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The detection of the Epoch of Reionization (EoR) delay power spectrum using a 'foreground avoidance method' highly depends on the instrument chromaticity. The systematic effects induced by the radio telescope spread the foreground signal in the delay domain, which contaminates the EoR window theoretically observable. Applied to the Hydrogen Epoch of Reionization Array (HERA), this paper combines detailed electromagnetic and electrical simulations in order to model the chromatic effects of the instrument, and quantify its frequency and time responses. In particular, the effects of the analogue receiver, transmission cables, and mutual coupling are included. These simulations are able to accurately predict the intensity of the reflections occurring in the 150-m cable which links the antenna to the backend. They also show that electromagnetic waves can propagate from one dish to another one through large sections of the array due to mutual coupling. The simulated system time response is attenuated by a factor 104 after a characteristic delay which depends on the size of the array and on the antenna position. Ultimately, the system response is attenuated by a factor 105 after 1400 ns because of the reflections in the cable, which corresponds to characterizable ka-modes above 0.7 $h\,\,\rm {Mpc}^{-1}$ at 150 MHz. Thus, this new study shows that the detection of the EoR signal with HERA Phase I will be more challenging than expected. On the other hand, it improves our understanding of the telescope, which is essential to mitigate the instrument chromaticity.

Characterizing the epoch of reionization (EoR) at z 6 via the redshifted 21 cm line of neutral Hydrogen (H i) is critical to modern astrophysics and cosmology, and thus a key science goal of many current and planned low-frequency radio telescopes. The primary challenge to detecting this signal is the overwhelmingly bright foreground emission at these frequencies, placing stringent requirements on the knowledge of the instruments and inaccuracies in analyses. Results from these experiments have largely been limited not by thermal sensitivity but by systematics, particularly caused by the inability to calibrate the instrument to high accuracy. The interferometric bispectrum phase is immune to antenna-based calibration and errors therein, and presents an independent alternative to detect the EoR H i fluctuations while largely avoiding calibration systematics. Here, we provide a demonstration of this technique on a subset of data from the Hydrogen Epoch of Reionization Array (HERA) to place approximate constraints on the brightness temperature of the intergalactic medium (IGM). From this limited data, at z=7.7 we infer "1σ"upper limits on the IGM brightness temperature to be ≤ 316 "pseudo"mK at κ =0.33 "pseudo"h Mpc-1 (data-limited) and ≤ 1000 "pseudo"mK at κ =0.875 "pseudo"h Mpc-1 (noise-limited). The "pseudo"units denote only an approximate and not an exact correspondence to the actual distance scales and brightness temperatures. By propagating models in parallel to the data analysis, we confirm that the dynamic range required to separate the cosmic H i signal from the foregrounds is similar to that in standard approaches, and the power spectrum of the bispectrum phase is still data-limited (at 106 dynamic range) indicating scope for further improvement in sensitivity as the array build-out continues.

The key challenge in the observation of the redshifted 21-cm signal from cosmic reionization is its separation from the much brighter foreground emission. Such separation relies on the different spectral properties of the two components, although, in real life, the foreground intrinsic spectrum is often corrupted by the instrumental response, inducing systematic effects that can further jeopardize the measurement of the 21-cm signal. In this paper, we use Gaussian Process Regression to model both foreground emission and instrumental systematics in ∼2 h of data from the Hydrogen Epoch of Reionization Array. We find that a simple co-variance model with three components matches the data well, giving a residual power spectrum with white noise properties. These consist of an 'intrinsic' and instrumentally corrupted component with a coherence scale of 20 and 2.4 MHz, respectively (dominating the line-of-sight power spectrum over scales kâ ≤ 0.2 h cMpc-1) and a baseline-dependent periodic signal with a period of ∼1 MHz (dominating over kâ ∼0.4-0.8 h cMpc-1), which should be distinguishable from the 21-cm Epoch of Reionization signal whose typical coherence scale is ∼0.8 MHz.

