Statistical analysis was performed using SPSS 13.0 (SPSS Inc., Chicago, IL, USA). The contingency table Chi-square test was used to compare the adequacy of specimens collected using SAP-1 with those collected via D & C and hysteroscopic biopsy. P < 0.05 was considered statistically significant. Negative for epithelial lesions and benign endometrium were considered negative, while atypical endometrial cells and suspected for malignant were considered positive. Histopathologic results were the gold standard. A four-fold table was created to calculate the accuracy, sensitive, specificity, PPV, and NPV.
The current study comprised of 1514 patients with endometrial carcinoma risk factors underwent SAP-1 sampling on an outpatient basis, and 375 of these women also underwent D & C or hysteroscopy. Characteristics including age distribution, menstrual status, and patients’ symptoms and signs are presented in Table 1. Most of the patients were over 40 years of age in both the cytology and histopathology groups (91.2% and 90.7%, respectively). The percentage of postmenopausal women was 69% and 63.5%, respectively, in the two groups. Among 1514 cases with cytological specimens, 576 (38%) patients had AUB, and 910 (60.1%) had ≥ 4 mm thickness endometrium measured by ultrasound. 169 (45.1%) out of 375 patients with histopathology had AUB, and 245 patients (65.3%) had ≥ 4 mm thickness endometrium.
As presented in Table 2, 1458 patients (96.3%) had adequate specimens for cytology out of the 1514 patients sampled using SAP-1, while 285 cases (76%) had adequate specimens for pathology out of the 375 patients who underwent D & C or hysteroscopic biopsy. There were 56 (3.7%) cytology and 90 (24%) biopsies that were inadequate. SAP-1 can provide more sufficient materials for cytology than D & C or hysteroscopic biopsy for histology (P < 0.01).
Of the 469 cytology specimens from premenopausal women, 452 patients (96.4%) had an adequate specimen, and 17 patients (3.6%) had an inadequate specimen. While in 137 cases of premenopausal women obtained biopsy specimens, 132 patients (96.4%) had an adequate biopsy, and only 5 patients (3.6%) had an inadequate biopsy. There was no difference (P = 0.919) between cytology and biopsy in premenopausal women.
However, 1006 specimens (86.3%) were adequate, and 37 specimens (3.7%) were inadequate out of the 1045 cytology samples obtained using SAP-1 in postmenopausal women. In 238 biopsy specimens obtained from postmenopausal women, 153 biopsy specimens (64.3%) were adequate, and 85 specimens (35.7%) were inadequate. It was easier to collect cytology specimens than histology specimens (P < 0.05). The results are shown in Table 3.
Of the 254 patients who had both of cytology and histology, 205 (80.7%) patients were diagnosed as negative and benign using cytology and histology. 11 (4.3%) patients were evaluated as positive by cytology, but they were confirmed as negative or benign lesions using histology. There were 28 patients who were positive for atypical cells, as determined by both cytology and histology. There were 10 (3.9%) patients who were diagnosed as negative or benign using cytology, while their occult lesions were discovered upon subsequent hysterectomy. The accuracy of cytology for detecting endometrial precursor and carcinoma was estimated at 91.7%, sensitivity at 73.6%, specificity at 94.9%, PPV at 71.9%, and NPV at 95.3%. The results are presented in Table 3.
In past decades, endometrial carcinoma has become the most prevalent gynecologic malignancy in developed cities such as Beijing, Shanghai, and Guangzhou in China. The increased morbidity of endometrial carcinoma is attributed to changes in lifestyle, such as a lack of exercise and increasing fat intake lead to obesity and high BMI. Obesity triggered several pathways including hormonal imbalance and hyperactive proliferative pathways to involve in pathogenesis of endometrial carcinoma. The effective procedure for reducing morbidity and mortality in endometrial carcinoma is to screen certain groups with risk factors and design a reliable tool suitable for a mass screening program.
