Impact of diabetes mellitus on epithelial ovarian cancer survival.

BACKGROUND: Diabetes mellitus (DM) is associated with poorer outcomes in some cancers. Its effect on ovarian cancer is less clear. We consider the effect of DM on overall survival (OS) and progression free survival (PFS) in patients with epithelial ovarian cancer (EOC). METHODS: A retrospective cohort study of 215 patients with EOC diagnosed between 2009 and 2016 was performed. Records were reviewed for standard demographic, pathologic and DM diagnosis data. Cox regression was used to evaluate the relationship between disease status and survival after adjustment for age, body mass index (BMI), parity, stage, grade, histology, debulking status, hypertension (HTN), menopause status and neoadjuant chemotherapy. RESULTS: Patients with DM (27.97, 95%CI: 23.63 to 32.30) had a significantly shorter OS rates compared to patients without DM (41.01, 95%CI: 38.84 to 43.17). The unadjusted hazard ratio (HR) for the association between OS time and DM was 4.76 (95%CI: 2.99 to 7.59, P < 0.001). Following adjustment for demographic and pathologic variables, the HR was 3.93 (95% CI: 2.01 to 7.68; P < 0.001). The PFS in patients with DM (14.10, 95%CI: 11.76 to 16.44) was significantly shorter compared to patients without DM (28.83, 95%CI: 26.13 to 31.54). The unadjusted HR for PFS and DM was 5.69 (95% CI: 3.05 to 10.61; P < 0.001). After adjustment for demographic and pathologic variables, the HR was 2.73 (95% CI, 1.18 to 6.95; P < 0.001). CONCLUSIONS: DM can negatively effect on PFS and OS in EOC patients independent of the effect of other variables.

Resistance to single-agent chemotherapy and its risk factors in low-risk gestational trophoblastic neoplasms.

AIM: Gestational trophoblastic neoplasm (GTN) is a rare disease which is classified into high- and low-risk groups. While the high-risk patients require combination therapy, the low-risk groups respond to single-agent chemotherapy. We studied resistance to single-agent chemotherapy and its risk factors among the low-risk GTN patients in Iran. METHODS: We followed 168 low-risk GTN patients who were treated between 2001 and 2011 in Valiasr Hospital, Tehran, Iran. We used a case-control design and studied odds ratios (OR) and corresponding 95% confidence intervals (CI) to evaluate association between drug resistance and different personal and clinical variables. RESULTS: Resistance to sequential single-agent chemotherapy was 19%, although all patients had a complete remission after a combination of chemotherapy and/or surgery. Patients who had International Federation of Gynecology and Obstetrics scores of 5-6 - considered as, the intermediate risk group - had a 14-fold higher resistance compared with the low score patients (OR = 14.28, 95% CI = 5.54-36.81). We found higher risk of resistance among patients with metastasis (OR = 8.42, 95% CI = 2.44-29.07), large tumor size (>3 cm) (OR = 7.73, 95% CI = 1.93-30.91), high ß-hCG (>100 000 IU/L) (OR = 5.86, 95% CI = 1.07-32.02) and/or a diagnosis more than 4 months after pregnancy (OR = 3.30, 95% CI = 1.08-10.02), compared with their reference group. We found no priority for the different chemotherapy regimens. CONCLUSION: Intermediate risk GTN patients had a higher risk of resistance to chemotherapy compared with low-risk patients. Clinical trials and cost-effectiveness studies are needed to suggest a better treatment program for the intermediate risk group.

Efficacy of combination therapy of oral zinc sulfate with imiquimod, podophyllin or cryotherapy in the treatment of vulvar warts.

AIM: Zinc sulfate is beneficial in the treatment of epithelial warts. We conducted this study to compare the efficacy of combination therapy of oral zinc sulfate with conventional treatments in the treatment of vulvar warts. MATERIAL AND METHODS: This study was a randomized controlled trial. The sample size was 42 in each group. Women aged 20-50 years were placed by the block randomized method into six groups: the podophyllin-, imiquimod- and cryotherapy-treated groups, and another three groups receiving 8-week combination therapy of 400 mg oral zinc sulfate with one of the above-mentioned treatments. Data were analyzed using anova and Fischer's exact test with spss16. RESULTS: A total of 228 patients were recruited and completed the study in six treatment groups. No significant difference was observed in the response to treatment among these groups. Relapse after 6 months was significantly higher in the podophyllin-, imiquimod- and cryotherapy-treated patients compared to patients receiving these treatments in combination with oral zinc sulfate (P<0.05). CONCLUSIONS: Combined therapy of oral zinc sulfate with conventional treatments of vulvar warts appears to reduce the relapse rate.

