Human peritoneal fluid exerts ovulation- and nonovulation-sourced oncogenic activities on transforming fallopian tube epithelial cells.

Secretory cells in the fallopian tube fimbria epithelium (FTE) are regarded as the main cells of origin of ovarian high-grade serous carcinoma (HGSC). Ovulation is the main cause of FTE oncogenesis, which proceeds through a sequence of TP53 mutations, chromosomal instability due to Rb/cyclin E aberration, in situ carcinoma (STIC), and metastasis to the ovary and peritoneum (metastatic HGSC). Previously, we have identified multiple oncogenic activities of the ovulatory follicular fluid (FF), which exerts the full spectrum of transforming activity on FTE cells at different stages of transformation. After ovulation, the FF is transfused into the peritoneal fluid (PF), in which the FTE constantly bathes. We wondered whether PF exerts the same spectrum of oncogenic activities as done by FF and whether these activities are derived from FF. By using a panel of FTE cell lines with p53 mutation (FT282-V), p53/CCNE1 aberrations (FT282-CCNE1), and p53/Rb aberrations plus spontaneous transformation, and peritoneal metastasis (FEXT2), we analyzed the changes of different transformation phenotypes after treating with FF and PF collected before or after ovulation. Similar to effects exhibited by FF, we found that, to a lesser extent, PF promoted anchorage-independent growth (AIG), migration, anoikis resistance, and peritoneal attachment in transforming FTE cells. The more transformed cells were typically more affected. Among the transforming activities exhibited by PF treatment, AIG, Matrigel invasion, and peritoneal attachment growth were higher with luteal-phase PF treatment than with the proliferative-phase PF treatment, suggesting an ovulation source. In contrast, changes in anoikis resistance and migration activities were similar in response to treatment with PF collected before and after ovulation, suggesting an ovulation-independent source. The overall transforming activity of luteal-phase PF was verified in an i.p. co-injection xenograft mouse model. Co-injection of Luc-FEXT2 cells with either FF or luteal-phase PF supported early peritoneal implantation, whereas co-injection with follicular-phase PF did not. This study, for the first time, demonstrates that PF from ovulating women can promote different oncogenic phenotypes in FTE cells at different stages of malignant transformation. Most of these activities, other than anoikis resistance and cell migration, are sourced from ovulation.

Bone Marrow Mesenchymal Stem Cells Promote Ovarian Cancer Cell Proliferation via Cytokine Interactions.

Bone marrow mesenchymal stem cells (BMSCs) are key players in promoting ovarian cancer cell proliferation, orchestrated by the dynamic interplay between cytokines and their interactions with immune cells; however, the intricate crosstalk among BMSCs and cytokines has not yet been elucidated. Here, we aimed to investigate interactions between BMSCs and ovarian cancer cells. We established BMSCs with a characterized morphology, surface marker expression, and tri-lineage differentiation potential. Ovarian cancer cells (SKOV3) cultured with conditioned medium from BMSCs showed increased migration, invasion, and colony formation, indicating the role of the tumor microenvironment in influencing cancer cell behavior. BMSCs promoted SKOV3 tumorigenesis in nonobese diabetic/severe combined immunodeficiency mice, increasing tumor growth. The co-injection of BMSCs increased the phosphorylation of p38 MAPK and GSK-3ß in SKOV3 tumors. Co-culturing SKOV3 cells with BMSCs led to an increase in the expression of cytokines, especially MCP-1 and IL-6. These findings highlight the influence of BMSCs on ovarian cancer cell behavior and the potential involvement of specific cytokines in mediating these effects. Understanding these mechanisms will highlight potential therapeutic avenues that may halt ovarian cancer progression.

Association between vaginal or cesarean delivery and later development of stress urinary incontinence or pelvic organ prolapse: A retrospective population-based cohort study.

