Keng Shen

Peking Union Medical College Hospital, Peping, Beijing, China

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Publications (152)173.06 Total impact

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    ABSTRACT: Owing to the rarity of sex cord tumor with annular tubules (SCTAT), it is difficult to recognize SCTAT clinically and there is no standard treatment. The aim of our study was to investigate the treatment outcomes and prognosis of patients with ovarian SCTAT. A cohort of 13 patients with SCTAT diagnosed and treated in Peking Union Medical College Hospital was studied. Data on clinicopathological characteristics, treatment, and prognosis were retrospectively reviewed and analyzed. SCTAT accounted for 1.4% of ovarian sex cord stromal tumors, with an average onset age of 22.6 years. All patients presented with menstrual disturbances or isosexual precocity at disease onset. Initial surgery was unilateral salpingo-oophorectomy in 11 cases. Recurrence rate was 46.2%, and 38.5% of patients experienced multiple recurrences. The disease free interval gradually shortened with increasing numbers of recurrences. Recurrent tumors were mostly ipsilateral to the primary tumor and located in retroperitoneum. Surgery remained the main treatment for recurrent cases. Serum estradiol and progesterone levels usually elevated at disease onset, decreased dramatically after operation, and they elevated again with the development of recurrence. The median progression-free survival (PFS) was 97.8 months, and the 1-year and 5-year PFS were 92% and 67%, respectively. Five-year overall survival (OS) was 100%. Unilateral salpingo-oophorectomy is a feasible treatment for primary SCTAT cases with intact capsules and without PJS. Complete tumor resection is suggested for recurrent cases and long-term follow-up is strongly recommended. Despite the high risk of recurrence, SCTAT prognosis is relatively favorable.
    BMC Cancer 04/2015; 15(1):270. DOI:10.1186/s12885-015-1277-y · 3.32 Impact Factor
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    ABSTRACT: The aim of the study reported here was to investigate the protective effect of gonadotropin-releasing hormone analog (GnRHa) against cyclophosphamide (CTX)-induced gonadotoxicity. Eighty Fischer 344 rats were divided randomly into four groups (20 per group). One group received normal saline, one GnRHa, one CTX, and one GnRHa+CTX. Several parameters were used to observe the ovarian reserve, including ovary weight, follicle number and diameter, concentrations of estradiol (E2) and follicle-stimulating hormone (FSH), and expressions of sex hormone receptors. When treatment was finished, the number of small follicles in the GnRHa+CTX group was significantly higher than in the CTX-alone group. Thirty days after treatment, the ovary weight, percentage of small follicles, mean follicular diameter, and serum concentrations of E2 and FSH in the GnRHa+CTX group all recovered, approaching normal levels. Sex hormone receptors did not show significant differences between the four groups. Combination treatment with GnRHa could prevent CTX-induced damage to ovarian reserve.
    OncoTargets and Therapy 01/2015; 8:661-7. DOI:10.2147/OTT.S78729 · 1.34 Impact Factor
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    ABSTRACT: To profile the characteristic and prognostic implications of venous thromboembolism (VTE) in Chinese ovarian clear cell carcinoma (CCC) patients. We identified all of the cases between 2000 and 2012 by searching our institutional Ovarian CCC Database. A comprehensive review of the medical documentation was performed to collect relevant data. Kaplan-Meier models and Cox regression were employed for survival analysis. Of the 227 patients, 33 (14.5%) experienced VTE events. There was no significant difference between VTE and non-VTE group patients regarding age, serum cancer antigen 125 or tumor size. The optimal cytoreduction rate was higher in patients without VTE (70.1%) than in those with VTE (51.5%). VTE events were more likely to occur at presentation (36.4%) and recurrence (33.3%), followed by an adjuvant chemotherapy period (18.2%). VTE was more common in patients with advanced-stage disease than those with early-stage disease (P=0.003), whereas pulmonary embolism (PE) was 10-fold as common in advanced-stage disease as in early-stage disease (8.6% vs. 0.8%, P = 0.012). Patients with advanced disease tended to have thrombi in the proximal veins. Two patients died of PE, as confirmed by autopsy. Patients with VTE had reduced survival compared to those without VTE (median overall survival 54 vs. 140 months, P<0.001; median progression-free survival 17 vs. 43 months, P<0.001). Overall, 14.5% of the patients with ovarian CCC experienced VTE, mainly before their cancer diagnosis or at a time of recurrence. VTE adversely impacted patient survival.
