Tumor Border Research Articles

Serous Ovarian Carcinoma: Detailed Analysis of Clinico-Pathological Characteristics as Prognostic Factors

Background/Objectives: Serous ovarian carcinoma (SOC) is the most common subtype of epithelial ovarian cancer, with high-grade (HGSOC) and low-grade (LGSOC) subtypes presenting distinct clinical behaviours. This study aimed to evaluate histopathologic features in SOC, correlating these with prognostic outcomes, and explore the potential clinical implications. Methods: We analysed 51 SOC cases for lymphovascular space invasion (LVSI), tumour border configuration (TBC), microvessel density (MVD), tumour budding (TB), the tumour–stroma ratio (TSR), the stromal type, tumour-infiltrating lymphocytes (TILs), and tertiary lymphoid structures (TLSs). A validation cohort of 54 SOC cases from The Cancer Genome Atlas (TCGA) was used for comparison. Results: In the discovery set, significant predictors of aggressive behaviour included LVSI, high MVD, high TB, and low TILs. These findings were validated in the validation set where the absence of TLSs, lower peritumoural TILs, immature stromal type, and low TSR were associated with worse survival outcomes. The stromal type was identified as an independent prognostic predictor in SOC across both datasets. Inter-observer variability analysis demonstrated substantial to almost perfect agreement for these features, ensuring the reproducibility of the findings. Conclusions: The histopathological evaluation of immune and stromal features, such as TILs, TLSs, TB, TSR, and stromal type, provides critical prognostic information for SOC. Incorporating these markers into routine pathological assessments could enhance risk stratification and guide treatment, offering practical utility, particularly in low-resource settings when molecular testing is not feasible.

Surgeon perspectives on a virtual reality platform for preoperative planning in complex bone sarcomas

Background and objectivesTreatment of primary bone and soft tissue sarcomas typically includes complete surgical resection with or without adjunctive modalities. Despite best efforts, for the most challenging clinical scenarios such as axial or pelvic sarcoma, five-year survival rates are reported to be between 27 and 40 %. Since quality of resection is a key determinant of oncologic outcomes, it is critical to preoperatively plan the surgical approach to improve resection accuracy, ensure sufficient surgical margins, and reduce the risk of local or metastatic recurrence. The computer conversion of 2-dimensional (2D) computerized tomography (CT) and magnetic resonance imaging (MRI) to a three-dimensional (3D) virtual reality (VR) avatar image may allow improved preoperative estimation of tumor size, location, adjacent anatomy, and spatial understanding of the tumor without relying on surgeon experience, memory, and imagination. The purpose of this study is to investigate the utility of a virtual reality platform in preoperative planning and surgical approach in a retrospective cohort of pelvic bone sarcoma cases. MethodsThe histopathology database at our institution was queried for all historical cases of bone and soft tissue sarcoma with surgical resection failure, defined as positive gross or microscopic margins. Four cases of pelvic bone sarcoma were chosen for retrospective review by fellowship-trained orthopedic tumor specialists. For each case, participants first studied conventional 2D preoperative CT images and answered a questionnaire pertaining to objective case parameters. Participants then interacted with case-specific 3D models while wearing a VR headset and answered the same questionnaire. The VR ‘avatar’ was created with custom-developed software. After using both modalities, participants completed a Likert-scale survey aiming to evaluate the VR technology's subjective impact on understanding tumor environment, surgical plan confidence, and its ability to improve communication with colleagues and patients. Four attending orthopedic oncologists, one orthopedic oncology fellow, and one senior orthopedic oncology resident participated in the study. ResultsFour cases of failed resection were evaluated by a group of both attending surgeons and a group of trainees composed of both residents and fellows. Tumor borders were clearly delineated in 0 % and 66.6 % cases when evaluating with conventional 2D imaging and VR, respectively. Participants changed adjacent structure involvement grade 22.2 % of the time after assessing involvement grade on the VR technology, with adjacent ligamentous structure grading changed most frequently in 55.5 % of cases. Users reported they would change the surgical approach or margins 44.4 % of the time after reviewing with VR technology. Initial 6 plane resection plans were changed in every user case. Subjective responses indicated that surgeons expressed more confidence in their approach, confidence with obtaining negative margins, and provided more detail regarding structures to be resected in specific planes. ConclusionPelvic tumors present unique surgical challenges due to complex 3D anatomy, the proximity of vital structures, consistency of the tumor, and the need to alter patient position during resection procedures. Using examples of failed pelvic bone sarcoma resections, our study found that VR imaging increased understanding of the tumor environment, characteristics, and ability to communicate with patients and colleagues.

