Clinical Efficacy and Safety of Endoscopic Treatment of Gastrointestinal Stromal Tumors in the Stomach.

Background/Aims: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the stomach. We evaluated the clinical outcomes of endoscopic treatment for gastric GISTs. Methods: This is a single center, retrospective study that enrolled 135 cases of gastric subepithelial tumors (SETs) resected by endoscopic procedures and confirmed as GISTs by histopathology from March 2005 to July 2019. The immediate and long-term clinical outcomes were analyzed retrospectively. Results: The mean patient age was 57.9 years, and the mean tumor size was 2.1 cm. Of the tumors, 43.0% were located in the body, followed by the fundus (26.7%) and cardia (17.0%). Most tumors (85.2%) were resected by endoscopic submucosal dissection, followed by endoscopic mucosal resection (6.7%), submucosal tunneling endoscopic resection (5.9%), and endoscopic full-thickness resection (2.2%). Macroperforation occurred in 4.4% and microperforation in 6.7% of the cases. The R0 resection rate was 15.6%. However, the rate of complete resection by the endoscopic view was 90.4%, of which 54.8% of cases were in the very-low-risk group, followed by the low-risk group (28.1%), intermediate-risk group (11.9%), and high-risk group (5.2%). During 36.5 months of follow-up, recurrence was found in four (3.4%) of the 118 patients who were monitored for more than 6 months (low-risk group, 1/37 [2.7%]; intermediate-risk group, 2/11 [18.2%]; high-risk group, 1/6 [16.7%]). Conclusions: Endoscopic treatment of a GIST appears to be a feasible procedure in selected cases. However, additional surgery should be considered if the pathologic results correspond to intermediate- or high-risk groups.

[Inverted Hyperplastic Polyp in Stomach: A Case Report and Literature Review].

An inverted hyperplastic polyp (IHP) found in stomach is rare and characterized by downward growth of hyperplastic mucosal component into the submucosa. Because of such characteristic, IHP can be misdiagnosed as subepithelial tumor or malignant tumor. In fact, adenocarcinoma was reported to have coexisted with gastric IHP in several previous reports. Because only 18 cases on gastric IHP have been reported in English and Korean literature until now, pathogenesis and clinical features of gastric IHP and correlation with adenocarcinoma have not been clearly established. Herein, we report a case of gastric IHP which was initially misdiagnosed as gastrointestinal stromal tumor and resected using endoscopic submucosal dissection. Literature review of previously published case reports on gastric IHP is also presented.

Effects of CH4893237, a new orally active estrogen receptor downregulator, on breast cancer xenograft models with low serum estrogen levels.

We compared the antitumor efficacy and estrogen receptor (ER) degradation of CH4893237, a new orally active selective ER downregulator, with fulvestrant and tamoxifen in human breast cancer xenografts with low levels of serum estrogen (E2) (50.6, 22.9 and <16.7 pg/ml), equivalent to the ranges in postmenopausal or aromatase inhibitor-treated breast cancer patients. In addition, using proteolysis assays, we tested the conformational changes induced in ERalpha and ERbeta by CH4893237, fulvestrant, and 4-OH tamoxifen (4OHT). In ZR-75-1 xenografts with 50.6 pg/ml E2, CH4893237 (100 and 300 mg/kg/day p.o.) as well as fulvestrant (1 and 3 mg/body/week s.c.) showed complete growth inhibition (>90%) and tamoxifen (30 and 100 mg/kg/day p.o.) showed moderate tamoxifen resistance. The antitumor activity of CH4893237 (300 mg/kg) was the same as that of fulvestrant (3 mg/body) but the rate of ER degradation induced by CH4893237 (300 mg/kg) was significantly stronger than that of fulvestrant (3 mg/body) (94.3 vs. 85.5%, P<0.01). In Br-10 xenografts with 22.9 pg/ml E2, CH4893237 (30 mg/kg) and fulvestrant (1 mg/body) showed potent growth inhibition (>70%) whereas tamoxifen (1, 10 and 100 mg/kg) showed strong tamoxifen resistance. In Br-10 xenografts with ovariectomized-level E2 (<16.7 pg/ml), tamoxifen (30 mg/kg) increased the tumor volume but CH4893237 (30 mg/kg) showed no agonistic activity. In the ERalpha and ERbeta proteolysis assays, the band pattern for CH4893237 was different from fulvestrant. Thus, CH48793237 showed potent antitumor efficacies without agonistic activity and superior ER degradation in human breast cancer xenografts with low serum E2. Furthermore, the proteolysis studies suggest that CH4893237 induces conformational changes of ER different from those induced by fulvestrant. Therefore, CH4893237 alone or in combination with an aromatase inhibitor may be an efficient treatment for postmenopausal breast cancer patients.