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International audience; Ice losses from the Greenland and Antarctic ice sheets have accelerated since the 1990s, accounting for a significant increase in the global mean sea level. Here, we present a new 29-year record of ice sheet mass balance from 1992 to 2020 from the Ice Sheet Mass Balance Inter-comparison Exercise (IMBIE). We compare and combine 50 independent estimates of ice sheet mass balance derived from satellite observations of temporal changes in ice sheet flow, in ice sheet volume, and in Earth's gravity field. Between 1992 and 2020, the ice sheets contributed 21.0±1.9 mm to global mean sea level, with the rate of mass loss rising from 105 Gt yr−1 between 1992 and 1996 to 372 Gt yr−1 between 2016 and 2020. In Greenland, the rate of mass loss is 169±9 Gt yr−1 between 1992 and 2020, but there are large inter-annual variations in mass balance, with mass loss ranging from 86 Gt yr−1 in 2017 to 444 Gt yr−1 in 2019 due to large variability in surface mass balance. In Antarctica, ice losses continue to be dominated by mass loss from West Antarctica (82±9 Gt yr−1) and, to a lesser extent, from the Antarctic Peninsula (13±5 Gt yr−1). East Antarctica remains close to a state of balance, with a small gain of 3±15 Gt yr−1, but is the most uncertain component of Antarctica's mass balance. The dataset is publicly available at https://doi.org/10.5285/77B64C55-7166-4A06-9DEF-2E400398E452 (IMBIE Team, 2021).

© Copyright 2022. Sociedad Meteorológica Estadounidense (AMS). Para obtener permiso para reutilizar cualquier parte de este Trabajo, comuníquese con permisos@ametsoc. org . Cualquier uso del material en este Trabajo que se determine como "uso justo" según la Sección 107 de la Ley de derechos de autor de EE. UU. (17 Código de EE. UU. § 107) o que cumpla las condiciones especificadas en la Sección 108 de la Ley de derechos de autor de EE. ) no requiere el permiso de la AMS. La republicación, la reproducción sistemática, la publicación en forma electrónica, como en un sitio web o en una base de datos de búsqueda, u otros usos de este material, excepto los exentos de la declaración anterior, requieren un permiso por escrito o una licencia de la AMS. Todas las publicaciones periódicas y monográficas de AMS están registradas en el Centro de Autorización de Derechos de Autor (https://www.copyright.com ). Se proporcionan detalles adicionales en la declaración de política de derechos de autor de AMS, disponible en el sitio web de AMS ( https://www.ametsoc.org/PUBSCopyrightPolicy ) ., In 2021, both social and economic activities began to return towards the levels preceding the COVID-19 pandemic for some parts of the globe, with others still experiencing restrictions. Meanwhile, the climate has continued to respond to the ongoing increase in greenhouse gases and resulting warming. La Niña, a phenomenon which tends to depress global temperatures while changing rainfall patterns in many regions, prevailed for all but two months of the year. Despite this, 2021 was one of the six-warmest years on record as measured by global mean surface temperature with an anomaly of between +0.21° and +0.28°C above the 1991–2020 climatology., Lake surface water temperatures from satellite data have been generated within the GloboLakes project funded by the UK National Environment Research Council (NE/J023345/2), with extensions funded by the EU Copernicus Climate Change Service (C3S) programme...

NASA/JPL and DLR/Airbus are conducting a joint study of a quantum gravity gradiometer (QGG) technology demonstration concept for advancing mass change measurements. The study outcomes also include near- and long-term science and technology roadmaps for this technology. Studies of gravity gradiometer concepts for mass change measurements have been reported in the literature for the past several years. These studies have considered various quantum metrological implementations, in standalone and constellation of satellite missions, as hybridization of the quantum methods with the conventional satellite-to-satellite tracking methods, and the infusion of quantum technologies in configurations other than a gradiometer to advance mass change measurements.In this paper we report the results of work by the science sub-group of this study team. We report on the technical formulation of a science validation scheme for the tech-demo concept. The scheme includes the validation of the observable measurement model, and validation of its performance characteristics at various time-resolutions and accuracies targeted by the tech-demo. We present these results against a backdrop of the developments in the atomic, molecular and optical physics community that will lead to the desired highest precision measurements. A discussion of such results is expected to prompt a wider engagement with the scientific community on the long-term planning and deployment of this quantum technology to benefit mass change observations.

For 25 years, geodesists have inferred that the displacement of the "geocenter" estimated from (SLR) satellite laser ranging represents fluctuation of Earth's fluid envelope relative to solid Earth. However, SLR determines the displacement of the (CN) center of network of geodetic sites relative to the (CM) center of mass of Earth, consisting of solid Earth, the oceans, the atmosphere, and continental water, snow, and ice. Because solid Earth's surface is deforming in elastic response to the changing load of continental water, atmosphere and oceans, CN only roughly approximates the (CE) center of mass of solid Earth. In this study, estimate the velocity of CM relative to the (CE) center of mass of Earth by first correcting SLR site displacements (estimated by the International Laser Ranging Service 2020) for their elastic response relative to CE produced by fluctuations of continental water, atmosphere and oceans. We maintain that by correcting for loading displacements relative to CE, we arrive at an estimate of the displacement of CE. We find that transforming the SLR series from CN to CE reduces the discrepancy between the seasonal oscillation of Earth's fluid envelope estimated by SLR and that assumed by GRACE (using the technique of Sun et al. 2017) by 40 per cent. In both SLR and GRACE, a total of 0.5 x 1016 kg of mass moves between hemispheres from southern oceans in August to snow-covered areas in North America and Europe (in particular in Canada and Siberia). The primary remaining difference between the two techniques is that mass in the northern hemisphere is maximum on February 5 in SLR, 20 days before it is maximum on Feb 25 in GRACE. Knowing the total transfer of the mass of between hemispheres places a boundary constraint on global models of circulation of water on land and in the oceans and atmospheres (that may be applied to forecasting extreme events such as flooding and drought).

