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Objective: To explore the serum cyclic polypeptide biomarkers for ovarian cancer diagnosis. Methods: A total of 54 patients with epithelial ovarian cancer confirmed by pathology in Cancer Hospital, Chinese Academy of Medical Sciences from March 2018 to September 2018 were selected as the study subjects, and 40 healthy women with normal examination results in the cancer screening center were selected as the control. All of the samples were randomly divided into training set and validation set at the ratio of 1∶1 with a random number. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead technology was used for detecting peptide profiling in serum samples to screen significantly differently expressed peptides between ovarian cancer group and control group of the training set (score>5). Receiver operating characteristic (ROC) curve analysis was used to screen differential peptide peaks with area under curve (AUC) ≥0.8, sensitivity and specificity>90% in the training set and validation set. Liquid chromatography-mass spectrometry (LC-MS/MS) was further used to determine the composition of differentially expressed peptides. Results: By comparing the peptide profiles of the two groups, 102 differential peptide peaks were initially detected in the mass-to-charge ratio range of 1 000 to 10 000. ROC curve analysis showed that there were 42 differential peptide peaks with AUC ≥0.8 in both training set and validation set, 19 of which were highly expressed in ovarian cancer group, and 23 were lowly expressed. There were 15 different peptide peaks in highly expressed ovarian cancer group with sensitivity and specificity over 90%. The mass-to-charge ratios were 7 744.27, 5 913.41, 5 329.87, 4 634.21, 4 202.02, 3 879.26, 3 273.35, 3 253.79, 3 234.34, 2 950.33, 2 664.51, 2 018.38, 1 893.37, 1 498.69 and 1 287.55. There were 15 different peptide peaks in lowly expressed ovarian cancer group with sensitivity and specificity over 90%, the mass-to-charge ratios were 9 288.46, 7 759.77, 5 925.24, 4 652.77, 4 210.42, 3 887.02, 3 279.90, 3 240.82, 2 962.15, 2 932.70, 2 022.42, 1 897.16, 1 501.69, 1 337.38 and 1 290.13. No protein composition was identified in 15 different peptide peaks in lowly expressed ovarian cancer group. The two protein compositions identified in 15 different peptide peaks in highly expressed ovarian cancer group were recombinant serglycin (SRGN) and fibinogen alpha chain (FGA), the mass-to-charge ratios of which were 1 498.696 and 5 913.417, respectively. The sensitivity and specificity of the two proteins for ovarian cancer diagnosis were 100%, 100% and 90.9%, 100%, respectively. Conclusion: SRGN and FGA are highly expressed in the serum of ovarian cancer patients, which may be potential diagnostic markers for ovarian cancer.

Objective: To explore the clinical features of poly ADP-ribose polymerase (PARP) inhibitor-related anemia in advanced and relapsed epithelial ovarian cancer (EOC). Methods: Patients diagnosed with advanced or relapsed EOC and treated with PARP inhibitor at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2015 to October 2020 were accrued. The data included PARP inhibitors, treatment details, and lab tests before treatment and during treatment were collected and the clinical characteristics of PARP inhibitor-related anemia were analyzed. Results: (1) A total of 98 patients with a median age of 56.5 years old (30-82 years old) were enrolled in this study. All patients were treated with PARP inhibitor (65 cases of olaparib, 17 cases of niraparib, and 16 cases of fluzoparib). The median treatment duration was 37.5 weeks (4-119 weeks). (2) The anemia rate was 40% (39/98), including 5% (5/98) of grade Ⅰ, 14% (14/98) of grade Ⅱ, 11% (11/98) of grade Ⅲ, and 9% (9/98) of grade Ⅳ. Fourteen patients with pre-treatment grade Ⅰ anemia had a higher rate of anemia events than the 80 patients without pre-treatment anemia, 7/14 vs 35% (28/80; χ 2 =4.281, P =0.039). (3) The median anemia occurrence time was 7.0 weeks (1-52 weeks), including 41% (16/39) of anemia cases occurred in 1-4 weeks, 26% (10/39) occurred in 5-8 weeks, 13% (5/39) occurred in 9-12 weeks, 3% (1/39) occurred in 13-16 weeks, 10% (4/39) occurred in 17-20 weeks, 8% (3/39) occurred ≥21 weeks. At the time of the lowest hemoglobulin tested, the median value of mean corpuscular volume (MCV) was 106 fl,which was higher than the up limit of normal range (100 fl), 74% (29/39) of anemia patients had an elevated MCV level; the median value of mean corpuscular hemoglobin (MCH) was 36 pg, 54% (21/39) of anemia patients had an elevated MCH level; the median value of mean corpuscular hemoglobin concentration (MCHC) was 320 g/L, 69% (27/39) of anemia patients had a higher MCHC level; 92% (36/39) of anemia patients had a normal level of serum iron; 79% (31/39) of anemia patients had a normal level of transferrin. 74% (29/39) of the anemia patients were macrocytic orthochromatic anemia. (4) Among the 39 patients with anemia, 20 patients (51%, 20/39) withhold the treatment of PARP inhibitor due to grade Ⅲ or Ⅳ anemia, including 10 patients (50%, 10/20) who resumed the PARP inhibitor treatment by suppling iron, folate, and vitamin B 12 . The median stopping time of PARP inhibitor was 5.5 weeks (2-10 weeks), while the other 10 patients terminated the PARP inhibitor treatment for not recovering from severe anemia. Conclusions: One of the common adverse effects of PARP inhibitors is anemia, which mostly happened in the first 3 months of treatment. In the treatment of EOC, PARP inhibitor-related anemia mainly manifest as macrocytic orthochromatic anemia, and most patients with normal serum iron and transferrin.

Background: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer., Patients and Methods: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 10 3 /μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review., Results: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%)., Conclusions: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting., Competing Interests: Disclosure MRM has received fees for serving on advisory boards from Tesaro, GSK, Clovis Oncology, AstraZeneca, and Zai Lab and speaker fees from AstraZeneca, Tesaro, GSK, Zai Lab, and Roche. The other authors have declared no conflicts of interest. Data sharing From the publication date, upon reasonable request to the corresponding author (researchers who provide a methodologically sound proposal and assuming use of the data to meet the goals of this proposal), individual participant data that underlie the results reported in this article (text, tables, and figures) can be made available after de-identification. The study protocol can also be made available with reasonable request., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To explore the clinicopathological characteristics and prognosis of patients with ovarian metastases from colorectal cancer. Methods: A total of 122 female patients with ovarian metastases from colorectal cancer underwent treatment in Cancer Hospital, Chinese Academy of Medical Sciences between 2010 and 2015 were recruited. The clinicopathological features, treatment details and survival data of these patients were retrospectively analyzed. Kaplan-Maier method was used for survival analysis, log rank test and Cox proportional hazards model were used for prognostic factor analysis. Results: The median overall survival (OS) was 19.7 months. The 1-year, 3-years and 5-years OS rates were 72.1%, 24.7% and 9.9%, respectively. A total of 99 (81.1%) patients underwent oophorectomy. The median OS of patients who underwent oophorectomy was 21.9 months, significantly longer than 10.3 months of patients without oophorectomy ( P <0.01). Ovary as the only site of metastasis, primary tumor resection, and oophorectomy were associated with improved survival (all P <0.01). Primary tumor resection and oophorectomy were independent prognostic factors for OS (both P <0.01). Conclusion: Patients with ovarian metastases from colorectal cancer might acquire a survival benefit from surgical resection of the primary tumor and ovaries.

