Paired primary-metastasis patient-derived organoids and mouse models identify phenotypic evolution and druggable dependencies of peritoneal metastasis from appendiceal cancer.

Peritoneal carcinomatosis is a common yet deadly manifestation of gastrointestinal cancers, with few effective treatments. To identify targetable determinants of peritoneal metastasis, we focused on appendiceal adenocarcinoma (AC), a gastrointestinal cancer that metastasizes almost exclusively to the peritoneum. Current treatments are extrapolated from colorectal cancer (CRC), yet AC has distinct genomic alterations, mucinous morphology and peritoneum restricted metastatic pattern.

Multimodal histopathologic models stratify hormone receptor-positive early breast cancer.

The Oncotype DX® Recurrence Score (RS) is an assay for hormone receptor-positive early breast cancer with extensively validated predictive and prognostic value. However, its cost and lag time have limited global adoption, and previous attempts to estimate it using clinicopathologic variables have had limited success. To address this, we assembled 6172 cases across three institutions and developed Orpheus, a multimodal deep learning tool to infer the RS from H&E whole-slide images.

The potential radiosensitization target PFKFB3 is related to response to radiotherapy in SweBCG91RT: a randomized clinical trial with long-term follow-up.

Background: Several cancer types have increased PFKFB3, a glycolytic enzyme for which potent inhibitors have been found. Inhibition of PFKFB3 impairs DNA repair after irradiation of cancer cells, making it a possible radiosensitization target. The SweBCG91RT trial, in which breast cancer patients were randomized to postoperative radiotherapy or not, was used to investigate PFKFB3 as a clinical marker of sensitivity to adjuvant radiotherapy.

Clinico-genomic features predict distinct metastatic phenotypes in cutaneous melanoma.

Metastasis drives mortality and morbidity in cancer. While some patients develop broad metastatic disease across multiple organs, others exhibit organ-specific spread. To identify mechanisms underlying metastatic organotropism, we analyzed clinico-genomic data from over 7,000 patients with metastatic cutaneous melanoma in three independent cohorts (one primary discovery and two validation cohorts including a nationwide electronic health record-derived deidentified database), leveraging machine learning approaches to clinical data.

Intracranial Disease Control and Survival among Patients with KRAS-mutant Lung Adenocarcinoma and Brain Metastases Treated with Stereotactic Radiosurgery.

Purpose: Precision medicine according to molecularly defined subgroups offers great potential to improve outcomes for patients with metastatic lung adenocarcinoma. This study describes clinical outcomes and the impact of co-occurring genetic alterations on outcomes following stereotactic radiosurgery (SRS) among patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma.

Methods And Materials: A total of 195 patients with KRAS-mutant lung adenocarcinoma were treated with SRS for brain metastases (BMs) between 2014 and 2018 with follow-up until 2022 or death.

Adenovirus Infections and Disease in Solid Organ Transplant Recipients: Incidence and Outcomes.

Background: We aimed to examine the epidemiology and outcomes of AdV disease in SOTr and assess the utility of AdV surveillance in SOTr <13 years.

Methods: SOTr transplanted at Rigshospitalet, 2010-2021, were included. The center had a screening program for SOTr <13 years with monthly plasma AdV tests the first 6 months following transplantation.

Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology.

Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different fields and has found substantial variability among results despite analysts having the same data and research question.

Apixaban removal during emergency surgery for type A acute aortic dissection: a prospective cohort study.

Background: Acute type A aortic dissection (ATAAD) has a high mortality, and acute aortic repair is the only curative treatment. In patients treated with factor Xa (FXa) inhibitors, the risk of severe disease-related complications such as cardiac tamponade and hemodynamic shock must be balanced against the potential for severe perioperative bleeding. The aim was to study intraoperative changes in plasma levels of the FXa inhibitor apixaban when using hemoadsorption during acute thoracic aortic repair.

Genetic Ancestry-Based Differences in Biomarker-Based Eligibility for Precision Oncology Therapies.

Importance: Although differences in the prevalence of key cancer-specific somatic mutations as a function of genetic ancestry among patients with cancer has been well-established, few studies have addressed the practical clinical implications of these differences for the growing number of biomarker-driven treatments.

Objective: To determine if the approval of precision oncology therapies has benefited patients with cancer from various ancestral backgrounds equally over time.

Design, Setting, And Participants: A retrospective analysis of samples from patients with solid cancers who underwent clinical sequencing using the integrated mutation profiling of actionable cancer targets (MSK-IMPACT) assay between January 2014 and December 2022 was carried out.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Preoperative factors predicting outcomes in patients with suspected perihilar cholangiocarcinoma referred for curative resection- a single-center 10-year experience.

