technically demanding and only performed in a limited number of centers worldwide. To the best of our knowledge, Except for one study conducted in India, no other research studies on this area have been conducted in South Asia. This study aimed to evaluate the effectiveness of AVS in the management of primary aldosteronism. Methods: A total of 32 patients who underwent AVS at the National Hospital of Sri Lanka from April 2021 to April 2023 were enrolled. Demographic, clinical and laboratory data were obtained retrospectively. A procedure was considered successful when adequate cannulation of both adrenal veins was demonstrated. Cortisol gradient across the adrenal vein (AV) and the peripheral vein was used to establish the success of venous cannulation. Lateralization was determined by the aldosterone gradient between the two sides. Continuous and categorical variables were summarized with mean, SD, and proportions, respectively. The mean and standard deviation of the contralateral suppression index (CSI) were estimated with an intercept-only Bayesian inference model. Results: Of the 32 patients, the average age was 52.47 +26.14 and 19 (59.4%) were males. Both AVs were successfully cannulated in 12 (37.5%). Among them, lateralization was demonstrated in 11(91.7%), and one was diagnosed as a bilateral disease. There were no total failures. Right AV cannulation was unsuccessful in 18 (56.25%), of which lateralization was demonstrated in 9 (50%), and others were inconclusive. Left AV cannulation was unsuccessful only in 2 (6.25%); one was lateralized, and the other remained inconclusive. The estimated mean of the CSI was 0.33 (89% credible interval 0.11-0.86). Seven patients underwent unilateral adrenalectomy and demonstrated significant improvement in blood pressure during follow-up. Two patients await surgery. Others were treated medically. Conclusions: Despite failure due to procedural difficulties, AVS remained useful in the management of patients with PA. Moreover, the success of the procedure needs experienced hands and advanced equipment to achieve optimal outcomes in PA.

Keywords: adrenal venous sampling, lateralization, contralateral suppression index, primary aldosteronism

Procedia PDF Downloads 37

Authors: E.A. Kuchma

Abstract:

Photodynamic therapy (PDT) is considered an alternative and minimally invasive cancer treatment modality compared to chemotherapy and radiation therapy. PDT includes three main components: a photosensitizer (PS), oxygen, and a light source. PS is injected into the patient's body and then selectively accumulates in the tumor. However, the light used in PDT (spectral range 400–700 nm) is limited to superficial lesions, and the light penetration depth does not exceed a few cm. The problem of PDT (poor visible light transmission) can be solved by using X-rays. The penetration depth of X-rays is ten times greater than that of visible light. Therefore, X-ray radiation easily penetrates through the tissues of the body. The aim of this work is to develop universal nanocomposites for X-ray photodynamic therapy of deep and superficial tumors using scintillation nanoparticles of gadolinium fluoride (GdF3), doped with Tb3+, coated with a biocompatible coating (PEG) and photosensitizer RB (Rose Bengal). PEG@GdF3:Tb3+(15%) – RB could be used as an effective X-ray, UV, and photoluminescent mediator to excite a photosensitizer for generating reactive oxygen species (ROS) to kill tumor cells via photodynamic therapy. GdF3 nanoparticles can also be used as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI).

Keywords: X-ray induced photodynamic therapy, scintillating nanoparticle, radiosensitizer, photosensitizer

Procedia PDF Downloads 54

Authors: J. Szpor, K. Witczak, M. Storman, A. Orchel, D. Hodorowicz-Zaniewska, K. Okoń, A. Klimkowska

Abstract:

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease. In comparison to fine needle aspiration (FNA), CNB provides more architectural information allowing for the evaluation of prognostic and predictive factors for breast cancer, including histological grade—one of three prognostic factors used to calculate the Nottingham Prognostic Index. Several studies have previously described the concordance rate between CNB and surgical excision specimen in determination of histological grade (HG). The concordance rate previously ascribed to overall grade varies widely across literature, ranging from 59-91%. The aim of this study is to see how the data looks like in material at authors’ institution and are the results as compared to those described in previous literature. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. Both materials were evaluated for the determination of histological grade (scale from 1 to 3). HG was assessed only in core needle biopsies containing at least 10 well preserved HPF with invasive tumor. The degree of concordance between CNB and surgical excision specimen for the determination of tumor grade was assessed by Cohen’s kappa coefficient. The level of agreement between core needle biopsy and surgical resection specimen for overall histologic grading was 73% (113 of 155 cases). CNB correctly predicted the grade of the surgical excision specimen in 21 cases for grade 1 tumors (Kappa coefficient κ = 0.525 95% CI (0.3634; 0.6818), 52 cases for grade 2 (Kappa coefficient κ = 0.5652 95% CI (0.458; 0.667) and 40 cases for stage 3 tumors (Kappa coefficient κ = 0.6154 95% CI (0.4862; 0.7309). The highest level of agreement was observed in grade 3 malignancies. In 9 of 42 (21%) discordant cases, the grade was higher in the CNB than in the surgical excision. This composed 6% of the overall discordance. These results correspond to the noted in the literature, showing that underestimation occurs more frequently than overestimation. This study shows that authors’ institution’s histologic grading of CNBs and surgical excisions shows a fairly good correlation and is consistent with findings in previous reports. Despite the inevitable limitations of CNB, CNB is an effective method for diagnosing breast cancer and managing treatment options. Assessment of tumour grade by CNB is useful for the planning of treatment, so in authors’ opinion it is worthy to implement it in daily practice.