    PLoS ONE 01/2015; 10(3-3):e0121818. DOI:10.1371/journal.pone.0121818 · 3.53 Impact Factor
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    ABSTRACT: Purpose To investigate tumor heterogeneity in the recurrence of epithelial ovarian cancer demonstrated by polycomb group (PcG) proteins. Methods Tissue microarrays containing matched primary and recurrent ovarian tumors from the same patients were constructed for detection of PcG protein expression. Survival analyses of clinicopathological parameters and expression of PcG proteins were performed on progression-free survival (PFS) and overall survival (OS) of patients. Genetic and epigenetic heterogeneity was explored in aspects of gene copy number and microRNA (miRNA) profiling. Results PcG proteins were heterogeneously expressed in primary versus recurrent tumors (P<0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of BMI1 and EZH2 in first-onset lymph node metastases with shortened PFS was demonstrated (P=0.010, P=0.019); and a significant association of intensive expression of BMI1 and EZH2 in recurrent tumors with shortened OS was demonstrated (P=0.042, P=0.047). Importantly, BMI1 and EZH2 expression provided significant independent prognostic parameters in multivariate analyses (P<0.05). Gene amplification did not always coincide with PcG protein expression. Eight miRNAs were found to be downregulated in recurrent tumors, among which miR-298 might indirectly regulate the expression of EZH2 through transcription factor ILF3. Conclusion Tumor heterogeneity exists in the recurrence of epithelial ovarian cancer, manifested by PcG protein expression and underlying genetic and epigenetic alterations. Intensive expression of BMI1 and EZH2 are predictors of earlier relapse and shorter OS, independent of grade and chemotherapy sensitivity. EZH2 and miR-298 have great potential to be new targets for treatment of recurrent ovarian cancer.
    OncoTargets and Therapy 09/2014; 7:1705-16. DOI:10.2147/OTT.S67570 · 1.34 Impact Factor
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    ABSTRACT: Objective: This study aimed to analyze the clinicopathological features of pure and mixed-type ovarian clear cell carcinoma (CCC) in Chinese patients. Methods: Patients with ovarian CCC treated in our institution between 1982 and 2012 were identified by reviewing the database and medical charts. Patients were assigned into 2 groups based on histology (pure or mixed). Comparison of clinicopathological parameters was performed to determine the similarities and/or differences between pure and mixed CCC. Kaplan-Meier model was used in survival analysis. Results: Of 341 patients with ovarian CCC, 46 (13.5%) mixed tumors were identified, and the most common combination was clear cell/endometrioid, accounting for 56.5%. Patients with mixed-type CCC tended to have higher level of serum cancer antigen 125 (P = 0.023) and advanced tumor stage (P = 0.001). No difference was observed in other features including age, tumor size, residual disease, lymph node metastasis, and coexisting endometriosis. Tumor recurrence occurred in 47.8% and 58.1% in patients with pure and mixed histology, respectively (P = 0.209). Two groups had comparable platinum-sensitive disease (42.1% in pure and 44.0% in mixed type, P = 0.860). Patients with pure CCC had an improved median survival (105 vs 56 months), although statistical significance was not achieved. Histology subclassification of mixed tumor revealed that patients with clear cell/endometrioid histology had better survival outcome than those with clear cell/serous type (median survival, 140 vs 43 months, P = 0.004; median progression-free survival, 49 vs 12 months, P = 0.001). Conclusions: Patients with mixed CCC tended to have elevated serum cancer antigen 125 and advanced tumor stage. However, no significant difference was observed between the pure and mixed tumors regarding prognosis.
