Pupillary responses as a biomarker of cognitive effort and the impact of task difficulty on reward processing in schizophrenia.

Negative symptoms of schizophrenia robustly predict functional outcomes but remain relatively resistant to available treatments. Better measures of negative symptoms, especially motivational deficits, are needed to better understand these symptoms and improve treatment development. Recent research shows promise in linking behavioral effort tasks to motivational negative symptoms, reward processing deficits, and defeatist attitudes, but few studies account for individual or group (patient v. control) differences in cognitive ability to perform the tasks. Individuals with poorer abilities might be less motivated to perform tasks because they find them more difficult to perform. This study used a personalized digit span task to control task difficulty while measuring task effort via pupillary responses (greater dilation indicates greater cognitive effort) at varying monetary rewards ($1 & $2). Participants with schizophrenia (N = 34) and healthy controls (N = 41) performed a digit span task with personalized max span lengths and easy (max- 2 digits) and overload (max+ 2 digits) conditions. Consistent with many studies, pupillary responses (cognitive effort) increased with greater difficulty until exceeding capacity. A similar pattern of reward responsivity was seen in both groups, such that greater reward increased dilation (effort) comparably for both groups when difficulty was within capacity. Neither patients nor controls exerted increased effort for greater reward when difficulty exceeded capacity. In patients, positive relationships were found between pupil dilation and defeatist performance beliefs if task difficulty was within capacity; a relationship that reversed if the task was too difficult. The findings demonstrate the importance of accounting for cognitive capacity and task difficulty when evaluating motivation and reward sensitivity and illustrate the utility of pupillary responses as an objective measure of effort in schizophrenia.

Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma.

BACKGROUND: Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS: Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS: Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS: Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.

At home adaptive dual target deep brain stimulation in Parkinson's disease with proportional control.

Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. Continuous DBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and globus pallidus (dual target DBS) in a prospective within-participant, clinical trial in six patients with Parkinson's disease (n = 6, 55-65 years, n = 2 females). Dual target cDBS was tested for Parkinson's disease symptom control annually over 2 years, measured by motor rating scales, on time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral aDBS using a novel distributed (off-implant) architecture. In the home setting, we collected tremor and dyskinesia scores as well as individualized ß and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by Unified Parkinson's Disease Rating Scale (UPDRS) to a greater degree than either region alone (P < 0.05, linear mixed model) in the cohort. The amplitude of ß-oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (P < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artefacts and demonstrated a correlation between STN ß amplitude and DBS amplitude. Proportional plus integral control of aDBS reduced average power, while preserving UPDRS III scores in the clinic (P = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n = 3, P > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of Parkinson's disease over DBS of either the STN or globus pallidus alone. When combined with proportional plus integral aDBS, stimulation power may be reduced, while preserving the increased benefit of dual target DBS.

Collaborative multidisciplinary management and expertise of cT2-3 locally advanced operable esophageal squamous cell carcinoma: a report of two cases.

Background: The accurate clinical staging of esophageal squamous cell carcinoma (ESCC) is pivotal for guiding treatment strategies. However, the current precision in staging for clinical T (cT)2 and cT3 stages remains unsatisfactory. This article discusses the role of multidisciplinary teams (MDTs) in the clinical staging and formulation of neoadjuvant treatment strategies for locally advanced operable ESCC. These challenges underscore the importance of precise staging in the decision-making process for appropriate therapeutic interventions. Case Description: Through the lens of two patient case studies with locally advanced resectable ESCC, the article showcases the intricate process of treatment planning undertaken by MDTs. It captures a range of expert perspectives from Japan, China, Hong Kong (China), Korea, the USA, and Europe, focusing on the challenges of differentiating between cT2 and cT3 stages of the disease, which is a critical determinant in the management and therapeutic approach for patients. Conclusions: The article concludes that the accurate staging of ESCC is a cornerstone in determining the most suitable treatment strategies. It underscores the vital role that MDTs play in both clinical staging and the decision-making process for treatment. Highlighting the limitations in current diagnostic methods, the article emphasizes the urgent need for advanced research and the refinement of diagnostic tools to improve the precision of staging, particularly between the cT2 and cT3 stages. It suggests that future research should consider whether a reclassification of these stages could be warranted to enhance treatment planning and outcomes for patients with ESCC.

