Is it time to acknowledge intramucosal colorectal carcinoma?

Aim: The term 'intramucosal carcinoma' in the colorectum is controversial when used as a synonym for high-grade dysplasia. However, setting clear definitions for this diagnosis (i.e.

Abdominal inflammatory myofibroblastic tumour: Clinicopathological and molecular analysis of 20 cases, highlighting potential therapeutic targets.

Aims: Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential, occurring at any age and at multiple sites. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of IMT, typically involving the abdomen. Most IMTs harbour kinase gene fusions, especially involving ALK and ROS1, but 20-30% of IMTs show no detectable translocations.

Treatment interval in curative treatment of colon cancer, does it impact (cancer free) survival? A non-inferiority analysis.

Background: In treatment of colon cancer, strict waiting-time targets are enforced, leaving professionals no room to lengthen treatment intervals when advisable, for instance to optimise a patient's health status by means of prehabilitation. Good quality studies supporting these targets are lacking. With this study we aim to establish whether a prolonged treatment interval is associated with a clinically relevant deterioration in overall and cancer free survival.

Node-negative colon cancer: histological, molecular, and stromal features predicting disease recurrence.

Background: Within the group of node-negative colon cancer patients, presumed to have a good prognosis, a significant percentage of patients develops cancer-recurrence. Current high-risk features prove inadequate to select these particular high-risk patients. In the process of tailor-made care and shared decision-making the need to identify these patients grows.

Prognosis of mucinous colon cancer is determined by histological biomarkers rather than microsatellite instability.

The prognostic value of microsatellite instability (MSI), as well as other histological characteristics such as lymphovascular invasion (LI), perineural invasion (PNI) and extramural vascular invasion (EMVI), is unclear in colorectal mucinous carcinoma (MC). This study aims to determine the relevance of these factors in MC patients and analyses the role of MSI in stage III MC patients treated with adjuvant chemotherapy. A cohort of 650 patients diagnosed with stages I-IV colonic MC from 2000 to 2010 was selected from PALGA, the nationwide Dutch pathology databank.

Significantly higher rates of multiple and proximally located adenomas among patients with diabetes mellitus: A cross-sectional population-based study.

Background: Diabetes mellitus (DM) is associated with a greater risk for colorectal cancer (CRC).

Objective: The objective of this article is to examine the endoscopic phenotype and histopathology of colorectal polyps in patients with vs without DM.

Methods: We conducted a cross-sectional study of patients who underwent colonoscopy at our university hospital and who completed a questionnaire.

Diabetes mellitus type 2 and subsite-specific colorectal cancer risk in men and women: results from the Netherlands Cohort Study on diet and cancer.

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC); however, studies differentiating between subsites of CRC are limited. We investigated how diabetes mellitus (DM) was associated with subsite-specific CRC risk in men and women.

Methods: The Netherlands Cohort Study on diet and cancer is a prospective study among 120 852 men and women aged 55-69 years old at baseline in 1986.

The emerging role of GATA transcription factors in development and disease.

The GATA family of transcription factors consists of six proteins (GATA1-6) which are involved in a variety of physiological and pathological processes. GATA1/2/3 are required for differentiation of mesoderm and ectoderm-derived tissues, including the haematopoietic and central nervous system. GATA4/5/6 are implicated in development and differentiation of endoderm- and mesoderm-derived tissues such as induction of differentiation of embryonic stem cells, cardiovascular embryogenesis and guidance of epithelial cell differentiation in the adult.

The relevance of pathological verification in suspected pancreatic cancer.

Objectives: This population-based study assessed which factors were associated with pathological verification of pancreatic cancer.

Methods: All patients diagnosed with a malignancy of the pancreas between 1993 and 2010 in the South of the Netherlands (N=3321) were included.

Results: Pancreatic cancer was pathologically verified in 59% of patients.

CHFR promoter methylation indicates poor prognosis in stage II microsatellite stable colorectal cancer.

Purpose: Data on the prognostic significance of promoter CpG island methylation in colorectal cancer (CRC) are conflicting, possibly due to associations between methylation and other factors affecting survival such as genetic alterations and use of adjuvant therapy. Here, we examine the prognostic impact of promoter methylation in patients with CRC treated with surgery alone in the context of microsatellite instability (MSI), BRAF and KRAS mutations.

Experimental Methods: One hundred and seventy-three CRCs were analyzed for promoter methylation of 19 tumor suppressor and DNA repair genes, the CpG island methylator phenotype (CIMP), MSI, the exon 15 V600E BRAF mutation and KRAS codon 12 and 13 mutations.

Promoter CpG island methylation of RET predicts poor prognosis in stage II colorectal cancer patients.

Improved prognostic stratification of patients with TNM stage II colorectal cancer (CRC) is desired, since 20-30% of high-risk stage II patients may die within five years of diagnosis. This study was conducted to investigate REarranged during Transfection (RET) gene promoter CpG island methylation as a possible prognostic marker for TNM stage II CRC patients. The utility of RET promoter CpG island methylation in tumors of stage II CRC patients as a prognostic biomarker for CRC related death was studied in three independent series (including 233, 231, and 294 TNM stage II patients, respectively) by using MSP and pyrosequencing.

Emerging evidence for CHFR as a cancer biomarker: from tumor biology to precision medicine.

