Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Chemotherapy initiation with single-course methotrexate alone or combined with dactinomycin versus multi-course methotrexate for low-risk gestational trophoblastic neoplasia: a multi-centric randomized clinical trial / 医学前沿

We aimed to evaluate the effectiveness and safety of single-course initial regimens in patients with low-risk gestational trophoblastic neoplasia (GTN). In this trial (NCT01823315), 276 patients were analyzed. Patients were allocated to three initiated regimens: single-course methotrexate (MTX), single-course MTX + dactinomycin (ACTD), and multi-course MTX (control arm). The primary endpoint was the complete remission (CR) rate by initial drug(s). The primary CR rate was 64.4% with multi-course MTX in the control arm. For the single-course MTX arm, the CR rate was 35.8% by one course; it increased to 59.3% after subsequent multi-course MTX, with non-inferiority to the control (difference -5.1%,95% confidence interval (CI) -19.4% to 9.2%, P = 0.014). After further treatment with multi-course ACTD, the CR rate (93.3%) was similar to that of the control (95.2%, P = 0.577). For the single-course MTX + ACTD arm, the CR rate was 46.7% by one course, which increased to 89.1% after subsequent multi-course, with non-inferiority (difference 24.7%, 95% CI 12.8%-36.6%, P < 0.001) to the control. It was similar to the CR rate by MTX and further ACTD in the control arm (89.1% vs. 95.2%, P =0.135). Four patients experienced recurrence, with no death, during the 2-year follow-up. We demonstrated that chemotherapy initiation with single-course MTX may be an alternative regimen for patients with low-risk GTN.

Expression and clinical significance of GRIM-19 in epithelial ovarian carcinoma / 中华妇产科杂志

Objective To investigate the expression and clinicopathological features of gene associated with retinoid-interferon mortality-19 (GRIM-19) in epithelial ovarian carcinoma.Methods The expression of GRIM-19 gene in tissues from 138 cases of epithelial ovarian carcinoma,102 cases of benign ovarian epithelial tumor and 46 cases of normal ovarian tissues were detected by Immunohistochemistry and Western blot methods.Assembled clinical survival data were analyzed with Kaplan-Meier and Cox regression models.Results The expression level of GRIM-19 in epithelial ovarian carcinoma (3.4 ± 2.0) was lower than that in benign ovarian tumor tissues (4.7 ± 2.9) and that in normal ovarian tissues (7.5 ± 2.2 ; P ＜0.01).The level of GRIM-19 expression was related to the survival time of epithelial ovarian carcinoma patients by Kaplan-Meier analysis (P =0.002).The shorter survival time of epithelial ovarian carcinoma patients was significantly associated with the level of GRIM-19 expression (P =0.001),clinical stage (P =0.001),volume of ascites (P =0.023) and the largest diameter of the primary tumor lesion (P =0.044) by Cox regression models.Conclusions The low expression of GRIM-19 in the epithelial ovarian carcinoma suggests that GRIM-19 may be a key gene involved in its carcinogenesis.The expression level of GRIM-19 may be also an independent prognostic factor for epithelial ovarian carcinoma patients.

GRIM-19 gene and tumor / 国际肿瘤学杂志

Genes associated with retinoid-interferon mortality (GRIM) are a group of genes,and GRIM-19 is one of the core genes.Studies have found that GRIM-19 is down-regulated in many types of tumors,and may be a new type of tumor suppressor and a new target for chemotherapy in tumors.

Identification of miR-23a as a novel microRNA normalizer for relative quantification in human uterine cervical tissues

Quantitative real-time RT-PCR (RT-qPCR) is being widely used in microRNA expression research. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in microRNA RT-qPCR studies. The aim of this study was to identify the most stable reference gene(s) for quantification of microRNA expression analysis in uterine cervical tissues. A microarray was performed on 6 pairs of uterine cervical tissues to identify the candidate reference genes. The stability of candidate reference genes was assessed by RT-qPCR in 23 pairs of uterine cervical tissues. The identified most stable reference genes were further validated in other cohort of 108 clinical uterine cervical samples: (HR-HPV- normal, n = 21; HR-HPV+ normal, n = 19; cervical intraepithelial neoplasia [CIN], n = 47; cancer, n = 21), and the effects of normalizers on the relative quantity of target miR-424 were assessed. In the array experiment, miR-26a, miR-23a, miR-200c, let-7a, and miR-1979 were identified as candidate reference genes for subsequent validation. MiR-23a was identified as the most reliable reference gene followed by miR-191. The use of miR-23a and miR-191 to normalize expression data enabled detection of a significant deregulation of miR-424 between normal, CIN and cancer tissue. Our results suggested that miR-23a and miR-191 are the optimal reference microRNAs that can be used for normalization in profiling studies of cervical tissues; miR-23a is a novel microRNA normalizer.

Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease / 中华妇产科杂志

Objective To investigate the expression of low molecular mass polypeptide-2 (LMP2)and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. Methods The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation) , 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of En Vision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. Results LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6. 79 ±2. 38, 5.26 ±2.63 and 3. 10 ±1.65, all P 0. 05). Conclusions High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophohlast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole.

