Endometriosis causes increased central sensitivity to noxious stimuli. Treatment with TSA significantly reduces lesion growth and may relieve pain symptoms in women with endometriosis, indicating that histone deacetylase inhibitors may be a promising therapeutic agent.

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Adenomyosis is a fairly common gynecologic disease with unknown pathogenesis. We sought to investigate as to whether the promoter of progesterone receptor isoform B (PR-B) is hypermethylated in adenomyosis and to investigate the treatment of ectopic endometrial stromal cells with trichostatin A (TSA), a histone deacetylase inhibitor (HDI), and 5-aza-2-deoxycytidine (ADC), a demethylation agent, on PR-B gene and protein expression, and on cell viability. Ectopic endometrial tissue specimens were obtained from 9 women with adenomyosis whereas control endometrial tissue samples were obtained from 8 women with surgically diagnosed benign ovarian cysts but without any clinical history of endometriosis/adenomyosis/ myoma. Endometrial stromal cells were isolated, purified, cultured, and analyzed by methylation-specific polymerase chain reaction (PCR), real-time reverse transcriptase PCR (RT-PCR), and Western blot analysis, cell viability assays, and fluorescence-activated cell sorting. We found that none of the normal endometrial stromal cells had PR-B promoter methylation. In contrast, 2 out of 3 ectopic endometrial stromall cells had PR-B hypermethylation (P < .05). The treatment with both TSA and ADC elevated PR-B gene and protein expression in ectopic, but not in normal, endometrial stromal cells. Both TSA and ADC treatment dose-dependently reduced cell viability of ectopic endometrial stromal cells. Trichostatin A and ADC treatment also suppressed the cell cycle progression in ectopic endometrial stromal cells. Thus, this study provides the first piece of evidence that adenomyosis has epigenetic aberration and may also be an epigenetic disease amenable to rectification by pharmacological means. This perspective may shed new light onto the pathogenesis of adenomyosis and lead to novel ways to treat the disease.

These results suggest that TF is involved in adenomyosis-associated heavy menstrual bleeding and dysmenorrhea and thus may be a potential therapeutic target in treating symptomatic adenomyosis and perhaps also chronic pelvic pain in women with adenomyosis.

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Background/Aims: Adenomyosis is a common condition with a poorly understood pathogenesis. Recent data suggest that it may be an epigenetic disease. This study investigated the expression and localization of class I histone deacetylases (HDACs) in women with and without adenomyosis. Methods: The ectopic and homologous eutopic endometrium of 50 women with adenomyosis and the endometrium of 18 age- and menstrual phase-matched women without adenomyosis were used for immunohistochemical analysis. Tissue sections were immunostained with HDAC1, -2, and -3. Microscopic evaluation to assess the presence and localization of HDAC1–3 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with adenomyosis was performed and compared with the normal endometrium. Results: We found that, compared with the normal endometrium, immunoreactivity against HDAC1 and HDAC3 was higher in both the eutopic and the ectopic endometrium. Increased HDAC2 in the eutopic endometrium was found to be associated with the severity of dysmenorrhea. Conclusion: Given the potential wide-ranging effect of histone deacetylation on gene expression, these findings suggest that HDACs may be involved in adenomyosis. They also suggest the possibility that HDAC2 may be involved in dysmenorrhea and its severity and that HDACs may be potential therapeutic targets in adenomyosis.

ObjectiveThe aim of this study was to compare the surgical outcomes of robotic-assisted radical hysterectomy (RRH) with traditional laparoscopic radical hysterectomy (TLRH) for the treatment of early-stage cervical cancer in a large retrospective cohort of a total of 933 patients.MethodsWe have enrolled 100 patients into the RRH and 833 patients into the TLRH group. The surgical outcomes include operating time, blood loss, transfusion rate, pelvic lymph node yield, hospitalization days, duration of bowel function recovery, catheter removal before and after 3 weeks, conversion to laparotomy, and intraoperative and postoperative complications. Follow-up results were also analyzed for all patients.ResultsBoth groups have similar patient and tumor characteristics but patients with a larger lesion size were preferably enrolled in the TLRH treatment group. The treatment with RRH was generally superior to TLRH with respect to operating time, blood loss, length of hospitalization, duration of bowel function recovery, and postoperative complications. On follow-up of patients, there were no relapses reported in the RRH group compared with 4% of relapse cases and 2.9% of deaths because of metastasis in the TLRH group. No conversion of laparotomy occurred in the RRH group. No significant difference was found with respect to intraoperative complications and blood transfusion between both groups.ConclusionsThe results from this study suggest that RRH is superior to TLRH with regard to surgical outcome and may pose a safe and feasible alternative to TLRH. The operating time and lymph node yield is acceptable. Our study is one of the largest single-center studies of surgical outcomes comparing RRH with TLRH during cervical cancer treatment and will significantly contribute to the safety of alternative treatment options for patients. Furthermore, the difference detected between TLRH and RRH group is further strengthened by the great expertise of the surgeon performing laparoscopic surgeries.