Objective: This study aimed to investigate the role of neoadjuvant bleomycin, etoposide, and cisplatin (BEP) regimen in patients with extensively advanced yolk sac tumors (YSTs)., Methods: Between July 1982 and December 2015, a total of 58 patients with YST were initially treated at our institution, among which 18 were evaluated to be inoperable and received neoadjuvant BEP regimen. They were either too debilitated by the disease [Eastern Cooperative Oncology Group Performance Status Scale (ECOG ps) ≥2] to undergo a major surgery or were with too extensively disseminated lesions to be optimally debulked. This cohort of patients was retrospectively reviewed., Results: One or 2 cycles of BEP regimen were prescribed to the majority of patients preoperatively. At the completion of neoadjuvant chemotherapy, 17 of them had ECOG ps of 1 or less. Seventeen (94.4%) exhibited clinical partial tumor regression, and 1 (5.6%) had clinical stable disease. Pathological complete tumor regression was observed in 2 (11.1%) patients, whereas the remaining 16 (88.9%) had nearly complete pathological regression. Seventeen patients were cytoreduced to no macroscopic residual disease; the remaining 1 was cytoreduced to macroscopic residual disease of 2 cm or less. No major surgical complications occurred. After a median follow-up of 83.5 months, 17 patients were free of recurrence. Five-year disease-free survival and overall survival were both 94.4%. Fertility-sparing surgery was carried out in all the 17 patients with the desire to preserve their fertility, and 5 infants were delivered in 6 patients who attempted conception., Conclusions: One or 2 cycles of neoadjuvant BEP regimen followed by cytoreductive surgery offer a chance for cure in extensively advanced patients with YSTs and help pave the way for fertility-sparing surgery.

Objective: The recent phase 3 trial AGO-OVAR16 demonstrated that pazopanib maintenance improved median progression-free survival in patients with ovarian cancer whose disease did not progress during first-line treatment. However, this improvement was not seen in the subset of East Asian patients. The current analysis evaluated the efficacy and safety of pazopanib maintenance in East Asian patients from AGO-OVAR16 and a separate East Asian study., Materials and Methods: East Asian patients from AGO-OVAR16 (n = 209) and the East Asian study (N = 145) were randomized 1:1 to receive pazopanib 800 mg/d or placebo for up to 24 months. The primary end point for each study was progression-free survival by RECIST (Response Evaluation Criteria in Solid Tumors) based on investigator assessment. Clinical and genetics data were analyzed separately by study or pooled according to separate predetermined statistical plans., Results: Pazopanib maintenance had a detrimental effect on median progression-free survival versus placebo in East Asian patients from the combined studies (n = 354; 17.9 vs 21.5 months; hazard ratio, 1.114; 95% confidence interval, 0.818-1.518; P = 0.4928). Pazopanib maintenance showed a disadvantage in overall survival in East Asian patients from AGO-OVAR16 versus placebo (hazard ratio, 1.706; 95% confidence interval, 1.010-2.883; P = 0.0465); overall survival analysis was not performed in the East Asian study because of insufficient event numbers. Pazopanib-treated patients had a significantly higher incidence of grade 3 or higher hypertension (27%) and neutropenia (13%) versus placebo., Conclusions: The treatment effect of maintenance pazopanib in East Asian patients seemed to differ from that in non-Asian patients. In study-specific and pooled analyses, none of the potential factors analyzed could satisfactorily explain the different efficacy results of pazopanib in East Asian patients.

Objective: To investigate the clinicopathological features and risk factors in patients with mucinous borderline ovarian tumors (MBOT). Methods: From 1999 to 2006, 66 MBOT patients in our hospital with more than ten-year follow-up were enrolled retrospectively. They were re-classified according to the literature. The clinicopathological features of different subgroups, including age, preoperative serum tumor markers, surgical methods, pathological features, surgical pathology staging, as well as the risk factors of recurrence and survival were analyzed. Results: Median age was 39 years in 66 patients. Before the surgery, 33.3% (20/60) patients had elevated CA125 and 51.7% (30/58) had elevated CA199. The accurate rate for fast frozen pathology of resected specimen was 73.4%. 21 patients underwent conservative surgery and 45 patients underwent extensive surgery. 57 patients underwent comprehensive operation and 43 cases (75.4%) resulted in stage Ⅰ. 48 of the 66 patients (72.7%) had intestinal-type tumors (IMBT) and 18 patients (27.3%) had endocervical-like tumors (EMBT). The median follow-up was 150 months. Eight recurrences (12.1%) were identified. The mean time between surgery to the initial recurrence was 26.4 months (13 to 50 months). Recurrence rate of IMBT was higher than that of EMBT (14.6% versus 5.6%) with no significance ( P >0.05). All patients with pseudomyxoma had disease recurrence. Recurrence rate of stage Ⅲ patients was significantly higher than that of stage Ⅰ patients (33.3% versus 9.3%, P <0.05). During the follow-up period, tumor-related death occurred in 2 cases with a 10-year survival rate of 95.4%. Kaplan-Meier method and Log Rank analysis showed that clinical staging and peritonealmyxoma were adverse prognostic factors ( P <0.05). Although the recurrence rate of patients undergoing conservative surgery was higher than that of patients with extensive surgery (23.8% versus 6.7%, P =0.047), the overall survival was almost the same between these two groups ( P >0.05). Conclusions: MBOT patients have relatively good prognosis. IMBT are more common than EMBT subtypes, but recurrence rate and patient survival were almost the same between these two groups. Patients with pseudomyxoma was more likely to have disease recurrence. Patients who underwent conservative surgery resulted in higher recurrence rate but did not affect the overall survival of patient. Pseudomyxoma and clinical staging were adverse prognostic factors in MBOT patients.

Platinum resistance is a critical barrier for clinicians to improve the survival of ovarian cancer. Our study evaluated the correlation between copy number variations (CNVs) of neurotrophic tyrosine receptor kinase 3 (NTRK3) and the prognosis of ovarian cancer, which might predict platinum resistance in ovarian cancer patients.Array comparative genomic hybridization (CGH) was used to test gene backgrounds between platinum-sensitive and platinum-resistant relapsed populations and CNVs of NTRK3 were indicated by cluster analysis. Fluorescence in situ hybridization (FISH) was adopted in 41 cases for further verification, which confirmed the results of array CGH. Spearman's rank correlation analysis and χ test were used to evaluate the accuracy of CNVs of NTRK3 which predicted platinum-sensitive or platinum-resistant recurrence.We detected CNVs of NTRK3 between 2 groups by array CGH, and amplification of NTRK3 was confirmed by FISH in the platinum-sensitive recurrence group with enlarged samples. The test concordance of 2 methods was 78.6%. Among 41 cases with satisfied FISH results, the median time to recurrence (TTR) of patients with amplified and nonamplified NTRK3 were respectively 18 and 5 months (P <.01). The cut-off value of TTR to differentiate platinum-sensitive or platinum-resistant recurrence was 6 months in accordance with clinical practice. According to the above standard, 15 cases with NTRK3 amplification were platinum-sensitive and 12 cases without NTRK3 amplification were platinum-resistant recurrences which demonstrated that the accuracy of NTRK3 amplification/nonamplification to predict recurrent types was 65.9% (27/41).CNVs of NTRK3 were associated with platinum-sensitive and platinum-resistant recurrences. Amplification of NTRK3 perfectly predicted platinum-sensitive relapse of ovarian cancer.