Purpose: Perihilar cholangiocarcinoma (pCCA) is a rare malignancy requiring resection of extrahepatic bile ducts with or without hepatectomy. Prognostic models for post-operative outcomes in pCCA are unusable in pre-operative decision-making as most are based on post-operative variables. Additionally, no pre-operative models include futile laparotomy or benign hilar stenosis (BHS) as possible outcomes.

Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.

High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC.

Pan-cancer analysis of biallelic inactivation in tumor suppressor genes identifies KEAP1 zygosity as a predictive biomarker in lung cancer.

The canonical model of tumor suppressor gene (TSG)-mediated oncogenesis posits that loss of both alleles is necessary for inactivation. Here, through allele-specific analysis of sequencing data from 48,179 cancer patients, we define the prevalence, selective pressure for, and functional consequences of biallelic inactivation across TSGs. TSGs largely assort into distinct classes associated with either pan-cancer (Class 1) or lineage-specific (Class 2) patterns of selection for biallelic loss, although some TSGs are predominantly monoallelically inactivated (Class 3/4).

Characterization of Mycelium Biocomposites under Simulated Weathering Conditions.

Expanded polystyrene (EPS) remains a popular packaging material despite environmental concerns such as pollution, difficulty to recycle, and toxicity to wildlife. The goal of this study is to evaluate the potential of an ecofriendly alternative to traditional EPS composed of a mycelium biocomposite grown from agricultural waste. In this material, the mycelium spores are incorporated into cellulosic waste, resulting in a structurally sound biocomposite completely enveloped by mycelium fibers.

Analysis of Shared Variants between Cancer Biospecimens.

Purpose: Mutational data from multiple solid and liquid biospecimens of a single patient are often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence.

Experimental Design: Utilizing 8,000 patient tumors from The Cancer Genome Atlas across 33 cancer types, we estimated the background rates of co-occurrence of mutations between discrete pairs of samples across cancers and by cancer type.

Automated classification of online reviews of otolaryngologists.

Objectives: The study aimed to extract online comments of otolaryngologists in the 20 most populated cities in the United States from healthgrades.com, develop and validate a natural language processing (NLP) logistic regression algorithm for automated text classification of reviews into 10 categories, and compare 1- and 5-star reviews in directly-physician-related and non-physician-related categories.

Methods: 1977 1-star and 12,682 5-star reviews were collected.

Management of Post-transplant Infections in Collaborating Hospitals (MATCH) Programme: a prospective cohort of all transplant recipients at Copenhagen University Hospital-Rigshospitalet, Denmark.

Purpose: The Management of Post-transplant Infections in Collaborating Hospitals (MATCH) programme, initiated in 2011 and still ongoing, was created to 1) optimise the implementation of existing preventive strategies against viral infections in solid organ transplant (SOT) recipients and allogenic haematopoietic stem-cell transplant (HSCT) recipients and 2) advance research in the field of transplantation by collecting data from a multitude of sources.

Participants: All SOT and HSCT recipients at Copenhagen University Hospital, Rigshospitalet, are followed in MATCH. By February 2021, a total of 1192 HSCT recipients and 2039 SOT recipients have been included.

Shareable artificial intelligence to extract cancer outcomes from electronic health records for precision oncology research.

Databases that link molecular data to clinical outcomes can inform precision cancer research into novel prognostic and predictive biomarkers. However, outside of clinical trials, cancer outcomes are typically recorded only in text form within electronic health records (EHRs). Artificial intelligence (AI) models have been trained to extract outcomes from individual EHRs.

Postoperative Exercise Training in Patients with Colorectal Liver Metastases A Randomized Controlled Trial.

Background: Postoperative morbidity can reduce quality of life, physical performance, and tolerability of postoperative chemotherapy in patients with colorectal liver metastases (CRLM). Exercise can improve these outcomes in some cancer populations. However, it remains unknown whether exercise can be delivered in the early postoperative period following surgery for CRLM without increasing the risk of harms.

Obesity-dependent selection of driver mutations in cancer.

Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma and cancers of unknown primaries, independent of clinical covariates, demographic factors and genetic ancestry.

Short-Term Surgical Outcomes After Robotic Liver Surgery: A Propensity-Score Matched Analysis With Conventional Open Liver Surgery at a High-Volume Centre in Denmark.

Background: The aim of this study was to investigate the perioperative outcomes of robotic liver surgery (RLS) and Open liver surgery (OLS) in a centre with a high number of operations.

Methods: A 1:1 propensity score matched (PSM) analysis of a retrospective database of RLS and OLS was performed. Cumulative sum (CUSUM) analysis was performed to identify learning curves.