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To investigate the safety and efficacy of adjuvant gonadotropin-releasing hormone agonist (GnRH-a) treatment followed by maintenance dienogest (DNG) therapy after uterus-sparing surgery.In this retrospective cohort study, a total of 190 patients with severe adenomyosis underwent uterus-sparing surgery between January 2010 and June 2020. Of these patients, 90 were analyzed. Forty-six patients (control group) received adjuvant 6-month GnRH-a therapy alone after uterus-sparing surgery, and 44 patients (maintenance group) received postoperative 6-month GnRH-a treatment followed by maintenance DNG therapy (2 mg per day orally). The median follow-up period was 18 months. The study was analyzed using generalized estimating equations (GEE).At baseline, the characteristics of patients in each group were comparable. Compared to the control group, the maintenance group had a significant improvement in the visual analog scale score of dysmenorrhea (P0.001), hemoglobin level (P=0.004), and uterine volume (P=0.004) from baseline to 18 months after uterus-sparing surgery. The symptom recurrence rate was significantly lower in the maintenance group than in the control group (4.6% vs. 37.0%, P0.001).The findings of this study suggest that combinatorial treatment with GnRH-a (adjuvant treatment) and DNG (maintenance therapy) represents a safe and effective short-term therapy after uterus-sparing surgery for adenomyosis.

Epithelial ovarian cancer is a highly heterogeneous and malignant female cancer with an overall low survival rate. Mutations in p53 are prevalent in the major ovarian cancer histotype, high-grade serous ovarian carcinoma (HGSOC), while p53 mutations are much less frequent in other ovarian cancer subtypes, particularly in ovarian clear cell carcinoma (OCCC). Advanced stage OCCC with wild-type (WT) p53 has a worse prognosis and increased drug resistance, metastasis, and recurrence than HGSOC. The mechanisms responsible for driving the aggressiveness of WT p53-expressing ovarian cancer remain poorly understood. Here, we found that upregulation of MEX3A, a dual-function protein containing a RING finger domain and an RNA-binding domain, was critical for tumorigenesis in WT p53-expressing ovarian cancer. MEX3A overexpression enhanced the growth and clonogenicity of OCCC cell lines. In contrast, depletion of MEX3A in OCCC cells, as well as ovarian teratocarcinoma cells, reduced cell survival and proliferative ability. MEX3A depletion also inhibited tumor growth and prolonged survival in orthotopic xenograft models. MEX3A depletion did not alter p53 mRNA level but did increase p53 protein stability. MEX3A-mediated p53 protein degradation was crucial to suppress ferroptosis and enhance tumorigenesis. Consistently, p53 knockdown reversed the effects of MEX3A depletion. Together, our observations identified MEX3A as an important oncogenic factor promoting tumorigenesis in ovarian cancer cells expressing WT p53. Significance: Degradation of p53 mediated by MEX3A drives ovarian cancer growth by circumventing p53 tumor suppressive functions, suggesting targeting MEX3A as a potential strategy for treating of ovarian cancer expressing WT p53.

Ovarian clear cell carcinoma (OCCC), a chemoresistant ovarian cancer, shows a modest response to anti-programmed death-1/programmed death ligand-1 (PD-1/PD-L1) therapies. The effects of anti-PD-1/PD-L1 therapies rely on cytotoxic T-cell response, which is triggered by antigen presentation mediated by major histocompatibility complex (MHC) class I. The loss of MHC class I with simultaneous PD-L1 expression has been noted in several cancer types; however, these findings and their prognostic value have rarely been evaluated in OCCC. We collected data from 76 patients with OCCC for clinicopathologic analysis. Loss of MHC class I expression was seen in 44.7% of the cases including 39.3% to 47.4% of the PD-L1 + cases and was associated with fewer CD8 + tumor-infiltrating lymphocytes (TILs). PD-L1 positivity was associated with a higher number of CD8 + TILs. Cox proportional hazard models showed that high (≥50/mm 2 ) CD8 + TILs was associated with shorter disease-specific survival (hazard ratio [HR]=3.447, 95% confidence interval [CI]: 1.222-9.720, P =0.019) and overall survival (HR=3.053, 95% CI: 1.105-8.43, P =0.031). PD-L1 positivity using Combined Positive Score was associated with shorter progression-free survival (HR=3.246, 95% CI: 1.435-7.339, P =0.005), disease-specific survival (HR=4.124, 95% CI: 1.403-12.116, P =0.010), and overall survival (HR=4.489, 95% CI: 1.553-12.972, P =0.006). Loss of MHC class I may contribute to immune evasion and resistance to anti-PD-1/PD-L1 therapies in OCCC, and CD8 + TILs and PD-L1 positivity using Combined Positive Score may have a negative prognostic value.

