Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer.

BACKGROUND: Ovarian cancer is the third most common gynaecological cancer worldwide, with an age-standardised incidence rate of 6.1 per 10,000 women. Standard therapy for advanced epithelial ovarian cancer (EOC) includes a combination of cytoreductive surgery and platinum-based chemotherapy. Cytoreductive surgery aims to remove as much of the visible tumour as possible. As extensive intraperitoneal metastases are typical of advanced EOC, cytoreductive surgery is usually an extensive procedure with the risk of excessive bleeding. Tranexamic acid given perioperatively is effective in reducing blood loss and allogeneic blood transfusion requirements in a variety of surgical settings. Therefore, tranexamic acid seems to be a promising agent for minimising blood loss and the need for blood transfusion among women with advanced EOC undergoing cytoreductive surgery. OBJECTIVES: To assess the effects of tranexamic acid for reducing blood loss associated with cytoreductive surgery in women with advanced EOC (stage III to IV). SEARCH METHODS: We searched the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2015), MEDLINE, EMBASE and conference proceedings to May 2015. We also checked registers of clinical trials, citation lists of included studies, key textbooks and previous systematic reviews for potentially relevant studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing tranexamic acid given during surgery versus placebo or no treatment, in adult women diagnosed with advanced EOC. DATA COLLECTION AND ANALYSIS: Two review authors (CK, AS) independently selected potentially relevant trials, extracted data, assessed risk of bias, compared results and resolved disagreements by discussion. MAIN RESULTS: We found only one study that met our inclusion criteria. This was a randomised double blind, placebo-controlled multicentre study conducted to evaluate the effectiveness of a single dose of intravenous tranexamic acid (15 mg/kg body weight) versus placebo, given immediately before surgery for reducing blood loss and the need for red blood cell transfusion. The mean total estimated blood loss was 668.34 mL and 916.93 mL for participants assigned to tranexamic acid and placebo groups, respectively. The mean difference (MD) of total estimated blood loss between the groups did not show a clinically important effect (MD - 248.59 mL; 95% confidence interval (CI) - 550.9 to 53.79; one study, 100 participants; moderate quality evidence). The mean number of transfused units of blood components was not different between the two groups (low quality evidence). There were no noted differences in the incidence of reoperation, readmission or thromboembolic events (very low quality evidence). We considered the methodology of the included study to be at low risk of selection, detection, and reporting biases. However, we were concerned about an imbalance of some baseline characteristics between the groups, and as there was no protocol for blood transfusion, the rate of blood transfusion may vary depending on the practice of each participating hospital. AUTHORS' CONCLUSIONS: Currently, there is insufficient evidence to recommend the routine use of tranexamic acid for reducing blood loss in women undergoing cytoreductive surgery for advanced EOC, as only limited data are available from a single, low quality RCT at low overall risk of bias.

Is Age an Independent Predictor of High-Grade Histopathology in Women Referred for Colposcopy after Abnormal Cervical Cytology?

This study was conducted to determine whether advancing age is an independent predictor of increased risk of high-grade pathologies among women referred for colposcopy after abnormal cervical cytology. Medical records were reviewed for women with abnormal cervical cytology who underwent colposcopy at Khon Kaen University Hospital. Logistic regression was used to determine the independent impact of age on the risk of high-grade pathologies. Mean age of the women was 42.8 years. Of 482 women, 97 (20.1%) were postmenopausal, and 92 (19.1%) were nulliparous. The rate of high-grade pathologies included cervical intraepithelial neoplasia 2-3, 99 (20.5%), adenocarcinoma in situ, 4 (0.8%), cervical cancer, 30 (6.2%), and endometrial cancer, 1 (0.2%). The prevalence of significant lesions was 26.9% (95% CI, 23.1%-31.2%). In total, 31 women had cancers (6.4%; 95% CI, 4.4%-9.0%). When controlling for smear types and parity, age was noted to be a significant independent predictor of high-grade histopathology. Women older than 35-40 years were approximately 2 times as likely to have severe histopathology as the younger women. This study illustrates the substantial risk of underlying significant lesions especially invasive cancer in Thai women with abnormal cervical cytology. Age was a significant independent factor predicting the risk of high-grade pathologies.