INTRODUCTION AND HYPOTHESIS: Child delivery mode may be associated with pelvic floor disorders. We explored the association between different delivery modes and later development of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) in Taiwanese women. METHODS: This was a retrospective population-based cohort study. Women who delivered babies between January 1, 2000, and December 31, 2018, were selected for this study. The study used Taiwan's National Health Insurance (NHI) Research Database. After propensity score matching, 51,587 women who underwent cesarean section (C/S) and 51,587 women who underwent vaginal delivery (VD) were recruited. Primary outcomes were the presence of SUI and POP after delivery. RESULTS: The incidence of SUI (1.6/1000 person-years) and POP (1.5/1000 person-years) was higher in the VD group than in the C/S group (0.8 and 0.6 in 1000 person-years). VD was associated with an increased risk of SUI [hazard ratio (HR): 2.79, 95% confidence interval (CI): 2.45-3.17] and POP (HR: 1.96, 95% CI: 1.75-2.19) compared to C/S. We also found that age (HR: 1.06, 95% CI: 1.05-1.08 in SUI, HR: 1.08, 95% CI: 1.07-1.09 in POP) and Charlson Comorbidity Index (CCI) (HR: 1.28, 95% CI: 1.12-1.46 in SUI, HR: 1.27, 95% CI: 1.13-1.43 in POP) were associated with an increased risk of SUI and POP. The cumulative incidence of SUI and POP was higher in the VD group than in the C/S group (log-rank test, P < 0.05). CONCLUSIONS: The current study was the largest retrospective cohort study regarding the influence of delivery mode on SUI and POP so far. VD was found to be associated with an increased risk of SUI and POP compared with C/S. Postpartum care for pelvic physical therapy should be provided particularly to women undergoing VD.

Comparison of Er:YAG and CO2 laser therapy for women with stress urinary incontinence.

OBJECTIVE: To compare the effectiveness of Er:YAG and CO2 laser therapies for treating female stress urinary incontinence (SUI). METHODS: This retrospective study included 139 women who were divided into four groups: group 1 received two therapy sessions with the Er:YAG laser, group 2 received two therapy sessions with the CO2 laser, group 3 received one therapy session with the Er:YAG laser, and group 4 received one therapy session with the CO2 laser. Patients completed three questionnaires to assess SUI symptom severity at baseline, 1 month, and 3 months after laser therapy. RESULTS: Urinary incontinence symptoms significantly improved in groups 1 and 2 at both the 1- and 3-month follow-up evaluations compared to the baseline (p < 0.001). Symptoms improved after one therapy session in groups 3 and 4 at the 3-month follow-up (p < 0.001). The Er:YAG laser was more effective than the CO2 laser in improving SUI symptoms (Urogenital Distress Inventory 6 and Incontinence Impact Questionnaire 7) 3 months after treatment, regardless of the number of sessions. Both Er:YAG and CO2 laser therapies were found to be effective in reducing symptoms associated with an overactive bladder, as demonstrated by improvements in overactive bladder symptom scores. Two sessions of laser therapy were more effective than one. CONCLUSION: Vaginal laser therapy could be an effective alternative treatment for mild to moderate SUI. The Er:YAG laser was more effective than CO2 laser therapy, with results lasting for at least 3 months. However, further large-scale, randomized, controlled trials are needed to confirm our findings.

Effects of the Overexpression of Progesterone Receptors on a Precancer p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line.