This talk will provide a status update on Level-2 data processing at JPL. Included will be an overview of data products currently delivered to the community, including gravity fields with the updated accelerometer transplant product. Assessments of data quality and error levels, along with detailed discussions of the solution strategy will be included. A comparison of LRI and KBR gravity fields will be provided.. A look towards an RL07 reprocessing of GRACE and GRACE-FO will additionally be provided. The reprocessing plans to incorporate the estimation of a full noise covariance model of the satellite observations in the gravity estimates. Preliminary results incorporating this strategy will be shown and discussed.

Global Climate is one chapter from the State of the Climate in 2019 annual report and is avail- able from https://doi.org/10.1175/BAMS-D-20-0104.1 Compiled by NOAA’s National Centers for Environmental Information, State of the Climate in 2019 is based on contributions from scien- tists from around the world. It provides a detailed update on global climate indicators, notable weather events, and other data collected by environmental monitoring stations and instru- ments located on land, water, ice, and in space. The full report is available from https://doi.org/10.1175/2020BAMSStateoftheClimate.1.

We describe a Simplified Gravitational Reference Sensor (S-GRS), an ultra-precise inertial sensor for future Earth geodesy missions. These sensors are used to measure or compensate for all non-gravitational accelerations of the host spacecraft so that they can be removed in the data analysis to recover spacecraft motion due to Earth's gravity field, which is the main science observable. Low-low satellite-to-satellite tracking missions like GRACE-FO that utilize laser ranging interferometers are technologically limited by the acceleration noise performance of their electrostatic accelerometers, in addition to temporal aliasing associated with Earth's dynamic gravity field. The S-GRS is estimated to be at least 40 times more sensitive than the GRACE accelerometers and more than 500 times more sensitive if operated on a drag-compensated platform. The improved performance is enabled by increasing the mass of the sensor's test mass, increasing the gap between the test mass and its electrode housing, removing the small grounding wire used in the GRACE accelerometers and replacing them with a UV LED-based charge management system. This level of improvement allows future missions to fully take advantage of the sensitivity of the GRACE-FO laser Ranging Interferometer in the gravity recovery analysis. The S-GRS concept is a simplified version of the flight-proven LISA Pathfinder GRS. Our performance estimates are based on models vetted during the LISA Pathfinder flight and the expected Earth orbiting spacecraft environment based on flight data from GRACE-FO. The relatively low volume, mass, and a power consumption enables use of the S-GRS on ESPA-class microsatellites, reducing launch costs or enabling larger numbers of satellite pairs to be utilized to improve the temporal resolution of Earth gravity field maps., Corrected typos, clarified some sentences, and added references

Quantification of uncertainty in surface mass change signals derived from GNSS measurements poses challenges, especially when dealing with large datasets with continental or global coverage. Our aim is to assign weights to GNSS estimates of vertical land displacement (VLD), which will be used in a future joint solution with GRACE observations. Thus, we study the structure and quantify the uncertainty present in VLD estimates derived from 3045 GNSS stations distributed across the continental US. Monthly means of daily positions are available for 15 years. First, we remove outliers by performing a 3σ test, and data screening via a number of correlation metrics between the input GNSS VLD estimates and external validation datasets (i.e., VLD predicted from GRACE/GRACE-FO and hydrology models). Afterwards, we employ various processing schemes to characterize the uncertainty of VLD through stochastic modeling and quantification of the spatially correlated errors. In particular, we test for white, colored and spatially correlated noise. When only white noise is considered nearly 30% of the stations exhibit noise level < 2 mm, 65% noise between 2-4 mm and 5% noise > 4 mm. In case of colored noise, error smaller than 2 mm, between 2-4 mm and >4mm, is mapped in 20%, 60% and 20% of the stations, respectively. Spatially correlated noise is in family but slightly smaller in magnitude compared to colored noise.

Knowledge of Earth system mass change is limited to spatial scales of approximately 300 km x 300 km, as this is near the native resolution of the data collected from the GRACE and GRACE-FO (G/GFO) satellite gravimetry missions. Measurements of surface height change at much finer spatial scales can additionally be exploited to derive mass change, albeit with the proper treatment of the data. Here, we jointly invert inter-satellite range-rate measurements from GRACE and GRACE-FO, surface height changes measured by in-situ GNSS receivers, and surface elevation changes from a multi-mission synthesis of radar and laser satellite altimeters to estimate mass change at spatial scales of 100 km x 100 km within a Bayesian framework over the time period 2002 - 2021. In this talk, we will focus on results over North America, where nearly 3,000 in-situ GNSS measurements are processed in combination with G/GFO, and over Antarctica, where Envisat, ICESat, CryoSat-2, and ICESat-2 measurements have been processed in combination with G/GFO. We find agreement between the geodetic data combination solution and the G/GFO-only solution at large basin scales, but unique knowledge of mass change is gained with the geodetic data combination solution at smaller spatial scales not observed by satellite gravimetry alone.

