Malignant Research Articles

Primary malignant perivascular epithelioid cell tumors with TFE3 rearrangement of bone: a clinicopathological analysis of two cases

Primary malignant perivascular epithelioid cell tumors with TFE3 rearrangement of bone: a clinicopathological analysis of two cases

Pitfalls in the Cytological Diagnosis of Nodal Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a hematopoietic neoplasm characterized by malignant Reed-Sternberg (RS) cells in an inflammatory background. Although the cytological features of HL are well elucidated in literature, yet many postulated factors cause its misdiagnosis. This study aims to assess the diagnostic reliability of fine needle aspiration cytology (FNAC) in HL and evaluate the factors contributing to a false-negative and false-positive diagnosis, taking histopathology as the gold standard. This was a retrospective study in which 47 cases of HL diagnosed on histopathology were compared with their prior cytological diagnosis. The patient's age ranged from 3 to 80 years (median: 36 years) with a M:F ratio of 2.9:1. Lymph node aspirations were performed from multiple anatomical sites, out of which the cervical was the most common (57.8%). FNAC was inconclusive in two cases due to unsatisfactory smears. The false-negative diagnosis of reactive lymphadenitis was given in four cases, and false-positive in four cases, which included three cases of non-HL, and one case of malignant small round blue cell tumor. The overall diagnostic accuracy of FNAC in the diagnosis of HL was 82.2%. The cytological diagnosis of HL can be challenging when classic RS cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node, and misinterpretation. A thorough clinical examination with evaluation of FNAC smears from multiple areas, and ancillary tests help improve the diagnostic accuracy of cytological diagnosis.

Paneth cell differentiation associated with neoadjuvant therapy in esophageal adenocarcinoma.

Paneth cells and Paneth cell metaplasia are well-known in pathology as foundational components in the gastrointestinal system. When within malignant cells (Paneth cell differentiation [PCD]), however, the function and significance of these cells is less well understood. Here, we present findings from the first study focused on PCD in postneoadjuvant esophageal adenocarcinoma (EAC) resection specimens. Patients with EAC treated with neoadjuvant chemoradioation and followed by esophagectomy between 2012 and 2018 in our institution were retrospectively evaluated. A tissue microarray was constructed, and special and immunohistochemical stains were performed. A total of 64 cases were collected, of which 8 had PCD, as highlighted by periodic acid-Schiff with diastase staining. Adenocarcinomas with PCD were more commonly seen in patients 60 to 70 years of age and typically had a poorly differentiated morphology, observationally fewer stromal mucinous changes, and less lymph node metastasis. β-catenin activation induced by neoadjuvant therapy was more frequent in the PCD-positive cases. Patients with PCD-positive disease had low programmed cell death 1 ligand 1 levels, no positive or equivocal ERBB2 (HER2) expression, and low CD8-positive T-cell infiltration; they were also mismatch repair proficient. Patients with PCD-positive disease showed a survival pattern inferior to that of patients with PCD-negative disease. When induced by neoadjuvant therapy in EAC, PCD is associated with high β-catenin activation, less expression of targetable biomarkers, and a potentially worse clinical prognosis.

Peptide hydrogel based electrochemical biosensor for simultaneous monitoring ofH2O2 and NO released from three-dimensional cultured breast cancer cells.

Anantifouling peptide hydrogel-based electrochemical biosensor was developedfor real-time monitoring of hydrogen peroxide (H2O2) and nitric oxide (NO) released by 3D cultured breast cancer cells upon drug stimulation. Platinum nanoparticles (Pt NPs) were electrodeposited on titanium mesh (Pt NPs/TM) to enhance sensitivity and shown topossess excellent electrocatalytic ability toward H2O2 and NO. The composite hydrogel formed by co-assembling of N-fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) and a fluorine methoxycarbonyl group-functionalized Lys-(Fmoc)-Asp was coated on Pt NPs/TM electrode surface to provide cellular scaffolding. Their favorable biocompatibility promoted cell adhesion and growth, while good hydrophilicity endowed the sensor with greatly enhanced antifouling capability in complex cell culture environments. The biosensor successfully determined H2O2 and NO secretion from both non-metastatic and metastatic breast cancer cells in real time. Our results demonstrated robust associations between reactive oxygen species (ROS) and reactive nitrogen species (RNS) production and cell malignancy, with the main difference in oxidative stress between the two subtypes of cells being NO release, particularly emphasizing RNS's critical leading in driving cancer metastasis and invasion progression. This sensor holds great potential for cell-release research under the in vivo-like microenvironment and could reveal RNS as an attractive therapeutic target for treating breast cancer.

