Dysmenorrhea in patients with adenomyosis: A clinical and demographic study.

OBJECTIVE: To identify the risk factors associated with dysmenorrhea in adenomyosis and to discuss the potential hormone-based understanding of pain mechanisms. STUDY DESIGN: Adenomyosis patients with mild or no dysmenorrhea (n = 40, Group 1) and moderate-to-severe dysmenorrhea (n = 80, Group 2) were recruited. Charts of all patients were recorded. An immunohistochemistry (IHC) analysis was performed to detect the cellular levels of estrogen receptor-α (ER-α), estrogen receptor-ß (ER-ß), gonadotropin-releasing hormone receptor (GnRH-R), and neurofilaments (NFs) in 60 cases. RESULTS: A history of cesarean section (CS) was positively related to the degree of dysmenorrhea in adenomyosis (OR (95 % CI): 4.397 (1.371-14.104)). The ER-α levels in the eutopic endometrium (EUE) of Group 2 were higher than those in the ectopic endometrium (ECE) of Group 1. Group 2 had higher NF levels in the ECE than in the EUE. CONCLUSION: A history of CS is a risk factor for adenomyosis with moderate-to-severe dysmenorrhea. For patients with adenomyosis, high ER-α levels in the EUE and high NF levels in the ECE may be related to moderate-to-severe dysmenorrhea. These hormone-based mechanisms may contribute to our understanding of the pathogenesis of dysmenorrhea in adenomyosis.

Clinical outcomes of vaginectomy and laser ablation for the treatment of post-hysterectomy women with vaginal high-grade squamous intraepithelial lesions: A retrospective study.

OBJECTIVE: To evaluate the clinical outcomes of vaginectomy and laser ablation for the treatment of vaginal high-grade squamous intraepithelial lesion (HSIL) patients who underwent previous hysterectomy for cervical HSIL or cancer. STUDY DESIGN: The clinicopathologic data and follow-up information of 167 post-hysterectomy vaginal HSIL patients who underwent laser ablation or vaginectomy were retrospectively reviewed from 2010 to 2018 at the Obstetrics and Gynecology Hospital of Fudan University. RESULTS: Of the 167 vaginal HSIL patients enrolled, 74 patients underwent vaginectomy, and 93 patients underwent laser ablation. At a median follow-up of 15 months, 13 (7.8 %) patients experienced progression to vaginal cancer, and 22 (13.2 %) patients had persistent/recurrent disease. Upon multivariate analysis, laser ablation (OR: 5.16, p = 0.02), cytology indicating HSIL (OR: 25.45, p = 0.00), and a shorter interval between previous hysterectomy and vaginal HSIL diagnosis (< 24 vs ≥ 24 months, OR: 0.10, p = 0.02) were associated with disease persistence/recurrence. In post-hysterectomy for cervical HSIL patients, the vaginectomy group had a significantly higher recurrence-free survival rate (RFS, 94.5 % vs 69.0 %, p = 0.00) and a similar progression-free survival rate (PFS, 96.4 % vs 91.4 %, p = 0.17) compared with the laser ablation group. Among post-hysterectomy for cervical cancer patients, RFS (89.5 % vs 65.7 %, p = 0.04) and PFS (100.0 % vs 82.9 %, p = 0.05) were both higher in the vaginectomy group than in the laser ablation group. CONCLUSION: Compared with laser ablation, vaginectomy resulted in better clinical outcomes among vaginal HSIL patients who had undergone previous hysterectomy for cervical neoplasia.

Long noncoding RNA TC0101441 induces epithelial-mesenchymal transition in epithelial ovarian cancer metastasis by downregulating KiSS1.

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC.

Analysis of the reproductive outcomes and the size of the unicornuate uterus measured by magnetic resonance imaging and their relationship.