Ice losses from the Greenland and Antarctic Ice Sheets have accelerated since the 1990s, accounting for a significant increase in global mean sea level. Here, we present a new 29-year record of ice sheet mass balance from 1992 to 2020 from the Ice Sheet Mass Balance Inter-comparison Exercise (IMBIE). We compare and combine 50 independent estimates of ice sheet mass balance derived from satellite observations of temporal changes in ice sheet flow, in ice sheet volume and in Earth’s gravity field. Between 1992 and 2020, the ice sheets contributed 21.0 ± 1.9 mm to global mean sea-level, with the rate of mass loss rising from 105 Gt yr-1 between 1992 and 1996 to 372 Gt yr-1 between 2016 and 2020. In Greenland, the rate of mass loss is 169 ± 9 Gt yr-1 between 1992 and 2020 but there are large inter-annual variations in mass balance with mass loss ranging from 86 Gt yr-1 in 2017 to 444 Gt yr-1 in 2019 due to large variability in surface mass balance. In Antarctica, ice losses continue to be dominated by mass loss from West Antarctica (-82 ± 9 Gt yr-1) and to a lesser extent from the Antarctic Peninsula (-13 ± 5 Gt yr-1). East Antarctica remains close to a state of balance (3 ± 15 Gt yr-1), but is the most uncertain component of Antarctica’s mass balance.

The Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow-On (GRACE-FO) provided twenty years of data on Earth’s time-varying gravity field. Due to their design, GRACE and GRACE-FO are inherently limited in their spatiotemporal coverage, limiting their resolution to a few hundred kilometers and temporally to roughly monthly solutions. To increase the global spatiotemporal resolution and allow for the determination of submonthly time-varying gravity field signals, a constellation of GRACE-type satellite pairs is a possible path forward. Advances in small form factor instrumentation for small satellites have become progressively inexpensive, reliable, and of higher quality. This leads us to consider that a constellation of GRACE-type small satellites could be part of future gravimetric satellite missions. In this work, we investigate the viability and limitations of a genetic-algorithm-based optimization and its objective function to generate satellite constellations to recover daily Earth system mass changes. The developed approach is used to create satellite constellations that are optimally designed to recover gravity variations of sufficient resolution at a range of temporal frequencies (i.e., daily to monthly). We analyze a constellation’s performance using a combination of observability in space, accounting for directionality, and homogeneity in time. This allows us to navigate through a vast search space in a relatively short period of time and estimate the relative performance of constellations to each other. Using evolutionary theory, we converge towards a set of optimally selected orbits. The characteristics of the designed constellations have been validated using high-fidelity numerical simulations. We summarize these results and discuss their implications for possible future constellations of small GRACE-like satellite pairs. The resulting constellations have an inherently improved spatiotemporal performance, which reduces temporal aliasing errors and allows the characterization of daily mass-change effects.

Groundwater provides nearly half of irrigation water supply, and it enables resilience during drought, but in many regions of the world, it remains poorly, if at all managed. In heavily agricultural regions like California’s Central Valley, where groundwater management is being slowly implemented over a 27-year period that began in 2015, groundwater provides two-thirds or more of irrigation water during drought, which has led to falling water tables, drying wells, subsiding land, and its long-term disappearance. Here we use nearly two decades of observations from NASA’s GRACE satellite missions and show that the rate of groundwater depletion in the Central Valley has been accelerating since 2003 (1.89 km3/yr, 1961–2021; 2.41 km3/yr, 2003–2021; 8.57 km3/yr, 2019–2021), a period of megadrought in southwestern North America. Results suggest the need for expedited implementation of groundwater management in the Central Valley to ensure its availability during the increasingly intense droughts of the future.

Unlike in breast cancer and melanoma, sentinel lymph node mapping in colon cancer is primarily used as an aid to the pathologist for accurate nodal staging. The study was undertaken to review the incidence of micro-metastasis and its impact on survival when treated with chemotherapy. The study was also undertaken to see if SLNM could guide limited colon resection in early T stage tumor as a paradigm shift. SLNM was done by subserosal injection of a blue dye. SLNs were ultra-staged by multilevel sectioning and remaining Specimen was then examined by conventional method. For the last 245 patients the specimen was divied ex vivo into two segments as segment A containing the tumor bearing portion of the colon and SLNs with attached mesentery, while segment B include distal part of the colon with attached mesentery. Nodal staging was separately examined. Of the 354 Pts, SLNM was successful in 99.9% of Pts with an average no of SLN/ Pt = 2.8 and total nodes 17.8/pt. Survival was directly related negatively with stage and nodal status. Pts with +ve LN did much better with chemotherapy than without chemotherapy. With 245 Pts, specimen A Vs B, no Pts had +ve node in specimen B with -ve LN in specimen A. SLNM results in more node/Pt, more positive node/Pt ,and more micro-metastasis who when treated with chemotherapy survive longer. Limited segmental resection in early T stage is possible when done with guidance by SLNM without compromising biology.

This talk will provide a status update on Level-2 data processing at JPL. Included will be an overview of data products currently delivered to the community. Assessments of data quality and error levels, along with detailed discussions of the solution strategy will be included. A comparison of LRI and KBR gravity fields will be provided, in addition to a discussion on efforts to combine both data types in the gravity retrieval. A look towards an RL07 reprocessing of GRACE and GRACE-FO will additionally be provided, along with preliminary results.

The GRACE missions have changed the way that we measure mass changes of ice sheets, glaciers and ice caps, with quantied uncertainties that factor processing errors, atmospheric and oceanic corrections, and removal of glacial isostatic adjustment (GIA). We present GRACE/GRACE-FO estimates of mass balance over the Greenland and Antarctic Ice Sheets and the World’s glaciers and ice caps (GIC). The data gap between missions is filled with GRACE-calibrated results from the input-output method for ice sheets and surface mass balance (SMB) reconstructions from regional atmospheric climate models and MERRA-2 reanalysis data for the glaciers and ice caps. Over Greenland, we report low losses during the cold years of 2017-2018 followed by record melt in 2019 and an onset of rapid melt for 2020. As warm air and ocean masses get blocked over Greenland more frequently because of interactions between the wobbling jet stream and topography, we observe more high melt events in this decade than recorded in prior centuries. In Antarctica, the ongoing rapid loss in West Antarctica dominates the mass balance, but we observe a steady increase in snowfall in the Atlantic sector of East Antarctica. The exercise provides a mass balance record that can be continuously improved with better corrections and improved processing, with reduced errors, so that we can provide better constraints for ice sheet models in charge of sea level projections and improve the validation of various Earth system models and global climate models.

