سرطان معده در FAP: افزایش نگران کننده میزان شیوع Gastric cancer in FAP: a concerning rise in incidence

Introduction The hereditary colorectal cancer syndrome familial adenomatous polyposis (FAP) is caused by a germline mutation in the adenomatous polyposis coli (APC) gene. The leading causes of cancer in FAP patients are colorectal, duodenal, and thyroid [1, 2]. Numerous guidelines have established surveillance recommendations for prevention of these FAP related cancers [3–۵]. Gastric cancer is not cited as a health risk in Western FAP patients with a reported lifetime risk of 0.6%, similar to the general population risk [6]. Gastric polyps are commonly noted on surveillance upper endoscopy recommended for duodenal polyposis. The most commonly observed lesions are fundic gland polyps (FGP). Bianchi et al. demonstrated FGP in 88% of FAP patients with low grade foveolar dysplasia seen in 38% and high grade foveolar dysplasia in 3%. Factors associated with the finding of foveolar dysplasia include FGP size, duodenal polyposis stage, antral gastritis, and lack of acid-suppressive therapy [7]. We report the sudden rise in the incidence of gastric cancer in FAP patients enrolled in a hereditary colon cancer registry and the associated demographic, endoscopic and histologic features in these patients. Methods ۷۶۷ patients with the clinical diagnosis or genotype of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (aFAP) who have had at least one esophagogastroduodenoscopy were accessed through the IRB approved Cologene™ database of the David G. Jagelman Inherited Colorectal Cancer Registries in the Sanford R. Weiss, M.D., Center for Hereditary Colorectal Neoplasia. Patients with gastric cancer were identified through the investigator and query of the Cologene™ database. From time of registration to time of diagnosis, all endoscopic surveillance procedures including EGD, endoscopic ultrasound, endoscopic mucosal resection, and endoscopic submucosal dissection were reviewed. Information extracted included polyp morphology, location, sizes, and histology. The follow-up period extended from either time of diagnosis to death or time of diagnosis to November, 2016. For statistics, continuous data were described as mean with and range as appropriate. Categorical data were described as raw numbers and percentages or proportions. The standardized incidence ratio (SIR) was calculated as the ratio of observed gastric cancer cases to the expected number of cases estimated using the SEER database of gastric cancer. Results Medical records of 767 FAP patients who underwent one or more upper endoscopies between January 2001 and November 2016 were reviewed. Since the inception of the registry in 1979, no case of gastric adenocarcinoma was seen until 2006. Nine more cases were diagnosed between 2012 and 2016 for a total of 10/767 (1.3%) cases resulting in a standardized incidence ratio of 140. All cases arose in patients with a carpeting of fundic gland polyposis and polypoid masses of gastric polyps in the proximal stomach including the fundus and body. The mean age at cancer diagnosis was 57 years (range 35–۷۵) and six were female. The average interval from initial colectomy to gastric cancer diagnosis was 23.1 years. Eight patients were asymptomatic including four patients diagnosed with stage I gastric adenocarcinoma. Stage IV adenocarcinoma was detected in 6 patients with liver (n=5) and peritoneal (n=1) metastases. Two patients with stage I gastric cancer had previous foregut surgery. One had a pancreaticoduodenectomy for an ampullary adenocarcinoma 15 years prior and the other underwent a prophylactic pancreas preserving duodenectomy for stage IV duodenal polyposis 10 years before the gastric cancer diagnosis. One patient with metastatic adenocarcinoma had a pancreas preserving duodenectomy 15 years prior for stage IV duodenal polyposis. All patients with stage I disease underwent curative gastrectomy. One died of postoperative complications within 3 weeks of surgery and three are alive 6, 8 and 9 months after surgery, respectively. Of the 6 diagnosed with metastatic disease, 4 died within a mean 4.5 months after diagnosis. Two have been receiving palliative chemoradiation for 2 and 19 months, respectively