PURPOSE: To evaluate the relationship between the uterine size measured by pelvic magnetic resonance and reproductive outcome in women with a unicornuate uterus. METHODS: This was a retrospective study including 140 patients affiliated with unicornuate uterus diagnosed by the pelvic MR prior to their first pregnancy in the Obstetrics and Gynecology Hospital of Fudan University from April 2010 to December 2017. All the length of the unicornuate uterus were re-measured and recorded by skilled radiologists during the study period. We divided all the 140 participants with complete pelvic MR imaging into four groups by the best reproductive outcomes, which refers to Group 1 (primary infertility, n = 21), Group 2 ( < 24 weeks' gestation, n = 34), Group 3 (preterm delivery, 24-35 weeks' gestation, n = 13), Group 4 ( ≥ 35 weeks' gestation, n = 72), followed them up and then analyzed the data. RESULTS: Measurements of 140 patients with hemi-uteri were retrieved for analysis. The mean length of the uterine was 4.90  ± 0.56 cm. There were no significant differences in the uterine cavity length, cervical length, endometrial thickness and uterine wall thickness between the four groups while the uterine length (P = 0.001) was statistically significant. Women with uterine lengths ≥  4.5 cm were more likely to experience full-term delivery compared with the other group (P = 0.001). Ordinal multiple logistic regression analysis showed that the uterine length [OR = 9.03 (95% CI: 2.90-28.13)] and uterine cavity length [OR = 0.32 (95% CI: 0.06-2.04)] were independent protective factors for better obstetric outcomes CONCLUSION: The uterine length is a reliable prognostic factor for the gestational week of delivery and an appropriate antenatal surveillance factor of women with unicornuate uterus.

The role of oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para-aortic lymphadenectomy.

BACKGROUND AND OBJECTIVES: This study is aimed to investigate the possibility of preoperative oral oil administration in displaying the chylous tubes and preventing chylous leakage in laparoscopic para-aortic lymphadenectomy. MATERIALS AND METHODS: In this retrospective nonrandomized study, of the 30 patients with gynecological malignancies who had indications for laparoscopic para-aortic lymphadenectomy up to renal vessels, 15 were administered preoperative oral oil (oil a administration) (control group) at our hospital between September 2017 and June 2018. The chylous tube displaying rates, incidences of chylous leakage, and other perioperative data of the two groups were compared. RESULTS: Successful display of chylous tubes was observed in 93.3% (14/15) patients in the oil administration group. The chylous leakage was zero in the oil administration group, and 33.3% (5/15) in the control group. The postoperative drainage duration (4.1 ± 1.0 days vs 7.6 ± 1.4 days, P = 0.000), somatostatin application time (0 day vs 5.9 ± 0.8 days), and postoperative hospital stay (6.0 ± 2.3 days vs 9.1 ± 2.1 days, P = 0.001) were significantly shorter in the oil administration group. The total cost is lower in the oil administration group (4972.52 ± 80.54 dollars vs 6260.80 ± 484.47 dollars, P = 0.000). CONCLUSIONS: Preoperative oil administration is a feasible and effective method to display the chylous tubes and to prevent the chylous leakage in para-aortic lymphadenectomy.

Drug therapy for adenomyosis: a prospective, nonrandomized, parallel-controlled study.

Objective To provide novel insights into the clinical treatment of adenomyosis. Methods Two hundred patients with adenomyosis were enrolled in this prospective, nonrandomized, parallel-controlled study with a 1-year follow-up in our hospital. Group 1 was treated with 3.75 mg leuprorelin acetate (LA) (n = 40), Group 2 was treated with 1.88 mg LA (n = 40), Group 3 underwent Mirena implantation (n = 40), Group 4 underwent Mirena implantation after treatment with 3.75 mg LA (n = 40), Group 5 underwent Mirena implantation after treatment with 1.88 mg LA (n = 20), and Group 6 received San-Jie-Zhen-Tong capsules alone (n = 20). Uterine volume, pain, cancer antigen 125 level, ovary function, adverse effects, and Mirena expulsion were evaluated. Results The uterine volume and pain scores were lower in the groups treated with 1.88 than 3.75 mg LA, but the lower dose was associated with significantly fewer hot flashes and sweating. The 1-year Mirena expulsion rate was higher in Group 3 than in Groups 4 and 5 (10.00% vs. 3.33%, respectively). Costs were significantly higher in Groups 1 and 4 than in Groups 2 and 5. Conclusion Administration of 1.88 mg LA may be an alternative therapy for Asian patients with adenomyosis. The combination of LA and Mirena could enhance the therapeutic effect. Registration number: ChiCTR-IPR-15005971.

