ABSTRACT
Although endometriosis is a benign disease, it is associated with cancer-related gene mutations, such as KRAS or PIK3CA. Endometriosis is associated with elevated levels of inflammatory factors that cause severe pain. In a previous study, we demonstrated that KRAS or PIK3CA mutations are associated with the activation of cell proliferation, migration, and invasion in a patient-derived immortalized endometriotic cell line, HMOsisEC10. In this study, we investigated the effects of these mutations on progesterone resistance. Since the HMOsisEC10 had suppressed progesterone receptor (PR) expression, we transduced PR-B to HMOsisEc10 cell lines including KRAS mutant and PIK3CA mutant cell lines. We conducted a migration assay, invasion assay, and MTT assay using dienogest and medroxyprogestrone acetate. All cell lines showed progesterone sensitivity with or without mutations. Regarding inflammatory factors, real-time quantitative RT-PCR revealed that the KRAS mutation cell line exhibited no suppression of Cox-2 and mPGES-1 on progesterone treatment, whereas IL-6, MCP-1, VEGF, and CYP19A1 were significantly suppressed by progesterone in both mutated cell lines. Our results suggest that KRAS mutation and PIK3CA mutation in endometriotic cells may not be associated with progesterone resistance in terms of aggressiveness. However, KRAS mutations may be associated with progesterone resistance in the context of pain.
ABSTRACT
Background: The objective of this study was to assess functional, quality of life, and satisfaction outcomes of a hand surgery short-term surgical mission (STSM) to Honduras, and determine whether patient demographics and surgery characteristics during a surgical mission correlate with outcome. Methods: A total of 63 patients who received upper extremity surgery at a week-long hand surgery STSM to Honduras in March 2013 participated in the study. A before-after study design was used. Before receiving surgery, participants completed the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire and the Short Form 12 Health Survey version 2 (SF12v2). Four months postoperatively, participants completed the QuickDASH, SF12v2, and Satisfaction Survey. Results: The mean QuickDASH score significantly improved preoperatively to postoperatively. Demographics measures of age, sex, education, and income did not correlate with QuickDASH scores. Preoperative QuickDASH statistically significantly correlated with surgery type: Carpal tunnel patients had the highest scores (worst functioning). Postoperatively, mass excision and scar contracture/skin graft patients were correlated with the lowest scores. Carpal tunnel and tendon surgery patients showed greatest correlation with QuickDASH improvement. SF-12 scores revealed improvements in mental domains and declines in physical domains. Conclusions: Hand surgery performed during STSMs can result in significant functional improvement, regardless of socioeconomic status. Patients benefited from both simpler and more complex operations. Four months after surgery, general health-related quality of life measures showed improved mental indices. Measured physical indices declined despite improved QuickDASH scores. This may be due to the early general postoperative state. Further outcome research in STSMs in additional countries and specialties is required to expand our conclusions to other STSM contexts and guide best practices in STSMs.
