Fertility-sparing surgery in children and adolescents with borderline ovarian tumors: a retrospective study.

OBJECTIVE: To describe the characteristics of children and adolescents with borderline ovarian tumors (BOTs) and evaluate the efficacy and safety of fertility-sparing surgery (FSS) in these patients. METHODS: Patients with BOTs younger than 20 years who underwent FSS were included in this study. RESULTS: A total of 34 patients were included, with a median patient age of 17 (range, 3-19) years; 97.1% (33/34) of cases occurred after menarche. Of the patients, 82.4% had mucinous borderline tumors (MBOTs), 14.7% had serous borderline tumors (SBOTs), and 2.9% had seromucinous borderline tumor (SMBOT). The median tumor size was 20.4 (range, 8-40)cm. All patients were at International Federation of Gynecology and Obstetrics stage I and all underwent FSS: cystectomy (unilateral ovarian cystectomy, UC, 14/34, 41.2% and bilateral ovarian cystectomy, BC, 1/34, 2.9%), unilateral salpingo-oophorectomy (USO; 18/34; 52.9%), or USO + contralateral ovarian cystectomy (1/34; 2.9%). The median follow-up time was 65 (range, 10-148) months. Recurrence was experienced by 10 of the 34 patients (29.4%). One patient with SBOT experienced progression to low-grade serous carcinoma after the third relapse. Two patients had a total of four pregnancies, resulting in three live births. The recurrence rate of UC was significantly higher in MBOTs than in USO (p = 0.005). The 5-year disease-free survival rate was 67.1%, and the 5-year overall survival rate was 100%. CONCLUSIONS: Fertility-sparing surgery is feasible and safe for children and adolescents with BOTs. For patients with MBOTs, USO is recommended to lower the risk of recurrence.

Identifying Serum Small Extracellular Vesicle MicroRNA as a Noninvasive Diagnostic and Prognostic Biomarker for Ovarian Cancer.

There remains a lack of effective and noninvasive methods for the diagnosis and prognosis prediction of epithelial ovarian carcinoma (EOC). Here, we investigated the possibility of serum-derived small extracellular vesicle (sEV) microRNAs (miRNAs) as potential biomarkers for distinguishing between benign and malignant adnexal masses and predicting the prognosis of EOC patients. A serum sEV miRNA model for identifying the EOC (sEVmiR-EOC) was successfully established in the training cohort. Furthermore, the sEVmiR-EOC model was confirmed in the testing cohort and validation cohort, demonstrating robust diagnostic accuracy. The sEVmiR-EOC model showed better performance than carbohydrate antigen 125 (CA125) in discriminating patients with stage I EOC from benign patients. Using EOC samples and follow-up data, we identified miR-141-3p and miR-200c-3p as potential prognostic predictors. Finally, we confirmed the change of the sEVmiR-EOC RiskScore between the preoperative and postoperative samples and found that the sEVmiR-EOC model could predict the prognosis of EOC patients.

Pharmacological Targeting of Bcl-2 Induces Caspase 3-Mediated Cleavage of HDAC6 and Regulates the Autophagy Process in Colorectal Cancer.

Compound 6d, a spiroindoline compound, exhibits antiproliferative capability against cancer cell lines. However, the exact underlying mechanism of this compound-mediated inhibitory capability remains unclear. Here, we showed that compound 6d is an inhibitor of Bcl-2, which suppresses CRC growth by inducing caspase 3-mediated intrinsic apoptosis of mitochondria. Regarding the underlying mechanism, we identified HDAC6 as a direct substrate for caspase 3, and caspase 3 activation induced by compound 6d directly cleaves HDAC6 into two fragments. Moreover, the cleavage site was located at D1088 in the DMAD-S motif HDAC6. Apoptosis stimulated by compound 6d promoted autophagy initiation by inhibiting interaction between Bcl-2 and Beclin 1, while it led to the accumulation of ubiquitinated proteins and the reduction of autophagic flux. Collectively, our findings reveal that the Bcl-2-caspase 3-HDAC6 cascade is a crucial regulatory pathway of autophagy and identify compound 6d as a novel lead compound for disrupting the balance between apoptosis and autophagy.

Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS.

Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.

Minimally invasive versus open radical trachelectomy for early-stage cervical cancer: protocol for a multicenter randomized controlled trial in China.

BACKGROUND: There are limited data comparing the oncologic and fertility outcomes of patients with early-stage cervical cancer (CC) treated by minimally invasive radical trachelectomy (MIRT) or abdominal radical trachelectomy (ART). The purpose of this multicenter study is to compare the oncologic and fertility outcomes of patients treated by MIRT or ART in a randomized controlled manner in China. METHODS: This is a noninferiority, randomized controlled trial performed at 28 Chinese centers; the study is designed to compare the oncologic and fertility outcomes of patients treated by MIRT (robot-assisted or laparoscopic RT) or ART. Patients will be recruited if they have been diagnosed with stage IA1 (with lymphovascular space invasion), IA2, or IB1 CC (with a maximum tumor diameter ≤ 2 cm) in the FIGO 2009 staging system and histological subtypes of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma and if they are also aged 18 to 40 years. These candidates will be randomly assigned to undergo MIRT or ART. The primary endpoint will be disease-free survival. Secondary endpoints will consist of overall and disease-free survival rates, fertility outcomes, and quality of life. A total of 414 patients are needed to accomplish the study goal, with 90.1% power at a 0.050 significance level to detect an equivalence hazard ratio of 0.75 in the ART group, considering 20% loss to follow-up. DISCUSSION: The results of the trial should provide robust evidence to surgeons regarding options for the surgical approach in patients with early-stage CC who have a strong willingness to preserve fertility. TRIAL REGISTRATION: ClinicalTrials.gov NCT03739944 . Registered on November 14, 2018.

Efficacy of different surgical approaches on survival outcomes in patients with early-stage cervical cancer: protocol for a multicentre longitudinal study in China.

INTRODUCTION: Recent studies have revealed that the oncological survival outcomes of minimally invasive radical hysterectomy (MIRH) are inferior to those of abdominal radical hysterectomy (ARH) in early-stage cervical cancer, but the potential reasons are unclear. METHODS AND ANALYSIS: Each expert from 28 study centres participating in a previously reported randomised controlled trial (NCT03739944) will provide successive eligible records of at least 100 patients who accepted radical hysterectomy for early-stage cervical cancer between 1 January 2009 and 31 December 2015. Inclusion criteria consist of a definite pathological evaluation of stages IA1 (with positive lymphovascular space invasion), IA2 and IB1 according to the International Federation of Gynecology and Obstetrics 2009 staging system and a histological subtype of squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. The primary endpoint is 5-year disease-free survival between the MIRH and ARH groups. The secondary endpoints include the MIRH learning curves of participating surgeons, 5-year overall survival between the MIRH and ARH groups, survival outcomes according to surgical chronology, surgical outcomes and sites of recurrence and potential risk factors that affect survival outcomes. A subgroup analysis in patients with tumour diameter less than 2 cm will follow the similar flow diagram. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Peking Union Medical College Hospital (registration no. JS-1711), and is also filed on record by all other 27 centres. The results will be disseminated through community events and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03738969.

Expanded activated autologous lymphocyte infusions improve outcomes of low- and intermediate-risk childhood acute myeloid leukemia with low level of minimal residual disease.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P < 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study.

Little is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

Laparoscopic vs. Abdominal Radical Hysterectomy for Locally Advanced Cervical Cancer.