RNAseq: Gene expression fold-change between sh-MEX3A and sh-Ctrl

Table S1. Short tandem repeat of ovarian teratocarcinoma and clear cell carcinoma cell line. Figure S1. MEX3A expression promoted tumorigenic ability and cell survival in WT p53 OC cells. Figure S2. The p53 pathway was enriched in upregulated genes in MEX3A-depleted OC cells expressing WT p53. Figure S3. Stabilized WT p53 protein in MEX3A-depleted cells was activated. MEX3A did not interact with or affect the level of mutant p53 protein. Figure S4. p53 depletion alone did not significantly affect cell proliferation or cell death in MEX3A expressing WT p53 OC cells. Figure S5. MEX3A and MDM2 in OC.

Epithelial ovarian cancer is a highly heterogeneous and malignant female cancer with an overall low survival rate. Mutations in p53 are prevalent in the major ovarian cancer histotype, high-grade serous ovarian carcinoma (HGSOC), while p53 mutations are much less frequent in other ovarian cancer subtypes, particularly in ovarian clear cell carcinoma (OCCC). Advanced stage OCCC with wild-type (WT) p53 has a worse prognosis and increased drug resistance, metastasis, and recurrence than HGSOC. The mechanisms responsible for driving the aggressiveness of WT p53-expressing ovarian cancer remain poorly understood. Here, we found that upregulation of MEX3A, a dual-function protein containing a RING finger domain and an RNA-binding domain, was critical for tumorigenesis in WT p53-expressing ovarian cancer. MEX3A overexpression enhanced the growth and clonogenicity of OCCC cell lines. In contrast, depletion of MEX3A in OCCC cells, as well as ovarian teratocarcinoma cells, reduced cell survival and proliferative ability. MEX3A depletion also inhibited tumor growth and prolonged survival in orthotopic xenograft models. MEX3A depletion did not alter p53 mRNA level but did increase p53 protein stability. MEX3A-mediated p53 protein degradation was crucial to suppress ferroptosis and enhance tumorigenesis. Consistently, p53 knockdown reversed the effects of MEX3A depletion. Together, our observations identified MEX3A as an important oncogenic factor promoting tumorigenesis in ovarian cancer cells expressing WT p53.Significance:Degradation of p53 mediated by MEX3A drives ovarian cancer growth by circumventing p53 tumor suppressive functions, suggesting targeting MEX3A as a potential strategy for treating of ovarian cancer expressing WT p53.

This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions.This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart.Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s).The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time.• Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. • Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.

To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence.The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021.Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence.Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls.In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.

Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

Endometrial stromal tumors are rare uterine tumors (

Objective: To investigate the effectiveness and safety of a new single-incision mini-sling (SIMS)—Ajust—compared with the standard transobturator midurethral sling (SMUS)—Align—for the treatment of female stress urinary incontinence (SUI). Materials and Methods: A retrospective cohort study was conducted between January 1, 2010 and August 31, 2012. Women with SUI who underwent either SMUS-Align or SIMS-Ajust were recruited. The primary outcomes included operation time, estimated operative blood loss, postoperative pain, and complications. The secondary outcomes included subjective and objective success, defined as an International Consultation on Incontinence Questionnaire (ICIQ) score of 0 or improvement as felt by the patient and a long-term complication, such as dyspareunia and mesh erosion after 6 months and 12 months of follow-up. Results: A total of 136 patients were enrolled, including 76 receiving SMUS-Align and 60 receiving SIMS-Ajust. Baseline characteristics of the patients in both groups were similar, without a statistically significant difference. Primary outcomes between both groups were similar, except that women treated with SIMS-Ajust had statistically significantly shorter operation time (p = 0.003), less intent to treat (p

