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Objective Interstitial lung disease (ILD) is a major cause of morbidity and mortality in connective tissue diseases (CTDs). We aimed to assess the effect of rituximab ± mycophenolate mofetil (MMF) compared with MMF on pulmonary function and prednisone dosage in patients with CTD-related ILD (CTD-ILD). Methods This retrospective study included 83 patients from Stanford and Centre Hospitalier de l'Universite de Montreal. Fifteen patients received rituximab ± MMF (rituximab group), and 68 patients received MMF only (control group). Results Median ILD duration at the start of treatment was longer in the rituximab group at 47 months (range: 4-170) versus 6.5 months (range: 0-164) in controls. Forced vital capacity (FVC) decreased by 3.0% (range: 11%-21%) after treatment in the rituximab group, whereas it increased by 2.0% (range: 14%-25%) in the control group (p = 0.025). Diffusing capacity of carbon monoxide (DLCO) decreased by 3.0% (range: 10%-12%) after treatment in the rituximab group, whereas it increased by 4.5% (range: 30%-36%) in the control group (p = 0.046). Mixed model analysis controlling for ILD duration, baseline DLCO, systemic sclerosis, pulmonary hypertension, and prednisone use showed no significant difference in FVC or DLCO between groups at 6 months or 1 year. The average daily prednisone dose score decreased after treatment in the rituximab group, whereas it remained unchanged in the control group (p = 0.017). Conclusion Rituximab ± MMF did not significantly change pulmonary function compared with MMF alone, but it did result in a relative decrease in average daily prednisone dose in a population with recalcitrant CTD-ILD.

PURPOSE: The purpose of this study was to develop a 3-dimensional (3D) printing method to create computed tomography (CT) realistic phantoms of lung cancer nodules and lung parenchymal disease from clinical CT images. MATERIALS AND METHODS: Low-density paper was used as substrate material for inkjet printing with potassium iodide solution to reproduce phantoms that mimic the CT attenuation of lung parenchyma. The relationship between grayscale values and the corresponding CT numbers of prints was first established through the derivation of exponential fitted equation from scanning data. Next, chest CTs from patients with early-stage lung cancer and coronavirus disease 2019 (COVID-19) pneumonia were chosen for 3D printing. CT images of original lung nodule and the 3D-printed nodule phantom were compared based on pixel-to-pixel correlation and radiomic features. RESULTS: CT images of part-solid lung cancer and 3D-printed nodule phantom showed both high visual similarity and quantitative correlation. R2 values from linear regressions of pixel-to-pixel correlations between 5 sets of patient and 3D-printed image pairs were 0.92, 0.94, 0.86, 0.85, and 0.83, respectively. Comparison of radiomic measures between clinical CT and printed models demonstrated 6.1% median difference, with 25th and 75th percentile range at 2.4% and 15.2% absolute difference, respectively. The densities and parenchymal morphologies from COVID-19 pneumonia CT images were well reproduced in the 3D-printed phantom scans. CONCLUSION: The 3D printing method presented in this work facilitates creation of CT-realistic reproductions of lung cancer and parenchymal disease from individual patient scans with microbiological and pathology confirmation.

BackgroundThe majority of patients with SARS-CoV-2 infection are diagnosed and managed as outpatients; however, little is known about the burden of pulmonary disease in this setting. Lung ultrasound (LUS) is a convenient tool for detection of COVID-19 pneumonia. Identifying SARS-CoV-2 infected outpatients with pulmonary disease may be important for early risk stratification.ObjectivesTo investigate the prevalence, natural history and clinical significance of pulmonary disease in outpatients with SARS-CoV-2.MethodsSARS-CoV-2 PCR positive outpatients (CV(+)) were assessed with LUS to identify the presence of interstitial pneumonia. Studies were considered positive based on the presence of B-lines, pleural irregularity and consolidations. A subset of patients underwent longitudinal examinations. Correlations between LUS findings and patient symptoms, demographics, comorbidities and clinical outcomes over 8 weeks were evaluated.Results102 CV(+) patients underwent LUS with 42 (41%) demonstrating pulmonary involvement. Baseline LUS severity scores correlated with shortness of breath on multivariate analysis. Of the CV(+) patients followed longitudinally, a majority showed improvement or resolution in LUS findings after 1–2 weeks. Only one patient in the CV(+) cohort was briefly hospitalised, and no patient died or required mechanical ventilation.ConclusionWe found a high prevalence of LUS findings in outpatients with SARS-CoV-2 infection. Given the pervasiveness of pulmonary disease across a broad spectrum of LUS severity scores and lack of adverse outcomes, our findings suggest that LUS may not be a useful as a risk stratification tool in SARS-CoV-2 in the general outpatient population.

