GAPPS is an autosomal dominant syndrome characterized by FGPs localized in the gastric body and fundus. GAPPS was first reported by Worthly et al. in 2012 [1]. Since then, there have been an increasing number of reports on GAPPS [5,6,7,8,9]; however, the clinical course, malignant transformation, and prognosis of GAPPS remain unclear. The prognosis of GAPPS depends on the malignancy of the FGPs. However, the clinical management of GAPPS is difficult because it is difficult to assess the exact status of the FGPs and to predict their malignant transformation. EGD is useful for early detection of GAPPS, and regular biopsy is necessary to predict malignant transformation. However, cases of rapid progression to gastric adenocarcinoma and metastasis despite frequent EGD have been reported. H. pylori infection suppresses FGPs, and patients with FAP who have FGPs have a lower H. pylori infection rate [1, 3, 7]. Furthermore, H. pylori is closely associated with GAPPS, although many patients with GAPPS have negative immunoglobulin G test results for H. pylori. However, the association between H. pylori infection and gastric cancer development is still unclear, and the usefulness of H. pylori eradication therapy for GAPPS is unknown [10, 11].
Histopathologically, FGP is a characteristic feature of GAPPS and is included in the diagnostic criteria. Hyperproliferative aberrant pits, which are polyp-like structures caused by irregular growth of proper gastric glands in diluted glandular fossa epithelialization, are also characteristic of GAPPS [7]. Immunohistologically, MUC5A and MUC6 are positive, while MUC2 is negative, and CDX2 and p53 are sporadically positive, indicating gastric-type adenocarcinoma [12]. Notably, lesions that are positive for MUC5A but negative for MUC2/MUC6 with elevated Ki-67 and strong proliferative potential have been reported. As the causative gene for GAPPS, a point mutation in APC promotor 1B has been reported, which is thought to contribute to tumorigenesis via β-catenin and Wnt signaling [13].
There are two aims in surgery for GAPPS: the first is prophylactic gastrectomy, and the second is excising concurrent cancer. In our four cases, one patient underwent prophylactic gastrectomy, one had gastric cancer, and the remaining two had suspected gastric cancer.
Regarding prophylactic TG for GAPPS, patients who fulfill the diagnostic criteria for GAPPS and those with FGPs progressing to dysplasia should undergo prophylactic TG [14]. Recently, this has been performed in Asian countries [5]. Prophylactic gastrectomy is associated with the risk of postoperative complications, such as infections, dumping syndrome, and weight loss. Furthermore, anastomotic strictures, bile reflux, and iron deficiency have also been reported as postsurgical complications of prophylactic gastrectomy [15]. Generally, prophylactic gastrectomy is performed for patients who are younger and healthier than those who undergo curative gastrectomy for gastric cancer. However, the postoperative complications after prophylactic gastrectomy are the same as those associated with curative gastrectomy [16]. Prophylactic TG for GAPPS remains controversial because GAPPS may progress rapidly even with regular surveillance. The ideal timing for prophylactic gastrectomy is also important. Prophylactic gastrectomy should be considered when GAPPS is diagnosed, but the timing of dysplasia and adenocarcinoma development varies widely. Therefore, the optimal timing of prophylactic gastrectomy is still controversial.
Regarding the treatment of concurrent suspected or confirmed gastric cancer with GAPPS, generally, these patients are mainly followed regularly with repeat biopsy. Therefore, even if adenocarcinoma is diagnosed, tumors are detected in an early stage.
In GAPPS patients, polyps are located in the upper stomach; therefore, TG is necessary. Although laparoscopic TG has recently been performed safely, RTG is challenging. Robotic surgery has several technical advantages compared with laparoscopic instruments, namely greater precision of the operator’s movements, tremor filtration, and improved ergonomics. These technical benefits are considered advantages of RTG over laparoscopic TG. Retrospective study has showed the lower complication rate in early gastric cancer patients with RTG, especially there was no leakage of anastomotic site. This study indicated the merit of the RTG was minimal damage of pancreas and lower incidence of pancreatic fistula [17]. In GAPPS patients, polyps are not located in the esophagus; therefore, TG is relatively easy to perform compared with esophagogastric junction cancer, making robotic gastrectomy useful. Furthermore, for relatively young patients undergoing surgery, cosmesis is more of a concern; therefore, minimally invasive surgery is useful.
In gastrectomy in GAPPS patients, although there are numerous polyps in the stomach, the serosa remains intact, and there is no stiffness of the stomach wall (Fig. 3a). As a result, it is easy to grasp the stomach wall (Fig. 3b). We encountered no stomach wall stiffness in our operations. This information is useful for the surgeons because GAPPS is a rare disease, few surgeons have experience with these patients.
To our knowledge, there are no reports of GAPPS patients undergoing robotic gastrectomy.