Objective To evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing the recurrence of postoperative adenomyosis-related symptoms. Materials and methods From January 2005 through December 2014, a retrospective study including 133 patients with symptomatic adenomyosis undergoing conservative uterine-sparing surgery followed by gonadotropin-releasing hormone agonist treatment was conducted. We excluded the 18 patients who did not meet the inclusion criteria. The patients of intervention group (n = 54) received a levonorgestrel-releasing intrauterine system (LNG-IUS), which was inserted after surgery. The patients without LNG-IUS insertion were enrolled in the control group (n = 61). The primary outcome was improvement of adenomyosis-related dysmenorrhea, which was evaluated by the visual analog scale (VAS) and by hemoglobin (Hgb) and CA-125 levels. Results Over a 12-month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a VAS score (mean ± SD: 6.5 ± 2.5 vs 4.1 ± 3.6, p = 0.001) and a greater elevation in the Hgb level (2.1 ± 1.9 vs 1.0 ± 1.7, p = 0.008) than the control group. At the end of the 24-month follow-up period, the intervention group also exhibited a greater reduction in dysmenorrhea as assessed with a VAS score (mean ± SD 6.1 ± 2.7 vs 3.7 ± 3.7, p = 0.002) and a greater elevation in the Hgb level (1.9 ± 2.1 vs 0.7 ± 1.8, p = 0.022) than the control group. The CA-125 level was significantly lower in the intervention group during the postoperative follow up (12th month follow-up, intervention vs control, 24.5 ± 28.8 vs 50.1 ± 44.0, p = 0.005; 24th month follow-up, 28.6 ± 26.2 vs 75.4 ± 68.5, p = 0.002). Conclusion The maintenance therapy of LNG-IUS is effective and well accepted for long-term therapy after conservative surgery for patients with adenomyosis.

Objective Conventional laparoscopic myomectomy (LM) has inherent limitations due to its rigid structure. The robotic system is a newly developed technology equipped with a flexible EndoWrist that offers good performance in delicate motions. Our objective was to share our clinical experience in the management of complex myomectomy using this robotic system. Materials and methods From October 2010 to March 2012, 21 patients with symptomatic complex uterine myomas were evaluated. Complex myomectomy was defined as surgery involving more than two fibroids, large fibroids, or preexisting pelvic adhesions. We recorded and analyzed the preoperative characteristics of the patients and the fibroids, the detailed surgical time, and several postoperative outcomes to evaluate the feasibility and efficacy of robotic-assisted LM (RALM) for complex fibroids. Results A total of 21 patients were enrolled in this study. The mean age of the patients was 40.1 ± 4.5 years and the mean size of the largest fibroid was 7.3 ± 3.5 cm. RALM achieved satisfactory results, including a short postoperative hospital stay (3.1 ± 0.9 days), a low conversion rate (none of our patients required conversion to either a minilaparotomy or conventional open surgery), and a low complication rate (1 case in 21 patients, 4.8%). The average estimated blood loss was 235.7 ± 283.3 mL. Conclusion Our study results demonstrated that RALM is a safe and effective method for handling complex fibroids.

Objective To improve the understanding of primary fallopian tube carcinoma (PFTC) through an analysis of possible clinical and pathologic determinants of prognosis. Methods A retrospective review of the database of a tertiary hospital in Taiwan for 1978–2007 was conducted to identify patients with a diagnosis of PFTC and to evaluate the clinicopathologic features associated with PFTC outcome. Results Fifty-eight patients (mean age 62.5 years) had a diagnosis of PFTC. Stage III/IV disease (55%) and poorly differentiated tumors (52%) were most common. The median follow-up was 93 months (range, 11–333 months). The 5-year disease-free survival rate was 59%, and the overall survival rate was 64%. Factors important in disease-free and overall survival in univariate analysis included the presence of pelvic and/or para-aortic lymph node metastases, International Federation of Gynecology and Obstetrics stage, high preoperative carbohydrate antigen 125 serum level, completion of optimal debulking surgery, and the use of paclitaxel-based chemotherapy; however, only patients with optimal cytoreduction had a decreased hazard of recurrence (hazard ratio [HR] 0.06; 95% confidence interval [CI] 0.01–0.23) and mortality (HR 0.08; 95% CI, 0.02–0.31) in multivariate analysis. Conclusion Advanced tumor stage, in particular the presence of lymph node metastases, worsened the prognosis of patients with PFTC. However, optimal debulking surgery significantly improved the prognosis, emphasizing the importance of the treatment strategy.