Trp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer

Colorectal cancer CRC remains one of the leading causes of cancer-related deaths worldwide, with chronic intestinal inflammation identified as a major risk factor. Notably, the tumor suppressor TP53 undergoes mutation at higher rates and earlier stages during human inflammation-driven colon tumorigenesis than in sporadic cases. We investigated whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice. We examined azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis in wild-type Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice. Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence. All groups could develop invasive tumors, but knockouts displayed the most aggressive features. Unlike wild-type CRC, knockouts selectively showed increased populations of Lgr5+ colon cancer stem-like cells. Trp53 loss also boosted laminin, possibly facilitating the disruption of the tumor border. This study highlights how Trp53 deletion promotes the perfect storm of inflammation and stemness, driving colon cancer progression. Trp53 deletion dramatically shortened AOM/DSS latency and improved tumor induction efficiency, offering an excellent inflammation-driven CRC model.

Clinical and MRI findings in patients with pediatric optic pathway glioma presenting with initial leptomeningeal dissemination

AIMAlthough leptomeningeal dissemination (LMD) is a hallmark of malignant brain tumors, optic pathway glioma (OPG) of various grades can initially present with LMD, which is thenceforth interpreted as an aggressive tumor. In this study, we aimed to evaluate the clinical and imaging findings of pediatric OPG (POPG) patients who presented with initial LMD to ensure a prompt diagnosis and better outcomes. MATERIALS AND METHODSBetween 2000 and 2022, 35 pediatric patients with pathologically proven OPG who presented with and without LMD at our institute were retrospectively reviewed. We compared the demographic and histopathology characteristics, MRI features, and clinical outcomes of the initial LMD group and the non-LMD group. RESULTSCompared with those in the non-LMD group (n=27), POPGs in the LMD group (n=8) were more symmetrically midline-positioned (75% versus 22.2%, p=0.006) and had more ill-defined tumor borders (25% versus 0%, p=0.007), and patients were more likely to develop hydrocephalus (100% versus 63%, p=0.042). There was no significant difference regarding the histopathology (p=0.686) and outcome of tumor recurrence/progression (p=0.341). However, the mortality rate was higher in the LMD group than in the non-LMD group (62.5% versus 18.5%, p=0.016). CONCLUSIONSFeatures of a more symmetrical midline-positioned POPG with indistinct tumor borders and hydrocephalus are risk factors for initial LMD regardless of histopathology. Compared with those without initial LMD, patients with POPG with initial LMD had poorer outcomes, which may suggest the need for a more aggressive treatment protocol.

Clinicopathological characteristics of unicentric Castleman disease: A single-center experience of 12 patients

BackgroundCastleman disease (CD) is an uncommon lymphoproliferative disorder with distinct pathological characteristics. Unicentric Castleman disease (UCD) presents as a single lymph node enlargement, often without significant symptoms. Complete surgical resection is the standard treatment for UCD. This study aimed to explore the clinicopathological features of UCD in a Taiwanese population. MethodsWe retrospectively identified 12 patients with UCD who had undergone surgical treatment between January 1, 2006 and June 30, 2022 at the National Taiwan University Hospital. Clinical and radiological findings were retrieved from medical records. All available pathological slides were reviewed. ResultsThe patients’ mean age was 38.1 years (range, 17 to 69); five (41.7%) were male, and seven (58.3%) were female. Nearly all cases of UCD were in the mediastinum, except for one case in the neck. Most patients were asymptomatic and without abnormal laboratory test results. Computed tomography revealed well-defined tumor borders, contrast enhancement, and occasional calcification. Ten patients underwent en bloc tumor resection, while the remaining two underwent partial resection. Among them, seven (58.3%) underwent video-assisted thoracoscopic surgery (VATS), and four (33.3%) underwent thoracotomy. The mean follow-up duration was 92 months. The patients who underwent total resection had no recurrence. ConclusionDetailed clinicopathological information on UCD in the Taiwanese population is present in our article. Both complete and partial surgery are effective for treatment. VATS may be preferred over thoracotomy due to less operative time and bleeding.