Objective: To study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer., Methods: The immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored., Results: The P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors., Conclusion: The P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.

Objective: To analyze efficacy of neoadjuvant chemotherapy for advanced ovarian cancer., Materials and Methods: A total of 107 patients with advanced ovarian cancer undergoing cytoreductive surgery were divided into a neoadjuvant chemotherapy group (n=61) and a primary debulking group (n=46) and retrospectively analyzed. Platinum-based adjuvant chemotherapy was applied to both groups after cytoreductive surgery ande overall and progression-free survival times were calculated., Results: No significant difference was observed in duration of hospitalization (20.8±6.1 vs. 20.2±5.4 days, p>0.05). The operation time of neoadjuvant chemotherapy group was shorter than the initial surgery group (3.1±0.7 vs. 3.4±0.8 h, p<0.05). There were no significant differences in median overall survival time between neoadjuvant chemotherapy group and surgery group (42 vs. 55 months, p>0.05). Similarly, there was no difference in median progression-free survival between neoadjuvant chemotherapy group and surgery group (16 vs. 17 months, p>0.05). The surgical residual tumor size demonstrated no significant difference between initial surgery and neoadjuvant chemotherapy groups (p>0.05). Multivariate analysis showed that more than 3 cycles of regimen with neoadjuvant chemotherapy was associated with more resistance to chemotherapy compared with patients without receiving neoadjuvant chemotherapy (OR: 5.962, 95%CI: 1.184-30.030, p<0.05)., Conclusions: Neoadjuvant chemotherapy can shorten the operation time. However, it does not improve survival rates of advanced ovarian cancer patients.

Malignant immature ovarian teratomas (IOTs) most often occur in women of reproductive age. It is unclear, however, what roles estrogenic signaling plays in the development of IOT. In this study, we examined whether estrogen receptors (ERα and β) promote the cellular malignancy of IOT. Estradiol (E2), PPT (propylpyrazole), and DPN (diarylpropionitrile) (ERα- and β-specific agonists, respectively), as well as ERα- or ERβ-specific short hairpin (sh)RNA were applied to PA-1 cells, a well-characterized IOT cell line. Cellular tumorigenic characteristics, for example, cell migration/invasion, expression of the cancer stem/progenitor cell marker CD133, and evidence for epithelial-mesenchymal transition (EMT) were examined. In PA-1 cells that expressed ERα and ERβ, we found that ERα promoted cell migration and invasion. We also found that E2/ERα signaling altered cell behavior through non-classical transactivation function. Our data show non-genomic E2/ERα activations of focal adhesion kinase-Ras homolog gene family member A (FAK-RhoA) and ERK governed cell mobility capacity. Moreover, E2/ERα signaling induces EMT and overexpression of CD133 through upregulation micro-RNA 21 (miR21; IOT stem/progenitor promoter), and ERK phosphorylations. Furthermore, E2/ERα signaling triggers a positive feedback regulatory loop within miR21 and ERK. At last, expression levels of ERα, CD133, and EMT markers in IOT tissue samples were examined by immunohistochemistry. We found that cytosolic ERα was co-expressed with CD133 and mesenchymal cell markers but not epithelial cell markers. In conclusion, estrogenic signals exert malignant transformation capacity of cancer cells, exclusively through non-genomic regulation in female germ cell tumors., (© 2013 Wiley Periodicals, Inc.)

Objective: To investigate the efficacy of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer., Methods: From August 2010 to June 2012, recurrent epithelial ovarian cancer patients were prospectively enrollmented in Cancer Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The entry criteria are as follows: (1) Histologically proven to be epithelial ovarian cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status > 60. (4) A life expectancy of at least more than 6 months.According to patients desires, they were assigned into two groups: assay-directed therapy group and physician's-choice therapy group, patients' clinical and pathological characteristics, response rate to chemotherapy and progression-free survival (PFS) were compared between two groups., Results: A total of 113 patients with recurrent epithelial ovarian cancer were prospectively enrollmented to assay-directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There was no difference in median age,types of recurrence, surgical-pathological stage, pathological type, tumor grade, times of recurrence, residual disease at secondary cytoreductive surgery between assay-directed group and physician's-choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57, P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control group 25% (7/28) were significantly different (P = 0.010), and the median PFS between two groups were also significantly different (5 months and 2 months, respectively, P = 0.003)., Conclusion: ATP-TCA directed chemotherapy could improve ORR and PFS in patients with recurrent epithelial ovarian cancer, especially in platinum-resistant patients.

Objective: To analyze the clinicopathologic characteristics, treatment and prognostic factors in malignant transformation of mature cystic teratoma (MCT) of ovary., Methods: The clinical data of 44 patients with MCT from January 1961 to June 2009 were reviewed., Results: The median age of the 44 patients was 48 years (range, 16 - 84 years). Mean tumor size was (16 ± 6) cm. Thirty-two cases were diagnosed squamous cell carcinoma (73%, 32/44), and 5 of them with the elevated level of serumal squamous cell antigen (SCC-Ag). Three of 37 cases (8%, 3/37) were identified with malignant transformation in image examinations. Rapid frozen section examination and multiple-location biopsy were performed in 8 cases, and 5 of them were detected with malignant diseases. Twenty-two patients with disease confined within the unilateral ovary (10 with intact capsule, and 12 with ruptured capsule). Diseases extended extra ovaries in the others 22 patients. The median cumulative overall survivals were 126 and 10 months, respectively. The difference between the two groups was significant (P < 0.01). Twenty-seven patients had no residual tumor after primary surgery. The median cumulative overall survivals between the patients with and without residual tumor were 10 and 84 months respectively, and there were significant difference between two groups (P < 0.01). Seven selected patients with malignant disease confined within unilateral ovary underwent fertility-sparing surgery, and 2 cases of them had successful pregnancies and delivery, while other 4 cases with ruptured capsule recurred., Conclusions: The most common pathology type of malignant transformation in mature cystic teratoma of the ovary is squamous cell carcinoma. Comprehensive pre-operation image examination and tumor marker level detection might be of great help in diagnosis. Tumor extension extraovary and residual tumor after surgery are the most significant poor prognostic factors. Early stage patient with ruptured capsule should be very discreet to choose fertility-sparing surgery.