Background Epithelial ovarian cancer is basically a heterogeneous disease with different chemosensitivity and distinct molecular alternations for each histological subtype. In order to assess whether the results of clinical trials can be extrapolated to a new country, it is critical to first examine whether the relative frequencies is homogenous across countries. Methods Cancer registry database from a single institution in Taiwan combined with systematic review of the global literature on the relative frequencies of histological subtypes between 2003 and 2012 was provided. Results Of 175 titles identified, 41 studies met inclusion/exclusion criteria. Globally, for each subtype, the median value of relative frequencies for serous subtype was 45.0%, with the Philippines (16.0%), Indonesia (22.7%), and Brazil (30.1%) as the three lowest countries and South Africa (68.0%), Greece (71.5%), and India (86.7%) as the three highest countries; for mucinous subtype, 11.4%, Italy (3.0%), Australia (3.4%), and Japan (5.4%) were the three lowest countries, while Indonesia (29.1%), Singapore (30.3%), and South Korea (38.6%) were the three highest countries; for endometrioid subtype, 12.6%, India (1.6%), Greece (5.7%), and Portugal (7.6%) were the three lowest countries, while Taiwan (24.8%), Egypt (25.0%), and Austria (25.5%) were the three highest countries; and for clear cell subtype, 5.3%, Pakistan (1.0%), Iran (2.0%), and Brazil (2.1%) were the three lowest countries while Thailand (16.0%), Taiwan (16.8%), and Spain (18.8%) were the three highest countries. Conclusions Relative frequencies of subtypes were not homogenous across countries. This diversity may reflect the geographical and ethnic variations. Globally, epithelial ovarian cancer is a heterogeneous disease with a heterogeneous distribution pattern.

Objective: Epithelial ovarian cancer and relapsed type II endometrial cancer share common characteristics. Although the role of intraperitoneal (IP) chemotherapy in the treatment of epithelial ovarian cancer has been well-established, its role in the treatment of relapsed type II endometrial cancer remains to be elucidated.Material and Methods: From January 2000 to December 2012, patients who were diagnosed with relapsed type II endometrial cancer and underwent secondary cytoreductive surgery, patients with residual tumors less than 1 cm in diameter were initially screened for this study. Of the screened patients, consecutive patients who received salvage IP chemotherapy (IP platinum plus intravenous paclitaxel) were considered the case group. The case study group was matched to a control group that was composed of patients who received salvage systemic chemotherapy (intravenous platinum plus intravenous paclitaxel) in a 1:2 ratio. The overall survival was compared between the case group and the control group, and the IP treatment-related toxicities were reported.Results: In total, 11 patients were assigned into the case group and 22 patients were assigned into the control group. The median overall survival (95% confidence interval) was 40.5 (25.5–56.2) months for the case group versus 28.0 (18.0–37.0) for the control group (hazard ratio=0.37 (95% confidence interval, 0.15–0.95); p=0.032, by the log-rank test). The most commonly observed toxicity was of gastrointestinal origin (81.8%). Toxicities that stemmed from hematological, cardiovascular, neurological, and catheter-related complications were similar to results published in other studies on IP chemotherapy for ovarian cancer.Conclusion: Salvage IP chemotherapy may potentially confer a longer overall survival than conventional systemic chemotherapy in the treatment of relapsed type II endometrial cancer.

We recruited consecutive patients with stage III epithelial ovarian, tubal, and peritoneal cancers who had optimal residual tumor after primary cytoreductive surgery and who received intraperitoneal chemotherapy between 2002 and 2012. Two propensity score-matched sample cohorts were created. We found that the addition of paclitaxel as a second intraperitoneal agent on a 3-week dosing schedule did not yield significant incremental survival benefits over the intraperitoneal delivery of a single cisplatin-based regimen. If our findings could be confirmed by a prospective randomized study, then it would be interesting to explore the efficacy of shifting back to a dose-dense intraperitoneal delivery of paclitaxel or a dose-dense delivery of a new formulation of paclitaxel for the patients with stage III epithelial ovarian, tubal, and peritoneal cancers.

Uterine sarcomas account for 3–7% of all uterine cancers. Because of their rarity, unknown etiology, and highly divergent genetic aberration, there is a lack of consensus on risk factors for occurrence and predictive poor outcomes as well as optimal therapeutic choices. Tumor types according to the World Health Organization classification include leiomyosarcoma, endometrial stroma sarcoma, and undifferentiated sarcoma. Staging is done using the 2014 Federation International Gynecology and Obstetrics and 2010 American Joint Committee on Cancer tumor, lymph node, and metastases systems. Tumor grade can be classified based on the French Federation of Cancer Centers Sarcoma Group system or the Broder’s system that incorporates tumor differentiation, mitotic count, and tumor necrosis. This review is a series of articles discussing uterine sarcoma, and this is Part I, which focuses on one of the subtypes of uterine sarcomas—uterine leiomyosarcoma. The clinical characteristics, diagnosis, outcome, and recent advances are summarized in this article.

Endometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities.

Studies have suggested that endometriosis may coexist with irritable bowel syndrome (IBS). Using a population-based cohort study, we followed subjects for a 5-year period to identify the risk of IBS after a diagnosis of endometriosis. This cohort study used the Taiwan National Health Insurance Database as a source of subjects. A total of 6076 patients with endometriosis from 2000 to 2005 were identified. Their data were compared with those of 30,380 age-matched controls without endometriosis who were randomly selected from the same database. All subjects were tracked for 5 years from the date of cohort entry to identify the risk of IBS. The Cox model was used to evaluate the 5-year event occurrence of IBS. Nine hundred twenty-six patients were diagnosed with IBS, including 256 in the case cohort (4.2 %) and 670 in the control cohort (2.2 %). The Kaplan-Meier survival curves demonstrated significantly lower event-free rates in the case cohort than in the control cohort (P = 0.001). After adjusting for urbanization level, monthly income, residential region and comorbidities, the hazard ratio (HR) within 5 years revealed a 1.79-fold (95 % confidence interval [CI] 1.55–2.07) greater risk among the cases than the controls. The HR was higher within the first year of follow-up (HR 1.90, 95 % CI 1.42–2.55) and in those women aged 25–34 years (HR 2.17, 95 % CI 1.61–2.92). The risk of IBS among endometriosis patients persisted over 5 years of follow-up. The association detected in this study might have proceeded through shared risk and pathogenic factors.

Taxol(®) remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resistant cell line (TR) was established at first. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol(®) versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol(®) (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

Acyclovir is a commonly used antiviral agent for the treatment of herpes simplex and herpes zoster infection. According to the Food and Drug Administration, it is classified as a category B drug and is safe for use during pregnancy [1]. Adverse effects of acyclovir include mild symptoms, such as nausea, vomiting, and diarrhea, to more severe symptoms, including neutropenia, hepatitis, and StevenseJohnson syndrome [2]. Reversible nephrotoxicity can be diagnosed in approximately 5e10% of patients undergoing intravenous (IV) administration. The precipitation of acyclovir crystals results in kidney damage and a rapid rise in serum creatinine [3,4]. However, drug-associated complications during pregnancy have not been documented. A 33-year-old pregnant woman, G2P1, at 31 weeks' gestation presented at the outpatient department with a 2-day history of generalized tiny vesicles on the erythematous base over her trunk and genital area. She was previously started on oral acyclovir (800 mg 4 times daily) under the impression of chickenpox by a dermatologist. Additionally, she reported abdominal tightness, poor intake, and general weakness. Fetal nonstress test showed uterine contractions. The patient was admitted for management of preterm labor in association with chickenpox. Upon admission, her blood pressure was 118/67 mmHg, dipstick test of urinalysis showed trace proteins, and laboratory findings revealed a hemoglobin level of 10.7 g/dL and a hematocrit of 33.9%. The differential counts of lymphocytes and monocytes were 10.7% and 11.2%

Background According to 3 randomized trials, the levonorgestrel-releasing intrauterine system significantly reduced recurrent endometriosis-related pelvic pain at postoperative year 1. Only a few studies have evaluated the long-term effectiveness of the device for preventing endometrioma recurrence, and the effects of a levonorgestrel-releasing intrauterine system as a maintenance therapy remain unclear. Objective The objective of the study was to evaluate whether a maintenance levonorgestrel-releasing intrauterine system is effective for preventing postoperative endometrioma recurrence. Study Design From May 2011 through March 2012, a randomized controlled trial including 80 patients with endometriomas undergoing laparoscopic cystectomy followed by six cycles of gonadotropin-releasing hormone agonist treatment was conducted. After surgery, the patients were randomized to groups that did or did not receive a levonorgestrel-releasing intrauterine system (intervention group, n = 40, vs control group, n = 40). The primary outcome was endometrioma recurrence 30 months after surgery. The secondary outcomes included dysmenorrhea, CA125 levels, noncyclic pelvic pain, and side effects. Results Endometrioma recurrence at 30 months did not significantly differ between the 2 groups (the intervention group, 10 of 40, 25% vs the control group 15 of 40, 37.5%; hazard ratio, 0.60, 95% confidence interval, 0.27–1.33, P = .209). The intervention group exhibited a lower dysmenorrhea recurrence rate, with an estimated hazard ratio of 0.32 (95% confidence interval, 0.12–0.83, P = .019). Over a 30 month follow-up, the intervention group exhibited a greater reduction in dysmenorrhea as assessed with a visual analog scale score (mean ± SD, 60.8 ± 25.5 vs 38.7 ± 25.9, P P = .014, 95% confidence interval, 1.9–16.1), and CA125 (median [interquartile range], –32.1 [–59.1 to 14.9], vs –15.6 [–33.0 to 5.0], P = .001) compared with the control group. The number-needed-to-treat benefit for dysmenorrhea recurrence at 30 months was 5. The number of recurrent cases requiring further surgical or hormone treatment in the intervention group (1 of 40, 2.5%, 95% confidence interval, –2.3% to 7.3%) was significantly lower than that in the control group (8 of 40, 20%, 95% confidence interval, 7.6–32.4%; P = .031). Conclusion Long-term maintenance therapy using a levonorgestrel-releasing intrauterine system is not effective for preventing endometrioma recurrence.

