Thyroid cancer progression from curable well-differentiated thyroid carcinoma to highly lethal anaplastic thyroid carcinoma is distinguished by tumor cell de-differentiation and recruitment of a robust stromal infiltrate. Combining an integrated thyroid cancer single-cell sequencing atlas with spatial transcriptomics and bulk RNA-sequencing, we define stromal cell subpopulations and tumor-stromal cross-talk occurring across the histologic and mutational spectrum of thyroid cancer. We identify distinct inflammatory and myofibroblastic cancer-associated fibroblast (iCAF and myCAF) populations and perivascular-like populations.
View Article and Find Full Text PDFImportance: Patients of physicians with higher adenoma detection rates (ADRs) during colonoscopy have lower colorectal cancer (CRC) risk after screening colonoscopy (ie, postcolonoscopy CRC). Among physicians with an ADR above the recommended threshold, it is unknown whether improving ADR is associated with a lower incidence of CRC in their patients.
Objective: To determine the association of improved ADR in physicians with a range of ADR values at baseline with CRC incidence among their patients.
Tenascin-C (TNC) is a secreted extracellular matrix protein that is highly expressed during embryonic development and re-expressed during wound healing, inflammation, and neoplasia. Studies in developmental models suggest that TNC may regulate the Wnt signaling pathway. Our lab has shown high levels of Wnt signaling and TNC expression in anaplastic thyroid cancer (ATC), a highly lethal cancer with an abysmal ~3-5 month median survival.
View Article and Find Full Text PDFBackground: Colorectal cancer is one of the most common forms of cancer in Norway, and typically develops from colorectal polyps. For benign colorectal polyps, endoscopic removal is recommended to avoid unnecessary surgery. This study identifies the extent of surgical treatment of benign polyps in the period 1 January 2008-31 December 2021.
View Article and Find Full Text PDFTo optimize colorectal cancer (CRC) surveillance, accurate information on the risk of developing CRC from premalignant lesions is essential. However, directly observing this risk is challenging since precursor lesions, i.e.
View Article and Find Full Text PDFImportance: Randomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking.
Objective: To estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy.
Unlabelled: Current morphologic features defining advanced adenomas (size ≥10 mm, high-grade dysplasia or ≥25% villous component) cannot optimally distinguish individuals at high risk or low risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy-number alterations (CNAs) are associated with adenoma-to-carcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features.
View Article and Find Full Text PDFGenomic and transcriptomic analysis has furthered our understanding of many tumors. Yet, thyroid cancer management is largely guided by staging and histology, with few molecular prognostic and treatment biomarkers. Here, we utilize a large cohort of 251 patients with 312 samples from two tertiary medical centers and perform DNA/RNA sequencing, spatial transcriptomics, and multiplex immunofluorescence to identify biomarkers of aggressive thyroid malignancy.
View Article and Find Full Text PDFThe relative abundance of Wnt receptors plays a crucial role in controlling Wnt signaling in tissue homeostasis and human disease. While the ubiquitin ligases that ubiquitylate Wnt receptors are well-characterized, the deubiquitylase that reverses these reactions remains unclear. Herein, we identify USP46, UAF1, and WDR20 (USP46 complex) as positive regulators of Wnt signaling in cultured human cells.
View Article and Find Full Text PDFBackground & Aims: Because post-polypectomy surveillance uses a growing proportion of colonoscopy capacity, more targeted surveillance is warranted. We therefore compared surveillance burden and cancer detection using 3 different adenoma classification systems.
Methods: In a case-cohort study among individuals who had adenomas removed between 1993 and 2007, we included 675 individuals with colorectal cancer (cases) diagnosed a median of 5.
Background And Aim: Bariatric surgery is the most effective treatment for obesity but is invasive and associated with serious complications. Endoscopic sleeve gastroplasty (ESG) is a less invasive weight loss procedure to reduce the stomach volume by full-thickness sutures. ESG has been adopted in many countries, but implementation at Scandinavian centres has not yet been documented.
View Article and Find Full Text PDFIn this correspondence we respond to critique of our randomized trial of Covid-19 transmission in fitness centers. The trial was performed in Norway during May and June 2020.
View Article and Find Full Text PDFObjectives: Meticulous inspection of the mucosa during colonoscopy, represents a lengthier withdrawal time, but has been shown to increase adenoma detection rate (ADR). We investigated if artificial intelligence-aided speed monitoring can improve suboptimal withdrawal time.
Methods: We evaluated the implementation of a computer-aided speed monitoring device during colonoscopy at a large academic endoscopy center.
Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019.
View Article and Find Full Text PDFObjective: High-quality colonoscopy (adequate bowel preparation, whole-colon visualisation and removal of all neoplastic polyps) is a prerequisite to start polyp surveillance, and is ideally achieved in one colonoscopy. In a large multinational polyp surveillance trial, we aimed to investigate clinical practice variation in number of colonoscopies needed to enrol patients with low-risk and high-risk adenomas in polyp surveillance.
Design: We retrieved data of all patients with low-risk adenomas (one or two tubular adenomas <10 mm with low-grade dysplasia) and high-risk adenomas (3-10 adenomas, ≥1 adenoma ≥10 mm, high-grade dysplasia or villous components) in the European Polyp Surveillance trials fulfilling certain logistic and methodologic criteria.
Background: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain.
Objective: To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality.
Design: Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening.