Distinct Involvement of the Sonic Hedgehog Signaling Pathway in Gastric Adenocarcinoma of Fundic Gland Type and Conventional Gastric Adenocarcinoma.

BACKGROUND/AIMS: Gastric adenocarcinoma of fundic gland type (GAFG), which is a rare variant of gastric cancer, is reportedly associated with both Wnt/ß-catenin signaling activation and guanine nucleotide binding protein, alpha stimulating complex (GNAS) mutations. This study aimed to elucidate potential roles of the Sonic hedgehog (Shh) signaling pathway in GAFG. METHODS: We performed immunostaining for ß-catenin and Shh signal-associated proteins, including Patched (Ptch), Smoothened (Smo), and Glioma-associated oncogene-1 (Gli1), and the direct sequencing of GNAS/BRAF/KRAS in 27 GAFGs, and compared them with 30 conventional gastric adenocarcinomas (CGAs). RESULTS: GAFGs exhibited significantly lower immunoreactivity scores for Ptch, Smo, and Gli1 than CGAs. Moreover, while the Ptch score was significantly lower in the GAFG tumor areas than in the non-neoplastic areas adjacent to GAFG, the score was significantly higher in the CGA tumor areas than in the non-neoplastic areas. Similar trends were observed in the scores for Smo and Gli1. ß-Catenin expression and GNAS mutations were found in 22 (81%) and 8 (30%) of the 27 GAFGs respectively. Gli1 expression was significantly associated with mutations in GNAS. CONCLUSION: GAFG and CGA exhibited distinct Ptch, Smo, and Gli1 expression patterns. Downregulation of the Shh signaling pathway, as well as activation of the Wnt/ß-catenin signaling pathway, may therefore be associated with tumorigenesis in GAFG.

Continuation of antithrombotic therapy may be associated with a high incidence of colonic post-polypectomy bleeding.

BACKGROUND AND AIM: Post-polypectomy bleeding (PPB) is the most common complication of endoscopic procedures. To reduce the risk of thromboembolic incidents, Japanese guidelines for gastroenterological endoscopy were revised to indicate that antithrombotic agents were not to be discontinued for endoscopic treatment. However, carrying out endoscopic procedures under antithrombotic medication potentially increases the incidence of hemorrhagic complications. The present study investigated the impact of the revised guidelines on the frequency of complications after colonoscopic procedures. METHODS: The surveillance period comprised the year before the initiation of the new guidelines (2012), which served as a control period, and 2 years after initiation of the new guidelines (2013 and 2014). During the control period, 3955 cases were examined colonoscopically and 1601 lesions were treated endoscopically. During the 2-year period under the new guidelines, 8749 colonoscopies and 3768 endoscopic treatments were carried out. Changes in treatment methods and rates of complications were compared. RESULTS: PPB rate was not significantly different before and after the revision (0.87% vs 1.01%). With the new guidelines, PPB rates in antithrombotic non-users and users were 0.60% and 3.13%, respectively (OR 5.11, P = 0.000). Multivariable analysis showed that the risks for PPB were as follows: heparin bridging therapy (OR 6.34, P = 0.0002); low-dose aspirin (LDA) continuation (OR 5.30, P = 0.0079); and lesion size (OR 1.06, P < 0.0001). CONCLUSION: The present study showed that the overall PPB rate under the new guidelines was not significantly higher when compared with the previous data obtained before the new guidelines were introduced.

Hemorrhagic polyps formed like fundic gland polyps during long-term proton pump inhibitor administration.

We report a rare case of hemorrhagic gastric polyps resulting in anemia during long-term proton pump inhibitor (PPI) administration that endoscopically looked like a fundic gland polyp (FGP). A 44-year-old man presented complaining of anemia and tarry stools. Esophagogastroduodenoscopy (EGD) demonstrated multiple white edematous polyps in the corpus and antrum, which were considered to be FGPs. We attempted endoscopic hemostasis but hemorrhaging increased because of hemorrhagic polyps and vulnerable gastric mucosa. Re-bleeding occurred several times. Polyp resection was performed at 24 polyp sites. We also ceased the administration of PPI. Microscopically, polyps showed characteristics of hyperplasia in the foveolar epithelium, extensions of fundic glands, and edema of the stroma. The proliferation of parietal and chief cells was also observed. Immunohistochemically, aquaporin-4 (AQP4) and KCNQ1-positive parietal cells and dilated mucous glands were found from the basal side to the apical side of the mucosa. These findings were compatible with the development of lesions associated with the long-term administration of PPI. EGD revealed an improvement in the vulnerability of gastric mucosa and the development of polyps, with no further gastric polyps observed 1 year after discharge. Bleeding from polyps resembling FGPs is generally rare, with indications that long-term PPI administration may induce such bleeding.