Resistance to single-agent chemotherapy in low-risk gestational trophoblastic neoplasia.

Background: Methotrexate (MTX) and actinomycin D (ActD) have been used as first-line chemotherapy agents in the treatment of low-risk gestational trophoblastic neoplasia (GTN). Although low-risk GTN is considered a curable disease, its reported primary remission rates of 49 to 93% reflect the difficulties of treatment and different factors influencing it. Hence, this study aimed to determine the remission rates and related factors of single-agent chemotherapy resistance in low-risk GTN patients. Methods: This retrospective study included patients with diagnosed low-risk GTN who received either MTX once a week (IM, 30mg/m2) or ActD once every two weeks (pulsed IV, 1.25mg/m2). Then, the patients were followed-up until complete remission or single-agent treatment failure to assess resistance rate and related factors. Results: Eighty-four patients were included in the study (18 patients were receiving MTX and 66 patients were receiving ActD). 85.7% of all participants achieved complete remission after first-line chemotherapy (72.2% in MTX vs 89.4% in ActD). There was a significant association for higher tumor size (P=0.046), the occurrence of metastasis (P=0.019), and pretreatment ß-HCG levels (P=0.005) with resistance to treatment. Conclusion: This study demonstrated higher tumor size, the occurrence of metastasis, and pretreatment ß-HCG levels have been associated with increased resistance to first-line chemotherapy agents.

Ovarian adenosarcoma in a postmenopausal woman: Case report and review of literature.

INTRODUCTION AND IMPORTANCE: Mullerian adenosarcoma is a rare malignancy that generally occurs in the uterine corpus but uncommonly, it may be found extrauterine. Ovarian adenosarcoma is extremely rare and often is presented in reproductive age women. Most of them are low grade and have à good prognosis except for adenosarcoma with sarcomatous overgrowth. CASE PRESENTATION: A 77-year-old menopausal woman presented with abdominal discomfort. She had severe ascites and elevated levels of CA-125, CA 19-9, and HE4 tumor markers. Adenosarcoma with sarcomatous overgrowth was diagnosed after the histopathological examination of the surgical biopsy. CONCLUSION: The possibility of endometriosis transformation to malignancy even in postmenopausal women may warrant continuous follow-up for early diagnosis of ovarian cancer, this potentially fatal disease. More studies are needed to find the best therapeutic approach to adenosarcoma with sarcomatous overgrowth.

A Systematic Review on Overall Survival and Disease-Free Survival Following Total Pelvic Exenteration.

BACKGROUNDS: Total Pelvic Exenteration (TPE) is a radical operation for malignancies in which all of the organs inside the pelvic cavity, including the female reproductive organs, the lower urinary tract, and a part of the rectosigmoid are removed. In this study, we aimed to conduct a systematic review to assess the overall survival (OS) and disease-free survival (DFS) following TPE. METHODS: This systematic review is composed of a comprehensive review of PubMed and Scopus databases with various related keywords to synthesis the overall survival and disease-free survival following TPE. The Synthesis Without Meta-analysis guideline was used to summarize the results. RESULTS: We included the results of 39 primary studies and the results revealed that one-year OS of gynecological cancer in patients who have undergone TPE ranged from 50.0% to 72.0% and the 5-years OS ranged from 6.0% to 64.6%. The one-year survival rate of colorectal cancer patients was reported to be over 80% in almost all studies. The 3-year survival rate of patients varied from 25% to 75% and the lowest 5-year survival rate was 8% and the highest survival rate was 92%. To synthesis the disease-free survival rate in colorectal cancer, ten studies were included and one-year recurrence rate was 9.1% and the one-year DFS was reported as 61.0%. Three-year recurrence rate study was 20.4% and 3 and 5-year DFS ranged from 22.0% to 78.0%. CONCLUSIONS: The results suggested that DFS in primary advanced cancers is higher than locally recurrence tumors. This review showed that patient overall survival and disease-free survival rates have increased over time, especially at high volume centers that are more experienced and possibly better equipped. Therefore, it can be suggested that the attitude towards PE as a palliative surgery can be turned into curative surgery.