Currently, epithelial ovarian cancer is viewed as a heterogeneous disease with five major histological subtypes. Clear cell carcinoma represents a specific histological subtype of epithelial ovarian cancer that demonstrates more aggressive clinical behavior and drug resistance compared with other subtypes. Nevertheless, clear cell carcinoma is treated in the same manner as the other subtypes without any particular consideration to its unique clinical characteristics. To improve the therapeutic efficacy of the current liposomal doxorubicin approach for the treatment of clear cell carcinoma, we aimed to develop a novel peptide-conjugated liposomal doxorubicin to actively target this subtype. Two phage clones (OC-6 and OC-26) that specifically bound to clear cell carcinoma were isolated from a phage peptide display library after biopanning procedures. The peptide sequences were translated and aligned (OCSP-6 for OC-6, and OCSP-26 for OC-26, respectively). Peptide-conjugated nanoparticles demonstrated better tumor endocytosis and time-dependent gradual increase of intracellular drug uptake than non-targeting liposomal nanoparticles. Furthermore, peptide-conjugated liposomal doxorubicin better controlled tumors than did non-targeting liposomal doxorubicin. The current work may pave a new way for the development of drugs that target each subtype of epithelial ovarian cancer in the future.

Heavy menstrual bleeding, or menorrhagia, is subjectively defined as a “complaint of a large amount of bleeding during menstrual cycles that occurs over several consecutive cycles” and is objectively defined as menstrual blood loss of more than 80 mL per cycle that is associated with an anemia status (defined as a hemoglobin level of

Background In the analysis of survival data for cancer patients, the problem of competing risks is often ignored. Competing risks have been recognized as a special case of time-to-event analysis. The conventional techniques for time-to-event analysis applied in the presence of competing risks often give biased or uninterpretable results. Methods Using a prospectively collected administrative health care database in a single institution, we identified patients diagnosed with stage III or IV primary epithelial ovarian, tubal, and peritoneal cancers with minimal residual disease after primary cytoreductive surgery between 1995 and 2012. Here, we sought to evaluate whether intraperitoneal chemotherapy outperforms intravenous chemotherapy in the presence of competing risks. Unadjusted and multivariable subdistribution hazards models were applied to this database with two types of competing risks (cancer-specific mortality and other-cause mortality) coded to measure the relative effects of intraperitoneal chemotherapy. Results A total of 1263 patients were recruited as the initial cohort. After propensity score matching, 381 patients in each arm entered into final competing risk analysis. Cumulative incidence estimates for cancer-specific mortality were statistically significantly lower (p = 0.017, Gray test) in patients receiving intraperitoneal chemotherapy (5-year estimates, 34.5 %; 95 % confidence interval [CI], 29.5–39.6 %, and 10-year estimates, 60.7 %; 95 % CI, 52.2–68.0 %) versus intravenous chemotherapy (5-year estimates, 41.3 %; 95 % CI, 36.2–46.3 %, and 10-year estimates, 67.5 %, 95 % CI, 61.6–72.7 %). In subdistribution hazards analysis, for cancer-specific mortality, intraperitoneal chemotherapy outperforms intravenous chemotherapy (Subdistribution hazard ratio, 0.82; 95 % CI, 0.70–0.96) after correcting other covariates. Conclusions In conclusion, results from this comparative effectiveness study provide supportive evidence for previous published randomized trials that intraperitoneal chemotherapy outperforms intravenous chemotherapy even eliminating the confounding of competing risks. We suggest that implementation of competing risk analysis should be highly considered for the investigation of cancer patients who have medium to long-term follow-up period. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2279-0) contains supplementary material, which is available to authorized users.