Site Of Origin Research Articles

Neuroendocrine carcinomas of the gastrointestinal tract : Morphology, molecular pathology, cellular origin

Neuroendocrine carcinomas (NEC) are poorly differentiated neuroendocrine neoplasms that can occur ubiquitously in the mucosa-bearing organs of the gastrointestinal tract. Based on their morphology, they are classified into large cell (LCNEC) and small cell NEC (SCNEC). The most common form of mixed differentiation is the combination with an adenocarcinoma, referred to as mixed adenoneuroendocrine carcinoma (MANEC). NEC/MANEC exhibit asignificantly poorer prognosis than the adenocarcinomas of their respective primary sites, which is inextricably linked to their typical histomorphology. Adenocarcinomas with aberrant expression of neuroendocrine markers do not show aworse clinical course. Molecularly, NEC/MANEC have aprofile comparable to the adenocarcinomas of their site of origin and aprofile divergent from neuroendocrine tumors. Analyses of gastric NEC/MANEC have shown frequent MYC amplifications, which are reflected in MYC signatures in various transcriptome analyses.The cellular origin of NEC remains asubject of controversial discussion. New insights are provided by aMYC-driven, genetically modified mouse model that led to the development of large gastric tumors. These tumors were histologically identified as LCNEC and were accompanied by both neuroendocrine and non-neuroendocrine precursor lesions. Using immunofluorescence, aderivation from resident neuroendocrine cells in the gastric corpus was demonstrated, suggesting that at least aportion of LCNEC may originate directly from neuroendocrine cells.

Planned relocation may reduce communities’ future exposure to coastal inundation but effect varies with emission scenario and geography

The planned, permanent relocation of entire communities away from sea level rise (SLR) and coastal floods is an already occurring climate change adaptation strategy. Yet, planned relocations are fraught undertakings with multiple goals, and may or may not achieve their most basic objective: to reduce risk. Here we assess risk of future coastal flooding before and after moving, for three dates and three emissions scenarios, for 17 communities from a global dataset. Most communities achieved exposure reduction with less future inundation in destinations than origin sites, but the extent varies across time and emissions scenario. In all cases, origin sites have projected exposure to SLR plus a once-per-year flood, with increasing exposure under high emissions scenarios and towards 2100. In nine cases, even destination sites have projected inundation exposure under some scenarios. Small-island-to-small-island relocations had more projected inundation in destinations than moves from a small-island-to-mainland, or from mainland-to-mainland.

Biphenotypic Sinonasal Sarcoma: Literature Review of a Peculiar Pathological Entity—The Neurosurgical Point of View

Background: Biphenotypic sinonasal sarcoma (BSNS) is a low-grade tumor of the sinonasal tract with frequent extension to the orbit and skull base. Due to its rare incidence and recent histopathological and molecular characterization, little data are available in regard to its natural history, treatment and surveillance protocol. Methods: A comprehensive literature review in Embase online electronic databases on BSNS was made. The analyzed factors included the patients’ sex and age, presenting symptoms and signs, anatomical origin and pattern of growth of the tumor, immunohistochemical and molecular features, time to treatment, type of treatment, surgical approach, extent of resection, peri- and post-operative complications, adjuvant therapies, clinical outcome, recurrence and overall survival rates. Results: This literature review involved 34 studies for an overall series of 149 cases of BSNS. The female (66.9%) and middle-aged populations (median 54.88 years old) were mainly affected. The most frequent clinical onset was nasal obstruction (81%), followed by facial discomfort (44%), epistaxis (15.5%) and ocular impairment (14.3%). Ethmoid sinus (67.8%) and nasal cavity (45.4%) were the most common anatomical site of tumor origin, while an extension to the orbit and skull base was registered in 28.7% and 24.5% of cases. Surgery was the main treatment, especially in the form of endoscopic endonasal approach (56.9%), and allowed for gross total resection in 79% of cases. The recurrence rate was 26.2%; three cases of tumor-related death were reported. Median follow-up was 4.6 years. Conclusions: Biphenotypic sinonasal sarcoma is a rare and unique tumoral entity in terms of biological and clinical behavior. Based on the current knowledge, surgery plays the leading role in treatment, accounting for gross total tumor resection in most cases, allowing for clinical symptom and sign resolution and presenting a low rate of perioperative complications. The type of approach and the aim of surgery should be assessed case by case according to patient and pathology features and the surgeon’s experience, as well as the aim of the treatment. Further studies including large surgical series and with long follow-up are required to define prognostic factors and guidelines of treatment for this peculiar pathological entity.