Comparison of small intestinal submucosa graft with split-thickness skin graft for cervicovaginal reconstruction of congenital vaginal and cervical aplasia.

STUDY QUESTION: What is the difference in vaginal-length gain and resumption of menstruation following cervicovaginal reconstruction using split-thickness skin (STS) graft versus small intestinal submucosa (SIS) graft for patients with congenital vaginal and cervical aplasia? SUMMARY ANSWER: No difference was found in the number of patients who resumed menstruation between the two groups; however, significantly greater vaginal-length gain was found in the STS group. WHAT IS ALREADY KNOWN: Hysterectomy and vaginoplasty are typically recommended for patients without a cervix or without a sufficient cervix to avoid postoperative re-obstruction. Advances in surgical techniques have enabled the use of autologous tissues or heterologous biological grafts for reconstructive procedures, allowing patients undergoing these procedures to preserve the possibility of conception. STUDY DESIGN, SIZE, DURATION: This was a retrospective study of 26 women who were diagnosed with congenital vaginal and cervical aplasia with a functional endometrial cavity and underwent cervicovaginal reconstruction using STS or SIS grafts between January 2012 and October 2015 at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PARTICIPANTS/MATERIALS, SETTING, METHOD: 15 women underwent cervicovaginal reconstruction using SIS graft and 11 underwent cervicovaginal reconstruction using STS graft. Clinical characteristics, perioperative data, resumption of menstruation, vaginal stenosis, length of the neovagina, vaginal-length gain, stricture of the cervix and body image were postoperatively assessed. MAIN RESULTS AND THE ROLE OF CHANCE: At a median follow-up of 21 (2-46) months, all but one of the patients experienced relief of abdominal pain and resumed menstruation. Re-obstruction of the cervix occurred in only one patient in the SIS group. The SIS group reported significantly higher body image scores and cosmetic satisfaction. Although the two groups had a similar vaginal length before surgery, the vaginal-length gain was significantly greater in the STS group (4.9 ± 1.7 cm in the SIS group versus 7.5 ± 0.7 cm in the STS group, P = 0.004) and the neovagina length at 6 months post-operation was significantly shorter in the SIS group (6.5 ± 0.7 cm in SIS the group versus 8.0 ± 0.5 cm in the STS group, P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: Due to a lack of long-term follow-up, patient satisfaction with sex life, pregnancy rates and outcomes after the two approaches require further evaluation. WIDER IMPLICATIONS OF THE FINDINGS: Combined laparoscopic and vaginal cervicovaginal reconstruction using SIS or STS graft is a safe and effective treatment for preserving uterus function in women with congenital vaginal and cervical aplasia. However, SIS graft must still be improved to achieve satisfactory vaginal length. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Sexual and functional outcomes of vaginoplasty using acellular porcine small intestinal submucosa graft or laparoscopic peritoneal vaginoplasty: a comparative study.