This study investigated the effects of progesterone receptors A (PRA) and B (PRB) on proliferation, migration, invasion, anchorage-independent growth (AIG), and apoptosis of FE25 cells, a precancer p53- and retinoblastoma-defective human fallopian tube epithelial cell line. We observed that the transfection of PRA (FE25-PRA) or PRB (FE25-PRB) into FE25 cells significantly increased the expression of PRA or PRB at both RNA and protein levels without affecting cell morphology. The FE25-PRA cells exhibited slower proliferation, whereas FE25-PRB showed faster cell proliferation than the control cells. In contrast, the FE25-PRA cells showed the highest migration and invasion abilities, whereas the FE25-PRB cells showed the lowest migration and invasion abilities. After treatment with progesterone, all cell types showed decreased AIG levels, increased apoptotic rates in Terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling assay (TUNEL) staining, and increased levels of apoptotic proteins ascertained based on cleaved caspase-3 levels. The half-maximal inhibitory concentration of carboplatin increased in FE25-PRB cells, but that of paclitaxel remained unchanged. Overall, this study suggests that PRA and PRB have distinct roles in regulating the behavior of FE25 cells, and targeting these receptors could be a potential therapeutic strategy for ovarian cancer treatment. If PRA or PRB overexpression is observed in high-grade serous carcinoma, progesterone could be considered as an adjuvant therapy for these specific cancer patients. However, further research is needed to confirm these findings and investigate the mechanisms underlying these effects.

Spontaneous Transformation of a p53 and Rb-Defective Human Fallopian Tube Epithelial Cell Line after Long Passage with Features of High-Grade Serous Carcinoma.

Ovarian cancer is one of the most lethal gynecological cancers, and 80% are high-grade serous carcinomas (HGSOC). Despite advances in chemotherapy and the development of targeted therapies, the survival rate of HGSOC has only moderately improved. Therefore, a cell model that reflects the pathogenesis and clinical characteristics of this disease is urgently needed. We previously developed a human fallopian tube epithelial cell line (FE25) with p53 and Rb deficiencies. After long-term culture in vitro, cells at high-passage numbers showed spontaneous transformation (FE25L). This study aimed to compare FE25 cells cultured in vitro for low (passage 16-31) and high passages (passage 116-139) to determine whether these cells can serve as an ideal cell model of HGSOC. Compared to the cells at low passage, FE25L cells showed increased cell proliferation, clonogenicity, polyploidy, aneuploidy, cell migration, and invasion. They also showed more resistance to chemotherapy and the ability to grow tumors in xenografts. RNA-seq data also showed upregulation of hypoxia, epithelial-mesenchymal transition (EMT), and the NF-κB pathway in FE25L compared to FE25 cells. qRT-PCR confirmed the upregulation of EMT, cytokines, NF-κB, c-Myc, and the Wnt/ß-catenin pathway. Cross-platform comparability found that FE25L cells could be grouped with the other most likely HGSOC lines, such as TYKNU and COV362. In conclusion, FE25L cells showed more aggressive malignant behavior than FE25 cells and hence might serve as a more suitable model for HGSOC research.

Statins as Repurposed Drugs in Gynecological Cancer: A Review.

Discovering new drugs is an expensive and time-consuming process, including target identification, bioavailability, pharmacokinetic (PK) tests, pharmacodynamic (PD) tests, toxicity profiles, recommended dosage test, and observation of the side effects, etc. Repurposed drugs could bypass some steps, starting from phase II trials, and shorten the processes. Statins, also known as HMG-CoA inhibitors (HMGCR), are commonly used to manage and prevent various cardiovascular diseases and have been shown to improve the morbidity and mortality of patients. In addition to the inhibitory effects on the production of cholesterol, the beneficial effects of statins on the prognosis and risk of various cancers are also shown. Statins not only inhibited cell proliferation, metastasis, and chemoresistance but affected the tumor microenvironment (TME). Thus, statins have great potential to be repurposed in oncology. Hence, we review the meta-analysis, cohort, and case-control studies of statins in gynecological cancers, and elucidate how statins regulate cell proliferation, apoptosis, tumor growth, and metastasis. Although the results in gynecological cancers remain controversial and the effects of different statins in different histotypes of gynecological cancers and TME are needed to elucidate further, statins are excellent candidates and worthy of being repurposed drugs in treating gynecological cancers.

Association of laparoscopy and laparotomy with adverse fetal outcomes: a retrospective population-based case-control study.