Objective: To evaluate the expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA and their relationship with clinical chemosensitivity in primary ovarian cancer, and to assess the predictive value of joint detection of both BRCA1 and ERCC1 genes for the treatment of primary ovarian cancer., Methods: Primary epithelial ovarian tumor samples were collected from 46 patients who underwent cytoreductive surgery. Real-time quantitative PCR was used to analyze the relative expression of BRCA1, ERCC1, TUBB3 and PRR13 mRNA in those cases. The correlation of clinical chemosensitivity and the test results was statistically analyzed. The efficacy of the joint prediction of clinical chemosensitivity by combining the two drug resistance gene detection was evaluated., Results: The BRCA1 mRNA relative expression logarithm in the clinical-resistant group was 0.673±2.143, and clinical-sensitive group -1.436±2.594 (P=0.008). The ERCC1 mRNA relative expression logarithm in the clinical-resistant group was -0.529±1.982 and clinical-sensitive group -3.188±2.601 (P=0.001). BRCA1 and ERCC1 expression level is negatively correlated with platinum-based chemosensitivity. The PRR13 expressions in the two groups were not significantly different (P=0.074), and the TUBB3 expressions between the two groups were also not significantly different (P=0.619). When the intercept point value BRCA1 mRNA expression logarithm was -0.6, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 73.3%, 75.0%, 84.6% and 60.0%, respectively, with the best comprehensive assessment. When the intercept point value of ERCC1 mRNA expression logarithm was -1, the predictive sensitivity, specificity, positive predictive value and negative predictive value were 80.0%, 68.8%, 82.8% and 64.7%, respectively, with the best comprehensive assessment. The combination detection of BRCA1 and ERCC1 can improve the chemotherapeutic sensitivity, specificity, positive predictive value and negative predictive value to 86.7%, 68.8%, 83.9% and 73.3%, respectively., Conclusions: BRCA1 and ERCC1 mRNA expression has a negative correlation with the clinical sensitivity of platinum-based chemotherapy. Combination detection of the two drug-resistance associated genes can improve the predictive efficacy of ovarian cancer chemosensitivity and beneficial to individual treatment of ovarian cancer.

Objective: To discuss the clinical characteristics, treatment and prognostic factors of brain metastasis from gynecological cancers., Methods: Clinical records of 25 brain metastasis patients from gynecological cancers admitted from January 1999 to January 2009 were reviewed retrospectively. The curative effects of different treatments were compared. The prognostic factors were determined using the Cox regression model., Results: There were 14 cases ovarian malignant tumor, 6 cases cervical carcinoma and 5 cases uterine malignant tumor. Seven cases (28%, 7/25) had solitary metastatic lesion in the brain. Extracranial metastases were detected in 18 cases (72%, 18/25). Five patients only received one kind of treatment, and the mean survival time was 4.0 months (0.5 to 9.5 months). Sixteen patients received combined treatment, 3 of them received combined treatment including surgery, and the mean survival time was 8.4 months (4.1 to 13.4 months); 13 of them received chemotherapy and radiotherapy, and the mean survival time was 14.2 months (4.3 to 58.1 months). Four patients received only palliative supportive care, and the survival time was only 0.1 to 1.0 month. The Cox regression model showed that Karnofsky performance status scale, with or without extracranial metastases and the treatment method were the independent prognostic factors of brain metastasis from gynecological cancers (P < 0.05)., Conclusion: The incidence of brain metastasis from gynecological cancers is low and the prognosis is very poor. Combined treatments may get better effects.

Objective: To explore the prognostic factors, as well as the menstrual and reproductive outcomes, of malignant ovarian germ cell tumors following a fertility-preserving treatment., Methods: A total of 145 patients with malignant ovarian germ cell tumors who had undergone fertility-preserving management in the past 20 years were analyzed retrospectively. The correlative factors for survival, recurrence, and reproductive status were evaluated. The median follow-up time was 9.5 years. Thirty-five cases suffered from dysgerminoma, 31 cases from endodermal sinus tumor, 63 cases from immature teratoma, two cases from embryonal carcinoma, 13 cases from mixed germ cell tumor, and one case had malignant struma. The overall five-year survival rate was 90.3%, whereas the ten-year survival rate was 89.2%. The five-year survival rates for the different stages were as follows: Stage I, 98.1%; Stage II, 5/5; Stage III, 73.3%; and recurrence, 64.1%. The five-year survival rates were 100% for dysgerminoma, 84.1% for endodermal sinuse tumors, 92.0% for immature teratoma, one of two cases for embryonal carcinoma, 76.9% for mixed germ cell tumors, and one case of malignant struma., Results: Thirty-five babies were delivered, whereas seven induced abortions were performed during the follow-up. The important prognostic factors included the International Federation of Gynecology and Obstetrics (FIGO) stage and standard chemotherapy. No statistical significance in the five-year survival rates was determined among the different histological types, surgery types, chemotherapy courses, and chemotherapy regimen. Fertility-preserving treatment should be considered for ovarian germ cell tumors without the limitation of the FIGO stage., Conclusion: Chemotherapy does not influence the menses, pregnancy, or offspring. Recurrent cases could obtain a good prognosis after the proper treatment.

Ovarian cancer is the most lethal gynecological malignancy affecting American women. Current hypotheses concerning the etiology of ovarian cancer propose that a reduction in the lifetime number of ovulations decreases ovarian cancer risk. Advanced serous carcinoma shares several biomarkers with fallopian tube epithelial cells, suggesting that some forms of ovarian carcinoma may originate in the fallopian tube. Currently, the impact of ovulation on the tubal epithelium is unknown. In CD1 mice, ovulation did not increase tubal epithelial cell (TEC) proliferation as measured by bromodeoxyuridine incorporation and proliferating cell nuclear antigen staining as compared to unstimulated animals. In superovulated mice, an increase in the number of pro-inflammatory macrophages was detected in the oviduct. Ovulation also increased levels of phospho-γH2A.X in TEC, indicating that these cells were susceptible to double-strand DNA breakage following ovulation. To determine which components of ovulation contributed to DNA damage in the fallopian tube, an immortalized baboon TEC cell line and a three-dimensional organ culture system for mouse oviduct and baboon fallopian tubes were developed. TEC did not proliferate or display increased DNA damage in response to the gonadotropins or estradiol alone in vitro. Oxidative stress generated by treatment with hydrogen peroxide or macrophage-conditioned medium increased DNA damage in TEC in culture. Ovulation may impact the fallopian tube epithelium by generating DNA damage and stimulating macrophage infiltration but does not increase proliferation through gonadotropin signaling.

