Arch Gynecol Obstet (2015) 291:1121–1126 DOI 10.1007/s00404-014-3523-y
GENERAL GYNECOLOGY
Accuracy of endometrial sampling compared to conventional dilatation and curettage in women with abnormal uterine bleeding Ibrahim A. Abdelazim • Khaled M. Abdelrazak Assem A. M. Elbiaa • Mohamed Al-Kadi • Amr H. Yehia
•
Received: 30 July 2014 / Accepted: 16 October 2014 / Published online: 4 November 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Objectives To compare the diagnostic accuracy of brush endometrial sampling with conventional dilatation and curettage in women with abnormal uterine bleeding. Patients and methods Two hundred and twenty (220) women with abnormal uterine bleeding were included in this comparative study; endometrial sampling was done before cervical dilatation using Tao Bruch followed by conventional dilatation and curettage (D&C). The histopathology report of the Tao Bruch samples was compared with that of the D&C samples and the D&C results were considered as the gold standard. Results 100 % of samples obtained by conventional D&C, while 98.2 % of the samples obtained by Tao Brush were adequate for histopathology examination. In this study; Tao Brush had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium, also, it had 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value
Ahmadi hospital Kuwait Oil Company (KOC) Company, all the authors have contributed significantly and are responsible for the content of this manuscript. I. A. Abdelazim (&) K. M. Abdelrazak A. A. M. Elbiaa M. Al-Kadi A. H. Yehia Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt e-mail: [email protected] I. A. Abdelazim Ahmadi Kuwait Oil (KOC) Company Hospital, P.O. Box: 9758, Ahmadi, Kuwait A. A. M. Elbiaa Obstetrics and Gynecology, Sabah Maternity Hospital, West Shuwaikh, Kuwait
(PPV) and 99 % negative predictive value (NPV) and accuracy for diagnosing endometritis (no significant difference compared to conventional D&C), while, it had 77.8 % sensitivity, 100 % specificity, 100 % PPV and 99 % NPV and accuracy for diagnosing endometrial polyps (no significant difference compared to conventional D&C) Conclusion Endometrial sampling using endometrial brush cytology (EBC) is safe, accurate, cost-effective outpatient procedure, avoids general anesthesia with high sensitivity and specificity for detection of endometrial hyperplasia and endometrial carcinoma. EBC could be used as complementary diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted or not available. Keywords Endometrial sampling Dilatation and curettage Abnormal uterine bleeding
Introduction Abnormal uterine bleeding is a major gynecological problem, accounting for 33 % of outpatient referrals, including 69 % of referrals in perimenopausal and postmenopausal age group [1]. Evaluation of abnormal uterine bleeding in women C40 years or menopausal women is of critical importance to confirm benign nature of the problem, and to exclude endometrial carcinoma, so that medical or conservative treatment can be offered and unnecessary radical surgery can be avoided [2]. Dilatation and curettage (D&C) is the gold standard for endometrial sampling, but in 60 % of cases less than half of the uterine cavity is curetted, with the added risk of general anesthesia, infection, and perforation [3, 4]. This has led to the advent of new and simple methods for
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endometrial sampling; including endometrial aspiration cytology and endometrial brush cytology [5–8] Tao Bruch can be used on an outpatient basis and is cost effective compared with D&C [9, 10]. However, there are still concerns regarding the adequacy of the sample obtained, non-sampling of focal intrauterine lesions during endometrial aspiration or endometrial brush cytology [6]. This comparative study was designed to compare the diagnostic accuracy of endometrial sampling using Tao Bruch with conventional dilatation and curettage in women with abnormal uterine bleeding.
Patients and Methods Over 2 years, women with abnormal uterine bleeding C40 years, presented to gynecology clinics of Ahmadi Hospital Kuwait Oil Company (KOC), were included in this comparative study. Detailed clinical assessment of the patients was followed by transvaginal sonography and laboratory investigations (complete blood count (CBC), coagulation profile, prolactin, thyroid and liver function tests). Women with local gynecological cause or possibility of pregnancy or history of contraception or endometrial thickness \4 mm were excluded from this study. Two hundred and twenty (220) women were included in this study after informed consent and approval of the study protocol by the institute ethics committee. Women included in this study were euthyroid with normal liver function tests, normal activated partial thromboplastin time (APTT) and normal platelet count. The endometrial sampling was performed by Tao Bruch in the ward prior to premedication ordered by anesthetist. Tao BruchTM (Cook Medical Incorporated, Bloomington, USA) has outer sheath which promotes error-free test results by protecting the sample from endocervical or vaginal contamination (Fig. 1). Tao Bruch was introduced without performing cervical dilatation (Fig. 2) and was rotated inside the uterine cavity to get the sample after withdrawal of outer sheath outside the uterus (Fig. 3). The advancement of the outer sheath to protect the sample obtained from contamination was followed by withdrawal of Tao Bruch protected by outer sheath (Fig. 4) and Tao Bruch sample was labeled as sample A. Women were then transferred to the operative theatre for conventional D&C and the obtained sample after conventional D&C was labeled as sample B. Both samples were sent to a pathologist, who was blinded to the methods of sampling and patients’ medical history for histopathology assessment. The histopathology report of the Tao Bruch samples was compared with that of the conventional D&C samples and the D&C results were considered as the gold standard.