    International Journal of Gynecological Cancer 09/2014; DOI:10.1097/IGC.0000000000000275 · 1.95 Impact Factor
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    ABSTRACT: Objective To analyze and compare the clinicopathological features and prognosis of ovarian clear cell carcinoma (CCC) with or without endometriosis in Chinese patients. Design Comparative study based on a retrospective review of medical charts. Setting A general university hospital. Patient(s) Two hundred ten patients diagnosed and treated with ovarian CCC between 2000 and 2012. Intervention(s) Patients were divided into two groups depending on coexisting endometriosis. A comparison of clinicopathological characteristics was performed. The Kaplan-Meier model and Cox regression were employed in survival analysis. Main Outcome Measure(s) Clinicopathological parameters and survival outcomes. Result(s) Of 210 patients, 79 (37.6%) were confirmed to have concurrent endometriosis. Patients with endometriosis were 8 years younger than those without. They were more likely to present at early stage (78.5%) with resectable tumors in primary surgery (with optimal cytoreduction rate at 89.9%) and platinum-sensitive disease (51.7%). Median overall survival for patients with endometriosis was 115 months, an increase of 52 months when compared with 63 months for patients without endometriosis. The 5-year survival rate in patients with endometriosis was 70.2%, while it was 52.6% for those without. Univariate and multivariate analysis showed that coexisting endometriosis was not an independent predictor of survival outcome. Tumor stage and optimal debulking were the independent prognostic factors for both overall survival and progression-free survival. Conclusion(s) Patients with ovarian CCC and coexisting endometriosis had distinct clinicopathological features and better survival outcome. However, endometriosis per se did not confer improved survival.
    Fertility and Sterility 09/2014; DOI:10.1016/j.fertnstert.2014.08.008 · 4.30 Impact Factor
  • HaiXia Li, JianFang Zeng, Keng Shen
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    ABSTRACT: Ovarian cancer is one of the major causes of death in women worldwide. Despite improvements in conventional treatment approaches, such as surgery and chemotherapy, a majority of patients with advanced ovarian cancer experience relapse and eventually succumb to the disease; the outcome of patients remains poor. Hence, new therapeutic strategies are urgently required. The phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) is activated in approximately 70 % of ovarian cancers, resulting in hyperactive signaling cascades that relate to cellular growth, proliferation, survival, metabolism, and angiogenesis. Consistent with this, a number of clinical studies are focusing on PI3K pathway as an attractive target in the treatment of ovarian cancer. In this review, we present an overview of PI3K pathway as well as its pathological aberrations reported in ovarian cancer. We also discuss inhibitors of PI3K pathway that are currently under clinical investigations and the challenges these inhibitors face in future clinical utility.
    Archives of Gynecology and Obstetrics 08/2014; 290(6). DOI:10.1007/s00404-014-3377-3 · 1.28 Impact Factor
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    ABSTRACT: Most patients with ovarian cancers relapse, and treatment failure has often been attributed to chemoresistance in tumor cells. Emerging evidence indicates that tumor heterogeneity may play an equally important role. Although the idea of tumor heterogeneity is not new, little attention has been focused on applying it to understand and control ovarian cancer progression. Recent advances in understanding its generation model, original basis, consequent problems, and derived therapies provide great potential for tumor heterogeneity to be a new insight in treatment of ovarian cancers.
    Histology and histopathology 07/2014; · 2.24 Impact Factor
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    ABSTRACT: Objectives: Quality of life (QoL) and sexual health have become increasingly important in cervical cancer survivors (CCSs). The aims of this review were to summarize research findings of QoL and sexual function in CCSs after treatment on the basis of self-reported questionnaires and to update the current knowledge of overall QoL and sexual function in CCSs. Methods: Studies from electronic database between May 1966 and May 2013 were rated on their internal validity as methodological assessment. Thirty-two studies were included, wherein 15 studies had a relatively good methodology. Results: Anorectal function, urinary symptoms, and lymphedema were commonly reported as physical symptoms. As to psychosocial domains, the studies illustrated that anxiety decreased with age, whereas depression generally increased with age. Sexual function was involved in most of the studies. Vaginal dryness, dyspareunia, short vagina, and sexual dissatisfaction were prominent issues of sexual dysfunction and vaginal changes in CCSs. In terms of treatment modality, radiotherapy was thought to be associated with worse QoL and sexual function in CCSs. Conclusions: The studies showed that QoL and sexual function in CCSs were compromised compared with the general population to different extents. Quality of life and sexual function should be paid with more attention in patients with cervical cancer after treatment.