Objective: To predict clinical chemotherapy sensitivity of primary ovarian cancer by jointing adenosine triphosphate (ATP)-tumor chemo-sensitivity assay (TCA) method in vitro and detection of drug resistance genes, provide reference for clinical treatment., Methods: Forty-seven primary epithelial ovarian tumor samples were collected from the patients who received cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissue were tested for their sensitivity to carboplatin (CBP), cisplatin (DDP), paclitaxel (PTX) and CBP + PTX using ATP-TCA method in vitro; at same time, real-time quantitative PCR was used to analysis BRCA1 and ERCC1 mRNA relative expression in forty-six specimens (1 frozen tumor samples mRNA were not detected due to serious degradation). The relationship between ATP-TCA test results, clinical indicators, and the effectiveness of the joint prediction on clinical chemo-sensitivity by combining these two methods were statistically analyzed using chi-square test., Results: (1) The results showns that three programs of DDP, CBP and PTX + CBP were significantly related with clinical results (P < 0.05) in vitro, in which the compliance rate in PTX + CBP program was the highest 83% (39/47), and the predictive sensitivity, predictive specificity, positive predictive value, negative predictive value and predictive accurate rate were 90%, 71%, 84% and 80%, respectively. PTX + CBP combined in vitro test results was also related with residual tumor size and neoadjuvant chemotherapy, which was more prone to drug resistance with residual tumor larger than 2 cm (P = 0.023) and with neoadjuvant chemotherapy (P = 0.011). (2) BRCA1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was 0.673 ± 2.143 and -1.436 ± 2.594 (P = 0.008), ERCC1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was -0.529 ± 1.982 and -3.188 ± 2.601 (P = 0.001). There were also significant correlation among the expression levels of BRCA1, ERCC1 mRNA and clinical efficacy (P < 0.01). (3) ATP-TCA and detection of drug resistance genes combined to predict the clinical application of PTX + CBP resistance may occur in 8/9 cases., Conclusions: ATP-TCA may be an ideal method of in vitro drug sensitivity testing method, which could effectively predict clinical chemotherapy sensitivity. Combination of the drug-resistant associated genes detection method and the ATP-TCA method can increase the predictive effectiveness of ovarian cancer chemosensitivity and guide individual chemotherapy of ovarian cancer.

Objective: To explore the value of adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in individualized treatment of recurrent epithelial ovarian cancer (REOC), and to evaluate the correlation between the in vitro chemosensitivity assay and clinical drug sensitivity., Methods: Sixty-nine REOC specimens were tested by ATP-TCA assay retrospectively. The patients were divided into strong sensitive, moderate sensitively and resistant groups according to the ATP-TCA assay results. The clinical results were evaluated according to imaging and serum CA125 analysis. The correlation between in vitro ATP-TCA assay and clinical outcome was statistically analyzed by χ(2) test. The progression free survival (PFS) and overall survival (OS) of each group were analyzed using Kaplan-Meier method., Results: The results of ATP-TCA assay had significant correlation with clinical outcome. The clinical chemotherapy outcome became better with increased drug sensitivity in vitro (χ(2) = 9.066, P = 0.004). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate for ATP-TCA method to predict the clinical chemotherapy sensitivity of REOC were 87.5%, 45.9%, 58.3%, 80.9% and 65.2%, respectively. The mean PFS of strong sensitive group, moderately sensitive group and resistant group were 187.1 days, 195.0 days and 60.3 days, respectively. The mean OS were 476.7, 335.7 and 237.5 days, respectively, following the start of TCA-directed therapy. The PFS and OS of the two sensitivity groups in vitro were significantly longer than that of the in vitro-resistant group (P < 0.01)., Conclusion: The results of ATP-TCA assay are well correlated with clinical treatment responses. The assay may be an important and useful method for individualized chemotherapy for recurrent ovarian cancer.

Objective: To evaluate the predictive value of the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in the chemotherapy applied in primary epithelial ovarian cancer (PEOC), and to analyze if the neoadjuvant chemotherapy have any influence on the postoperative chemosensitivity., Methods: ATP-TCA results from 61 PEOC specimens were analyzed retrospectively. Patients were divided into sensitive group and resistant group according to the ATP-TCA results. Sensitive index (SI) was applied to analyze the ATP-TCA results. The correlation between in vitro results and clinical outcome was assessed by univariate and multivariate analysis., Results: SI set at > 250 had the highest test sensitivity, specificity, positive and negative predictive value of 91.6%, 73.9%, 84.6% and 85.0%, respectively. The ATP-TCA results had significant correlation with clinical outcome (chi(2) = 26.9, P < 0.001). Patients with tumors shown to be resistant had a higher risk of recurrence in comparison with those who were tested as sensitive (P = 0.030, OR = 0.033, 95%CI 0.002 approximately 0.724). The median progression-free survival (PFS) and overall survival (OS) of in vitro-sensitive patients were 26 months and 39 months, respectively, significantly longer than those in the in vitro drug-resistant group of patients (PFS 10 months and OS 25 months) (both P < 0.01). Neoadjuvant chemotherapy had a significant correlation with the clinical chemoresistance (chi(2) = 15.214, P < 0.001)., Conclusion: ATP-TCA assay may effectively predict the chemosensitivity of primary ovarian cancer, and predict the early recurrence of the tumor.

Objective: To discuss the prognostic factors of recurrent ovarian epithelial carcinoma and to analyze the curative effect of post-relapse treatment., Methods: The clinical records of 293 patients with ovarian epithelial carcinoma were reviewed retrospectively. There were 199 recurrent cases during the following up., Results: All the 199 patients received chemotherapy. And 173 patients only received chemotherapy. 16 patients received surgery and chemotherapy and the other 10 patients received radiotherapy and chemotherapy. 158 patients received platinum-based chemotherapy again and 41 patients received chemotherapy without platinum. The response rate of all the patients was 43.7% (87/199), the response rate of only chemotherapy was 39.9% (69/173), the response rate of surgery and chemotherapy was 75.0% (12/16), and the response rate of radiotherapy and chemotherapy was 60.0% (6/10). The patients were divided into four groups according to the progression free interval (PFI). The response rates in groups that PFI < or = 6 months, 7 - 12 months, 13 - 24 months and > 24 months were 5.1%, 47.2%, 82.1% and 96.0%, respectively. The median survival time in the 16 patients received second cyto-reductive surgery was 41 months. Multivariate analysis revealed that PFI was significantly correlated with prognosis of recurrent ovarian epithelial carcinoma (OR = 0.589, P = 0.021)., Conclusion: PFI is an individual prognostic factor for survival of recurrent ovarian epithelial carcinoma. PFI is significantly associated with the response rate of chemotherapy. Optimal secondary cytoreductive surgery may improve the overall survival of recurrent patients. The response rate of paclitaxel plus platinum chemotherapy in platinum-sensitive patients is higher than that of other platinum-based chemotherapy.

Objective: To explore a new approach in gene therapy of ovarian cancer, we used RNAi to inhibit survivin gene expression, and explore the effect of survivin and neu RNAi on growth, apoptosis and chemosensitivity of ovarian cancer cell line SKOV3/DDP cells., Methods: Expression vector of survivin gene-targeting siRNA was constructed using pSilencer 1.0-U6 vector containing U6 promotor (pSilencer-survivin) and transfected into SKOV3/DDP cells by lipofectamine. The untransfected group and pSilencer-control group were used as control. The expressions of survivin mRNA and protein were identified by RT-PCR and Western blot assay. The proliferation of SKOV3/DDP cells was determined by MTT assay. The apoptosis rate and cell cycle distribution were analyzed by flow cytometry. Cisplatin (DDP) resistance experiment was performed in SKOV3/DDP cells with RNAi., Results: Survivin RNAi plasmid knocked-down survivin expression in SKOV3/DDP cells obviously, arrested the cells at G(1)/G(0) phase, inhibited the cell proliferation and promoted cell apoptosis. The IC(50) of DDP to SKOV3/DDP cells transfected with survivin siRNA was dropped., Conclusion: Survivin RNAi can partly suppress the expression of survivin in SKOV3/DDP cells, inhibit the cell proliferation and promote cell apoptosis. Survivin RNAi can enhance the cell sensitivity to apoptosis induced by cisplatin, which implies that survivin RNAi may partly reverse the drug resistance of ovarian cancer. RNAi could be a new approach for gene therapy of cancer.