From Pixels to Pathology: Employing Computer Vision to Decode Chest Diseases in Medical Images.

Radiology has been a pioneer in the healthcare industry's digital transformation, incorporating digital imaging systems like picture archiving and communication system (PACS) and teleradiology over the past thirty years. This shift has reshaped radiology services, positioning the field at a crucial junction for potential evolution into an integrated diagnostic service through artificial intelligence and machine learning. These technologies offer advanced tools for radiology's transformation. The radiology community has advanced computer-aided diagnosis (CAD) tools using machine learning techniques, notably deep learning convolutional neural networks (CNNs), for medical image pattern recognition. However, the integration of CAD tools into clinical practice has been hindered by challenges in workflow integration, unclear business models, and limited clinical benefits, despite development dating back to the 1990s. This comprehensive review focuses on detecting chest-related diseases through techniques like chest X-rays (CXRs), magnetic resonance imaging (MRI), nuclear medicine, and computed tomography (CT) scans. It examines the utilization of computer-aided programs by researchers for disease detection, addressing key areas: the role of computer-aided programs in disease detection advancement, recent developments in MRI, CXR, radioactive tracers, and CT scans for chest disease identification, research gaps for more effective development, and the incorporation of machine learning programs into diagnostic tools.

Aortic Arch Reconstruction Using Nonvalved Femoral Vein Homograft in High-Risk Neonates.

Aortic arch obstruction is often present with complex concomitant congenital heart defects (CHDs). The use of nonvalved femoral vein homograft (FVH) to reconstruct the aortic arch has distinct surgical advantages, including simplified reconstruction. We present an intraoperative video of a Yasui procedure utilizing FVH for aortic reconstruction in a 12-day-old (2.2 kg) neonate with right ventricular outflow tract obstruction, malalignment ventricular septal defect, aortic valve atresia, aortic arch hypoplasia, atrial septal defect, and ductal dependent systemic circulation. Further, we report outcomes for a series of three additional neonatal patients with complex CHD and aortic arch obstruction who underwent FVH arch reconstruction.

Perioperative and oncologic outcomes of pulmonary resection for synchronous oligometastatic non-small cell lung cancer: Evidence for surgery in advanced disease.

OBJECTIVES: Recent randomized trials have demonstrated a survival advantage with the use of local consolidative therapy in oligometastatic non-small cell lung cancer; however, the indications for and outcomes after pulmonary resection as a component of local consolidative therapy remain ill defined. We sought to characterize the perioperative and long-term survival outcomes among patients with resected oligometastatic non-small cell lung cancer. METHODS: Patients presenting to a single center (2000-2017) with oligometastatic non-small cell lung cancer (≤3 synchronous metastases, intrathoracic nodal disease counted as a single site) who underwent resection of the primary tumor were retrospectively identified. Charts were reviewed, and demographic, clinical, pathologic, oncologic, and survival outcomes were recorded. Survival outcomes were analyzed from the date of surgery. RESULTS: A total of 52 patients met inclusion criteria, among whom most (38, 73.1%) were ever smokers, had nonsquamous tumors (48, 92.3%), had no intrathoracic nodal disease (33, 63.5%), and had 1 to 2 sites of metastases (49, 94.2%). The majority (41, 78.9%) received systemic therapy, predominantly in the neoadjuvant setting (24/41, 58.5%). After resection, there were no 30- or 90-day deaths. After a median follow-up of 94.6 months (95% CI, 69.0-139.1), 37 patients (71.2%) progressed and 38 patients (73.1%) died. Median postoperative progression-free survival and overall survival were 9.4 (5.5-11.6) months and 51.7 (22.3-65.3) months, respectively. CONCLUSIONS: Pulmonary resection as a means of maximum locoregional control in oligometastatic non-small cell lung cancer is feasible and safe, and may be associated with durable long-term survival benefits. The frequency of systemic postoperative progression highlights an urgent need to characterize perioperative and oncologic outcomes after pulmonary resection in the current era of novel systemic therapies.

Modelling marine microplastics accumulation zones through freshwater discharge sources: Simulated release from the Onkaparinga River and Torrens River, South Australia.

