Expression of cyclooxygenase-2 in association with clinicopathological prognostic factors and molecular markers in epithelial ovarian cancer

OBJECTIVES: This study examines whether expression of COX-2 is associated with clinicopathological features and other molecular markers of ovarian cancer. METHODS: Sixty-four paraffin-embedded tissue specimens were obtained from patients with ovarian cancer who received cytoreductive surgery and combination chemotherapy. Tissue specimens were subjected to immunohistochemical analysis using antibodies to COX-2, p53, and VEGF. RESULTS: Increased COX-2 expression significantly correlated with histologic type (mucinous 5.6% vs. non-mucinous 65.2%, P<0.001). COX-2 expression was also significantly associated with stage, tumor grade, residual disease status, and presence of ascites. COX-2 expression correlated positively with expression of p53 (P=0.006) and VEGF (P=0.025). Although survival was lower in patients with high COX-2 expression than in those without high COX-2 expression (P<0.001), only tumor grade and stage were independent prognostic indicators. In patients with non-mucinous cancer, COX-2 expression correlated with stage (P<0.001) and presence of ascites (P=0.033). CONCLUSIONS: Our results suggest that expression of COX-2 in ovarian cancers is specific to histologic type of tumor and is associated with poor clinicopathologic prognostic factors. Expression of COX-2 also correlates well with expression of p53 and VEGF.     

SYNCRIP controls miR-137 and striatal learning in animal models of methamphetamine abstinence

Abstinence from prolonged psychostimulant use prompts stimulant withdrawal syndrome. Molecular adaptations within the dorsal striatum have been considered the main hallmark of stimulant abstinence. Here we explored striatal miRNA–target interaction and its impact on circulating miRNA marker as well as behavioral dysfunctions in methamphetamine (MA) abstinence. We conducted miRNA sequencing and profiling in the nonhuman primate model of MA abstinence, followed by miRNA qPCR, LC–MS/MS proteomics, immunoassays, and behavior tests in mice. In nonhuman primates, MA abstinence triggered a lasting upregulation of miR-137 in the dorsal striatum but a simultaneous downregulation of circulating miR-137. In mice, aberrant increase in striatal miR-137-dependent inhibition of SYNCRIP essentially mediated the MA abstinence-induced reduction of circulating miR-137. Pathway modeling through experimental deduction illustrated that the MA abstinence-mediated downregulation of circulating miR-137 was caused by reduction of SYNCRIP-dependent miRNA sorting into the exosomes in the dorsal striatum. Furthermore, diminished SYNCRIP in the dorsal striatum was necessary for MA abstinence-induced behavioral bias towards egocentric spatial learning. Taken together, our data revealed circulating miR-137 as a potential blood-based marker that could reflect MA abstinence-dependent changes in striatal miR-137/SYNCRIP axis, and striatal SYNCRIP as a potential therapeutic target for striatum-associated cognitive dysfunction by MA withdrawal syndrome.     

Development of cyclosporin A-loaded hyaluronic microsphere with enhanced oral bioavailability

To develop a hyaluronic microsphere with the improved oral bioavailability of poorly water-soluble cyclosporin A (CsA), the microspheres were prepared with varying ratios of sodium hyaluronate (HA)/sodium lauryl sulfate (SLS)/CsA using a spray-drying technique. The effects of HA and SLS on the dissolution and solubility of CsA in microspheres were investigated. The CsA-microsphere prepared with HA/SLS/CsA at the ratio of 4/2/1 gave the highest solubility and dissolution rate of CsA among those formulae tested. As solubility and dissolution rate of CsA were increased about 17- and 2-fold compared to CsA powder, respectively, this CsA-microsphere was selected as an optimal formula for oral delivery in rats. The CsA-microsphere and Sandimmun neoral sol gave significantly higher blood levels compared with CsA powder alone. Moreover, the AUC, T(max) and C(max) values of CsA in CsA-microsphere were not significantly different from those in Sandimmun neoral sol in rats, indicating that CsA-microsphere was bioequivalent to the commercial product in rats. Our results demonstrated that the CsA-microsphere prepared with HA and SLS, with improved bioavailability of CsA, might have been useful to deliver a poorly water-soluble CsA.     