Objective: To investigate the clinical and pathological characteristics, treatment methods, and prognosis of synchronous primary cancers of the endometrium and ovary., Methods: The clinical data of 43 patients with synchronous primary cancers of the endometrium and ovary were retrospectively reviewed. The survival was calculated by Kaplan-Meier method and compared using the log-rank test., Results: The median age at diagnosis was 49 years (range, 28-73 years). The most common symptoms were abnormal vaginal bleeding (69.8%) and abdominal or pelvic pain (44.2%).Pelvic masses were found in 39.5% of the patients and enlarged corpus in 27.9% at physical examination, while pelvic masses were found in 67.4% of the 43 patients (29 cases) and thickening or abnormal endometrium in 23.3% (10 cases) during ultrasound examination. Of 25 patients examined by CT/MRI, pelvic masses were found in 13 cases and enlarged uterus in 11 cases. All 15 patients who underwent endometrial biopsies were proven to have endometrial carcinomas. Serum CA125 level was found to be elevated in 22 of the 34 examined cases (64.7%) with a median value of 500 U/ml (range, 39-3439 U/ml). FIGO stages of endometrial carcinomas: IA 18 cases, IB 20 cases, IC 2 cases, IIA 3 cases; Stages of ovarian carcinomas: IA 19 cases, IB 4 cases, IC 7 cases, II 4 cases, III C 9 cases. Twenty-four patients (55.8%) were in stage I both endometrial and ovarian carcinomas. Thirty-one patients underwent total hysterectomy plus bilateral salpingo-oophorectomy with omentectomy and appendectomy, meanwhile, 12 patients had pelvic lymph node dissection. Thirty-eight of the 43 patients (88.4%) had a pathologically proven endometrial adenocarcinoma. The predominant ovarian histology was endometrioid or mixed tumor with endometrioid components (30/43, 69.8%). Postoperatively, 26 patients (60.5%) received adjuvant chemotherapy alone, 12 had chemotherapy plus radiotherapy, only one patient had radiation alone and the remaining 4 cases received no adjuvant treatment. The 3- and 5-year survival rates of the group were 87.4% and 71.1%, respectively. The 3- and 5-year survival rates of patients with both endometrioid and ovarian carcinomas were higher than that of those with non-endometrioid or mixed subtypes (93.8%, 82.0% vs. 79.7%, 69.0%). The 3-year and 5-year survival rates of patients with early stage disease were better than those of the other patients (93.3%, 93.3% vs. 69.7%, 36.7%). Recurrence developed in 15 patients (34.9%). It was showed by univariate analysis that lower CA125 level, early FIGO stage, and adjuvant chemotherapy plus radiotherapy significantly and positively affect the 5-year survival rates, while only early FIGO stage and chemotherapy plus radiotherapy were revealed by multivariate analysis as independent prognostic factors., Conclusion: Synchronous primary cancers of the endometrium and ovary are different from either primary endometrial carcinoma or ovarian cancer, while it can usually be detected in early stage and with a good prognosis. The impact of the CA125 level on prognosis needs to be further studied. Surgical treatment alone may be enough for early stage patients. Chemotherapy plus radiotherapy may be necessary for advanced stage patients.

The purpose of this study was to analyze prognostic factors for ovarian metastases from primary gastric cancer, helping establish optimal strategy in ameliorating survival for this entity. Clinical data of 68 consecutive patients histologically diagnosed with ovarian metastases from primary gastric cancer were accrued from 1096 cases with female gastric cancer. Metachronous surgery was performed on 36 patients and 32 received synchronous surgery. There were 14 patients treated with surgery alone and 54 with combined modality therapy. After the median follow-up time of 9.1 months, the median survival time (MST) of 12.4 months was observed for all patients. Patients treated with synchronous surgery tended to have an inferior survival compared with those treated with metachronous surgery (MST: 10.9 vs 14.3 months; P = 0.100). Combined modality showed a significantly better MST compared with surgery alone (13.6 vs 7.9 months; P = 0.004). Chemotherapy cycles (more than four or less than or equal to four) were found to have an impact on survival (MST: 14.3 vs 9.4 months; P = 0.031). Peritoneal metastases, lymphovascular involvement, and unilateral ovarian metastasectomy were independent unfavorable prognostic factors. Combined modality therapy as primary therapy resulted in good outcome, and more aggressive chemotherapy (more than four cycles) was accompanied by an improvement in survival. Innovative systemic treatments need to be explored in treatment of peritoneal metastases and lymphovascular involvement. Bilateral oophorectomy was considered when ovarian metastases were histologically diagnosed.

Objective: To investigate the clinical characteristics of clear cell carcinoma of the ovary and to compare the survival of the patients treated by three different chemotherapy regimens., Methods: Between 1984 and 2005, the clinical data of 88 surgically treated patients with clear cell carcinoma of the ovary were retrospectively analyzed. Of the 88 patients, 55 (62.5%) had tumor in stage I, 2 in stage II, 22 in stage II, 3 in stage IV and 6 in indefinite stage. These patients underwent either bilateral salpingo-oophorectomy with hysterectomy and omemtectomy or cytoreduction surgery. Of 55 stage I patients, 20 received pelvic lymohadenectomy. All patients were given postoperative chemotherapy, 43 patients received CAP/CP, 33 paclitaxel combination with carboplatinum/cisplatin (TC/TP) and 12 CPT-11 plus MMC., Results: The response rate, recurrence rate, 3- and 5-year survival was 35.0%, 30.2% (13/43), 67.4% (29/43), 43.9% and 29.3%, respectively in patients treated with CAP/CP; 73.9%, 18.2% (6/33), 45.5% (15/33), 57.3% and 40.5%, respectively in the patients with TC/TP; 71.4%, 16.7% (2/12), 25.0% (3/12), 70.7% ( 3-yr survival, no available 5-yr survival), respectively in the patients with CPT-11 + MMC (P < 0.05). During follow-up, 47 (53.4%) patients were found to have recurrence, it was 45.4% (25/55) in stage I patients including 29.6% (8/27) in stage I a + I b and 60.7% (17/28) in stage I c, 75.0% (18/24) in stage II + III and 4/6 in the indefinite FIGO stage. The recurrences rate was 27.8% (5/18) in stage I patients with pelvic lymphadenectomy vs. 51.3% (19/37) in those without. It was 67.3% in 46 patients with elevated CA125, and 38.1% in the other 42 patients with normal or unavailable CA125 (P < 0.05). The overall 3- and 5-year survival rate of 88 patients was 48.7% and 40.9% , respectively, with 72.5% and 66.8% in stage I, 100.0% and 70.5% in stage Ia + Ib, 68.5% and 60.3% in stage Ic, 41.8% and 20.8% in stage II + III, 0 in stage IV (P < 0.05). The 3- and 5-year survival in stage I with pelvic lymphadenectomy was 88.5% and 75.8% vs. 70.3% and 65.1% in those without (P < 0.05). The 3- and 5-year survival of the patients with optimal (residual disease less than 2 cm) was 36.7% and 23.1% vs. 22.2% and 0 in those with suboptimal cytoreduction (P < 0.05), it was 46.8% and 38.8% in the patients with elevated CA125 vs. 46.7% and 43.5% in those with normal one (P > 0.05)., Conclusion: Our data show that ovarian clear cell cancer patient have a poor response to CAP/CP and may have a better response to TC/TP, especially to CPT-11 plus MMC. However, the overall prognosis is still poor and further clinical investigations are needed to improve it.

