NMFClustering: Accessible NMF-based clustering utilizing GPU acceleration.

Non-negative Matrix Factorization (NME) is an algorithm that can reduce high dimensional datasets of tens of thousands of genes to a handful of metagenes which are biologically easier to interpret. Application of NMF on gene expression data has been limited by its computationally intensive nature, which hinders its use on large datasets such as single-cell RNA sequencing (scRNA-seq) count matrices. We have implemented NMF based clustering to run on high performance GPU compute nodes using Cupy, a GPU backed python library, and the Message Passing Interface (MPI). This reduces the computation time by up to three orders of magnitude and makes the NMF Clustering analysis of large RNA-Seq and scRNA-seq datasets practical. We have made the method freely available through the GenePatten gateway, which provides free public access to hundreds of tools for the analysis and visualization of multiple 'omic data types. Its web-based interface gives easy access to these tools and allows the creation of multi-step analysis pipelnes on high performance computing (HPC) culsters that enable reproducible in silco research for non-programmers.

NMF Clustering: Accessible NMF-based Clustering Utilizing GPU Acceleration.

Non-negative Matrix Factorization (NMF) is an algorithm that can reduce high dimensional datasets of tens of thousands of genes to a handful of metagenes which are biologically easier to interpret. Application of NMF on gene expression data has been limited by its computationally intensive nature, which hinders its use on large datasets such as single-cell RNA sequencing (scRNA-seq) count matrices. We have implemented NMF based clustering to run on high performance GPU compute nodes using CuPy, a GPU backed python library, and the Message Passing Interface (MPI). This reduces the computation time by up to three orders of magnitude and makes the NMF Clustering analysis of large RNA-Seq and scRNA-seq datasets practical. We have made the method freely available through the GenePattern gateway, which provides free public access to hundreds of tools for the analysis and visualization of multiple 'omic data types. Its web-based interface gives easy access to these tools and allows the creation of multi-step analysis pipelines on high performance computing (HPC) clusters that enable reproducible in silico research for non-programmers.

Co-Localization of Gastrointestinal Stromal Tumors (GIST) and Peritoneal Mesothelioma: A Case Series.

PURPOSE: Gastrointestinal stromal tumor (GIST) is associated with increased risk of additional cancers. In this study, synchronous GIST, and peritoneal mesothelioma (PM) were characterized to evaluate the relationship between these two cancers. METHODS: A retrospective chart review was conducted for patients diagnosed with both GIST and PM between July 2010 and June 2021. Patient demographics, past tumor history, intraoperative reports, cross-sectional imaging, peritoneal cancer index (PCI) scoring, somatic next-generation sequencing (NGS) analysis, and histology were reviewed. RESULTS: Of 137 patients who underwent primary GIST resection from July 2010 to June 2021, 8 (5.8%) were found to have synchronous PM, and 4 patients (50%) had additional cancers and/or benign tumors. Five (62.5%) were male, and the median age at GIST diagnosis was 57 years (range: 45-76). Seventy-five percent of GISTs originated from the stomach. Of the eight patients, one patient had synchronous malignant mesothelioma (MM), and the remaining had well-differentiated papillary mesothelioma (WDPM), which were primarily located in the region of the primary GIST (89%). The median PCI score was 2 in the WDPM patients. NGS of GIST revealed oncogenic KIT exon 11 (62.5%), PDGFRA D842V (25%), or SDH (12.5%) mutations, while NGS of the MM revealed BAP1 and PBRM1 alterations. CONCLUSIONS: One in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.

A Novel System to Improve Case Capture for Surgery Morbidity and Mortality Conference.

INTRODUCTION: Complications are often under-reported at surgical morbidity and mortality (M&M) conferences due to the sole reliance on voluntary case submission. While most institutions have databases used for targeted initiatives in quality improvement, these are not routinely used for M&M. We aimed to increase case capture for M&M conferences by developing a novel system that augments the existing case submission system with cases representing complications from quality improvement databases and the electronic health record (EHR). METHODS: We developed and implemented a novel system for increasing the capture rate of complications for M&M conferences by developing custom software that combines data from the following sources: an existing voluntary case submission system for M&M, local quality databases-National Surgical Quality Improvement Program and Vizient, and an EHR-based case capture tool. We evaluated this system on a retrospective cohort of all postoperative complications at a single center in a 32-mo period and in a prospective cohort over a 4-mo period after system implementation. RESULTS: In the retrospective cohort, we identified 433 complications among all data sources. Inclusion of the new system introduced 280 new potential cases for M&M review over the 32-mo period. After implementation, the system provided 31% of cases presented at M&M conference that would have otherwise been omitted. CONCLUSIONS: A novel system that includes complications identified in the EHR and quality improvement databases increased the case capture volume for surgical M&M conference, which provides an objective case referral system that can identify complementary quality improvement opportunities.

Gastrointestinal Stromal Tumor: New Insights for a Multimodal Approach.

Over the past 20 years, gastrointestinal stromal tumor (GIST) has evolved into an increasingly complex clinical entity with ever more challenges. While surgical resection is the gold standard, advancements in genetic testing, therapeutic options, immunotherapy, and management of metastatic disease necessitate a comprehensive, multimodal approach for these tumors. This chapter highlights the importance of genomic testing of GIST, the use of neoadjuvant and adjuvant therapy for localized disease, surgical principles for GIST, as well as current and new approaches for addressing metastatic disease.

Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity.

