Single center outcomes from parenchymal-sparing resections and microwave ablations for neuroendocrine tumor liver metastases.

BACKGROUND: Reported outcomes after surgical debulking in patients with advanced neuroendocrine tumor liver metastases (NETLM) are sparse. METHODS: NETLM patients that underwent surgical debulking from 2019 to 2021 were reviewed. Trends in perioperative liver function, complications, symptom response, and progression-free survival were examined. RESULTS: 1069 liver lesions were debulked from 53 patients using a combination of parenchymal-sparing resections (PSR) and ultrasound-guided microwave ablations (MWA). Post-operative transaminitis and thrombocytopenia were common, and severity correlated with increasing number of lesions. Laboratory markers for synthetic liver function did not differ according to the number of lesions debulked. 13% of patients sustained a Clavien-Dindo grade 3 or 4 complication which was not associated with the number of lesions targeted. All patients with preoperative symptoms had improvement after surgery. Median time to progression was 10.9 months. CONCLUSIONS: PSR with MWA for large numbers of NETLM is safe and effective for symptom control and does not affect synthetic liver function.

Clinical utility of a microRNA classifier in cytologically indeterminate thyroid nodules with RAS mutations: A multi-institutional study.

BACKGROUND: Molecular testing guides the management of cytologically indeterminate thyroid nodules. We evaluated the real-world clinical benefit of a commercially available thyroid mutation panel plus microRNA risk classifier in classifying RAS-mutated nodules. METHODS: We performed a subgroup analysis of the results of molecular testing of Bethesda III/IV nodules using the ThyGenX/ThyGeNEXT-ThyraMIR platform at 3 tertiary-care centers between 2017 and 2021, defining a positive result as 10% or greater risk of malignancy. RESULTS: We identified 387 nodules from 375 patients (70.7% female, median age 59.3 years) who underwent testing. Positive nodules (32.3%) were associated with increased surgical intervention (74.4% vs 14.9%, P < .0001) and carcinoma on surgical pathology (46.4% vs 3.4%, P < .0001) compared to negative modules. RAS mutations were the most common mutations, identified in 71 of 380 (18.7%) nodules, and were classified as ThyraMIR- (28 of 71; 39.4%) or ThyraMIR+ (43 of 71; 60.6%). Among RAS-mutated nodules, there was no significant difference in operative rate (P = .2212) or carcinoma diagnosis (P = .6277) between the ThyraMIR+ and ThyraMIR- groups, and the sensitivity, specificity, negative predictive value, and positive predictive value of ThyraMIR were 64.7%, 34.8%, 40.0%, and 59.5%, respectively. CONCLUSION: Although testing positive is associated with malignancy in surgical pathology, the ThyraMIR classifier failed to differentiate between benign and malignant RAS-mutated nodules. Diagnostic lobectomy should be considered for RAS-mutated nodules, regardless of microRNA expression status.

Number of Hepatic Resections and Association with Complication after Metastatic Neuroendocrine Tumor Debulking: An American College of Surgeons NSQIP Database Study.

BACKGROUND: Neuroendocrine tumor liver metastases (NELM) are a major source of morbidity and mortality in neuroendocrine tumor patients and can be treated with hepatic debulking surgery (HDS). This study aims to identify variables associated with postoperative morbidity in NELM HDS. STUDY DESIGN: This analysis uses the American College of Surgeons NSQIP targeted hepatectomy-specific Participant User File from 2014 to 2020. Surgeries were grouped by number of hepatic resections performed (1 to 5, 6 to 10, greater than 10). Multivariable logistic regression and matching were used to identify prognostic factors of morbidity. RESULTS: A total of 1,163 patients were included. A total of 1,011 (87%) had 1 to 5 hepatic resections, 101 (8.7%) had 6 to 10 resections, and 51 (4.4%) had greater than 10 resections. The overall complication rate was 35%, and surgical and medical complications reached 30% and 13%, respectively. Mortality occurred in 11 patients (0.9%). Significantly higher rates of any (34% vs 35% vs 53%, p = 0.021) and surgical complications (29% vs 28% vs 49%, p = 0.007) were noted for those undergoing greater than 10 resections (1 to 5 resections, 6 to 10, greater than 10). "Bleeding requiring transfusion" (p < 0.0001) occurred more frequently in the greater than 10 resection group. On multivariable logistic regression, greater than 10 resections were an independent risk factor for any (odds ratio [OR] 2.53, p = 0.002; OR 2.52, p =. 0013) and surgical (OR 2.53, p = 0.003; OR 2.88, p = 0.005) complications compared with 1 to 5 resections and 6 to 10 resections, respectively. Medical complications (OR 2.34, p = 0.020) and length of stay greater than 5 days (OR 1.98, p = 0.032) were also increased with greater than 10 vs 1 to 5 resections. CONCLUSIONS: As reported by NSQIP, NELM HDS were performed safely with low mortality. However, more hepatic resections, especially greater than 10, were associated with increased postoperative morbidity and length of stay.

Surgery for metastatic pancreatic neuroendocrine tumors: a narrative review.

Background and Objective: Pancreatic neuroendocrine tumors (PanNETs) are derived from the islet cells of the pancreas and have been increasing in incidence. Most of these tumors are nonfunctional although some can secrete hormones and lead to hormone-specific clinical syndromes. Surgery is the mainstay of treatment for localized tumors, however, surgical resection is controversial in metastatic PanNETs. This narrative review seeks to summarize the current literature surrounding surgery, specifically in the controversial area of metastatic PanNETs, review current treatment paradigms, and understand the benefits of surgery in this group of patients. Methods: Authors searched PubMed using the terms "surgery pancreatic neuroendocrine tumor", "metastatic neuroendocrine tumor", and "liver debulking neuroendocrine tumor" from January 1990 to June 2022. Only English language publications were considered. Key Content and Findings: There is no consensus among the leading specialty organizations regarding surgery for metastatic PanNETs. When considering surgery for metastatic PanNETs, tumor grade and morphology, location of the primary tumor, extra-hepatic or extra-abdominal disease, as well as liver tumor burden and metastatic distribution should be considered. Because the liver is the most common site of metastasis and liver failure is the most common cause of death in patients with hepatic metastases, attention is centered here on debulking and other ablative techniques. Liver transplantation is rarely used for hepatic metastases but could be beneficial in a small subset of patients. Retrospective studies have demonstrated improvement in survival and symptoms after surgery for metastatic disease, but the lack of prospective randomized control trials significantly limits analysis of surgical benefits in patients with metastatic PanNETs. Conclusions: Surgery is the standard of care for localized PanNETs, while it remains controversial in metastatic disease. Many studies have shown a survival and symptomatic benefit to surgery and liver debulking in select groups of patients. However, most of the studies on which recommendations are based in this population are retrospective in nature and are subject to selection bias. This presents an opportunity for future investigation.

Light It Up! The Use of DOTATATE in Diagnosis and Treatment of Neuroendocrine Neoplasms.

Radiolabeled somatostatin analogs are increasingly used in the diagnosis and treatment of neuroendocrine tumors. Diagnostic imaging with 68Ga-DOTATATE PET/CT has demonstrated the improved sensitivity in detecting primary and metastatic neuroendocrine lesions compared with conventional imaging and prior generation somatostatin receptor imaging. Peptide receptor radionuclide therapy with 177Lu-DOTATATE is now frequently included in the management of neuroendocrine neoplasms, with prospective randomized control studies demonstrating its beneficial impact on survival and quality of life. Nonetheless, peptide rector radionuclide therapy is still considered palliative rather than curative and may be accompanied by adverse effects.

Extended postoperative thromboprophylaxis after pancreatic resection for pancreatic cancer is associated with decreased risk of venous thromboembolism in the minimally invasive approach.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with increased venous thromboembolism (VTE). We sought to compare rates of bleeding complications and VTE in patients receiving extended postoperative thromboprophylaxis (EPT) to those who did not, and identify risk factors for VTE after pancreatectomy for PDAC. METHODS: This is a retrospective review of pancreatectomies for PDAC. EPT was defined as 28 days of low molecular weight heparin. Multivariable analysis (MVA) was performed to identify independent risk factors of VTE. RESULTS: Of 269 patients included, 142 (52.8%) received EPT. Of those who received EPT, 7 (4.9%) suffered bleeding complications, compared to 6 (4.7%) of those who did not (p = 0.938). There was no significant difference in VTE rate at 90 days (2.8% vs. 2.4%, p = 0.728) or at 1 year (6.3% vs. 7.9%, p = 0.624). On MVA, risk factors for VTE included worse performance status, lower preoperative hematocrit, R1/R2 resection, and minimally invasive (MIS) approach. Among those who received EPT, there was no difference in VTE rate between MIS and open approach. CONCLUSIONS: EPT was not associated with a difference in VTE risk or bleeding complications. MIS approach was associated with a higher risk of VTE; however, this was significantly lower among those who received EPT.

Surgical considerations and outcomes of minimally invasive approaches for gastric cancer resection.