In 21-cm cosmology, precision calibration is key to the separation of the neutral hydrogen signal from very bright but spectrally smooth astrophysical foregrounds. The Hydrogen Epoch of Reionization Array (HERA), an interferometer specialized for 21-cm cosmology and now under construction in South Africa, was designed to be largely calibrated using the self-consistency of repeated measurements of the same interferometric modes. This technique, known as redundant-baseline calibration resolves most of the internal degrees of freedom in the calibration problem. It assumes, however, on antenna elements with identical primary beams placed precisely on a redundant grid. In this work, we review the detailed implementation of the algorithms enabling redundant-baseline calibration and report results with HERA data.We quantify the effects of real-world non-redundancy and how they compare to the idealized scenario in which redundant measurements differ only in their noise realizations. Finally, we study how non-redundancy can produce spurious temporal structure in our calibration solutions-both in data and in simulations-and present strategies for mitigating that structure.

Radio frequency interference (RFI) is an ever-present limiting factor among radio telescopes even in the most remote observing locations. When looking to retain the maximum amount of sensitivity and reduce contamination for Epoch of Reionization studies, the identification and removal of RFI is especially important. In addition to improved RFI identification, we must also take into account computational efficiency of the RFI-Identification algorithm as radio interferometer arrays such as the Hydrogen Epoch of Reionization Array (HERA) grow larger in number of receivers. To address this, we present a deep fully convolutional neural network (DFCN) that is comprehensive in its use of interferometric data, where both amplitude and phase information are used jointly for identifying RFI. We train the network using simulated HERA visibilities containing mock RFI, yielding a known ‘ground truth’ data set for evaluating the accuracy of various RFI algorithms. Evaluation of the DFCN model is performed on observations from the 67 dish build-out, HERA-67, and achieves a data throughput of 1.6 × 105 HERA time-ordered 1024 channelled visibilities per hour per GPU. We determine that relative to an amplitude only network including visibility phase adds important adjacent time–frequency context which increases discrimination between RFI and non-RFI. The inclusion of phase when predicting achieves a recall of 0.81, precision of 0.58, and F2 score of 0.75 as applied to our HERA-67 observations.

Foreground power dominates the measurements of interferometers that seek a statistical detection of highly-redshifted H i emission from the Epoch of Reionization (EoR). The chromaticity of the instrument creates a boundary in the Fourier transform of frequency (proportional to k ∥) between spectrally smooth emission, characteristic of the strong synchrotron foreground (the "wedge"), and the spectrally structured emission from H i in the EoR (the "EoR window"). Faraday rotation can inject spectral structure into otherwise smooth polarized foreground emission, which through instrument effects or miscalibration could possibly pollute the EoR window. For instruments pursuing a "foreground avoidance" strategy of simply measuring in the EoR window, and not attempting to model and remove foregrounds, as is the plan for the first stage of the Hydrogen Epoch of Reionization Array (HERA), characterizing the intrinsic instrument polarization response is particularly important. Using data from the HERA 19-element commissioning array, we investigate the polarization response of this new instrument in the power-spectrum domain. We perform a simple image-based calibration based on the unpolarized diffuse emission of the Global Sky Model, and show that it achieves qualitative redundancy between the nominally redundant baselines of the array and reasonable amplitude accuracy. We construct power spectra of all fully polarized coherencies in all pseudo-Stokes parameters, and discuss the achieved isolation of foreground power due to the intrinsic spectral smoothness of the foregrounds, the instrument chromaticity, and the calibration. We compare to simulations based on an unpolarized diffuse sky model and detailed electromagnetic simulations of the dish and feed, confirming that in Stokes I, the calibration does not add significant spectral structure beyond that expected from the interferometer array configuration and the modeled primary beam response. Furthermore, this calibration is stable over the 8 days of observations considered. Excess power is seen in the power spectra of the linear polarization Stokes parameters, which is not easily attributable to leakage via the primary beam, and results from some combination of residual calibration errors and actual polarized emission. Stokes V is found to be highly discrepant from the expectation of zero power, strongly pointing to the need for more accurate polarized calibration.