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Fig. 1 Tao BruchTM for endometrial sampling
Fig. 2 Introduction of Tao BruchTM inside uterine cavity without cervical dilatation
Fig. 3 Tao BruchTM rotated inside uterine cavity after withdrawal of outer sheath
Arch Gynecol Obstet (2015) 291:1121–1126
1123 Table 1 The characteristics of the studied population Variables
Mean ± SD
Range
Age (years)
48.6 ± 5.6
40–51
Age of menarche (years)
11.8 ± 2.1
11–15
Parity
4.5 ± 3.2
2–6
Endometrial thickness (cm)
9.6 ± 1.8
10–13
Table 2 Histopathology results of the specimens obtained by conventional D&C and Tao Brush Histopathology results
Histopathology results of the specimens obtained by conventional dilatation and curettage (D&C)
Histopathology results of the specimens obtained by Tao Brush
Proliferative endometrium
67
67
Secretory endometrium
59
59
Endometrial hyperplasia without atypia
47
47
Endometrial hyperplasia with atypia
11
11
Endometritis
13
11a
Endometrial polyp
7
5b
EIN (endometrial intraepithelial neoplasia)
2
2
Endometrial adenocarcinoma
6
6
Endometrial adenosquamous carcinoma
3
3
Endometrial adenosarcoma
1
1
Mixed mullerian tumor (MMT)
1
1
Total
217 (100 %)
213 (98.2 %)
Fig. 4 Withdrawal of Tao BruchTM outside uterine cavity protected by outer sheath
Sample size justification The required sample size was calculated using G* Power software version 3.17 for sample size calculation (*Heinrich Heine Universita¨t; Du¨sseldorf; Germany), setting the a-error probability at 0.05, power (1- b error probability) at 0.95 % and effective sample size (w) at 0.3. The effective pffiffiffiffiffiffiffiffiffiffiffi size (w) was calculated as follows w ¼ v2 =N , where X2 is the Chi square test and N is the total sample size. The number of participants needed to produce a statistically acceptable figure was 220 women. Statistical analysis Data were collected, tabulated then statistically analyzed using the Statistical Package for Social Sciences (SPSS) computer software version 18. Numerical variables were presented as mean and standard deviation (±SD), while categorical variables were presented as number and percentage. Chi square test (X2) was used for comparison between two studied groups as regard qualitative values. A difference with a P value\0.05 was considered statistically significant. Sensitivity is the proportional detection of individuals with the disease of interest in the population. Specificity is the proportional detection of individuals without the disease of interest in the population. Positive predictive value (PPV) is the proportion of all individuals with positive tests, who have the disease. Negative predictive value (NPV) is the proportion of all individuals with negative tests who are non-diseased.
Results Three (3) women were excluded at the beginning of this study due to failure to introduce Tao Brush inside uterine
a
Two cases of endometritis cannot diagnosed by Tao Brush sampling, because tissues sent were inadequate for histopathological examination
b
Two cases of endometrial polyps cannot diagnosed by Tao Brush sampling, because tissues sent were inadequate for histopathological examination
cavity to get endometrial samples without cervical dilatation in three attempts (endometrial samples were obtained in those women by conventional D&C under general anesthesia). After exclusion of those 3 patients, 217 women with abnormal uterine bleeding were included in this study, the mean age of the studied population was 48.6 ± 5.6 years and mean age of menarche was
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Table 3 Accuracy of Tao Bruch cytology to diagnose causes of abnormal uterine bleeding in studied population Variables
Proliferative endometrium (%)
Secretory endometrium (%)
Endometrial hyperplasia (%)
Endometrial carcinoma (%)
Endometritis
Sensitivity = true positive/true positive ? false negative X 100
100
100
100
100
13/ 13 ? 2 = 86.7 % P = 0.4 ([0.05) (X2 test)
Endometrial polyps
7/7 ? 2 = 77.8 % P = 0.16 ([0.05) (X2 test)
Specificity = true negative/true negative ? false positive 9 100
100
100
100
100
204/ 204 ? 0 = 100 %
210/ 210 ? 0 = 100 %
PPV = true positive/(true positive ? false positive) 9 100
100
100
100
100
13/ 13 ? 0 = 100 %
7/7 ? 0 = 100 %
NPV = true negative/(true negative ? false negative) 9 100
100
100
100
100
204/ 204 ? 2 = 99 % P* = 1 ([0.05) (X2 test)
210/ 210 ? 2 = 99 % P* = 1 ([0.05) (X2 test)
Accuracy = true positive ? true negative/(True positive ? true negative ? false positive ? false negative) 9 100
100
100
100
100
217/219 = 99 %
217/219 = 99 %
P** = 1 ([0.05) (X2 test)
P** = 1 ([0.05) (X2 test)
NPV Negative predictive value, PPV Positive predictive value X2 Chi Square test P represents P value when the sensitivity of Tao brush to diagnose endometritis or endometrial polyps compared to sensitivity of conventional dilatation and curettage P* represents P value when the NPV of Tao brush to diagnose endometritis or endometrial polyps compared to NPV of conventional dilatation and curettage P** represents P value when the accuracy of Tao brush to diagnose endometritis or endometrial polyps compared to accuracy of conventional dilatation and curettage
