Parity as a Prognostic Factor in Patients with Advanced-Stage Epithelial Ovarian Cancer.

AIM: This study aimed to determine the prognostic factors influencing the overall survival (OS) of Iranian women with epithelial ovarian cancer (EOC). METHODS: Information about newly diagnosed patients with confirmed EOC at Motahari Clinic, Shiraz, Iran, from January 1, 2001, to December 31, 2016, was retrospectively reviewed and analyzed. Cox-adjusted proportional hazards (PH) and stratified Cox (SC) models were used to determine the potential prognostic factors. RESULTS: The mean (±SD) age at the diagnosis of 385 patients with EOC was 49.0 (±13.2) years old. Early-stage EOC (ESEOC) and advanced-stage EOC (ASEOC) were diagnosed in 34.3% and 65.7% of the total patients, respectively. The median (95% CI) OS was 35 (28-41) months. For ESEOC patients, a stage II-tumor led to a lower OS in the multivariable analysis compared to a lower stage tumor (P= 0.025). For ASEOC patients, age≥65 years at diagnosis (P=0.008) led to a lower OS. ASEOC patients with 2-5 parities (P=0.014) and >5 parity (P=0.001) demonstrated better OS than nulliparous women. CONCLUSION: Patients with ESEOC, higher tumor stage was associated with a shorter OS. The age at diagnosis harmed the OS of patients with ASEOC. More than one parity improved OS in ASEOC patients.

Predictive Value of Kanagawa Cancer Center Scoring System for Lymph Node Metastasis and Need for Lymphadenectomy in Patients With Endometrial Cancer: A Validation Study.

OBJECTIVES: The objective of this study was to determine the predictive value of Kanagawa Cancer Center (KCC) scoring system for lymph node metastasis and need for lymphadenectomy in patients with endometrial cancer. METHODS: This cross-sectional study was conducted during a 2-year period in a gynecologic oncology referral center in Southern Iran. We included a total number of 94 patients with endometrial cancer. Preoperative assessment included tumor volume, myometrium invasion, histology, and CA125. The KCC was calculated for all the patients. All the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy along with dissection of pelvic and para-aortic lymph nodes. The histopathology of the dissected lymph nodes was considered as criterion standard, and the predictive value of KCC was evaluated accordingly. RESULTS: The mean ± SD age of the patients was 56.8 ± 10.2 years. Overall, 26 patients (27.7%) tested positive for lymph node involvement. The sensitivity, specificity, positive predictive value, and negative predictive value of KCC for lymph node involvement was found to be 35.3%, 100%, 100%, and 64.7%, respectively. Overall, the predictive value according to the area under the curve measured by receiver operating characteristic curve was found to be 0.890 (0.823-0.956) indicative of moderate accuracy. Lymph node involvement was associated with higher Federation of Gynecology and Obstetrics stage (P < 0.001), higher tumor volume (P = 0.003), higher histological subtype (P < 0.001), positive CA125 (P < 0.001), and higher KCC score (P < 0.001). CONCLUSIONS: The KCC scoring system has a moderate accuracy for predicting the lymph node involvement in patients with endometrial cancer.

Cytokines, chemokines, and chemokine receptors quantitative expressions in patients with ovarian cancer.

BACKGROUND: Cytokines, chemokines, and chemokine receptors regulate the proliferation and survival of tumor cells, angiogenesis, and metastasis to other organs. This network of ligands and receptors has been used in molecular targeting of cancer. METHODS: We compared the mRNA expression of CXCR3, CXCL-10, CXCR4, CXCL-12, IL-4, and IL-10 in tissues of benign and malignant ovarian tumors by qRT-PCR method and evaluated serum IL-10 and CA-125 content of these patients by ELISA during one year. RESULTS: Our result showed a trend toward a higher expression of CXCR4 in malignant ovarian tissues compared with the benign ovarian cysts (P>0.05). However, SDF-1, IP-10, IL-4, CXCR3, and IL-10 had a lower trend in mRNA expression in malignant ovarian tissues compared to the benign cyst tissues. Except for IL-4 (P=0.01) and SDF-1 (P=0.02), the data for other factors were not statistically significant. A trend toward higher concentration of IL-10 was observed in the serum of ovarian cancer patients compared to those with benign cysts; however, the difference was not significant. CA-125 concentration in the serum of ovarian cancer patients was higher than that of benign cyst patients (P=0.05). CONCLUSION: According to results obtained, we hypothesize that the lower expression of SDF-1 in malignant tissues may have an important role in ovarian tumor growth. However, this hypothesis requires more investigation. Higher levels of CA125 and IL-10 in the serum of patients might indicate that the combination of these biomarkers could be used for distinguishing patients with ovarian cancer from those with benign cysts.

Adipose derived stem cells isolated from omentum: a novel source of chemokines for ovarian cancer growth.