21 cm cosmology is a promising new probe of the evolution of visible matter in our universe, especially during the poorly constrained Cosmic Dawn and Epoch of Reionization. However, in order to separate the 21 cm signal from bright astrophysical foregrounds, we need an exquisite understanding of our telescopes so as to avoid adding spectral structure to spectrally smooth foregrounds. One powerful calibration method relies on repeated simultaneous measurements of the same interferometric baseline to solve for the sky signal and for instrumental parameters simultaneously. However, certain degrees of freedom are not constrained by asserting internal consistency between redundant measurements. In this paper, we review the origin of these degeneracies of redundant-baseline calibration and demonstrate how they can source unwanted spectral structure in our measurement and show how to eliminate that additional, artificial structure. We also generalize redundant calibration to dual-polarization instruments, derive the degeneracy structure, and explore the unique challenges to calibration and preserving spectral smoothness presented by a polarized measurement.

Spectral structures due to the instrument response is the current limiting factor for the experiments attempting to detect the redshifted 21 cm signal from the Epoch of Reionization (EoR). Recent advances in the delay spectrum methodology for measuring the redshifted 21 cm EoR power spectrum brought new attention to the impact of an antenna’s frequency response on the viability of making this challenging measurement. The delay spectrum methodology provides a somewhat straightforward relationship between the time-domain response of an instrument that can be directly measured and the power spectrum modes accessible to a 21 cm EoR experiment. In this paper, we derive the explicit relationship between antenna reflection coefficient (S11) measurements made by a Vector Network Analyzer (VNA) and the extent of additional foreground contaminations in delay space. In the light of this mathematical framework, we examine the chromaticity of a prototype antenna element that will constitute the Hydrogen Epoch of Reionization Array (HERA) between 100 and 200 MHz. These reflectometry measurements exhibit additional structures relative to electromagnetic simulations, but we find that even without any further design improvement, such an antenna element will support measuring spatial k modes with line-of-sight components of k∥ > 0.2h Mpc− 1. We also find that when combined with the powerful inverse covariance weighting method used in optimal quadratic estimation of redshifted 21 cm power spectra the HERA prototype elements can successfully measure the power spectrum at spatial modes as low as k∥ > 0.1h Mpc− 1. This work represents a major step toward understanding the HERA antenna element and highlights a straightforward method for characterizing instrument response for future experiments designed to detect the 21 cm EoR power spectrum.

In order to study the "Cosmic Dawn" and the Epoch of Reionization with 21 cm tomography, we need to statistically separate the cosmological signal from foregrounds known to be orders of magnitude brighter. Over the last few years, we have learned much about the role our telescopes play in creating a putatively foreground-free region called the "EoR window." In this work, we examine how an interferometer's effects can be taken into account in a way that allows for the rigorous estimation of 21 cm power spectra from interferometric maps while mitigating foreground contamination and thus increasing sensitivity. This requires a precise understanding of the statistical relationship between the maps we make and the underlying true sky. While some of these calculations would be computationally infeasible if performed exactly, we explore several well-controlled approximations that make mapmaking and the calculation of map statistics much faster, especially for compact and highly redundant interferometers designed specifically for 21 cm cosmology. We demonstrate the utility of these methods and the parametrized trade-offs between accuracy and speed using one such telescope, the upcoming Hydrogen Epoch of Reionization Array, as a case study.

The Ca2+ antagonists are a novel group of drugs useful in management of a variety of cardiac disorders. They differ from one another in terms of their chemistry, tissue specificity and selectivity. As a group, however, they share the common property of slowing Ca2+ entry through voltage-activated, ion-selective channels. Some of them exhibit other properties, including that of interfering with Na+ transport. At least one of them, diltiazem, has an intracellular action. Specific high and low affinity binding sites have been identified for two of the major groups of Ca2+-antagonists, with the binding sites for verapamil and its derivatives being distinct from those which can be occupied by the dihydropyridines. The number (Bmax) and affinity (KD) of these binding sites changes under certain pathological conditions-including a reduction in ischaemia and in spontaneous hypertension, an increase in the latter, at present, only demonstrated for the dihydropyridine binding sites. The sensitivity of a particular tissue to these drugs will depend upon a number of factors including the number of binding sites that are present, the contribution made by the Ca2+ entering through the voltage-activated channels to the functioning of the tissue, and properties which are peculiar to a particular type of Ca2+ antagonist, for example, whether, as in the case of verapamil, they exhibit use-dependence. [ABSTRACT FROM AUTHOR]