11.8 ± 2.1 years, while the mean parity was 4.5 ± 3.2 and mean endometrial thickness was 9.6 ± 1.8 cm Table 1. The presenting symptoms of the studied population were; menorrhagia or heavy menstrual bleeding (83 women), polymenorrhagia (67 women), metrorrhagia or intermenstrual bleeding (41 women) and postmenopausal bleeding (26 women). The sample was labeled as inadequate by the histopathologist when no endometrial tissue was present in the specimen sent for examination. 100 % of the samples obtained by conventional D&C, while 98.2 % of the samples obtained by Tao Brush were adequate for histopathological examination Table 2. The histopathological examination of 217 samples obtained by conventional D&C from studied women revealed proliferative endometrium in 67 cases, secretory endometrium in 59 cases, endometrial hyperplasia in 58 cases, endometritis in 13 cases, endometrial polyps in 7 cases and malignant endometrium in 13 cases [2 cases of endometrial intraepithelial neoplasia (EIN), 6 cases of endometrial adenocarcinoma, 3 cases of endometrial adenosquamous carcinoma, 1 case of endometrial
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adenosarcoma, 1 case of mixed mullerian tumor (MMT)], Table 2. In this study, Tao Brush had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium, also, it had 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value (PPV) and 99 % negative predictive value (NPV) and accuracy for diagnosing endometritis (no significant difference compared to conventional D&C, P [ 0.05, using X2 test), while, it had 77.8 % sensitivity, 100 % specificity, 100 % PPV and 99 % NPV and accuracy for diagnosing endometrial polyps (no significant difference compared to conventional D&C, P [ 0.05, using X2 test) Table 3.
Discussion Endometrial biopsy is important step in the assessment of abnormal uterine bleeding to rule out endometrial carcinoma, so that medical or conservative surgery can be
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offered and unnecessary radical surgery can be avoided. Various methods of endometrial sampling are used in practice, including invasive and non-invasive inpatient or outpatient basis [11, 12]. Conventional dilatation and curettage (D&C) is an invasive inpatient procedure performed under general anesthesia. Endometrial aspiration cytology and endometrial brush cytology are used as outpatient non-invasive methods, which give adequate endometrial samples in 98 % of cases and the probability of getting an adequate sample increases when central endometrial thickness is more than 5 mm [13, 14], this is why patients with endometrial thickness \4 mm were excluded from this study, also, in this study, the samples obtained by Tao Brush were adequate for histopathological examination in 98.2 %. Tao Bruch endometrial sampling can be performed without anesthesia or analgesia during routine pelvic examination. In this study; the brush endometrial sampling was done in the ward, followed by general anesthesia and conventional D&C to maintain synchronization during sampling, which is needed during this comparative study. Many authors concluded that the endometrial aspiration sampling is an accurate and acceptable outpatient sampling technique when compared with D&C [15–17]. In this study, endometrial brush cytology using Tao Brush had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium compared to conventional D&C. A systematic quantitative review of published medical literature to determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding was carried by Clark and colleagues. Although, Clark and colleagues concluded that outpatient endometrial biopsy has modest accuracy in diagnosing endometrial hyperplasia and additional endometrial assessment should be undertaken, especially if symptoms persist or intrauterine structural abnormalities are suspected, Sarwar et al. [19] concluded that the endometrial aspiration cytology had a 100 % sensitivity, 98 % specificity, and 100 % NPV for detection of endometrial hyperplasia and atypia in women with postmenopausal bleeding [18]. Mechado and colleagues reviewed 1,535 reports of endometrial biopsies taken from outpatients using the Cornier aspiration Pipelle, in pre- and postmenopausal patients with abnormal vaginal bleeding, to establish the accuracy of endometrial biopsy with Cornier aspiration Pipelle in diagnosis of endometrial cancer and atypical endometrial hyperplasia. The Cornier aspiration Pipelle was 84.2 % sensitive, 99.1 % specific, 96.9 % accurate, with 94.1 % PPV and 93.7 % NPV for detection of endometrial carcinoma and atypical hyperplasia, and they
1125
concluded that endometrial biopsy taken with the Cornier aspiration Pipelle is an accurate method for diagnosis of endometrial cancer and its precursor atypical hyperplasia [20]. Three hundred and sixty endometrial cancer patients who had preoperative endometrial sampling to evaluate the ability of preoperative endometrial sampling to accurately diagnose high-grade endometrial tumors were included in Gloria et al. study. Gloria et al. [21] concluded that endometrial aspiration sampling was 93.8 % sensitive for diagnosing low-grade endometrial cancer and it was 99.2 % sensitive for diagnosing high-grade endometrial cancer, also, they concluded that the endometrial aspiration sampling is sensitive and accurate for diagnosis of highgrade endometrial tumors. A meta-analysis to assess the accuracy of endometrial sampling devices in detection of endometrial carcinoma and atypical hyperplasia was done by Dijkhuijen and colleagues. They concluded that the endometrial aspiration sampling is superior to other endometrial techniques in detection of endometrial carcinoma and atypical hyperplasia in pre- and postmenopausal women [22]. One thousand and fifty-six (1,056) postmenopausal women was included in Mossa et al. [23] study to compare