Cervical pathology in high-risk human papillomavirus- positive, cytologically normal women.

This study was undertaken to evaluate the prevalence of significant cervical pathology among women who are high-risk human papillomavirus (HR-HPV)-positive/cytology negative, the most common combination of positive co-tests. The records of 244 women HR-HPV-positive/cytology-negative who had undergone colposcopy at Srinagarind Hospital, Khon Kaen University during January 2010 and April 2014 were reviewed. Mean age was 46.4 years. Of these 224 women, 75 were positive for HPV types 16/18 (33.5%) and 123 were positive for non-16/18 types (54.9%). HR-HPV was not genotyped in the remaining 26 women (11.6%). Prevalence of significant lesions for the entire cohort was 2.4%, and 2.6% and 3.3%, respectively, for those with HPV 16/18 and other oncogenic HPV types. One woman with HPV 16/18 (1.3%) had invasive cervical cancer. Multiparous women were more likely to be infected with HPV 16/18 compared to nulliparous women (36.3% versus 17.6%, respectively). In conclusion, the prevalence of significant cervical lesion among our study population was 2.4%. Multiparous women were more likely to be infected with HPV 16/18 compared to nulliparous women.

Chitinase 3 like 1 is associated with tumor angiogenesis in cervical cancer.

Elevated serum levels of a secreted glycoprotein chitinase 3 like 1 (CHI3L1) are associated with poor prognosis and short survival time of patients with cervical cancer (CxCa). Our previous microarray data showed the increased expression of CHI3L1 in invasive CxCa compared to normal tissue, implicating a potential role of CHI3L1 in CxCa. To establish the pathological role of CHI3L1 in the development of CxCa, this study focused on its expression in CxCa and angiogenic impacts in tumor vessel formation. CHI3L1 activated angiogenesis by promoting endothelial cell migration and tube formation in vitro but failed to protect CxCa cell lines, CaSki and HeLa against apoptosis induced by γ-irradiation. In addition, the capability of CHI3L1 to induce proliferation and migration of CaSki and HeLa cells was cell type specific. In an analysis of 103 specimens from CxCa patients, increased expression levels of CHI3L1 mRNA and protein in invasive CxCa were 4-fold (P<0.05) and 2-fold (P<0.01), respectively, stronger than those in normal subjects. The immunostaining of CHI3L1 was positively correlated with VEGF expression (P=0.0019) and microvessel density (P=0.0110). Moreover, CHI3L1 expression was also positively associated with cancer metastasis (P=0.011). The data suggest the crucial role of CHI3L1 by promoting angiogenesis, which may contribute to the development and progression of CxCa. The findings help establish CHI3L1 as a prognostic biomarker and therapeutic target for CxCa patients.

Elevated preoperative platelet to lymphocyte ratio associated with decreased survival of women with ovarian clear cell carcinoma.

This study was conducted to establish whether the preoperative platelet to lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard analysis was used to determine the independent effect of PLR. Thirty-six patients were reviewed. Elevated PLRs were more commonly noted in patients with an advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR carried a higher rate of disease progression during primary therapy than that those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with elevated PLR was notably worse than that for patients with normal PLR (10 vs 34 months). Despite the impact of elevated PLR on PFS, it was found to be marginally significant when controlling for commonly applied prognostic markers. It, however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion, an elevated PLR appears to be directly associated with adverse survival rather than being a surrogate for other indicators of a poor prognosis. PLR may be a useful biomarker for predicting survival of women with OCCC and merits further large-scale studies.

Incidences of cervical intraepithelial neoplasia 2-3 or cancer pathologic diagnoses in patients with a high grade squamous intraepithelial lesion pap smear attending a colposcopy clinic at srinagarind hospital.

