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.

Processing of ferromanganese fumes into high-purity manganese sulphate monohydrate.

A novel process for recovering manganese (Mn) values from two types of ferromanganese (FeMn) fumes (wastes from smelters) was developed incorporating several stages of leaching, roasting, and precipitation. Fumes containing high K (as K2O) were first leached in water at ambient conditions to recover K, purified to remove metal impurities, and precipitated as 99.9% pure K2SO4. The residues containing Mn and remaining impurities were then leached in sulfuric acid at 80 °C using oxalic acid as reductant yielding Mn sulphate liquors. The leach liquors were then purified to remove Fe at 95°C as jarosite at pH 2.8 and Fe(III) hydroxides at pH 5.5. Base and transition metal impurities were removed as sulfides. K, Na, Ca, and Mg were separated from Mn in a novel step based on precipitation of Mn hydroxide from the Mn sulphate liquors. Subsequent redissolution of Mn hydroxide in sulfuric acid under reducing conditions using oxalic acid produced a high purity Mn sulphate liquors containing <5 ppm of these impurities. After evaporation by boiling manganese sulphate monohydrate (MSM) was crystallized, achieving purity >99.5%. Another fume containing oil contaminants having low K was subjected to sulfation roasting to produce Mn sulphate. The calcine was water leached to produce Mn sulfate liquors and treated in a similar process to make high purity MSM. Novelty aspects of the proposed process include the recovery of K as a by-product and separation of Mn2+ from other impurities by its selective precipitation to produce a high purity Mn sulphate solution for MSM recovery. Implications: Ferro-manganese smelters discharge wastes (fumes) that are collected by bag filters or electrostatic precipitators and then store them on the ground with coverage to prevent their dispersion into the surrounding atmosphere. The work presented propose a process to reprocess these wastes into high purity manganese sulphate monohydrate (MSM). Processing of wastes containing high potassium as KOH also yields high purity potassium sulfate used as fertilizers. Some smelters spray oil onto the fume dumps to prevent material being blown onto the surrounding area. The oil-contaminated fumes have to be first roasted to burn off the oil, before they can be processed. The process developed therefore converts a hazardous waste into high purity MSM and potassium sulphate used in many applications.

Structural Characteristics of a Conical-Frustum-Patterned Stretchable Heater in an External-Force Environment.

Stretchable heaters are mechanically and biomedically advantageous because they are more flexible than the conventional microheaters. To determine the way that a heater can be used appropriately in a wide range of application fields, studies on the mechanical and thermal characteristics regarding various film configurations are underway. In this study, the mechanical characteristics of conical-frustum-patterned stretchable heaters with various configurations with upper-radius (R1), bottom-radius (R2), and height (h) aspect ratios were numerically investigated when tensile forces and bending moments were applied to the film of heater. The temperature and von Mises stress of the film were analyzed using the commercial software COMSOL ver. 5.2. The structural characteristics of a conical-frustum-patterned stretchable heater were evaluated under external load, and results are graphically depicted.

Association of Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms with Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.

Osteoporosis and osteoporotic fractures are strongly associated with mortality and morbidity, both in developing and developed countries. Menopause accelerates bone loss due to estrogen deficiency and age-related linear bone loss. We investigated plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms in postmenopausal women with osteoporotic vertebral compression fractures (OVCFs). In this case-control study, 355 postmenopausal women were genotyped for the presence of PAI-1 gene polymorphisms -844A > G, -675 4G > 5G, 43G > A, 9785A > G, and 11053T > G. Genetic polymorphisms of PAI-1 were analyzed by the polymerization chain reaction restriction fragment length polymorphism assay, and their association with disease status and folate and homocysteine levels was determined in 158 OVCF patients and 197 control subjects. The PAI-1 -675 5G5G (adjusted odds ratio (AOR), 3.302; p = 0.017) and 43GA + AA (AOR, 2.087; p = 0.042) genotype frequencies showed significant association with the increased prevalence of OVCFs in postmenopausal women. In addition, we performed gene-environment interaction studies and demonstrated an association between PAI-1 gene polymorphisms and OVCF prevalence. Our novel finding is the identification of several PAI-1 genetic variants that increase susceptibility to OVCF. Our findings suggest that polymorphisms in PAI-1 may contribute to OVCF, and that they can be developed as biomarkers for evaluating OVCF risk.

[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.

Erythroid cell-specific alpha-globin gene regulation by the CP2 transcription factor family.

We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of alpha-globin occurred following dimerization between CP2b and CP2c in erythroid K562 and MEL cells, but this dimerization did not activate the alpha-globin promoter in nonerythroid 293T cells, indicating that an additional erythroid factor is missing in 293T cells. PIAS1 was confirmed as a CP2 binding protein by the yeast two-hybrid screen, and expression of CP2b, CP2c, and PIAS1 in 293T cell induced alpha-globin promoter activation. These results show that ubiquitously expressed CP2b exerts potent erythroid cell-specific alpha-globin gene expression by complexing with CP2c and PIAS1.