Histology-Tailored Approach to Soft Tissue Sarcoma.

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.

HRD and other targetable mutations in ovarian cancer: The importance of tumor site of origin and cell type

HRD and other targetable mutations in ovarian cancer: The importance of tumor site of origin and cell type

Intracranial voltage profiles from untangled human deep sources reveal multisource composition and source allocation bias.

Intracranial potentials are used as functional biomarkers of neural networks. As potentials spread away from the source populations, they become mixed in the recordings. In humans, interindividual differences in the gyral architecture of the cortex pose an additional challenge, as functional areas vary in location and extent. We used source separation techniques to disentangle mixing potentials obtained by exploratory deep arrays implanted in epileptic patients of either sex to gain access to the number, location, relative contribution and dynamics of co-active sources. The unique spatial profiles of separated generators made it possible to discern dozens of independent cortical areas for each patient, whose stability maintained even during seizure, enabling the follow up of activity for days and across states. Through matching these profiles to MRI, we associated each with limited portions of sulci and gyri, and determined the local or remote origin of the corresponding sources. We also plotted source-specific 3D coverage across arrays. In average, individual recording sites are contributed to by 3-5 local and distant generators from areas up to several centimeters apart. During seizure, 13-85 % of generators were involved, and a few appeared anew. Significant bias in location assignment using raw potentials is revealed, including numerous false positives when determining the site of origin of a seizure. This is not amended by bipolar montage, which introduce additional errors of its own. In this way, source disentangling reveals the multisource nature and far intracranial spread of potentials in humans, while efficiently addressing patient-specific anatomofunctional cortical divergence.Significance Statement Field potentials are used to better localize zones showing normal and pathological activity. However, as potentials spread throughout the brain volume, they mix with others and make their place of origin uncertain, even when recorded intracranially. We used advanced algorithms to disentangle the activity of each these zones by their unique spatial profiles, which allowed us to determine the 3D outline of normal and epileptic areas and follow their activity for days. Dozens of independent sources per patient can be explored and precisely located. The findings show that standard stereoEEG recordings are contributed by 3-5 populations, which after separation will help to plan clinical intervention to break epileptic networks by more accurately marking epileptic foci and avoiding false positives.

Revisiting PD: Unraveling the brain-first and body-first perspectives

Parkinson’s disease (PD) has undergone significant advancements in diagnosis and treatment over the past century, with apparent dopaminergic cell degeneration on dopamine transporter scans and a strong response to medication being key features. However, the etiology remains complex, involving various pathogenic mechanisms beyond alpha-synuclein accumulation. The recent brain-first versus body-first hypothesis, emerging from advances in functional imaging and clinical symptom clustering, suggests distinct starting points of alpha-synuclein pathology-either in the brain or the body, with subsequent spread via neural connections. This theory, exemplified by the alpha-synuclein origin site and connectome (SOC) model, proposes that body-first PD may originate in the enteric nervous system and spread to the brain, while brain-first PD starts within the central nervous system, such as the olfactory bulb or amygdala. While the SOC model offers valuable insights into the progression of PD, it raises several controversies. Critics argue that the model may oversimplify the disease’s complexity, failing to account for overlapping symptoms and the varying progression rates observed in different subtypes. Furthermore, there are concerns about the lack of longitudinal data and the potential for reclassification of PD subtypes over time. Despite these challenges, the ongoing development of imaging techniques that reflect in-vivo pathology holds promise for resolving these controversies and advancing the selection of patients for disease-modifying therapies.