Background: Peptide receptor radionuclide therapy (PRRT) is an effective treatment for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). We investigated a 2-decade experience with PRRT to determine whether PRRT confers a survival advantage to patients who progress after surgery versus other therapies., Methods: We identified patients from our clinic who had resection/cytoreduction of GEP-NETs, then disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The Kaplan-Meier method assessed progression-free survival (PFS) and overall survival (OS), calculated from progression after surgery (no-PRRT group) or the start of PRRT. Cox regression with time-dependent covariates controlled for immortal time bias and other confounders., Results: Overall, 237 patients progressed after surgery; 95 received PRRT and 142 did not. No differences existed in sex, T or N stage, tumor grade/differentiation, primary site, or time to progression; 94% of PRRT patients had metastases at diagnosis versus 77% in the no-PRRT group. Median PFS was longer in the PRRT group versus the no-PRRT group (32.4 vs. 11.0 months, p < 0.001), as was median OS (49.8 vs. 38.4 months; p = 0.009). In subgroup analysis, the PRRT group had improved PFS in small bowel NETs and pancreatic NETs. Time-dependent covariate analysis revealed a lower risk of death associated with PRRT (hazard ratio 0.61, p = 0.028) after adjusting for sex, age, M stage, tumor grade, and primary site., Conclusion: Surgical resection and cytoreduction is an effective treatment for patients with GEP-NETs, but most patients with metastatic disease develop recurrent disease. Surgery followed by PRRT after progression conferred superior PFS and OS over no PRRT/other therapies, and is an effective strategy for managing patients with GEP-NETs., (© 2024. Society of Surgical Oncology.)

Purpose: Renal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT., Methods: A retrospective cohort of 448 NET patients treated with either 177 Lu-DOTATATE or 90 Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions., Results: Of the 448 PRRT treated patients, 335 received 177 Lu-DOTATATE (74.78%) and 113 were treated with 90 Y-DOTATOC (25.22%). Comparing patients treated with 177 Lu-DOTATATE to those treated with 90 Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with 90 Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with 177 Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received 177 Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with 90 Y-DOTATOC, but there was no difference in OS., Conclusion: There was no significant renal, but minor hematological toxicity, in patients treated with 177 Lu-DOTATATE compared with 90 Y-DOTATOC. Compared to 90 Y-DOTATOC, 177 Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with 177 Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT., (© 2024. The Author(s).)