BACKGROUND: This study aimed to evaluate fetal adverse outcomes of laparoscopy and laparotomy in pregnant women to determine the safety of these surgical approaches. METHODS: This was a retrospective nationwide case-control study of women who became pregnant for the first time between 2000 and 2012 in Taiwan. The case (with adverse fetal outcomes) and control groups comprised 208,604 and 417,124 participants, respectively. Participants who underwent appendectomy, cholecystectomy, ovarian cystectomy, or myomectomy were treated with either laparoscopy or laparotomy. A conditional logistic regression model was used to calculate the odds ratios (ORs) for adverse fetal outcomes. RESULTS: The laparotomy and laparoscopy groups comprised 632 and 536 patients, respectively. Women who underwent laparoscopy had a significantly higher risk of adverse fetal outcomes (adjusted OR [AOR] = 2.33; 95% CI 1.66-2.99) than those who underwent laparotomy. Adverse fetal outcomes were found to be significantly associated with laparoscopy among women aged 20-39 years (AOR = 2.30; 95% CI 1.70-3.31). Regarding surgical indication, unlike laparotomy, laparoscopic cholecystectomy and appendectomy were not associated with adverse fetal outcomes. However, laparoscopic myomectomy and ovarian surgeries were associated with a higher incidence of adverse fetal outcomes than the laparotomy group (AOR = 2.29 [95% CI 1.57-3.35, p < 0.0001] and AOR = 2.52 [95% CI 1.58-4.04, p = 0.0001], respectively). CONCLUSIONS: Pregnant women who underwent laparoscopic surgery experienced significantly more adverse fetal outcomes than those who underwent laparotomy. Therefore, pregnant women undergoing either laparotomy or laparoscopy should be informed of the risk of adverse fetal outcomes.

The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy.

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches. METHODS: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct. RESULTS: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis. CONCLUSIONS: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.

A clear cancer cell line (150057) derived from human endometrial carcinoma harbors two novel mutations.

BACKGROUND: Cell lines are extremely useful for both basic and clinical research. Thus, establishing endometrial cancer cell lines with malignant histology is important. This study aimed to extensively characterize an endometrial clear cell carcinoma cell line. METHODS: This cell line, named 150,057, was derived from the endometrial clear cell cancer of a 63-year-old woman. The morphology, chromosomes, chemosensitivity, tumor markers, xenotransplantation characteristics, and cancer-related genes of the cell line were characterized. RESULTS: This cell line exhibited adequate growth, being passaged more than 70 times. The morphology of the cells was polygonal with a cobblestone-like appearance. Karyotyping of the cell line revealed a hypodiploid chromosomal number. 150057 cells expressed CA19-9 and CA125. The cell line was sensitive to doxorubicin, paclitaxel, carboplatin, and cisplatin. After the cells were transplanted into the subcutaneous region of non-obese diabetic-severe combined immunodeficiency mice, they generated xenograft tumors with similar histology as the original tumor. A total of 59 somatic nucleotide mutations were identified in 25 of the 53 examined tumor suppressor genes and oncogenes. Two novel mutations were found in FGFR3 and ARID1A. CONCLUSION: We established and characterized an endometrial clear cell carcinoma cell line that may be useful in carcinogenesis and treatment research for endometrial cancer.

Human fallopian tube epithelial cells exhibit stemness features, self-renewal capacity, and Wnt-related organoid formation.