Accuracy of a non-invasive mapping system for the localisation of re-entrant VT site of origin and its relationship to myocardial scar on cross-sectional imaging

Abstract Introduction View in ventricular onset (VIVO) is a non-invasive mapping system used for localising the site of earliest activation in ventricular arrhythmia, utilising a mathematical algorithm, patient specific cardiac model (constructed using cross-sectional imaging data), 3D images of the patient’s torso (for localising surface electrodes), and a 12-lead electrocardiogram (ECG).(1, 2) Several publications have examined its role in the localisation of premature ventricular contractions (PVCs), and a 5 patient case series assessed its role in scar related re-entrant VT.(1-4) However, its validity in a larger cohort and of the relationship to the relevant myocardial scar has not been investigated. Objective Assess the accuracy of the VIVO mapping system in localising the VT-SoO for patients with scar related re-entrant VT and its relationship to the relevant myocardial scar on cross-sectional imaging. Methods 20 patients with structural heart disease (18 ischaemic cardiomyopathy (ICM), 1 dilated cardiomyopathy (DCM), 1 hypertrophic cardiomyopathy (HCM)) (Male n=18, 63±14 years) and recent cross-sectional cardiac imaging, were recruited over a 16-month period (table 1). All patients had a clinical indication for VT ablation and were on optimal medical therapy, 19 had an implantable cardiac defibrillator. Invasive electro-anatomical mapping (EAM) was performed with the Advisor HD Grid multipolar catheter and maps were generated using Omnipolar electrograms (EGMs). The VT-SoO was identified using an activation- or pace-map by an experienced operator and the location defined using the American heart association’s 17 segment model of the left ventricle during the procedure.(5) VIVO maps were reviewed by a second independent operator and a segment allocated, scar segments were obtained from cross-sectional imaging. A "complete match" was defined as exact segment concordance between allocated segments, "partial match" as adjacent segments, and "no match" if it does not satisfy either of those requirements. Results Mean left ventricular ejection fraction was 35.5 ± 10.6%. Mean procedure time was 242 ± 70 minutes, with a mean ablation time of 20 ± 11.1 minutes. A total of 32 re-entrant VTs were mapped. The VT exit site was identified in all cases (11 activation-map; 21 pace-map). A complete match between the EAM and VIVO map was seen in 75% of VTs and partial match in a further 15% (table 2). The VT-SoO was located withing the myocardial scar (or directly adjacent to is) in 83% of accurately mapped VTs. Procedural success (defined as freedom from device treated episodes) was seen in 90% of patients at mean follow up of 7.3 ± 4.7 months. Conclusion VIVO non-invasive mapping system was able to accurately map the VT-SoO in scar dependent VT, and identify the relevant myocardial scar as seen on cross sectional imaging. Further research assessing its ability to accurately identify relevant ablation targets is ongoing.

Endoscopic surgery for squamous cell carcinoma in the nasal cavity and ethmoid sinus: A retrospective observational study

ObjectiveReports of endoscopic surgery for squamous cell carcinoma of the nasal cavity and ethmoid sinus are limited. Herein, we present a comprehensive account of the results obtained from performing endoscopic surgery based on the concept of en bloc resection. MethodsThis was a retrospective observational study of patients who underwent nasal endoscopic surgery for squamous cell carcinoma of the nasal cavity and ethmoid sinus at a hospital between July 2018 and December 2021. Primary endpoints were overall survival, relapse-free survival, and local recurrence-free survival. Data on tumor stage, tumor site of origin, postoperative treatment, and papilloma-related status were reviewed. Statistical analyses included the Kaplan–Meier method, Cox regression analysis, and Fisher's exact test. ResultsTwenty-two patients with a median age of 62 (range 27–84) years, comprising 15 male and 7 female, were included in this study, and the median duration of observation was 2.1 (range 0.6–4.3) years. The 2-year overall survival, relapse-free survival, and recurrence-free survival rates were 91.0%, 69.9%, and 79.0%, respectively. Cancer of the nasal cavity was significantly superior to that of the ethmoid sinus in terms of local recurrence-free survival (p = 0.03). The patients who underwent postoperative treatment had significantly worse recurrence-free survival rates than those who did not receive postoperative treatment (p = 0.03). ConclusionsThis study examined the results of the endoscopic treatment for squamous cell carcinoma of the nasal cavity and ethmoid sinus with the concept of en bloc resection. Patients with ethmoid sinus carcinoma had a greater risk for local recurrence, and the prognosis for patients requiring postoperative treatment was poor.