BACKGROUND: The main site of ovarian cancer metastasis is the omentum. Omental adipose tissue is known for contribution to the tumor growth and metastasis through different mechanisms. AIMS: In the present study, adipose derived stem cells (ASCs) were isolated from the omentum of patients with ovarian cancer and those with ovarian cysts and the expression of chemokines, chemokine receptors and cytokines were analyzed. MATERIALS AND METHODS: ASCs were isolated from omental adipose tissues obtained of 10 ovarian cancer and 25 ovarian benign cyst patients. Our investigations were done by quantitative real time-polymerase chain reaction, flowcytometry, western blot and also enzyme-linked immunosorbent assay. RESULT: Expression of CXCL-10 and CCR5 showed statistically significant difference between omentum derived ASCs of ovarian cancer patients compared with those with benign cysts (P < 0.05). Expression of interleukin-10 also detected in the supernatant of cultured malignant ASCs. CONCLUSION: Omental adipose tissue may play crucial roles for tumor promotion through the expression of tumor promoting chemokines. Accordingly, tumor surrounding adipose tissue may be a novel target for immunotherapy of cancer.

Vascular endothelial growth factor (VEGF) improves the sensitivity of CA125 for differentiation of epithelial ovarian cancers from ovarian cysts.

BACKGROUND: The present study aimed to compare the diagnostic value of preoperative serum levels of CA125 and vascular endothelial growth factor (VEGF), and the combination of both biomarkers for differentiating early stage epithelial ovarian cancers from ovarian cysts. MATERIALS AND METHODS: In this study, preoperative and postoperative serum levels of CA125 and VEGF of 30 patients with epithelial ovarian cancers (cancer arm) compared with that of 30 patients with benign ovarian cysts (cyst arm). Initial eligibility included having an ovarian cystic or solid mass detected by transvaginal ultrasonography at the hospital clinic. Included patients had to have localized pelvic disease and no clinical or imaging evidence of extrapelvic disease, ascites and distant metastasis. Initial exclusion criteria included prior history of malignancy or any type of cancer treatment. After surgery, only patients with pathologic diagnosis of early stage epithelial ovarian cancer and ovarian cyst were included. RESULTS: Preoperative serum levels of CA125 (P < 0.001) and VEGF (P < 0.001) were significantly higher in the study arm compared to the control arm. In addition, postoperative serum levels of CA125 (P < 0.001) and VEGF (P < 0.001) in study arm were significantly decreased compared to preoperative serum levels. At usual clinical cut-off levels of 17.6 pg/ml for VEGF and 35 U/ml for CA125, the sensitivity and specificity for detecting early stage epithelial ovary cancer were 90 and 57 % for VEGF and 66.6 and 73 % for CA125, respectively. At 100 % specificity for each test, the addition of VEGF to CA125 increased the sensitivity of early ovarian cancer detection from 60 to 73.3 %. CONCLUSION: This study indicates that the addition of VEGF serum value improves the specificity and the sensitivity of CA125 to detect early stage epithelial ovarian cancers, and to differentiate these neoplasms from ovarian cyst.

The Effect of Extrafascial Hysterectomy After Completion of External Beam Radiotherapy for Treatment of Locally Advanced Stages (IIB-III) of Cervical Cancer.

BACKGROUND: Worldwide, cervical cancer is one of the most challenging gynecologic cancers in treatment. OBJECTIVES: This study was designed with the aim of comparing patients treated with External Beam Radiotherapy (EBRT) and Interactivity Brachytherapy (ICBT) with EBRT and extrafascial hysterectomy in locally advanced stages of cervical cancer (IIB-III). PATIENTS AND METHODS: The present study was designed as a case-control which was performed on the patients with cervical cancer in locally advanced stages (IIB-III) admitted to Namazi and Faghihi hospitals (university hospitals in Shiraz) between 2008-2011. 51 patients were included in two distinct groups: 25 patients were treated with EBRT and Interactivity Brachytherapy (group A). 26 patients were treated with EBRT and extrafascial hysterectomy group B. RESULTS: In group A, the number of patients with FIGO stage IIb and III were 16 and 9, respectively, and 17 and 9 in group B. The median duration of follow-up was 24 months. There were no significant differences between two groups in metastasis and recurrence rate (P > 0.05). 5-years overall survival rate was 54.8% [95% CI: 39-70.9] in group A and in group B was 50.9% [95% CI: 41.5-60] and The LOG-rank test which controls the effect of treatment modalities on overall survival rate, did not show any significant difference between two groups (P = 0.407). CONCLUSION: The results of our study showed that the trend of treatment using EBRT along with intracavity brachytherapy may have the same outcome as the method of using EBRT and extrafascial hysterectomy. Overall, it seems that external beam radiation followed by extrafascial hysterectomy could be a proper substitute for brachytherapy.

Prevalence of high-risk human papillomavirus types 16 and 18 in healthy women with cytologically negative pap smear in Iran.

