A Comparison of Cellular Immune Response and Immunological Biomarkers in Laparoscopic Surgery for Colorectal Cancer and Benign Disorders.

Background: Surgical trauma causes immune impairment, but it is largely unknown whether surgery for cancer and benign diseases instigate comparable levels of immune inhibition. Here, we compared the impact of laparoscopic surgery on immunological biomarkers in patients with colorectal cancer (CRC) and ventral hernia (VH).

Methods: Natural Killer cell activity (NKA), leukocyte subsets, and soluble programmed death ligand 1 (sPD-L1) were measured in blood samples collected from CRC (n = 29) and VH (n = 9) patients preoperatively (PREOP) and on postoperative day (POD) 1, 3-6, 2 weeks and 3 months.

The Transcriptional Landscape of Coding and Noncoding RNAs in Recurrent and Nonrecurrent Colon Cancer.

A number of patients with colon cancer with local or local advanced disease suffer from recurrence and there is an urgent need for better prognostic biomarkers in this setting. Here, the transcriptomic landscape of mRNAs, long noncoding RNAs, snRNAs, small nucleolar RNAs (snoRNAs), small Cajal body-specific RNAs, pseudogenes, and circular RNAs, as well as RNAs denoted as miscellaneous RNAs, was profiled by total RNA sequencing. In addition to well-known coding and noncoding RNAs, differential expression analysis also uncovered transcripts that have not been implicated previously in colon cancer, such as RNA5SP149, RNU4-2, and SNORD3A.

Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study.

Introduction: Management of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical management instead of surveillance strategy, there are between 54% and 82% of bowel resections without evidence of residual tumour or lymphatic spread. As surgical management entails risks of complications and surveillance strategy entails risks of residual tumour or recurrence, a clinical dilemma arises when choosing a management strategy.

Delta tocotrienol as a supplement to FOLFOXIRI in first-line treatment of metastatic colorectal cancer. A randomized, double-blind, placebo-controlled phase II study.

Purpose: Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether -tocotrienol, a vitamin E analogue, with possible neuroprotective and anti-inflammatory effects, reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo-controlled trial in mCRC patients receiving first-line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI).

Material And Methods: Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either -tocotrienol or placebo at the Department of Oncology, Vejle Hospital, Denmark.

Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in-vitro sensitivity testing: a phase 2, single-center, open-label, and non-comparative study.

Background: Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method's feasibility and clinical outcome as applied to patients with no satisfactory treatment options.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

Background & Aims: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs.

Endorectal Ultrasound Shear-Wave Elastography of Complex Rectal Adenoma and Early Rectal Cancer.

Purpose: To investigate the diagnostic performance of endorectal ultrasound (ERUS), shear-wave elastography (SWE), and magnetic resonance imaging (MRI) in patients with a complex rectal adenoma or an early rectal cancer, i.e., T1 or T2 adenocarcinoma in a clinical setting, and to evaluate the association between SWE and stromal fraction (SF) and apparent diffusion coefficient (ADC) and SF.

CT and 3 Tesla MRI in the TN Staging of Colon Cancer: A Prospective, Blind Study.

(1) Background: Computer tomography (CT) scanning is currently the standard method for staging of colon cancer; however, the CT based preoperative local staging is far from optimal. The purpose of this study was to investigate the sensitivity and specificity of magnetic resonance imaging (MRI) compared to CT in the T- and N-staging of colon cancer. (2) Methods: Patients underwent a standard contrast-enhanced CT examination.

The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer.

Introduction: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants.

Methods: We screened 98 patients aged 18-40 with CRC diagnosed in 2010-2013 for variants in , , , , , , , , , , , , , , , , and using Next Generation Sequencing.

The Impact of Patient Characteristics and Tumor Biology on the Accuracy of Preoperative Staging of Colon Cancer in Denmark. A Nationwide Cohort Study.

Background: Colon cancer is a common disease in western populations. The aim of this study was to assess the impact of mismatch repair (MMR) deficiency and other patient and tumor characteristics on the accuracy of preoperative staging by comparing histopathological T- and N-categories of the resected specimen with the preoperative clinical stage in a nationwide cohort of patients treated for colon cancer by elective bowel resection with curative intent.

Methods: A register study of a cohort extracted from the Danish Colorectal Cancer Group (DCCG) database, which holds prospective data on all new cases of colon and rectum cancer in Denmark.

Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations.

Biliary tract cancers (BTC) are rare and often diagnosed in late stages with advanced, nonresectable disease. The targeted agents panitumumab and bevacizumab have shown promising outcomes in combination with chemotherapy in other gastrointestinal (GI) cancers. We wanted to investigate if panitumumab or bevacizumab was the most promising drug to add to chemotherapy.

