Surgical Resection Of Tumor Research Articles

Maintaining quality of life after major lung resection for carcinoid tumor

BackgroundPulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients’ daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program.MethodsPatients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables.ResultsA total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19–81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10.ConclusionsExcellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients’ lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented.

Prognostic impact of pre-referral tumor resection in unilateral Wilms tumor: A single-institute experience from a lower middle-income country.

The objectives of this study were to evaluate the prognostic impact of pre-referral surgical resection of Wilms tumor (WT) performed at non-oncology centers, and to strategize an improved care plan for this very curable pediatric tumor. In this study conducted in a large pediatric cancer center in Pakistan, we retrospectively reviewed the electronic medical records (EMR) of 149 patients with unilateral WT from September 2008 to August 2017. Based on treatment approach, patients were categorized into two groups: (i) pre-referral tumor resection (PTR: n=75), and (ii) post-neoadjuvant chemo nephrectomy (PCN: n=74). The proportion of metastatic disease in PTR and PCN groups was 33.3% and 35.1%, respectively. In the PTR subset, median time to admission after PTR was 5weeks (mean 11, SEM 2.8, range: 2-202) weeks, with 53.3% (n=40) presenting more than 4weeks after PTR. Twenty patients had no cross-sectional imaging prior to PTR and underwent surgery after abdominal ultrasound only. On baseline imaging at our center, 58.7% (n=44) of the PTR group had radiologically evaluable disease (four metastases only, 19 local residual tumor only, 21 both localized tumor and visible metastases). Disease staging was uncertain in 23 patients because of no or inadequate histology specimens and/or lymph node sampling in patients with no evaluable disease. Statistically significant differences were recorded for the two subsets regarding tumor volume, extent and nodularity, renal vein and renal sinus involvement, lymph node status, tumor rupture and histopathologic features, and tumor stage, with a 10-year event-free survival (EFS) for PCN and PTR of 74.3% and 50.7%, respectively (p<.001). In the PTR group, EFS for those presenting within 4weeks and later was 91.4% versus 15.0%, respectively (p<.0001). Suboptimal pre-referral surgical intervention results in poor survival outcomes in unilateral WT. Our findings highlight the need for a comprehensive action plan for educating healthcare professionals engaged in WT diagnosis and referral process. PCN in a multidisciplinary team approach can reduce surgical morbidity and seems to be a better strategy to improve the survival rates in low-resource settings.

Impact of Preoperative Mapping and Intraoperative Neuromonitoring in Minimally Invasive Parafascicular Surgery for Deep-Seated Lesions

Transsulcal tubular retractor-assisted minimally invasive parafascicular surgery changes the surgical strategy for deep-seated lesions by promoting a deficit-sparing approach. When integrated with preoperative brain mapping and intraoperative neuromonitoring (IONM), this approach may potentially improve patient outcomes. In this study, we assessed the impact of preoperative brain mapping and IONM in tubular retractor-assisted neuro-oncological surgery. This retrospective single-center cohort study included patients who underwent transsulcal tubular retractor-assisted minimally invasive parafascicular surgery for resection of deep-seated brain tumors from 2016 to 2022. The cohort was divided into 3 groups: group 1, no preoperative mapping or IONM (17 patients); group 2, IONM only (25 patients); group 3, both preoperative mapping and IONM (38 patients). We analyzed 80 patients (33 males and 47 females) with a median age of 46.5 years (range: 1-81 years). There was no significant difference in mean tumor volume (26.2 cm3 [range 1.07-97.4 cm3]; P= 0.740) and mean preoperative depth of the tumor (31 mm [range 3-65 mm], P= 0.449) between the groups. A higher proportion of high-grade gliomas and metastases was present within group 3 (P= 0.003). IONM was related to fewer motor (P= 0.041) and language (P= 0.032) deficits at hospital discharge. Preoperative mapping and IONM were also related to shorter length of stay (P= 0.008). Preoperative and intraoperative brain mapping and monitoring enhance transsulcal tubular retractor-assisted minimally invasive parafascicular surgery in neuro-oncology. Patients had a reduced length of stay and prolonged overall survival. IONM alone reduces postoperative neurological deficit.