We present a case of a 69-year-old man who underwent tracheobronchoplasty for tracheobronchomalacia using a single-lumen endotracheal tube and a Y-shaped bronchial blocker for airway management. Tracheobronchoplasty is performed by sewing mesh to plicate the posterior, membranous wall of the distal trachea and main bronchi through a right posterolateral thoracotomy. The goals of airway management include continuous left-lung ventilation and lung protection from aspiration. Ideally, only conventional airway management tools are used. This case demonstrates that a single-lumen endotracheal tube with a bronchial blocker can be a straightforward strategy for airway management during tracheobronchoplasty.

Background: Cardiac fluorodeoxyglucose positron-emission tomography (FDG-PET) has emerged as a standard imaging modality for the diagnosis of cardiac sarcoidosis (CS); however, there is a scarcity of data on the use of serial FDG-PET to guide immunosuppressive therapy. The aim of this work was to report our experience using serial FDG-PET for the diagnosis and management of patients with CS, focusing on its utility in ongoing immunosuppression management. Methods and Results: We studied consecutive patients with CS managed at Stanford University from 2010 to 2017. We evaluated our experience using FDG-PET for diagnosis and guidance of immunosuppressive therapy titration in CS. Among 34 patients diagnosed with CS, 16 (47%), 12 (35%) and 14(41%) presented with heart block, heart failure, and ventricular arrhythmias, respectively. FDG-PET proved beneficial in the initial diagnosis in 21 patients (62%). A total of 128 FDG-PET scans were performed (median 3 per patient). Ninety-four FDG-PET scans (73%) resulted in a change in therapy, with 42FDG-PET scans (33%) instrumental for tapering prednisone. Among patients who were initiated on prednisone, the mean dose of prednisone at 1 year was 9.5mg/d. Over a median follow-up of 2.3years, 48% of patients were successfully weaned from prednisone completely, and 20% were weaned to a maintenance dosage of 5–10mg/d. During the follow-up period, transplant-free survival was 88%. Conclusions: The use of serial cardiac FDG-PET for the diagnosis and management of CS was critical for guiding immunosuppression management and resulted in low chronic steroid doses and good disease control within 1 year of diagnosis.

Purpose Computed tomography (CT) findings of bronchiolitis obliterans syndrome (BOS) can be nonspecific and variable. This study aims to measure the incremental value of automated quantitative lung CT analysis to clinical CT interpretation. A head-to-head comparison of quantitative CT lung density analysis by parametric response mapping (PRM) with qualitative radiologist performance in BOS diagnosis was performed. Materials and methods Inspiratory and end-expiratory CTs of 65 patients referred to a post-bone marrow transplant lung graft-versus-host-disease clinic were reviewed by 3 thoracic radiologists for the presence of mosaic attenuation, centrilobular opacities, airways dilation, and bronchial wall thickening. Radiologists' majority consensus diagnosis of BOS was compared with automated PRM air trapping quantification and to the gold-standard diagnosis of BOS as per National Institutes of Health (NIH) consensus criteria. Results Using a previously established threshold of 28% air trapping on PRM, the diagnostic performance for BOS was as follows: sensitivity 56% and specificity 94% (area under the receiver operator curve [AUC]=0.75). Radiologist review of inspiratory CT images alone resulted in a sensitivity of 80% and a specificity of 69% (AUC=0.74). When radiologists assessed both inspiratory and end-expiratory CT images in combination, the sensitivity was 92% and the specificity was 59% (AUC=0.75). The highest performance was observed when the quantitative PRM report was reviewed alongside inspiratory and end-expiratory CT images, with a sensitivity of 92% and a specificity of 73% (AUC=0.83). Conclusions In the CT diagnosis of BOS, qualitative expert radiologist interpretation was noninferior to quantitative PRM. The highest level of diagnostic performance was achieved by the combination of quantitative PRM measurements with qualitative image feature assessments.

