Saima Batool ( Department of Radiology, CMH, Lahore. )
Shahid Manzur ( Department of Radiology, Bahawal Victoria Hospital, Bahwalpur. )
Saleem Raza ( Department of Radiology, CMH, Lahore. )
Objective: To determine the accuracy of Doppler ultrasound in the diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding while taking histopathological findings as the gold standard.
Methods: The cross-sectional study was done at the Department of Radiology, Bahawal Victoria Hospital, Bahawalpur, from April 1 to September 30, 2009, and comprised 128 patients above 50 years of age having history of post-menopausal bleeding and who were referred to the department. Name, age and hospital registration number were recorded on a proforma. Doppler ultrasound was performed and endometrial thickness and uterine artery resistive index were recorded on transabdominal ultrasonography. Patients with endometrial thickness of more than 5mm and uterine artery resistive index of less than 0.7 were considered to be having endometrial carcinoma. Histopathology findings were also recorded using the hospital registration number of the patient. The findings of Doppler ultrasound scan were validated with the findings of histopathology.
Results: Of the 128 patients, 48 (37.5%) were between the ages of 51 and 55 years; 46 (35.93%) were in the 56-60 age group; and 34 (26.57%) were over 65 years. On the basis of Doppler ultrasound findings, 106 (82.8%) patients were diagnosed as having endometrial carcinoma, while 22 (17.19%) were declared negative. Ultrasonography results were compared with histopathology findings. The percentages of true positive, true negative, false positive and false negative were calculated. There were 103 (80.47%) true positive; 12 (9.37%) false positive; 10 (7.81%) true negative; and 3 (2.35%) false negative. Specificity, sensitivity, positive predictive value and negative predictive value were found to be 97.16%, 76%, 89.56% and 76.92% respectively.
Conclusion: The use of Doppler ultrasonography in non-invasive diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding was quite useful with good sensitivity, specificity, as well as positive and negative predictive values. There were no procedural complications.
Keywords: Post-menopausal bleeding, Endometrial carcinoma, Doppler ultrasonography, Resistive index, Endometrial thickness. (JPMA 63: 28; 2013).
Post-menopausal bleeding is a common clinical problem accounting for approximately 5% of visits to a general gynaecologist.1 Post-menopausal bleeding has been defined as vaginal bleeding occurring at least 6 months after complete cessation of periods in women not taking hormonal replacement therapy (HRT), or non-cyclic vaginal bleeding occurring in post-menopausal women who are receiving HRT.2
Abnormal vaginal bleeding may be caused by a number of gynaecologic or non-gynaecologic disorders. Endometrial atrophy is reported to be the most common cause of post-menopausal bleeding.3 Other causes include endometrial hyperplasia, endometrial polyps, endometrial carcinoma, and submucosal leiomyomas. Though most studies indicate that endometrial atrophy is the most common cause of post-menopausal bleeding, the results of recent studies with hysterosonography indicate that anatomic abnormalities, such as leiomyomata and polyps, are much more common than has been generally believed.4
A diagnosis of endometrial carcinoma should be excluded in all women of peri-menopausal or post-menopausal age presenting with abnormal vaginal bleeding.2 Intermenstrual and post-menopausal bleeding is the initial symptom in 75% to 90% of patients with endometrial carcinoma.5 Early diagnosis and treatment are important because the 5-year survival of patients varies from 90% to 100% in patients with little or no myometrial involvement, to 40% to 60% in patients with deep myometrial invasion.6 Early diagnosis of invasive carcinoma is also desirable, which allows for appropriate treatment, while surgical cure is still possible. Unfortunately, screening tests for endometrial carcinoma are not available, because the endometrium is not as accessible as the cervix, which is successfully screened by the Pap smear test. Historically, dilation and curettage has been considered the gold standard for the diagnosis and often the treatment of endometrial disease, but that requires general anaesthesia.
Pulsed Doppler indices and colour Doppler vascularity of the endometrium have been used to differentiate between benign and malignant endometrial pathology. Resistive index (RI) ranging from 0.40 to 0.70 has been reported to differentiate benign from malignant endometria accurately, with most authors recommending a threshold value of 0.40.7 Proposed values for the pulsatility index (PI) range from 1.00 to 2.00.8
In these studies, the values of RI and PI obtained below the given threshold indicated malignant disease.8 Other investigators, however, found endometrial thickness to be a better predictor of endometrial pathology than any of the Doppler indices evaluated to date.9 The present study was carried out to assess the accuracy of Doppler ultrasound in the diagnosis of endometrial carcinoma in Pakistani women presenting with post-menopausal bleeding while taking histopathological findings as the gold standard.
Patients and Methods
The cross-sectional study comprised 128 patients above 50 years of age having history of post-menopausal bleeding. Who had been referred to the Radiology Department of Bahawal Victoria Hospital, Bahawalpur, Pakistan, by consulting gynaecologists from April 1 to September 30, 2009. Non-probability purposive sampling technique was used. Only those patients were included in the study who had an endometrial thickness of more than 5mm on ultrasonography (US). Patients having an endometrial thickness of less than 5mm and uterine artery resistive index of more than 0.7 on Doppler ultrasound were not included in the study.
Name, age and hospital registration number were recorded on a proforma. Patients were informed that the data collected would be used in a study and that issues related to confidentiality and anonymity would be taken due care of. After taking informed consent, Doppler ultrasound was performed, by using Logiq P-5 General Electric Ultrasound machine equipped with multiple probes of varying frequencies. Endometrial thickness and uterine artery resistive index were recorded. Patients having endometrial thickness more than 5mm and uterine artery resistive index less than 0.7 were labelled as endometrial carcinoma.
