ObjectiveTo systematically review the diagnostic value between serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) for endometrial cancer (EC). MethodsWe electronically searched databases including PubMed, The Cochrane Library, Web of Science, ScienceDirect, EBSCO, CNKI and VIP to collect diagnostic accuracy studies of serum HE4 and/or CA125 versus golden standard (pathology) for EC from inception to August 2014. Two reviewers independently screened literature, extracted data and assessed the risk bias of included studies by QUADAS-2 tool. Then, meta-analysis was performed by Meta-Disc 1.4 software. ResultsA total of 20 studies involving 4 351 participants were included. The results of meta-analysis showed that:the pooled sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), and negative likelihood ratio (-LR), and diagnostic odds ratio (DOR) of HE4 in the diagnosis of EC were 0.56 (95%CI 0.54 to 0.58), 0.89 (95%CI 0.88 to 0.90), 6.19 (95%CI 4.31 to 8.88), 0.49 (95%CI 0.44 to 0.56), and 14.27 (95%CI 9.50 to 21.42), respectively. The area under the curve (AUC) of SROC was 0.855 9. The pooled Sen, Spe, +LR,-LR, and DOR of CA125 in the diagnosis of EC were 0.33 (95%CI 0.31 to 0.34), 0.80 (95%CI 0.78 to 0.82), 2.07 (95%CI 1.45 to 2.95), 0.83 (95%CI 0.76 to 0.91), and 2.65 (95%CI 1.63 to 4.32), respectively. The SROC AUC was 0.657 5. ConclusionCompared with CA125, HE4 has higher diagnostic accuracy for EC. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
目的:总结分析子宫内膜癌临床特点、治疗方法的疗效及与各预后高危因素之间的关系，以提高临床诊疗水平。方法:回顾性分析我院1998年1月～2005年12月收治住院的子宫内膜癌患者499例的临床病理资料，总结患者的一般情况、临床特点并进行随访，分析内膜癌高危因素对预后的影响。采用寿命表法计算患者生存率，Wilcoxon (Gehan) 比分法及Cox比例风险模型分析预后因素。结果:(1) 手术－病理分期I、Ⅱ、Ⅲ期患者5年生存率分别为94%、100％、75.3％，IV期患者1年生存率57.1%、2年生存率11.4％。(2) 单因素分析显示：病理类型、手术－病理分期、组织学分级、肌层浸润深度、淋巴结转移和是否行淋巴结切除术是影响预后的高危因素。（3）多因素分析显示：病理类型、手术－病理分期、组织学分级和肌层浸润深度是影响患者预后的独立危险因素。结论:(1) 对具有高危因素的患者，如特殊病理类型、手术－病理分期期别晚、组织学分级为G3和深肌层浸润，应辅以术后治疗以提高生存率。(2)分期越晚，生存率越低（Plt;0.05）。
Objective To assess the clinical effectiveness and safety of laparoscopy versus laparotomy for endometrial cancer. Methods The databases such as The Cochrane Library, PubMed, EMbase, Ovid, CNKI, WanFang Data, and VIP were searched to collect the randomized control trials (RCTs) about the clinical effectiveness and safety of laparoscopy and laparotomy for endometrial cancer. The retrieval time was from January 1998 to September 2012. Two reviewers independently screened the literature according to the inclusive and exclusive criteria, extracted the data, and assessed the methodological quality of included studies. Then the meta-analysis was performed by using RevMan 5.0 software. Results A total of 10 RCTs involving 6 993 patients were included. Meta-analysis showed that, compared with laparotomy, laparoscopy had lesser amount of intraoperative bleeding, lower decrease of hemoglobin before and 1-day after operation, shorter time of both waiting for postoperative gas and hospital stay, lower incidence of postoperative complications, longer operation time, and higher incidence of intraoperative complications. Additionally, there were no differences between the 2 groups in the number of pelvic and para-aortic lymph nodes removed during operation, as well as the postoperative recurrence and mortality rates in 3-5 year follow-up. Conclusion Compared with laparotomy, laparoscopy shows lesser amount of intraoperative bleeding, lower decrease of hemoglobin before and 1-day after operation, shorter time of both waiting for postoperative gas and hospital stay, lower incidence of postoperative complications. But laparotomy shows lower incidences of intraoperative complications, and shorter operation time. Both operations are similar in the number of pelvic and para-aortic lymph nodes removed during operation, as well as the postoperative recurrence and mortality rates in 3-5 year follow-up. For quantity limitation and low methodological quality of included studies, this conclusion still needs to be further proved by performing more high-quality and large scale RCTs.