The aim of this study was to evaluate the outcomes of women with high-grade squamous intraepithelial lesion (HSIL) smears who had undergone the "see and treat" approach compared to those who underwent a conventional approach. The records of women with HSIL smears undergoing colposcopy at Srinagarind Hospital were reviewed. In those undergoing the conventional approach, the final histological diagnosis was made on the most severe histological results obtained after initial colposcopy. In the "see and treat" group, the final histological diagnosis was made on the examination of LEEP specimens obtained after initial colposcopy. Overtreatment in the see and treat group was defined as the LEEP specimens containing cervical intraepithelial neoplasia (CIN) 1 or less. During the study period, 302 women with HSIL underwent colposcopy. Twenty (6.6%) were nulliparous. One hundred and ninety-four (64.2%) underwent conventional management while the remaining 108 (35.8%) received the see and treat management. The prevalence of underlying high-grade lesions in women undergoing the conventional approach was significantly higher than that observed among women undergoing the see and treat approach (89.2% and 47.2%, respectively, P<0.001). The overtreatment rate in the see and treat group was 52.8%. Multivariate analysis revealed that only parity status was a statistically significant factor for predicting the overtreatment after undergoing the see and treat approach. In conclusion, the overtreatment rate among women undergoing see and treat in this study is notably high and therefore this approach should not be routinely practiced.

Accuracy of colposcopically directed biopsy in diagnosis of cervical pathology at Srinagarind Hospital.

OBJECTIVE: To determine the accuracy of colposcopically directed biopsy (CDB) in diagnosis of precancerous or cancerous lesion of the uterine cervix as a quality index of the institute. MATERIALS AND METHODS: We retrospectively reviewed the medical records of the women who had colposcopic examination at the Department of Obstetrics and Gynecology, Srinagarind Hospital from January, 2005 to December, 2010. The women with satisfactory colposcopic examination who had CDB and further interventions such as loop electrosurgical excision procedure (LEEP)/conization, and/or hysterectomy were included in study. The pathological reports of the specimens from CDB were analyzed comparing with LEEP/conization or hysterectomy according to the highest degree of abnormalities. Pathological reports of HSIL (high grade squamous intraepithelial lesion) or more severe were classified as positive, while LSIL (low grade squamous intraepithelial lesion) or less severe were classified as negative. RESULTS: There were 320 patients included, 259 having highest pathological reports of HSIL or more. The accuracy of CDB to detect HSIL or more of the uterine cervix was 87.8% with sensitivity, specificity, PPV and NPV of 84.9%, 100%, 100%, and 61%, respectively. CONCLUSIONS: The accuracy of CDB in diagnosis of cervical pathology in our institute was acceptable and comparable to those of others. CDB is a reliable method to obtain the pathological diagnosis in women with abnormal cervical cytologic screening.

Proportion of gynecologic cancer patients using complementary and alternative medicine.

BACKGROUND AND OBJECTIVES: Complementary and alternative medicine (CAM) for treatment of cancer and for supportive care of cancer patients must be clearly separated. There is encouraging evidence for CAM in the latter area, such as acupuncture and progressive muscle relaxation for chemotherapy-related nausea and vomiting, and aromatherapy for decreasing anxiety and increasing quality of life. However, there are limited data about CAM used by gynecologic cancer patients, especially in Thai women. Therefore, the authors aimed to investigate the proportion and types of CAM using in our gynecologic cancer patients. METHODS: This cross-sectional survey was conducted between October to December, 2008. Totals of 50 admitted and 50 walk-in gynecologic cancer patients 1 month after diagnosis, aged more than 20 years and able to give informed consent, were selected for one-by-one interview by random walking survey. RESULTS: Among the 100 interviewed patients, aged 21-69 (mean=50.12), there were 46 cases of cervical cancers, 35 of ovarian cancers, 18 of endometrial cancers (two of these also had ovarian cancers), 2 of malignant gestational trophoblastic diseases, 1 of vulvar cancer, and 1 liver cancer (in a patient with ovarian cancer). Some 67% (95% CI, 57.8-76.2%) of them used CAM. As diet modifications, 11 used Chinese vegetarian, 8 common vegetarian, 5 Cheewajit, and 1 macrobiotics. Five of them used dietary supplements while colonic detoxification was emplyed in three. As herbal medicines, 27 used Thai herbs, 4 Chinese herbs, and 1 a herbal sauna. Twelve were receiving Thai massage. As exercises, 23 used aerobics and 5 stretching. Interestingly, 62 of them used Buddhist praying while only 3 employed native magic. CONCLUSIONS: The three most common forms of CAM used by our gynecologic cancer patients were Buddhist praying (62/67, 92.5%), followed by herbal medicines (27/67, 40.3%) and exercises (25/67, 37.3%).