BACKGROUND: Fallopian tube epithelial cells (FTEC) were thought to be the origin of high-grade serous ovarian carcinoma (HGSOC). Knowledge of the stemness or initiating characteristics of FTEC is insufficient. Previously, we have characterized the stemness cell marker of FTEC, this study aims to further characterize the clonogenicity and spheroid features of FTEC. METHODS: We successfully derived FTECs from the epithelial layer of the human fallopian tubes. We examined the morphology, proliferation rate, doubling time, and clonal growth of them. At passage 3, the sphere formations on gelatin-coated culture, suspension culture, and matrigel culture were observed, and the expression of LGR5, SSEA3, SSEA4, and other stemness markers was examined. Furthermore, tissue-reconstituted organoids from coculture of FTEC, fallopian stromal cells (FTMSC) and endothelial cells (HUVEC) were examined. RESULTS: FTEC exhibited cuboidal cell morphology and maintained at a constant proliferation rate for up to nine passages (P9). FTEC could proliferate from a single cell with a clonogenic efficiency of 4%. Flow cytometry revealed expressions of normal stem cell markers (SSEA3, SSEA4, and LGR5) and cancer stem cell markers (CD24, CD44, CD117, ROR1, and CD133). FTEC formed spheres and colonies when cultured on low attach dish. In the presence of Matrigel, the stemness and colony formation activity were much enhanced. In co-culturing with FTMSC and HUVEC, FTEC could form organoids that could be blocked by Wnt inhibitor DKK1. Expressions of LGR5 and FOXJ1 expression were also decreased by adding DKK1. CONCLUSION: We demonstrated abundantly presence of stem cells in human FTECs which are efficient in forming colonies, spheres and organoids, relying on Wnt signaling. We also reported for the first time the generation of organoid from reconstitutied cell lineages in the tissue. This may provide a new model for studying the regneration and malignant transformation of the tubal epithelium.

Proton pump inhibitors reduce breast cancer risk in gastric ulcer patients: A population-based cohort study.

We aim to evaluate breast cancer risk relating to PPIs usage in women with peptic ulcer. From 2000 to 2013, incidence rates of breast cancer were compared between the two cohorts (with or without PPIs). Each study cohort consisted of 4838 women. The incidence density rate of breast cancer in the PPI cohort was 0.29 that in the comparison cohort (10.0 vs 31.6 per 10 000 person-years), with an adjusted HR (hazard ratio) of 0.32 (95% CI = 0.20-0.49) for the PPI cohort. In conclusion, the medication of PPIs is associated with reduced breast cancer risk for women with gastric ulcer.

Thyroid cancer risk in women with infertility and association with fertility medications in Taiwan.

BACKGROUND: The current study evaluated whether the risk of developing thyroid cancer in Asian women was associated with infertility and the use of fertility drugs. METHODS: The authors conducted a large, retrospective cohort study using Taiwan's National Health Insurance Research Database. From the insurance claims data, a total of 13,356 women aged 20 to 49 years who were diagnosed with infertility from 2000 through 2013 were included in the infertile group, and 53,424 women without a history of infertility were selected as fertile comparisons and were frequency matched by age and year of diagnosis. Both groups were followed up to 2013 to calculate incident thyroid cancer. Poisson regression analysis was used to estimate the incidence rate ratio (IRR). RESULTS: The incidence of thyroid cancer was 1.9-fold greater in the infertile group compared with the comparison group (2.85 vs 1.53 per 10,000 person-years), with an adjusted IRR of 1.80 (95% confidence interval [95% CI], 1.70-1.92) for the infertile group. Higher cancer incidence was demonstrated for the infertile group after 7 years of follow-up, with an adjusted IRR of 4.39 (95% CI, 4.03-4.78) compared with the comparison group. Among infertile women, those who had taken the fertility drug clomiphene were found to have a reduced incidence of thyroid cancer compared with those who were treated without the drug (2.69 vs 3.42 per 10,000 person-years), with an adjusted IRR of 0.86 (95% CI, 0.75-0.99). However, the cancer incidence in infertile women being treated with clomiphene was nearly 6-fold greater than that in fertile women taking the drug. CONCLUSIONS: The results of the current study provide evidence that women with infertility are at an increased risk of developing thyroid cancer.

Association between depression risk and polycystic ovarian syndrome in young women: a retrospective nationwide population-based cohort study (1998-2013).