Development and validation of a machine-learning model for preoperative risk of gastric gastrointestinal stromal tumors

BackgroundGastrointestinal stromal tumors (GISTs) have malignant potential, and treatment varies according to risk. However, no specific protocols exist to preoperatively assess the malignant potential of gastric stromal tumors (gGISTs). This study aimed to use machine learning (ML) to develop and validate clinically relevant preoperative models to predict the malignant potential of gGISTs. MethodsWe screened patients diagnosed with gGISTs at the Affiliated Hospital of North Sichuan Medical College. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to identify risk factors. Subsequently, an ensemble of ML models was deployed to determine the optimal classifier. Additionally, we harnessed SHapley Additive exPlanations (SHAP) for tailored risk profiling. ResultsWe enrolled 318 patients with gGISTs. Utilizing LASSO regression and multifactorial logistic regression, we analyzed the training dataset, revealing that the presence of endoscopic ultrasound (EUS) high-risk features, tumor border clarity, tumor diameter, and monocyte-to-lymphocyte ratio (MLR) were significant predictors of high malignancy risk in gGIST. As determined by our ML approach, the logistic classification model demonstrated optimal performance, with an area under the receiver operating characteristic curve of 0.919 and 0.925 for the training and test sets, respectively. Furthermore, decision curve analysis substantiated the clinical relevance of the model. ConclusionHigh-risk EUS features, ill-defined tumor margins, larger tumor diameters, and elevated MLR independently predicted heightened malignant potential in gGIST. We developed logistic regression models based on these factors, which were further interpreted using the SHAP methodology. This analytical approach facilitated personalized therapeutic decision-making for diverse patient populations.

Single-cell and spatial omics unravel the spatiotemporal biology of tumour border invasion and haematogenous metastasis.

Solid tumours exhibit a well-defined architecture, comprising a differentiated core and a dynamic border that interfaces with the surrounding tissue. This border, characterised by distinct cellular morphology and molecular composition, serves as a critical determinant of the tumour's invasive behaviour. Notably, the invasive border of the primary tumour represents the principal site for intravasation of metastatic cells. These cells, known as circulating tumour cells (CTCs), function as 'seeds' for distant dissemination and display remarkable heterogeneity. Advancements in spatial sequencing technology are progressively unveiling the spatial biological features of tumours. However, systematic investigations specifically targeting the characteristics of the tumour border remain scarce. In this comprehensive review, we illuminate key biological insights along the tumour body-border-haematogenous metastasis axis over the past five years. We delineate the distinctive landscape of tumour invasion boundaries and delve into the intricate heterogeneity and phenotype of CTCs, which orchestrate haematogenous metastasis. These insights have the potential to explain the basis of tumour invasion and distant metastasis, offering new perspectives for the development of more complex and precise clinical interventions and treatments.

Attention based UNet model for breast cancer segmentation using BUSI dataset.

Breast cancer, a prevalent and life-threatening disease, necessitates early detection for the effective intervention and the improved patient health outcomes. This paper focuses on the critical problem of identifying breast cancer using a model called Attention U-Net. The model is utilized on the Breast Ultrasound Image Dataset (BUSI), comprising 780 breast images. The images are categorized into three distinct groups: 437 cases classified as benign, 210 cases classified as malignant, and 133 cases classified as normal. The proposed model leverages the attention-driven U-Net's encoder blocks to capture hierarchical features effectively. The model comprises four decoder blocks which is a pivotal component in the U-Net architecture, responsible for expanding the encoded feature representation obtained from the encoder block and for reconstructing spatial information. Four attention gates are incorporated strategically to enhance feature localization during decoding, showcasing a sophisticated design that facilitates accurate segmentation of breast tumors in ultrasound images. It displays its efficacy in accurately delineating and segregating tumor borders. The experimental findings demonstrate outstanding performance, achieving an overall accuracy of 0.98, precision of 0.97, recall of 0.90, and a dice score of 0.92. It demonstrates its effectiveness in precisely defining and separating tumor boundaries. This research aims to make automated breast cancer segmentation algorithms by emphasizing the importance of early detection in boosting diagnostic capabilities and enabling prompt and targeted medical interventions.