BIOM-26. RAPID IDENTIFICATION OF IDH1-R132 VARIANTS IN GLIOMA WITH LOCKED NUCLEIC ACID LOOP-MEDIATED ISOTHERMAL AMPLIFICATION (LNA-LAMP)

Abstract Point mutations that impact the catalytic site of isocitrate dehydrogenase 1 (IDH1) are associated with an extended overall survival of approximately 3.8 years for glioma patients compared to 1 year for those with wild-type IDH1. The difference in survival benefit is associated with the maximal surgical resection of IDH1 mutant tumors, making intraoperative knowledge of the mutational status valuable. Unfortunately, current methods used to determine IDH1-R132 mutational status are incompatible with obtaining real-time results. We have developed a panel of assays that use LNA-LAMP to identify commonly encountered IDH1-R132 variants (R132H, R132C, R132G, R132S, R132L) within 40 minutes. These assays require little preanalytical processing, no complex equipment, and yield results which are easily interpreted by the naked eye. Tumor samples are initially subjected to a 5-minute alkaline digest, then added directly to LNA-LAMP reactions containing primers unique to each IDH1-R132 variant. Discrimination between the wild-type and mutant allele is achieved with the integration of locked nucleic acids within primers. A reaction with an IDH1-R132R specific primer serves as the sample positive control, as all tumor lysates are expected to contain wild-type IDH1 DNA. Lysates are incubated for 35 minutes in a hot water bath, followed by visual interpretation using a pH-based colorimetric indicator, where samples positive for the mutation appear a vibrant yellow while those lacking the mutation remain pink. This method has been rigorously tested with patient-derived tumor lysates, yielding reproducible and accurate results, and has an analytical sensitivity of about 20% mutant DNA in a background of wild-type DNA. This sensitivity is comparable to that of Sanger Sequencing while simultaneously offering a more cost-effective and efficient workflow. LNA-LAMP is amenable for use in the intraoperative window to allow patients with an IDH1-R132 mutation the benefit of a maximal surgical resection.

NIMG-48. ASSOCIATIONS BETWEEN HETEROGENEITY OBSERVED IN O-6-METHYLGUANINE-DNA METHYLTRANSFERASE (MGMT) ASSAY MEASUREMENTS AND MGMT-BASED IMAGING SIGNATURE BASED ON MRI AND DEEP LEARNING

Abstract BACKGROUND O-6-methylguanine-DNA methyltransferase(MGMT), a gene promoter, corresponds with the efficacy of standard therapy for Glioblastoma (GBM) patients. If a single sample is sequenced, an appropriate diagnosis of MGMT methylation may be hampered by intratumoral heterogeneity. This work proposes a non-invasive in-vivo estimation of MGMT methylation using deep learning and multi-parametric MRI (mpMRI). Further, it quantifies spatial heterogeneity and establishes the associations between MGMT assay measurement and MGMT imaging signature heterogeneity. METHODS For this study, mpMRI structural scans (T1, T2, FLAIR and T1-Gd) of 498 newly diagnosed GBM patients were considered. These patients underwent surgical tumor resection, and MGMT methylation testing was retrospectively collected. By overlaying local and regional 2D patches of size 32 X 32 over the whole tumor on mpMRI scans, a 10-fold cross-validated deep convolutional neural network model was trained considering five layers on the discovery cohort (n=458). The trained model was applied to an independent multi-sample cohort (n=40) to compute the MGMT methylation at the pixel level for imaging-derived maps generation and heterogeneity quantification. The independent cohort included the patients for whom multiple tissue specimens were sequenced for MGMT methylation. RESULTS The patch-based deep model produced an area under the ROC curve of 0.76 (95% CI: 0.71–0.82) for MGMT status prediction. This model showed a strong association between homogeneously MGMT methylated and heterogeneous cases with MGMT Assay measurement of multiple samples with Pearson’s correlation coefficients of 0.64 (p &amp;lt; 0.05) and 0.78 (p &amp;lt; 0.01), respectively. Further, heterogeneity with a significantly higher variance was also observed in heterogeneous cases in developed MGMT imaging signature. CONCLUSION The proposed model efficiently determines MGMT promoter methylation and quantifies GBM spatial heterogeneity non-invasively. Also, it showed a significant association between the heterogeneity observed in MGMT-based imaging signature and MGMT assay measurements.