Functional neuroendocrine neoplasms (NENs) are those associated with specific symptoms related to the hormonal secretion of the NENs. Although less than 25 % of NENs are functional at diagnosis, 1 the associated syndromes significantly increase the patient burden of disease. Management of hormonal NEN symptoms may involve tumor resection or other reduction strategies (e.g., chemotherapy, embolotherapy, etc), but also specific therapies directed at decreasing hormonal synthesis, secretion, or end-organ effects. In this review, we focus on specific symptomatic management of many of the NEN syndromes, which may be pursued in addition to management primarily directed at tumor bulk and growth. A continued focus on symptom management related to the hormonal secretions of NENs, in the context of other efforts to reduce tumor bulk and growth, could significantly improve patient wellbeing., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JSD: Crinetics Pharmaceuticals related clinical research trial If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Iowa Neuroendocrine Tumor (NET) Clinic was founded and developed by two remarkable physicians, Thomas and Sue O'Dorisio. Tom was an Endocrinologist and close friend and colleague of Aaron Vinik. Both men were pioneers in studies of gastrointestinal hormones and the management of patients with NETs. Sue was a Pediatric Oncologist and research scientist with great expertise in new drug development and clinical trials. She and Tom were leaders in bringing somatostatin analogs and somatostatin-conjugated radioligands to the clinic for the therapy and diagnosis of NETs. All three physicians received lifetime achievement awards for their contributions to the field of NETs. This is the story of how the Iowa NET Clinic developed over the years to become a model for the multidisciplinary mantagement of patients with NETs, culminating in its designation as a European Neuroendocrine Tumor Society NET Center of Excellence, and the receipt of a Specialized Project of Research Excellence (SPORE) grant for the study of NETs from the National Institutes of Health., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Introduction: The available data for the safety and efficacy of repeat peptide receptor radionuclide therapy (PRRT) are almost exclusively from European centers. We present an updated experience with repeat PRRT in a cohort of US patients with neuroendocrine tumors (NETs) at our NET center of excellence., Methods: We used our single-center longitudinal NET registry to identify patients who had been previously treated with at least one dose of PRRT (PRRT 1, either 177 Lu DOTATATE or 90 Y DOTATOC) and following radiographic disease progression were re-treated with a second course of PRRT (PRRT 2). We reviewed patient, tumor and treatment characteristics, objective response rates, and toxicities after PRRT 1 and PRRT 2., Results: A total of 11 patients were included in the analysis. 45.5% (5/11) of patients received 177 Lu DOTATATE PRRT only, both for PRRT1 and PRRT 2, while 54.5% (6/11) of patients received 90 Y DOTATOC PRRT for PRRT1. At first restaging scan after PRRT2 (3-6 months), 18.2% (2/11), 36.4% (4/11), and 27.3% (3/11) of patients had PR, SD, and PD, respectively; 2/11 patients (18.2%) died before the first restaging scan. Therefore, 5/11 (45.5%) patients were noted to have disease progression. Median PFS for PRRT1 was 25.4 months and median PFS for PRRT2 was 13.1 months (p = 0.0001). We did not find a statistically significant difference between the occurrence of short and long-term hematological toxicities as well as renal toxicity after PRRT1 and PRRT2., Conclusion: We show that repeat PRRT may benefit select patients and have an acceptable safety profile. In our cohort, PFS was significantly lower after PRRT2 as compared to PRRT1., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Screening for carcinoid heart disease (CHD), has historically lacked consensus expert guidelines. In 2017, the North American Neuroendocrine Tumor Society (NANETS) released expert recommendations for CHD screening among NET patients to improve CHD detection. The objective of this study is to evaluate CHD screening trends and utility of screening guidelines over more than two decades at a single tertiary care center., Materials and Methods: Patients with NETs referred for abdominal surgical evaluation at a single tertiary care center were included, 300 patients from 1999 to 2018 and 34 patients from 2021 to 2022. Lab values for the following NANETS-proposed criteria at any point during their treatments were recorded: NETs with liver metastasis, blood serotonin >5 times upper limit of normal (>1000 ng/mL), NT-ProBNP >260 pg/mL and clinical features suggestive of CHD., Results: 85 % (285/334) of patients included in this study met one or more expert-recommended CHD screening criteria. However, 40 % (132/285) of patients meeting one or more criteria received CHD screening via echocardiogram at some point following NET diagnosis. While rates of screening for patients increased from the first decade to the second decade (32 % vs 40.6 %), the rates were much higher after guideline publication (70 %, 24/34). Furthermore, patients meeting multiple screening criteria were more likely to have evidence of structural valve disease., Conclusions: Results of this study suggest that utilization of these four expert-recommended screening criteria have greatly increased rates of CHD screening via echocardiogram and could assist in improving early CHD detection, especially for patients meeting multiple criteria., (© 2024 The Author(s).)

The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.

Background: Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are rare, aggressive tumors with poor prognosis. The World Health Organization 2017 and 2019 classifications further subdivided G3 NENs into G3 neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). Current guidelines favor medical management in most of these patients, and the role of surgical management is not well defined. We performed a systematic literature review and meta-analysis of surgical management versus nonsurgical management for G3 GEP NENs., Materials and Methods: A PRISMA-compliant systematic review of the MEDLINE, Embase, Scopus, and Cochrane Library databases (end-of-search date: 16 July 2021) was conducted. Individual patient survival data were reconstructed, and random-effects meta-analyses were performed., Results: Fourteen studies comprising 1810 surgical and 910 nonsurgical patients were systematically reviewed. Publication bias adjusted meta-analysis of 12 studies (1788 surgical and 857 nonsurgical patients) showed increased overall survival (OS) after surgical compared with nonsurgical management for G3 GEP NENs [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.31-0.53]. Subgroup meta-analyses showed increased OS after surgical management for both pancreatic and gastrointestinal primary sites separately. In another subgroup meta-analysis of G3 GEP NETs (not NECs), surgical management was associated with increased OS compared with nonsurgical management (HR 0.26, 95% CI 0.11-0.61)., Conclusions: Surgical management of G3 GEP NENs may provide a potential survival benefit in well-selected cases. Further research is needed to define which patients will benefit most from surgical versus nonsurgical management. The current literature is limited by inconsistent reporting of survival outcomes in surgical versus nonsurgical groups, tumor grade, differentiation, primary tumor site, and selection criteria for surgical and nonsurgical management., (© 2022. Society of Surgical Oncology.)