The foremost and greatest barrier to end-stage heart failure treatment: the impact of caregiver shortage.

We examined the number of patients abandoning cardiac replacement therapy due to the inability to secure a designated caregiver. At Osaka University Hospital Heart Center, when we receive a consultation for a patient with severe heart failure from another hospital, a heart failure team makes a visit to the referring hospital as soon as possible. We retrospectively analyzed this hospital-visit database. We received 199 severe heart failure consultations from 2016-2023. Issues identified during hospital visits included age ≥ 65years (8%), inability to confirm the patient's intention (8.5%), and explicit refusal of therapy (2.5%). Medical problems included multiple organ failure (18.1%), obesity (13.1%), diabetes (9.5%), malignancy (5.5%), chronic dialysis (1.0%), and other systemic diseases (12.6%). Adherence problems included poor medication compliance (3.5%), history of heavy drinking (2.5%), and smoking (2.0%). Social problems included inadequate family support in 16.1% of patients. Of the 199 patients, 95 (48.0%) proceeded to a heart transplant and LVAD indication review meeting at Osaka University Hospital. The remaining 104 patients (52.0%) did not proceed to the meeting. Reasons included improvement of heart failure with conservative treatment in 37 cases (35.6%), death before discussion in 21 cases (20.2%), medical contraindications in 18 cases (18.3%), lack of caregivers in 18 cases (18.3%; 9.5% of 199 cases), and patient refusal in 5 cases (4.8%). Approximately 10% of patients consulted at Osaka University Hospital Heart Center for severe heart failure abandoned cardiac replacement therapy due to the lack of caregivers.

Determination of Antioxidant, Cytotoxicity, and Anti-human Lung Cancer Properties of Silver Nanoparticles Green-Formulated by Foeniculum vulgare Extract Combined with Radiotherapy.

The current investigation involved the silver nanoparticles green synthesis utilizing the aqueous extract derived from the Foeniculum vulgare leaves (AgNPs@FV). The effectiveness of these newly developed nanoparticles in conjunction with radiotherapy was evaluated on lung cancer cells. The synthesized AgNPs@FV underwent characterization through various analytical techniques such as energy dispersive X-ray (EDX), field emission-scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and ultraviolet-visible (UV-Vis) spectrophotometry. The efficacy of AgNPs@FV in conjunction with radiotherapy against human lung cancer was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The AgNPs@FV exhibited a spherical morphology ranging in size from 10.16 to 42.74 nm. The EDX diagram of nanoparticles shows energy signals at 3.02 and 2.64 keV, which are attributed to Ag Lβ and Ag Lα, respectively. During the antioxidant evaluation, AgNPs@FV and butylated hydroxytoluene (BHT) displayed IC50 values of 166 and 59 µg/mL, respectively. The cells treated with AgNPs@FV in conjunction with radiotherapy were evaluated using the MTT assay over 48h to determine cytotoxicity and anti-human lung cancer characteristics on normal (human umbilical vein endothelial cell (HUVEC)) and lung cancer cells and exhibited IC50 values of 211, 166, and 296µg/mL against NCI-H2126, NCI-H1299, and NCI-H1437, respectively. Furthermore, the malignant lung cell viability decreased when treated with a combination of AgNPs@FV and radiotherapy. Based on the aforementioned findings, it is possible that the newly developed AgNPs@FV could serve as a novel chemotherapeutic medication or adjunct for addressing lung cancer following the completion of clinical trials involving human subjects.

Shear-wave elastography as a supplementary tool for axillary staging in patients undergoing breast cancer diagnosis