Value of serum CA125 detection for predicting recurrence and prognosis in ovarian epithelial cancer / 中华妇产科杂志

Objective To analyze the association of serum CA125 level at the different phases with recurrence and survival, for providing simple and efficient methods about predicting recurrence and prognosis in epithelial ovarian cancer.Methods The clinical-pathological data from 151 patients were collected, who were histologically confirmed as primary ovarian cancer between Jan 2002 and Dec 2005.All the patients were followed up.The relationship between serum CA125 level at different phases and clinical-pathological data were analyzed, including prognostic associated factors, 2-year or 5-year recurrent rate, 5-year survival rate, progression-free survival times, and overall survival times.Results Serum CA125 level at pre-surgery and the end of 3-course chemotherapy were associated with most of the clinical-pathological parameters,included stage, pathological grade, amount of ascites, residual tumor size, type of recurrence, 2-year and 5-year recurrent rate, and 5-year survival rate ( all P ＜ 0.05 ).Progression-free survival and overall survival times were shorter in the patients with higher CA125 level at pre-surgery or abnormal CA125 level at the end of 3-course chemotherapy (P ＜0.01 ).There was no relationship between the ratio of CA125 level at pre- and post-surgery and recurrence or prognosis ( all P ＞ 0.05).Conclusion Serum CA125 level at pre-surgery and the end of 3-course chemotherapy can be used for predicting the recurrence and prognosis of epithelial ovarian cancer.

Study on high risk factors associated with positive margin of cervix conization in patient with cervical intraepithelial neoplasia / 中华妇产科杂志

Objective To assess the high risk factors associated with the positive margin of conization in patients with cervical intraepithelial neoplasia (CIN). Methods From January 2000 to February 2008, 1699 consecutive patients with CIN undergoing conization was reviewed retrospectively in order to analyze the relationship between the positive margin of conization with clinical prognostic factors,such as patients age, disease grade, size of lesion, the procedure of excision and menopause. X<'2> tests was used to compare the different frequencies of factors in groups of positive and negative margin conization, then seven factors with positive margin were processed into unconditional logistic regression analysis. Results The rate of the positive margin in 1699 patients was 14.01% (238/1699). The mean age of patients with positive margins was (39±9 ) years old, while patients with negative margins was ( 39±8 ) years old, which didn't reach statistical difference(P>0.05). The rate of the positive margin was 8.63% in cold knife cone (CKC) and 18.66% in loop electrosurgical excision procedure (LEEP), which showed significant difference( P<0.01 ). Among 1699 patients, 90 patients were with CIN Ⅰ ,339 patients were with CIN Ⅱ ,1113 patients were with CIN Ⅲ [ including 972 with severe dysplasia and 141 with cancer in situ(CIS) ],87 patients were with cervical cancer stage Ⅰ al, 70 patients were with stage Ⅰ a2 or advanced stages. The rate of positive margin was 1.11% ( 1/90), 3.83% ( 13/339), 10.70% (104/972), 26.24% (37/141),35. 63% (31/87) and 74.29% (52/70),respectively. There was statistic difference among them, except CIN Ⅰ and CIN Ⅱ . When combined CIN Ⅰ with CIN Ⅱ , then compared with CIN Ⅲ, cervical cancer withⅠ al and Ⅰ a2, it also showed statistical difference (P<0.05 ) . The rate of positive margin in postmenopausal women was 21.54% (28/130), which was significantly higher than 13.38% (210/1569)in premenopausal women (P=0.010 ). The logistic regression analysis showed that the procedure of excision, grade of disease, size of lesion, surface of cervix, and menopause were high risk factors associated with the positive margin, the risk ratio were 5.147, 3.048, 1.271, 1.905 and 1.860, respectively.Conclusions High grade, the extent of CIN disease, LEEP and postmenopausal age are high-risk factors associated with positive margin in patients treated by conization. It should be warranted in those patients when designing conization treatment.

Case report and literature review of epithelioid trophoblastic tumor / 中华妇产科杂志

Objective To evaluate the clinical characteristics of epithelioid trophoblastic tumor (ETT).Methods Six cases of ETT treated in Women's Hospital,School of Medicine,Zhejiang University from 2005 to 2007 were retrospectively analyzed,together with a literature review.Results Six cases of ETT were diagnosed pathologically after surgery.The age of patients ranged from 27 to 46 years.The most common presentation was abnormal vaginal bleeding(5/6).The preceding gestational events were hydatidiform mole in 1 case,abortion in 2 cases,and term delivery in 3 cases.The interval between the preceding gestation and the diagnosis of ETT ranged from 15-48 months.The serum human chorionic gonadotropin(hCG)level was 46-121 147 IU/L.Four cases presented with metastasis,including lung metastasis in all of the 4 cases,liver metastasis in 1 case,and pancreas metastasis in another 1 case.The main therapies were surgery combined with chemotherapy.All of the 6 cases received total abdominal hysterectomy.and 1 case also had lung lobectomy.One ease had a recurrence but refused any treatment again,and was lost to follow up;the therapy of 1 case unfinished;another 4 cases were without evidence of disease 9 to 19 months after surgery.Condusions The confirmation of ETF diagnosis is difficult before surgery.Surgical management is mostly recommended in ETT. The role of chemotherapy in ETT is not clear yet.