outpatient endometrial sampling cytology with conventional biopsy in postmenopausal women with abnormal uterine bleeding and/or abnormal and they concluded that endometrial brush cytology (EBC) is a reliable, well-tolerated outpatient diagnostic tool for endometrial sampling in detecting early-stage cancer in postmenopausal patients at high risk for endometrial cancer. Also in this study, EBC had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial carcinoma compared to conventional D&C [13 cases of malignant endometrium were diagnosed (2 cases of EIN, 6 cases of endometrial adenocarcinoma, 3 cases of endometrial adenosquamous carcinoma, 1 case of endometrial adenosarcoma, 1 case of MMT)]. Tao Brush, in this study, had 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value (PPV) and 99 % negative predictive value (NPV) and accuracy for diagnosing endometritis, while, it had 77.8 % sensitivity, 100 % specificity, 100 % PPV and 99 % NPV and accuracy for diagnosing endometrial polyps, because the accuracy is high when an adequate endometrial sample is obtained and in this study, 4 specimens were reported as inadequate for histopathology evaluation (two of them were diagnosed as endometrial polyps and the other two were diagnosed as endometritis by conventional D&C). In this study, in spite of the low sensitivity of the Tao Brush for diagnosing endometritis and endometrial polyps (86.7 and 77.8 %, respectively), this difference was statistically insignificant compared to conventional dilatation and
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curettage, it had a high NPV values and accuracy, also, Kuruvilla et al. [24], found that the most common histological diagnosis missed with an inadequate endometrial sample was endometrial polyp. Three (3) women were excluded at the beginning of this study due to the failure to introduce Tao Brush inside uterine cavity to get endometrial samples without cervical dilatation in three attempts (endometrial samples were obtained in those women by conventional D&C under general anesthesia). No intra-operative or postoperative complications were recorded in this study, this leads to the conclusion that the endometrial sampling using endometrial brush cytology (EBC) is safe, accurate, cost-effective outpatient procedure, avoids general anesthesia with high sensitivity and specificity for detection of endometrial hyperplasia and endometrial carcinoma and could be used as complementary diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted or not available [6, 9, 25]. Conflict of interest All authors declared no conflict of interest (COI) exists in relation to this article or manuscript.
References 1. Goldenstein SR (2010) Modern evaluation of endometrium. Obstet Gynecol 116:168–176 2. Oehler MK, Rees MC (2003) Menorrhagoea: an update. Acta Obstet Gynecol Scand 82(5):404–422 3. Telner DE, Jakubovicz D (2007) Approach to diagnosis and management of abnormal uterine bleeding. Can Fam Physicians 53:58–64 4. Justin Clark T, Janesh K, Gupta (2002) Endometrial sampling of gynaecological pathology. Obstet Gynaecol 4:169–174 5. Vigod SN, Stewart DE (2002) Management of abnormal uterine bleeding by northern, rural and isolated primary care physicians: PART I—How are we doing? BMC Women Health 2:10. doi:10. 1186/1472-6874-2-10 6. Brand A, Duduc-Lissoir J, Ehlen TG, Plante M (2000) Diagnosis of endometrial cancer in women in women with abnormal vaginal bleeding. SOGC Clinical Practice Guidelines. J Soc Obst Gynae Can 22(1):102–104 7. Fakhar Shazia, Saeed Gulshan, Khan Amir Hussain, Alam Ali Yawar (2008) Validity of Pipelle endometrial sampling in patients with abnormal uterine bleeding. Ann Saudi Med 28(3):188–191 8. Abdelazim Ibrahim Anwar, Aboelezz Amro, AbdulKareem Amr Fathy (2013) Pipelle endometrial sampling versus conventional dilatation & curettage in patients with abnormal uterine bleeding. J Turk Ger Gynecol Assoc 14:1–5 9. Indraccolo U, Bracalenti C, Di Iorio R, Indraccolo SR (2012) Could endometrial cytology be helpful in detecting endometrial malignancies? Eur J Gynaecol Oncol 33(1):60–61
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Arch Gynecol Obstet (2015) 291:1121–1126 10. Abdelhamid AM (2013) The success rate of pregnancy in IUI cycles following endometrial sampling. A randomized controlled study: endometrial sampling and pregnancy rates. Arch Gynecol Obstet 288(3):673–678 11. Opmeer BC, van Doorn HC, Heintz AP, Burger CW, Bossuyt PM, Mol BW (2007) Improving the existing diagnostic strategy by accounting for characteristics of the women in the diagnostic work up for postmenopausal bleeding. BJOG 114(1):51–58 12. Van den Bosch T, Van Schoubroeck D, Domali E, Vergote I, Moerman P, Amant F, Timmerman D (2007) A thin and regular endometrium on ultrasound is very unlikely in patients with endometrial malignancy. Ultrasound Obstet Gynecol 29(6):674–679 13. Polena V, Mergui JL, Zerat L, Sananes S (2007) The role of PipelleÒ Mark II sampling in endometrial disease diagnosis. Eur J Obstet Gynecol Reprod Biol 134(2):233–237 14. Elsandabesee D, Greenwood P (2005) The performance of Pipelle endometrial sampling in a dedicated postmenopausal bleeding clinic. J Obstet Gynecol 25(1):32–34 15. Chaudry A, Javaid M (2005) Clinical usefulness of Pipelle endometrial sampling. Pak Armed Forces Med J 55:122–125 16. Asif AZ (1999) An acceptable outpatient technique for endometrial biopsy. J College Physician Surg Pak 9(1):14–16 17. Behnamfar F, Khamehchian T, Mazoochi T, Fahiminejad T (2004) Diagnostic value of endometrial sampling with Pipelle suction curettage for identifying endometrial lesions in patients with abnormal uterine bleeding. J Res Med Sci 3:123–125 18. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK (2001) Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial hyperplasia. Acta Obstet Gynecol Scand 80(9):784–793 19. Sarwar A, Haque ul A (2005) Types and frequencies of pathologies in endometrial curetting of abnormal uterine bleeding. Int J of Path 3:65–70 20. Machado F, Moreno J, Carazo M, Leon J, Fiol G, Serna R (2003) Accuracy of endometrial biopsy with the Cornier Pipelle for diagnosis of endometrial cancer and atypical hyperplasia. Eur J Gynaecol Oncol 24(3–4):279–281 21. Huang GS, Gebb JS, Einstein MH et al (2007) Accuracy of preoperative endometrial sampling for the detection of highgrade endometrial tumors. Am J Obstet Gynecol 196(3):243.e1–243.e5 22. Dijkhuijen FP, Mole BW, Brolmann HA, Heintz AP (2000) The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a Meta analysis. Cancer 89:1765–1772 23. Mossa B, Ebano V, Marziani R (2010) Reliability of outpatient endometrial brush cytology vs biopsy in postmenopausal symptomatic women. Eur J Gynaecol Oncol 31(6):621–626 24. Kuruvilla A, Sohan K, Ramsewak S (2004) Outpatient endometrial sampling as the sole primary method for assessing abnormal uterine bleeding in women over 35 years in Trinidad. Int J Gynecol Obstet 3(1) 25. Bunyavejchevin S, Triratanachat S, Kankeow K, Limpaphayom KK (2001) Pipelle versus fractional curettage for the endometrial sampling in postmenopausal women. J Med Assoc Thai 84:326–330
GENERAL GYNECOLOGY
Accuracy of endometrial sampling compared to conventional dilatation and curettage in women with abnormal uterine bleeding Ibrahim A. Abdelazim • Khaled M. Abdelrazak Assem A. M. Elbiaa • Mohamed Al-Kadi • Amr H. Yehia
•
Received: 30 July 2014 / Accepted: 16 October 2014 / Published online: 4 November 2014 Ó Springer-Verlag Berlin Heidelberg 2014
Abstract Objectives To compare the diagnostic accuracy of brush endometrial sampling with conventional dilatation and curettage in women with abnormal uterine bleeding. Patients and methods Two hundred and twenty (220) women with abnormal uterine bleeding were included in this comparative study; endometrial sampling was done before cervical dilatation using Tao Bruch followed by conventional dilatation and curettage (D&C). The histopathology report of the Tao Bruch samples was compared with that of the D&C samples and the D&C results were considered as the gold standard. Results 100 % of samples obtained by conventional D&C, while 98.2 % of the samples obtained by Tao Brush were adequate for histopathology examination. In this study; Tao Brush had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium, also, it had 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value
Ahmadi hospital Kuwait Oil Company (KOC) Company, all the authors have contributed significantly and are responsible for the content of this manuscript. I. A. Abdelazim (&) K. M. Abdelrazak A. A. M. Elbiaa M. Al-Kadi A. H. Yehia Obstetrics and Gynecology, Ain Shams University, Cairo, Egypt e-mail: [email protected] I. A. Abdelazim Ahmadi Kuwait Oil (KOC) Company Hospital, P.O. Box: 9758, Ahmadi, Kuwait A. A. M. Elbiaa Obstetrics and Gynecology, Sabah Maternity Hospital, West Shuwaikh, Kuwait
(PPV) and 99 % negative predictive value (NPV) and accuracy for diagnosing endometritis (no significant difference compared to conventional D&C), while, it had 77.8 % sensitivity, 100 % specificity, 100 % PPV and 99 % NPV and accuracy for diagnosing endometrial polyps (no significant difference compared to conventional D&C) Conclusion Endometrial sampling using endometrial brush cytology (EBC) is safe, accurate, cost-effective outpatient procedure, avoids general anesthesia with high sensitivity and specificity for detection of endometrial hyperplasia and endometrial carcinoma. EBC could be used as complementary diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted or not available. Keywords Endometrial sampling Dilatation and curettage Abnormal uterine bleeding
Introduction Abnormal uterine bleeding is a major gynecological problem, accounting for 33 % of outpatient referrals, including 69 % of referrals in perimenopausal and postmenopausal age group [1]. Evaluation of abnormal uterine bleeding in women C40 years or menopausal women is of critical importance to confirm benign nature of the problem, and to exclude endometrial carcinoma, so that medical or conservative treatment can be offered and unnecessary radical surgery can be avoided [2]. Dilatation and curettage (D&C) is the gold standard for endometrial sampling, but in 60 % of cases less than half of the uterine cavity is curetted, with the added risk of general anesthesia, infection, and perforation [3, 4]. This has led to the advent of new and simple methods for
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endometrial sampling; including endometrial aspiration cytology and endometrial brush cytology [5–8] Tao Bruch can be used on an outpatient basis and is cost effective compared with D&C [9, 10]. However, there are still concerns regarding the adequacy of the sample obtained, non-sampling of focal intrauterine lesions during endometrial aspiration or endometrial brush cytology [6]. This comparative study was designed to compare the diagnostic accuracy of endometrial sampling using Tao Bruch with conventional dilatation and curettage in women with abnormal uterine bleeding.