ObjectiveTo evaluate the cost-effectiveness of robot-assisted laparoscopic surgery (RALS) versus conventional laparoscopic surgery (CLS) for early-stage endometrial cancer (EC) from a societal perspective. MethodsA decision-tree model was constructed to conduct cost-utility analysis, simulating the short-term intraoperative to postoperative clinical progression of patients. Primary evaluation metrics included cumulative costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). The willingness-to-pay (WTP) threshold was set at three times the 2024 per capita gross domestic product (GDP) of China. The sensitivity analyses were performed to assess robustness of the model. ResultsThe base-case analysis revealed that patients in the RALS group gained 0.09 more QALYs at an additional cost of ¥39 079.52 compared with CLS group, the derived ICER was ¥437 157.36/QALYs, exceeding the predefined WTP threshold. The results suggested that RALS does not demonstrate superior cost-effectiveness compared with CLS in the management of early-stage EC. Univariate sensitivity analysis indicated that, when the annual surgical volume per robotic device reaches 809 cases, or the cost of Endowrist consumables per robotic surgery drops below ¥6 568.46, RALS will emerge as a more cost-effective surgical strategy. The probabilistic sensitivity analysis revealed that that RALS becomes more cost-effective when the WTP threshold exceeds ¥402 145.80. Conclusion From a Chinese societal perspective, robotic-assisted laparoscopic surgery for early-stage endometrial cancer is not cost-effective compared with conventional laparoscopic surgery at the current WTP threshold of three times per capita GDP.
Objective To evaluate the clinical effectiveness, safety and cost-effectiveness of postoperative radiotherapy on endometrial carcinoma. Methods We searched The Cochrane Library, The Cochrane Central Register of Controlled Trials (CENTRAL), The National Research Register, Health Technology Assessment Database (HTA), MEDLINE, EMbase, CancerLit, CBMdisc, VIP, WANFANG DATABASE and CNKI to March 2007. Relevant journals were also hand searched. Study selection and assessment, data collection and analyses were undertaken by two reviewers independently according to the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analyses were performed. Results Three RCTs involving 1126 patients were included. Each of the 3 RCTs compared adjuvant radiotherapy (external beam radiotherapy, EBRT) versus chemotherapy. Two trials (730 patients) compared adjuvant radiotherapy versus CAP chemotherapy (carboplatin + adriamycin + cisplatin). The other trial (396 patients) compared adjuvant radiotherapy versus AP chemotherapy (adriamycin + cisplatin). The meta-analyses showed that for patients with endometrial cancer at stage Ic, II or III, there were no significant differences between adjuvant radiotherapy and CAP in 5-year overall survival (OS), 5-year progress-free survival (PFS) and 5-year recurrence (local, distant, total). For patients with endometrial cancer at stage III or IV, adjuvant radiotherapy was superior to AP regimen on 5-year OS and 5-year PFS. The incidence of grade 3/4 toxicities of digestive system and urogenital system was similar between the two groups of patients. The chemotherapy group showed a higher incidence of grade 3/4 toxicities of hematology than the radiotherapy group. Conclusion The effect of adjuvant pelvic radiotherapy for endometrial carcinoma at stage Ic, II or III is similar to that of adjuvant chemotherapy. However, for endometrial carcinoma at stage III or IV, the effect of radiotherapy is superior to that of chemotherapy. Radiotherapy has a lower role of myelosuppression than chemotherapy. No significant difference was observed between the radiotherapy and chemotherapy in grade 3/4 toxicities of the digestive system and the urogenital system.
Objective To explore the role of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in estrogen-induced proliferation of endometrial cancer, and explore whether metformin inhibits the proliferation of endometrial cancer cells through ERα and ERβ. Methods Stable transfected Ishikawa cells were constructed by lentivirus. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were detected by methyl thiazolyl tetrazolium assay. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell cycle were detected by flow cytometry. In addition, quantitative real-time polymerase chain reaction and Western blotting assays were used to detect changes in the expression of cyclinD1 and P21 involved in cell cycle regulation. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were observed by adding metformin to estrogen treatment. Results Down-regulation of ERα inhibited the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERα also inhibited the expression of cyclinD1 and promoted the expression of P21 (P<0.05). Down-regulation of ERα counteracted the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Down-regulation of ERβ promoted the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERβ also promoted the expression of cyclinD1 and inhibited the expression of P21 (P<0.05). Down-regulation of ERβ enhanced the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Metformin inhibited the proliferation of estrogen-induced Ishikawa cells (P<0.05), while in the down-regulated ERα Ishikawa cells or down-regulated ERβ Ishikawa cells, the inhibition of metformin on Ishikawa cells disappeared (P<0.05). Conclusions ERα may promote estrogen-induced proliferation of endometrial cancer cells, while ERβ may inhibit estrogen-induced proliferation of endometrial cancer cells. In addition, ERα and ERβ may also mediate the inhibitory effect of metformin on endometrial cancer cells.