Role of adjuvant chemoradiotherapy and chemotherapy in patients with resected gallbladder carcinoma: a multi-institutional analysis (KROG 19-04)

Objective:The effectiveness of adjuvant treatments for resected gallbladder carcinoma (GBC) has remained unclear due to lack of randomized controlled trials; thus, the aim of present study was to evaluate the role of adjuvant treatments, including chemoradiotherapy (CRT) and/or chemotherapy (CTx), in patients with resected GBC.Methods:A total of 733 GBC patients who received curative-intent surgical resection were identified in a multi-institutional database. Of 733 patients, 372 (50.8%) did not receive adjuvant treatment, whereas 215 (29.3%) and 146 (19.9%) received adjuvant CTx and CRT, respectively. The locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) of the adjuvant treatment groups were compared according to tumor stage (stage II vs. stage III–IV).Results:In stage II disease (n = 381), the 5-year LRFS, RFS, and OS were not significantly different among the no-adjuvant therapy, CTx, and CRT groups, and positive resection margin, presence of perineural invasion, and Nx classification were consistently associated with worse LRFS, RFS, and OS in the multivariate analysis (P < 0.05). For stage III–IV (n = 352), the CRT group had significantly higher 5-year LRFS, RFS, and OS than the no-adjuvant therapy and CTx groups (67.8%, 45.2%, and 56.9%; 37.9%, 28.8%, and 35.4%; and 45.0%, 30.0%, and 45.7%, respectively) (P < 0.05).Conclusions:CRT has value as adjuvant treatment for resected GBC with stage III–IV disease. Further study is needed for stage II disease with high-risk features.     

Venous Thromboembolism Risk in Asian Patients with Inflammatory Bowel Disease: A Population-Based Nationwide Inception Cohort Study

Background/AimsInflammatory bowel disease (IBD) is associated with the occurrence of venous thromboembolism (VTE). However, to date, there have been few studies on the risk of VTE in Asian IBD patients. We aimed to estimate the incidence of VTE in Asian IBD patients and to determine if IBD is related to increased VTE risk.MethodsWe performed a population-based cohort study between 2004 and 2015 using Korean National Health Insurance data. IBD and VTE were defined by ICD-10 codes. Incidence rates of VTE were calculated among patients with IBD and among age- and sex-matched controls. Hazard ratios were estimated using Cox regression with adjustment for multiple variables. We performed additional analyses stratifying by age, sex, Charlson comorbidity index (CCI) score, and disease type.ResultsAmong the 45,037 patients with IBD (IBD cohort) and 133,019 matched controls (non-IBD cohort) included in our analysis, 411 IBD patients and 641 controls developed VTE. The IBD cohort had a higher incidence rate ratio and risk of VTE than the non-IBD cohort (incidence rate ratio 1.92 and hazard ratio 1.93). Older age, female sex, higher CCI scores, cardiovascular disease, chronic kidney disease, use of steroids, and hospitalization were significant risk factors for VTE in patients with IBD.ConclusionsThe IBD patients in this study were approximately two times more likely to develop VTE than the non-IBD individuals. Our findings support the need for thromboprophylaxis in Asian IBD patients with various factors that further increase the risk of VTE.     

Triple Therapy-Based on Tegoprazan,a New Potassium-Competitive Acid Blocker,for First-Line Treatment of Helicobacter pylori Infection: A Randomized,Double-Blind,Phase III,Clinical Trial

Background/AimsWe examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication.MethodsA randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)-based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases.ResultsIn total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences.ConclusionsTPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT03317223","term_id":"NCT03317223"}}NCT03317223).     

