Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses

Background: Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment. A second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity. A third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process. Objectives: To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard). Search methods: We searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers. Selection criteria: Studies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation. Data collection and analysis: Authors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds. Main results: All studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%). Similarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%). Results were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%). Our additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively. In cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer. In three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections. In heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise. Authors' conclusions: In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative). If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed. The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice

Objective: To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). Materials & methods: This retrospective multicentre cohort st

Diagnostic value of microRNA panel in endometrial cancer:A systematic review

PURPOSE: We conducted a systematic review to evaluate the overall diagnostic accuracy of miRNAs in detecting endometrial cancer. MATERIALS AND METHODS: A systematic search of Medline, Embase, Cinahl and the Cochrane Controlled Register of Trials was performed to identify studies reporting on the diagnostic value of miRNA in EC patients. Included were diagnostic studies looking at miRNA expression in women diagnosed with endometrial cancer. Two reviewers independently selected studies and assessed quality of studies using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) score system. Data extraction was completed and the vote-counting strategy was used to rank miRNAs. RESULTS: 26 studies were included with a total number of 1,400 EC patients reporting on 106 differentially expressed miRNAs. The most frequently found up-regulated miRNA was miR-205 followed by miR-200c, -223, -182, -183 and -200a. In addition, miR-135b, miR-429, miR-141 and miR-200b were also frequently up-regulated. There was less consensus on down-regulated miRNAs. CONCLUSIONS: miRNAs yield a promising diagnostic biomarker potential in endometrial cancer, especially miR-205, the miR-200 family and miR-135b, -182, -183 and -223. However, no sufficient high quality data are available to draw hard conclusions. More research is needed to validate the diagnostic potential of these miRNAs in larger studies. In addition, the potential of urine as a non-invasive biofluid should be investigated in more detail

Feasibility and Effectiveness of the Exercise Program in Endometrial Cancer; Feasibility and Acceptability Survivorship Trial (EPEC-FAST)

To evaluate the feasibility of an individualized exercise program in the standard care for endometrial cancer patients aimed to improve quality of life and other health outcomes. This was a single-arm prospective intervention trial to assess the feasibility of an individualized exercise intervention in endometrial cancer patients after treatment. The exercise intervention consisted of weekly individualized training sessions, for 10 weeks, at a local gym facility. The program started six weeks post-operatively. Primary outcomes were feasibility aspects including number of eligible patients, recruitment and adherence rates. Secondary outcomes included quality of life outcomes and anthropometric measures. A total of 54 women were eligible for participation, of which 22 (41%) consented to the study. Overall attendance was 86%, and there were no adverse events. There was a significant improvement in quality of life outcomes, including role (p = 0.02), emotional (p = 0.02) and cognitive functioning (p = 0.04). In addition, there was a significant improvement in visceral fat percentage (p = 0.039) and physical fitness (six-minute walk test p 0.001). The maximum weight loss achieved was 6.0 kg after 3 months and 8.4 kg after 6 months. An individualized one-to-one exercise intervention in endometrial cancer patients is feasible in terms of recruitment, adherence and safety

Body mass index and sexual function in women with gynaecological cancer

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Usefulness of microRNA detection in the diagnostics of endometrial cancer

Item does not contain fulltextINTRODUCTION: MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and contribute to the development of cancer. They have been shown to be stable in tissue samples and may be promising diagnostic biomarkers for endometrial cancer. MATERIAL AND METHODS: A retrospective cohort study of women diagnosed with endometrial cancer between January 2017 and December 2017 was performed at the Royal Cornwall Hospital. Archived formalin-fixed paraffin-embedded samples were obtained from patients with endometrial cancer and healthy women. MicroRNA was isolated and quantitative real-time polymerase chain reaction was used to detect expression levels of miRNAs. RESULTS: A total of 76 women were included: 36 endometrial cancer patients, 40 healthy controls. A distinct panel of miR-200a, miR-200b, miR-200c, miR-205, and miR-182 showed an area under the curve of 0.958, sensitivity 92%, specificity 89%, positive predictive value of 89% (95% CI 82%-94%) and negative predictive value of 91% (95% CI 85%-96%) in diagnosing endometrial cancer. High miR-182 expression levels were significantly related to high-grade endometrioid tumors compared with low-grade tumors. CONCLUSIONS: We demonstrated high diagnostic accuracy of miRNA for detecting endometrial cancer. In addition, miRNA contributed to an improvement in distinguishing between high-grade and low-grade endometrioid tumors