Phosphaturic mesenchymal tumor: Clinicopathological features with outcomes in 10 patients with review of literature.

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal tumors, associated with long-standing, non-specific but often debilitating symptoms in the affected patients. These tumors display characteristic histopathological features and in case, identified timely, can be a boon for patients, given an excision is completely curative. To evaluate the clinical and histopathological features of 10 PMTs, diagnosed at our institution, along with clinical outcomes in those patients. This was a retrospective study, wherein 10 PMTs, diagnosed from January 2013 to July 2022, were included. The average age at the time of diagnosis was 40 years with an M:F ratio of 4:1. Clinical features included lumps, weakness, bone pain, difficulty in moving and walking, and pathologic fractures. The biochemical analysis showed normal serum calcium levels (average = 9.5 mg/dL), with low serum phosphorus (average = 2.2 mg/dL) and raised serum fibroblast growth factor 23 (FGF23) levels, in all the cases, wherever available. On histopathology, all tumors showed cells arranged in a hemangiopericytomatous pattern, including oval to short spindle forms. Multinucleate giant cells were present in nine tumors, and characteristic "grungy calcifications" was observed in eight tumors. Prominent pseudo cystic spaces were seen in eight tumors. A significant number of mitotic figures and tumor necrosis were not seen in any tumor. In five cases where follow-up was available, there was complete resolution of symptoms post-resection with no recurrence or metastasis. All those patients were free of disease until the last follow-up. This constitutes the first largest comprehensive study on these rare tumors from our country. PMTs can be diagnosed based on certain histopathological features and correlation with clinicoradiological and biochemical findings. These are invariably benign neoplasms. Patients are relieved of their debilitating symptoms after adequate surgical tumor resection. Therefore, their correct and timely diagnosis is crucial.

Abstract 14737: A Case of an Intracardiac Sarcoma Arising From Metastatic Spread of a Primary Phyllodes Tumor of the Breast

Background: Malignant phyllodes tumors with cardiac involvement are rare, presenting diagnostic and management challenges. The benefits of medical and surgical therapies remain unclear. Large-bore aspiration devices are currently only approved for retrieval of venous thromboemboli but may present a valid option for diagnosis and treatment of intracardiac masses in high risk patients. Case Summary: We present the case of a 57-year-old female with a malignant phyllodes tumor of the breast and bilateral pulmonary emboli who presented with an incidental complex intracardiac mass on transthoracic echocardiography (1). A follow-up transesophageal echocardiogram demonstrated masses within the superior vena cava, right atrium, and right ventricle (2a-2b). Aspiration thrombectomy was performed given clinical stability and concern for thrombi with high risk of worsening clot burden. A large-bore aspiration device was used to retrieve the masses in multiple passes (3), which were pathologically consistent with spindle cell sarcoma. A cardiac MRI was completed following aspiration, and multiple mobile masses persisted in the right ventricle (4). The patient was discharged on day nine of hospitalization with therapeutic chemotherapy planned. She had one session of chemotherapy before a fatal cardiac arrest from unknown cause three months after discharge. Discussion: Phyllodes tumors rarely metastasize to the heart, and effective modalities for their diagnosis and management are unclear. Treatment strategies include wide surgical resection of the primary tumor, however mortality remains high in the setting of metastatic spread. Current guidelines recommend following principles of soft tissue sarcomas with chemotherapy. Large-bore aspiration devices may be an effective way to resect intracardiac tumors for both diagnostic and therapeutic purposes as an alternative to invasive surgical intervention for high-risk patients.

Second-Line Chemotherapy for Intrahepatic Cholangiocarcinomas: What Is the Real Gain?

