Delta neutrophil index and symptomatic time are effective factors for predicting perforated appendicitis.

ABSTRACT: Appendicitis is a common intra-abdominal inflammatory disease, and morbidity increases with age when perforation occurs. Because, not all patients require emergency surgery, there have been numerous studies on factors for predicting perforated appendicitis. In this study, we aimed to confirm whether the delta neutrophil index (DNI) and the time from symptom onset to surgery are effective predictors for perforated appendicitis in different age groups.This was a retrospective study conducted on 542 appendicitis patients who underwent surgery at Kangdong Sacred Heart Hospital. The simple group consisted of 431 subjects, and the perforation group consisted of 111 subjects.Multiple logistic regression analyses demonstrated that age, neutrophil percentage, DNI, C-reactive protein (CRP), and symptomatic time were significant predictors of perforation. Analysis of the receiver-operating characteristic curve showed that the DNI was the most reliable predictive value. In the analyses according to age, the perforation rate was higher in the >65-year-age group; these patients also had a higher DNI, CRP, and symptomatic time. In the DNI analysis using receiver operating characteristic (ROC) analysis, the area under the curve was higher in the >65-year-age group than in other age groups. In addition, the cutoff values have been determined and perforation occurred significantly in the group with a DNI value of 2.1 or higher and a symptomatic time of 33 hours or longer.DNI is effective in predicting perforation in patients with appendicitis compared with other inflammatory factors. Furthermore, the simultaneous measurement of symptomatic time and DNI is helpful in predicting perforation and determining whether emergency surgery is necessary.

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress.

BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.

Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR).

BACKGROUND: Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. METHODS/DESIGN: Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. DISCUSSION: This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01589367.

Interleukin-32ß stimulates migration of MDA-MB-231 and MCF-7cells via the VEGF-STAT3 signaling pathway.

BACKGROUND: IL-32 is known to play an important role in inflammatory and autoimmune disease responses. In addition to its role in these responses, IL-32 and its different isoforms have in recent years been implicated in the development of various cancers. As of yet, the role of IL-32 in breast cancer has remained largely unknown. RESULTS: By performing immunohistochemical assays on primary breast cancer samples, we found that the level of IL-32ß expression was positively correlated with tumor size, number of lymph node metastases and tumor stage. In addition, we found that breast cancer-derived MDA-MB-231 cells exogenously expressing IL-32ß exhibited increased migration and invasion capacities. These increased capacities were found to be associated with an increased expression of the epithelial mesenchymal transition (EMT) markers vimentin and Slug, the latter of which is responsible for the increase in vimentin transcription. To next investigate whether IL-32ß enhances migration and invasion through a soluble factor, we determined the levels of several migration-stimulating ligands, and found that the production of VEGF was increased by IL-32ß. In addition, we found that IL-32ß-induced VEGF increased migration and invasion through STAT3 activation. CONCLUSION: The IL-32ß-VEGF-STAT3 pathway represents an additional pathway that mediates the migration and invasion of breast cancer cells under the conditions of normoxia and hypoxia.