Terrestrial water storage (TWS) data derived from past Gravity Recovery and Climate Experiment (GRACE; April 2002–June 2017) and current GRACE-Follow On (GRACE-FO; June 2018–present) missions provide insights into mass transport within, and between, different Earth’s systems (e.g., atmosphere, oceans, groundwater, and ice sheets). However, there are currently temporal gaps within GRACE-derived TWS record (20 months) and between GRACE and GRACE-FO missions (11 months), within GRACE-FO-derived TWS record (2 months), and similar gaps could be experienced between GRACE-FO and GRACE-II missions. In this study, we compare the performance of different data-driven techniques in filling TWS gaps for 62 global watersheds. Additionally, these techniques are being applied to reconstruct TWS globally on a grid scale (1° × 1°). We used artificial neural networks (ANNs), support vector machines (SVMs), and multiple linear regression (MLR) models to predict TWS data (04/2002 – 03/2020) based on the knowledge of relevant climatic datasets such as rainfall, temperature, evapotranspiration, vegetation indices, climate indices. The performance of the developed models was evaluated using several standard measures such as the root mean square error (RMSE), correlation coefficient (R), and Nash-Sutcliff efficiency coefficient (NSE). Our preliminary results indicate: (1) ANN models show higher performance over the examined watersheds compared to the other models (RMSE: 5.20; R: 0.93; NSE: 0.88), (2) the performances of ANN, MLR, and SVM models depend mainly on the nature of factors that control TWS in each of the examined hydrologic systems, and (3) higher model performance is achieved when the model input data were further spectrally decomposed. Results of our research could be used to validate GRACE-FO datasets. Our research will promote additional and improved use of GRACE products by the scientific community, end-users, and decision makers by providing a continuous uninterrupted TWS record from GRACE and GRACE-FO missions.

The 2017-2027 US National Academy of Sciences Decadal Survey for Earth Science and Applications from Space classified mass change as one of five designated observables having the highest priority in terms of Earth observations required to better understand the Earth system over the next decade. In response to this designation, NASA initiated multi-center studies with an overarching goal of defining observing system architectures for each designated observable. Here, we discuss the progress made and future plans for the Mass Change Designated Observable study. Progress includes the development of a Science and Applications Traceability Matrix, a tool that links science objectives to measurement techniques and accuracies, for the 15 science and applications objectives listed in the Decadal Survey, as well as the definition of as many as three different architectural classes for which to achieve those objectives. We will describe the Value Framework that is under way to assess and evaluate each observing system architectural option. Preliminary results assessing the science value versus cost/risk of observing system architectures will be presented. In addition, future plans for the Mass Change Designated Observable Study will be discussed.

// Alison K. Bauer 1 , Brad L. Upham 2 , Elizabeth A. Rondini 3 , Meredith A. Tennis 4 , Kalpana Velmuragan 1 and David Wiese 5 1 Department of Environmental and Occupational Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 2 Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA 3 Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA 4 Department of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 5 McLaren Regional Medical Center, Flint, MI, 48532, USA Correspondence to: Alison K. Bauer, email: alison.bauer@ucdenver.edu Keywords: adenocarcinoma, innate immunity, non-small cell lung carcinoma, prognostic, toll-like receptor Received: September 30, 2016 Accepted: June 02, 2017 Published: July 22, 2017 ABSTRACT Introduction. Lung cancer remains the highest cause of cancer mortality worldwide. Toll-like receptors (TLR) are innate immune receptors that have both pro- and anti-tumorigenic properties. Based on findings from epidemiological studies and in rodents, we hypothesized that elevated TLR expression would be a positive prognostic indicator of disease in non-small cell lung carcinoma patients. Results. Higher mRNA expression of TLR1-3 and 5-8 were significantly associated with increased overall survival (OS) when analyzed individually or as a group in both non-small cell lung carcinoma (NSCLC) patients and in the adenocarcinoma (ADC) subtype. Significant co-expression of many TLR combinations in ADC patients were also observed via RNA sequencing. Immunostaining demonstrated TLR4 and 8 significantly correlated in tumor tissue, similar to RNA. Methods. We used kmplot.com to perform a meta-analysis on mRNA expression of TLR1-10 to determine any significant associations with OS in NSCLC and the ADC subtype. cBioportal was also used simultaneously to assess co-expression in TLR1-10 in ADC patients via RNA sequencing and to identify any molecular alterations. Lastly, immunostaining for a subset of TLRs was conducted on ADC patients. Conclusions. Expression of innate immune receptors TLR1-10 is associated with improved survival outcomes in NSCLC. Thus, further evaluation of their predictive capacity and therapeutic utility is warranted.