Intracorporeal anastomosis in right hemicolectomy for colon cancer: short-term outcomes with the DaVinci Xi robot.

Intracorporeal anastomosis (IA) may improve outcomes compared with extracorporeal anastomosis (EA) in minimally invasive right colectomy. This is a prospective series of robotic right hemicolectomies (RRC) with IA from one institution. 35 consecutive patients with verified or suspected right colon cancer undergoing RRC with IA, and historic control groups of 22 RRC and 40 laparoscopic right colectomies (LRC), both with EA.

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer.

The treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs.

Early identification of treatment benefit by methylated circulating tumor DNA in metastatic colorectal cancer.

Background: The early identification of treatment effect is wanted in several settings, including the management of metastatic colorectal cancer (mCRC). A potential universal marker is circulating tumor DNA (ctDNA). Our prospective study explored the association between progression-free survival (PFS) and overall survival (OS), and early change of ctDNA after one cycle of chemotherapy in patients with mCRC.

A streamlined mass spectrometry-based proteomics workflow for large-scale FFPE tissue analysis.

Formalin fixation and paraffin-embedding (FFPE) is the most common method to preserve human tissue for clinical diagnosis, and FFPE archives represent an invaluable resource for biomedical research. Proteins in FFPE material are stable over decades but their efficient extraction and streamlined analysis by mass spectrometry (MS)-based proteomics has so far proven challenging. Herein we describe a MS-based proteomic workflow for quantitative profiling of large FFPE tissue cohorts directly from histopathology glass slides.

Long-term risk of colorectal cancer after screen-detected adenoma: Experiences from a Danish gFOBT-positive screening cohort.

Fecal occult blood test (FOBT) screening for colorectal cancer (CRC) is implemented in several countries. Approximately half of all FOBT-positive persons have screen-detected adenomas. Despite removal of these, patients with large/multiple adenomas have increased risk of later developing new advanced adenomas and CRC.

Phase II study of gemcitabine, oxaliplatin and capecitabine in patients with KRAS exon 2 mutated biliary tract cancers.

Molecular markers may identify subgroups of patients with clinically distinct behavior and response to treatment. In some gastrointestinal tumors, KRAS has prognostic value and negative predictive value. This is the first prospective study to report the outcome of combination chemotherapy in biliary tract cancer patients with KRAS mutation.

Correlation Between Tumor-Specific Mutated and Methylated DNA in Colorectal Cancer.

Purpose: Analysis of circulating tumor DNA (ctDNA) is a potential improvement in precision medicine. In colorectal cancer (CRC), somatic mutations such as and in the blood (mut-ctDNA) are investigated for prognostic and predictive purposes. However, they are only present in approximately 60% of patients.

Gene Methylation as a Universal, Longitudinal Plasma Marker for Evaluating the Clinical Benefit from Last-Line Treatment with Regorafenib in Metastatic Colorectal Cancer.

There is a need for biomarkers to improve the clinical benefit from systemic treatment of colorectal cancer. We designed a prospective, clinical study where patients receiving regorafenib as last-line treatment had sequential blood samples drawn. Effect and toxicity was monitored.

Long-Term Patient-Reported Outcomes After High-Dose Chemoradiation Therapy for Nonsurgical Management of Distal Rectal Cancer.

Purpose: Surgery is standard treatment for rectal cancer, but neoadjuvant chemoradiation therapy (CRT) may result in clinical complete response (cCR) in select patients, allowing for nonsurgical management (NSM). Prospective studies of NSM strategies are sparse, however, and long-term data on quality of life (QoL) are limited. We conducted a single-arm phase 2 trial of high-dose CRT for NSM of distal rectal cancer; we report secondary long-term patient-reported outcomes (PROs), local regrowth, and overall survival in patients managed nonsurgically.

Prognostic Value of Serum NPY Hypermethylation in Neoadjuvant Chemoradiotherapy for Rectal Cancer: Secondary Analysis of a Randomized Trial.

Objectives: Long-term prevention of metastatic disease remains a challenge in locally advanced rectal cancer, and robust pretreatment prognostic factors for metastatic progression are lacking. We hypothesized that detecting circulating tumor-specific DNA (ctDNA) based on hypermethylation of the neuropeptide Y gene (meth-ctDNA) could be a prognostic marker in the neoadjuvant setting; we examined this in a secondary, explorative analysis of a prospective trial.

Materials And Methods: Serum samples were prospectively collected in a phase III trial for locally advanced rectal cancer.