BackgroundPreoperative evaluation of axillary lymph node status is crucial for the selection of both systemic and surgical treatment in early breast cancer. This study assessed the particular role of additional shear wave elastography (SWE) in axillary staging in patients undergoing initial breast cancer diagnostics.MethodsOne hundred patients undergoing axillary lymph node biopsy due to a sonographically suspicious axillary lymph node were prospectively evaluated with SWE using virtual touch tissue imaging quantification (VTIQ). Mean values of tissue stiffness for axillary tissue and lymph node tissue were measured prior to core-cut biopsy of the lymph node. All lymph nodes were clip-marked during the biopsy. Cut-off values to differentiate between malignant and benign lymph nodes were defined using Youden’s index.ResultsLymph nodes with evidence of malignant tumor cells in the final pathological examination showed a significantly higher velocity as measured by SWE, with a mean velocity of 3.48 ± 1.58 m/s compared to 2.33 ± 0.62 m/s of benign lymph nodes (p < 0.0001). The statistically optimal cutoff to differentiate between malignant and benign lymph nodes was 2.66 m/s with a sensitivity of 69.8% and a specificity of 87.5%.ConclusionsLymph node metastases assessed with SWE showed significantly higher elasticity values compared to benign lymph nodes. Thus, SWE provides an additional useful and quantifiable parameter for the sonographic assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support the guidance of definitive biopsy work-up.Critical relevance statementShear-wave elastography provides an additional useful and quantifiable parameter for the assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support guiding the definitive biopsy work-up.Key PointsSWE is a quantifiable ultrasound parameter in breast cancer diagnosis.SWE shows a significantly higher velocity in malignant lymph nodes.SWE is useful in improving the sensitivity and specificity of axillary staging.Graphical

Growing teratoma syndrome: diagnostic challenges and outcomes.

The aim of this case report is to emphasize the significance of the growing teratoma syndrome. Growing teratoma syndrome is frequently misdiagnosed due to its low prevalence, with an estimated incidence of 19% among all immature ovarian teratomas and a lack of experience among healthcare professionals. It is characterized by the growth of benign tumoral tissue during or after chemotherapy for malignant germ cell tumors. Our case is about a 46-year-old patient diagnosed with an immature teratoma who was treated unsuccessfully with surgery and chemotherapy. The patient was then referred to our hospital for a second opinion, where this unknown entity was diagnosed and underwent complete surgical debulking, including abdominal wall resection and subsequent repair. Physicians need to be aware of rapidly growing masses during or after chemotherapy because early recognition of this syndrome is essential for the adequate treatment of our patients.

Importance and implementation of radiological modalities in the diagnostics of soft tissue tumors

Malignant soft tissue tumors, in particular, require amultimodal treatment concept involving interdisciplinary cooperation between radiologists, pathologists, surgeons and oncologists at special tumor centers. The foundations of the treatment decision are the imaging diagnostics and the diagnosis confirmation based on tissue samples. The (local) extent and growth behavior of atumor are among the most important findings of imaging as they have adirect influence on the surgical procedure. The most important diagnostic procedure here is magnetic resonance imaging (MRI). The T1-weighted and fat-suppressed sequences after i.v. contrast administration are used to visualize the extent of the tumor. In synopsis with diffusion-weighted and T2-weighted sequences, adifferentiation between vital tumor tissue and tumor necrosis is additionally possible. This also enables targeted sampling from vital tumor parts so that the patient can be assigned to the appropriate treatment concept as quickly as possible.

Temporal Optimization in the Synthesis of Multifunctional Nano Agents for Enhanced MRI Contrast, Hyperthermia Therapy, and ROS Generation.

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments. The objective of this investigation is to scrutinize the relationship between the reaction duration and the characteristics of carbon-doped silica core-shell iron oxide nanoparticles (CSIONPs). Specifically, we focus on CSIONP-12, CSIONP-24, and CSIONP-36, synthesized by using varying reaction periods. Through a comprehensive analysis, we primarily evaluate the impact of these formulations on T1 and T2 magnetic resonance imaging (MRI), aiming to elucidate their mechanisms and therapeutic potential in promoting hyperthermia and ROS-mediated cancer therapy. CSIONP-24 emerges as a compelling candidate due to its dual influence on magnetic hyperthermia and ROS generation, suggesting its promise in enhancing cancer treatment outcomes. Furthermore, the findings underscore the exceptional T1-T2 MRI capabilities of this technology, underscoring its versatility and efficacy in the nuanced realm of cancer theranostic.

Predicting prognosis and drug sensitivity in bladder cancer: an insight into Pan-programmed cell death patterns regulated by M6A modifications