All colon cancer patients with lymph node (LN) positive disease are treated with chemotherapy. Patients with node negative disease are usually cured by surgery alone. Yet about 20% of patients develop recurrence within 5 years despite node negative status. This may often be the result of missed micrometastases by conventional examination. Sentinel lymph node (SLN) mapping was developed to find those nodes detected by blue dye which was ultrastaged to detect micrometastases. Consecutive patients, underwent SLN mapping with the blue dye with success rate of 99.2%. Average number of LN was 18.3, average number of SLN was 3/patient and overall nodal positivity was 45%. Ten patients had skip metastases. Overall survival of 235 patients was 84 months with survival of node negative patients 97 months versus 68 months for node positive patients. For stage I–IV patients, overall survival was as follows: stage I—115 months, stage II—90 months, stage III—84 months and stage IV—24 months respectively. Patients with micrometastases after chemotherapy had average survival of 108 months versus those without chemotherapy was 50 months. Thus, SLN mapping techniques is highly successful, easily reproducible and finds micrmoetastases in over 15% of patients which could have been missed by conventional pathological examination. These patients when treated with adjuvant chemotherapy have similar survival as those of node negative disease. Similarly, patients without any nodal metastases after SLN mapping and ultrastaging, may be considered as true node negative disease and may avoid further adjuvant chemotherapy.

Background American Joint Committee on Cancer uses tumor size for "T" staging of many solid tumors for its effect on prognosis. However, tumor size has not been incorporated in tumor (T), nodal status (N), metastasis (M) staging for colon cancer. Hence, the National Cancer Data Base was used to determine whether tumor size correlates with TNM staging and survival. Methods For the 300,386 patients, tumor size was divided into S 1 (0 to 2 cm), S 2 (>2 to 4 cm), S 3 (>4 to 6 cm), and S 4 (>6 cm). Statistical comparison was done for TNM stage, grade, and nodal status with tumor size. Kaplan–Meier survival analysis was done for each "S" stage. Results Of the 300,386 patients, 13% were classified as S 1 , 39% S 2 , 30% S 3 and 18% as S 4 . Right colon was the most common site (48%). Tumor size positively correlated with grade, T stage, and nodal stage. Tumor size was inversely associated with survival. Conclusion Tumor size is positively correlated with important prognostic factors and negatively impacted survival.

Background Nodal positivity is correlated with a poorer prognosis in breast cancer. A study was composed to compare nodal positivity in patients with single versus multiple lesions found on magnetic resonance imaging (MRI) and mammogram (MMG). Methods A retrospective study of breast cancer patients undergoing MRI and MMG was performed. Nodal positivity was compared in patients with additional invasive lesions found on MRI versus single invasive lesions found on MRI and MMG. Results A total of 425 patients were included. The overall nodal positivity was 23.8%. Patients with single versus multiple malignant lesions had nodal positivity of 20.9% vs 31.1% ( P = .04). MRI detected multiple lesions in 120 patients, 80 of which were not detected by MMG (18.8%). Comparing single lesions with additional malignant lesions detected by MRI only, nodal positivity increased from 20.9% to 51.6% ( P = .0002). Conclusions Patients with additional invasive lesions on MRI had significantly higher nodal positivity than single invasive lesions. Hence, addition of MRI in early-stage breast cancer may have prognostic value because of detection of potential node-positive patients.

e15795 Background: Surgery remains the only curative treatment option in pancreatic adenocarcinoma, yet in more than 50% of the patients (pts) the disease is too advanced or at very high risk and considered inoperable. They are either managed with no treatment or other nonsurgical methods. Hence, we analyzed a large cohort of pancreatic adenocarcinoma pts undergoing No Treatment vs Chemotherapy, Radiation or Chemoradiation to determine their impact on survival. Methods: Only pancreatic adenocarcinoma pts who had no surgery in the National Cancer Database (NCDB) from 2004–2014 were included. Of that group, patients with unknown or missing data about chemotherapy or radiation treatment or less than 3 years of survival data were excluded. Pts were stratified into 4 groups: Chemotherapy, Radiation Therapy, Chemoradiation and No Treatment. Overall 1-, 2- and 3-year survival was calculated and the groups were compared using Pearson’s chi-squared. Results: Of the total 309,709 pancreatic cancer pts in the NCDB 2004–2014, 111,421 (36.0%) remained after application of the study criteria. Of these, 43,203 (38.8%) received chemotherapy only, 2,453 (2.2%) received radiation only, 15,764 (14.1%) received chemoradiation and 50,001 (40.0%) had no treatment. Overall survival for 1, 2, and 3 years was best in the chemoradiation group with a 1 year survival of (40.0%) compared to chemotherapy only (22.4%), radiation only (14.9%) and no treatment (9.6%). Overall, only (19.0%) of pts survived for 1 year, (5.4%) survived for 2 years and (2.3%) survived for 3 years. (Table) Conclusions: Survival in pancreatic adenocarcinoma pts remains dismal without surgery. Best survival in nonsurgical pts was seen after combination Chemoradiation therapy and worst survival in No Treatment group. Hence, whenever possible, a combination Chemoradiation should be offered even as palliation in non-surgical pancreatic adenocarcinoma pts.[Table: see text]