The role of germline BRCA1 mutations in hereditary breast and ovarian cancer (HBOC) has been well established in women in Western countries. However, relatively few studies have been carried out in Chinese population. In the present study, we investigated the frequency and spectrum of germline BRCA1 mutations in Chinese HBOC patients, all of whom were from northern part of China. A total of 25 women with HBOC and ten relatives were analyzed. Mutation screening was performed by a combination of denaturing high-performance liquid chromatography and sequencing. Seven protein-truncating mutations were identified. They were 667delG, 3347A --> T, 3478del5, 4255delCT, 1235A --> G, 2064G --> T, and 5589del8. The first four of the mutations were putative ones never reported before. The prevalence of the protein-truncating mutations in this HBOC series was 40.0%, which is similar to that observed in Western hereditary ovarian cancer patients but higher than that reported in Chinese women with sporadic breast and ovarian cancer. Among the ten relatives we analyzed, six shared the same mutations with their affected relatives. No ovarian cancer was detected after 19 months of follow-up. This study showed that BRCA1 mutations play an important role in Northern Chinese HBOC.

Objective: To compare the efficacy of combination regiments of taxol given weekly plus carboplatin and taxol given every three weeks plus carboplatin. To observe the toxicity of the two regiments. To observe the two-year survival rate in the two groups., Methods: Total 125 eligible patients in 13 centers of CGOG were entered into the two arms of this randomized clinical trial, of whom 51 were entered into weekly taxol group and 74 entered into 3 weeks taxol group., Results: 81.6% (102/125) of patients had satisfactory decreasing of CA125 level after optimal cytoreductive surgery and chemotherapy. 86.3% (44/51) of patients is in weekly group and 78.4% (58/74) of patients in three weeks group (P > 0.05). Relapse frequency is 29.7% in every three weeks group and 19.6% in weekly group (P > 0.05). Median interval to relapse is 15.7 months in every three weeks group and 13.6 months in weekly group (P > 0.05). One-year survival rate is 95.2% in every three weeks and 93.9% in weekly group (P > 0.05). Two-year survival rate is 78.7% in every three weeks and 85.3% in weekly group (P > 0.05). Grade III and IV myelosuooression is 45.9% in three weeks group and, 27.5% in weekly group (P < 0.05)., Conclusion: (1) The two regiments had equal efficacy. (2) Myelosuppression was less frequency in the weekly group than in every three weeks group. (3) Weekly taxol therapy has mild toxicity and is more suitable for the old and feeble patients. Weekly taxol therapy can be conveniently administered in outpatients department.

Objective: To determine the correlation between results of ATP bioluminescence tumor chemosensitivity assay (ATP-TCA) of human ovarian cancer specimens in vitro and clinical chemo-therapeutic responses of patients., Methods: Thirty-four freshly taken ovarian cancer specimens (28 cases) and ascites (6 cases) and 9 chemotherapeutic drugs were tested in vitro for cancer chemosensitivity by ATP-TCA., Results: Among the 34 ovarian cancer cases, the efficacy of ATP-TCA is 94.0%, the sensitivity, the specificity, the positive and negative predicting values, and an overall predicting value in vitro and vivo were 90.0%, 91.7%, 94.7%, 84.6% and 90.6%, respectively., Conclusion: The results of ATP-TCA assay are correlated well with clinical treatment responses. The assay may be an important and useful method for individual-based chemotherapy of cancers.

Objective: To explore the clinical characteristics of ovarian cancer in hereditary breast/ovarian cancer., Methods: Ninety-one cases of hereditary breast/ovarian cancer were analyzed in terms of age, histological features, stage, familial history, survival time and prognostic factors by SPSS statistical software., Results: The overall median survival time of the patients was 47 months, and the 2-and 5-year survival rates were 71.2% and 33.5%, respectively. The median age at diagnosis of ovarian cancer was 52 years with the majority of patients (60.4%) diagnosed before 55. Among 39 cases with double primary cancers, there are 20 cases (51.3%) with interval no less than 60 months. The most frequent histological types of ovarian cancer is serous adeno-carcinoma (59.3%). Most patients were in stage III or IV (76.9%) with poor differentiation (59.3%)., Conclusion: The age of diagnosis in ovarian cancer in patients with hereditary breast/ovarian cancer is earlier than that of sporadic ones. Most of the cases were advanced with poor differentiation. Stage and differentiation are the prognostic factors. In patients with double primary cancers, the clinical pathological characteristics of ovarian cancer had the main effect on their prognosis. The survival of hereditary ovarian cancer is similar to that of sporadic ones.

Objective: To investigate serum CA(125) levels and the value of serum CA(125) in differential diagnosis of benign pelvic mass., Methods: We retrospectively analyzed 492 patients with benign pelvic mass, including 237 cases of benign ovarian tumor and 255 other benign gynecological diseases. Sixty cases of ovarian epithelial cancer were randomly chosen as control group., Results: The median of serum CA(125) in patients with pelvic tuberculosis, uterine adenomyosis, ovarian endometriosis and ovarian fibroma were all higher than the cut-off level of CA(125) (35 kU/L), being 465.0, 88.9, 59.0 and 44.5 kU/L, respectively. Those of ovarian epithelial cancer patients were significantly higher than in benign pelvic mass (P < 0.01). The highest value of CA(125) among all the benign cases was 1281.0 kU/L, which was seen in a case of ovarian thecoma. The highest median value was 465.0 kU/L, detected in a patient with pelvic tuberculosis., Conclusions: Serum CA(125) levels in some benign pelvic mass are higher than the cut-off level of CA(125), such as pelvic tuberculosis, uterine adenomyosis, ovarian fibroma and ovarian endometriosis. The medians of serum CA(125) in benign pelvic mass are much lower than in ovarian epithelial cancer. Serum CA(125) is of significance in the differential diagnosis between hysteromyoma and uterine adenomyosis.

