The ‘Cambridge surveillance protocol’ is advised for
CDH1 mutation carriers who do not (yet) want to undergo a prophylactic gastrectomy, to individuals at 50% risk of being carrier who are not (yet) willing to be tested for the mutation as well as for members from HDGC families without a known
CDH1 mutation [
62]. This protocol comprises
H.Pylori-testing, annual gastroscopy with ‘high definition’ endoscope, careful inspection of mucosa during 30 minutes, insufflation and desufflation of the stomach, biopsies of mucosal abnormalities and 30 random biopsies from different gastric regions (antrum, angulus, corpus, fundus, cardia) [
40]. The endoscopy should be performed using a white light high definition endoscope in a dedicated session with at least 30 minutes allocated to allow for a careful inspection of the mucosa on inflation and deflation, and to allow time for multiple biopsies to be taken [
40]. Use of mucolytics such as acetylcysteine may be helpful to obtain good views. Endoscopy permits direct inspection and biopsy of suspicious areas, but diffuse GC is difficult to detect at an early and treatable stage since the lesions tend to spread into the lamina propria without visible exophytic masses. The major problems include difficulties to identify (sub)mucosal lesions and biases in sampling in macroscopically normal-appearing gastric mucosa [
63]. Such specimens therefore need to be evaluated by pathologists with expertise with this type of lesions. Several studies have shown that even though
CDH1 mutation carriers had negative biopsies prior to prophylactic gastrectomy, foci were detected in their gastrectomy specimens [
49,
53,
58,
59]. Other techniques, such as chromoendoscopic techniques, trimodal imaging, confocal endomicroscopy and molecular imaging techniques are currently not recommended, but need to be further explored in a research setting [
40].