Diversity bias in colorectal surgery: a global perspective.

There is a specific lack of data on equity and injustices among colorectal surgeons regarding diversity. This study aimed to explore colorectal surgeon's lived experience of diversity bias with a specific focus on gender, sexual orientation or gender identity and race or religion. A bespoke questionnaire was designed and disseminated to colorectal surgeons and trainees through specialty association mailing lists and social media channels.

A Snapshot of the International Views of the Treatment of Rectal Cancer Patients, a Multi-regional Survey: International Tendencies in Rectal Cancer.

Background: Management of rectal cancer has a number of potentially appropriate alternatives for each patient. Despite acceptance of standards, practices may vary among regions. There is significant paucity of data in this area.

Value of upper gastrointestinal endoscopy for gastric cancer surveillance in patients with Lynch syndrome.

In our study, we evaluated the effectiveness of upper gastrointestinal (GI) endoscopy as an instrument for early gastric cancer (GC) detection in Lynch syndrome (LS) patients by analyzing data from the registry of the German Consortium for Familial Intestinal Cancer. In a prospective, multicenter cohort study, 1128 out of 2009 registered individuals with confirmed LS underwent 5176 upper GI endoscopies. Compliance was good since 77.

A narrative celebrating the recent contributions of women to colorectal surgery.

Background: To interview extraordinary women who have made recent significant contributions to the field of colorectal surgery.

Design: The authors asked some of the many extraordinary women who have made significant contributions to the field of colorectal surgery to answer several questions. These women were selected from many potential candidates based upon their extraordinary recent contributions to the field of colorectal surgery.

Disease expression in juvenile polyposis syndrome: a retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers.

Purpose: Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% of cases by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.

Methods: We performed a retrospective, questionnaire-based European multicenter survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.

Cancer risk and survival in carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database.

Background: Most patients with gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.

Objective And Design: This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in carriers up to 75 years of age.

Results: 3119 patients were followed for a total of 24 475 years.

Genomic and transcriptomic heterogeneity of colorectal tumours arising in Lynch syndrome.

Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing. Here, we provide a first molecular characterization of LS tumours and of matched tumour-distant reference colonic mucosa based on whole-genome DNA-sequencing and RNA-sequencing analyses.

A proposed staging system and stage-specific interventions for familial adenomatous polyposis.

Background And Aims: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.

Obesity, Aspirin, and Risk of Colorectal Cancer in Carriers of Hereditary Colorectal Cancer: A Prospective Investigation in the CAPP2 Study.

Purpose: In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS).

Patients And Methods: Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design).

Quality of colonoscopy in Lynch syndrome.

Lynch syndrome (LS) accounts for 2 - 4 % of all colorectal cancers. Affected family members have a germline mutation in one of the DNA mismatch repair genes MLH1, PMS2, MSH2, or MSH6, and a lifetime risk for development of colorectal cancer of 25 - 75 %. Current guidelines recommend annual to biannual surveillance colonoscopy in mutation carriers.

Quality of life after surgery in individuals with familial colorectal cancer: does extended surgery have an adverse impact?

Background: There is controversy regarding the optimum surgical treatment of patients presenting with colorectal cancer with known or suspected genetic cancer syndromes. Although standard segmental resection may be curative, a high risk of metachronous malignancy leads many to advocate extended surgery. The current study was designed to assess whether or not extended surgery adversely impacts quality of life compared to segmental surgery.

Surgical treatment of hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome).

The surgical management of the Lynch syndrome patient with colorectal cancer needs to be individualized. Because of the increased incidence of synchronous and metachronous colorectal neoplasms, most favor an extended resection at the time of diagnosis of colorectal cancer. Age of diagnosis, stage of the tumor, co-morbidities, surgical expertise, surgical morbidity, and patient wishes should be taken into account when considering a surgical procedure.

Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.

Background: Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer.

Methods: In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years.

Risks of less common cancers in proven mutation carriers with lynch syndrome.

Purpose: Patients with Lynch syndrome are at high risk for colon and endometrial cancer, but also at an elevated risk for other less common cancers. The purpose of this retrospective cohort study was to provide risk estimates for these less common cancers in proven carriers of pathogenic mutations in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6.

Patients And Methods: Data were pooled from the German and Dutch national Lynch syndrome registries.

Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.

Background: Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo.

Ten recently identified associations between nsSNPs and colorectal cancer could not be replicated in German families.

Ten non-synonymous single nucleotide polymorphisms (nsSNPs), which were recently associated with colorectal cancer risk in a comprehensive, array based study (AKAP9 M463I, DKK3 G335R, AMPD1 Q12X, LIPC L356F, PSMB9 V32I, THBS1 N700S, CA6 S90G, ASCC3 C1995S, DHX36 S416C and CPA4 G303C) were re-evaluated in the present study based on 626 German familial non-HNPCC colorectal cancer patients and 736 healthy controls. No associations of any of the 10 nsSNPs with colorectal cancer could be replicated. The combined analyses indicated that further research based on additional independent samples is required.

Unregulated smooth-muscle myosin in human intestinal neoplasia.

A recent study described a recessive ATPase activating germ-line mutation in smooth-muscle myosin (smmhc/myh11) underlying the zebrafish meltdown (mlt) phenotype. The mlt zebrafish develops intestinal abnormalities reminiscent of human Peutz-Jeghers syndrome (PJS) and juvenile polyposis (JP). To examine the role of MYH11 in human intestinal neoplasia, we searched for MYH11 mutations in patients with colorectal cancer (CRC), PJS and JP.

APC inactivation associates with abnormal mitosis completion and concomitant BUB1B/MAD2L1 up-regulation.

Background & Aims: Chromosomal instability, a hallmark of most colorectal cancers, has been related to altered chromosome segregation and the consequent deficit in genetic integrity. A role for the tumor suppressor gene APC has been proposed in colorectal cancer that leads to compromised chromosome segregation even though the molecular mechanism is not yet understood. Here, we tackled the genetic basis for the contribution of APC to chromosomal instability in familial adenomatous polyposis and sporadic colorectal cancer.

Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers clinically affected with Lynch syndrome: a report by the German HNPCC Consortium.

Purpose: Lynch syndrome is linked to germline mutations in mismatch repair genes. We analyzed the genotype-phenotype correlations in the largest cohort so far reported.

Patients And Methods: Following standard algorithms, we identified 281 of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124) or MSH2 (n = 157).

Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer.

CCND1 encodes cyclin D1, which plays an important role in the G1 to S phase transition of the cell cycle. A common polymorphism (c.G870A) increases alternate splicing.

Germ line mutations of mismatch repair genes in hereditary nonpolyposis colorectal cancer patients with small bowel cancer: International Society for Gastrointestinal Hereditary Tumours Collaborative Study.

Purpose: The aim of study was to determine the clinical characteristics and mutational profiles of the mismatch repair genes in hereditary nonpolyposis colorectal cancer (HNPCC) patients with small bowel cancer (SBC).

Experimental Design: A questionnaire was mailed to 55 members of the International Society for Gastrointestinal Hereditary Tumours, requesting information regarding patients with HNPCC-associated SBC and germ line mismatch repair gene mutations.

Results: The study population consisted of 85 HNPCC patients with identified mismatch repair gene mutations and SBCs.

N-acetyltransferase (NAT) 2 acetylator status and age of onset in patients with hereditary nonpolyposis colorectal cancer (HNPCC).

N-acetyltransferase (NAT) 2 is an essential polymorphic enzyme involved in the metabolism of various xenobiotics, including potential carcinogens. The individual differences in the NAT2 metabolic capacity are caused by allelic variants of the NAT2 gene which are determined by a pattern of single nucleotide polymorphisms (SNPs) resulting in slow (SA), intermediate (IA) or rapid acetylator (RA) phenotypes. Highly penetrant germline mutations in mismatch repair (MMR) genes are the cause of the disease in hereditary nonpolyposis colorectal cancer (HNPCC).

A new method for optimizing multiplex DNA microsatellite analysis in low quality archival specimens.

Background: Testing microsatellite instability seems to be a useful tool for the initial screening of putative non-polyposis colorectal cancer (HNPCC), preceding analysis of germ-line mutations of DNA mismatch repair genes. However, diagnosis of microsatellite instability becomes complicated when highly-damaged DNA from formalin-fixed paraffin-embedded tissue specimens has to be investigated.

Materials And Methods: A new methodical approach was established based on special multiplex PCR regimes (e.