e17042 Background: During debulking surgery (Surg) for advanced ovarian cancer (OvCa), lymph node (LN) sampling is not routinely performed. Hence, prognostic implications of LN involvement following debulking surg and chemotherapy (ChemoRx) were analyzed from the National Cancer Database (NCDB). Methods: Only Stage III and IV patients (pts) from NCDB 2006–2014 undergoing debulking surg and ChemoRx were included. Group A: pts with debulking surg without bowel resection; Group B: pts with major bowel resection and Group C: pts with bowel and bladder resection. Pts were further subdivided according to the use of 1) NeoAdjuvant (NeoAdj) 2) Adjuvant (Adj) and 3) NeoAdj and Adj ChemoRx. Survival analysis was done based on -ve or +ve LN status. Pearson Chi Square testing was used to evaluate the survival between -ve and +ve LN pts. Results: A total of 13839 Pts were included. There were 5757 Pts (41.59%) with -ve LN status, versus 8082 Pts (68.4%) with +ve LN status. Out of 10,737 Stage III and 3,102 Stage IV pts, there were 6,828 in Group A, 6,413 in Group B and 598 in Group C pts. For all patients in Groups A, B, and C, the 5 yr overall survival was better in LN -ve than LN +ve pts. The overall survival for both LN -ve and LN +ve pts was better in Adjuvant chemoRx in all 3 groups, except for Stage III Group C LN-ve pts, where NeoAdj was better (75% vs 37.5%). Overall survival was also slightly better in Stage III vs Stage IV pts. (Table-1). Conclusions: Even though LN dissection is not routinely done during debulking surgery, overall pts with LN metastasis do worse than LN -ve pts irrespective of the timing of ChemoRx. Hence, LN sampling during debulking surg should be strongly considered, as it may provide important prognostic information. Table-1: 5 yr Survival by LN status [Table: see text]

e15042 Background: Lymph node (LN) metastasis (mets) is the strongest prognostic factor in colon cancer (CCa), however, its significance in Stage IV disease remains controversial. We analysed National Cancer Database (NCDB) to determine the impact of nodal mets on survival in Stage IV CCa patients (pts). Methods: From 2004-2014, NCDB pts with pathologic Stage IV CCa were divided into groups based on LN status and No. of +ve LNs. Only Stage IV CCa pts who underwent surgical resection of their primary tumor with available pathologic data as well as chemotherapy data were included. Kaplan-Meier method and log rank test were used to compare 5-year overall survival. Results: A total of 33574 pts data met the criteria of the study. Adenocarcinoma represented 82.3% of the total pts. Majority of the pts (82.61%) had +ve LN status. Mean survival was 36.3 vs 24.2 months in -ve LN vs +ve LN pts respectively. Overall 5yr survival was better in LN -ve pts ( 23.4%) versus LN +ve pts ( 10.2%) Survival for all years was inversely related to the number of +ve LN ( Table). For LN +ve or LN -ve pts, receiving any form of chemotherapy was associated with significantly improved survival when compared to no chemotherapy. Conclusions: LN status and No. of +ve LNs impact the prognosis of CCa, even in stage IV. Receiving some form of chemotherapy improves the prognosis for both pts with +ve or -ve LN status. These findings suggest that separation of Stage IV LN negative versus positive patients may be warranted in staging and treatment. 5 year survival according to LN status and No. of positive LN. [Table: see text]

Introduction. Breast cancer recurrence can develop years after primary treatment. Crosstalk between breast cancer cells and their stromal microenvironment may influence tumor progression. Our primary study aim was to determine whether endothelin-1 (ET-1) expression in tumor and stroma predicts breast cancer relapse. The secondary aim was to determine ET-1/endothelin receptor A (ETAR) role on signaling pathways and apoptosis in breast cancer. Experimental Design. Patients with histologically documented stages I–III invasive breast cancer were included in the study. ET-1 expression by immunohistochemistry (IHC) in tumor cells and stroma was analyzed. Association between ET-1 expression and clinical outcome was assessed using multivariate Cox proportional hazard model. Kaplan-Meier curves were used to estimate disease-free survival (DFS). In addition, the effect of ET-1/ETAR on signaling pathways and apoptosis was evaluated in MCF-7 and MDA-MB-231 breast cancer cells. Results. With a median followup of 7 years, ET-1 non-enriched tumor phenotype had a significant association with favorable disease-free survival (HR=0.16; 95% CI 0.03–0.77; P value Conclusions. We found ET-1 expression in tumor and stroma to be an independent prognostic marker for breast cancer recurrence. Prospective studies are warranted to examine whether ET-1 expression in tumor/stroma could assist in stratifying patients with hormone receptor positive breast cancer for adjuvant therapy.

Review of literature was performed on studies with prognostic impact of micrometastasis in colorectal cancer. Among 16 studies included, micrometastasis was detected in 26.5% of patients. Most analysis revealed that micrometastasis carries a poorer prognosis compared to node negative disease (NND). The results of those studies were compared with our pilot study of 109 patients with colon cancer, showing improved prognosis of micrometastasis after being upstaged and treated with chemotherapy when compared with NND.

Background Magnetic resonance imaging (MRI) in breast cancer can detect more than 15% additional lesions than mammography. We investigated lymph node metastases rates in patients with multifocal or multicentric disease detected by MRI compared with patients with a single lesion detected by mammography and magnetic resonance imaging. Methods A retrospective analysis of breast cancer patients undergoing MRI and mammography was performed. The objective was to compare lymph node metastases rates in patients with additional lesions detected by MRI versus a single lesion detected by mammography or MRI. Results Of 413 patients, 318 were included for the study. The overall nodal metastases rate was 24.8%. MRI detected multiple lesions in 83 (26.1%) patients; 67 (21.1%) patient MRI findings were not detected by mammography. The lymph node metastases rate was 37.3% when ≥2 lesions were detected compared with 20.2% when a single malignant lesion was detected ( P = .01). The evaluation of the 67 patients with additional lesions detected by MRI revealed 32 patients with invasive lesions, 29 with benign lesions, and 6 with in situ disease. Comparing patients with single malignant lesions with patients with additional malignant lesions detected by MRI, the lymph node metastases rate increased from 20.2% to 50% ( P = .002). Conclusions Our study shows a significant increase in the lymph node metastases rate in patients with additional malignant lesions detected by MRI. This finding suggests that MRI-detected malignant lesions are biologically significant and may predict more aggressive disease.

e15698Background: Skip metastases (Mets) may appear later in breast cancer (BrCa) and melanoma (M) patients (pts) after sentinel lymph node mapping (SLNM) causing understaging and undertreatment. H...

e16223Background: Pancreatic cancer (PCa) patients (Pts) have dismal survival with surgery alone; hence chemotherapy (ChemoRx) has been used often. We analyzed the role of lymph node (LN) and margi...

