For health professionals

A Hereditary Diffuse Gastric Cancer (HDGC) Workshop was held in Cambridge on 20 and 21st November 2008 and organised by Dr Rebecca Fitzgerald together with Professor Carlos Caldas, Professor David Huntsman, Mr Richard Hardwick and Mrs Sarah Dwerryhouse.

Familial gastric cancer is a rare but important entity since the clinical implications may be profound. Familial gastric cancer may occur in isolation or as part of a syndrome affecting multiple cancer sites. When clinical criteria suggest an hereditary autosomal dominant syndrome then patients may be offered genetic testing for mutations in E-cadherin (CDH-1), the gene responsible for 30% Hereditary Diffuse Gastric Cancer cases. There are a number of uncertainties around the optimal clinical management of these families with regards to genetic testing, endoscopic surveillance, prophylactic gastrectomy and histopathological processing and diagnosis.

The aim of this workshop was therefore to bring together experts in the field from around the world in order to combine our experiences and to come up with consensus statements and clear clinical guidelines.

The workshop started with a lecture given by David Huntsman from Vancouver who summarised the progress that has been made in our understanding and management of this condition over the past ten years. Nina Hallowell (Edinburgh) and Sarah Downing (Cambridge) then introduced three patients who were able to give first hand accounts of their experiences including genetic testing, endoscopic surveillance and surgery. Their openness and vivid accounts were very thought provoking and set the scene for the rest of the workshop.

The following morning we reviewed the evidence and current clinical practices across specific areas; namely genetics, pathology, endoscopy and surgery. Paul Pharoah (Cambridge) presented the updated linkage analysis which confirmed that lobular breast cancer is a significant risk for these individuals whereas colon cancer is less of a risk. Fatima Carneiro (Portugal) shared her extensive experience of analysing gastrectomy specimens from prophylactic surgery which provoked much discussion about the natural history of the microscopic signet ring foci which are invariably present in mutation carriers. This was followed by a discussion on endoscopic surveillance led by Rebecca Fitzgerald (Cambridge) which resulted in vigorous debate about the utility of endoscopy since is now appears that these microscopic lesions are present and can be detected endoscopically when enough biopsies are taken. Hence endoscopy may be more useful in those awaiting results of genetic testing or in those for whom their mutation status is uncertain. Richard Hardwick (Cambridge) led the discussion on prophylactic surgery which is increasingly the option of choice for individuals with a germline mutation. Our international experts from New Zealand (Parry Guilford and Vanessa Blair) and Stanford (Jeff Norton) then shared their extensive research and clinical experiences which were invaluable since patients’ cultural perspectives can have profound influences on decision making, for example within the Maori communities.

These excellent lectures set the scene for the break-out sessions in the afternoon which culminated in the presentation of draft clinical guidelines for genetic testing and counselling (Chairs: Carlos Caldas and Daniel Chung), endoscopic surveillance (Rebecca Fitzgerald and Krish Ragunath), prophylactic gastrectomy (Richard Hardwick and Jeff Norton) and pathological processing and diagnosis (Fatima Carneiro and Han van Krieken) . These guidelines will be published in due course in order to standardise our clinical care and fuel research to better understand this condition.

All agreed that the workshop was an invaluable opportunity for experts to meet and exchange ideas. The informal nature of the meeting in the splendid surroundings of Trinity College and Cambridge Research Institute also made it a most enjoyable experience.