An unusual liver tumor with challenging morphologic features and immunophenotype: A case report of metastatic HPV-driven basaloid anal squamous cell carcinoma

Abstract Introduction/Objective Basaloid squamous cell carcinoma (BSCC), a rare subtype of squamous cell carcinoma, occurs most commonly in esophagus, lungs, and head and neck. Anal BSCC is extremely rare and has a 10-20% rate of metastasis. High-risk HPV (HR-HPV) is the main causative agent. BSCC occurrence in an atypical site without a known primary tumor, and with atypical immunoprofile can be a diagnostic challenge. Methods/Case Report We report an 83-year-old female with history of breast carcinoma who presented for worsening chest pain. Imaging studies showed pulmonary nodules, 1.8 cm hepatic mass, and pelvic nodules. Liver biopsy showed infiltrating nests of carcinoma with solid and cribriform patterns and luminal necrosis. Some tumor nests had basaloid features with peripheral palisading. Tumor was positive for CK7 and pankeratin; and negative for ER, SOX10, GATA3, GCDFP-15 (Breast markers), CDX2 (GI marker), P63 and P40 (squamous markers), INSM1, Synaptophysin (Neuroendocrine) and TTF1 (lung adenocarcinoma). There was microfocal staining with CK20 and SATB2. Tumor morphology and immunophenotype were not entirely specific to the site of origin. Further search into patient’s medical history showed a recent anal mucosal biopsy revealing a high-grade squamous epithelial lesion with diffuse P16 reactivity. The slides for the anal lesion were reviewed and showed morphologic features similar to the liver biopsy. Additional studies showed both tumors were positive for HR-HPV ISH, P16 (diffuse), and CK5/6 (patchy); and negative for P63. The morphologic features and immunoprofile were supportive of metastasis from HPV-driven BSCC of anus. Subsequent PET Scan revealed a rectal/anal mass. Results (if a Case Study enter NA) NA Conclusion For tumors with unusual morphology and immunophenotype, complete medical history review, and communication with clinician are important tools in achieving correct diagnosis. HR-HPV ISH is a new tool that can be very useful in reaching correct diagnosis in metastatic anogenital or oropharyngeal squamous carcinomas with basaloid features.

Comparison of Ampullary and Pancreatic Adenocarcinomas: Smaller Invasion, Common Adenomatous Components, Resectability, and Histology are Factors for Improved Survival for Patients with Ampullary Adenocarcinoma.