The team aimed to explore the possible functional significance of M6A regulation in Pan-programmed cell death (PCD) among patients with bladder cancer (BLCA). In BLCA patients, the analysis was conducted on the13 patterns of programmed cell death (PCD) and the regulation of M6A. Transcriptome, genomics, and clinical data were collected from TCGA-BLCA, GEO32548, and IMvigor210. Consensus clustering analysis, functional enrichment analysis, and other prognostic tools were used to validate the Pan-PCD. Finally, in vitro experiments and transcription sequencing were performed to understand the potential influence of the PI3K pathway on Pan-PCD in BLCA patients. Diverse PCD patterns were simultaneously activated, and M6A regulators exhibited significant variability in bladder malignant tissues. The machine learning algorithm established an 8-gene M6A-related Pan-PCD signature. This signature was validated in three independent datasets, and BLCA patients with higher risk scores had worse prognosis. An unsupervised clustering approach identified activated and suppressed Pan-PCD subgroups of BLCA patients, with distinct responses to immunotherapy and drug sensitivity. In addition, the PI3K pathway was identified as a key mechanism for various forms of programmed cell death, encompassing apoptosis, pyroptosis, autophagy, and cell death dependent on lysosomes. This research revealed that the Pan-PCD model was a more promising approach for BLCA patients under M6A regulation. A new signature from M6A-related Pan-PCD was proposed, with prognostic value for survival or drug sensitivity. The PI3K pathway was a key mechanism for multiple PCDs in BLCA patients.

Delta-6 desaturase FADS2 is a tumor-promoting factor in cholangiocarcinoma.

Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced invivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.

Targeting MCM2 activates cancer-associated fibroblasts-like phenotype and affects chemo-resistance of liposarcoma cells against doxorubicin.

Liposarcoma is one of the most common soft tissue malignancies. We previously discovered upregulation of minichromosome maintenance 2 (MCM2) expression in liposarcoma tissues. Hereon, we attempt to clarify the biological influence and mechanisms of MCM2 in liposarcoma. The mRNA level of MCM2 expression was detected through the use of quantitative real-time PCR. Immunohistochemistry staining and western blot were employed to detect protein expression of MCM2. The protein expression of fibroblast-activation protein and α-smooth muscle actin was examined by immunofluorescence. Protein concentrations of interleukin (IL)-6, transforming growth factor β, and IL-8 were measured via ELISA. Furthermore, liposarcoma cell viability was assessed through cell counting kit-8 assay, and liposarcoma cell invasiveness and migration were evaluated through transwell assay. For assessing proliferation and apoptosis of liposarcoma cells, colony formation assay and flow cytometry were used. For constructing a mouse tumor model, SW872 cells were introduced into mouse flank via subcutaneous injection. MCM2 expression was boosted in liposarcoma tissues and cells when compared with the controls. MCM2-activated cancer-associated fibroblasts (CAFs)-like phenotype, presenting as increased fibroblast-activation protein expression, α-smooth muscle actin expression, cell migration, IL-6 concentration, IL-8 concentration, and transforming growth factor β concentration. Functional experiments indicated that MCM2-activated-CAFs facilitated proliferation, migration, and invasion of liposarcoma cells. Additionally, 1 μM doxorubicin treatment could not affect proliferation and apoptosis of liposarcoma cells, whereas combined use of MCM2 knockdown and 1 μM doxorubicin evidently repressed cell proliferation and promoted apoptosis. In vivo, silencing of MCM2 impaired tumor growth in mice. MCM2 overexpression promoted CAFs formation and tumor progression, showing potential value in treatment of liposarcoma.

Optimization of Gene Selection for Cancer Classification in High-Dimensional Data Using an Improved African Vultures Algorithm

This study presents a novel method, termed RBAVO-DE (Relief Binary African Vultures Optimization based on Differential Evolution), aimed at addressing the Gene Selection (GS) challenge in high-dimensional RNA-Seq data, specifically the rnaseqv2 lluminaHiSeq rnaseqv2 un edu Level 3 RSEM genes normalized dataset, which contains over 20,000 genes. RNA Sequencing (RNA-Seq) is a transformative approach that enables the comprehensive quantification and characterization of gene expressions, surpassing the capabilities of micro-array technologies by offering a more detailed view of RNA-Seq gene expression data. Quantitative gene expression analysis can be pivotal in identifying genes that differentiate normal from malignant tissues. However, managing these high-dimensional dense matrix data presents significant challenges. The RBAVO-DE algorithm is designed to meticulously select the most informative genes from a dataset comprising more than 20,000 genes and assess their relevance across twenty-two cancer datasets. To determine the effectiveness of the selected genes, this study employs the Support Vector Machine (SVM) and k-Nearest Neighbor (k-NN) classifiers. Compared to binary versions of widely recognized meta-heuristic algorithms, RBAVO-DE demonstrates superior performance. According to Wilcoxon’s rank-sum test, with a 5% significance level, RBAVO-DE achieves up to 100% classification accuracy and reduces the feature size by up to 98% in most of the twenty-two cancer datasets examined. This advancement underscores the potential of RBAVO-DE to enhance the precision of gene selection for cancer research, thereby facilitating more accurate and efficient identification of key genetic markers.