The presence of actionable alterations in advanced biliary tract cancer patients opened new therapeutic possibilities for second-line treatments. However, for around 60% of the patients, chemotherapy remains the only therapeutic option. The aim of our study was to evaluate outcomes and prognostic parameters in patients with intrahepatic cholangiocarcinomas treated with second-line chemotherapy. A total of 255 consecutive metastatic intrahepatic cholangiocarcinoma (ICC) patients were retrospectively reviewed and clinicopathologic and survival data were collected. Fourty-four percent of ICC patients underwent second-line chemotherapy. In particular, younger ICC patients with better ECOG PS status, and with disease control after first-line chemotherapy were those who were treated with second-line treatments. Median progression-free survival in the patients treated with second-line chemotherapy was 3 months. Finally, the patients affected by intrahepatic cholangiocarcinoma with better ECOG PS, with prior surgical resection of the primary tumor, who responded to first-line chemotherapy, and had better progression-free survival with second-line chemotherapy, were associated with better outcomes in multivariate analysis. Not all patients seem to benefit from second-line chemotherapy. To improve therapeutic decisions, performance status and disease control with first-line chemotherapy should lead to the decision on the usefulness of second-line treatments in advanced ICC patients.

Development of a fibroblast activation protein-targeted PET/NIR dual-modality probe and its application in head and neck cancer.

Purpose: The combination of near-infrared (NIR) and positron emission tomography (PET) imaging presents an opportunity to utilize the benefits of dual-modality imaging for tumor visualization. Based on the observation that fibroblast activation protein (FAP) is upregulated in cancer-associated fibroblasts (CAFs) infiltrating all solid tumors, including head and neck squamous cell carcinoma (HNSCC), we developed the novel PET/NIR probe [68Ga]Ga-FAP-2286-ICG. Preclinically, the specificity, biodistribution and diagnostic properties were evaluated. Methods: Cell uptake assays were completed with the U87MG cell to evaluate the specificity of the [68Ga]Ga-FAP-2286-ICG. The tumor-targeting efficiency, biodistribution and optimal imaging time window of the [68Ga]Ga-FAP-2286-ICG were studied in mice bearing U87MG xenografts. HNSCC tumor-bearing mice were used to evaluate the feasibility of [68Ga]Ga-FAP-2286-ICG for tumor localization and guided surgical resection of HNSCC tumors. Results: The in vitro experiments confirmed that [68Ga]Ga-FAP-2286-ICG showed good stability, specific targeting of the probe to FAP, and the durable retention effect in high-expressing FAP tumors U87MGcell. Good imaging properties such as good tumor uptake, high tumor-to-background ratios (5.44 ± 0.74) and specificity, and tumor contouring were confirmed in studies with mice bearing the U87MG xenograft. PET/CT imaging of the probe in head and neck cancer-bearing mice demonstrated specific uptake of the probe in the tumor with a clear background. Fluorescence imaging further validated the value of the probe in guiding surgical resection and achieving precise removal of the tumor and residual lesions. Conclusion: In a preclinical model, these attractive [68Ga]Ga-FAP-2286-ICG PET/NIR imaging acquired in head and neck cancer make it a promising FAP-targeted multimodal probe for clinical translation.

Can we improve electrocorticography using a circular grid array in brain tumor surgery?