Diagnosis and Prevention of Hypersensitivity Reactions to Iodinated Contrast Media

Iodinated contrast media (ICM) have become one of the major causes of drug hypersensitivity reactions (HSRs) related to increasing numbers of ICM-based radiological imaging procedures. Strategies for diagnosing and preventing ICM-induced HSRs have not been uniformly standardized yet. However, advances have been made based on the results of recent research. A previous history of hypersensitivity to ICM is the most significant risk factor for developing HSR by ICM. Avoidance of culprit agents and premedication is the main strategy to prevent recurrences of HSRs in high-risk patients. In addition, we strongly recommend identifying sensitized ICM using skin tests to determine immunoglobulin E-mediated or delayed-type allergy and to guide the choice of an alternative contrast agent. ICM provocation test procedures have been established and are helpful in selected cases. In this paper, we review how to evaluate patients who have experienced immediate or delayed HSRs caused by ICM to minimize the risk of recurrence and discuss unmet needs that require further research.     

Prevalence and risk of colorectal polyps among the Korean population under 50 years

Colorectal cancer is a common cancer; generally, adults aged ≥ 50 years are screened using stool occult blood tests and colonoscopy. However, colorectal adenoma and cancer have been found in patients under the aged of 50, and studies on characteristics and risk factors in young patients are lacking. We evaluated the prevalence and risk factors of colorectal adenoma and cancer in young adults aged under 50 years.We retrospectively analyzed 570 individuals aged under 50 years who underwent colonoscopy at the Haeundae Paik Hospital, Korea, from January to June 2018. Logistic regression model was used to identify the risk factors for colorectal adenoma and colorectal cancer.The prevalence of colorectal adenoma in group of 19–29 years was 3.2% (1 of 31), 30–39 years was 13.8% (30 of 217) and in the group of 40–49 years was 21.1% (68 of 322) (P = .009). In multivariable analysis, age over 45 years (adjusted odds ratio [OR], 1.941; 95% confidence interval [CI], 1.187–3.172; P = .008) and male sex (adjusted OR, 1.711; 95% CI, 1.044–2.806; P = .033) were independent risk factors for colorectal neoplasia including cancer.The prevalence of colorectal adenoma increases as the age increased in young adults under 50 years of age, especially after the age of 45 years, the risk of colorectal neoplasia increases; hence, early screening should be considered before the age of 50 years.     

Comparison of the effects of inhalational and total intravenous anesthesia on quality of recovery in patients undergoing endoscopic transsphenoidal pituitary surgery: a randomized controlled trial

Background: Endoscopic transsphenoidal pituitary surgery has shown promising results. However, fast and high-quality recovery after this procedure remains a challenge for neuroanesthesiologists. This study aimed to compare the quality of recovery after transsphenoidal pituitary surgery between patients who received inhalational anesthesia with sevoflurane and patients who received propofol-based total intravenous anesthesia (TIVA).Methods: Eighty-two patients undergoing transsphenoidal pituitary surgery were randomized to receive either sevoflurane inhalation with manual infusion of remifentanil (sevoflurane group) or effect-site target-controlled infusion of propofol and remifentanil (TIVA group). The primary outcome was the 40-item Quality of Recovery (QoR-40) score on postoperative day 1. The QoR-40 questionnaire was completed by patients the day before surgery and on postoperative days 1 and 2. Emergence agitation and recovery characteristics were also assessed.Results: There were no significant differences between the groups in the global QoR-40 scores on both postoperative days 1 and 2 (difference -8.7, 95% CI -18.0 to 0.7, and P = 0.204; -3.6, 95% CI -13.0 to 5.8, and P > 0.999, respectively). The time to verbal response and time to extubation were significantly shorter in the sevoflurane group than in the TIVA group (P < 0.001 and P < 0.001, respectively). However, the incidence of emergence agitation was lower in the TIVA group than in the sevoflurane group (P < 0.001).Conclusions: Both inhalational anesthesia with sevoflurane and propofol-based TIVA were appropriate anesthetic techniques for patients undergoing endoscopic transsphenoidal pituitary surgery in terms of the quality of recovery up to 2 days postoperatively. Rapid emergence was observed in the sevoflurane group, while smooth emergence was observed in the TIVA group.