    International Journal of Gynecological Cancer 07/2014; DOI:10.1097/IGC.0000000000000207 · 1.95 Impact Factor
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    ABSTRACT: Objective The aim of the study was to identify the role of neoadjuvant chemotherapy (NACT) in the treatment of the patients with advanced stage ovarian yolk sac tumor (OYST). Methods The comparative study was based on 53 cases with advanced stage OYST registered at Peking Union Medical College Hospital from 1995 to 2010. Twenty one cases were treated with NACT followed by interval debulking surgery (IDS). Thirty two cases were treated with primary debulking surgery (PDS). Data on patient characteristics, treatment and survival were analyzed and compared between two groups to assess the outcome of NACT. Results After NACT, the overall status of the patients was improved significantly. Patients in NACT had better optimal cytoreduction rate and less peri-operative morbidities. Seven patients (13.2%) suffered from relapse. There was a significantly better PFS for patients with ovarian tumor size > 20 cm in the NACT than those underwent PDS. Residual disease > 2 cm was the independent risk factor of relapse. Conclusions NACT is the better treatment option for some patients with advanced stage OYST, especially for those with unresectable tumors and poor general condition.
    Gynecologic Oncology 07/2014; 134(1). DOI:10.1016/j.ygyno.2014.02.029 · 3.69 Impact Factor
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    ABSTRACT: The aim of this study is to evaluate the accuracy of magnetic resonance imaging (MRI) in the preoperative assessments of primary tumor size, parametrial invasion, and pelvic lymph node metastasis in patients with early-stage cervical cancer.
    International Journal of Gynecological Cancer 07/2014; 24(7). DOI:10.1097/IGC.0000000000000169 · 1.95 Impact Factor
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    ABSTRACT: Objective To explore appropriate treatment modality of microinvasive cervical cancer (MIC) and to analyze prognosis and risk factors of recurrence. Methods A cohort of 324 Chinese patients with MIC diagnosed and treated at Peking Union Medical College Hospital was retrospectively reviewed. Demographic features, treatment modalities, pathologic parameters, risk factors of residual disease, survival and risk factors of recurrence were analyzed. Results Of all patients, 280 cases were staged IA1 and 44 cases staged IA2 MIC. Twenty-five cases (7.7%) were found to have lympho-vascular space involvement (LVSI), but no parametrial involvement or ovarian metastasis was detected. Only one staged IA2 patient with LVSI was found to have lymph node metastasis. 32.4% patients (82/253) had residual diseases after conization. No significant difference of LVSI, lymph node metastasis and residual disease after coniztion was found between stage IA1 and IA2 MIC patients. Multivariate logistic analysis showed positive margin was the only independent risk factor of residual disease after conization (odds ratio [OR], 4.18; p<0.001). Recurrence occurred in five cases, but no mortality was found. Progression-free survival for stage IA1 patients treated by conization or hysterectomy was similar (92.3% and 98.8%, p=0.07). Cox regression analysis revealed LVSI as an independent risk factor for recurrence in stage IA1 patients (OR, 12.14; p=0.01). Conclusion For stage IA1 patients with negative resection margin and no LVSI, conization can be an ideal treatment modality. For stage IA2 patients, more conservative surgery such as simple hysterectomy may be considered. LVSI is an independent risk factor for recurrence in patients with stage IA1 cervical cancer.
    Journal of Gynecologic Oncology 06/2014; 25(4). DOI:10.3802/jgo.2014.25.4.293 · 1.60 Impact Factor
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    ABSTRACT: To study the clinical features, treatment and prognosis of struma ovarii.
    Zhonghua fu chan ke za zhi 06/2014; 49(6):451-454.