Intraoperative electrocorticography (iECoG) is used as an adjunct to localize the epileptogenic zone during surgical resection of brain tumors in patients with focal epilepsies. It also enables monitoring of after-discharges and seizures with EEG during functional brain mapping with electrical stimulation. When seizures or after-discharges are present, they complicate accurate interpretation of the mapping strategy to outline the brain’s eloquent function and can affect the surgical procedure. Recurrent seizures during surgery requires urgent treatment and, when occurring during awake craniotomy, often leads to premature termination of brain mapping due to post-ictal confusion or sedation from acute rescue therapy. There are mixed results in studies on efficacy with iECoG in patients with epilepsy and brain tumors influencing survival and functional outcomes following surgery. Commercially available electrode arrays have inherent limitations. These could be improved with customization potentially leading to greater precision in safe and maximal resection of brain tumors. Few studies have assessed customized electrode grid designs as an alternative to commercially available products. Higher density electrode grids with intercontact distances less than 1 cm improve spatial delineation of electrophysiologic sources, including epileptiform activity, electrographic seizures, and afterdischarges on iECoG during functional brain mapping. In response to the shortcomings of current iECoG grid technologies, we designed and developed a novel higher-density hollow circular electrode grid array. The 360-degree iECoG monitoring capability allows continuous EEG recording during surgical intervention through the aperture with and without electrical stimulation mapping. Compared with linear strip electrodes that are commonly used for iECoG during surgery, the circular grid demonstrates significant benefits in brain tumor surgery. This includes quicker recovery of post-operative motor deficits (2.4 days versus 9 days, p = 0.05), more extensive tumor resection (92.0% versus 77.6%, p = 0.003), lesser reduction in Karnofsky Performance scale postoperatively (−2 versus −11.6, p = 0.007), and more sensitivity to recording afterdischarges. In this narrative review, we discuss the advantages and disadvantages of commercially available recording devices in the operating room and focus on the usefulness of the higher-density circular grid.

Current State of Functional MRI in the Presurgical Planning of Brain Tumors.

Surgical resection of brain tumors is challenging because of the delicate balance between maximizing tumor removal and preserving vital brain functions. Functional MRI (fMRI) offers noninvasive preoperative mapping of widely distributed brain areas and is increasingly used in presurgical functional mapping. However, its impact on survival and functional outcomes is still not well-supported by evidence. Task-based fMRI (tb-fMRI) maps blood oxygen level-dependent (BOLD) signal changes during specific tasks, while resting-state fMRI (rs-fMRI) examines spontaneous brain activity. rs-fMRI may be useful for patients who cannot perform tasks, but its reliability is affected by tumor-induced changes, challenges in data processing, and noise. Validation studies comparing fMRI with direct cortical stimulation (DCS) show variable concordance, particularly for cognitive functions such as language; however, concordance for tb-fMRI is generally greater than that for rs-fMRI. Preoperative fMRI, in combination with MRI tractography and intraoperative DCS, may result in improved survival and extent of resection and reduced functional deficits. fMRI has the potential to guide surgical planning and help identify targets for intraoperative mapping, but there is currently limited prospective evidence of its impact on patient outcomes. This review describes the current state of fMRI for preoperative assessment in patients undergoing brain tumor resection. Keywords: MR-Functional Imaging, CNS, Brain/Brain Stem, Anatomy, Oncology, Functional MRI, Functional Anatomy, Task-based, Resting State, Surgical Planning, Brain Tumor © RSNA, 2023.

Malignant Neoplasms Arising in the Cardiac Pacemaker Cavity: A Systematic Review.

Cancer is the abnormal proliferation of physiologically inadequate cells. Studies have identified the cardiac pacemaker pocket as a site of rare neoplasms. To evaluate the clinical outcomes, treatment, prognosis, and individualized management of tumors originating in the cardiac pacemaker pocket, a systematic review was conducted using case reports and case series available in the PubMed/Medline, Science Direct, Cochrane Central, LILACS, and Scientific Electronic Library Online (Scielo) databases. Pacemaker pocket tumors affected patients with a mean age of 72.9 years, with a higher incidence in males (76.9%, n = 10). The average time for neoplasm development was 4.4 years (54.07 months). The most prevalent model was Medtronic (38.4%, n = 5), with titanium (83.3%) being the most common metal composition. Chemotherapy was the most performed procedure among patients (38.4%), followed by radiation therapy (38.4%) and surgical tumor resection (30.7%). Six analyzed cases (46.1%) resulted in death, and four patients (30.7%) achieved a cure. Patients with pacemakers should be routinely evaluated for the occurrence of malignant tumors at the site of device implantation.

Dynamic Susceptibility Contrast-Enhanced Perfusion-Weighted Imaging in Differentiation Between Recurrence and Pseudoprogression in High-Grade Glioma: A Meta-analysis.

