Zhengyu Li

The clinical features and management of Lynch syndrome‐associated ovarian cancer

AbstractAimLynch syndrome (LS) is one of the most common hereditary cancer syndromes, characterized by mutations in mismatch repair genes and autosomal dominant inheritance. Women with LS have an additional increased risk of gynecologic malignancies, including endometrial cancer (EC) and ovarian cancer (OC). Compared with EC, OC is relatively under investigation. This review thoroughly summarizes the current clinical evidence of surveillance, screening, and prevention strategies, and describes the molecular and clinical characteristics of LS‐associated OC.MethodsAn electronic search from databases of PubMed and Google Scholar was carried out using key words pertaining to Lynch syndrome and ovarian cancer. A review of the literatures including review articles, experimental, and observational studies published between 2000 and 2021 was conducted.ResultsThe lifetime risk of OC in women with LS of MLH1, MSH2, and MSH6 mutations is approximately 7%, with the median age at onset being 46 years, 10–15 years earlier than that in sporadic cases. Histologically, LS‐associated OCs are primarily endometrioid (40%), high‐grade (25%), and low‐grade (11%) serous, or clear cell (6%) in nature. Eighty‐five percent of patients are diagnosed at an early stage, presenting with a good prognosis at 84% 5‐year survival. Optimal screening strategies for OC in LS are controversial; combined screening of patients' clinical and family history, immunohistochemical analysis, and microsatellite instability testing for mismatch repair deficiency have been proven efficient.ConclusionThe clinical features were different between ovarian cancer in Lynch syndrome and sporadic cases. More research are needed for a greater understanding of the prevention and medical treatment of LS‐associated OC.

High L1CAM expression predicts poor prognosis of patients with endometrial cancer

Abstract Backgroud: Previous studies have reported that the levels of L1 cell adhesion molecule (L1CAM) indicate poor prognosis of patients with various solid tumors. However, the prognostic significance of L1CAM in endometrial cancer has remained controversial. Herein, we conducted a systematic review and meta-analysis to evaluate the prognostic value of L1CAM in endometrial cancer. Methods: All studies related to the association between L1CAM expression and clinical characteristics of endometrial cancer were identified by searching the PubMed, MEDLINE, EMBASE, and Web of Science databases. Primary outcomes of the meta-analysis were the hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Secondary outcomes were odds ratios (ORs) for clinicopathological characteristics. Publication bias and sensitivity analysis were conducted to ensure reliability of the results. Results: Overall, 17 studies encompassing 7146 patients were eligible for the meta-analysis. Results showed L1CAM overexpression to be significantly associated with decreased overall survival (HR = 2.87, 95% CI; 1.81–4.55, P < .001) and disease-free survival (HR = 3.32, 95% CI; 1.99–5.55, P < .001) in patients with endometrial cancer. High L1CAM expression was also related to adverse clinicopathological characteristics. Conclusion: This systematic review demonstrated that high L1CAM expression is correlated with poor survival outcomes and adverse clinicopathological parameters in patients with endometrial cancer.

Para‐aortic lymphadenectomy did not improve overall survival among women with type I endometrial cancer

AbstractObjectiveTo compare outcomes and prognosis among women with type I endometrial cancer undergoing hysterectomy and bilateral salpingo‐oophorectomy (H‐BSO) with or without systematic pelvic lymphadenectomy (PLD) or para‐aortic lymphadenectomy (PALD).MethodsRetrospective review of women postoperatively diagnosed with type I endometrial cancer who underwent H‐BSO at a university hospital in Chengdu, China (January 2010 to June 2012). Women were divided into no lymphadenectomy (PLD−/PALD−), systematic pelvic lymphadenectomy (PLD+/PALD−), or combined pelvic and para‐aortic lymphadenectomy (PLD+/PALD+) groups. Follow‐up was by telephone. Postoperative outcomes and prognosis were compared and risk factors were analyzed.ResultsIn total, 333 women met the inclusion criteria: 121 underwent PLD+/PALD−, 166 underwent PLD+/PALD+, and 46 underwent PLD−/PALD−. There were no differences in pre‐operative characteristics among the groups (all P>0.05). The PLD+/PALD+ group had a higher laparotomy rate (P=0.001), the PLD−/PALD− group had shorter operation time (P=0.001) and lower blood loss (P<0.001). There were no differences between the PLD+/PALD− and PLD+/PALD+ groups. Overall, 291 women had sufficient follow‐up data; there was no difference in overall survival, and PALD was not a predictor of survival.ConclusionPostoperative outcomes were similar among all surgical groups; a survival benefit of PALD was not demonstrated.