Effectiveness of Megestrol for the Treatment of Patients with Atypical Endometrial Hyperplasia or Endometrial Endometrioid Adenocarcinoma (Stage IA, Well Differentiated).

OBJECTIVE: We aimed to evaluate treatment responses and recurrence rate of atypical endometrial hyperplasia (AEH) and endometrial endometrioid adenocarcinoma (EA) with Stage IA Grade 1 to megestrol in Iranian patients who are candidates for medical treatments. METHODS: In a retrospective cohort study that was conducted on 50 patients with AEH and 22 patients with EA who were referred to the oncology clinic of Imam Khomeini Hospital, Tehran, Iran, during 2006-2016, we recruited all patients with AEH or EA of Stage IA Grade 1 and their disease was diagnosed during endometrial curettage with or without hysteroscopy. Patients were initially treated with 160 mg of megestrol daily, along with aspirin up to 3 months, and then after 3-4 weeks of discharge of the drugs, patients underwent curettage with hysteroscopy. FINDINGS: The patients with AEH had 31 complete responses and five progressive diseases, and the patients with EA had seven complete responses and seven progressive diseases. After treatment, 25 cases with AEH and 5 cases with EA had an intention to get pregnant, whereas eight patients with AEH and 1 case with endometrial cancer became pregnant. Recurrence occurred in the 2 cases with AEH and 2 cases with endometrial cancer which the time of recurrence in the patients with AEH was longer than in patients with endometrial cancer (P = 0.011). CONCLUSION: Megestrol is an effective therapeutic agent in endometrial hyperplasia or low-grade endometrial cancer patients who are willing to conserve their childbearing.

Uterine involvement in epithelial ovarian cancer and its risk factors.

BACKGROUND: Epithelial ovarian cancer (EOC) is an extremely aggressive and lethal carcinoma. Specific data that identify high-risk groups with uterine involvement are not available. Thus, this study aimed to evaluate a gross number of women with EOC to obtain the frequency of uterine involvement and its risk factors. METHODS: This retrospective observational study was conducted on 1900 histologically confirmed EOC women, diagnosed and treated in our tertiary hospital from March 2009 to September 2020. Data including their demographic, medical and pathological findings were collected. RESULTS: From 1900 histologically confirmed EOC women, 347 patients were eligible for participations. The mean age of study patients was 51.31 ± 11.37 years with the age range of 25 to 87 years. Uterine involvement was detected in 49.6% (173) of the patients either macroscopic (47.4%) or microscopic (52.6%) types. Uterine involvement was significantly associated with having AUB (P-value = 0.002), histological type of ovary tumor (P-value < 0.001), ovarian cancer stage (P-value < 0.001), and abnormal CA-125 concentration (P-value = 0.004). Compared to the other study patient, the patients with metastatic uterine involvement had significantly higher stage (p-value< 0.001), higher grade of ovary tumor (p-value = 0.008), serous histological type (p-value< 0.001), and a higher level of CA-125 concentration (p-value< 0.001). on the other hand, the patients with synchronous uterine cancer were significantly younger (p-value = 0.013), nulliparous (p-value< 0.001), suffered from AUB symptoms (p-value< 0.001) and had endometroid histological type (p-value = 0.010) of ovary cancer in comparison to other study patients. CONCLUSION: Considering the high prevalence of uterine involvement in EOC patients, ultrasound evaluation and/or endometrium biopsy assessment should be done before planning any treatment.

Can primary optimal cytoreduction be predicted in advanced epithelial ovarian cancer preoperatively?