STUDY QUESTION: Is polycystic ovarian syndrome (PCOS) in women associated with the increasing incidence of depression in an East Asian population? SUMMARY ANSWER: Younger PCOS patients (aged 15-29 years), but not middle-aged patients, have an increased risk of depression in Taiwan. WHAT IS KNOWN ALREADY: During reproductive age, 6-10% of women have PCOS. Among them, ~40% experience depression, mostly at young ages. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based cohort study analysing depression risk in Taiwanese women using data from a nationwide database containing 1998-2013 data of nearly 1 million people. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 15- to 50-year-old women newly diagnosed with PCOS during 1998-2013 from the Taiwan National Health Insurance Research Database as the PCOS cohort (n = 7684) and then randomly matched them 4 : 1 by sex, age and index year with women without PCOS as the comparison cohort (n = 30 736). We used multivariable Cox proportional hazard regression analysis to determine the association between PCOS and depression risk [hazard ratio (HR) with 95% confidence interval (CI)]. MAIN RESULTS AND THE ROLE OF CHANCE: The incidence of depression was higher in the PCOS group than in the comparison group (6.67 vs. 4.82 per 1000 person-years; adjusted HR = 1.28, 95% CI = 1.12-1.46). PCOS patients aged 15-29 years had a significantly higher depression risk (adjusted HR = 1.39, 95% CI = 1.18-1.65); no such significant association was noted among patients aged 30-39 years and 40-50 years. LIMITATIONS, REASONS FOR CAUTION: A history of malignancy, which may increase depression, could not be obtained for our study patients. Moreover, we could not obtain a family history of depression, a relevant risk factor for depression. Finally, the database has no records of body mass index, which may influence depression outcome. WIDER IMPLICATIONS OF THE FINDINGS: In Taiwan, younger PCOS patients (15-29 years), but not the middle-aged patients, have an increased risk of depression. Our findings provide vital information to patients, clinicians, the Taiwan Government and other developing Asian countries to improve the PCOS treatment strategies in the future. Routine screening for depression in PCOS patients may be implemented into the health practice. STUDY FUNDING/COMPETING INTEREST(S): This study was supported in part by the Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW108-TDU-B-212-133 004), China Medical University Hospital, Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 107-2321-B-039 -004-), Tseng-Lien Lin Foundation, Taichung, Taiwan and Katsuzo and Kiyo Aoshima Memorial Funds, Japan. No competing interest existed. TRIAL REGISTRATION NUMBER: N/A.

Association of hysterectomy with bipolar disorder risk: A population-based cohort study.

BACKGROUND: Hormonal fluctuations may trigger the onset of bipolar disorder. We designed a longitudinal follow-up study to evaluate the association between hysterectomies and bipolar disorder risk. METHODS: We conducted a large retrospective cohort study using Taiwan's National Health Insurance Research Database. A total of 4,337 women aged 30 to 50 years who underwent the hysterectomy during 2000-2013 were selected and 17,348 patients without hysterectomy were selected for comparison (1:4 match). Poisson regression analysis was used to calculate the incidence rate ratio (IRR) and 95% confidence interval (CI). RESULTS: During the follow-up of 7.93 years, 20 participants with hysterectomy and 28 without hysterectomy developed bipolar disorder. Receiving hysterectomy was associated with the risk of developing bipolar disorder (adjusted IRR = 2.80; 95% CI = 2.54-3.09). Women with hysterectomy had a higher risk of bipolar disorder in follow-up durations of <1 year (adjusted IRR = 2.18 with 95% CI = 1.94-1.45) and ≥1 year (adjusted IRR = 2.85 with 95% CI = 2.58-3.15). Endometriosis and Premarin use increased bipolar disorder incidence in the hysterectomy group (adjusted IRR = 3.17 [95% CI = 2.83-3.56] and 4.22 [95% CI = 3.71-4.80], respectively). CONCLUSION: This study concluded that women with hysterectomy have an increased risk of bipolar disorder. Endometriosis and hormone therapy may add to the risk of bipolar disorder after hysterectomy. Knowledge about how surgical or natural hormonal withdrawal influences mood is fundamental and emphasizes the importance of coordinated psychiatric and gynecological care.

