Objective To explore the risk factors for the recurrence of endometrioma and the risk factors for the recurrence of endometriosis-related pain after long-term follow-up. Methods This study retrospectively analyzed 358 women with endometriomas who had a minimum of 5-years follow up after laparoscopic endometrioma excision, which was performed at Peking Union Medical College Hospital from January 2009 to April 2013. All women were divided into recurrence group and nonrecurrence group. Analysis was performed with regard to preoperative history, laboratory analysis, findings during surgery, and symptoms during follow-up, including improvement and recurrence. Results The cumulative incidence rates of recurrence from 5 to 10 years after surgery were 15.4, 16.8, 19.3, 22.5, 22.5, and 22.5%, respectively. Significant differences were found between two groups in terms of age at surgery (RR: 0.764, 95% CI: 0.615–0.949, p = 0.015), duration of dysmenorrhea (RR: 1.120, 95% CI: 1.054–1.190, p < 0.001), presence of adenomyosis (RR: 1.629, 95% CI: 1.008–2.630, p = 0.046), CA125 level (RR: 1.856, 95% CI: 1.072–3.214, p = 0.021) and severity of dysmenorrhea. The severity of dysmenorrhea (RR: 1.711, 95% CI: 1.175–2.493, p = 0.005) and postoperative pregnancy (RR: 0.649, 95% CI: 0.460–0.914, p = 0.013) were significantly correlated with endometrioma recurrence in the multivariate analysis. No significant associations were found between the recurrence rate and gravida, parity, body mass index, infertility, leiomyoma presence, the size of ovarian endometrioma, the presence of deep infiltrating endometriosis, disease stage or postoperative medication. Conclusions The severity of dysmenorrhea and postoperative pregnancy were independent risk factors for the recurrence of ovarian endometriomas after surgery during the long-time follow up.

ObjectivesSince other genital infections enhance HIV susceptibility by inducing inflammation and evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of high-risk human papillomavirus (HPV) infections, we investigated the relationship between the composition of the vaginal microbiota and the risk of high-risk HPV infection.MethodsThe study included 151 healthy women (65 HPV-positive and 86 HPV-negative) aged 20–65 at enrollment. Total genome DNA from samples was extracted using the hexadecyltrimethylammonium bromide (CTAB) CTAB method. The vaginal microbiota composition was determined by sequencing barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500.ResultsOf the 30 most abundant bacteria at the genus level, we found only six bacteria with a statistical difference between HPV-positive and HPV-negative women: Bacteroides, Acinetobacter, Faecalibacterium, Streptococcus, Finegoldia, and Moryella. Lactobacillus was the predominant genus and was detected in all women, but there was no significant difference between the two groups for L. iners, L. jensenii, and L. gasseri. Furthermore, we found 26 types of bacteria with a statistical difference at the species level between the two groups. Anaerobic bacteria such as Bacteroides plebeius, Acinetobacter lwoffii, and Prevotella buccae were found significantly more frequently in HPV-positive women, which is the most important finding of our study.ConclusionOur findings suggest a possible role for the composition of the vaginal microbiota as a modifier of high-risk HPV infection, and specific microbiota species may serve as sensors for changes in the cervical microenvironment associated with high-risk HPV infection. The exact molecular mechanism of the vaginal microbiota in the course of high-risk HPV infection and cervical neoplasia should be further explored. Future research should include intervention in the composition of the vaginal microbiota to reverse the course of high-risk HPV infection and the natural history of cervical neoplasia.

Background The prevalence of Lynch syndrome and screening strategies for this disorder in Chinese patients with endometrial cancer have seldom been investigated. Such data would be essential for the screening, prevention, genetic counseling, and treatment of Lynch syndrome. The purpose of this prospective study was to determine the accuracy of the mismatch repair (MMR) protein immunohistochemistry (IHC), microsatellite instability (MSI) test, and clinical diagnostic criteria in screening for Lynch syndrome-associated endometrial cancer (LS-EC) in a prospective Chinese cohort. Methods All patients with newly diagnosed endometrial cancer (EC) were evaluated using clinical diagnostic criteria (Amsterdam II criteria and the revised Bethesda guidelines), MSI test, and IHC of MMR proteins in tumor tissues. For all patients, the screening results were compared with results of germline sequencing for pathogenic variants of MMR genes. Results Between December 2017 and August 2018, a total of 111 unselected patients with newly diagnosed EC were enrolled. Six patients (5.4%) harbored a pathogenic germline mutation of MMR genes: 1 had a mutation in MutL homolog 1 ( MLH1 ), 2 in MutS homolog 2 ( MSH2 ), and 3 in MutS homolog 6 ( MSH6 ). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for identifying LS-EC were 33.3%, 88.6%, 14.3%, and 95.9%, for the clinical criteria, 66.7%, 75.0%, 14.3%, and 97.3% for IHC of MMR proteins, 100%, 89.9%, 33.3%, and 100% for MSI test, and 100%, 72.4%, 20.0% and 100% for combined IHC and MSI test, respectively. The combination of IHC and MSI test had higher sensitivity and PPV than the clinical criteria ( p = 0.030). MSI test and IHC were highly concordant for LS-EC screening (73/77, 94.8%). Conclusion The accuracy of the combination of IHC of MMR proteins and MSI test for screening LS among Chinese patients with EC was superior to that of the clinical criteria. Trial registration NCT03291106. Registered on September 25, 2017