INTRODUCTION: Prediction of optimal cytoreduction in patients with advanced epithelial ovarian caner preoperatively. METHODS: Patients with advanced epithelial ovarian cancer who underwent surgery for the first time from Jan. to June 2008 at gynecologic oncology ward of TUMS (Tehran University of Medical Sciences) were eligible for this study. The possibility of predicting primary optimal cytoreduction considering multiple variables was evaluated. Variables were peritoneal carcinomatosis, serum CA125, ascites, pleural effusion, physical status and imaging findings.Univariate comparisons of patients underwent suboptimal cytoreduction carried out using Fisher's exact test for each of the potential predictors. The wilcoxon rank sum test was used to compare variables between patients with optimal versus suboptimal cytoreduction. RESULTS: 41 patients met study inclusion criteria. Statistically significant association was noted between peritoneal carcinomatosis and suboptimal cytoreduction. There were no statistically significant differences between physical status, pleural effusion, imaging findings, serum CA125 and ascites of individuals with optimal cytoreduction compared to those with suboptimal cytoreduction. CONCLUSIONS: Because of small populations in our study the results are not reproducible in alternate populations. Only the patient who is most unlikely to undergo optimal cytoreduction should be offered neoadjuvant chemotherapy, unless her medical condition renders her unsuitable for primary surgery.

Assessment of Cervical Cancer Molecular-Based Screening Tools; HPV-DNA Detection versus E6/E7 mRNA Testing; First Report of a Prospective Cohort Study among Iranian Women.

BACKGROUND: Human papillomavirus (HPV) has been found as the most considerable causes of cervical cancer. Recently, several molecular methods have been introduced to increase the accuracy of the screening programs and decrease the mortality rate. Among these methods, mRNA-based methods have more advantages as they assess the expression level of HPV E6 and E7 oncogenic mRNAs. This study aimed to evaluate the results of HPV RNA- and DNA-based methods among Iranian women population with normal cytology results. METHODS: Overall, 4640 women were enrolled referred to the Gynecology Oncology Ward of Vali-e-Asr Hospital, private and academic clinics, Tehran, Iran from Jan 2016 to Apr 2018. To assess the HPV-DNA infection INNO-LiPA® HPV Genotyping Extra-II kit was used. For HPV-RNA assessment, Aptima HPV Assay and in house HPV-RNA genotyping methods were applied. RESULTS: The positivity rates of HPV infection according to DNA- and RNA-based methods were 18.0% and 11.2%, respectively (P<0.001). The positive predictive value, negative predictive value, specificity and sensitivity of DNA-based method in contrast with RNA-based method were 59.2% (56.6-61.6), 99.4% (99.0-99.6), 91.7% (90.8-92.6) and 95.2% (93.0-96.9) respectively. CONCLUSION: At the present study for prognosis of cervical cancer, RNA-based method seemed to be more specific in contrast to DNA-based method. Patient follow up and further studies will be conducted in order to clarify the clinical sensitivity and specificity of the two methods.

Complementary Role of Ultrasound in Management of Gestational Trophoblastic Disease.

BACKGROUND: Transvaginal Ultrasonography is a noninvasive and inexpensive medical imaging tool used for the diagnosis of various diseases. OBJECTIVES: To identify an effective method to identify high-risk patients for developing malignancy after molar evacuation. PATIENTS AND METHODS: A prospective serial assessment of 19 patients with gestational trophoblastic disease was performed. Clinical and laboratory data, transvaginal ultrasound and Doppler findings were evaluated the day before evacuation. They were followed-up in the first week after evacuation and every two weeks during the next two months, then every month until the sixth month. RESULTS: Ovarian theca lutein cysts (P = 0.018) (among pre-evacuation factors) and first week ultrasound (P = 0.02) can help in detecting high-risk patients. Even though, when ß-hCG titer is not available in a high-risk patient, post evacuation myometrial involvement (P = 0.005) is a useful sign for detecting persistency. CONCLUSIONS: Some ultrasonographic features of molar pregnancy have capability to predict malignancy in the course of disease.

Differentiation of benign from malignant adnexal masses by functional 3 tesla MRI techniques: diffusion-weighted imaging and time-intensity curves of dynamic contrast-enhanced MRI.