Usefulness of microRNA detection in the diagnostics of endometrial cancer

Introduction MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and contribute to the development of cancer. They have been shown to be stable in tissue samples and may be promising diagnostic biomarkers for endometrial cancer. Material and methods A retrospective cohort study of women diagnosed with endometrial cancer between January 2017 and December 2017 was performed at the Royal Cornwall Hospital. Archived formalin-fixed paraffin-embedded samples were obtained from patients with endometrial cancer and healthy women. MicroRNA was isolated and quantitative real-time polymerase chain reaction was used to detect expression levels of miRNAs. Results A total of 76 women were included: 36 endometrial cancer patients, 40 healthy controls. A distinct panel of miR-200a, miR-200b, miR-200c, miR-205, and miR-182 showed an area under the curve of 0.958, sensitivity 92%, specificity 89%, positive predictive value of 89% (95% CI 82%-94%) and negative predictive value of 91% (95% CI 85%-96%) in diagnosing endometrial cancer. High miR-182 expression levels were significantly related to high-grade endometrioid tumors compared with low-grade tumors. Conclusions We demonstrated high diagnostic accuracy of miRNA for detecting endometrial cancer. In addition, miRNA contributed to an improvement in distinguishing between high-grade and low-grade endometrioid tumors

Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses

Background: Women with suspected early-stage ovarian cancer need surgical staging which involves taking samples from areas within the abdominal cavity and retroperitoneal lymph nodes in order to inform further treatment. One potential strategy is to surgically stage all women with suspicious ovarian masses, without any histological information during surgery. This avoids incomplete staging, but puts more women at risk of potential surgical over-treatment. A second strategy is to perform a two-stage procedure to remove the pelvic mass and subject it to paraffin sectioning, which involves formal tissue fixing with formalin and paraffin embedding, prior to ultrathin sectioning and multiple site sampling of the tumour. Surgeons may then base further surgical staging on this histology, reducing the rate of over-treatment, but conferring additional surgical and anaesthetic morbidity. A third strategy is to perform a rapid histological analysis on the ovarian mass during surgery, known as 'frozen section'. Tissues are snap frozen to allow fine tissue sections to be cut and basic histochemical staining to be performed. Surgeons can perform or avoid the full surgical staging procedure depending on the results. However, this is a relatively crude test compared to paraffin sections, which take many hours to perform. With frozen section there is therefore a risk of misdiagnosing malignancy and understaging women subsequently found to have a presumed early-stage malignancy (false negative), or overstaging women without a malignancy (false positive). Therefore it is important to evaluate the accuracy and usefulness of adding frozen section to the clinical decision-making process. Objectives: To assess the diagnostic test accuracy of frozen section (index test) to diagnose histopathological ovarian cancer in women with suspicious pelvic masses as verified by paraffin section (reference standard). Search methods: We searched MEDLINE (January 1946 to January 2015), EMBASE (January 1980 to January 2015) and relevant Cochrane registers. Selection criteria: Studies that used frozen section for intraoperative diagnosis of ovarian masses suspicious of malignancy, provided there was sufficient data to construct 2 x 2 tables. We excluded articles without an available English translation. Data collection and analysis: Authors independently assessed the methodological quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) domains: patient selection, index test, reference standard, flow and timing. Data extraction converted 3 x 3 tables of per patient results presented in articles into 2 x 2 tables, for two index test thresholds. Main results: All studies were retrospective, and the majority reported consecutive sampling of cases. Sensitivity and specificity results were available from 38 studies involving 11,181 participants (3200 with invasive cancer, 1055 with borderline tumours and 6926 with benign tumours, determined by paraffin section as the reference standard). The median prevalence of malignancy was 29% (interquartile range (IQR) 23% to 36%, range 11% to 63%). We assessed test performance using two thresholds for the frozen section test. Firstly, we used a test threshold for frozen sections, defining positive test results as invasive cancer and negative test results as borderline and benign tumours. The average sensitivity was 90.0% (95% confidence interval (CI) 87.6% to 92.0%; with most studies typically reporting range of 71% to 100%), and average specificity was 99.5% (95% CI 99.2% to 99.7%; range 96% to 100%). Similarly, we analysed sensitivity and specificity using a second threshold for frozen section, where both invasive cancer and borderline tumours were considered test positive and benign cases were classified as negative. Average sensitivity was 96.5% (95% CI 95.5% to 97.3%; typical range 83% to 100%), and average specificity was 89.5% (95% CI 86.6% to 91.9%; typical range 58% to 99%). Results were available from the same 38 studies, including the subset of 3953 participants with a frozen section result of either borderline or invasive cancer, based on final diagnosis of malignancy. Studies with small numbers of disease-negative cases (borderline cases) had more variation in estimates of specificity. Average sensitivity was 94.0% (95% CI 92.0% to 95.5%; range 73% to 100%), and average specificity was 95.8% (95% CI 92.4% to 97.8%; typical range 81% to 100%). Our additional analyses showed that, if the frozen section showed a benign or invasive cancer, the final diagnosis would remain the same in, on average, 94% and 99% of cases, respectively. In cases where the frozen section diagnosis was a borderline tumour, on average 21% of the final diagnoses would turn out to be invasive cancer. In three studies, the same pathologist interpreted the index and reference standard tests, potentially causing bias. No studies reported blinding pathologists to index test results when reporting paraffin sections. In heterogeneity analyses, there were no statistically significant differences between studies with pathologists of different levels of expertise. Authors' conclusions: In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative). If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed. The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients