Publications by authors named "Iris D Nagtegaal"

Background And Aims: Implementation of population screening programs resulted in an increase in early colorectal cancer (CRC, pT1). For these small CRC, endoscopic local resection is the preferred treatment. However, the presence of lymph node metastasis (LNM) and risk of local recurrence might require additional surgery.

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The immune microenvironment of colorectal cancer is a major component of the disease and influences not only tumor progression and patient outcome but also therapy response. Expanding on existing studies which have explored the prognostic value of the adaptive immune response with lymphocytes, our study integrates innate immune cells, specifically eosinophils, in a combined analysis. To evaluate the prognostic significance of eosinophils within the context of lymphocyte infiltration, we analyzed a large collective of 1625 colorectal cancer cases from four different centers.

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Lymph nodes (LNs) containing only acellular mucin are considered negative for metastasis in treated colorectal cancers (CRCs). However, no data exist on how to stage these LNs in untreated CRCs. We collected 63 untreated CRC cases with LNs containing only acellular mucin from 27 US institutions and 23 additional cases from the Dutch Nationwide Pathology Databank.

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Background: Exercise during neoadjuvant chemoradiotherapy (NCRT) has potential to mitigate treatment-related declines in physical fitness, and to improve clinical outcomes, including toxicity and tumor response. However, optimal frequency and timing of exercise remains to be determined. Therefore, this pilot trial aimed to assess feasibility of 2 different exercise interventions during NCRT in patients with esophageal and rectal cancer and to evaluate potential clinical effects.

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For the classification of colorectal polyps, we implemented an approach in which students are encouraged to use their imagination. First, students received surveys with histological pictures via an online tool, had to create associations for the observed tissue structures, and use these in an identification key. Subsequently, an interactive lecture linked their descriptions to correct terminology, followed by an exam.

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Background: Selection of suitable candidates for intraoperative tumour detection and cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is important for improving outcomes for patients with colorectal peritoneal metastases. Previous research demonstrated the use of single-photon emission computed tomography (SPECT), intraoperative radiodetection, and near-infrared fluorescence (NIRF)-guided surgery with a dual-labelled 111In-labelled dodecane tetra-acetic acid (DOTA)-labetuzumab-IRDye800CW tracer to detect peritoneal metastases before operation. The aim of this study was to validate these results.

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Aims: Tumour-stroma ratio (TSR) scores of biopsy material in rectal carcinoma (RC) could aid a biomarker-based, upfront and personalised treatment strategy selection for RC patients. In a large retrospective, multicentre cohort, we aimed to validate the predictive value of biopsy-scored TSR on neoadjuvant therapy response, and secondarily, disease-free and overall survival (DFS, OS).

Methods And Results: Scanned haematoxylin and eosin-stained RC biopsy slides were collected from Leiden University Medical Center (N = 116) and from the clinical PROCTOR-SCRIPT (N = 142) and RAPIDO (N = 271) trials.

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Tumour deposits (TD) are a crucial biomarker in colorectal cancer, closely associated with nearby structures such as blood vessels, lymphatic vessels, and peripheral nerves. These anatomical structures serve as pathways that facilitate the spread of tumour cells throughout the body. This study aims to investigate how TD access these anatomical gateways and how these variations impact patient survival.

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This study investigates the impact of extended invitation intervals on the stage distribution of screen-detected and interval colorectal cancers (CRCs) in the Netherlands' fecal immunochemical test (FIT)-based screening program during the COVID-19 pandemic. Using data from individuals with negative FIT results in 2017-2019 and subsequent screening round in 2019-2021, we examined whether delays of up to 6 months affected CRC stage at diagnosis. We performed multivariate logistic regression to assess the association between invitation intervals and cancer stage.

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Objective: The diagnosis of inflammatory bowel disease (IBD) associated with high-grade dysplasia (HGD) has a significant impact on clinical management, including colectomy. However, the prognosis of HGD remains unclear due to diagnostic uncertainty and low-quality data on subsequent synchronous and metachronous neoplasia. We aimed to evaluate a diagnostic strategy with dedicated gastrointestinal (GI) pathologist consensus of revised HGD and the impact on synchronous and metachronous neoplasia rates.

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Aims: We compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta-analysis of cohorts and individual case series.

Methods And Results: We identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome.

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Approximately 10% of affected individuals have an inherited component. Deleterious germline variants increase the lifetime risk for PDAC and are often associated with an elevated risk for extra-pancreatic malignancies.