Despite high mortality rates from gastric cancer, surgical management remains critical for curative potential. Optimal outcomes of gastric cancer resection depend on a multitude of variables, including the extent of resection, scope of lymphadenectomy, method of reconstruction, and potential for a minimally invasive approach. Laparoscopic gastrectomy, compared with open gastrectomy, has been analyzed in numerous randomized control trials. Generally, those trials demonstrated statistically similar postoperative complication rates, mortality, and oncologic outcomes between the two approaches. Although laparoscopic gastrectomy requires longer operative times, significant improvements in estimated blood loss, postoperative length of stay, and return of bowel function have been noted in patients who undergo laparoscopic gastrectomy. These short-term benefits, along with equivalent oncologic results, have influenced national guidelines in both Eastern and Western countries to recommend laparoscopy, especially for early stage disease. Although robotic gastrectomy has not been as widely validated in effective trials, studies have reported equivalent oncologic outcomes and similar or improved postoperative complication and recovery rates after robotic gastrectomy compared with open gastrectomy. Comparing the two minimally invasive gastrectomy approaches, robotic surgery was associated with improved estimated blood loss, incidence of pancreatic sequela, and lymph node harvests in some studies, whereas laparoscopy resulted in lower operative times and hospital costs. Ultimately, when applying outcomes from the literature to clinical patient care decisions, it is imperative to recognize these studies' range of inclusion criteria, delineating between patients originating from Eastern or Western countries, the use of neoadjuvant chemotherapy, the volume of surgeon experience, and the extent of gastrectomy, among others.

Current state of minimally invasive pancreatic surgery.

The growth in minimally invasive pancreatic surgery (MIPS) has been accompanied by a recent surge in evidence-based data available to analyze patient outcomes. A small complement of randomized control trials as well as a multitude of observational studies have demonstrated both consistent similarities and differences between MIPS and the open approach, although abundant questions remain. This review highlights the available literature and emphasizes key factors for evaluating laparoscopic and robotic pancreatic surgery.

Microsurgical vascular bypass in the setting of pediatric limb length discrepancy.

Management of pediatric iatrogenic arterial occlusions can be challenging clinically, leading to chronic complications such as claudication and limb length discrepancy. We report the case of a 6-month-old female patient who had experienced iatrogenic right external iliac and common femoral arterial occlusion. At the age of 8 years, she had developed claudication and a limb length discrepancy of 3.2 cm. She underwent common iliac artery to superficial femoral artery and profunda artery bypass via a branched autologous reverse great saphenous vein using microsurgical techniques for the distal anastomoses. In the present report, we have focused on the musculoskeletal improvements, benefits of microsurgery in pediatric vessels, and maximization of epiphyseal perfusion.

Space-Specific Deficits in Visual Orientation Discrimination Caused by Lesions in the Midbrain Stimulus Selection Network.

Perceptual decisions require both analysis of sensory information and selective routing of relevant information to decision networks. This study explores the contribution of a midbrain network to visual perception in chickens. Analysis of visual orientation information in birds takes place in the forebrain sensory area called the Wulst, as it does in the primary visual cortex (V1) of mammals. In contrast, the midbrain, which receives parallel retinal input, encodes orientation poorly, if at all. We discovered, however, that small electrolytic lesions in the midbrain severely impair a chicken's ability to discriminate orientations. Focal lesions were placed in the optic tectum (OT) and in the nucleus isthmi pars parvocellularis (Ipc)-key nodes in the midbrain stimulus selection network-in chickens trained to perform an orientation discrimination task. A lesion in the OT caused a severe impairment in orientation discrimination specifically for targets at the location in space represented by the lesioned location. Distracting stimuli increased the deficit. A lesion in the Ipc produced similar but more transient effects. We discuss the possibilities that performance deficits were caused by interference with orientation information processing (sensory deficit) versus with the routing of information in the forebrain (agnosia). The data support the proposal that the OT transmits a space-specific signal that is required to gate orientation information from the Wulst into networks that mediate behavioral decisions, analogous to the role of ascending signals from the superior colliculus (SC) in monkeys. Furthermore, our results indicate a critical role for the cholinergic Ipc in this gating process.

Selective attention in birds.

The natural world constantly inundates our senses with an abundance of information. Selective attention enables us to navigate this abundance intelligently by selecting the information that is most relevant, at each moment in time, for differential processing and decision-making. The attributes of attention have been studied in humans for over a century. In his influential 19(th) century treatise, The Principles of Psychology, philosopher and psychologist William James defined attention as: "… the taking possession by the mind, in clear and vivid form, of one out of what seem several simultaneously possible objects or trains of thought … It implies withdrawal from some things in order to deal effectively with others." (James, 1890). James' definition elegantly captures two key hallmarks of attention: the enhanced processing of task-relevant information (target information) and the suppression of task-irrelevant information (distracting information).