PURPOSE: Gastrointestinal stromal tumors (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA, and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations. EXPERIMENTAL DESIGN: We compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST. Additionally, we compiled an international cohort (TransAtlantic GIST Collaborative, TAGC) of 236 patients and reviewed sequencing results, cross-sectional imaging, and operative reports. Subgroup analyses were performed for tumors located proximally versus distally. Risk factors for KIT versus non-KIT tumors were identified using multivariate regression analysis. A random forest machine learning model was then developed to determine feature importance. RESULTS: Within the NCDB cohort, non-KIT mutants dominated distal tumor locations (P < 0.03). Proximal GIST were almost exclusively KIT mutant (96%) in the TAGC cohort, whereas 100% of PDGFRA and SDH-mutant GIST occurred in the distal stomach. On multivariate regression analysis, tumor location was associated with KIT versus non-KIT mutations. Using random forest machine learning analysis, stomach location was the most important feature for predicting mutation status. CONCLUSIONS: We provide the first evidence that the mutational landscape of gastric GIST is related to tumor location. Proximal gastric GIST are overwhelmingly KIT mutant, irrespective of morphology or age, whereas distal tumors display non-KIT genomic diversity. Anatomic location of gastric GIST may therefore provide immediate guidance for clinical treatment decisions and selective confirmatory genomic testing when resources are limited.

Rising Cost of Thyroid Surgery in Adult Patients.

BACKGROUND: The aim of this study is to describe the economic trends in adults who underwent elective thyroidectomy. METHODS: We performed a population-based study utilizing the Premier Healthcare Database to examine adult patients who underwent elective thyroidectomy between January 2006 and December 2014. Time was divided into three equal time periods (2006-2008, 2009-2011, and 2012-2014). To examine trend in patient charges, we modeled patient charges using generalized linear regressions adjusting for key covariates with standard errors clustered at the hospital level. RESULTS: Our study cohort consisted of 52,012 adult patients who underwent a thyroid operation. During the study period, the most common procedure changed from a thyroid lobectomy to bilateral thyroidectomy. Over the study period, there was an increase in the proportion of completion thyroidectomies from 1.1% to 1.6% (P < 0.001), malignant diagnoses from 21.7% to 26.8% (P < 0.001), procedures performed at teaching hospitals from 27.7% to 32.9% (P < 0.001), and procedures performed on an outpatient basis from 93.85% to 97.55% (P < 0.001). The annual increase in median patient charge adjusted for inflation was $895 or 4.3% resulting in an increase of 38.8% over 9 y. Higher thyroidectomy charges were associated with male patients, malignant surgical pathology, patients undergoing limited or radical neck dissection, experiencing complications, those with managed health care insurance, and a prolonged length of stay. CONCLUSIONS: Despite recent changes in thyroid surgery practices to decrease the economic burden of hospitals, costs continue to rise 4.3% annually. Additional prospective studies are needed to identify factors associated with this increasing cost.

TIRADS Interobserver Variability Among Indeterminate Thyroid Nodules: A Single-Institution Study.

OBJECTIVES: A high proportion of cytologically indeterminate, Afirma Gene Expression Classifier "suspicious" thyroid nodules are benign. The Thyroid Imaging Reporting and Data System (TIRADS), was proposed by the American College of Radiology in 2017 to help classify thyroid nodules based on ultrasound characteristics in a standardized fashion to guide management. We aim to determine the interobserver variability of TIRADS classification among cytologically indeterminate and Afirma suspicious nodules. METHODS: We retrospectively queried cytopathology archives for thyroid fine-needle aspiration specimens obtained between February 2012 and September 2016 with associated (1) indeterminate diagnosis, (2) ultrasound imaging at our institution, (3) Afirma suspicious result, and (4) surgery at our institution. We compared the TIRADS variability of the 3 blinded radiologists using intraclass correlation coefficients. RESULTS: Our cohort consisted of 127 nodules. Intraclass correlation coefficients can be interpreted as follows: less than 0.4, poor; 0.4 to 0.59, fair; 0.6 to 0.74, good; 0.75 to 1.00, excellent. The intraclass correlation coefficients of the raw TIRADS score and category variability was 0.561 (95% confidence interval [CI]: 0.464-0.651) or fair and 0.547 (95% CI, 0.449-0.640) or fair, respectively. When analyzing composition, echogenicity, shape, margin, and echogenic foci, the ICCs were 0.552 (95% CI, 0.454-0.643), fair; 0.533 (95% CI, 0.432-0.627), fair; 0.359 (95% CI, 0.248-0.469), poor; 0.192 (95% CI, 0.084-0.308), poor; and 0.549 (95% CI, 0.451- 0.641), fair, respectively. CONCLUSIONS: Our results show that among the subset of cytologically indeterminate and Afirma suspicious nodules, TIRADS interobserver variability was fair. Shape and margin criteria were the biggest sources of disagreement. Large prospective studies are needed to evaluate the interobserver variability of TIRADS in this subset of thyroid nodules.

Bilateral chylothorax following reoperative central neck dissection for metastatic papillary thyroid cancer.

Locoregional recurrence of papillary thyroid cancer (PTC) can occur in up to 30% of patients within 10 years after initial treatment. Reoperative surgery can be challenging due to scarring, fibrosis and distorted anatomy and may be associated with increased complications compared with initial operations. Chylothorax is an extremely rare and potentially life-threatening complication that can be associated with neck dissections and thyroid surgery. In this report, we describe an unusual case of bilateral chylothorax following a left central neck dissection for recurrent PTC.