Indocyanine green uptake by human tumor and non‑tumor cell lines and tissue.

Indocyanine green (ICG) is a potential promising dye for a better intraoperative tumor border definition and an improved patient outcome by potentially improving tumor border visualization compared with traditional white light guided surgery. Here, the cellular uptake of ICG in human squamous cell carcinoma (SCC026) and immortalized non-cancer skin (HaCaT) cell lines was evaluated to study the tumor-specific cellular uptake of ICG. The spatial distribution of ICG inside tumor tissue was investigated in tissue sections of head and neck squamous cell carcinoma at a microscopic level. ICG uptake and internalization was observed in living cells after 2.5 h and in the nucleus after 24 h. In dead cells, higher and faster uptake was observed. In the tissue sections, higher ICG signal intensity could be detected in connective tissue and surrounding clusters and blood vessels. In conclusion, no distinct ICG uptake by tumor cells was detected in cancer cell lines and tumor tissue. ICG localization in certain regions of tumor tissue appears to be a result of enhanced tissue permeability and retention, but not specific to tumor cells.

Raman and autofluorescence spectroscopy for in situ identification of neoplastic tissue during surgical treatment of brain tumors.

Raman spectroscopy (RS) is a promising method for brain tumor detection. Near-infrared autofluorescence (AF) acquired during RS provides additional useful information for tumor identification and was investigated in comparison with RS for delineating brain tumors in situ. Raman spectra were acquired together with AF in situ within the solid tumor and at the tumor border during routine brain tumor surgeries (218 spectra; glioma WHO II-III, n = 6; GBM, n = 10; metastases, n = 10; meningioma, n = 3). Tissue classification for tumor identification in situ was trained on ex vivo data (375 spectra; glioma/GBM patients, n = 20; metastases, n = 11; meningioma, n = 13; and epileptic hippocampi, n = 4). Both in situ and ex vivo data showed that AF intensity in brain tumors was lower than that in border regions and normal brain tissue. Moreover, a positive correlation was observed between the AF intensity and the intensity of the Raman band corresponding to lipids at 1437cm- 1, while a negative correlation was found with the intensity of the protein band at 1260cm- 1. The classification of in situ AF and RS datasets matched the surgeon's evaluation of tissue type, with correct rates of 0.83 and 0.84, respectively. Similar correct rates were achieved in comparison to histopathology of tissue biopsies resected in selected measurement positions (AF: 0.80, RS: 0.83). Spectroscopy was successfully integrated into existing neurosurgical workflows, and in situ spectroscopic data could be classified based on ex vivo data. RS confirmed its ability to detect brain tumors, while AF emerged as a competitive method for intraoperative tumor delineation.

The infiltrative margins in glioblastoma: important is what has been left behind.

Supramaximal resection beyond the contrast-enhancing tumor borders represents an emerging surgical strategy for patients with newly diagnosed glioblastoma. A recent study provides evidence detailing the interactive effects of more aggressive surgery with other clinical predictors of outcome, supporting guidance for surgical decision-making and informing clinical trialists about the need to stratify for extent of resection.

Assessment of the bony resection margin distance in bone-invasive oral cancer using laser-induced breakdown spectroscopy

ObjectivesInadequate resection margins of less than 5 mm impair local tumor control. This weak point in oncological safety is exacerbated in bone-infiltrating tumors because rapid bone analysis procedures do not exist. This study aims to assess the bony resection margin status of bone-invasive oral cancer using laser-induced breakdown spectroscopy (LIBS).Materials and methodsLIBS experiments were performed on natively lasered, tumor-infiltrated mandibular cross-sections from 10 patients. In total, 5,336 spectra were recorded at defined distances from the tumor border. Resection margins < 1 mm were defined as very close, from 1–5 mm as close, and > 5 mm as clear. The spectra were histologically validated. Based on the LIBS spectra, the discriminatory power of potassium (K) and soluble calcium (Ca) between bone-infiltrating tumor tissue and very close, close, and clear resection margins was determined.ResultsLIBS-derived electrolyte emission values of K and soluble Ca as well as histological parameters for bone neogenesis/fibrosis and lymphocyte/macrophage infiltrates differ significantly between bone-infiltrating tumor tissue spectra and healthy bone spectra from very close, close, and clear resection margins (p < 0.0001). Using LIBS, the transition from very close resection margins to bone-infiltrating tumor tissue can be determined with a sensitivity of 95.0%, and the transition from clear to close resection margins can be determined with a sensitivity of 85.3%.ConclusionsLIBS can reliably determine the boundary of bone-infiltrating tumors and might provide an orientation for determining a clear resection margin.Clinical relevanceLIBS could facilitate intraoperative decision-making and avoid inadequate resection margins in bone-invasive oral cancer.