BACKGROUND: Because human papillomavirus (HPV) is one of the causal factors in cervical cancer, understanding the epidemiology of this infection is an important step towards developing strategies for prevention. MATERIALS AND METHODS: We evaluated the prevalence of high-risk human papillomavirus Types 16 and 18 in cervical samples from 402 healthy women with normal Pap smears by testing with type-specific primers in the polymerase chain reaction. Participants were seen at two gynecological clinics affiliated to the Shiraz University of Medical Sciences in Iran. RESULT: The prevalence of positive HPV findings was 5.5%; high-risk HPV human papillomavirus Type 16 prevalence was 2% and no patient harbored HPV-18. The prevalence of HPV was 4.5% in younger age group and gradually increased to 20% in the 4 th decade. CONCLUSION: The prevalence of high-risk HPV was highest in the youngest women and gradually decreased with age. Overall, the prevalence of HPV in our population is low.

Genetic variation in TGF-beta 1 gene promoter and risk of gestational trophoblastic disease.

OBJECTIVE: To examine the relationship of transforming growth factor beta 1 (TGF-beta 1) gene polymorphisms at promoter positions -509 (C/T) and -800 (G/A) with the risk of gestational trophoblastic disease (GTD) as compared to normal controls STUDY DESIGN: Polymerase chain reaction-restriction fragment length polymorphism was performed on peripheral blood of 102 patients with GTD and 124 normal, healthy, pregnant women as the control group. RESULTS: In this study, TGF-beta 1 gene polymorphisms at positions -509 (C/T) and -800 (G/A) failed to correlate with GTD. CONCLUSION: Our findings suggest that promoter gene polymorphisms of TGF-beta 1 do not play major roles in GTD and may not be risk factors for this disease.

Weekly intramuscular methotrexate in the treatment of low-risk gestational trophoblastic neoplasia.

OBJECTIVE: The objective of this study was to determine the efficacy of weekly intramuscular (IM) methotrexate without dose escalation as first-line chemotherapy for low-risk gestational trophoblastic neoplasia (LRGTN). METHODS: Thirty-three women with post-molar LRGTN in the division of gynecology oncology at the Shiraz University of Medical Sciences were treated with weekly IM methotrexate at 30 mg/m(2) without dose escalation. The serum level of beta-hCG was detected every week. After the first negative beta-hCG level, one more cycle was administered as consolidation. Complete response (CR) was defined as the attainment of serum beta-hCG level of 5 IU/L or less measured on three consecutive weeks. RESULTS: Twenty-one of 33 women (63.6%) achieved CR with weekly IM injection of 30 mg/m(2) methotrexate. Ten of 12 patients with weekly IM methotrexate failure had a CR after one to three courses of dactinomycin administered at 1.25 mg/m(2) intravenously every 2 weeks. Two patients needed multiple-agent chemotherapy for remission. CONCLUSIONS: Weekly methotrexate without dose escalation may be an appropriate option for primary chemotherapy of patients with LRGTN.

A review of topotecan in combination chemotherapy for advanced cervical cancer.

Treatment of advanced, recurrent or persistent cervical cancer includes radiotherapy and chemotherapy. Radiation has been the primary treatment modality for locoregionally advanced cervical cancer. Concomitant systemic cisplatin chemotherapy and radiation have shown high response rates with improvements in durable remissions and overall survival. Cisplatin has been the standard medication for the treatment of advanced cervical cancer. Combinations with other chemotherapeutic agents have been the subject of clinical trials with varying results. The toxicity of combination chemotherapy and tolerability of patients are other factors that should be considered in the management of patients with advanced disease. Recently topotecan, in combination with cisplatin, achieved increased response and overall survival rates without further compromising the patients' quality of life. This review focuses on the mechanism of action and toxicities of topotecan, as well as its role as a radio-sensitizer and chemotherapeutic agent in the management of advanced, recurrent, or persistent cervical cancer. Other combination modalities and dosages are also discussed.

Association study of IL-10 and IFN-gamma gene polymorphisms in Iranian women with preeclampsia.

Preeclampsia (PE) is one of the most serious disorders of human pregnancy and Th1/Th2 imbalance may play a role in its etiology. Considering that cytokine production is under genetic control, in this study we have investigated IFN-gamma+874 (T/A) and three bi-allelic IL-10 promoter polymorphisms in a total of 134 preeclamptic women compared to 164 healthy women. It was shown that the IL-10 -1082 G allele frequency increases significantly in patients compared to the control group (P=0.045). No significant differences were found in any other genotype or allele frequencies of IL-10 and IFN-gamma genes between the two groups. In addition, the frequencies of three common IL-10 haplotypes (GCC, ACC, ATA) did not show any significant difference between the study groups. Since the presence of G nucleotide at position -1082 of IL-10 gene is associated with reduced cytokine production, therefore, the higher frequency of IL-10 -1082 G allele in preeclamptic patients compared to controls may be considered as a genetic susceptibility factor for the development of PE.