The relationship between primary colon cancer and occult nodal metastases (OMs) detected by cytokeratin immunohistochemistry (CK-IHC) is unknown. We sought to investigate the correlation of clinicopathologic features of colon cancer with OMs and to identify predictors of OM.Patients with colon cancer from 5 tertiary referral cancer centers enrolled in a prospective trial of staging had standard pathologic analysis performed on all resected lymph nodes (using hematoxylin and eosin staining [HE]). Nodes negative on HE underwent CK-IHC to detect OMs, which were defined as micrometastases (N1mic) or isolated tumor cells (N0i+). Patients who were negative on both HE and CK-IHC were defined as node negative (NN), and those positive on HE were node positive (NP). The relationships between tumor characteristics and OMs were analyzed using the Kruskal-Wallis and the Fisher exact test.OMs were identified in 23.4% (25/107) of patients. No significant differences were found in demographics, tumor location, tumor size, and number of nodes examined between groups. Compared with the NN group, patients with OMs had more tumors that were T3/T4 (72% vs 57%; P.001), had tumors of higher grade (28% vs 12%; P = .022), and had tumors with lymphovascular invasion (16% vs 3%; P.001).Adverse primary pathologic colon cancer characteristics correlate with OMs. In patients with negative nodes on HE and stage T3/T4 colon cancer, lymphovascular invasion, or high tumor grade, consideration should be given to performing CK-IHC. The detection of OMs in this subset may influence decisions regarding adjuvant chemotherapy and risk stratification.

The aim of this study to analyze whether ultrastaging of initially negative nonsentinel lymph nodes (non-SLNs) would increase nodal positivity in colon cancer and rectal cancer.After SLN mapping (SLNM), SLNs were ultrastaged by 4 hematoxylin and eosin and 1 immunohistochemistry sections. A blinded pathologist reexamined initially negative non-SLNs by 3 additional hematoxylin and eosin and 1 immunohistochemistry sections.In 156 colon cancer and 44 rectal cancer patients, 2,755 nodes were identified (494 SLNs and 2,261 non-SLNs). Metastases were detected in 20.9% of SLNs and 8.6% of non-SLNs (P.0001). After ultrastaging non-SLNs, only .58% became positive for metastases in 12 patients. Of these, 10 already had positive lymph nodes, hence no change of staging occurred. Ultrastaging upstaged only 2 of 200 patients (1%).The chance of finding additional metastases by ultrastaging of all non-SLNs is extremely low (1%) and of little benefit.

Methylene blue (M), as a dye in sentinel lymph node mapping (SLNM), has been introduced as an alternative to lymphazurin (L) after the recent shortage of L. M has been evaluated in breast cancer in multiple studies with favorable results. Our study compares L with M in the SLNM of gastrointestinal (GI) tumors.Between Jan 2005 and Aug 2008, 122 consecutive patients with GI tumors were enrolled. All patients (pts) underwent SLNM with either L or M by subserosal injection of 2-5 mL of dye. Efficacy and rates of adverse reactions were compared between the two dyes. Patients were prospectively monitored for adverse reactions including anaphylaxis, development of blue hives, and tissue necrosis.Of 122 pts, 60 (49.2%) underwent SLNM using L and 62 (50.8%) underwent SLNM using M. Colon cancer (CrCa) was the most common site in both groups. The success rate of L and M in SLNM was 96.6% and 96.7%, respectively, with similar numbers of total number of lymph nodes per pt, SLNs per pt (3), nodal positivity, skip metastasis, and accuracy. The only adverse reaction in the L group was oxygen desaturation5% in 5% (3/60) of pts, compared with none in the M group. Cost per vial of L was $210 vs $7 for M.The success rate, nodal positivity, average SLNs per patient, and overall accuracy were similar between L and M. Absence of anaphylaxis and lower cost make M more desirable than L in SLNM of GI tumors.

The requirement for nodal analysis currently confounds the oncological propriety of focused purely endoscopic resection for early-stage colon cancer and complicates the evolution of innovative alternatives such as natural orifice transluminal endoscopic surgery (NOTES) and its hybrids. Adjunctive sentinel node biopsy (SNB) deserves consideration as a means of addressing this shortfall.Data from two prospectively maintained databases established for multicentric studies of SNB in colon cancer that employed similar methodologies were pooled to establish technique potency selectively in T1/T2 disease (both overall and under optimized conditions) and to project potential clinical impact.Of 891 patients with T1-4, M0 intraperitoneal colon cancer, 225 had T1/T2 disease. Sentinel nodes were either not found or were falsely negative in 18 patients with T1/T2 cancers (8%) as compared with 17% (112/646) in those with T3/T4 disease (P = 0.001). Negative predictive value (NPV) in the former exceeded 95%, while sensitivity [including immunohistochemistry (IHC)] was 81%. In the 193 patients with T1/T2 disease recruited from those centers contributing22 patients, sensitivity was 89% and NPV 97%. Thus, in this cohort, SNB could have correctly prompted localized resection (obviating en bloc mesenteric dissection) in 75% (144) of patients, including 59 with T1 lesions potentially amenable to intraluminal resection alone as their definitive treatment. Forty-four patients (23.4%) would still have conventional resection, leaving three patients (1.6% overall) understaged (11% false-negative rate).These findings support the further investigation of SNB as oncological augment for localized resective techniques. Specific prospective study should pursue this goal.