Poly (ADP-ribose) polymerase (PARP) inhibitor regimens for ovarian cancer in phase III randomized controlled trials: a network meta-analysis

We aimed to evaluate poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) regimens in BRCA-mutated ovarian cancer for patients responsive to front-line platinum (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) or platinum-sensitive relapsed (olaparib, rucaprib, niraparib) patients in phase III randomized controlled trials. A network meta-analysis was utilized to generate the direct and indirect comparisons. The primary outcomes for network meta-analysis were efficacy (hazard ratios for progression-free survival in BRCA mutation cohort) and toxicity (odds ratios for all grade 3-4 adverse events). The American Society of Clinical Oncology (ASCO) value framework was used to assess the cost-effectiveness of the PARPi regimens. Network meta-analysis indicated no statistically significant differences in efficacy and toxicity among the assessed upfront or relapsed PARPi regimens (95% CI included 1). The ASCO value framework indicated that current PARPi regimens were similar in clinical benefits, toxicity, and net health benefit in the upfront (bevacizumab and olaparib, veliparib and chemotherapy, olaparib) and relapsed setting (olaparib, rucaprib, niraparib). The addition of bevacizumab to olaparib ($353.72) increased the cost per unit net health benefit for patients compared with olaparib monotherapy ($260.57). The upfront PARPi regimens had lower toxic scores than the regimens used at relapse. The choice of PARPi regimens both in the upfront and relapsed setting should consider not only efficacy and toxicity but also costs in BRCA mutation patients. Current combining PARPi regimens are not recommended for such patients in the upfront setting from the cost-effective perspective. Upfront PARPi regimens are less toxic than those used at relapse.

Staging procedures fail to benefit women with borderline ovarian tumours who want to preserve fertility: a retrospective analysis of 448 cases

Abstract Background To evaluate the effect of clinicopathologic factors on the prognosis and fertility outcomes of BOT patients. Methods We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from 2008 to 2015. The DFS outcomes, potential prognostic factors and fertility outcomes were evaluated. Results Four hundred forty-eight patients were included; 52 recurrences were observed. Ninety-two patients undergoing FSS achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups. Staging surgery was not an independent prognostic factor for DFS. Laparoscopy resulted in better prognosis than laparotomy in patients with stage I tumours and a desire for fertility preservation. Conclusion Patients with BOT fail to benefit from surgical staging. Laparoscopy is recommended for patients with stage I disease who desire to preserve fertility. Physicians should pay more attention to risk of recurrence in patients who want to preserve fertility.

SNHG1 represses the anti-cancer roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin signaling

As a flavonoid, baicalein exhibits remarkable anti-cancer roles in several cancers. However, the factors regulating the antitumorigenic roles of baicalein in cervical cancer remain undefined. Here, we revealed that long noncoding RNA SNHG1 is implicated in the tumor-suppressive roles of baicalein. Functional assays demonstrated that ectopic expression of SNHG1 attenuates the roles of baicalein in repressing cervical cancer cell viability, inducing apoptosis, and repressing migration. SNHG1 silencing promotes the tumor-suppressive roles of baicalein in cervical cancer cell viability, apoptosis, and migration. Xenograft assays showed that SNHG1 reverses the tumor-suppressive roles of baicalein in repressing cervical cancer growth in vivo. Mechanistic investigations revealed that SNHG1 directly binds miR-3127-5p and up-regulates FZD4, a target of miR-3127-5p. Via regulating miR-3127-5p/FZD4, SNHG1 activates Wnt/β-catenin signaling. Moreover, SNHG1 reverses the repressive role of baicalein on Wnt/β-catenin signaling. The effect of SNHG1 on the antitumorigenic process of baicalein was abolished by Wnt/β-catenin signaling inhibitor ICG-001. Together, our observations demonstrated that SNHG1 represses the tumor-suppressive roles of baicalein in cervical cancer through regulating miR-3127-5p/FZD4/Wnt/β-catenin axis, and suggested that targeting SNHG1 represents a potential strategy to enhance the tumor-suppressive roles of baicalein in cervical cancer. Impact statement Baicalein exhibits anti-cancer roles in several cancers. However, the factors influencing the antitumorigenic efficiencies of baicalein in CC remain largely unclear. Here, we provide convincing evidences that lncRNA SNHG1 attenuates the tumor-suppressive roles of baicalein in CC cell viability, apoptosis, migration, and CC tumor growth. This study further demonstrates that the influences of SNHG1 in the antitumorigenic process of baicalein are achieved through modulating the miR-3127-5p/FZD4Wnt/β-catenin axis. SNHG1 attenuates the repressive role of baicalein on Wnt/β-catenin. Therefore, SNHG1 is a novel modulator of the tumor-suppressive roles of baicalein and SNHG1 represents a therapeutic intervention target to reinforce the tumor-suppressive roles of baicalein in CC.