Is a 3 mm Surgical Margin Safe for Basal Cell Carcinoma in the Head and Neck that is Less than 2 cm, Considering Different Risk Factors?

Background Basal cell carcinoma (BCC) is the most common type of nonmelanoma skin cancer. Typically, resection requires a safety margin of ≥4 mm. When removing tumor cells, achieving complete excision with minimal safety margins and reconstructing the defect to preserve the original appearance are important. In this study, we used a 3-mm resection margin to confirm recurrence and re-resection rates. Methods Electronic medical records and photographic data were obtained for patients with primary BCC lesions less than 2 cm in diameter who underwent wide excision with a 3-mm surgical margin from January 2015 to November 2021. We analyzed factors determining recurrence and re-resection rates, such as tumor size, location, age, sex, underlying diseases (including immunosuppression state), ethnicity, subtypes, tumor borders, etc. Results This study included 205 patients. The mean age and follow-up period were 73.0 ± 11.5 years and 10.2 ± 8.0 months, respectively. The recurrence and re-resection rates were 1.95% and 25.85%, respectively. A statistically significant correlation was found between recurrence rate and tumor border ( p = 0.013) and the re-resection rate was correlated statistically with location ( p = 0.022) and immunosuppressed patients ( p = 0.006). Conclusion We found that a 3-mm excision margin provided sufficient safety in small facial BCC, resulting in ease of surgery and better aesthetic outcomes. However, surgical margins must be determined case by case by integrating various patient factors. In particular, a surgical margin of ≥4 mm is required for BCC in high-risk areas, immunosuppressed patients, or poorly defined border.

Clinical applicability of signal heterogeneity and tumor border assessment on T2-weighted MR images to distinguish astrocytic from oligodendroglial origin of gliomas

Background and purposeRadiological features on magnetic resonance imaging (MRI) were attributed to oligodendroglioma, although the diagnostic accuracy in a real-world clinical setting remains partially elusive. This study investigated the accuracy and robustness of tumor heterogeneity and tumor border delineation on T2-weighted MRI to distinguish oligodendroglioma from astrocytoma. Materials and methodsEight readers from three different specialties (radiology, neurology, neurosurgery) with varying levels of experience blindly rated 79 T2-weighted MR images of patients with either oligodendroglioma or astrocytoma. After the first reading session, all readers were re-invited for a second reading session within three weeks. Diagnostic accuracy, including area under the receiver operator characteristics curve (AUC), and intra-observer variability and inter-observer variability were used as outcome measures. ResultsPooled sensitivity and specificity to distinguish oligodendroglioma from astrocytoma for the use of tumor heterogeneity were 59.9 % respectively 74.5 %, and 85.7 % respectively 40.1 % for tumor border. A second reading session did not result in a significant change in sensitivity or specificity for tumor heterogeneity (P = 0.752 and P = 0.733, respectively) or tumor border (P = 0.309 and P = 0.271, respectively). An AUC of 0.825 was achieved with regard to predicting oligodendroglial origin of gliomas. Intra-observer agreement ranged from moderate to very good for tumor heterogeneity (kappa-value 0.43–0.87) and tumor border (0.40–0.84). A moderate inter-oberserver agreement was achieved for tumor heterogeneity and tumor border (kappa-value of 0.50 and 0.45, respectively). ConclusionThis study demonstrates that tumor heterogeneity and tumor borders on T2-weighted MRI could be used with moderate Finter-observer agreement to non-invasively distinguish oligodendroglioma from astrocytoma.

Histomolecular Validation of [18F]-FACBC in Gliomas Using Image-Localized Biopsies.

