Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.

Background Colorectal cancer (CRC) is a major worldwide cause of cancer-related mortality. Colonoscopy programs based on guideline-recommended surveillance intervals have been put in place to reduce the morbidity and mortality associated with CRC. We were interested to evaluate clinical practice adherence to guideline-recommended surveillance intervals, the potential extent of early repeat colonoscopies, and causes of nonadherence to guideline recommendations. Methods We performed a literature search for articles reporting on guideline adherence for surveillance colonoscopies. Exclusion criteria included inflammatory bowel disease and hereditary CRC syndrome cohorts. Primary outcome was correct interval assignment in patients undergoing surveillance colonoscopy. Groups were assessed for adherence according to their respective guideline recommendations (North American or European). Results 16 studies were included in the analysis. The mean colonoscopy surveillance interval adherence rate was 48.8 % (95 % confidence interval [CI] 37.3 – 60.4). For North American guidelines, surveillance interval assignments were adherent to guideline recommendations in 44.7 % (95 %CI 24.2 – 66.3) of patients after detection of low risk lesions and in 54.6 % (95 %CI 41.4 – 67.4) after detection of high risk lesions. For European guidelines, surveillance interval assignments were adherent to recommendations in 24.4 % (95 %CI 1.1 – 63.4) of patients after detection of low risk lesions and in 73.6 % (95 %CI 35.5 – 98.8) after detection of high risk lesions. Conclusions The worldwide adherence to surveillance colonoscopy guidelines was low, with more than 50 % of patients undergoing repeat colonoscopies either too early or too late. Early repeat colonoscopies occurred with the highest frequency for patients in whom only hyperplastic polyps or low risk adenomas were found.

Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3-or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T EM ), central memory T cells (T CM) IntroductionBasophils are the least abundant of the granulocyte population, accounting for only 0.5%-1% of circulating leukocytes, and, together with eosinophils and mast cells (MCs), have long been associated with allergic diseases and helminth infections. [1][2][3][4] Like MCs, basophils express the tetrameric form of the high-affinity receptor for IgE (Fc⑀RI) and are a major source of histamine, which is stored in their cytoplasmic basophilic granules. Basophils and MCs belong to distinct cell lineages and are biologically very different. 5 Basophils are short-lived circulating cells (estimated half-life of 2 days) that differentiate and mature in the BM, whereas MCs are long-lived, tissue-resident cells that differentiate in peripheral tissues from locally recruited circulating CD34 ϩ precursors released from the BM. MCs are easily detectable at the interface of the organism with the external world; in contrast, basophils are rarely found in normal tissues, but can be detected by immunohistochemistry in inflamed tissues of patients with asthma, allergic rhinitis, and various allergic skin diseases. 1,6,7 However, the presence of basophils in the mucosa of patients with inflammatory diseases that are independent of IgE has not been reported.The CD4 T cells play a key role in orchestrating the pathologic immune reaction of chronic inflammatory disorders. It is now known that Th17 effectors play a crucial role in pulmonary cystic fibrosis (CF). 8 Similarly, Th17 and Th1 cells are involved in mucosa-associated chronic disorders such as inflammatory bowel disease (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC). 9-11 Specifically, CD is a chronic and relapsing T cell-driven inflammatory disease of the entire gastrointestinal tract. CD4 effector T cells are generated in draining lymph nodes and recruited into the intestinal tissues, where they contribute to the inflammatory process and tissue destruction. 9 Once initiated, inflammation is first characterized by the expression of proinflammatory cytokines involved in innate immunity (ie, IL-12, TNF-␣, and IL-23), followed by those involved in adaptive immunity (ie, . 9,12 APC-derived IL-1␤, together with IL-6, promotes the development of human Th17 cells in vitro. 13 IL-23 promotes the expansion of memory Th17 cells. 14 In mice, IL-23 drives pathogenic Th17/Th1 cells. 15 Double IL-17-and IFN-␥-producing CD4 T cells ar...

We describe one of the largest series of adult adrenal GNs. Adrenal GNs may secrete testosterone or be part of a composite tumor with pheochromocytoma. The association of adrenal GN with MSH2 mutation seems to be a coincidental finding.

CD172a+ cells producing IL-1β and TNF are increased in inflamed tissues in Crohn’s disease and can be targeted by CD47 fusion protein.