In glioma patients that have undergone surgical tumor resection, the ability to reliably distinguish between pseudoprogression (PsP) and a recurrent tumor (RT) is of key clinical importance. Accordingly, this meta-analysis evaluated the utility of dynamic susceptibility contrast-enhanced perfusion-weighted imaging as a means of distinguishing between PsP and RT when analyzing patients with high-grade glioma. The PubMed, Web of Science, and Wanfang databases were searched for relevant studies. Pooled analyses of sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) values were conducted, after which the area under the curve (AUC) for summary receiver operating characteristic curves was computed. This meta-analysis ultimately included 21 studies enrolling 879 patients with 888 lesions. Cerebral blood volume-associated diagnostic results were reported in 20 of the analyzed studies, and the respective pooled sensitivity, specificity, PLR, and NLR values were 86% (95% confidence interval [CI], 0.81-0.89), 83% (95% CI, 0.77-0.87), 4.94 (95% CI, 3.61-6.75), and 0.18 (95% CI, 0.13-0.23) for these 20 studies. The corresponding AUC value was 0.91 (95% CI, 0.88-0.93), and the publication bias risk was low ( P = 0.976). Cerebral blood flow-related diagnostic results were additionally reported in 6 of the analyzed studies, with respective pooled sensitivity, specificity, PLR, and NLR values of 85% (95% CI, 0.78-0.90), 85% (95% CI, 0.76-0.91), 5.54 (95% CI, 3.40-9.01), and 0.18 (95% CI, 0.12-0.26). The corresponding AUC value was 0.92 (95% CI, 0.89-0.94), and the publication bias risk was low ( P = 0.373). The present meta-analysis results suggest that dynamic susceptibility contrast-enhanced perfusion-weighted imaging represents an effective diagnostic approach to distinguishing between PsP and RT in high-grade glioma patients.

Polarization-sensitive optical coherence tomography for renal tumor detection in ex vivo human kidneys

Kidney cancer is a kind of high mortality cancer because of the difficulty in early diagnosis and the high metastatic dissemination in treatments. The surgical resection of tumors is the most effective treatment for renal cancer patients. However, precise assessment of tumor margins is a challenge during surgical resection. The objective of this study is to demonstrate an optical imaging tool in precisely distinguishing kidney tumor borders and identifying tumor zones from normal tissues to assist surgeons in accurately resecting tumors from kidneys during the surgery. 30 samples from six human kidneys were imaged using polarization-sensitive optical coherence tomography (PS-OCT). Cross-sectional, enface, and spatial information of kidney samples were obtained for microenvironment reconstruction. Polarization parameters (phase retardation, optic axis direction, and degree of polarization uniformity (DOPU) and Stokes parameters (Q, U, and V) were utilized for multi-parameter analysis. To verify the detection accuracy of PS-OCT, H&E histology staining and dice-coefficient were utilized to quantify the performance of PS-OCT in identifying tumor borders and regions. In this study, tumor borders were clearly identified by PS-OCT imaging, which outperformed the conventional intensity-based OCT. With H&E histological staining as golden standard, PS-OCT precisely identified the tumor regions and tissue distributions at different locations and different depths based on polarization and Stokes parameters. Compared to the traditional attenuation coefficient quantification method, PS-OCT demonstrated enhanced contrast of tissue characteristics between normal and cancerous tissues due to the birefringence effects. Our results demonstrated that PS-OCT was promising to provide imaging guidance for the surgical resection of kidney tumors and had the potential to be used for other human kidney surgeries in clinics such as renal biopsy.

Fluorescence lifetime of injected indocyanine green as a universal marker of solid tumours in patients.

The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.