The information on the clinicopathologic/outcome differences between ampullary adenocarcinoma (AC) and pancreatic adenocarcinoma (PC) has been conflicting to the extent that it still is questioned whether ACs need to be recognized separately from PCs. The characteristics of 413 ACs were compared with those of 547 PCs. The ACs had a better prognosis than the PCs (5-year survival, 57 % vs 23 %; p < 0.001). Even the pancreatobiliary (PB)-type ACs had a better prognosis (5-year survival, 46 % vs 23 %; p < 0.001). Several differences also were identified as contributing factors: (1) the preinvasive adenomatous component often constituted a significant proportion of the mass in ACs (>50 % of the tumor in 16 % vs 1.5 %; p < 0.001); (2) the mean size of the carcinoma was smaller in ACs (2.5 vs 3.2 cm; p < 0.001): when matched for invasion size, the survival advantage of AC was minimized, and when matched for invasion size larger than 2 cm, the survival advantage of AC lost its statistical significance; (3) lymph node (LN) metastases were less common in ACs (49 % vs 71 %; p < 0.001); (4) the definitive R1 rate was lower in ACs (4 % vs 23.5 %; p < 0.001); and (5) non-PB and non-tubular adenocarcinoma types were more common in ACs (17 % vs 3 %; p < 0.001). Comparatively, ACs have better clinical survival than PCs. Potential contributing factors are the relative abundance of the preinvasive component, smaller invasion, lower LN metastasis rate, higher resectability, and common occurrence of less aggressive histologic phenotypes (intestinal, medullary, mucinous). However, this survival advantage is sustained even in PB-type ACs, highlighting the importance of accurately determining the site of origin.

Signet ring cell carcinoma of the urinary bladder presenting with carcinocythemia and skeletal metastasis: A case report

Cancer of unknown primary accounts for approximately 3 &amp;ndash; 5% of all malignancies and is typically associated with a dismal prognosis. We describe a 65-year-old man who presented with skeletal metastasis and circulating tumor cells exhibiting signet ring (SR) morphology. The patient was diagnosed with SR cell carcinoma (SRCC) through a bone marrow biopsy. This case report aimed to emphasize the importance of clinicians&amp;rsquo; awareness of SRCC of the urinary bladder. The primary site of tumor origin was not identified as antemortem. The patient died 2 months after being admitted for pulmonary embolism. At autopsy, the urinary bladder was determined to be the primary site of the tumor. Primary SRCC of the urinary bladder is extremely rare. There are currently no established consensus guidelines for its management. Surgery continues to be the primary treatment option when the condition is localized.

The Other Site of Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a rare malignant soft tissue sarcoma (STS), accounting for almost 50% of pediatric STSs. Due to its heterogeneity, RMS presents challenges in diagnosis and treatment, with prognosis varying depending on multiple factors. Tumors localized in the other site (OTH)-including the paraspinal, perianal, thoracic, abdominal, pelvic, and perineal regions-are generally classified as unfavorable. This study assesses the clinical features and prognoses of RMS in OTH locations depending on its site of origin. An explorative analysis of RMS cases from the SEER 17 database 2000-2020 was conducted. Patients of all ages with histologically confirmed RMS as primary malignant disease classified under OTH, were included. OTH was categorized in four granular site classifications. Overall survival (OS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier estimators. Factors independently influencing survival, including a site classification model presented in this study, were identified through Cox regression analysis. Out of 4168 patients with RMS, 990 cases of RMS with the OTH site met the inclusion criteria. The median age was 16 years. The predominant histological subtypes were embryonal (33.0%) and alveolar (25.5%). Most tumors were ≥ 5 cm (median 9 cm) and located primarily in the pelvic region (41.5%). The 3-, 5-, and 10-year OS rates were 45.4% ± 3.332 (95% CI), 40.7 ± 3.332, and 38.6% ± 3.332, respectively, while DSS rates were 43.3% ± 3.136 (95% CI), 38.3% ± 3.136, and 35.1% ± 3.332. In the multivariate analysis age, histological type, site in a granular categorization, stage, regional lymph node examination, and regional lymph node involvement (pathologically proven) were independently associated with survival. Through both univariate and multivariate analyses, an OTH favorable group could be established. The OTH favorable group consists of the anal region, gallbladder and biliary tract, and breast. RMS in OTH shows significant differences in prognosis, putting the current categorization as unfavorable into question and making a more detailed classification necessary. Furthermore, pathological regional lymph node assessment is specifically in the OTH localization recommended.