Visuospatial selective attention in chickens.

Voluntary control of attention promotes intelligent, adaptive behaviors by enabling the selective processing of information that is most relevant for making decisions. Despite extensive research on attention in primates, the capacity for selective attention in nonprimate species has never been quantified. Here we demonstrate selective attention in chickens by applying protocols that have been used to characterize visual spatial attention in primates. Chickens were trained to localize and report the vertical position of a target in the presence of task-relevant distracters. A spatial cue, the location of which varied across individual trials, indicated the horizontal, but not vertical, position of the upcoming target. Spatial cueing improved localization performance: accuracy (d') increased and reaction times decreased in a space-specific manner. Distracters severely impaired perceptual performance, and this impairment was greatly reduced by spatial cueing. Signal detection analysis with an "indecision" model demonstrated that spatial cueing significantly increased choice certainty in localizing targets. By contrast, error-aversion certainty (certainty of not making an error) remained essentially constant across cueing protocols, target contrasts, and individuals. The results show that chickens shift spatial attention rapidly and dynamically, following principles of stimulus selection that closely parallel those documented in primates. The findings suggest that the mechanisms that control attention have been conserved through evolution, and establish chickens--a highly visual species that is easily trained and amenable to cutting-edge experimental technologies--as an attractive model for linking behavior to neural mechanisms of selective attention.

Magnetic tracking of eye position in freely behaving chickens.

Research on the visual system of non-primates, such as birds and rodents, is increasing. Evidence that neural responses can differ dramatically between head-immobilized and freely behaving animals underlines the importance of studying visual processing in ethologically relevant contexts. In order to systematically study visual responses in freely behaving animals, an unobtrusive system for monitoring eye-in-orbit position in real time is essential. We describe a novel system for monitoring eye position that utilizes a head-mounted magnetic displacement sensor coupled with an eye-implanted magnet. This system is small, lightweight, and offers high temporal and spatial resolution in real time. We use the system to demonstrate the stability of the eye and the stereotypy of eye position during two different behavioral tasks in chickens. This approach offers a viable alternative to search coil and optical eye tracking techniques for high resolution tracking of eye-in-orbit position in behaving animals.

A hydrodynamic sensory antenna used by killifish for nocturnal hunting.

The perception of sensory stimuli by an animal requires several steps, commencing with the capture of stimulus energy by an antenna that, as the interface between the physical world and the nervous system, modifies the stimulus in ways that enhance the animal's perception. The mammalian external ear, for example, collects sound and spectrally alters it to increase sensitivity and improve the detection of directionality. In view of the morphological diversity of the lateral-line system across species and its accessibility to observation and experimental intervention, we sought to investigate the role of antennal structures on the response characteristics of the lateral line. The surface-feeding killifish Aplocheilus lineatus is able to hunt in darkness by detecting surface capillary waves with the lateral-line system atop its head. This cephalic lateral line consists of a stereotyped array of 18 mechanosensitive neuromasts bordered by fleshy ridges. By recording microphonic potentials, we found that each neuromast has a unique receptive field defined by its sensitivity to stimulation of the water's surface. The ridges help determine these receptive fields by altering the flow of water over each neuromast. Modification of the hydrodynamic environment by the addition of a supplemental ridge changes the pattern of water movement, perturbs the receptive fields of adjacent neuromasts and impairs the fish's localization ability. On the basis of electrophysiological, hydrodynamic and behavioral evidence, we propose that the ridges constitute a hydrodynamic antenna for the cephalic lateral line.

Intraseasonal dynamics and dominant sequences in H3N2 influenza.

Long-term influenza evolution has been well studied, but the patterns of sequence diversity within seasons are less clear. H3N2 influenza genomes sampled from New York State over ten years indicated intraseasonal changes in evolutionary dynamics. Using the mean Hamming distance of a set of amino acid or nucleotide sequences as an indicator of its diversity, we found that influenza sequence diversity was significantly higher during the early epidemic period than later in the influenza season. Diversity was lowest during the peak of the epidemic, most likely due to the high prevalence of a single dominant amino acid sequence or very few dominant sequences during the peak epidemic period, corresponding with rapid expansion of the viral population. The frequency and duration of dominant sequences varied by influenza protein, but all proteins had an abundance of one distinct sequence during the peak epidemic period. In New York State from 1995 to 2005, high sequence diversity during the early epidemic suggested that seasonal antigenic drift could have occurred primarily in this period, followed by a clonal expansion of typically one clade during the peak of the epidemic, possibly indicating a shift to neutral drift or purifying selection.