We set to identify prognostic factors in a retrospective cohort of consecutive patients with stage I-II diffuse large B-cell lymphoma treated with rituximab-chemotherapy with or without radiotherapy from 2001 through 2017 at our institution. We identified 143 patients with median follow-up of 7.7 years. The majority were male (59.4%), had stage II (53.1%), had stage-modified IPI 0-1 (smIPI, 58.1%), and had non-bulky disease (7 cm, 68.5%). 99 patients (69.2%) received rituximab-chemotherapy followed by radiotherapy, and 44 patients (30.8%) received rituximab-chemotherapy alone. The 5-year progression-free survival (PFS) and overall survival (OS) were 81.2% and 88.9%, respectively. The 5-year PFS for those with smIPI 0-1 versus 2-4 was 89.5% versus 69.7%, respectively (

Evaluations of patients with pulmonary hypertension (PH) commonly include chest CT imaging. We hypothesized that cardiac chamber volumes calculated from the same CT scans can yield additional information to distinguish PH related to left-sided heart disease (World Health Organization group 2) from other PH subtypes.Patients who had PH confirmed by right heart catheterization and contrast-enhanced chest CT studies were enrolled in this retrospective multicenter study. Cardiac chamber volumes were calculated using automated segmentation software and compared between group 2 and non-group 2 patients with PH.This study included 114 patients with PH, 27 (24%) of whom were classified as group 2 based on their pulmonary capillary wedge pressure. Patients with group 2 PH exhibited significantly larger median left atrial (LA) volumes (118 mL vs 63 mL; P .001), larger median left ventricular (LV) volumes (90 mL vs 76 mL; P = .02), and smaller median right ventricular (RV) volumes (173 mL vs 210 mL; P = .005) than did non-group 2 patients. On multivariate analysis adjusted for age, sex, and mean pulmonary arterial pressure, group 2 PH was significantly associated with larger median LA and LV volumes (P .001 and P = .008, respectively) and decreased volume ratios of RA/LA, RV/LV, and RV/LA (P = .001, P = .004, and P .001, respectively). Enlarged LA volumes demonstrated a high discriminatory ability for group 2 PH (area under the curve, 0.92; 95% CI, 0.870-0.968).Volumetric analysis of the cardiac chambers from nongated chest CT scans, particularly with findings of an enlarged left atrium, exhibited high discriminatory ability for identifying patients with PH due to left-sided heart disease.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer’s safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6., Knottin is a cystine knot peptide. Here, the authors develop a knottin-based tracer for positron emission tomography and demonstrate its ability to detect cancer and idiopathic pulmonary fibrosis through selective binding to integrin αvβ6.

8537 Background: Five-year survival for stage I-II lung cancer is quite low even after complete surgical resection. Current guidelines recommend adjuvant treatment only for selected patients with stage II or higher disease. A prediction model that identifies patients at high risk of recurrence who may benefit from adjuvant treatment is greatly needed. Many existing prediction models include a small number of genes that were found to be significant in previous studies. We propose using artificial intelligence to analyze a microarray of > 20,000 well-annotated genes to create a model that predicts recurrence after surgical resection of stage I-II lung cancer. Methods: We identified 275 patients who underwent surgical resection for pathologic stage I-II lung adenocarcinoma or squamous cell carcinoma from 2009 to 2019 in our institution’s prospective surgical database. We excluded patients who had follow up time less than 3 years or received adjuvant therapy and had not had a recurrence, as well as patients with missing specimen blocks. Patient characteristics and recurrence information were obtained from chart review. The patients were divided into training (192 patients) and validation (83 patients) cohorts, and the recurrence status for the validation cohort was initially blinded. Gene expression levels were generated using Clariom S human array (ThermoFisher) from 10um sections cut from the formalin-fixed, paraffin-embedded surgical specimen blocks. The artificial intelligence algorithm Support Vector Machine (SVM) was used to create a prediction model for recurrence using the gene expression and recurrence status of the patients in the training cohort. The model was then tested on the validation cohort using Kaplan-Meier analysis and the area under the receiver operator curve (AUROC). Results: The recurrence prediction model separated the validation cohort into 15 (18.1%) patients in the high-risk group and 68 (81.9%) patients in the low-risk group. Kaplan-Meier analysis showed the five-year disease-free survival was significantly higher in the low-risk group compared to the high-risk group (86 vs. 50%, HR = 4.41, p = 0.0025). The AUROC for predicting recurrence was 0.744. Conclusions: Our model uses artificial intelligence to successfully predict recurrence after surgical resection for stage I-II non-small cell lung cancer. With an AUROC of 0.744, our model outperforms previously described models with AUROC up to 0.6. Our model separates patients into high-risk and low-risk groups, which will make management decisions clearer compared to other models that also include an intermediate-risk group. Patients in the low-risk group had 86% five-year disease-free survival; patients in the high-risk group had 50% five-year disease-free survival and may benefit from increased postoperative surveillance or adjuvant therapy.