Origin of ventricular fibrillation triggers in a model of localized repolarization heterogeneity

BackgroundHeterogeneities in ventricular repolarization contribute significantly to the genesis of ventricular fibrillation (VF). Although clinical arrhythmias are spontaneously triggered by premature ventricular complexes, these triggers are difficult to document and little is known about their site of origin. ObjectiveTo characterize spontaneous VF initiation in an experimental model of repolarization heterogeneity and to identify the origin of triggers in relation to the spatial dispersion of repolarization. MethodsSpatially limited repolarization heterogeneity was created in isolated perfused porcine right ventricles (N =16) by local administration of pinacidil (20 μM) into a terminal branch of the right coronary artery. High-resolution optical mapping and pseudo-ECG were performed in control conditions and after pinacidil perfusion. ResultsNo arrhythmia occurred at baseline, but 74 VF episodes were observed in 13 hearts (82%) after pinacidil perfusion and were most often initiated by a ventricular trigger with short coupling interval (297±66ms). Sixteen VF initiations were optically mapped in four hearts. Mapping showed triggers originating in all cases from the border zone between altered and normal repolarization areas where local action potential duration and repolarization time gradients were steep (15.9 and 15.8 ms/mm versus 1.5 and 3.0 ms/mm in non-trigger sites). Optical action potential traces were compatible with a phase-two reexcitation mechanism. The subsequent VF cycles were driven by activities located in the same region. ConclusionsThis model of localized repolarization heterogeneity is able to produce spontaneous VF initiation. Our study demonstrates that VF triggers originate consistently from the border zone of repolarization dispersion.

Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets.

Neuroendocrine transdifferentiation (NEtD), also commonly referred to as lineage plasticity, emerges as an acquired resistance mechanism to molecular targeted therapies in multiple cancer types, predominately occurs in metastatic epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors and metastatic castration-resistant prostate cancer treated with androgen receptor targeting therapies. NEtD tumors are the lethal cancer histologic subtype with unfavorable prognosis and limited treatment. A comprehensive understanding of molecular mechanism underlying targeted-induced plasticity could greatly facilitate the development of novel therapies. In the past few years, increasingly elegant studies indicated that NEtD tumors share key the convergent genomic and phenotypic characteristics irrespective of their site of origin, but also embrace distinct change and function of molecular mechanisms. In this review, we provide a comprehensive overview of the current understanding of molecular mechanism in regulating the NEtD, including genetic alterations, DNA methylation, histone modifications, dysregulated noncoding RNA, lineage-specific transcription factors regulation, and other proteomic alterations. We also provide the current management of targeted therapies in clinical and preclinical practice.

Using Empirical Performance Data to Source Bluebunch and Snake River Wheatgrass Plant Materials to Restoration Sites in the Eastern Great Basin, USA.

To infer adaptation of plant material, restoration practitioners often consider only surrogate geographic or climatic information. However, empirical biomass data could assist in deciding what material to use where. To test this approach, we transplanted seven bluebunch wheatgrass (BBWG; Pseudoroegneria spicata) and five Snake River wheatgrass (SRWG; Elymus wawawaiensis) populations to three sites ranging from low to high precipitation (LPPT, MPPT, and HPPT). We measured establishment-year (2011) biomass at all sites and 2012-16 biomass at MPPT and HPPT. When data were standardized by site, P-7 and Anatone produced the mostBBWG biomass across sites and Wahluke the least in both 2011 and 2012-16, while E-58X produced the most SRWG biomass and Secar and E-49X the least in 2011 and 2012-16, respectively. Among BBWG populations in 2011, relative performance of P-7 (G6 generation) and Goldar increased and Whitmar decreased at wetter sites, while Columbia was stable (high) and Wahluke was stable (low) over sites. Among SRWG populations in 2011, Secar, Secar78, and E-58X increased at drier sites and Discovery at wetter sites. However, once established, populations of both species were much more similar for trend. In 2012-16, trend somewhat increased for five BBWG populations from MPPT to HPPT, was stable for Wahluke, but declined for Columbia, while all five SRWG populations declined at HPPT. These results suggest that, once established, BBWG is mostly stable across sites, while SRWG is less adapted to wetter sites. In 2012-16, BBWG populations originating at drier (or wetter) sites mostly performed relatively better at MPPT (or HPPT), suggesting adaptation to site. However, in the establishment year (2011), this relationship did not hold, suggesting seedling vigor and immature growth rate play a stronger role than precipitation at the site of origin.