Advancements and challenges in CAR T cell therapy in autoimmune diseases.

Chimeric antigen receptor (CAR) T cells are highly effective at targeting and eliminating cells of the B cell lineage. CAR T cell therapy has become a standard-of-care treatment for patients with relapsed or refractory B cell malignancies. In addition, the administration of genetically modified T cells with the capacity to deplete B cells and/or plasma cells has tremendous therapeutic potential in autoimmune diseases. In the past few years, CD19-based and B cell maturation antigen (BCMA)-based CAR T cell therapies have been applied to various B cell-mediated autoimmune diseases including systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis and multiple sclerosis. The scientific rationale behind this approach is that deep depletion of B cells, including autoreactive B cell clones, could restore normal immune function, referred to as an immune reset. In this Review, we discuss important aspects of CAR T cell therapy in autoimmune disease, including considerations relating to patient selection, safety, efficacy and medical management. These considerations are based on the early experiences of CAR T cell therapy in autoimmune diseases, and as the field of CAR T cell therapy in autoimmune diseases continues to rapidly evolve, these issues will remain subject to ongoing refinement and adaptation.

Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment

The combination of cisplatin and pemetrexed remains the gold standard chemotherapy for malignant pleural mesothelioma (MPM), although resistance and poor response pose a significant challenge. Cytidine deaminase (CDA) is a key enzyme in the nucleotide salvage pathway and is involved in the adaptive stress response to chemotherapy. The cytidine analog capecitabine and its metabolite 5′-deoxy-5-fluorocytidine (5’-DFCR) are converted via CDA to 5-fluorouracil, which affects DNA and RNA metabolism. This study investigated a schedule-dependent treatment strategy, proposing that initial chemotherapy induces CDA expression, sensitizing cells to subsequent capecitabine treatment. Basal CDA protein expression was low in different mesothelioma cell lines but increased in the corresponding xenografts. Standard chemotherapy increased CDA protein levels in MPM cells in vitro and in vivo in a schedule-dependent manner. This was associated with epithelial-to-mesenchymal transition and with HIF-1alpha expression at the transcriptional level. In addition, pretreatment with cisplatin and pemetrexed in combination sensitized MPM xenografts to capecitabine. Analysis of a tissue microarray (TMA) consisting of samples from 98 human MPM patients revealed that most human MPM samples had negative CDA expression. While survival curves based on CDA expression in matched samples clearly separated, significance was not reached due to the limited sample size. In non-matched samples, CDA expression before but not after neoadjuvant therapy was significantly associated with worse overall survival. In conclusion, chemotherapy increases CDA expression in xenografts, which is consistent with our in vitro results in MPM and lung cancer. A subset of matched patient samples showed increased CDA expression after therapy, suggesting that a schedule-dependent treatment strategy based on chemotherapy and capecitabine may benefit a selected MPM patient population.

Immune profiling and functional analysis of NK and T cells in ataxia telangiectasia

Ataxia telangiectasia (AT) is a rare autosomal-recessive disorder characterized by profound neurodegeneration, combined immunodeficiency, and an increased risk for malignant diseases. Treatment options for AT are limited, and the long-term survival prognosis for patients remains grim, primarily due to the emergence of chronic respiratory pathologies, malignancies, and neurological complications. Understanding the dysregulation of the immune system in AT is fundamental for the development of novel treatment strategies. In this context, we performed a retrospective longitudinal immunemonitoring of lymphocyte subset distribution in a cohort of AT patients (n = 65). Furthermore, we performed FACS analyses of peripheral blood mononuclear cells from a subgroup of 12 AT patients to examine NK and T cells for the expression of activating and functional markers. We observed reduced levels of peripheral blood CD3+CD8+ cytotoxic T cells, CD3+CD4+ T helper cells, and CD19+ B cells, whereas the amount of CD3−-CD56+ NK cells and CD3+CD56+ NKT-like cells was similar compared with age-matched controls. Notably, there was no association between the age-dependent kinetic of T-, B-, or NK-cell counts and the occurrence of malignancy in AT patients. Additionally, our results indicate an altered NK- and T-cell response to cytokine stimulation in AT with increased levels of TRAIL, FasL, and CD16 expression in NK cells, as well as an elevated activation level of T cells in AT with notably higher expression levels of IFN-γ, CD107a, TRAIL, and FasL. Together, these findings imply function alterations in AT lymphocytes, specifically in T and NK cells, shedding light on potential pathways for innovative therapies.