To determine if pre-treatment non-target lung FDG-PET uptake predicts for symptomatic radiation pneumonitis (RP) following lung stereotactic ablative radiotherapy (SABR).We reviewed a 258 patient database from our institution to identify 28 patients who experienced symptomatic (grade ⩾ 2) RP after SABR, and compared them to 57 controls who did not develop symptomatic RP. We compared clinical, dosimetric and functional imaging characteristics between the 2 cohorts including pre-treatment non-target lung FDG-PET uptake.Median follow-up time was 26.9 months. Patients who experienced symptomatic RP had significantly higher non-target lung FDG-PET uptake as measured by mean SUV (p 0.0001) than controls. ROC analysis for symptomatic RP revealed area under the curve (AUC) of 0.74, with sensitivity 82.1% and specificity 57.9% with cutoff mean non-target lung SUV 0.56. Predictive value increased (AUC of 0.82) when mean non-target lung SUV was combined with mean lung dose (MLD). We developed a 0-2 point model using these 2 variables, 1 point each for SUV 0.56 or MLD 5.88 Gy equivalent dose in 2 Gy per fraction (EQD2), predictive for symptomatic RP in our cohort with hazard ratio 10.01 for score 2 versus 0 (p 0.001).Patients with elevated pre-SABR non-target lung FDG-PET uptake are at increased risk of symptomatic RP after lung SABR. Our predictive model suggests patients with mean non-target lung SUV 0.56 and MLD 5.88 Gy EQD2 are at highest risk. Our predictive model should be validated in an external cohort before clinical implementation.

Case Presentation A 38-year-old woman presented with 2 months of dry cough, progressive shortness of breath, central chest pain, nausea, vomiting, and dizziness. She was previously healthy and was not taking any medications. She denied fever, night sweats, or weight loss. She had a two pack-year smoking history and had quit smoking at 27 years of age. She denied drug use and had no recent travel history. Family history was pertinent for ovarian cancer, breast cancer, and colon cancer.

Lung transplant is performed to treat a number of end-stage pulmonary diseases. Because many of the imaging features of post-transplant complications are nonspecific, accurate interpretation of surveillance scans following lung transplantation requires knowledge of modern surgical techniques and predictable post-procedure complications based on the time course after surgery. Computed tomography (CT) is the mainstay of lung transplantation imaging and will be the primary focus of this review.

Background Emerging data support aggressive local treatment of oligometastatic non–small-cell lung cancer (NSCLC) patients. We sought to determine whether the metabolic burden of disease found by fluorodeoxyglucose positron emission tomography at the time of high-dose radiotherapy (RT) for oligometastatic NSCLC can serve as a prognostic biomarker. Materials and Methods We conducted a retrospective cohort study of 67 RT treatment courses in 55 patients with oligometastatic NSCLC who had undergone high-dose RT to all sites of active disease at our institution. The metabolic tumor volume, total lesion glycolysis (TLG), and maximum standardized uptake value of all lesions were measured on the pretreatment fluorodeoxyglucose positron emission tomography scans. Cox regression analysis was used to assess the influence of imaging and clinical factors on overall survival (OS). Results On univariate analysis, a greater metabolic tumor volume and TLG were predictive of shorter OS (hazard ratio of death, 2.42 and 2.14, respectively; P = .009 and P = .004, respectively). The effects remained significant on multivariate analysis. Neither the maximum standardized uptake value nor the number of lesions was significantly associated with OS. Patients within the highest quartile of TLG values (> 86.8 units) had a shorter median OS than those within the lower 3 quartiles (12.4 vs. 30.1 months; log-rank P = .014). Conclusion The metabolic tumor burden was prognostic of OS and might help to better select oligometastatic NSCLC patients for locally ablative therapy.