STUDY QUESTION: Can vaginoplasty in patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) be achieved using an acellular porcine small intestinal submucosa (SIS) graft? SUMMARY ANSWER: Vaginoplasty using SIS graft was successfully achieved in women with MRKHS, and the anatomical and functional outcomes of this procedure were comparable to those of laparoscopic peritoneal vaginoplasty. WHAT IS KNOWN ALREADY: There is a great variety of vaginal reconstruction techniques, which suggests there is no single superior surgical technique. STUDY DESIGN, SIZE, DURATION: This prospective observational study included 34 patients with congenital vaginal agenesis who underwent vaginoplasty using SIS graft (the SIS group) between December 2011 and July 2013, and 41 patients with the same disease who underwent laparoscopic peritoneal vaginoplasty (the Davydov group) between January 2008 and July 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patient and surgical data, follow-up information, and the female sexual function index (FSFI) scores in the two groups were analysed and compared. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with the laparoscopic Davydov procedure, the operating time of vaginoplasty using SIS graft was significantly shorter, and the estimated blood loss was significantly less. Patients in the SIS group had an earlier return of bowel activity, and an earlier return to work. However, the total cost in the SIS group was significantly higher than that in the Davydov group due to the cost of the SIS graft ($3525 per graft). Most patients (28/34 in the SIS group and 37/41 in the laparoscopic Davydov group) returned for their follow-up 9 months post-surgery. The mean length of the neovagina in the SIS group seemed slightly shorter than that in the Davydov group (6.8 ± 0.9 cm versus 7.3 ± 1.3 cm, P = 0.081). Thirteen patients (46%) in the SIS group and 11 (29%) in the Davydov group had a neovagina <7 cm long (P = 0.453), whereas 4 patients (14%) in the SIS group and 3 patients (8%) in the Davydov group had a neovagina <6 cm long (P = 0.201). Sixteen patients in the SIS group and 25 in the Davydov group subsequently had a sexual partner and became sexually active. Four patients in the SIS group and six in the Davydov group reported low total FSFI scores (≤23). There was no statistically significant difference in the total FSFI scores and the scores of all six domains of the FSFI between the two groups. The average time of continuous mould wearing in the SIS group was statistically significantly longer than that in the Davydov group (7.8 ± 3.3 months versus 4.8 ± 1.6 months, P = 0.001). In the patients with a neovaginal length of ≥6 cm, the FSFI score of the women (26.6 ± 2.3 versus 21.5 ± 1.5, P < 0.001) and the satisfactory score of their partner (8.6 ± 1.2 versus 6.6 ± 1.2, P < 0.001) were both statistically significantly higher than patients with a neovaginal length of <6 cm. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is that it is non-randomized. Further randomized studies are warranted to compare the effects of these two procedures. WIDER IMPLICATIONS OF THE FINDINGS: Despite the need to wear a mould for longer, vaginoplasty using SIS graft provides an attractive, alternative treatment for women with MRKHS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Chinese National Nature Sciences Foundation (grant number 81471416) and the National Key Clinical Faculty Construction Program of China. No competing interests are declared. TRIAL REGISTRATION NUMBER: N/A.

Acellular porcine small intestinal submucosa graft for cervicovaginal reconstruction in eight patients with malformation of the uterine cervix.