Patients and Methods Over 2 years, women with abnormal uterine bleeding C40 years, presented to gynecology clinics of Ahmadi Hospital Kuwait Oil Company (KOC), were included in this comparative study. Detailed clinical assessment of the patients was followed by transvaginal sonography and laboratory investigations (complete blood count (CBC), coagulation profile, prolactin, thyroid and liver function tests). Women with local gynecological cause or possibility of pregnancy or history of contraception or endometrial thickness \4 mm were excluded from this study. Two hundred and twenty (220) women were included in this study after informed consent and approval of the study protocol by the institute ethics committee. Women included in this study were euthyroid with normal liver function tests, normal activated partial thromboplastin time (APTT) and normal platelet count. The endometrial sampling was performed by Tao Bruch in the ward prior to premedication ordered by anesthetist. Tao BruchTM (Cook Medical Incorporated, Bloomington, USA) has outer sheath which promotes error-free test results by protecting the sample from endocervical or vaginal contamination (Fig. 1). Tao Bruch was introduced without performing cervical dilatation (Fig. 2) and was rotated inside the uterine cavity to get the sample after withdrawal of outer sheath outside the uterus (Fig. 3). The advancement of the outer sheath to protect the sample obtained from contamination was followed by withdrawal of Tao Bruch protected by outer sheath (Fig. 4) and Tao Bruch sample was labeled as sample A. Women were then transferred to the operative theatre for conventional D&C and the obtained sample after conventional D&C was labeled as sample B. Both samples were sent to a pathologist, who was blinded to the methods of sampling and patients’ medical history for histopathology assessment. The histopathology report of the Tao Bruch samples was compared with that of the conventional D&C samples and the D&C results were considered as the gold standard.
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Fig. 1 Tao BruchTM for endometrial sampling
Fig. 2 Introduction of Tao BruchTM inside uterine cavity without cervical dilatation
Fig. 3 Tao BruchTM rotated inside uterine cavity after withdrawal of outer sheath
Arch Gynecol Obstet (2015) 291:1121–1126
1123 Table 1 The characteristics of the studied population Variables
Mean ± SD
Range
Age (years)
48.6 ± 5.6
40–51
Age of menarche (years)
11.8 ± 2.1
11–15
Parity
4.5 ± 3.2
2–6
Endometrial thickness (cm)
9.6 ± 1.8
10–13
Table 2 Histopathology results of the specimens obtained by conventional D&C and Tao Brush Histopathology results
Histopathology results of the specimens obtained by conventional dilatation and curettage (D&C)
Histopathology results of the specimens obtained by Tao Brush
Proliferative endometrium
67
67
Secretory endometrium
59
59
Endometrial hyperplasia without atypia
47
47
Endometrial hyperplasia with atypia
11
11
Endometritis
13
11a
Endometrial polyp
7
5b
EIN (endometrial intraepithelial neoplasia)
2
2
Endometrial adenocarcinoma
6
6
Endometrial adenosquamous carcinoma
3
3
Endometrial adenosarcoma
1
1
Mixed mullerian tumor (MMT)
1
1
Total
217 (100 %)
213 (98.2 %)
Fig. 4 Withdrawal of Tao BruchTM outside uterine cavity protected by outer sheath
Sample size justification The required sample size was calculated using G* Power software version 3.17 for sample size calculation (*Heinrich Heine Universita¨t; Du¨sseldorf; Germany), setting the a-error probability at 0.05, power (1- b error probability) at 0.95 % and effective sample size (w) at 0.3. The effective pffiffiffiffiffiffiffiffiffiffiffi size (w) was calculated as follows w ¼ v2 =N , where X2 is the Chi square test and N is the total sample size. The number of participants needed to produce a statistically acceptable figure was 220 women. Statistical analysis Data were collected, tabulated then statistically analyzed using the Statistical Package for Social Sciences (SPSS) computer software version 18. Numerical variables were presented as mean and standard deviation (±SD), while categorical variables were presented as number and percentage. Chi square test (X2) was used for comparison between two studied groups as regard qualitative values. A difference with a P value\0.05 was considered statistically significant. Sensitivity is the proportional detection of individuals with the disease of interest in the population. Specificity is the proportional detection of individuals without the disease of interest in the population. Positive predictive value (PPV) is the proportion of all individuals with positive tests, who have the disease. Negative predictive value (NPV) is the proportion of all individuals with negative tests who are non-diseased.