Background: This study aimed to investigate the specific vaginal microbiome in the differential diagnosis of endometriosis/adenomyosis (EM/AM)-associated chronic pelvic pain (CPP) from other types of CPP, and to explore the role of the vaginal microbiome in the mechanism of EM/AM-associated CPP. Methods: We recruited 37 women with EM/AM-associated CPP, 25 women with chronic pelvic pain syndrome (CPPS) without EM/AM, and 66 women without CPPS into our study. All of the participants were free from human papillomavirus (HPV) infection. Sequencing of barcoded 16S rRNA gene fragments (V4) was used to determine the vaginal microbiome composition on the Illumina HiSeq2500 System.Taxonomic and functional bioinformatics analyses were performed using t-test, linear discriminant analysis effect size (LEfSe), MetaStat, and PICRUSt algorithms.Results: At the species level, EM/AM-associated CPP was found to be associated with a predominance of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis, and a concomitant paucity of Lactobacillus jensenii, Lactobacillus reuteri, and Lactobacillus iners. When the relative abundance of Clostridium disporicum was over 0.001105% and that of Lactobacillus reuteri was under 0.1911349%, the differential diagnostic sensitivity and specificity were 81.08% and 52.0%, respectively.When serum CA125 was combined, the sensitivity increased to 89.19%, but the specificity remained at 52.0%. The PICRUSt results identified 7 differentially regulated pathways within the 3 groups that may be of relevance.Conclusions: Compared to that of CPPS patients without EM/AM and women without CPPS, the vaginal microbiome of patients with EM/AM-associated CPP shows significantly higher alpha (phylogenetic) diversity, as well as higher counts of Clostridium butyricum, Clostridium disporicum, Alloscardovia omnicolens, and Veillonella montpellierensis. These differences in the vaginal microbiome may interfere with local functional pathways, which could provide a direction for innovative metabolite-specific targeted treatment. The combination of vaginal biomarkers and serum CA125 may provide an original method to differentiate EM/ AM-associated CPP.

IntroductionIn the last three decades, minimally invasive surgery (MIS) for radical hysterectomy (RH) has become a popular treatment option for early-stage cervical cancer. However, a recently published randomised controlled trial (LACC trial) and an epidemiological study in the USA revealed strong evidence against the survival advantage of MIS for RH. However, the influencing factors of research centres and the learning curves of surgeons in these studies lacked sufficient evaluation. The efficacy of different surgical approaches for early-stage cervical cancer in the clinical and survival outcomes remains to be validated.Methods and analysisPatients diagnosed with FIGO (2009) stage IA1 (with lymphovascular space invasion), IA2 or IB1 cervical cancer with histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma will be recruited in this multicentre randomised controlled study. Patients will be randomly assigned to undergo MIS (robot-assisted or laparoscopic RH) or abdominal RH. Within 2 years, 1448 patients in 28 centres in China will be recruited to meet the criteria of a non-inferiority threshold of HR of 1.6 with bilateral nominal α <0.05 and power of 0.8. All surgeries will be performed by the indicated experienced surgeons. At least 100 RH cases in the individual past one decade of practice will be analysed as proof of learning curves. The primary objective of this study is 5-year disease-free survival. The secondary objectives include the overall survival rate, progression-free survival rate, disease-free survival rate, cost-effectiveness and quality of life.Ethics and disseminationThis study has been approved by the Institutional Review Board of Peking Union Medical College Hospital and is filed on record by all other centres. Written informed consent will be obtained from all eligible participants before enrolment. The results will be disseminated through community events, academic conferences, student theses and peer-reviewed journals.Trial registration numberNCT03739944.