Comparison of Resection Assisting Devices in the Process of Collecting Brain Tumor Tissue for Basic Research: Microdebrider Versus Ultrasonic Aspirator

Brain tumors display significant inter and intratumoral heterogeneity, impacting disease progression and outcomes. Preserving surgically resected tissue is vital for ensuring accurate research results to enhance understanding of tumor pathophysiology. This study evaluates tissue integrity and viability of tissue resected using 2 surgical devices for tumor resection: a mechanical microdebrider (MD) and an ultrasonic aspirator (UA). Tumor samples were obtained from patients undergoing surgical resection of primary and secondary intracranial tumors. Cell viability was assessed, and histopathological analysis of Hematoxylin and Eosin -stained tissues was performed. Adherent monolayer and neurospheres cell cultures were established from paired samples. RNA isolation and quantitative polymerase chain reaction of housekeeping genes were conducted to compare genetic integrity. The cellular viability was comparable between samples obtained using both the MD and the UA, with a mean viability of 75.2% ± 15.6 and 70.7% ± 16.8, respectively (P = 0.318). Histopathological evaluation indicated no discernible differences in cellular integrity between the devices. Cell culture success rates and growth characteristics were similar for both devices. RNA concentration and integrity were well-maintained in both MD and UA samples, with no significant differences (P= 0.855). Quantitative polymerase chain reaction analysis of housekeeping genes showed consistent results across matched tissues from both devices and different tumor pathologies. Surgical handheld devices provide valuable, high-quality tissue samples for research. Surgeon preference, tumor pathology, and anatomical location dictate device choice. Both MD and UA devices are reliable for obtaining quality tissue specimens, facilitating translational neuro-oncology research.

Neoadjuvant systemic oncolytic vesicular stomatitis virus is safe and may enhance long-term survivorship in dogs with naturally occurring osteosarcoma

Osteosarcoma is a devastating bone cancer that disproportionally afflicts children, adolescents, and young adults. Standard therapy includes surgical tumor resection combined with multiagent chemotherapy, but many patients still suffer from metastatic disease progression. Neoadjuvant systemic oncolytic virus (OV) therapy has the potential to improve clinical outcomes by targeting primary and metastatic tumor sites and inducing durable antitumor immune responses. Here we describe the first evaluation of neoadjuvant systemic therapy with a clinical-stage recombinant oncolytic vesicular stomatitis virus (VSV), VSV-IFNβ-NIS, in naturally occurring cancer, specifically appendicular osteosarcoma in companion dogs. Canine osteosarcoma has a similar natural disease history as its human counterpart. VSV-IFNβ-NIS was administered prior to standard of care surgical resection, permitting microscopic and genomic analysis of tumors. Treatment was well-tolerated and a "tail" of long-term survivors (∼35%) was apparent in the VSV-treated group, a greater proportion than observed in two contemporary control cohorts. An increase in tumor inflammation was observed in VSV-treated tumors and RNA-seq analysis showed that all the long-term responders had increased expression of a Tcell anchored immune gene cluster. We conclude that neoadjuvant VSV-IFNβ-NIS is safe and may increase long-term survivorship in dogs with naturally occurring osteosarcoma, particularly those that exhibit pre-existing antitumor immunity.

Do surgical tumour resection and chemotherapy lead to liver inflammation and outgrowth of liver metastases? Insights from a clinically adapted pancreatic cancer mouse model

Do surgical tumour resection and chemotherapy lead to liver inflammation and outgrowth of liver metastases? Insights from a clinically adapted pancreatic cancer mouse model

Fatores prognósticos e complicações atribuídas à ressecção cirúrgica de mastocitoma cutâneo em 62 cães atendidos no hospital veterinário da UNESP-Jaboticabal de 2013 a 2019

Mast cell tumors, which are neoplasms with variable behavior, from less aggressive to highly metastatic tumors, account for 16%–21% of cutaneous neoplasms in dogs. The diagnosis and grading of mast cell tumors are based on cytological analysis and histological evaluation, which facilitate appropriate planning for surgical and chemotherapeutic treatment. Surgical resection with safety margins of 2–3 cm is considered the best therapeutic option; however, postoperative complications, such as delayed healing, necrosis, suture dehiscence, and occurrence of seroma, are reported. It is essential to understand the biology of mast cell tumors because prognostic factors directly influence the efficacy of the treatment and the quality of life of the patient. Here, we conducted a retrospective study of dogs submitted to surgical resection of cutaneous mast cell tumors, and analyzed the prognostic factors and occurrence of postoperative complications. The results showed that low grade mast cell tumors were associated with a lower occurrence of ulceration, metastasis, recurrence, lack of need for adjuvant therapy, and occurrence of paraneoplastic syndrome compared to those of a higher grade. We also compared the association between demanding or compromised margins with the presence of postoperative complications. The results showed that high grade mast cell tumors have a greater metastatic potential and that the presence of neoplastic cells in the adjacent tissues leads to a greater malignancy and postoperative complications.