Background: Grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are aggressive tumors with poor survival outcomes for which medical management is generally recommended. This study sought to evaluate outcomes of surgically treated G3 GEP-NEN patients., Methods: A single-institutional prospective NEN database was reviewed. Patients with G3 GEP-NENs based on World Health Organization (WHO) 2019 definitions included well-differentiated neuroendocrine tumors (G3NET) and poorly differentiated neuroendocrine carcinomas (G3NEC). Clinicopathologic factors were compared between groups. Overall survival from G3 diagnosis was assessed by the Kaplan-Meier method., Results: Surgical resection was performed for 463 patients (211 G1, 208 G2, 44 G3). Most had metastatic disease at presentation (54% G1, 69% G2, 91% G3; p < 0.001). The G3 cohort included 39 G3NETs and 5 G3NECs, 22 of pancreatic and 22 of midgut origin. Median overall survival (mOS; in months) was 268.1 for G1NETs, 129.9 for G2NETs, 50.5 for G3NETs, and 28.5 for G3NECs (p < 0.001). Over the same period, 31 G3 patients (12 G3NETs, 19 G3NECs) were treated non-surgically, with mOS of 19.0 for G3NETs and 12.4 for G3NECs., Conclusions: Surgical resection of G3 GEP-NENs remains controversial due to poor prognosis, and surgical series are rare. This large, single-institutional study found significantly lower mOS in patients with resected G3NENs than those with G1/G2 tumors, reflecting more aggressive tumor biology and a higher proportion with metastatic disease. The mOS for resected G3NETs and G3NECs exceeded historical non-surgical G3NEN series (mOS 11-19 months), suggesting surgery should be considered in carefully selected patients with G3NENs, especially those with well-differentiated tumors., (© 2022. Society of Surgical Oncology.)

Background: Management of duodenal neuroendocrine tumors (DNETs) is not standardized, with smaller lesions (< 1-2 cm) generally treated by endoscopic mucosal resection (EMR) and larger DNETs by surgical resection (SR). This study reviewed how patients were selected for treatment and compared outcomes., Patients and Methods: Patients with DNETs undergoing resection were identified through institutional databases, and clinicopathologic data recorded. χ 2 and Wilcoxon tests compared variables. Survival was determined by Kaplan-Meier, and Cox regression tested association with survival., Results: Among 104 patients, 64 underwent EMR and 40 had SR. Patients selected for SR had larger tumor size, younger age, and higher T, N, and M stage. There was no difference in progression-free (PFS) or overall survival (OS) between SR and EMR. In 1-2 cm DNETs, there was no difference in PFS between SR and EMR [median not reached (NR), P = 0.1]; however, longer OS was seen in SR (median NR versus 112 months, P = 0.03). In 1-2 cm DNETs, SR patients were more likely to be node-positive and younger. After adjustment for age, resection method did not correlate with survival. Comparison of surgically resected DNETs versus jejunoileal NETs revealed longer PFS (median NR versus 73 months, P < 0.001) and OS (median NR versus 119 months, P = 0.004) DISCUSSION: In 1-2 cm DNETs, there was no difference in survival between EMR and SR after adjustment for age. Recurrences could be salvaged, suggesting that EMR is a reasonable strategy. Compared with jejunoileal NETs, DNETs treated by SR had improved PFS and OS., (© 2021. Society of Surgical Oncology.)