Endometrial biopsy of these patients was carried out in the Gynaecology Department and sent to the Pathology Department of the Bahawal Victoria Hospital. Their results were also recorded using hospital registration number almost after 1 week. These results were compared with ultrasound findings. All data was entered into SPSS 10 for statistical analysis. Endometrial thickness greater than 5mm and uterine artery resistive index less than 0.7 was considered positive for endometrial carcinoma. Histopathology findings were compared with those of Doppler ultrasound. A 2x2 table was generated to calculate the sensitivity, specificity as well as positive and negative predictive values as well as accuracy of the Doppler ultrasound.
The age of the 128 patients ranged from 51 to over 65 years, with 48 (37.5%) being in the 51-55 age group; 46 (35.93%) within 56-60 years; and 34 (26.57%) over 65 years. The mean age was 57.93±4.07 years (Table-1).
A total of 106 (82.81%) patients were found to have endometrial carcinoma, while 22 (17.19%) were negative (Table-2).
These results were compared with histopathology findings. The incidence of true positive, true negative, false positive and false negative were calculated. Of all the patients, 103 (80.47%) were found to be true positive; 12 (9.37%) false positive; 10 (7.81%) true negative; and 3 (2.35%) were false negative. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were found to be 97.16%, 76%, 89.56% and 76.92% respectively (Table-3).
Endometrial carcinoma is the most common malignancy of the female genital tract. According to the Surveillance Epidemiology and End Results (SEER) database10 the incidence of endometrial carcinoma in women aged 30 to 34 years is 2.3/100,000; increases to 6.1/100,000 between ages 35 and 40 years; and rises dramatically to 36.2/100,000 in women aged 40 to 49 years. In post-menopausal women not having HRT, any bleeding is considered \\\'\\\'cancer until proven otherwise,\\\'\\\' although the incidence of malignancy in such patients ranges from 2% to 10% depending on the risk factors.11 Endometrial curettage, first described in 1843,12 is the most common operation performed on women across the world. As early as the 1950s, a review of 6907 curettage procedures13 found that the technique missed endometrial lesions in 10% of cases. Of these, 80% were polyps. In the 1970s, vacuum-suction curettage devices allowed sampling without anaesthesia in clinical setting. The most popular was the Vabra aspirator (Berkeley Medevices, Berkeley, California). This device was found to be 86% accurate in diagnosing cancer.14 Lately, less expensive, smaller, less painful plastic catheters with their own internal pistons to generate suction have become popular. One of these, the Pipelle device (Unimar, Wilton, Connecticut), was found to have similar efficacy but better patient acceptance compared with the Vabra aspirator.15
In an important study, Guido et al16 studied the Pipelle biopsy in patients who had known carcinoma undergoing hysterectomy. Out of a total of 65 patients, a Pipelle biopsy provided adequate tissue for analysis in 63 (97%), but malignancy was detected in only 54 patients (83%). Of the 11 with false-negative results, 5 (8%) had disease confined to endometrial polyps and 3 (5%) had tumour localised to less than 5% of the surface area of the cavity. The surface area of the endometrial involvement in that study was 5% or less of the cavity in 3 of 65 (5%); 5% to 25% of the cavity in 12 of 65 (18%), of which the Pipelle missed four cases; 26% to 50% of the cavity in 20 of 65 (31%), of which the Pipelle missed four; and greater than 50% of the cavity in 30 of 65 patients (46%), of which the Pipelle missed none.
These results provide an insight into the way endometrial carcinoma can be distributed over the endometrial surface or confined to a polyp, because tumours localised in a polyp or a small area of endometrium may go undetected. The investigators in that study concluded that the \\\'\\\'Pipelle is excellent for detecting global processes in the endometrium\\\'\\\'. It seems that undirected sampling, whether through curettage or various types of suction aspiration, is often fraught with error, especially in cases in which the abnormality is not global, but focal (polyps, focal hyperplasia, or carcinoma involving small areas of the uterine cavity).
Ultrasonography (US), especially a transvaginal approach, is the initial imaging modality in patients with suspected endometrial cancer. Endometrial cancer most often appears as thickened endometrium that is more than 5mm in a post-menopausal woman or 15mm in a pre-menopausal woman. Echogenecity varies, but alteration of endometrial texture or focal increased echogenecity may be seen.17 These appearances are not specific and can be observed in endometrial hyperplasia and polyps.18 Saline infusion sonohysterography improves diagnosis for endometrial cancer with reported 89% sensitivity, 46% specificity, 16% PPV, and 97% NPV.19 Risk of disseminating malignant cells by saline infusion sonohysterography is small (approximately 7%).20 Colour Doppler US often reveals increased vascularity with a multivessel pattern, in contrast to the pedicle artery sign seen in endometrial polyps.21 Spectral Doppler indices may have low impedance flow, but there is significant overlap in Doppler indices of benign and malignant conditions of the endometrium.22
Myometrial invasion is depicted as irregularity of the endometrium — myometrium border and disruption of the subendometrial halo. The accuracy of US in diagnosing the depth of invasion is approximately 73% to 93%, but US is better for grade 2-3 tumours and should not be used as the sole criterion for the decision to perform extensive surgery.21 Although US can be used to estimate the depth of invasion, a recent meta-analysis has shown that contrast-enhanced magnetic resonance imaging has better overall performance.22
The use of Doppler ultrasonography in the diagnosis of endometrial carcinoma in patients presenting with post-menopausal bleeding is useful with good sensitivity, specificity, PPV and NPV. Besides, there are no procedural complications.
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