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    ABSTRACT: To retrospectively explore the value of apparent diffusion coefficient (ADC) histogram in assessing local aggressiveness of cervical cancer. 53 patients with cervical cancer, including 7 cases at stage IB1, 17 cases at stage IB2 and 29 cases at stage IIA, were subjected to preoperative MRI including diffusion-weighted imaging with b values of 0 and 800 s/mm(2). The average of mean ADC values (ADCmean), minimum ADC values (ADCmin) and the 5th to 85th percentile ADC values every 10 % (ADC5 %, ADC15 %, ADC85 %) were measured. ADC values were compared between subgroups according to pathologic subtype, histological differentiation, depth of cervical infiltration, and lymph node metastases. ADCmean and ADCmin for adenocarcinoma were 1,170.3 ± 97.8 × 10(-6) and 748.7 ± 157.5 × 10(-6) mm(2) s(-1), respectively, significantly higher than that of squamous cell carcinoma (SCC) (1,053.8 ± 134.3 × 10(-6) and 615.6 ± 170.2 × 10(-6) mm(2) s(-1), respectively). ADCmean and ADC5 %-ADC85 % of well or moderately tumor were significantly higher than poorly differentiated tumor, but ADCmin was not significantly different among different differentiated cervical cancer. Only ADC5 %-ADC45 % could discriminate well or moderately differentiated SCC from poorly differentiated SCC. ADC5 % for distinguishing well/moderately from poorly differentiated cervical cancer had a largest AUC (0.83). There was no statistical difference in ADC value for different depth of cervical infiltration or lymph node metastases. ADC values are helpful in assessing pathologic subtype and the differentiation of cervical cancer.
    Archives of Gynecology 04/2014; 290(2). DOI:10.1007/s00404-014-3221-9 · 1.28 Impact Factor
  • Keng Shen, Jinghe Lang
    Zhonghua fu chan ke za zhi 04/2014; 49(4):241-2.
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    ABSTRACT: To evaluate the prognosis and fertility outcomes of patients with early stage of cervical cancer treated by vaginal radical trachelectomy (VRT) in combination with laparoscopic pelvic lymphadenectomy.
    Zhonghua fu chan ke za zhi 04/2014; 49(4):249-53.
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    ABSTRACT: IntroductionRadical hysterectomy (RH) has negative consequences on sexual function due to a shortened vagina, vaginal dryness, and dyspareunia. Peritoneovaginoplasty aims to extend vagina by vesical peritoneum and anterior rectal wall to improve postoperative sexual function.AimThe aim of this study was to investigate whether vaginal extension can improve sexual function and quality of life and the problem of sexual dysfunction in early-stage cervical cancer survivors (CCSs) in China.Methods Case-control and questionnaire-based methods were employed. Thirty-one patients who had undergone vaginal extension following RH and 28 patients with matching factors after RH alone were enrolled in the study.Main Outcome MeasuresBoth groups were assessed retrospectively by questionnaires at least 6 months after treatment. The European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire cervical cancer module and the Sexual Function Vaginal Changes Questionnaire are validated measurements for disease- and treatment-specific issues.ResultsVaginal length was 10.03 ± 1.26 cm and 5.92 ± 1.05 cm in study and control group, respectively (P < 0.05). In the study group, 67.7% patients and 64.3% of control group resumed sexual activity at the time of interview, averaging 6 months between treatment and sexual activity. While difficulty emptying bladder, incomplete emptying, and constipation were the most commonly reported symptoms, no significant difference was observed regarding pelvic floor symptoms. Reduced vagina size and shortened vagina was significantly more prominent in the control group, whereas both group presented with hypoactive sexual desire (88.1%), orgasm dysfunction (71.8%), and low enjoyment or relaxation after sex (51.3%).Conclusion Shortened vagina was significantly less reported in study group, while no difference was observed in other sex-related dimensions. Vaginal extension does not worsen pelvic floor symptoms. Sexual rehabilitation interventions are of significance and should be paid more attention to the CCSs in China. Ye S, Yang J, Cao D, Zhu L, Lang J, Chuang LT, and Shen K. Quality of life and sexual function of patients following radical hysterectomy and vaginal extension. J Sex Med **;**:**–**.