This study is to compare the survival outcomes of laparoscopic radical hysterectomy (LRH) to those of abdominal radical hysterectomy (ARH) for patients with locally advanced cervical cancer (LACC). Patients with the International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IIB LACC who underwent radical hysterectomy between 2001 and 2015 were identified. The disease-free survival (DFS) and overall survival (OS) were compared according to the surgical approach and were adjusted based on clinicopathologic characteristics. A total of 396 patients were included in the study, with 179 (45.2%) and 217 (54.8%) patients in the ARH and LRH groups, respectively. The LRH group showed a significantly lower amount of estimated blood loss, lower blood transfusion rate and shorter length of hospital stay. Overall, there were no significant differences in the 5-year DFS and 5-year OS between the LRH and ARH groups with the Kaplan-Meier method. However, multivariate analyses identified LRH as an independent prognostic factor for a poor DFS (hazard ratio [HR] 2.5; 95% confidence interval [95% CI] 0.19 to 0.87; p = 0.02). The analysis of stage IB2 disease and the squamous subtype (61.9% and 87.9% of all participants, respectively) reached the same conclusion. When stratifying by FIGO stage, the patients with IB2 (n = 348) in the ARH group had a significantly better DFS (HR 0.14, 95% CI 0.05-0.42, p < 0.01) and OS (HR 0.17, 95% CI 0.04-0.67, p = 0.11) than those in the LRH group in the Cox regression model. However, no differences were found in patient with stage IIA1, IIA2, or IIB in Cox regression model. When stratifying by histological types, for the patients with squamous carcinomas (n = 375), in Cox model, ARH had a significantly superior DFS compared with those who underwent LRH (HR 0.45, 95% CI 0.25-0.82, p = 0.01), but the OS was not statistically significant (HR 0.57, 95% CI 0.27-1.20, p = 0.14). However, no differences were found in patient with adenocarcinoma and adenosquamous carcinomas in the Cox model. Therefore, ARH was associated with a higher DFS than LRH in patients with LACC, especially in patients with stage IB2 disease or the squamous subtype.

Simultaneous detection and comprehensive analysis of HPV and microbiome status of a cervical liquid-based cytology sample using Nanopore MinION sequencing.

Human papillomavirus (HPV) is a major pathogen that causes cervical cancer and many other related diseases. HPV infection related cervical microbiome could be an induce factor of cervical cancer. However, it is uncommon to find a single test on the market that can simultaneously provide information on both HPV and the microbiome. Herein, a novel method was developed in this study to simultaneously detect HPV infection and microbiota composition promptly and accurately. It provides a new and simple way to detect vaginal pathogen situation and also provide valuable information for clinical diagnose. This approach combined multiplex PCR, which targeted both HPV16 E6E7 and full-length 16S rRNA, and Nanopore sequencing to generate enough information to understand the vagina condition of patients. One HPV positive liquid-based cytology (LBC) sample was sequenced and analyzed. After comparing with Illumina sequencing, the results from Nanopore showed a similar microbiome composition. An instant sequencing evaluation showed that 15 min sequencing is enough to identify the top 10 most abundant bacteria. Moreover, two HPV integration sites were identified and verified by Sanger sequencing. This approach has many potential applications in pathogen detection and can potentially aid in providing a more rapid clinical diagnosis.

Surgical, Urinary, and Survival Outcomes of Nerve-sparing Versus Traditional Radical Hysterectomy: A Retrospective Cohort Study in China.

PURPOSE: The purpose of this retrospective study was to compare the surgical, urinary, and survival outcomes between nerve-sparing radical hysterectomy (NSRH) and traditional radical hysterectomy (TRH) for stage IB cervical cancer, in which all the primary procedures were performed by a single physician. METHODS: Patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO) stage IB were included if they received radical hysterectomy of class III or type C in 1 center between February 2001 and November 2015. The epidemiological, clinicopathologic, surgical, and urinary data were collected and compared between the NSRH and TRH groups. The follow-up period ended in December 2016. RESULTS: A total of 406 patients were identified, including 111 (27.3%) in the TRH group and 295 (72.7%) in the NSRH group. Most epidemiological and clinicopathologic characteristics were balanced between the 2 groups. The NSRH and TRH groups had similar mean operating times and comparable short-term postoperative complications, but NSRH had less mean estimated blood loss and a shorter mean postoperative stay (all P <0.001). Within 12 months from surgeries, patients in the NSRH group had less residual urine and fewer urinary dysfunctions. For the 371 patients with definite survival outcomes, in the multivariate analysis, both overall survival (hazard ratio=1.79, 95% confidence interval: 0.64-5.02) and disease-free survival (hazard ratio=1.50, 95% confidence interval: 0.72-3.11, P=0.280) of the NSRH group were similar to those of the TRH group. CONCLUSION: NSRH for stage IB cervical cancer patients had better urinary outcomes than TRH without sacrificing the safety and survival benefits.