FRI066 Treatment History And Comorbidities Reported By Patients With Hypothalamic Obesity Treated With Setmelanotide In A Phase 2 Trial

Abstract Disclosure: C.L. Roth: Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc., Saniona. Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. M. Gottschalk: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc. Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. J. Miller: Other; Self; Study funding from Rhythm Pharmaceuticals, Inc. G. Yuan: Employee; Self; Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. S. Malhotra: Employee; Self; Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. M.J. Abuzzahab: Consulting Fee; Self; Pfizer, Inc., Consynance, Rhythm Pharmaceuticals, Inc., Endo Pharmaceuticals. Background: Hypothalamic obesity (HO) is an acquired form of severe obesity that can occur following surgical resection or radiotherapy of brain tumors. Multiple factors associated with the development of HO—including degree of hypothalamic damage from tumor treatment, comorbidities (eg, pituitary deficiencies), polypharmacy used to treat comorbidities, and unique pathophysiology—confer treatment challenges; HO is often unresponsive to lifestyle modifications and traditional obesity pharmacotherapies. In a Phase 2, 16-week trial of setmelanotide in patients with HO, 16 of 18 patients (88.9% [90% confidence interval, 69.0%-98.0%]; P&amp;lt;0.0001) achieved ≥5% body mass index (BMI) reduction from baseline, with a mean percent BMI change of −15.4% in patients adhering to treatment (n=17). We assessed patient histories (ie, tumor treatments, prior attempts to lose weight, and comorbidities) reported in the trial to further characterize this patient population. Methods: Patients aged ≥6 to ≤40 years with documented evidence of HO were enrolled in an open-label Phase 2 trial (NCT04725240) and received setmelanotide once daily for 16 weeks. The primary endpoint was the proportion of patients with ≥5% BMI reduction from baseline at Week 16. Tumor treatments, prior attempts to lose weight, and comorbidities are summarized narratively. Results: Eighteen patients with HO (age range, 6-24 years) were treated with setmelanotide. HO was diagnosed in patients following treatment of craniopharyngioma (n=14), hamartoma (n=3), or juvenile pilocytic astrocytoma (n=1). Six patients (33.3%) had tumor recurrence and/or multiple tumor treatments. Thirteen patients (72.2%) reported prior lifestyle modifications (ie, calorie restriction [n=4], low-carbohydrate diet [n=6], dietary tracking/modification [n=4], food access restriction [n=1], personal training [n=1]) and/or pharmacotherapy use (ie, exenatide [n=3], semaglutide [n=1], liraglutide [n=2], metformin [n=2], methylphenidate [n=2], dextroamphetamine [n=1], lisdexamfetamine [n=2], naltrexone [n=3], oxytocin [n=3], phentermine [n=1]) without substantial benefit. Comorbidities occurring in ≥25% of patients were diabetes insipidus (n=14), hypothyroidism (n=14), growth hormone deficiency (n=11), adrenal insufficiency (n=10), hypogonadism (n=8), pan/hypopituitarism (n=8), psychiatric disorders (n=8), vision problems (n=6), gastrointestinal symptoms (n=6), obstructive sleep apnea (n=5), and hypothalamic-pituitary disorder (n=3). All patients adhering to treatment (n=17, including those with pituitary deficiencies and common comorbidities)) experienced BMI reductions with setmelanotide. Conclusions: Despite complex medical histories, hypothalamic damage, and various prior failed interventions, setmelanotide reduced BMI in patients with HO in a Phase 2 trial. Presentation: Friday, June 16, 2023