    Journal of Sexual Medicine 04/2014; 11(5). DOI:10.1111/jsm.12498 · 3.15 Impact Factor
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    ABSTRACT: Cervical cancer is currently the first or second leading cause of cancer-related mortality among women in developing countries. This study was conducted in order to determine whether neoadjuvant cisplatin and 5-flourouracil (NAPF) prior to surgery is superior to primary surgical treatment (PST) as a treatment option for patients with International Federation of Gynaecology and Obstetrics (FIGO) stage IB2/IIA2 cervical cancer. A retrospective review of 195 patients with early-stage bulky cervical cancer was performed. The patients were divided into two groups, according to whether they received NAPF prior to surgery. The surgical profiles and complications, risk factors of recurrence and survival were compared between the groups. The response rate to NAPF was found to be 61.2%. There were no differences in operative time and intra-operative complications between the two groups, whereas the estimated blood loss in the NAPF and PST groups were 620.1±394.9 and 434.8±233.7 ml, respectively (P=0.000). When compared with PST, NAPF remarkably reduced tumor size (22.5 vs. 93.3%, P=0.000). Furthemore, the ratio of deep stromal invasion was significantly lower in responders to NAPF compared with that in non-responders (46.7 vs. 76.3%, respectively; P=0.004) and in the PST group (46.7 vs. 70.0%, respectively; P=0.004). No reduction of high-risk factors (HRFs) was observed. The NAPF group, even the responder subgroup, exhibited no significant improvement in progression-free survival (PFS) and overall survival (OS) compared to the PST group. In conclusion, despite the reduction of intermediate-risk factors (IRFs), neoadjuvant chemotherapy (NAC) with the NAPF regimen prior to radical surgery (RS) did not improve the prognosis in patients with FIGO stage IB2/IIA2 cervical cancer.
    Molecular and Clinical Oncology 03/2014; 2(2):240-244. DOI:10.3892/mco.2013.227
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    ABSTRACT: Ovarian cancer, particularly high-grade serous ovarian carcinoma (HG-SOC), is still the main cause of death among gynecological malignancies. However, the molecular mechanisms related to its malignant biological behavior are still unclear. Recent studies indicate that microRNAs (miRNAs) play an important role in tumor metastasis. Here, we report that miR-1236-3p expression was downregulated in HG-SOC when compared to that in normal fallopian tube tissue. Manipulation of miR-1236-3p significantly influenced the morphology, migration and invasion of ovarian cancer cell lines (A2780 and SKOV3). With dual-luciferase reporter assay, we demonstrated that miR‑1236-3p binds to the 3'UTR of zinc-finger E-box binding homeobox 1 (ZEB1) mRNA, and functions as a negative regulator of ZEB1. Furthermore, we revealed that manipulation of miR-1236-3p modulates ZEB1 expression and influences expression of its downstream genes E-cadherin and N-cadherin at both the mRNA and protein levels. We also found an inverse relationship between miR‑1236-3p and ZEB1 expression in the HG-SOC tissue samples. Taken together, our results indicate that miR-1236-3p regulates ovarian cancer metastasis by directly targeting ZEB1, and it may play an important role in the diagnosis and treatment of ovarian cancer.
    Oncology Reports 02/2014; 31(4). DOI:10.3892/or.2014.3046 · 2.19 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the clinical manifestations, diagnosis, treatment, and prognosis of primitive neuroectodermal tumors (PNETs) in the female genital tract. From April 2001 to May 2013, the clinicopathologic characteristics, treatments, outcomes, and prognosis of 11 patients with PNET in the female genital tract were analyzed retrospectively at our hospital. The location of PNET in the 11 patients presented here included vulva (2 patients), cervix (2 patients), uterus and its ligament (5 patients), and the ovaries (2 patients). Ages ranged from 18 to 59 years (median, 31 years).The main clinical manifestations of PNET in the female genital tract are irregular vaginal bleeding (6 patients), pelvic mass, uterine enlargement, and rapidly increasing vulvar mass (8 patients), and vulvar pain and lower abdominal pain (5 patients). The CA125 levels of 8 patients were elevated before the operations and reduced to normal when the diseases were controlled, while the levels increased as the tumor was progressive. Results for the most commonly used immunohistochemistry studies revealed CD99 in 11 of the 11 tumors, synaptophysin in 6 of the 7 positive tumors, and neuron-specific enolase in 6 of the 6 tumors. Ten patients underwent surgical resection. Nine of them underwent preoperative or/and postoperative combination chemotherapy. The follow-up of 10 patients were available and ranged from 1 to 145 months (median, 30.5 months), 3 of whom experiencing recurrence. Primitive neuroectodermal tumor is very rare and can originate from any part of the female genital tract. The tumors had different manifestations but the same pathologic features. CA125 may be an important marker for prognosis and follow-up of PNET of the female internal genital tract.
    International Journal of Gynecological Cancer 01/2014; DOI:10.1097/IGC.0000000000000082 · 1.95 Impact Factor