Objective To assess the clinical effectiveness, safety and cost-effectiveness of adjuvant radiotherapy(RT) for endometrial cancer compared to other treatmen. Method The following electronic databases were searched: MEDLINE, EMBAS, CancerLit, CBMdisc, CNKI. The Cochrane Library (Issue 3, 2007). Correlative websites, such as ‘google’, were searched by hand. The studies included in the references of eligible studies were additionally searched RCTs of adjuvant radiotherapy before March, 2007 comparing adjuvant radiotherapy with other treatment for endometrial cancer were included. Eligible RCTs were assessed for quality by two reviewers independently: criteria of concealment of treatment, blinding, standard validity and reliability of outcome measures, withdraw rate, intention-to-treat analysis and homogeneity between centers were analyzed for each study. All data were performed by a meta-analysis. Result Seven RCTs met the inclusion criteria/ Methodological quality was level B. Five RCTs were compared adjuvant radiotherapy (external beam radiotherapy (EBRT) and /or intracavitary radiotherapy (ICRT) with other treatment, Two RCTs including one RCT was compared two different fractionation schedules for postoperative vagina high-dose-rate(HDR) irradiation in endometrial carcinoma the other RCT was compared two different radiotherapy method (pelvic radiotherapy and vagina radiotherapy vs vagina radiotherapy) for endometrial carcinoma. No survival different were identified; none of the studies was powered enough to show a survival benefit. But who received RT had fewer local (pelvic and/or vagina) recurrences compared to women not receiving RT. Adverse effects is found more often in RT than in not RT, there is less localrecurrences in combined radiotherapy (pelvic radiotherapy and vagina radiotherapy) than in vagina radiotherapy. lowdose vagina radiotherapy had few vagina shortening than high-dose radiotherapy, there are the same 5-overall surviva, local recurrences and distant recurrences. Conclusions Adjuvant radiotherapy for endometrial can cer can better control local recurrences than observation for postoperative endometrial cancer. Effects about overall survival, distant recurrences and disease-free survival are similar; low-dose vagina radiotherapy has few vagina shortening than high-dose radiotherapy, there are the same 5-years overall survival, local recurrences and distant recurrences for endometrial cancer, there is less local recurrences in combined radiotherapy (pelvic radiotherapy plus vagina radiotherapy) than in vagina radiotherapy for endometrial cancer; postoperative high-dose brachytherapy can get good cost-effectiveness; Effect of adjuvant radiotherapy for overall survival and disease-free survival of endometrial carcinoma are needed to further assessed by rigorously designs, randomized, double-blind, placebo-controlled trials adjuvant radiotherapy for endometrial carcinoma.
ObjectiveTo systematically review the value of human epididymis protein 4 (HE4) in early diagnosis of endometrial cancer. MethodsDatabases including The Cochrane Library (Issue 1, 2013), PubMed, MEDLINE (Ovid), CNKI, CBM and WanFang Data were electronically searched for relevant studies on HE4 versus the golden standard (pathological examination) in the diagnosis of endometrial cancer from inception to April 2013. Meanwhile, relevant journals were also manually searched. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the included studies using the QUADAS items. Then, meta-analysis was performed using RevMan 5.1 and Meta-DiSc 1.0. ResultsFinally, a total of 16 studies involving 2 299 women (1 088 endometrial cancer patients diagnosed according to the golden standard, of which, 504 with benign uterine disease and 707 with normal cervical) were included. The results of meta-analysis showed that, as for HE4 in early diagnosis of endometrial cancer (SEN=57%, 95%CI 0.54 to 0.60; SPE=92%, 95%CI 0.91 to 0.94; +LR=6.92, 95%CI 5.00 to 9.58;-LR=0.46, 95%CI 0.39 to 0.55; DOR=18.38, 95%CI 12.21 to 27.69; AUC=0.881 7). ConclusionThe current study indicates that serum HE4 is more sensitive and low specific when applied in patients with endometrial cancer, which is worth of being used in clinic. Due to the limitation of low quality of the included studies, more high quality trials are required to verify the above conclusion.