Background: Vaginal dysbiosis may paly role in increased risk of human papillomavirus (HPV) infection.This study aims to explore potential vaginal microbiome biomarkers, to predict persistent high-risk HPV (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) 2+, and to find novel treatment targets for HPV infection.Methods: A total of 329 women aged 20-69 were enrolled in this study, including 59 with cervical persistent HPV infection irrespective of cytology status (group A), 139 with incident HPV infection (group B), and 131 without HPV infection (group C). Vaginal microbiome composition was determined by sequencing of barcoded 16S rDNA gene fragments (V4) on Illumina HiSeq2500.Results: In genus level, the relative abundance of Prevotella, Porphyromonas and Enterococcus were significantly the highest in group A, while Bacteroides was the lowest in group A. In species level, we found the relative abundance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis were the highest in group A while Lactobacillus iners was significantly under-represented in group A than the other two, and Prevotella disiens was over-represented in group C than the other two groups.Conclusions: A predominance of Prevotella bivia, Enterococcus durans and Porphyromonas uenonis with a concomitant paucity of Lactobacillus iners and Prevotella disiens may relate to HPV persistent infection. Furthermore, the relative abundance of Prevotella bivia being over 0.05554% with Prevotella disiens being under 0.02196% may be a good predictor for appearance CIN2+ for those diagnosed with the other 12 types of HR-HPV persistent infection but normal ThinPrep cytology test (TCT) testing. The exact molecular mechanism of the vaginal microbiome in the course of persistent HR-HPV infection and cervical neoplasia should be further explored. Future research should include intervention of vaginal microbiome composition to reverse the course of HR-HPV infection and the natural history of cervical neoplasia.

ObjectiveThe selection of individualized treatment for recurrent cervical cancer is challenging. This study aimed to investigate the impact of various therapies on survival outcomes after recurrence.MethodsEligible patients were diagnosed with recurrent cervical cancer between March 2012 and April 2018. Postrecurrence progression-free survival (PFS) and overall survival (OS) were investigated in the whole cohort and in subgroups, categorized by recurrence site and prior radiotherapy history, using a multivariate model that incorporated treatment for primary and recurrent tumors, histological pathology, and FIGO staging.ResultsTwo hundred and sixty recurrent cervical cancer patients were included. As of March 1, 2020, the median postrecurrence PFS and OS were 7.0 (range 0-94) and 24.0 (1.8-149.1) months, respectively. In a multivariate model measured by PFS, radiotherapy was superior to other therapies for the whole cohort (p=0.029) and recurrence only within the pelvic cavity (p=0.005), but the advantages of radiotherapy disappeared in patients with a history of radiotherapy (p values &gt;0.05). For recurrence only beyond the pelvic cavity, combination therapy resulted in improved PFS (p=0.028). For recurrence both within and beyond the pelvic cavity, no therapy regimen provided additional PFS benefits (p values &gt;0.05). Radiotherapy and combination therapy were also associated with improved postrecurrence OS for recurrence within the pelvic cavity (p=0.034) and only beyond the pelvic cavity (p=0.017), respectively.ConclusionsIn cervical cancer patients, postrecurrence radiotherapy can improve PFS and OS for patients with recurrence within the pelvic cavity and without prior radiotherapy. For recurrence beyond the pelvic cavity or cases with a history of radiotherapy, combination or individualized therapy may provide potential survival benefits.

Background The pathological characteristics, treatment strategies and prognosis of ovarian primary primitive neuroectodermal tumor (PNET) were unclear due to the rarity of PNET. All cases treated at Peking Union Medical College Hospital (PUMCH) between 1975 and 2016 and published in the English literature between 1980 to 2017 were reviewed. Results Finally four cases from PUMCH and 15 cases in the literature were included. The median age was 25 years (range 13–79), and the median diameter of the tumors was 13.4 cm (range 5.0–30.0). The most common initial symptoms were abdominal pain, bloating and a pelvic mass. Diagnosis primarily depended on immunohistochemical and fluorescence in situ hybridization data. Treatment consisted of surgery, various chemotherapy regimens and/or radiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 15 and 52%, respectively. For patients with OS and PFS > 12 months, the median ages were 21 years (range 13–35) and 17 years (range 13–35), respectively, while for patients with OS < 12 months and PFS < 12 months, the median ages were 48 years (range 14–79) and 25 years (range 18–79), respectively. Conclusions No standard therapy for ovarian primary PNET exists, and an individualized strategy is recommended. Young patients seem to have better prognoses.