EREDITARY HEMORRHAGIC telangiectasia (HHT) (Online Mendelian Inheritance in Man [OMIM] #187300) is a dominantly inherited genetic vascular disorder characterized by recurrent epistaxis; cutaneous telangiectasia; and visceral arteriovenous malformations (AVMs) that affect many organs, including the lungs, gastrointestinal tract, liver, and brain. Diagnosis is based on the Curaçao criteria and is considered definite if at least 3 of 4 criteria are fulfilled. 1 The criteria are spontaneous and recurrent epistaxis, Author Affiliations are listed at the end of this article.

Purpose: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by arteriovenous malformations (AVM), mostly cutaneous and mucous (telangiectases), but also involving the lungs (PAVM), liver (HAVM) and brain (CAVM). We studied the relationship between the phenotype and genotype in patients with a proven mutation in either ENG (HHT1) or ACVRL1 (HHT2). Methods: Clinical features and their age of onset were compared between HHT1 and HHT2. The type of mutation was also analyzed. Clinical manifestations were distinguished from lesions found by screening. Results: Ninety-three HHT1 patients and 250 HHT2 patients were included. Epistaxis occurred later in HHT2, with incomplete penetrance (P Ͻ 0.0001). Symptomatic PAVMs were more frequent in HHT1 (34.4 vs. 5.2%, P Ͻ 0.001), as were cerebral abscesses (7.5 vs. 0.8%, P ϭ 0.002).Gastrointestinal bleeding occurred more frequently in HHT2 (16.4 vs. 6.5%, P ϭ 0.017). Symptomatic hepatic involvement was only seen in HHT2 patients. PAVMs were more frequently detected in asymptomatic HHT1 patients (54 vs. 12.8%, P Ͻ 0.0001). PAVMs and HAVMs were often family clustered in HHT1 and HHT2, respectively. Truncating mutations were associated with a higher frequency of epistaxis and telangiectasis, in HHT2. Conclusion: This study shows major differences between HHT1 and HHT2 phenotypes, which should be taken into account for future clinical studies. Genet Med 2007:9(1):14-22.

Main RecommendationsESGE recommends that individuals with hereditary gastrointestinal polyposis syndromes should be surveilled in dedicated units that provide monitoring of compliance and endoscopic performance measures. Strong recommendation, moderate quality of evidence, level of agreement 90 %.ESGE recommends performing esophagogastroduodenoscopy, small-bowel examination, and/or colonoscopy earlier than the planned surveillance procedure if a patient is symptomatic. Strong recommendation, low quality of evidence, level of agreement 100 %.

The three mammalian receptors UNC5H1, UNC5H2, and UNC5H3 (also named UNC5A, UNC5B, and UNC5C in human) that belong to the family of the netrin-1 receptors, UNC5H, were initially proposed as mediators of the chemorepulsive effect of netrin-1 on specific axons. However, they were also recently shown to act as dependence receptors. Such receptors induce apoptosis when unbound to their ligand. We show here that the expression of the human UNC5A, UNC5B, or UNC5C is down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers. In colorectal tumors, this down-regulation is associated with loss of heterozygosity occurring within UNC5A, UNC5B, and UNC5C genes but may also be partially related to epigenetic processes because histone deacetylase inhibitor increased UNC5C expression in various cancer cell lines. Moreover, sequencing of UNC5C gene in patients with colorectal tumors revealed the presence of missense mutations. The loss͞reduction of expression may be a crucial mechanism for tumorigenicity because the expression of UNC5H1, UNC5H2, or UNC5H3 inhibits tumor cell anchorage-independent growth and invasion. Moreover, these hallmarks of malignant transformation can be restored by netrin-1 addition or apoptosis inhibition. Hence, UNC5H1, UNC5H2, and UNC5H3 receptors may represent tumor suppressors that inhibit tumor extension outside the region of netrin-1 availability by inducing apoptosis.

Endoscopic resection is an efficient and acceptably safe technique for treating SDA. Further studies need to assess whether systematic bleeding prophylaxis will reduce the incidence of delayed hemorrhage after endoscopic resection.

The European Society of Gastrointestinal Endoscopy (ESGE) together with the United European Gastroenterology (UEG) recently developed a short list of performance measures for small-bowel endoscopy (i. e. small-bowel capsule endoscopy and device-assisted enteroscopy) with the final goal of providing endoscopy services across Europe with a tool for quality improvement. Six key performance measures for both small-bowel capsule endoscopy and for device-assisted enteroscopy were selected for inclusion, with the intention being that practice at both a service and endoscopist level should be evaluated against them. Other performance measures were considered to be less relevant, based on an assessment of their overall importance, scientific acceptability, and feasibility. Unlike lower and upper gastrointestinal endoscopy, where performance measures had already been identified, this is the first time that small-bowel endoscopy quality measures have been proposed.

The European Society of Gastrointestinal Endoscopy (ESGE) together with the United European Gastroenterology (UEG) recently developed a short list of performance measures for small-bowel endoscopy (i.e. small-bowel capsule endoscopy and device-assisted enteroscopy) with the final goal of providing endoscopy services across Europe with a tool for quality improvement. Six key performance measures both for small-bowel capsule endoscopy and for device-assisted enteroscopy were selected for inclusion, with the intention being that practice at both a service and endoscopist level should be evaluated against them. Other performance measures were considered to be less relevant, based on an assessment of their overall importance, scientific acceptability, and feasibility. Unlike lower and upper gastrointestinal endoscopy,

This prospective series shows a higher duodenal polyposis progression rate and cumulative risk of late-stage (stage IV) duodenal polyposis in FAP patients compared with previous series. These results suggest that current modalities for surveillance and management of these patients need revision.