Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer

An ecological and lifespan approach of social influences on childhood pain experiences

Pediatric pain is a common experience that not only impacts the child but also their social environment (e.g., parents, peers, school functioning). Several models have been formulated to gain a better understanding of the social context interwoven with pediatric pain, with the Social Communications Model the most well-known and comprehensive model. More recent model development has focused on providing an explanation of specific pathways to adaptive or maladaptive pain-related functioning in children (e.g., Interpersonal Fear-Avoidance Model, Ecological Resilience-Risk Model). The purpose of the current chapter is to provide an overview of both the Interpersonal Fear-Avoidance Model and the Ecological Resilience-Risk Model, followed by a critical evaluation of their merit in furthering our understanding of pediatric chronic pain across development and within the broader social context (e.g., peers and school environment). The chapter will conclude with directions for future research, model development and clinical practice