Germline and somatic mutations of multi-gene panel in Chinese patients with epithelial ovarian cancer: a prospective cohort study.

BACKGROUND: Multiple targeted gene sequencing is seldom performed in both germline and somatic testing for ovarian cancer. This study is to evaluate the specific genetic alterations, including both somatic and germline mutations, in Chinese patients with epithelial ovarian cancer (EOC) in a prospective cohort study. MATERIALS AND METHODS: Mutations in a customed 21-gene panel that included BRCA1, BRCA2, and 19 other tumor suppressor genes related to homologous recombination (HR) deficiency or non-HR deficiency were detected by targeted exon capture and next-generation sequencing (NGS) technology across all coding exons and exon-intron (±20 base pairs) boundaries. Patients were enrolled consecutively and unselectively without age or family history consideration. Sixty-two unselected patients with epithelial ovarian cancer were enrolled in our study to be tested for paired somatic and germline mutations. All patients were tested using a 21-gene panel that included BRCA1, BRCA2, CHEK2, PALB2, BRIP1, TP53, PTEN, STK11, CDH1, ATM, BARD1, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PMS1, PMS2, RAD50, and RAD51C. RESULTS: Mutation analysis revealed that 77.4% (48/62) of patients carried one or more of 64 identified genetic alterations, including 19 germline and 45 somatic deleterious mutations. Twelve individuals shared both germline and somatic mutations. BRCA mutants existed in 17 of 62 (27.4%) patients. Of the 64 mutations detected, 46 (74.2%) were in 7 other HR or non-HR genes, including TP53, PTEN, ATM, CHEK2, PALB2, RAD51C, and STK11. In somatic mutation analysis, TP53 showed frequent pathogenic or likely pathogenic mutations in 56.5% (35/62) of enrolled cases, among which six cases harbored a loss of heterozygosity. CONCLUSIONS: This is the first report of multi-gene panel testing for germline and somatic mutations among Chinese EOC patients, which revealed a broader deleterious variants than only BRCA testing. REGISTRATION: Registration No. NCT03015376, clinicaltrials.gov , registered on January 10, 2017.

Efficacy of different surgical approaches in the clinical and survival outcomes of patients with early-stage cervical cancer: protocol of a phase III multicentre randomised controlled trial in China.

INTRODUCTION: In 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 ANALYSIS: Patients 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 DISSEMINATION: This 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 NUMBER: NCT03739944.

The prophylactic effects of long-acting granulocyte colony-stimulating factor for febrile neutropenia in newly diagnosed patients with epithelial ovarian cancer: a randomised controlled study.

OBJECTIVE: This study explored the prophylactic effects of long-acting granulocyte colony-stimulating factor (G-CSF) for febrile neutropenia (FN) in newly diagnosed patients with epithelial ovarian cancer (EOC). METHODS: Patients were randomised into a study group (long-acting G-CSF for all chemotherapy cycles) and a control group (short-acting G-CSF for first cycle and treatment per physician discretion for subsequent cycles) at a ratio of 1:2. The incidences of FN and myelosuppression and the number of clinical visits, medication doses, complete blood count (CBC) tests and adverse events were compared between the two groups. A regression model was used to determine the risk factors for FN. RESULTS: From 30 November 2018 to 1 April 2019, 84 cases were included in the final analysis; there were 24 (28.6%) and 60 (71.4%) patients in the study and control groups, respectively, and 605 chemotherapy cycles. The study group or chemotherapy cycles utilising long-acting G-CSF had significantly fewer utilisations and doses of short-acting G-CSF; clinical visits; CBC tests; and incidences of FN and myelosuppression; and less G-CSF-associated pain. The utilisation of G-CSF was the only independent factor for FN in a binary regression model. CONCLUSION: Long-acting G-CSF could effectively reduce the incidences of FN and myelosuppression and had mild adverse effects in newly diagnosed patients with EOC receiving chemotherapy. TRIAL REGISTRATION NUMBER: NCT03740464.