Hysterectomy associated with de novo lower urinary tract symptoms in a Taiwanese population: a nationwide, population-based study.

INTRODUCTION AND HYPOTHESIS: The effect of hysterectomy on vesicourethral functions remains controversial. The objective of this study was to examine the association between hysterectomy and de novo lower urinary tract symptoms (LUTSs). METHODS: We identified 8514 patients who had undergone hysterectomy between January 1, 2000, and December 31, 2012, from Taiwan's National Health Insurance (NHI) Research Database. A control cohort, comprising 34,056 age-matched patients who had not undergone hysterectomy, was created for comparison. All hysterectomy and control patients were followed up until diagnosis as having LUTSs (dysuria, urinary retention, incontinence, and increased urinary frequency and urgency), withdrawal from the NHI system, death, or December 31, 2013. Patients were excluded if LUTSs were diagnosed before or at the time of hysterectomy. RESULTS: The adjusted hazard ratio (aHR) of subsequent de novo LUTSs was higher in the hysterectomy patients [1.57, 95% confidence interval (CI) 1.46-1.70] than in the controls during the follow-up period. Compared with the controls, the highest risk of de novo LUTSs was noted in patients who had undergone vaginal hysterectomy (VH; aHR 1.89, 95% CI 1.57-2.28) followed by those who had undergone laparoscopy-assisted VH (LAVH; aHR 1.74, 95% CI 1.56-1.94). CONCLUSIONS: We found that undergoing hysterectomy was associated with increased risks of developing lower urinary tract symptoms in women. This association was more pronounced for women undergoing the vaginal or laparoscopically assisted hysterectomy. Further large-scale prospective studies or clinical trials are needed to explore whether causality exists.

Pelvic organ prolapse surgery following hysterectomy with benign indication: a national cohort study in Taiwan.

INTRODUCTION AND HYPOTHESIS: Hysterectomy and pelvic organ prolapse (POP) surgeries are two of the most common gynecologic surgeries conducted for benign conditions. This nationwide retrospective cohort study explored the risk of subsequent POP surgery following hysterectomy without simultaneous POP surgery. METHODS: This study identified 7298 patients who underwent hysterectomy between January 1, 2000, and December 31, 2012, from the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed comprising 29,192 age-matched patients who had not undergone hysterectomy. All hysterectomy and control patients were followed until they required POP surgery, withdrew from the NHI system, died, or December 31, 2012. Patients were excluded if they underwent POP surgery before or at the time of hysterectomy. RESULTS: The adjusted hazard ratio (aHR) of subsequent POP surgery in subjects with hysterectomy was higher [2.60, 95% confidence interval (CI) 1.79-3.78] than that of controls during the follow-up period. Compared with patients who had not undergone hysterectomy, the highest risks of subsequent POP surgery was noted in those who had undergone vaginal hysterectomy (VH; HR 6.29, 95% CI 1.54-25.79) followed by those who underwent laparoscopy-assisted VH (LAVH; HR 3.77, 95% CI 2.43-5.85). CONCLUSIONS: Hysterectomy may increase the risk of subsequent POP surgery, and various hysterectomy techniques, particularly VH and LAVH, may increase the risk of subsequent POP surgery.

Haemoglobin in pelvic fluid rescues Fallopian tube epithelial cells from reactive oxygen species stress and apoptosis.