STUDY QUESTION: Can surgical reconstruction of the cervix and vagina in patients be achieved using an acellular porcine small intestinal submucosa (SIS) graft? SUMMARY ANSWER: Our experiences of combined laparoscopic and vaginal cervicovaginal reconstruction using an SIS graft in eight patients were positive, with successful reconstruction and no complications, cervical stenosis or vaginal stenosis. WHAT IS KNOWN ALREADY: In patients with agenesis and dysgenesis of the uterine cervix and vagina, surgical reconstruction of the internal genitalia is a challenging problem for gynecologists. Hysterectomy with the creation of an artificial vagina was the treatment of choice in the 1990s. Recently, conservative management has been gradually adopted to avoid extirpation of the uterus, including the canalization techniques, the uterovaginal anastomosis and the reconstruction of cervical and vaginal agenesis with some autologous tissues. STUDY DESIGN, SIZE, DURATION: This prospective observational study from January 2012 to March 2013 included 8 patients aged 10-18 years with malformation of the cervix (1 with cervical agenesis, 1 with a cervical body consisting of a fibrous band and 6 with obstruction of the cervical os) and vagina (4 with complete vaginal aplasia and 4 with a 1-3 cm long vaginal pouch) diagnosed by physical examination and magnetic resonance imaging. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight patients underwent combined laparoscopic and vaginal cervicovaginal reconstruction using an SIS graft during the end of menstruation. A T-shaped intrauterine device connected with a 14-French Foley catheter was inserted into the uterine cavity to keep the newly created cervix patent, and then a permanent lower uterine cerclage was placed. Patients were assessed post-operatively at 1, 2, 4, 6, 12 and 15 months, and data on menstruation and the morphology of the neovagina and cervix were recorded. MAIN RESULTS AND THE ROLE OF CHANCE: The mean ± SD age of the patients was 14.5 ± 2.8 (10-18) years. All patients had a history of cyclic abdominal pain, and the average delay in diagnosis was 4.5 ± 4.0 (0-12) months. One patient had a previous history of unsuccessful attempt at canalization and two post-operative hematometra drainages before referral. The mean operating time was 201 ± 67 (120-330) min, with a mean estimated blood loss of 157 ± 154 (30-500) ml. The first case was converted to laparotomy, and the others were successfully completed. None of the patients had a complication or required blood transfusion. All the patients showed resumption of menstruation. The patients were followed for 8 ± 4 (4-15) months, and no cervical or vaginal stenosis occurred in any of the cases. LIMITATIONS, REASONS FOR CAUTION: The sample size of this study was small. A larger study that compared this method with previous techniques regarding the complication and success rates would increase the value of the study. WIDER IMPLICATIONS OF THE FINDINGS: A combined laparoscopic and vaginal cervicovaginal reconstruction with an SIS graft is a potential alternative to the management of congenital agenesis and dysgenesis of uterine cervix and vagina. STUDY FUNDING/COMPETING INTEREST(S): The work was supported by National Key Clinical Faculty Construction Program of China. No competing interests are declared.

Vaginoplasty using acellular porcine small intestinal submucosa graft in two patients with Meyer-von-Rokitansky-Küster-Hauser syndrome: a prospective new technique for vaginal reconstruction.

The objective of this case study is to present our experience of a surgical approach for vaginal agenesis using an acellular porcine small intestinal submucosa (SIS) graft. The present report involved 2 patients diagnosed as having vaginal agenesis due to Meyer-von-Rokitansky-Küster-Hauser syndrome. The operation procedure involved the creation of a neovaginal tunnel and then a mold wrapped with the SIS graft was placed in the neovagina. The duration of surgery was less than 45 min with minimal blood loss and no operative and postoperative complications. Epithelialization of the neovagina was achieved within 2 months after surgery. The neovagina created with this procedure was the same as that of a normal adult vagina histologically and physiologically. In conclusion, the creation of a neovagina using a SIS graft resulted in a favorable outcome and this approach may be a potential alternative to the management of vaginal agenesis.

FSH stimulates expression of the embryonic gene HMGA2 by downregulating let-7 in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas.

FSH may increase the risk of ovarian malignancy and play a key role in ovarian carcinogenesis, although the mechanism(s) are undefined. HMGA2 overexpression has been observed to be an early genetic event in tumorigenesis. The present study was designed to investigate the effect of FSH on let-7, HMGA2 and p53 expression in normal fimbrial epithelial cells of ovarian high-grade serous carcinomas (HGSCs). A primary human Fallopian tube (FT) fimbrial epithelium ex vivo culture system of low-grade serous carcinomas (LGSCs) and HGSCs was established. The levels of HMGA2, let-7, p53 and FSHR were evaluated by western blotting and reverse transcription (RT)-PCR. Treatment with FSH significantly increased HMGA2 expression in a time-dependent manner and the let-7 expression levels decreased gradually over time in the normal fimbrial epithelial cells of HGSCs. However, we did not observe similar results in LGSCs. In addition, knockdown of let-7 suppressed HMGA2 expression. p53 was not detected in the normal fimbrial epithelial cells before or after FSH administration. Our results indicate that FSH increases the expression of HMGA2 by downregulating the expression of let-7 in normal fimbrial epithelial cells of HGSCs, but no occurrence of p53 mutation. The susceptibility of fimbria to FSH in HGSCs compared with those in LGSCs is different.