Comparison of laparoscopic versus open radical hysterectomy in patients with early-stage cervical cancer: a multicenter study in China

Recently, the safety of minimally invasive surgery in the treatment of cervical cancer has been questioned. This study was designed to compare the disease-free survival and overall survival of abdominal radical hysterectomy and laparoscopic radical hysterectomy in patients with early-stage cervical cancer. A total of 1065 patients with early-stage cervical cancer who had undergone abdominal/laparoscopic radical hysterectomy between January 2013 and December 2016 in seven hospitals were retrospectively analyzed. The 1:1 propensity score matching was performed in all patients. Patients with tumor size ≥2 cm and <2 cm were stratified and analyzed separately. Disease-free survival and overall survival were compared between matched groups. After confirming the normality by the Shapiro-Wilks test, the Mann-Whitney U test and the χ After matching, a total of 812 patients were included in the disease-free survival and overall survival analyses. In the entire cohort, the laparoscopic radical hysterectomy group had a significantly shorter disease-free survival (HR 1.65, 95% CI 1.00 to 2.73; p=0.048) but not overall survival (HR 1.60, 95% CI 0.89 to 2.88; p=0.12) when compared with the abdominal radical hysterectomy group. In patients with tumor size ≥2 cm, the laparoscopic radical hysterectomy group had a significantly shorter disease-free survival (HR 1.93, 95% CI 1.05 to 3.55; p=0.032) than the abdominal radical hysterectomy group, whereas no significant difference in overall survival (HR 1.90, 95% CI 0.95 to 3.83; p=0.10) was found. Additionally, in patients with tumor size <2 cm, the laparoscopic radical hysterectomy and abdominal radical hysterectomy groups had similar disease-free survival (HR 0.71, 95% CI 0.24 to 2.16; p=0.59) and overall survival (HR 0.59, 95% CI 0.11 to 3.13; p=0.53). Laparoscopic radical hysterectomy was associated with inferior disease-free survival compared with abdominal radical hysterectomy in the entire cohort, as well as in patients with tumor size ≥2 cm. For the surgical treatment of patients with early-stage cervical cancer, priority should be given to open abdominal radical hysterectomy.

Application of novel tumor-free techniques in laparoscopic radical hysterectomy for early cervical cancer

Surgical Approach and Use of Uterine Manipulator Are Not Associated with LVSI in Surgery for Early-stage Cervical Cancer

In 2018, the Laparoscopic Approach to Cervical Cancer trial reported that patients undergoing minimally invasive surgery for cervical cancer (CC) had poorer outcomes than patients undergoing open surgery. Several hypotheses have been made to explain the results. We aimed to investigate whether laparoscopic procedures and use of a uterine manipulator increase the risk of lymphovascular space invasion (LVSI) in early-stage CC. A retrospective study. A Chinese women's and children's hospital. Patients with early-stage CC who underwent radical hysterectomy in West China Second University Hospital between April 2019 and May 2020. Laparoscopic surgery (with uterine manipulator and uterine manipulator-free) and open surgery. A total of 979 patients diagnosed with CC were registered in West China Second University Hospital for surgical treatment. Of these, 525 patients underwent laparoscopic surgery and 454 patients underwent open surgery. In total, 735 patients with early-stage cancer underwent radical hysterectomy and pelvic lymphadenectomy, including 357 by laparoscopic surgery and 378 by open surgery. For those who underwent radical hysterectomy and pelvic lymphadenectomy, the incidence of LVSI was 48.41% and 47.34% in laparoscopic and open groups, respectively (p = .771). After 1:1 propensity score matching with age, International Federation of Gynecology and Obstetrics stage, pathology, and tumor size, the incidence of LVSI was 45.54% and 51.79% in laparoscopic and open groups, respectively (p = .186). Subdividing the laparoscopic group into uterine manipulator and uterine manipulator-free groups, the incidence of LVSI was 45.22% and 48.35%, respectively (p = .580). After propensity score matching with age, International Federation of Gynecology and Obstetrics stage, pathology, and tumor size, the incidence of LVSI was 45.78% and 55.42% in these 2 groups, respectively (p = .214). Multiple factor analysis revealed that lymph node metastasis and deep stromal invasion were associated with LVSI (p value <.05 in both groups). The surgical approach and use of a uterine manipulator are not associated with LVSI in surgery for early-stage CC. Lymph node metastasis and deep stromal invasion are associated with LVSI.

Comparison of adverse events of laparoscopic versus open surgery on cervical cancer