Plastic pollution is fast becoming one of the most prominent contamination issues facing the marine environment. Microplastics are a major subset of plastic waste now present in all global oceans, with their numbers standing only to increase. This study applies a coupled hydrodynamic model and Lagrangian particle-tracking model to predict and simulate microplastic transport in South Australian waters. Virtual particles representing microplastics were released daily for 365 days from two major freshwater input sources along the coastline of Adelaide, Australia. These particles entered the Gulf St Vincent and were tracked over two model years using LTRANS software. The model identified general gulf circulation as circular, clockwise, with net southward particle transport from particle release sites. A potential accumulation zone associated with a local eddy was identified. Concentrations of particles that passed through local marine parks were also calculated in response to the potential concerns they pose in vulnerable protected areas.

Robot-Assisted Resection of Left Ventricular Papillary Fibroelastoma Arising From the Mitral Chordal Apparatus.

The application of robot-assisted thoracoscopy to cardiac surgery affords an opportunity to leverage the exceptional intraoperative exposure, visualization, and dexterity of the robotic platform. Here, we report the case of a 72-year-old woman who presented to our institution for evaluation of a left ventricular mass that was identified following workup for an embolic event. We present an intraoperative video that provides technical details of the robot-assisted resection of the lesion, which was found to be a left ventricular papillary fibroelastoma arising from the mitral chordal apparatus. This case highlights the advantages provided by the robotic platform, which permitted complete, minimally invasive surgical excision of the lesion while minimizing the burden of surgical trauma.

Benchmarking Outcomes for Molecularly Characterized Synchronous Oligometastatic Non-Small-Cell Lung Cancer Reveals EGFR Mutations to Be Associated With Longer Overall Survival.

PURPOSE: Local consolidative therapy (LCT) for patients with synchronous oligometastatic non-small-cell lung cancer is an evolving treatment strategy, but outcomes following LCT stratified by genetic mutations have not been reported. We sought to identify genomic associations with overall survival (OS) and progression-free survival (PFS) for these patients. METHODS: We identified all patients presenting between 2000 and 2017 with stage IV non-small-cell lung cancer and ≤ 3 synchronous metastatic sites. Patients were grouped according to mutational statuses. Primary outcomes included OS and PFS following initial diagnosis. RESULTS: Of 194 included patients, 121 received comprehensive LCT to all sites of disease with either surgery or radiation. TP53 mutations were identified in 40 of 78 (55%), KRAS in 32 of 95 (34%), EGFR in 24 of 109 (22%), and STK11 in nine of 77 (12%). At median follow-up of 96 months, median OS and PFS were 26 (95% CI, 23 to 31) months and 11 (95% CI, 9 to 13) months, respectively. On multivariable analysis, patients with EGFR mutations had lower mortality risk (hazard ratio [HR], 0.53; 95% CI, 0.29 to 0.98; P = .044) compared with wild-type patients, and patients with STK11 mutations had higher risk of progression or mortality (HR, 2.32; 95% CI, 1.12 to 4.79; P = .023) compared with wild-type patients. TP53 and KRAS mutations were not associated with OS or PFS. Among 71 patients with known EGFR mutational status who received comprehensive LCT, EGFR mutations were associated with lower mortality compared with wild-type (HR, 0.45; 95% CI, 0.22 to 0.94; P = .032). CONCLUSION: When compared with wild-type patients, those with EGFR and STK11 mutations had longer OS and shorter PFS, respectively. EGFR mutations were associated with longer OS among oligometastatic patients treated with comprehensive LCT in addition to systemic therapy.

Neither myonuclear accretion nor a myonuclear domain size ceiling is a feature of the attenuated hypertrophic potential of aged human skeletal muscle.