Neoadjuvant chemotherapy followed by radical hysterectomy for stage IB2-to-IIB cervical cancer: a retrospective cohort study.

INTRODUCTION: This study was to evaluate the surgical and survival effects of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) for cervical cancer with stages IB2 to IIB of FIGO 2009 staging. METHODS: From February 2, 2001 to November 11, 2015, 428 patients received NAC followed by RH in a tertiary hospital, in which all the major procedures were performed by one surgeon. Surgical and survival outcomes were evaluated between the NAC and primary RH groups. RESULTS: A total of 279 (65.2%) patients received NAC, and the overall clinical and complete pathological response rates were 65.9% and 10.8%, respectively. Compared with primary RH patients, NAC patients had more advanced stages, higher recurrence rate, longer median duration of RH, and more median estimated blood loss. After adjusted with baseline risk factors, no significant differences in progression-free or overall survival were observed between the NAC and primary RH groups. However, the responders to NAC had better survival outcomes. CONCLUSIONS: There were no surgical or survival benefits of NAC for patients with cervical cancer of stages IB2 to IIB except for the responders to NAC.

Comparison of screening strategies for Lynch syndrome in patients with newly diagnosed endometrial cancer: a prospective cohort study in China.

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.

The impact of the surgical routes and learning curve of radical hysterectomy on the survival outcomes in stage IB cervical cancer: A retrospective cohort study.

OBJECTIVE: Little is known about the definite reasons of the disadvantage of minimally invasive surgery in the treatment of early stage cervical cancer. This study is to compare survival outcomes of patients with stage IB cervical cancer who received radical hysterectomy (RH) by one surgeon in different periods. METHODS: A retrospective analysis was performed on stage IB cervical cancer patients who received RH from February 2001 to November 2015 at a tertiary hospital. All the major procedures were performed by one surgeon. The clinicopathological characteristics and survival outcomes were compared with laparoscopic RH (LRH) and abdominal RH (ARH) groups in the periods of 2001-2005, 2006-2010, and 2011-2015. RESULTS: Totally 406 patients were included in the study, 135 (33.3%) and 271 (66.7%) in ARH and LRH groups respectively. The 5-year disease-free survival (DFS) of all patients increased from 2001 to 2005 to 2006-2010 but decreased in 2011-2015. No significant differences exist in the 5-year DFS and overall survival (OS) rates in the first 50 patients of LRH and ARH groups. The subgroup analysis in stage IB1 patients (68.2% of all participants) reached the same conclusions. CONCLUSION: For RH patients, in which all major procedures were performed by one surgeon, the DFS did not exhibit substantial improvement in the period of 2001-2015 since the extensive adoption of LRH. The learning curve probably explains the disadvantage of LRH.

The Urodynamics and Survival Outcomes of Different Methods of Dissecting the Inferior Hypogastric Plexus in Laparoscopic Nerve-Sparing Radical Hysterectomy of Type C: A Randomized Controlled Study.

BACKGROUND: Little data exist about the impact of dissection methods on bladder function during nerve-sparing radical hysterectomy (NSRH). This randomized controlled trial compared the urodynamic and survival outcomes of different methods dissecting the inferior hypogastric plexus (IHP) during laparoscopic NSRH. METHODS: Eligible patients presenting with stage IB cervical cancer from 9 May 2013 to 27 October 2015 were randomized at a ratio of 1:1 and subjected to waterjet (study group) or traditional blunt (control group) dissection of the IHP for laparoscopic type C radical hysterectomy. Participants were subjected to urodynamic evaluations before and after NSRH. The primary measurement was the proportion of patients with residual urine (RU) ≤ 100 ml, while secondary measurements included urodynamic parameters, disease-free survival (DFS), and overall survival (OS). RESULTS: In total, 191 women met the inclusion criteria, and 160 patients were included in the final analysis, with 80 randomized to each group. At 14 days after NSRH, the study group had more patients with RU ≤ 100 ml than the control group (82.5% vs. 62.5%, p = 0.005). The study group had similar urodynamic outcomes of preoperative and postoperative tests. Comparison with the study group and preoperative tests revealed the control group had significant bladder function impairment at 4 months after NSRH. After a median follow-up of 33 months, the dissection methods had no significant impact on DFS or OS. CONCLUSIONS: Waterjet dissection of the IHP in laparoscopic NSRH resulted in a more rapid return of normal urodynamics without compromising survival outcome. ClinicalTrials.gov Identifiers NCT03015376 (PUMCH-OBGYN-2013), NCT03291236 (SOCM-1).