Keywords: breast cancer, concordance, core needle biopsy, histological grade

Procedia PDF Downloads 208

Authors: Hossein Bazmara, Kaamran Raahemifar, Mostafa Sefidgar, Madjid Soltani

Abstract:

Angiogenesis is formation of new blood vessels from existing vessels. Due to flow of blood in vessels, during angiogenesis, blood flow plays an important role in regulating the angiogenesis process. Multiple mathematical models of angiogenesis have been proposed to simulate the formation of the complicated network of capillaries around a tumor. In this work, a multi-scale model of angiogenesis is developed to show the effect of blood flow on capillaries and network formation. This model spans multiple temporal and spatial scales, i.e. intracellular (molecular), cellular, and extracellular (tissue) scales. In intracellular or molecular scale, the signaling cascade of endothelial cells is obtained. Two main stages in development of a vessel are considered. In the first stage, single sprouts are extended toward the tumor. In this stage, the main regulator of endothelial cells behavior is the signals from extracellular matrix. After anastomosis and formation of closed loops, blood flow starts in the capillaries. In this stage, blood flow induced signals regulate endothelial cells behaviors. In cellular scale, growth and migration of endothelial cells is modeled with a discrete lattice Monte Carlo method called cellular Pott's model (CPM). In extracellular (tissue) scale, diffusion of tumor angiogenic factors in the extracellular matrix, formation of closed loops (anastomosis), and shear stress induced by blood flow is considered. The model is able to simulate the formation of a closed loop and its extension. The results are validated against experimental data. The results show that, without blood flow, the capillaries are not able to maintain their integrity.

Keywords: angiogenesis, endothelial cells, multi-scale model, cellular Pott's model, signaling cascade

Procedia PDF Downloads 399

Authors: Leander Van Neste, Kirk Wojno

Abstract:

The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

Procedia PDF Downloads 136

Authors: Emily Moore, Andrew Gaukroger, Matthew Solan, Lucy Bailey, Alexandra Boxall, Andrew Carne, Chintu Gadamsetty, Charlotte Morley, Katy Western, Iwona Kolodziejczyk

Abstract:

Introduction: Rupture of the Achilles tendon is common and has a long recovery period. Most cases are managed non-operatively. Foot and Ankle Surgeons advise an ultrasound scan to check the gap between the torn ends. A large gap (with the ankle in equinus) is a relative indication for surgery. The definitive decision regarding surgical versus non-operative management can only be made once an ultrasound scan is undertaken and the patient is subsequently reviewed by a Foot and Ankle surgeon. To get to this point, the patient journey involves several hospital departments. In nearby trusts, patients reattend for a scan and go to the plaster room both before and after the ultrasound for removal and re-application of the cast. At a third visit to the hospital, the surgeon and patient discuss options for definitive treatment. It may take 2-3 weeks from the initial Emergency Department visit before the final treatment decision is made. This “wasted time” is ultimately added to the recovery period for the patient. In this hospital, Achilles rupture patients are seen in a weekly multidisciplinary OneStop Heel Pain clinic. This pathway was already efficient but subject to occasional frustrating delays if a key staff member was absent. A new pathway was introduced with the goal to reduce delays to a definitive treatment plan. Method: A retrospective series of Achilles tendon ruptures managed according to the 2019 protocol was identified. Time taken from the Emergency Department to have both an ultrasound scan and specialist Foot and Ankle surgical review were calculated. 30 consecutive patients were treated with our new pathway and prospectively followed. The time taken for a scan and for specialist review were compared to the 30 consecutive cases from the 2019 (pre-COVID) cohort. The new pathway includes 1. A new contoured splint applied to the front of the injured limb held with a bandage. This can be removed and replaced (unlike a plaster cast) in the ultrasound department, removing the need for plaster room visits. 2. Urgent triage to a Foot and Ankle specialist. 3. Ultrasound scan for assessment of rupture gap and deep vein thrombosis check. 4. Early decision regarding surgery. Transfer to weight bearing in a prosthetic boot in equinuswithout waiting for the once-a-week clinic. 5. Extended oral VTE prophylaxis. Results: The time taken for a patient to have both an ultrasound scan and specialist review fell > 50%. All patients in the new pathway reached a definitive treatment decision within one week. There were no significant differences in patient demographics or rates of surgical vs non-operative treatment. The mean time from Emergency Department visit to specialist review and ultrasound scan fell from 8.7 days (old protocol) to 2.9 days (new pathway). The maximum time for this fell from 23 days (old protocol) to 6 days (new pathway). Conclusion: Teamwork and innovation have improved the experience for patients with an Achilles tendon rupture. The new pathway brings many advantages - reduced time in the Emergency Department, fewer hospital visits, less time using crutches and reduced overall recovery time.