BACKGROUND: The aim of this study was to evaluate and compare the accuracy of diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) value, and time-intensity curve (TIC) type analysis derived from dynamic contrast-enhanced MR imaging (DCE-MRI) in differentiating benign from malignant adnexal masses. MATERIALS AND METHODS: 47 patients with 56 adnexal masses (27 malignant and 29 benign) underwent DWI and DCE-MRI examinations, prior to surgery. DWI signal intensity, mean ADC value, and TIC type were determined for all the masses. RESULTS: High signal intensity on DWI and type 3 TIC were helpful in differentiating benign from malignant adnexal masses (p<0.001). The mean ADC value was significantly lower in malignant adnexal masses (p<0.001). An ADC value<1.20?10-3 mm2/s may be the optimal cutoff for differentiating between benign and malignant tumors. The negative predictive value for low signal intensity on DWI, and type 1 TIC were 100%. The pairwise comparison among the receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) of TIC was significantly larger than the AUCs of DWI and ADC (p<0.001 for comparison of TIC and DWI, p<0.02 for comparison of TIC and ADC value). CONCLUSIONS: DWI, ADC value and TIC type derived from DCE-MRI are all sensitive and relatively specific methods for differentiating benign from malignant adnexal masses. By comparing these functional MR techniques, TIC was found to be more accurate than DWI and ADC.

Priority Setting for Improvement of Cervical Cancer Prevention in Iran.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Organized cervical screening and vaccination against human papilloma virus (HPV) have been successful interventions for prevention of invasive cervical cancer (ICC). Because of cultural and religious considerations, ICC has low incidence in Iran and many other Muslim countries. There is no organized cervical screening in these countries. Therefore, ICC is usually diagnosed in advanced stages with poor prognosis in these countries. We performed a priority setting exercise and suggested priorities for prevention of ICC in this setting. METHODS: We invited experts and researchers to a workshop and asked them to list important suggestions for ICC prevention in Iran. After merging similar items and removing the duplicates, we asked the experts to rank the list of suggested items. We used a strategy grid and Go-zone analysis to determine final list of priorities for ICC prevention in Iran. RESULTS: From 26 final items suggested as priorities for prevention of ICC, the most important priorities were developing national guidelines for cervical screening and quality control protocol for patient follow-up and management of precancerous lesions. In addition, we emphasized considering insurance coverage for cervical screening, public awareness, and research priorities, and establishment of a cervical screening registry. CONCLUSION: A comprehensive approach and implementation of organized cervical screening program is necessary for prevention of ICC in Iran and other low incidence Muslim countries. Because of high cost for vaccination and low incidence of cervical cancer, we do not recommend HPV vaccination for the time being in Iran.

Does Postevacuation ß -Human Chorionic Gonadotropin Level Predict the Persistent Gestational Trophoblastic Neoplasia?

ß -human chorionic gonadotropin (HCG) level is not a reliable marker for early identification of persistent gestational trophoblastic neoplasia (GTN) after evacuation of hydatidiform mole. Thus, this study was conducted to evaluate ß -HCG regression after evacuation as a predictive factor of malignant GTN in complete molar pregnancy. Methods. In this cross-sectional study, we evaluated a total of 260 patients with complete molar pregnancy. Sixteen of the 260 patients were excluded. Serum levels of HCG were measured in all patients before treatment and after evacuation. HCG level was measured weekly until it reached a level lower than 5 mIU/mL. Results. The only predictors of persistent GTN are HCG levels one and two weeks after evacuation. The cut-off point for the preevacuation HCG level was 6000 mIU/mL (area under the curve, AUC, 0.58; sensitivity, 38.53%; specificity, 77.4%), whereas cut-off points for HCG levels one and two weeks after evacuation were 6288 mIU/mL (AUC, 0.63; sensitivity, 50.46%; specificity, 77.0%) and 801 mIU/mL (AUC, 0.80; sensitivity, 79.82%; specificity, 71.64%), respectively. Conclusion. The rate of decrease of HCG level at two weeks after surgical evacuation is the most reliable and strongest predictive factor for the progression of molar pregnancies to persistent GTN.

Normal and tumour cervical cells respond differently to vaginal lactobacilli, independent of pH and lactate.