Molecular analysis of the mutation status for EGFR and KRAS are now routine in the management of non-small cell lung cancer. Radiogenomics, the linking of medical images with the genomic properties of human tumors, provides exciting opportunities for non-invasive diagnostics and prognostics. We investigated whether EGFR and KRAS mutation status can be predicted using imaging data. To accomplish this, we studied 186 cases of NSCLC with preoperative thin-slice CT scans. A thoracic radiologist annotated 89 semantic image features of each patient’s tumor. Next, we built a decision tree to predict the presence of EGFR and KRAS mutations. We found a statistically significant model for predicting EGFR but not for KRAS mutations. The test set area under the ROC curve for predicting EGFR mutation status was 0.89. The final decision tree used four variables: emphysema, airway abnormality, the percentage of ground glass component and the type of tumor margin. The presence of either of the first two features predicts a wild type status for EGFR while the presence of any ground glass component indicates EGFR mutations. These results show the potential of quantitative imaging to predict molecular properties in a non-invasive manner, as CT imaging is more readily available than biopsies.

Left heart disease is associated with left atrial enlargement and is a common cause of pulmonary hypertension (PH). We investigated the relationship between left atrium maximal axial cross-sectional area (LA-MACSA), as measured on chest computed tomography (CT), and PH due to left heart disease (World Health Organization group 2) in patients with right heart catheterization-proven PH.A total of 165 patients with PH who had undergone right heart catheterization with pulmonary artery pressure and pulmonary capillary wedge pressure (PCWP) measurements and nongated chest CTs were included. LA-MACSA, LA anterior-posterior, and LA transverse measurements were independently obtained using the hand-drawn region-of-interest and distance measurement tools on standard PACS by 2 blinded cardiothoracic radiologists. Nonparametric statistical analyses and receiver operating characteristic curve were performed.Forty-three patients had group 2 PH (PCWP15 mm Hg), and 122 had nongroup 2 PH (PCWP≤15 mm Hg). Median LA-MACSA was significantly different between the group 2 PH and nongroup 2 PH patients (2312 vs. 1762 mm, P0.001). Interobserver concordance correlation for LA-MACSA was high at 0.91 (P0.001). At a threshold of 2400 mm, LA-MACSA demonstrated 93% specificity for classifying group 2 PH (area under the curve, 0.73; P0.001).LA-MACSA is a readily obtainable and reproducible measurement of left atrial enlargement on CT and can distinguish between group 2 and nongroup 2 PH with high specificity.

Purpose To determine if regional ventilation within irradiated lung volume predicts change in pulmonary function test (PFT) measurements after stereotactic ablative radiotherapy (SABR) of lung tumors. Methods We retrospectively identified 27 patients treated from 2007 to 2014 at our institution who received: (1) SABR without prior thoracic radiation; (2) pre-treatment 4-dimensional computed tomography (4-D CT) imaging; (3) pre- and post-SABR PFTs 20BED3 ) as the quotient of mean ventilation (mean Jacobian-based per-voxel volume change on deformably registered inhale/exhale 4-D CT phases) within the 20Gy biologically effective dose ( α / β =3Gy) isodose volume and that of the total lung volume (TLV). Results Most patients had moderate to very severe COPD by GOLD criteria ( n =19, 70.1%). Higher VR 20BED3 significantly predicted worse change in Forced Expiratory Volume/s normalized by baseline value (ΔFEV 1 /FEV 1pre , p =0.04); n =7 had VR 20BED3 >1 (high regional ventilation) and worse ΔFEV 1 /FEV 1pre (median=−0.16, range=−0.230 to −0.20). Five had VR 20BED3 1 /FEV 1pre (median=0.13, range=0.07 to 0.20). In a multivariable linear model, increasing VR 20BED3 and time to post-SABR PFT predicted decreasing ΔFEV 1 /FEV 1pre ( R 2 =0.25, p =0.03). Conclusions After SABR to high versus low functioning lung regions, we found worsened or improved global pulmonary function, respectively. If pre-SABR VR 20BED3 is validated as a predictor of eventual post-SABR PFT in larger studies, it may be used for individualized treatment planning to preserve or even improve pulmonary function after SABR.

