A Systematic Review of the Bimanual Examination as a Test for Ovarian Cancer

Ebell, Mark H.; Culp, MaryBeth; Lastinger, Krista; Dasigi, Tara

doi:10.1016/j.amepre.2014.10.007

Cited by 20 publications

(14 citation statements)

References 27 publications

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“…Ovarian cancer is a common malignancy that affects the ovaries (23)(24)(25). Previous studies have demonstrated that Klotho is involved in the development and progression of several types of human tumor (26,27); however, the effects of Klotho on ovarian cancer have not been clearly reported.…”

Section: Discussionmentioning

confidence: 99%

Reduced Klotho expression contributes to poor survival rates in human patients with ovarian cancer, and overexpression of Klotho inhibits the progression of ovarian cancer partly via the inhibition of systemic inflammation in nude mice

You-liang

Wang

Xiong

et al. 2017

Molecular Medicine Reports

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Klotho is a recently discovered anti‑aging gene, which has been reported as a tumor suppressor in numerous human malignancies; however, the role of Klotho in human ovarian cancer remains to be elucidated. The aim of the present study was to detect the expression of Klotho and evaluate its association with the progression of human ovarian cancer. A clinical follow‑up study of 120 patients with ovarian cancer and 78 normal controls was conducted. The expression levels of Klotho were determined by western blotting and immunohistochemistry. The results demonstrated that high Klotho expression levels were detected in all normal controls, whereas the positive rate of Klotho was 61.6% in the ovarian cancer group, which was significantly decreased compared with in the control group (P<0.01). Furthermore, reduced Klotho expression was significantly correlated with decreased survival rates in patients with ovarian cancer (P=0.025). Subsequently, Klotho levels were detected in seven human ovarian cancer cell lines by western blotting. The results demonstrated that the highest levels of Klotho were detected in CaOV3 cells, medium levels of Klotho were detected in CaOV4 and SKOV‑3 cells, and almost no Klotho was detected in the other four cell lines: OVCA 432, OVCAR‑5, OVCAR‑8 and A2780 cells. The association between Klotho levels and cell proliferation was determined by MTT assay, and the results indicated that higher levels of Klotho inhibited the proliferation of A2780 and OVCAR‑5 cells, whereas reduced Klotho expression promoted cell growth of CaOV3 and SKOV‑3 cells. In addition, the plasma levels of inflammatory cytokines in tumor‑bearing mice and normal control mice were detected by enzyme‑linked immunosorbent assay, and plasma interleukin (IL)‑6 and IL‑1β levels were elevated in all tumor‑bearing mice. Notably, the mRNA expression levels of IL‑6 were significantly higher in the liver, ovaries and kidneys of Klotho‑/‑ mice compared with in wild type mice (P<0.01), thus indicating that aberrant Klotho expression may contribute to systemic inflammation in Klotho‑/‑ mice. Finally, the in vivo antitumor role of aberrant Klotho expression was determined in a nude mice model. A2780 cells were transfected with pCMV6‑Klotho and the stably transfected cells were screened; the mice were injected with the stably transfected cells. The results indicated that tumor volume and tumor weight were significantly decreased in the pCMV6‑Klotho group compared with in the pCMV6 vector group (P<0.01). These findings suggest that overexpression of Klotho may suppress tumor growth in animal models. In conclusion, Klotho was demonstrated to act as a potent tumor suppressor in human ovarian cancer cells. Reduced Klotho expression was detected in the specimens of patients with ovarian cancer, and overexpression of Klotho significantly inhibited cell proliferation of human ovarian cancer cells. Therefore, Klotho may be considered a useful key target for the molecular therapy of human ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Reduced Klotho expression contributes to poor survival rates in human patients with ovarian cancer, and overexpression of Klotho inhibits the progression of ovarian cancer partly via the inhibition of systemic inflammation in nude mice

You-liang

Wang

Xiong

et al. 2017

Molecular Medicine Reports

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show abstract

“…For ovarian cancer diagnosis, screening biomarkers have been widely studied, but few have satisfactory performance for clinical applications [ 4 , 5 ]. Ovarian cancer remains a poor prognostic disease as vague or nonspecific symptoms lead to delayed diagnosis [ 8 ]. Thus, there is an urgent need to improve early detection methods and identify new diagnostic biomarkers for the disease [ 4 , 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, bimanual pelvic examination, cancer antigen (CA) 125 and transvaginal sonography are widely employed as main diagnostic tools for early diagnosis of ovarian cancer [ 3 – 5 ]. Unfortunately, several high-quality studies have demonstrated that the bimanual pelvic examination lacks accuracy as a screening method for ovarian cancer [ 6 – 8 ]. CA125, a tumor-specific antigen, is frequently used to detect ovarian cancer and is elevated in 80% of women with advanced ovarian carcinomas [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis

Zhou

Leng

et al. 2016

PLoS ONE

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BackgroundQuantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of ovarian cancer. Many studies have evaluated these approaches, but the results were too inconsistent to be conclusive. This study is the first to systematically evaluate the accuracy of circulating cfDNA for the diagnosis of ovarian cancer by conducting meta-analysis.MethodsWe searched PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure (CNKI) databases systematically for relevant literatures up to December 10, 2015. All analyses were conducted using Meta-DiSc1.4 and Stata 12.0 software. Sensitivity, specificity and other measures of accuracy of circulating cfDNA for the diagnosis of ovarian cancer were pooled. Meta-regression was performed to identify the sources of heterogeneity.ResultsThis meta-analysis included a total of 9 studies, including 462 ovarian cancer patients and 407 controls. The summary estimates for quantitative analysis of circulating cfDNA in ovarian cancer screen were as follows: sensitivity, 0.70 (95% confidence interval (CI), 0.65–0.74); specificity, 0.90 (95% CI, 0.87–0.93); positive likelihood ratio, 6.60 (95% CI, 3.90–11.17); negative likelihood ratio, 0.34 (95% CI, 0.25–0.47); diagnostic odds ratio, 26.05 (95% CI, 14.67–46.26); and area under the curve, 0.89 (95% CI, 0.83–0.95), respectively. There was no statistical significance for the evaluation of publication bias.ConclusionsCurrent evidence suggests that quantitative analysis of cfDNA has unsatisfactory sensitivity but acceptable specificity for the diagnosis of ovarian cancer. Further large-scale prospective studies are required to validate the potential applicability of using circulating cfDNA alone or in combination with conventional markers as diagnostic biomarker for ovarian cancer and explore potential factors that may influence the accuracy of ovarian cancer diagnosis.

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“…Thus, bimanual pelvic examination, transvaginal sonography (TVS) and carbohydrate antigen (CA) 125 levels are widely employed diagnostic tools for the early detection of ovarian cancer. Unfortunately, several high-quality studies have demonstrated that bimanual pelvic examination lacks accuracy as a screening method for distinguishing benign from malignant lesions [4]. TVS is accurate in detecting abnormalities in ovarian volume and morphology but is less reliable in differentiating benign from malignant ovarian tumours, and its diagnostic accuracy is largely affected by the experience of the examiner [5].…”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of urine HE4 in patients with ovarian cancer: a meta-analysis

et al. 2016

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Urine HE4 has been reported as the potential novel diagnostic biomarker for ovarian cancer in several studies, but their results were inconsistent. Therefore, we conducted a systematic analysis to evaluate the diagnostic value of urine HE4 in detecting ovarian cancer. A comprehensive electronic and manual search was conducted for relevant literatures through several databases up to May 5, 2016. The quality of the studies included in the systematic review was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. All analyses were conducted using Meta-DiSc 1.4 and STATA 12.0 software. A total of seven publications were included in this study, and these studies included 413 ovarian cancer patients and 573 controls. The summary estimates were: sensitivity 0.76 (95% confidence interval [CI]: 0.72–0.80), specificity 0.92 (95% CI: 0.89–0.94), positive likelihood ratio 8.39 (95%CI: 4.81–14.63), negative likelihood ratio 0.23 (95% CI: 0.13–0.39), diagnostic odds ratio 37.90 (95% CI: 18.69–76.83), and area under the curve 0.93. According to our results, urine HE4 has greater diagnostic value in detecting ovarian cancer. In addition, considering the high heterogeneity, further research studies with more well-designed and large sample sizes are needed in the future.

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A Systematic Review of the Bimanual Examination as a Test for Ovarian Cancer

Cited by 20 publications

References 27 publications

Reduced Klotho expression contributes to poor survival rates in human patients with ovarian cancer, and overexpression of Klotho inhibits the progression of ovarian cancer partly via the inhibition of systemic inflammation in nude mice

Reduced Klotho expression contributes to poor survival rates in human patients with ovarian cancer, and overexpression of Klotho inhibits the progression of ovarian cancer partly via the inhibition of systemic inflammation in nude mice

Circulating Cell Free DNA as the Diagnostic Marker for Ovarian Cancer: A Systematic Review and Meta-Analysis

Diagnostic accuracy of urine HE4 in patients with ovarian cancer: a meta-analysis

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