The effect of reconstruction algorithms on semi-quantitative measurements in 18F-FDG PET/CT imaging.

This study was carried out to understand whether Q.Clear and ordered subset expectation maximization (OSEM), reconstruction algorithms used in fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) applications, and parameters such as time of flight (TOF) and point spread function (PSF) cause different results in semi-quantitative measurements. Raw PET data of 264 patients who were referred to 18F-FDG PET/CT imaging with the purpose of evaluation of known or suspicious malignant disease were reconstructed separately with Q.Clear (GE Healthcare), a BPL, an OSEM algorithm, PSF (SharpIR®) and TOF (VUE Point FX®) methods. Each patient's liver, mediastinal blood pool, metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake values (SUV) (SUVmax, SUVmean, and SUVpeak) of a total of 264 lesions selected from the patients were performed. β350+ToF yielded higher measurement results than all other variables for all of the lesion SUVmax, lesion SUVmean, L/AP SUVmax, and L/AP SUVmean parameters. OSEM+ToF and OSEM+TOF+PSF algorithms yielded higher mean and median SUVmax values for the reference structures (liver and mediastinum) and for lesions SUVmax and SUVmean values were statistically significantly lower than the β350+ToF method. The method with the lowest mean value for the L/Liver SUVmax variable was OSEM+ToF 4iter16ss (mean=1.76), while the method with the highest mean value was β350+ToF (mean=2.26). β350+ToF was the reconstruction method with the highest ratios for L/AP SUVmax and SUVmean for both lesions below and above 1 cm. β350+ToF algorithm had also statistically significantly higher results for these variables compared to all other parameters in malignant lesions. When comparing 18F-FDG PET/CT images, the use of different reconstruction algorithms may lead to misleading results, especially in the evaluation of response to treatment of malignancies.

Microwave dielectric properties of normal, fibroelastotic, and malignant human lung tissue.

Technological development of microwave treatment and detection techniques for lung cancer requires accurate and comprehensive knowledge of the microwave dielectric properties of human lung tissue. We characterize the dielectric properties of room temperature human lung tissue from 0.5 to 10 GHz for three lung tissue groups: normal, fibroelastotic, and malignant. We fit a two-pole Debye model to the measured frequency-dependent complex permittivity and calculate the median Debye parameters for the three groups. We find that malignant lung tissue is approximately 10% higher in relative permittivity and conductivity compared to normal lung tissue; this trend matches previously reported normal vs. malignant data for other biological tissues. There is little contrast between benign lung tissue with fibroelastosis and malignant lung tissue. We extrapolate our data from room temperature to 37οC using a temperature-dependence model for animal lung tissue and use the Maxwell-Garnett dielectric mixing model to predict the dielectric properties of inflation-dynamic human lung tissue; both approximations correspond with previously reported dielectric data of bovine and porcine lung tissue.

Management and Outcomes of Children with Malignant Germ Cell Tumor.

To assess the clinico-pathological features, management and outcomes, amongst extracranial malignant germ cell tumors (MGCTs) in children treated primarily at a tertiary care center in a resource-challenged nation. The prospectively maintained data for children below 14 y of age treated for extracranial MGCT from May 1994 to January 2023 was analyzed for patient characteristics, management, event-free survival (EFS) and overall survival (OS) and factors effecting survival. Events was defined as death, recurrence and progression. Multivariate logistic regression analysis was performed to identify the factors independently predicting unfavorable outcomes. One hundred and seventy-seven children (37% males) with a median (IQR) age at presentation of 30 mo (range 2-168 mo) were included. The cohort consisted of 87 (49%) extra-gonadal and 90 (51%) gonadal cases. Disease was metastatic at presentation in 48 (27%) with lungs being the most common site. Neoadjuvant chemotherapy (NACT) was given to 119 (67%) and finally 162/177 (92%) had undergone resection of the primary tumor. Endodermal sinus tumor (EST) was the commonest histological subtype in 141 children (73%). Twenty-two (12%) patients had died giving a 5-y OS of 84.7% (95% CI 78.3- 91.1). Recurrence occurred in 25 patients, and an additional 5 patients had progression giving a 5-y EFS of 69.9% (95% CI 62.5- 77.3). Stage III (p = 0.05), Stage IV (p = 0.006) and extra-gonadal site (p = 0.05) were significantly associated with poorer EFS. Children with MGCT have a favorable outcome with 5-y OS of 84.7% and EFS of 69.9%. Stage III and IV disease and extra-gonadal sites were independent predictors of a poor outcome.