Cervical cancer is a human papilloma virus (HPV)-related cancer, but most HPV infections are transient or intermittent and resolve spontaneously. Thus, other factors, such as cervical microflora, which are dominated by lactobacilli, must be involved in invasive cervical carcinoma development after HPV infection. Previous studies have demonstrated that lactobacilli have antitumour effects, and it is possible that vaginal lactobacilli prevent cervical cancer. Here we examined the proliferative and apoptotic responses of normal and tumour cervical cells to common vaginal lactobacilli components by investigating human normal fibroblast-like cervical (normal cervical) and HeLa (cervical tumour) cell responses to Lactobacillus gasseri and Lactobacillus crispatus. The effects of different lactobacilli components, such as culture supernatants, cytoplasmic extracts, cell-wall extracts and live cells, were determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, trypan blue staining, lactate dehydrogenase assay and colorimetric caspase-3 activity assay. Changes in caspase-3 and human chorionic gonadotropin ß (hCGß) expression were analysed by quantitative RT-PCR. Tumour cell growth inhibition by culture supernatants was higher than that by pH- and lactate-adjusted controls. However, the effects of the supernatants on normal cells were similar to those of lactate-adjusted controls. Apoptosis was inhibited by supernatants, which was consistent with higher hCGß expression since hCG inhibits apoptosis. Our study demonstrated that common vaginal lactobacilli exert cytotoxic effects on cervical tumour cells, but not on normal cells, and that this cytotoxicity is independent of pH and lactate. Our results encourage further studies on the interaction between lactobacilli and cervical cells, and administration of common vaginal lactobacilli as probiotics.

A prospective study to evaluate the correlation between Reid colposcopic index impression and biopsy histology.

OBJECTIVE: To determine the strength of correlation between colposcopic impression using Reid index and biopsy histology. METHODS: In a colposcopy referral clinic in Tehran University, Iran. Colposcopy was carried out using Reid colposcopic index (RCI) scoring system and directed biopsy on 344 women between March 2004 and October 2005 by fellows supervised by a board-certified gynecologic oncologist. Results were retrospectively compared with a previous study carried out on 353 women by the same physicians. In this previous study, the colposcopy findings did not use RCI index; the significance of association between these 2 studies was assessed by chi(2) and kappa statistics. RESULT: The association between colposcopic impression and biopsy histology was highly significant (p < .001), both in RCI colposcopy group and general colposcopy group. However, the strength of the correlation between colposcopy impression and biopsy histology in RCI colposcopy group was more than the general colposcopy group (0.74 vs 0.45). The positive predictive value of any colposcopic abnormality for any histologic abnormalities in the RCI group was 92%. The negative predictive value of a benign colposcopic impression was 70.5%. The sensitivity was 74%, and the specificity was 90.7%. CONCLUSIONS: The good correlation between colposcopic impression and histological diagnosis by using Reid index in colposcopy would produce higher agreement and strength of the correlation. Therefore, the Reid index can be used as a reproducible technique which is easy to learn in colposcopic clinic.

A study to evaluate the utility of presurgical CA125 to predict optimal tumor cytoreduction of epithelial ovarian cancer.

OBJECTIVE: To determine the ability of a preoperative serum CA125 to predict optimal primary tumor cytoreduction in patients with stage III and IV epithelial ovarian cancer (EOC). MATERIALS AND METHODS: The records of patients with advanced stage who underwent primary surgery for EOC at Tehran University, Vali-Asr Hospital between 2000 and 2002 were reviewed. Inclusion criteria included FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative CA125, and an operative note clearly defining volume of residual disease. Without optimal cytoreduction was determined using the receiver operator curve (ROC). RESULTS: One hundred and twenty cases of advanced stage EOC were identified, of which 90 cases of stage III/IV met our inclusion criteria. Serum CA125 < or = 400 was identified with OD > or = 75% of the time. Conversely, optimal cytoreduction was performed in < or = 40% of patients with CA125 > or =4000. The area under the ROC curve for CA125 was 0.680. The optimal cytoreduction rate for those with and without ascites was 38% and 77%, respectively (P<0.001). In a multivariate analysis using CA125, age, and ascites, the area under the curve was 0.696. CONCLUSION: We conclude that CA125 level did not reliably predict optimal cytoreduction in patients with stage III-IV EOC.