Ageing limits growth capacity of skeletal muscle (e.g. in response to resistance exercise), but the role of satellite cell (SC) function in driving this phenomenon is poorly defined. Younger (Y) (~ 23 years) and older (O) men (~ 69 years) (normal-weight BMI) underwent 6 weeks of unilateral resistance exercise training (RET). Muscle biopsies were taken at baseline and after 3-/6-week training. We determined muscle size by fibre CSA (and type), SC number, myonuclei counts and DNA synthesis (via D2O ingestion). At baseline, there were no significant differences in fibre areas between Y and O. RET increased type I fibre area in Y from baseline at both 3 weeks and 6 weeks (baseline: 4509 ± 534 µm2, 3 weeks; 5497 ± 510 µm2 P < 0.05, 6 weeks; 5402 ± 352 µm2 P < 0.05), whilst O increased from baseline at 6 weeks only (baseline 5120 ± 403 µm2, 3 weeks; 5606 ± 620 µm2, 6 weeks; 6017 ± 482 µm2 P < 0.05). However, type II fibre area increased from baseline in Y at both 3 weeks and 6 weeks (baseline: 4949 ± 459 µm2, 3 weeks; 6145 ± 484 µm2 (P < 0.01), 6 weeks; 5992 ± 491 µm2 (P < 0.01), whilst O showed no change (baseline 5210 ± 410 µm2, 3 weeks; 5356 ± 535 µm2 (P = 0.9), 6 weeks; 5857 ± 478 µm2 (P = 0.1). At baseline, there were no differences in fibre myonuclei number between Y and O. RET increased type I fibre myonuclei number from baseline in both Y and O at 3 weeks and 6 weeks with RET (younger: baseline 2.47 ± 0.16, 3 weeks; 3.19 ± 0.16 (P < 0.001), 6 weeks; 3.70 ± 0.29 (P < 0.0001); older: baseline 2.29 ± 0.09, 3 weeks; 3.01 ± 0.09 (P < 0.001), 6 weeks; 3.65 ± 0.18 (P < 0.0001)). Similarly, type II fibre myonuclei number increased from baseline in both Y and O at 3 weeks and 6 weeks (younger: baseline 2.49 ± 0.14, 3 weeks; 3.31 ± 0.21 (P < 0.001), 6 weeks; 3.86 ± 0.29 (P < 0.0001); older: baseline 2.43 ± 0.12, 3 weeks; 3.37 ± 0.12 (P < 0.001), 6 weeks; 3.81 ± 0.15 (P < 0.0001)). DNA synthesis rates %.d-1 exhibited a main effect of training but no age discrimination. Declines in myonuclei addition do not underlie impaired muscle growth capacity in older humans, supporting ribosomal and proteostasis impairments as we have previously reported.

Benefits and Risks of a Staged-Bilateral VIM Versus Unilateral VIM DBS for Essential Tremor.

Background: Despite over 30 years of clinical experience, high-quality studies on the efficacy of bilateral versus unilateral deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus for medically refractory essential tremor (ET) remain limited. Objectives: To compare benefits and risks of bilateral versus unilateral VIM DBS using the largest ET DBS clinical trial dataset available to date. Methods: Participants from the US St. Jude/Abbott pivotal ET DBS trial who underwent staged-bilateral VIM implantation constituted the primary cohort in this sub-analysis. Their assessments "on" DBS at six months after second-side VIM DBS implantation were compared to the assessments six months after unilateral implantation. Two control cohorts of participants with unilateral implantation only were also used for between-group comparisons. Results: The primary cohort consisted of n = 38 ET patients (22M/16F; age of 65.3 ± 9.5 years). The second side VIM-DBS resulted in a 29.6% additional improvement in the total motor CRST score (P < 0.001), with a 64.1% CRST improvement in the contralateral side (P < 0.001). An added improvement was observed in the axial tremor score (21.4%, P = 0.005), and CRST part B (24.8%, P < 0.001) score. Rate of adverse events was slightly higher after bilateral stimulation. Conclusions: In the largest ET DBS study to date, staged-bilateral VIM DBS was a highly effective treatment for ET with bilateral implantation resulting in greater reduction in total motor tremor scores when compared to unilateral stimulation alone.

Automated deep brain stimulation programming with safety constraints for tremor suppression in patients with Parkinson's disease and essential tremor.