Results Three (3) women were excluded at the beginning of this study due to failure to introduce Tao Brush inside uterine
a
Two cases of endometritis cannot diagnosed by Tao Brush sampling, because tissues sent were inadequate for histopathological examination
b
Two cases of endometrial polyps cannot diagnosed by Tao Brush sampling, because tissues sent were inadequate for histopathological examination
cavity to get endometrial samples without cervical dilatation in three attempts (endometrial samples were obtained in those women by conventional D&C under general anesthesia). After exclusion of those 3 patients, 217 women with abnormal uterine bleeding were included in this study, the mean age of the studied population was 48.6 ± 5.6 years and mean age of menarche was
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Table 3 Accuracy of Tao Bruch cytology to diagnose causes of abnormal uterine bleeding in studied population Variables
Proliferative endometrium (%)
Secretory endometrium (%)
Endometrial hyperplasia (%)
Endometrial carcinoma (%)
Endometritis
Sensitivity = true positive/true positive ? false negative X 100
100
100
100
100
13/ 13 ? 2 = 86.7 % P = 0.4 ([0.05) (X2 test)
Endometrial polyps
7/7 ? 2 = 77.8 % P = 0.16 ([0.05) (X2 test)
Specificity = true negative/true negative ? false positive 9 100
100
100
100
100
204/ 204 ? 0 = 100 %
210/ 210 ? 0 = 100 %
PPV = true positive/(true positive ? false positive) 9 100
100
100
100
100
13/ 13 ? 0 = 100 %
7/7 ? 0 = 100 %
NPV = true negative/(true negative ? false negative) 9 100
100
100
100
100
204/ 204 ? 2 = 99 % P* = 1 ([0.05) (X2 test)
210/ 210 ? 2 = 99 % P* = 1 ([0.05) (X2 test)
Accuracy = true positive ? true negative/(True positive ? true negative ? false positive ? false negative) 9 100
100
100
100
100
217/219 = 99 %
217/219 = 99 %
P** = 1 ([0.05) (X2 test)
P** = 1 ([0.05) (X2 test)
NPV Negative predictive value, PPV Positive predictive value X2 Chi Square test P represents P value when the sensitivity of Tao brush to diagnose endometritis or endometrial polyps compared to sensitivity of conventional dilatation and curettage P* represents P value when the NPV of Tao brush to diagnose endometritis or endometrial polyps compared to NPV of conventional dilatation and curettage P** represents P value when the accuracy of Tao brush to diagnose endometritis or endometrial polyps compared to accuracy of conventional dilatation and curettage
11.8 ± 2.1 years, while the mean parity was 4.5 ± 3.2 and mean endometrial thickness was 9.6 ± 1.8 cm Table 1. The presenting symptoms of the studied population were; menorrhagia or heavy menstrual bleeding (83 women), polymenorrhagia (67 women), metrorrhagia or intermenstrual bleeding (41 women) and postmenopausal bleeding (26 women). The sample was labeled as inadequate by the histopathologist when no endometrial tissue was present in the specimen sent for examination. 100 % of the samples obtained by conventional D&C, while 98.2 % of the samples obtained by Tao Brush were adequate for histopathological examination Table 2. The histopathological examination of 217 samples obtained by conventional D&C from studied women revealed proliferative endometrium in 67 cases, secretory endometrium in 59 cases, endometrial hyperplasia in 58 cases, endometritis in 13 cases, endometrial polyps in 7 cases and malignant endometrium in 13 cases [2 cases of endometrial intraepithelial neoplasia (EIN), 6 cases of endometrial adenocarcinoma, 3 cases of endometrial adenosquamous carcinoma, 1 case of endometrial
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adenosarcoma, 1 case of mixed mullerian tumor (MMT)], Table 2. In this study, Tao Brush had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium, also, it had 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value (PPV) and 99 % negative predictive value (NPV) and accuracy for diagnosing endometritis (no significant difference compared to conventional D&C, P [ 0.05, using X2 test), while, it had 77.8 % sensitivity, 100 % specificity, 100 % PPV and 99 % NPV and accuracy for diagnosing endometrial polyps (no significant difference compared to conventional D&C, P [ 0.05, using X2 test) Table 3.
