Genotypic and Phenotypic Characteristics of Hereditary Colorectal Cancer

The genomic causes and clinical manifestations of hereditary colorectal cancer (HCRC) might be stratified into 2 groups, namely, familial (FCRC) and a limited sense of HCRC, respectively. Otherwise, FCRC is canonically classified into 2 major categories; Lynch syndrome (LS) or associated spectra and inherited polyposis syndrome. By contrast, despite an increasing body of genotypic and phenotypic traits, some FCRC cannot be clearly differentiated as definitively single type, and the situation has become more complex as additional causative genes have been discovered. This review provides an overview of HCRC, including 6 LS or associated spectra and 8 inherited polyposis syndromes, according to molecular pathogenesis. Variants and newly-identified FCRC are particularly emphasized, including MUTYH (or MYH)-associated polyposis, Muir-Torre syndrome, constitutional mismatch repair deficiency, EPCAM-associated LS, polymerase proofreading-associated polyposis, RNF43- or NTHL1-associated serrated polyposis syndrome, PTEN hamartoma tumor syndrome, and hereditary mixed polyposis syndrome. We also comment on the clinical utility of multigene panel tests, focusing on comprehensive cancer panels that include HCRC. Finally, HCRC surveillance strategies are recommended, based on revised or notable concepts underpinned by competent validation and clinical implications, and favoring major guidelines. As hereditary syndromes are mainly attributable to genomic constitutions of distinctive ancestral groups, an integrative national HCRC registry and guideline is an urgent priority.

Small-Bowel Capsule Endoscopy—Optimizing Capsule Endoscopy in Clinical Practice

The small bowel is the longest organ within the gastrointestinal tract. The emergence of small bowel capsule endoscopy (SBCE) over the last 20 years has revolutionized the investigation and diagnosis of small bowel pathology. Its utility as a non-invasive and well-tolerated procedure, which can be performed in an outpatient setting, has made it a valuable diagnostic tool. The indications for SBCE include obscure gastrointestinal bleeding, small bowel Crohn’s disease, and, less frequently for screening in polyposis syndromes, celiac disease, or other small bowel pathology. Currently, there are several small bowel capsules on the market from different manufacturers; however, they share many technological features. The European Society of Gastrointestinal Endoscopy (ESGE) only recently developed a set of key quality indicators to guide quality standards in this area. Many of the technical aspects of capsule endoscopy still feature a degree of uncertainty in terms of optimal performance. Incomplete studies due to slow transit through the bowel, poor imaging secondary to poor preparation, and the risk of capsule retention remain frustrations in its clinical utility. Capsule review is a time-consuming process; however, artificial intelligence and machine learning offer opportunities to improve this. This narrative review examines our current standing in a number of these aspects and the potential to further the application of SBCE in order to maximize its diagnostic utility.

Danish guidelines for management of non-APC-associated hereditary polyposis syndromes

Hereditary Polyposis Syndromes are a group of rare, inherited syndromes characterized by the presence of histopathologically specific or numerous intestinal polyps and an increased risk of cancer. Some polyposis syndromes have been known for decades, but the development in genetic technologies has allowed the identification of new syndromes.. The diagnosis entails surveillance from an early age, but universal guideline on how to manage and surveille these new syndromes are lacking. This paper represents a condensed version of the recent guideline (2020) from a working group appointed by the Danish Society of Medical Genetics and the Danish Society of Surgery on recommendations for the surveillance of patients with hereditary polyposis syndromes, including rare polyposis syndromes.

Epithelial gastric polyps

Gastric polyps are lesions projected above the mucosal surface, which are detected in approximately 1–6% of upper gastrointestinal endoscopies. Based to their shape, polyps are classified as pedunculate, semi-pedunculate, sessile and flat. Depending on the histopathological type, some of them have the potential to transform into adenocarcinoma. Polyps can be of epithelial and non-epithelial origin. The first group, which is discussed in greater detail in this paper, includes fundic gland polyps, hyperplastic, adenomatous and hamartomatous polyps. Non-epithelial polyps include stromal tumours, leiomyomas, fibrous inflammatory polyps, fibroids, fibromyomas, lipomas, ectopic pancreas, neuroendocrine tumours, neuromas, and some vascular lesions. Multiple polyps in patients under the age of 40 years require more extensive diagnosis for hereditary polyposis syndromes, which are associated with an increased risk of gastric cancer, as well as other gastrointestinal and extra-gastrointestinal malignancies. In recent years, there has been a clear decrease in the proportion of hyperplastic polyps and an increase in the proportion of fundic gland polyps among all gastric polyps, which is probably related to the increased use of proton pump inhibitors and a reduced incidence of Helicobacter pylori infections. About 90% of gastric polyps are detected accidentally and usually do not cause clinical symptoms, but large polyps may be responsible for anaemia, bloody stools, abdominal pain, and even pyloric obstruction, which may be manifested by vomiting, severe flatulence, lack of appetite or progressive weight loss.

Genetics in Colorectal Cancer

Colorectal cancer are the third most commonly diagnosed form of cancer globally, which about 11% of all cancer diagnoses. Obesity, together with kind of sedentary lifestyle, red meat consumption, tobacco, and alcohol consumption are considered as predisposing factors of progression of CRC. In the development of colorectal cancer, genetic factors having a role in its incidence. The hereditary type of colorectal cancer was divided into two types is polyposis and Lynch syndrome which have each and different mechanism and genetic pattern. Lynch syndrome contributes for 3–5% of CRC cases and is caused by a germline mutation in one of four genes associated with the DNA mismatch repair (MMR) system: MLH1, MSH2, MSH6, or PMS2. In polyposis, there are some types such as Familial Adenomatous Polyposis (FAP) which mostly caused by APC mutation, MYH-associated polyposis, and the rare hamartomatous polyposis syndromes. Genetic testing and better family history documentation can enable those with a hereditary predisposition for the neoplasm to take preventive measures. Some genetic testing can be used such as Microsatellite instability (MSI), immunohistochemistry (IHC), DNA sequencing and protein truncation that used for each type of hereditary colorectal cancer.