Objective.Deep brain stimulation (DBS) programming for movement disorders requires systematic fine tuning of stimulation parameters to ameliorate tremor and other symptoms while avoiding side effects. DBS programming can be a time-consuming process and requires clinical expertise to assess response to DBS to optimize therapy for each patient. In this study, we describe and evaluate an automated, closed-loop, and patient-specific framework for DBS programming that measures tremor using a smartwatch and automatically changes DBS parameters based on the recommendations from a closed-loop optimization algorithm thus eliminating the need for an expert clinician.Approach.Bayesian optimization which is a sample-efficient global optimization method was used as the core of this DBS programming framework to adaptively learn each patient's response to DBS and suggest the next best settings to be evaluated. Input from a clinician was used initially to define a maximum safe amplitude, but we also implemented 'safe Bayesian optimization' to automatically discover tolerable exploration boundaries.Main results.We tested the system in 15 patients (nine with Parkinson's disease and six with essential tremor). Tremor suppression at best automated settings was statistically comparable to previously established clinical settings. The optimization algorithm converged after testing15.1±0.7settings when maximum safe exploration boundaries were predefined, and17.7±4.9when the algorithm itself determined safe exploration boundaries.Significance.We demonstrate that fully automated DBS programming framework for treatment of tremor is efficient and safe while providing outcomes comparable to that achieved by expert clinicians.

Evoked potentials generated by deep brain stimulation for Parkinson's disease.

BACKGROUND AND OBJECTIVES: The goal of this review is to describe the general features, mechanisms, technical recording factors, and clinical applications of brain evoked potentials (EPs) generated by deep brain stimulation (DBS) for Parkinson's disease (PD). RESULTS: Evoked potentials in response to DBS pulses occur on the timescale of milliseconds and are found both locally at the site of stimulation and remotely in the cortex. DBS evoked potentials arise from a complex integration of antidromic and orthodromic conduction pathway responses, and provide information valuable for understanding the mechanisms and circuits involved in symptom treatment. Furthermore, these signals may provide biomarkers for improving DBS outcomes and function. For example, evoked potentials may have utility as control signals for DBS programming or adaptive DBS. Despite their promise there are still critical gaps in our understanding of the mechanisms by which evoked potentials arise and how these signals may be measured and applied in the clinical setting. Technical challenges of recording a highly transient signal at sufficient resolution without the interference of stimulation artifact present a barrier to understanding better DBS-induced EPs. CONCLUSIONS: We describe the current scientific landscape of evoked potentials to facilitate and stimulate further investigation.

Peripheral inflammation levels associated with degree of advanced brain aging in schizophrenia.

Brain structural abnormalities have been demonstrated in schizophrenia (SZ); these resemble those seen in typical aging, but are seen at younger ages. Furthermore, SZ is associated with accelerated global brain aging, as measured by brain structure-based brain predicted age difference (Brain-PAD). High heterogeneity exists in the degree of brain abnormalities in SZ, and individual differences may be related to levels of peripheral inflammation and may relate to cognitive deficits and negative symptoms. The goal of our study was to investigate the relationship between brain aging, peripheral inflammation, and symptoms of SZ. We hypothesized older brain-PAD in SZ vs. healthy comparison (HC) participants, as well as positive relationships of brain-PAD with peripheral inflammation markers and symptoms in SZ. We analyzed data from two cross-sectional studies in SZ (n = 26; M/F: 21/5) and HC (n = 28; 20/8) (22-64 years). Brain-PAD was calculated using a previously validated Gaussian process regression model applied to raw T1-weighted MRI data. Plasma levels of inflammatory biomarkers (CRP, Eotaxin, Fractalkine, IP10, IL6, IL10, ICAM1, IFNγ, MCP1, MIP1ß, SAA, TNFα, VEGF, VCAM1) and cognitive and negative symptoms were assessed. We observed a higher brain-PAD in SZ vs. HC, and advanced brain age relative to chronological age was related to higher peripheral levels of TNFα in the overall group and in the SZ group; other inflammatory markers were not related to brain-PAD. Within the SZ group, we observed no association between cognitive or negative symptoms and brain-PAD. These results support our hypothesis of advanced brain aging in SZ. Furthermore, our findings on the relationship of the pro-inflammatory cytokine TNFα with higher brain-PAD of SZ are relevant to explain heterogeneity of brain ages in SZ, but we did not find strong evidence for cognitive or negative symptom relationships with brain-PAD.

Initial Clinical Outcome With Bilateral, Dual-Target Deep Brain Stimulation Trial in Parkinson Disease Using Summit RC + S.