Discussion Endometrial biopsy is important step in the assessment of abnormal uterine bleeding to rule out endometrial carcinoma, so that medical or conservative surgery can be
Arch Gynecol Obstet (2015) 291:1121–1126
offered and unnecessary radical surgery can be avoided. Various methods of endometrial sampling are used in practice, including invasive and non-invasive inpatient or outpatient basis [11, 12]. Conventional dilatation and curettage (D&C) is an invasive inpatient procedure performed under general anesthesia. Endometrial aspiration cytology and endometrial brush cytology are used as outpatient non-invasive methods, which give adequate endometrial samples in 98 % of cases and the probability of getting an adequate sample increases when central endometrial thickness is more than 5 mm [13, 14], this is why patients with endometrial thickness \4 mm were excluded from this study, also, in this study, the samples obtained by Tao Brush were adequate for histopathological examination in 98.2 %. Tao Bruch endometrial sampling can be performed without anesthesia or analgesia during routine pelvic examination. In this study; the brush endometrial sampling was done in the ward, followed by general anesthesia and conventional D&C to maintain synchronization during sampling, which is needed during this comparative study. Many authors concluded that the endometrial aspiration sampling is an accurate and acceptable outpatient sampling technique when compared with D&C [15–17]. In this study, endometrial brush cytology using Tao Brush had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium compared to conventional D&C. A systematic quantitative review of published medical literature to determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding was carried by Clark and colleagues. Although, Clark and colleagues concluded that outpatient endometrial biopsy has modest accuracy in diagnosing endometrial hyperplasia and additional endometrial assessment should be undertaken, especially if symptoms persist or intrauterine structural abnormalities are suspected, Sarwar et al. [19] concluded that the endometrial aspiration cytology had a 100 % sensitivity, 98 % specificity, and 100 % NPV for detection of endometrial hyperplasia and atypia in women with postmenopausal bleeding [18]. Mechado and colleagues reviewed 1,535 reports of endometrial biopsies taken from outpatients using the Cornier aspiration Pipelle, in pre- and postmenopausal patients with abnormal vaginal bleeding, to establish the accuracy of endometrial biopsy with Cornier aspiration Pipelle in diagnosis of endometrial cancer and atypical endometrial hyperplasia. The Cornier aspiration Pipelle was 84.2 % sensitive, 99.1 % specific, 96.9 % accurate, with 94.1 % PPV and 93.7 % NPV for detection of endometrial carcinoma and atypical hyperplasia, and they
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concluded that endometrial biopsy taken with the Cornier aspiration Pipelle is an accurate method for diagnosis of endometrial cancer and its precursor atypical hyperplasia [20]. Three hundred and sixty endometrial cancer patients who had preoperative endometrial sampling to evaluate the ability of preoperative endometrial sampling to accurately diagnose high-grade endometrial tumors were included in Gloria et al. study. Gloria et al. [21] concluded that endometrial aspiration sampling was 93.8 % sensitive for diagnosing low-grade endometrial cancer and it was 99.2 % sensitive for diagnosing high-grade endometrial cancer, also, they concluded that the endometrial aspiration sampling is sensitive and accurate for diagnosis of highgrade endometrial tumors. A meta-analysis to assess the accuracy of endometrial sampling devices in detection of endometrial carcinoma and atypical hyperplasia was done by Dijkhuijen and colleagues. They concluded that the endometrial aspiration sampling is superior to other endometrial techniques in detection of endometrial carcinoma and atypical hyperplasia in pre- and postmenopausal women [22]. One thousand and fifty-six (1,056) postmenopausal women was included in Mossa et al. [23] study to compare outpatient endometrial sampling cytology with conventional biopsy in postmenopausal women with abnormal uterine bleeding and/or abnormal and they concluded that endometrial brush cytology (EBC) is a reliable, well-tolerated outpatient diagnostic tool for endometrial sampling in detecting early-stage cancer in postmenopausal patients at high risk for endometrial cancer. Also in this study, EBC had 100 % sensitivity, 100 % specificity, 100 % predictive values and accuracy for diagnosing endometrial carcinoma compared to conventional D&C [13 cases of malignant endometrium were diagnosed (2 cases of EIN, 6 cases of endometrial adenocarcinoma, 3 cases of endometrial adenosquamous carcinoma, 1 case of endometrial adenosarcoma, 1 case of MMT)]. Tao Brush, in this study, had 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value (PPV) and 99 % negative predictive value (NPV) and accuracy for diagnosing endometritis, while, it had 77.8 % sensitivity, 100 % specificity, 100 % PPV and 99 % NPV and accuracy for diagnosing endometrial polyps, because the accuracy is high when an adequate endometrial sample is obtained and in this study, 4 specimens were reported as inadequate for histopathology evaluation (two of them were diagnosed as endometrial polyps and the other two were diagnosed as endometritis by conventional D&C). In this study, in spite of the low sensitivity of the Tao Brush for diagnosing endometritis and endometrial polyps (86.7 and 77.8 %, respectively), this difference was statistically insignificant compared to conventional dilatation and
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curettage, it had a high NPV values and accuracy, also, Kuruvilla et al. [24], found that the most common histological diagnosis missed with an inadequate endometrial sample was endometrial polyp. Three (3) women were excluded at the beginning of this study due to the failure to introduce Tao Brush inside uterine cavity to get endometrial samples without cervical dilatation in three attempts (endometrial samples were obtained in those women by conventional D&C under general anesthesia). No intra-operative or postoperative complications were recorded in this study, this leads to the conclusion that the endometrial sampling using endometrial brush cytology (EBC) is safe, accurate, cost-effective outpatient procedure, avoids general anesthesia with high sensitivity and specificity for detection of endometrial hyperplasia and endometrial carcinoma and could be used as complementary diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted or not available [6, 9, 25]. Conflict of interest All authors declared no conflict of interest (COI) exists in relation to this article or manuscript.
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