On the Origin of Abdominal Venous Leiomyosarcomas: The Role of the Sex-Hormone Drainage Pathways.

We hypothesized that abdominal venous leiomyosarcoma (AV-LMS) disproportionately originates in veins of the sex-hormone drainage pathway (SHDP). Our purpose was to classify the anatomical origin of AV-LMS in a large cohort using imaging and explore prognostic implications. A retrospective review of imaging of all patients presenting with abdominal non-uterine LMS at a single tertiary oncology center was performed. Inclusion criteria were a biopsy-proven LMS of non-uterine abdominal/pelvic origin with pretreatment enhanced computed tomography (CT)/magnetic resonance imaging (MRI). Patients with uterine LMS or prior radiation were excluded. LMS site of origin was assigned by one expert radiologist and indeterminate sites were reviewed with a second external expert radiologist. Locations of inferior vena cava (IVC) tumors were subclassified based on a modification of prior literature. SHDP was defined as originating from ovarian/testicular vein, distal left renal vein, adrenal vein or mid-IVC (IIA). One hundred fifty-five (155) patients were included (92/152 (61%) female) with distant metastases found at presentation in 23/155 (14.8%). Most common organs of origins were veins (84/152, 55.3%), gastrointestinal (24, 15.8%), genital (11, 7.2%) and paratesticular/spermatic cord (11, 7.2%). For venous LMS, the adrenal (both sexes), mid-IVC (IVC IIA, females) and ovarian veins had the highest relative predilection for abdominal non-uterine LMS. Eighty-four (84/152, 55.3%) of tumors were SHDP. On multivariable analysis, both size and SHDP were significant predictors of distant metastases at presentation (P = 0.01), while sex, age, organ system/site and grade were not. For both sexes, tumors arising from SHDP constitute the majority of AV-LMS and may impart a significantly lower risk of metastatic disease at presentation. Among veins, the adrenal veins had the highest predilection for LMS.

Racial disparities in end-of-life care among patients with neuroendocrine tumors.

60 Background: Due to the rising incidence of neuroendocrine tumors (NETs), the prevalence of NETs now surpasses many other malignancies. Due to a slower course of disease and lack of awareness among care teams, end-of-life (EOL) care is typically underutilized in patients with NETs. Owing to a heavy symptom burden (related to disease burden and/or functionality), patients with NETs often struggle due to lack of palliative care and eventually EOL care support. Prior studies have revealed that Black patients with advanced cancer are more likely to receive aggressive care and suffer a significant decline in quality of life at EOL. However, similar data investigating racial differences in EOL among patients with NETs are lacking. Methods: The National Inpatient Sample (NIS) was queried between years 2016-2020 to identify all hospitalizations (regardless of site of origin) with NETs utilizing the appropriate ICD-10 codes (neuroendocrine carcinomas were excluded). Hospitalizations of White and Black patients with documented inpatient mortality events were then extracted. Demographic and clinical data were analyzed using independent sample t-test, Chi-square test, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). NIS discharge weights were applied to calculate national estimates. Statistical analyses were performed with SPSS 28.0. A p-value of &lt;0.05 was considered statistically significant. Results: A total of 6,265 hospitalizations with NETs were included, of which 5,125 (81.8%) and 1,140 (18.2%) had White and Black patients respectively. Black patients were younger, more likely to be females, and less likely to have a do not resuscitate (DNR) code status. There was no significant difference in CCI between the groups. Palliative care consultation was less likely to be performed among Black patients (adjusted OR=0.70, p&lt;.001). Black patients also had longer mean length of stay in the hospital (10.25 vs 8.42 days, p&lt;.001). Black patients were also more likely to receive aggressive care in the form of mechanical ventilation at EOL (Table). Conclusions: This is the largest analysis demonstrating significant racial disparities in EOL care among patients with NETs. Black patients had longer inpatient stay, were less likely to receive inpatient palliative care consultation, have a DNR order and more likely to receive aggressive care at EOL. These findings may have implications for informing healthcare decision making for EOL care among Black patients with NETs. WhiteN=5125 BlackN=1140 aOR (95% CI) p-value Age (years) 67.67 ± 11.89 65.14 ± 11.29 - &lt;.001 Females 46.1% 50.9% - .004 CCI 11.0 ± 3.22 10.9 ± 3.42 - .538 Mean length of stay 8.42 ± 10.03 10.25 ± 15.75 - &lt;.001 Palliative 62.6% 54.5% 0.70 (.61-.80) &lt;.001 DNR 64.9% 60.1% 0.80 (.70-.92) .002 Blood transfusion 13.2% 15.4% 1.18 (.98-1.41) .052 Mechanical ventilation 28.8% 38.6% 1.55 (1.35-1.77) &lt;.001 Vasopressor 9% 9.6% 1.07 (.86-1.33) .47