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Upper age limits are currently fixed for all fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening programs. A risk-stratified upper age limit may be beneficial. Therefore, we assessed differences in interval CRC risk among individuals who had reached the upper age limit of screening (75 years).

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Background: There is no clinically relevant serological marker for the early detection of oesophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's oesophagus (BE).

Objective: To develop and test a blood-based assay for EAC and BE.

Design: Oesophageal MicroRNAs of BaRRett, Adenocarcinoma and Dysplasia () was a large, international, multicentre biomarker cohort study involving 792 patient samples from 4 countries (NCT06381583) to develop and validate a circulating miRNA signature for the early detection of EAC and high-risk BE.

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Article Synopsis
  • This study explores the significance of tumor budding (TB) in colorectal cancer, particularly focusing on intratumoral budding (ITB) in resection specimens and its feasibility in biopsy samples.* -
  • The research found that high-grade TB, whether intratumoral or peritumoral, is linked with worse outcomes such as advanced cancer stages and lower overall survival rates.* -
  • Results indicated that ITB is a strong predictor of overall survival and can help in improving risk assessment and predicting responses to neoadjuvant therapy in cancer patients, highlighting the need for TB evaluation in biopsies.*
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Background: Most tyrosine kinase inhibitors (TKIs) have failed in clinical trials for metastatic colorectal cancer (mCRC). To leverage the additional lower-affinity targets that most TKIs have, high-dose regimens that trigger efficacy are explored. Here, we studied unprecedented drug exposure-response relationships in vitro using mCRC patient-derived tumour organoids (PDTOs).

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Background: As a result of recent advances in the development of small microelectromechanical system mirrors, a novel forward-looking optical coherence tomography (OCT) probe with a uniquely large field of view is being commercially developed. The aim of this study is to prospectively assess the feasibility of this advanced OCT probe in interpreting ex vivo images of colorectal polyp tissue and to identify necessary steps for further development.

Methods: A total of 13 colorectal lesions from 9 patients, removed during endoscopic resection, were imaged ex vivo with the OCT device and compared with histopathological images that served as the gold standard for diagnostics.

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Background: Histopathological growth patterns are one of the strongest prognostic factors in patients with resected colorectal liver metastases. Development of an efficient, objective and ideally automated histopathological growth pattern scoring method can substantially help the implementation of histopathological growth pattern assessment in daily practice and research. This study aimed to develop and validate a deep-learning algorithm, namely neural image compression, to distinguish desmoplastic from non-desmoplastic histopathological growth patterns of colorectal liver metastases based on digital haematoxylin and eosin-stained slides.

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Background And Aims: This study aimed to provide evidence on the harm-to-benefit ratio of fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening by previous fecal hemoglobin (f-Hb) concentrations, as reflected in the number needed to screen (NNS) and number needed to scope (NNSc).

Methods: Participants in up to 4 FIT screening rounds of the Dutch CRC screening program were included. The main outcomes of this study were the NNS and NNSc to detect 1 CRC and/or advanced neoplasia (AN) in screening rounds 2, 3, or 4, conditional on previous f-Hb concentrations.

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Tumor deposits (TD) are tumor nodules in the lymphatic drainage area of colorectal cancer patients, and they are currently classified in the N category in the TNM classification. However, due to the associated poor prognosis, some small cohort studies suggest that TD belong in the M category. A retrospective study using The Surveillance, Epidemiology, and End Results program (SEER) data was performed in Stages III and IV colon carcinoma (CC) patients to evaluate the prognostic impact of TD.

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Article Synopsis
  • Lymph node metastases are important for understanding colorectal cancer, and the study looks at how two features, extranodal extension and tumor deposits, affect patient outcomes.
  • The research included 20 studies with over 7,700 cases to compare how these two features relate to survival after treatment.
  • Results suggest that having tumor deposits usually leads to worse survival rates compared to having extranodal extension, but further studies are needed to confirm these findings.
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Background: The clinical value of different modes of CRM involvement in rectal cancer patients is unclear. This study aims to determine the clinical impact of different modes of circumferential resection margin (CRM) involvement in patients with a locally advanced rectal carcinoma.

Patients And Methods: A cohort of patients who were diagnosed with stage III rectal cancer between June 2014 and June 2020 was selected from the prospective Dutch nationwide pathology databank (PALGA).

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