Novel insights in the biology of cancer have switched the paradigm of a "one-size-fits-all" cancer treatment to an individualized biology-driven treatment approach. In recent years, a diversity of biomarkers and targeted therapies has been discovered. Although these examples accentuate the promise of personalized cancer treatment, for most cancers and cancer subgroups no biomarkers and effective targeted therapy are available.

Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC.

Red meat intake has been linked to increased colorectal cancer (CRC) risk. Although the underlying mechanisms remain unclear, experimental studies suggest a role for dietary heme iron. Because heme iron was shown to promote specific mutations, it would be insightful to link heme iron data to CRC with mutations in key genes in an observational, population-based study.

Chromosome 5q loss in colorectal flat adenomas.

Purpose: Flat adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behavior compared with their polypoid counterparts. Here, we aimed to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, that is, chromosomal instability, between flat and polypoid colorectal adenomas.

Experimental Design: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high-resolution array comparative genomic hybridization platform, microsatellite instability (MSI) status, and for mutations in the adenomatous polyposis coli (APC) gene.

Nonpolypoid colorectal neoplasms: gender differences in prevalence and malignant potential.

Objective: Colonoscopy may fail to prevent colorectal cancer, especially in the proximal colon and in women. Nonpolypoid colorectal neoplasms may potentially explain some of these post-colonoscopy cancers. In the present study, we aimed to examine the prevalence and malignant potential of nonpolypoid colorectal neoplasms in a large population, with special attention to gender and location.

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas.

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance.

Body size, physical activity and risk of colorectal cancer with or without the CpG island methylator phenotype (CIMP).

Background: We investigated how body size and physical activity influence the risk of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC).

Methods: In the Netherlands Cohort Study (n = 120,852), risk factors were self-reported at baseline in 1986. After 7.

Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer.

Objective: To prospectively assess the accuracy of gadofosveset-enhanced magnetic resonance imaging (MRI) for nodal staging and restaging in rectal cancer.

Background: Accurate preoperative assessment of nodal disease in rectal cancer impacts treatment management. Staging with modern imaging techniques (computed tomography, MRI and endorectal ultrasound) is insufficiently accurate for clinical decision making.

Loss of SerpinA5 protein expression is associated with advanced-stage serous ovarian tumors.

Epithelial ovarian cancer, the most lethal neoplasm of the female genital tract, is usually diagnosed at an advanced stage as obvious symptoms are absent at early stages. This disease is believed to originate from malignant transformation of the ovarian surface epithelium or fallopian tube. Histologically, several subtypes are being recognized, with serous histology accounting for the majority of cases.

Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: diet-gene interactions and promoter CpG island hypermethylation in colorectal cancer.

Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). Among 609 CRC cases and 1,663 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852), we estimated CRC risk according to methyl donor intake across genotypes of folate metabolizing enzymes and methyltransferases.Although diet-gene interactions were not statistically significant, methionine intake was inversely associated with CRC among subjects having both common rs2424913 and rs406193 DNMT3B C > T genotypes (highest versus lowest tertile: RR = 0.

The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications.

The N-myc downstream regulated gene (NDRG) family of proteins consists of 4 members, NDRG1-4, which are well conserved through evolution. The first member to be discovered and responsible for the family name was NDRG1, because its expression is repressed by the proto-oncogenes MYCN and MYC. All family members are characterized by an α/β hydrolase-fold motif; however, the precise molecular and cellular function of these family members has not been fully elucidated.

Absence of tumor invasion into pelvic structures in locally recurrent rectal cancer: prediction with preoperative MR imaging.

Purpose: To retrospectively assess the accuracy of preoperative magnetic resonance (MR) imaging for identification of tumor invasion into pelvic structures in patients with locally recurrent rectal cancer scheduled to undergo curative resection.

Materials And Methods: The institutional review board approved this study, and informed consent was waived because of the retrospective nature of the study. Preoperative MR images in 40 consecutive patients with locally recurrent rectal cancer scheduled to undergo curative treatment between October 2003 and November 2006 were analyzed retrospectively.

Butyrate enemas improve intestinal anastomotic strength in a rat model.

Introduction: Anastomotic leakage is a common clinical complication with incidences up to 10% to 17% in colorectal surgery, leading to high morbidity and mortality. Butyrate is the product of colonic fermentation of indigestible carbohydrates and is considered beneficial to gastrointestinal healing. The aim of this study was to investigate the effect of intraluminal supplementation of butyrate on colonic anastomotic strength in a rat model.

Effect of butyrate enemas on inflammation and antioxidant status in the colonic mucosa of patients with ulcerative colitis in remission.

Background & Aims: Butyrate, produced by colonic fermentation of dietary fibers is often hypothesized to beneficially affect colonic health. This study aims to assess the effects of butyrate on inflammation and oxidative stress in subjects with chronically mildly elevated parameters of inflammation and oxidative stress.

Methods: Thirty-five patients with ulcerative colitis in clinical remission daily administered 60 ml rectal enemas containing 100mM sodium butyrate (n=17) or saline (n=18) during 20 days (NCT00696098).

Childhood and adolescent energy restriction and subsequent colorectal cancer risk: results from the Netherlands Cohort Study.

Background: Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study.

Methods: Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were 55-69 years of age (n = 120 852).