Multielectrode catheter-induced ectopy mapping: a novel technique for ablation of infrequent premature ventricular contractions

BackgroundAblation of infrequent premature ventricular complexes (PVC) is challenging. ObjectivesA novel mapping strategy for patients with infrequent PVCs, called “multielectrode catheter-induced ectopy mapping” (MECIE-mapping) is described, aiming at performing a hybrid activation/template matching map by taking advantage of multielectrode catheter-induced arrhythmogenicity. MethodsPatients referred to three tertiary centers for PVC ablation were prospectively enrolled if they had infrequent PVCs (less than 1 PVC per minute) at onset of procedure, preventing the realization of an accurate activation map. A detailed MECIE-map was created using the arrhythmogenic property of multielectrode catheters, corresponding to a local activation time (LAT) map generated by annotating LAT from mechanical PVCs. Selecting mechanical PVCs with ≥ 99% concordance with the clinical PVC spotted the site of origin where ablation was delivered. The primary endpoint was long-term success, defined as an > 80% reduction in PVC burden during follow-up. Results29 patients were included, with 25 [IQR 7-30] PVCs in the initial 30 minutes of procedure. During MECIE-mapping, 67 [IQR 1-332] points with ≥ 99% concordance were acquired. The best LAT was 34.0±9.5 ms before QRS onset. Pace-mapping was 97.4±3.1% compared to the clinical PVC. Ablation was locally performed. After 13.2±5.1 months of follow-up, 27 patients (93.1 %) had 80% reduction in PVC burden, and only two patients had a symptomatic recurrence. ConclusionsA detailed MECIE-map taking advantage of multielectrode catheter arrhythmogenicity may be generated to spot the origin of PVCs, a strategy resulting in a good procedural success rate.

Brain-first forms of Parkinson's disease are over-represented in patients with non-responsive resting tremor

Motor subtypes in Parkinson's Disease (PD) are unstable over time, limiting mechanistic insights and biomarker discovery. We focused on Rest Tremor (RT) as a symptom to test for phenotype stability and link it to specific circuits and disease mechanisms. Using the PPMI cohort data over 5 years we found that RT is more stable than classical Tremor-Dominant definitions, a stability also seen for RT response to therapy. At time of diagnosis, the population of therapy-resistant RT patients was enriched with a brain-first PD profile as predicted by a-Synuclein origin site and connectome (SOC) model. Resistant-RT patients have lower gastrointestinal and cardiovascular symptoms, lower prevalence of probable REM-Sleep behaviour disorder, and higher dopaminergic asymmetry compared to therapy-responsive or no tremor patients. Treating RT as a distinct phenomenon revealed a relative phenotypic stability with treatment response being linked to different patterns of disease progression.