Keywords: orthopaedics, achilles rupture, ultrasound, innovation

Procedia PDF Downloads 91

Authors: Moizza Tahir, Uzma Bashir, Aisha Akhtar, Zainab Ansari, Sameen Ansari, Muhammad Ali Tahir

Abstract:

Cancer burden has globally increased. Among cutaneous cancers basal cell carcinoma constitute vast majority of skin cancer. There is need for appropriate diagnostic, therapeutic and prognostic significance evaluation for skin cancers Present study report intraoperative frozen section (FS) histopathological clearance for excision of BCC in a tertiary care center and find the frequency of involvement of surgical margin with reference to anatomical site, with size and surgical technique. It was prospective open label interventional study conducted at Dermatology department of tertiary care hospital Rawalpindi Pakistan in lais on with histopathology department from January 2023 to April 2024. Total of thirty-six (n = 36) patients between age 45-80 years with basal cell carcinoma of 10-20mm on face were included following inclusion exclusion criteria by purposive sampling technique. Informed consent was taken. Surgical excision was performed and intraoperative frozen section histopathology clearance of tumor margin was taken from histopathologist on telephone. Surgical reconstruction was done. Final Histopathology report was reexamined on day 10th for margin and depth clearance. Descriptive statistics were calculated for age, gender, sun exposure, reconstructive technique, anatomical site, and tumor free margin report on frozen section analysis. Chi square test was employed for statistical significance of involvement of surgical margin with reference to anatomical site, size and decision on reconstructive surgical technique, p value of <0.05 was considered significant. Total of 36 patients of BCC were enrolled, males 12 (33.3%) and females were 24 (66.6%). Age ranged from 45 year to 80 year mean of 58.36 ±SD7.8. Size of BCC ranged from 10mm to 35mm mean of 25mm ±SD 0.63. Morphology was nodular 18 (50%), superficial spreading 11(30.6%), morphoeic 1 (2.8%) and ulcerative in 6(16.7%) cases. Intraoperative frozen section for histopathological margin clearance with 2-3 mm safety margin and surgical technique has p-value0.51, for anatomical site p value 0.24 and size p-0.84. Intraoperative frozen section (FS) histopathological clearance for BCC face with 2-3mm safety margin with reference to reconstructive technique, anatomical site and size of BCC were insignificant.

Keywords: basal cell carcinoma, tumor free amrgin, basal cell carcinoma and frozen section, safety margin

Procedia PDF Downloads 15

Authors: Chung-Ming Lo, Kevin Li-Chun Hsieh

Abstract:

The central nervous system in the World Health Organization defines grade 2, 3, 4 gliomas according to the aggressiveness. For brain tumors, using image examination would have a lower risk than biopsy. Besides, it is a challenge to extract relevant tissues from biopsy operation. Observing the whole tumor structure and composition can provide a more objective assessment. This study further proposed a computer-aided diagnosis (CAD) system based on a convolutional neural network to quantitatively evaluate a tumor's malignancy from brain magnetic resonance imaging. A total of 30 grade 2, 43 grade 3, and 57 grade 4 gliomas were collected in the experiment. Transferred parameters from AlexNet were fine-tuned to classify the target brain tumors and achieved an accuracy of 98% and an area under the receiver operating characteristics curve (Az) of 0.99. Without pre-trained features, only 61% of accuracy was obtained. The proposed convolutional neural network can accurately and efficiently classify grade 2, 3, and 4 gliomas. The promising accuracy can provide diagnostic suggestions to radiologists in the clinic.

Keywords: convolutional neural network, computer-aided diagnosis, glioblastoma, magnetic resonance imaging

Procedia PDF Downloads 121