Purpose: Nodal micrometastasis and circulating tumor cells detected by multimarker quantitative real-time reverse transcription-PCR (qRT-PCR) may have prognostic importance in patients with colorectal cancer. Experimental Design: Paraffin-embedded sentinel lymph nodes from 67 patients and blood from 34 of these patients were evaluated in a prospective multicenter trial of sentinel lymph node mapping in colorectal cancer. Sentinel lymph nodes were examined by H&E staining and cytokeratin immunohistochemistry. Sentinel lymph nodes and blood were examined by a four-marker qRT-PCR assay (c-MET, melanoma antigen gene-A3 family, β1→4-N-acetylgalactosaminyltransferase, and cytokeratin-20); qRT-PCR results were correlated with disease stage and outcome. Results: In H&E-negative sentinel lymph node patients that recurred, cytokeratin immunohistochemistry and qRT-PCR detected metastasis in 30% and 60% of patients, respectively. Disease-free survival differed significantly by multimarker qRT-PCR upstaged sentinel lymph node (P = 0.014). qRT-PCR analysis of blood for circulating tumor cells correlated with overall survival (P = 0.040). Conclusion: Molecular assessment for micrometastasis in sentinel lymph node and blood specimens may help identify patients at high risk for recurrent colorectal cancer, who could benefit from adjuvant therapy.

Background Sentinel lymph node (SLN) mapping (M) for staging in colorectal cancer (CRCa) remains controversial and needs to be validated. This study analyzes results of SLNM at a multi-institutional level for CRCa. Methods Group A patients underwent SLNM with 1 to 3 mL of 1% lymphazurin. First 1 to 4 blue lymph nodes were designated as SLNs and had focused analysis. Group B had standard resection and nodal staging. Patients with a minimum of 2 years of follow-up were analyzed for recurrence. Results Overall nodal metastasis were 50% for 500 group A patients versus 35% for 368 group B patients. In SLNM patients success, accuracy, sensitivity, and negative predictability values were 98%, 96%, 90%, and 93%, respectively. With a 2-year minimum follow-up, 153 group A patients had 7% recurrences compared with 25% in 162 group B patients. Conclusion SLNM is highly feasible and accurate for staging CRCa with higher detection of nodal metastasis and lower recurrences.

The advent of sentinel lymph node mapping (SLNM) has had a profound impact on the surgical management of breast cancer and melanoma over the past decade. However, SLNM in gastrointestinal malignancies is still in its infancy. The role of SLNM in gastrointestinal malignancies is to increase staging accuracy and to reduce the understaging associated with standard surgical and pathological techniques. Numerous authors have described the successful use of SLNM in colon, rectal, gastric, esophageal, and anal canal malignancies, with a high degree of accuracy and upstaging by detailed pathological analysis of the sentinel nodes. Over the past 2 years, research and publications related to gastrointestinal lymphatic mapping have dramatically increased worldwide.

Inaccurate staging of colorectal cancer (CRC) has been attributed to the failure to detect lymph node metastases by conventional pathology. We have previously reported the use of lymphatic mapping to accurately identify those lymph nodes most likely to harbor micrometastatic disease and permit focused pathologic examination. Mutation of K-ras allele at codons 12 or 13 occurs frequently in early stages of CRC development. The purpose of our study was to assess sentinel lymph nodes (SLN) for occult CRC micrometastases using a unique peptide nucleic acid (PNA) clamp PCR assay specific for K-ras mutations. Seventy-two paraffin-embedded primary CRC and paired SLN were evaluated by PNA clamp PCR for K-ras mutations. Thirty primary tumors (42%) were positive for K-ras mutations, and in 5 of these cases the SLN were positive for metastases by Hematoxylin and Eosin staining. PNA clamp PCR identified occult metastases in an additional 6 patients, upstaging 24% of K-ras positive primary CRCs (p = 0.014). No K-ras mutations were detected among the 20 noncancer lymph nodes assessed. This study demonstrates the utility, specificity and sensitivity of PNA clamp PCR assay in identifying occult micrometastases in the SLN of CRC patients by single-base mutation analysis.

Although the expression of thymidylate synthase (TS) in metastatic colorectal cancer (CRC) may be a better predictor of response to 5-fluorouracil chemotherapy than TS expression in primary CRC, this enzyme has not been well studied in tumor-draining regional lymph nodes. We retrospectively examined TS expression in 12 primary CRC lesions (pT3) and matched sentinel lymph nodes. Of the 8 primary tumors that were TS-positive, 50 per cent (4/8) had tumor-positive lymph nodes and 50 per cent (4/8) had tumor-negative nodes. Of the 4 primary tumors that were TS-negative, 75 per cent (3/4) had tumor-positive nodes and 25 per cent (1/4) had tumor-negative nodes [κ = -0.1386, 95 per cent confidence interval: (-0.4820, 0.2048), P = 0.4284]. Of the 8 TS-positive primaries, 25 per cent (2/8) had TS-positive nodes and 75 per cent (6/8) had TS-negative nodes. Of the 4 TS-negative primaries, 50 per cent (2/4) had TS-positive nodes and 50 per cent (2/4) had TS-negative nodes [κ = -0.0131, 95 per cent confidence interval: (-0.2958, 0.2696), P = 0.9274]. Two of the three TS-negative primaries that had metastasized to regional lymph nodes were associated with TS-positive lymph nodes. Our findings indicate that expression of TS by a primary CRC does not correlate with nodal metastases or nodal TS expression. Nodal expression of TS may be important in predicting response to 5-fluorouracil when a primary CRC is TS-negative.