Pelvic Exenteration for Recurrent and Persistent Cervical Cancer.

BACKGROUND: Pelvic exenteration (PE) for primary and recurrent cervical cancer has resulted in favorable survival outcomes, but there are controversies about specific prognosis factors, and up to now, there have been no published reports from China. This study aimed to share our experiences of PE, which were performed in a single institution. METHODS: From January 2009 to January 2016, 38 patients with recurrent or persistent cervical cancer were included in the study, and they were followed up until January 2017. Epidemiological and clinicopathological characteristics of patients were compared for survival outcomes in univariate and Cox hazard regression analysis. RESULTS: There were thirty-one and seven patients with recurrent and persistent cervical cancer, respectively. The median age of patients was 45 years (range 29-65 years). Total, anterior, and posterior PE consisted of 52.6%, 28.9%, and 18.4% of cases, respectively. Early and late complications occurred in 21 (55.3%) patients and 15 (39.5%) patients, respectively. Two (5.3%) patients died due to complications related to surgeries within 3 months after PE. The median overall survival (OS) and disease-free survival (DFS) were 28.5 months (range 9-96 months) and 23 months (range 4-96 months), respectively, and 5-year OS and DFS were 48% and 40%, respectively. Cox hazard regression analysis showed that, the margin status of the incision and mesorectal lymph node status were independent risk factors for OS and DFS. CONCLUSION: In our patients with recurrent and persistent cervical cancer, the practice of PE might achieve favorable survival outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03291275; https://clinicaltrials.gov/ct2/show/NCT03291275?term=NCT03291275&rank=1.

Lymph nodes metastasis in cervical cancer: Incidences, risk factors, consequences and imaging evaluations.

AIM: The aim of this study was to determine the incidence, risk factors, consequences and accuracy of imaging evaluation of lymph node (LN) metastasis in a cohort of 406 patients treated with radical hysterectomy (RH), lymphadenectomy of pelvic LN (PLN) and para-aortic LN (PALN), which was performed primarily by one physician. METHODS: From February 2001 to November 2015, patients with cervical cancer of FIGO stage IB were included, if they received RH of class III or type C performed by Dr. M. Wu in Peking Union Medical College Hospital. Follow-up ended in December 2016. Incidences and accuracy of imaging evaluation of LN metastasis were described, and predictive factors of LN metastasis and its impact on survival outcomes were determined in univariate and multivariate models. RESULTS: Among 406 patients with clinical stage IB, 57 (14.0%) had lymphatic metastasis. In multivariate model, positive parametrium was independent factor for general LN metastasis (odds ratio [OR] 5.1; 95% confidence interval [95% CI], 2.1-12.1) and PLN metastasis (OR 5.3; 95% CI, 2.2-12.8). Positive PLN was independent factor for metastasis to common iliac LN and PALN. After adjusted with clinico pathologic factors, general and site-specific LN metastases were independent risk factors of progression-free survival and overall survival (all P values <0.05). Preoperative imaging evaluation had low sensitivity but high specificity for predicting LN metastasis. Various imaging methods had similar predictive accuracy. CONCLUSION: Lymphatic metastasis was significantly related to the clinico pathologic characters and survival of cervical cancer. More sensitive preoperative evaluation is needed for predicting the LN metastasis.