Fallopian tube fimbrial epithelium is considered to be the major site of origin of ovarian high-grade serous carcinoma, with p53 loss being the earliest and universal change. We previously reported that reactive oxygen species (ROS) in the ovulatory follicular fluids (FFs) are mutagenic and cytotoxic to fimbrial epithelial cells, which are bathed in the peritoneal fluid mixed with FFs. Here, we observed that ferryl haemoglobin (Hb), which was abundantly present in ovulatory FFs and pelvic peritoneal fluids, could rescue p53-deficient immortalized fimbrial epithelial (FE25) cells and oviduct epithelial cells from Trp53-null mice from lethal ovulatory ROS stress. Ferryl Hb and FF containing high Hb levels protected FE25 cells from apoptosis, mainly by consuming extracellular ROS and reducing NADPH oxidase-mediated cell death. The remaining extracellular ROS could still induce DNA double-strand breaks in the fimbrial epithelial cells. Our study revealed that ferryl Hb in peritoneal fluid rescued ROS-stressed, DNA-damaged fimbrial epithelial cells from death, and suggested that peritoneal blood from various sources may contribute to the ovulation-induced transformation of Fallopian tube epithelium. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Mutagenic, surviving and tumorigenic effects of follicular fluid in the context of p53 loss: initiation of fimbria carcinogenesis.

Ovulation is the strongest risk factor for ovarian high-grade serous carcinoma (HGSC) that largely originates from the fallopian tube fimbriae and always carries loss-of-function mutations of TP53 in both early and late lesions. Mature ovarian follicle contains high level of reactive oxygen species (ROS). When released from ovulation, follicular fluid (FF) bathes the fimbriae and may lead to DNA double-strand break (DSB) and neoplastic transformation. In this study, we examined the mutagenic and tumorigenic activities of human pre-ovulatory FFs. A subset (6/11) of FFs was found with high levels of ROS whereas the antioxidant capacities were indifferent. These ROS(high) FFs induced intracellular ROS and DSBs in the secretory cell population of fimbriae epithelium. When p53 and Rb were turned down, the FF-exposed secretory cells overcame apoptosis and expanded the population carrying ROS and DSB. The cancer initiation and promotion effects of FF were further recapitulated in Trp53 (-/-) mice. When introduced into the mammary fat pad, ROS(high) but not ROS(low) FFs induced early-onset B-cell lymphoma. Cotreatment with physiological concentration of melatonin, a potent antioxidant, ameliorated the mutagenic and tumorigenic effect of ROS(high) FF in vitro and in vivo. The study revealed ROS and mitogens in mature ovarian follicles could initiate the transformation of fimbria epithelium in the context of p53 loss and melatonin is a potent preventive agent.

Association of maximum uterine diameter with postoperative complications in laparoscopic supracervical hysterectomy: A retrospective cohort study.

OBJECTIVE: To determine the maximum uterine diameter threshold associated with an elevated risk of complications following laparoscopic supracervical hysterectomy (LSH). METHODS: This was a retrospective cohort study from a single tertiary referral center. We enrolled patients who underwent LSH for benign indications at our hospital between January 2013 and June 2023. The primary outcome was the occurrence of surgical complications within the 30-day timeframe of hysterectomy. The covariate included the year of the procedure, patient age, body mass index, parity, American Society of Anesthesiologists classification, comorbidities, history of previous abdominal and pelvic surgery, and preoperative anemia, blood loss, surgical time, hospital stay and pathology. The exclusion criteria comprised those who underwent hysterectomy for malignancy, individuals who underwent total vaginal hysterectomy or laparoscopically assisted vaginal hysterectomy, and those with missing data on uterine maximum diameter, study outcomes, or covariates. RESULTS: We included a final sample of 120 patients, revealing a median uterine diameter of 9.12 cm, with 9.2% experiencing complications. The median uterine weight among 40 patients was 275 g. Receiver operating characteristic (ROC) curve analysis suggested a potential cutoff of 11.55 cm for predicting complications, with an area under the ROC curve of 0.67. Multivariate logistic regression confirmed a significant association between uterine diameter exceeding the cutoff and increased complication risk (OR 33.925, 95% CI: 2.294-501.690, P = 0.0103). A correlation (r = 0.762, P < 0.001) between uterine weight and diameter indicated the latter's suitability for preoperative assessment of uterine weight. CONCLUSION: The maximum uterine diameter with an optimal cutoff of 11.55 cm was associated with increased complication risk.