BACKGROUND: Deep brain stimulation (DBS) is an effective therapy in advanced Parkinson disease (PD). Although both subthalamic nucleus (STN) and globus pallidus (GP) DBS show equivalent efficacy in PD, combined stimulation may demonstrate synergism. OBJECTIVE: To evaluate the clinical benefit of stimulating a combination of STN and GP DBS leads and to demonstrate biomarker discovery for adaptive DBS therapy in an observational study. METHODS: We performed a pilot trial (n = 3) of implanting bilateral STN and GP DBS leads, connected to a bidirectional implantable pulse generator (Medtronic Summit RC + S; NCT03815656, IDE No. G180280). Initial 1-year outcome in 3 patients included Unified PD Rating Scale on and off medications, medication dosage, Hauser diary, and recorded beta frequency spectral power. RESULTS: Combined DBS improved PD symptom control, allowing >80% levodopa medication reduction. There was a greater decrease in off-medication motor Unified PD Rating Scale with multiple electrodes activated (mean difference from off stimulation off medications -18.2, range -25.5 to -12.5) than either STN (-12.8, range -20.5 to 0) or GP alone (-9, range -11.5 to -4.5). Combined DBS resulted in a greater reduction of beta oscillations in STN in 5/6 hemispheres than either site alone. Adverse events occurred in 2 patients, including a small cortical hemorrhage and seizure at 24 hours postoperatively, which resolved spontaneously, and extension wire scarring requiring revision at 2 months postoperatively. CONCLUSION: Patients with PD preferred combined DBS stimulation in this preliminary cohort. Future studies will address efficacy of adaptive DBS as we further define biomarkers and control policy.

Surgical Complexity of Pulmonary Resections Performed for Oligometastatic NSCLC.

INTRODUCTION: Pulmonary resection has been established as an important component of local consolidative therapy (LCT) for oligometastatic NSCLC. However, technical aspects of such surgical procedures have not been well characterized. We sought to review the complexity of operations performed within a large cohort of patients with oligometastatic NSCLC. METHODS: We identified patients treated at a single institution between 2000 and 2017 with stage IV NSCLC, with three or fewer synchronous metastases, and who underwent surgical resection of the primary tumor. Medical records were reviewed, and aspects of surgical complexity were recorded. Descriptive analyses were performed. RESULTS: Among 194 patients with oligometastatic NSCLC, 173 (89%) received LCT and 30 (15%) underwent resection of the primary tumor. Thoracotomy was performed in 25 patients (83%), and procedures included 25 (83%) lobectomies, three (10%) pneumonectomies, and two (7%) sublobar resections. Mean blood loss was 200 (50-600) mL, and operative time was 200 (72-492) minutes. Proximal pulmonary artery control was needed in four (15%). Sleeve resection was needed in four (15%). Unplanned procedural change was required in two patients (7%). Chest wall resection occurred in three patients (11%). Lymph nodes were characterized as hard or densely adherent in nine (33%), and operations were described as more difficult than usual in 16 cases (59%). CONCLUSIONS: Surgery has emerged as a key strategy for LCT among patients with oligometastatic NSCLC. These operations can be performed safely, yet frequently require advanced techniques and complex resection strategies. As such, health care teams must be prepared for the technical challenges of these cases.

Current Surgical Indications for Non-Small-Cell Lung Cancer.

With recent strides made within the field of thoracic oncology, the management of NSCLC is evolving rapidly. Careful patient selection and timing of multi-modality therapy to permit the optimization of therapeutic benefit must be pursued. While chemotherapy and radiotherapy continue to have a role in the management of lung cancer, surgical therapy remains an essential component of lung cancer treatment in early, locally and regionally advanced, as well as in selected, cases of metastatic disease. Recent and most impactful advances in the treatment of lung cancer relate to the advent of immunotherapy and targeted therapy, molecular profiling, and predictive biomarker discovery. Many of these systemic therapies are a part of the standard of care in metastatic NSCLC, and their indications are expanding towards surgically operable lung cancer to improve survival outcomes. Numerous completed and ongoing clinical trials in the surgically operable NSCLC speak to the interest and importance of the multi-modality therapy even in earlier stages of NSCLC. In this review, we focus on the current standard of care indications for surgical therapy in stage I-IV NSCLC as well as on the anticipated future direction of multi-disciplinary lung cancer therapy.