Coccidioidomycosis, commonly called "valley fever," "San Joaquin fever," "desert fever," or "desert rheumatism," is a multi-system illness caused by infection with Coccidioides fungi (C. immitis or C. posadasii). This organism is endemic to the desert Southwest regions of the United States and Mexico and to parts of South America. The manifestations of infection occur along a spectrum from asymptomatic to mild self-limited fever to severe disseminated disease.Review of the English-language literature.There are five broad indications for surgical intervention in patients with coccidioidomycosis: Tissue diagnosis in patients at risk for co-existing pathology, perforation, bleeding, impingement on critical organs, and failure to resolve with medical management. As part of a multidisciplinary team, surgeons may be responsible for the care of infected patients, particularly those with severe disease.This review discusses the history, microbiology, epidemiology, pathology, diagnosis, and treatment of coccidioidomycosis, focusing on situations that may be encountered by surgeons.

The authors present an excellently documented case that demonstrates the radiologic-pathologic correlation of 2009 influenza A (H1N1) and its complications and discuss possible reasons for severe complications in patients with compromised immune status.

Mutations in DNA accrue relentlessly, largely via stochastic processes. Random changes accumulate, eventually disabling genetic components which result in the formation of the cancer phenotype. Given the infrequency of measured nucleotide changes and the requirement for several mutations to occur in the same cell, it has been postulated that the rate of mutation must become elevated early in the course of evolution of the cancer. Recently, large scale sequencing of tumor DNA has sought to directly measure random mutations. We discuss the implications of these findings and the factors that must be considered in order for fruitful determination of whether a mutator phenotype is a necessary precursor for cancer.

Human alkyladenine DNA glycosylase (hAAG) excises alkylated purines, hypoxanthine, and etheno bases from DNA to form abasic (AP) sites. Surprisingly, elevated expression of hAAG increases spontaneous frameshift mutagenesis. By random mutagenesis of eight active site residues, we isolated hAAG-Y127I/H136L double mutant that induces even higher rates of frameshift mutation than does the wild-type hAAG; the Y127I mutation accounts for the majority of the hAAG-Y127I/H136L-induced mutator phenotype. The hAAG-Y127I/H136L and hAAG-Y127I mutants increased the rate of spontaneous frameshifts by up to 120-fold in S. cerevisiae and also induced high rates of microsatellite instability (MSI) in human cells. hAAG and its mutants bind DNA containing one and two base-pair loops with significant affinity, thus shielding them from mismatch repair; the strength of such binding correlates with their ability to induce the mutator phenotype. This study provides important insights into the mechanism of hAAG-induced genomic instability.

The multiplicity of mutations found in human cancers reflects the consequences of breakdown in genome maintenance and helps to provide insight into the origins of malignancy. Keywords: genetic instability; DNA damage; DNA repair; mutation; cancer

5009 Background: To evaluate the role of surgical staging of patients with grade 1 endometrioid uterine cancer. Methods: Data including stage, histology, grade, lymph nodes involvement and disease-specific survival were extracted from Surveillance, Epidemiology, and End Results Program from 1988 to 2001. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Results: 12,712 women were diagnosed with endometrioid carcinoma which included 3,867 (30.4%) with grade 1, 5,285 (41.6%) with grade 2, and 3,560 (28%) with grade 3 disease. The 5-year disease specific survival of patients with grade 1, 2, and 3 disease was 97.78% ± 0.29, 92.14% ± 0.45, and 78.04% ± 0.82, respectively. Of all the patients with nodal involvement, 10% had grade 1, 39% had grade 2 and 51% had grade 3 disease (p < 0.001). Positive nodes were found in 3% of grade 1, 9% of grade 2 and 18% in grade 3 tumors (p < 0.001). Of the 3,867 patients with grade 1 disease, 3,281 (84.9%) had stage I, 317 (8.2%) had stage II, 166 (4.3%) had stage III, and 103 (2.7%) had stage IV disease. Fifteen percent of the patients with grade 1 disease had extra-uterine spread, including 8% to the cervix, 4% to the pelvis and 3% to the upper abdomen or distant metastases. Conclusions: Grade 1 uterine cancers have a risk of extra-uterine spread. Given that the information obtained from a thorough staging procedure clearly influences adjuvant treatment decisions, complete surgical staging is recommended. No significant financial relationships to disclose.