Objective: To study the clinical characteristics, treatment and prognostic factors of ovarian Setoli-Leydig cell tumor., Methods: During 1962 - 2002, a total of 11 patients with Setoli-Leydig cell tumor were retrospectively analyzed., Results: Microscopically, seven of the neoplasms were well differentiated, 3 were moderately differentiated and 1 was poorly differentiated. Nine of the tumors were stage Ia, 1 was stage IIc and 1 was stage IIIc. The most frequent symptoms were abdominal-pelvic masses. Six patients presented with androgenization and virilization, 3 of which had their serum testosterone tested, and the levels were elevated. Five patients presented with metromenorrhagia and abnormal vaginal bleeding. One of them was both androgenized and estrogenized. In addition, five patients had diseases associated with excessive estrogenic stimulation, such as uterine myoma and endometrial hyperplasia. Two patients suffered from breast cancer. All patients were subjected to operation. And 5 patients with poorly differentiated or stage II-III tumors were subjected to postoperational chemotherapy. After 6 months to 34 years follow-up, no patient died of this disease. Three patients who received conservative surgery achieved normal menstruation 1 - 3 months after operation, and one of them gave birth to a child., Conclusions: Ovarian Setoli-Leydig cell tumor has good prognosis. Surgery alone is a currently acceptable treatment for patients with well-differentiated early stage tumors. For patients with poorly differentiated or advanced tumors, postoperational chemotherapy seems to be necessary. Conservative surgery should be the treatment of choice in young patients who need future fertility.

Objective: To analyze the clinical characteristics of female pelvic tuberculosis for the differentiation from ovary carcinoma., Methods: Twenty patients who were confirmed having pelvic tuberculosis from March 1994 to May 2002 were retrospectively studied., Results: Poor economic condition, history of tuberculosis or contact with tuberculosis, and fever were among the most important factors in differentiating pelvic tuberculosis from advanced ovarian cancer. Pelvic mass and ascites were present in all of the 20 patients, abdominal distension in 16, abdominal pain in 12, fever in 16, lost of weight in 13, and diarrhea in 6. The level of serum CA125 ranged from 65 U/L to 1,069 U/L. Peritoneal effusion cytology was studied in 16 cases before operation., Conclusions: The clinical differentiation of female pelvic tuberculosis from ovary carcinoma was difficult. Pelvic tuberculosis should be considered in young women presented with pelvic mass, ascites, fever, an elevated CA125 level and negative cytology, and with a history of tuberculosis or contact with tuberculosis.

Objective: To evaluate the clinical characteristics, survival rate and prognosis of young patients with epithelial ovarian carcinoma., Methods: The clinic data of 455 women with epithelial ovarian carcinoma were reviewed. Kaplan-Meier method was used to calculate the survival rate. Cox proportional hazards regression model was used to determine the independent effect of each variable on survival., Results: Of 445 patients with epithelial ovarian carcinoma, 92 were < or = 40 years of age and 363 were older. Higher incidence of early-stage, well differentiation and mucous cell type but lower incidence of serous cell type, ascites and residual tumors were found in the younger group. The overall 5-year survival rates were 79.55% in < or = 40 years group and 28.2% in > 40 years group (P < 0.001). Univariate analysis showed that the survival rate of patients < or = 40 years was significantly higher than that of > 40 years. Only age, stage and residual disease were found to be the significant independent prognostic factors by the multivariate analysis., Conclusion: Epithelial ovarian carcinoma in patients with age

Background & Objective: Epithelial ovarian cancer is moderate sensitivity to chemotherapy; the survival has been improved by aggressive cytoreductive surgery followed by combination chemotherapy with cisplatin-based regimen.However,there is a controversy about chemotherapeutic sensitivity of its lymph node metastasis. This study was designed to evaluate chemotherapeutic sensitivity and prognosis of lymph node metastases in epithelial ovarian cancer., Methods: The authors retrospectively analyzed 50 cases of epithelial ovarian cancer with lymph node metastases in Cancer Hospital,Chinese Academy of Medical Sciences, Peking Union Medical College from June 1986 to February 2001, which included 32 cases with stage III-IV, and 18 with recurrent disease. All the 50 patients were with valuable metastatic lymph nodes,and among these patients 38 were also with valuable abdominal-pelvic tumor. Forty-six patients received 1-3 courses of neoadjuvant chemotherapy,cytoreductive surgery, and postoperative chemotherapy. The response rate was evaluated by the response criteria for solid tumor. The chemotherapy included neoadjuvant chemotherapy, and chemotherapy for patients with residual tumor after operation or recurrence. Forty-five patients received platinum-based chemotherapy regimens [including CP (cyclophosphamide+cisplatin), CAP (cyclophosphamide+epirubicin+cisplatin), TC (paclitaxel+carboplatin), TP (paclitaxel+cisplatin), cisplatin+mitomycin+vincristine+etoposide+carboplatin, gemcitabine+carboplatin,IEP(ifosphamide+etoposide+cisplatin regimens) and 1 patient received melphalan, 1 patient with CF(cyclophosphamide+5-fluorouracil)regimen, 3 patients with ifosphamide+etoposide., Results: The overall response rates of lymph node metastasis and abdominal-pelvic tumor were 68.0% and 71.1%, respectively (P >0.05). The response rates of lymph node metastasis and abdominal-pelvic tumor for stage III-IV were 78.1% and 76.7%, respectively (P >0.05); both were 50% for recurrent patients with epithelial ovarian cancer., Conclusion: Either in stage III-IV or in recurrent patients with epithelial ovarian cancer, chemotherapeutic sensitivity of lymph node metastasis was similar to that of abdominal and pelvic tumor. The prognosis was related to the optimality of cytoreductive surgery, and the intensity of chemotherapy.

Background & Objective: Lymphadenectomy in pelvic and para-aortic is one of the contents of FIGO staging operation in ovary cancer. The significance of lymphadenectomy in patients with epithelial ovarian cancer at second exploratory operation is unclear. This study was designed to assess the significance of lymphadenectomy in the patients with epithelial ovarian cancer at second exploratory operation., Methods: Fifteen patients with stage III and IV epithelial ovarian cancer were treated in the Cancer Hospital of Peking Union Medical College between July 1994 and October 1996 were analyzed retrospectively., Results: The degrees of differentiation were as follows: high degree in 2 patients, moderate in 7, low in 6, of the 15 patients, none of them performed lymphadenectomy and none of them was lymph node positive at second look operation. Four of 10 patients with negative findings at second look operation were recurrent, but there were no positive findings in pelvic and para-aortic lymph node., Conclusions: Lymphadenectomy at second look operation in patients with negative lymph node at primary surgery is unnecessary.

Radioimmunoimaging (RI I) assay with 99mTc labeled anti-CEA monoclonal antibody was performed in 31 patients with suspected primary or recurrent malignant ovarian tumor. The radiation dose raging from 920MBq to 110MBq(1mgIgG) was administered i.v. for each patient. Anterior-posterior views of the pelvis and abdomen were obtained routinely with gamma-camera during 18-24 hour after the application of antibody. The results of RII were compared with the findings in operation or CT examination. Sensitivity in diagnosis was 100% (13/13), specificity was 94%(16/17) and metastatic foci sensitivity was 63%(10/16). The serum CA125 in this study appeared to be correlated with the results of RII. However, in 2 patients with normal serum CA125 titers RII revealed true positive. The preliminary clinical results of RII with 99mTc-MAb showed that RII is a promising method for the detection of malignant ovarian tumors.