Gliomas have a heterogeneous nature, and identifying the most aggressive parts of the tumor and defining tumor borders are important for histomolecular diagnosis, surgical resection, and radiation therapy planning. This study evaluated [18F]-FACBC PET for glioma tissue classification. Pre-surgical [18F]-FACBC PET/MR images were used during surgery and image-localized biopsy sampling in patients with high- and low-grade glioma. TBR was compared to histomolecular results to determine optimal threshold values, sensitivity, specificity, and AUC values for the classification of tumor tissue. Additionally, PET volumes were determined in patients with glioblastoma based on the optimal threshold. [18F]-FACBC PET volumes and diagnostic accuracy were compared to ce-T1 MRI. In total, 48 biopsies from 17 patients were analyzed. [18F]-FACBC had low uptake in non-glioblastoma tumors, but overall higher sensitivity and specificity for the classification of tumor tissue (0.63 and 0.57) than ce-T1 MRI (0.24 and 0.43). Additionally, [18F]-FACBC TBR was an excellent classifier for IDH1-wildtype tumor tissue (AUC: 0.83, 95% CI: 0.71-0.96). In glioblastoma patients, PET tumor volumes were on average eight times larger than ce-T1 MRI volumes and included 87.5% of tumor-positive biopsies compared to 31.5% for ce-T1 MRI. The addition of [18F]-FACBC PET to conventional MRI could improve tumor classification and volume delineation.

Interim Phase II Results Using Panitumumab-IRDye800CW during Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence-guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but exhibit the greatest potential impact for improving patient care when the surgeon receives limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in patients with OPSCC. Twelve consecutive patients with OPSCC were enrolled as part of a nonrandomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. The results from this patient with OPSCC cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Intra-arterial Pressure-Enabled Drug Delivery Significantly Increases Penetration of Glass Microspheres in a Porcine Liver Tumor Model

PurposeTo test the hypothesis that Pressure-Enabled Drug Delivery (PEDD) would improve the delivery of surrogate therapeutic glass microspheres (GMs) via hepatic artery infusion to liver tumors when compared with a conventional endhole microcatheter. Materials and MethodsThe study was conducted in transgenic pigs (Oncopigs) with induced liver tumors. Tumors were infused intra-arterially with fluorescently labeled GM. PEDD with a specialized infusion device (TriNav; TriSalus Life Sciences, Westminster, Colorado) was compared with conventional endhole microcatheter delivery in both lobar and selective infusions. Near-infrared imaging was used to detect GM fluorescent signal in tumors. Image analysis with a custom deep learning algorithm (Visiopharm A/S) was used to quantitate signal intensity in relation to the tumor border. ResultsWith lobar infusions, significant increases in GM signal intensity were observed in and around tumors after PEDD (n = 10) when compared with those after conventional delivery (n = 7), with PEDD increasing penetration into the tumor by 117% (P = .004). In selective infusions, PEDD (n = 9) increased penetration into the tumor by 39% relative to conventional delivery (n = 8, P = .032). Lobar PEDD of GMs to the tumor was statistically equivalent to conventional selective delivery (P = .497). ConclusionsPEDD with a TriNav device significantly improved GM uptake in liver tumors relative to conventional infusion in both lobar and selective procedures. Lobar GM delivery with PEDD was equivalent to conventional selective delivery with an endhole device, suggesting that proximal PEDD infusions may enable effective delivery without selection of distal target vessels.

Enhancing Intraoperative Tissue Identification: Investigating a Smart Electrosurgical Knife's Functionality During Electrosurgery.

Detecting the cancerous growth margin and achieving a negative margin is one of the challenges that surgeons face during cancer procedures. A smart electrosurgical knife with integrated optical fibers has been designed previously to enable real-time use of diffuse reflectance spectroscopy for intraoperative margin assessment. In this paper, the thermal effect of the electrosurgical knife on tissue sensing is investigated. Porcine tissues and phantoms were used to investigate the performance of the smart electrosurgical knife after electrosurgery. The fat-to-water content ratio (F/W-ratio) served as the discriminative parameter for distinguishing tissues and tissue mimicking phantoms with varying fat content. The F/W-ratio of tissues and phantoms was measured with the smart electrosurgical knife before and after 14 minutes of electrosurgery. Additionally, a layered porcine tissue and phantom were sliced and measured from top to bottom with the smart electrosurgical knife. Mapping the thermal activity of the electrosurgical knife's electrode during animal tissue electrosurgery revealed temperatures exceeding 400 °C. Electrosurgery for 14 minutes had no impact on the device's accurate detection of the F/W-ratio. The smart electrosurgical knife enables real-time tissue detection and predicts the fat content of the next layer from 4 mm ahead. The design of the smart electrosurgical knife outlined in this paper demonstrates its potential utility for tissue detection during electrosurgery. In the future, the smart electrosurgical knife could be a valuable intraoperative margin assessment tool, aiding surgeons in detecting tumor borders and achieving negative margins.

Independent Risk Factors for Postoperative Recurrence of Patients with Primary Extramammary Paget's Disease: A Retrospective Analysis.

Extramammary Paget's disease (EMPD) is a rare skin cancer with unclear pathogenesis, insidious progression, and high recurrence rate. The purpose of this study was to investigate the clinical features and postoperative recurrence factors of primary EMPD. We retrospectively analyzed the medical records of 40 patients with primary EMPD who underwent wide local excision surgery at a single medical center between 2009 and 2019. Risk factors for recurrence of primary EMPD were analyzed using multivariate binary logistic regression. The study included 40 patients with primary EMPD, comprising 31 males (77.5%) and 9 females (22.5%), with a median age of 75.52 years (range 52-99 years). The most common lesion location was the scrotum (22 cases, 55.0%), followed by the vulva, penis, scrotum, underarm and anus. Multivariable regression analysis revealed significant differences in the presence of ill-defined tumour borders, exudation and nodules in the primary lesion affecting the relapse of primary EMPD (p<0.05). Our findings indicate that ill-defined tumour borders, exudation and nodules in the primary site should be considered as independent risk factors for disease recurrence, which may provide useful suggestions for the diagnosis, treatment and follow-up of primary EMPD.

ETMR-08. DECODING TUMOR-NEURONAL COMMUNICATION IN PEDIATRIC BRAIN TUMORS: INSIGHTS FROM ETMR 3D MODEL REVEALING MECHANO-SIGNALING DYNAMICS AND THERAPEUTIC OPPORTUNITIES

Abstract INTRODUCTION Exploring tumor-neuronal interactions is essential for comprehending brain tumor proliferation, chemotherapy resistance, and patient survival. While glioma research has made significant strides, our understanding of tumor-neuronal interactions in pediatric brain tumors, notably Embryonal Tumors with Multilayered Rosettes (ETMRs), remains limited. METHODS To elucidate tumor-neuronal interactions in ETMRs, we developed a 3D model by co-aggregating the human ETMR cell line BT-183 with human induced pluripotent stem cells (iPSCs) and allowing them to mature into forebrain organoids for 30 days, forming ETMR-forebrain organoids (ETMR-FBO). We further employed single-cell RNA sequencing to compare the gene expression profile of healthy forebrain organoids (FBO) with the ETMR-FBOs. Additionally, we conducted immunohistochemistry of 3D model sections for comparative evaluation and spatial transcriptomics of murine and human primary ETMR samples. RESULTS Our integrated dataset of 48,764 cells of healthy FBOs (n = 4) and ETMR-FBOs (n = 6) revealed that ETMR tumor cells impeded the neuronal differentiation of the FBO cells. The ETMR-FBOs exhibited a significant enrichment of neuro-stem cells (67% vs 49%), accompanied by a reduction of more differentiated neuronal cells. Comparative trajectory analysis confirmed a blockage of neuronal maturation/differentiation in ETMR-FBOs compared to controls without ETMR cells. Immunohistochemistry further confirmed an enrichment of SOX2-positive/synaptophysin-negative neuronal progenitors in the organoid areas closest to the tumor border. Additionally, we identified upregulated extracellular matrix-related pathways, particularly integrin and YAP/TEAD signaling, in the neuro-stem cell compartment of ETMR-FBOs. This implies a tumor-specific mechano-signaling mechanism influencing the neuronal differentiation state of the tumor microenvironment. CONCLUSION Our findings suggest that mechano-signaling-related tumor-neuronal interactions in ETMR contribute to the formation of an immature neuronal niche. Targeting mechano-signaling may hold promise for innovative therapies by disrupting tumor architecture and enhancing susceptibility to chemotherapy.