Dilation and curettage have been used clinically for many years, and originally it was intended to serve as a screening tool for endometrial carcinoma, but researchers realized that specimen adequacy and diagnosis accuracy were unsatisfactory. Yarandi et al. reported that the accuracy of D & C was 40.5%, sensitivity 40.5%, specificity 72.3%, PPV 77.1% and NPV 25.1%, and in 52.7% of the patients, D & C failed to detect intrauterine disorders, especially focal lesions of the endometrium. Moreover, most patients complained of pain and severe discomfort during the operation, and they had persistent bleeding for several days after the procedure. In Mossa et al.'s study, the patients undergoing D & C had higher pain scores compared with those who underwent brush cytology. For these reasons, D & C is not an ideal screening method.
Currently, several sampling devices were used to take endometrium cytology samples from patients; samplers include Endoflower, Tao Brush, and Endocyte. For Tao Brush sampling, only 1% of all specimens were shown to be nondiagnostic. Buccoliero et al. estimated that out of 519 patients, the samples of biopsy obtained using the Tao Brush was inadequate in 361 patients (39%), and samples obtained using the Endoflower were inadequate in 15 patients (2%). In addition, Buccoliero et al. showed the same results in another study that compared the Endoflower to biopsy in patients receiving tamoxifen.
SAP-1, a direct endometrial sampler device, is especially designed for minimal pain during sampling, it meets the requirements for endometrial samplers, which include: (1) Avoiding contamination from the endocervix and vagina; (2) procuring an adequate representative sample of the entire endometrium to detect focal lesions; and (3) the procedure should be safe, easy to use, and well-tolerated by the patients. The device has to be noninvasive or minimally invasive, cost-effective, and user-friendly to be accepted by primary care physicians and patients for repeated tests. A soft loop can be flexible within the endometrial cavity, and the spindles can easily obtain adequate endometrial cells with minimal chance of injuring myometrium and bleeding. We are the first to evaluate the adequacy of its specimens compared with D & C and hysteroscopic biopsy.
In the current study, adequate specimens obtained using the SAP-1 sampler (96.3%) are superior to those obtained using D & C (76%). In addition, most patients experienced no pain during SAP-1 sampling, claiming that they had the same feeling as the insertion of a cytobrush for cervical sampling.
Our previously-proposed screening strategy involved women of 40 years of age or older, or postmenopausal women as the target screening population. In Buccoliero et al.'s study, of 107 asymptomatic postmenopausal women with a thin endometrium (<4 mm), a biopsy obtained sufficient material for the diagnosis in only 24% of the cases. Our study also shows that there are no differences in specimen adequacy between the SAP-1 sampler and D & C in premenopausal women. However, for postmenopausal women, the SAP-1 sampler provides more adequate specimens than does D & C or hysteroscopic biopsy.
Conventional smears have not been widely applied in endometrial carcinoma screening attributes of overlapping cells and a heavy background. Endometrial cells degenerate more easily than other cells. In addition, the three-dimensional structure is an important ECT reference to evaluate the condition of the endometrium. Requirements for a stable fixation system and preparation technique include: (1) Preserving the morphology of endometrial epithelial and stromal cells and the endometrial glandular structure; and (2) eliminating obscuring factors such as excess red blood cells, mucus, overlapping cells, and inflammatory cells. The 95% alcohol fixation and conventional cytology cannot earn a place in endometrial cancer screen due to regression cells and high background levels, such as excess blood, mucus, overlapping cells, and inflammatory cells. According to previous Japanese publications, conventional cytology was initially used to examine the endometrial lesion, with a sensitivity about 78%, specificity of 95%, PPV of 56%, and NPV of 98%. Transvaginal ultrasonography was previously thought to be an efficient tool because of conventional cytology's low accuracy. Compared with a conventional smear, thin-layer cytology provided more cell clumps and a clearer background, as shown by Norimatsu et al.
To improve the diagnostic accuracy of endometrial cytology, a thin-layer method was proposed for endometrial carcinoma and precursor screening. Remondi et al. used the Endoflower sampler and the Thinprep preparation to evaluate 768 postmenopausal women, and found an accuracy of 93.6%, sensitivity of 92%, specificity of 95%, PPV of 73%, and NPV of 99%. The sensitivity, specificity, PPV, and NPV for the Uterobrush were 88.9%, 100%, 100% and 98.9%, respectively. Direct uterine sampling with the Tao Brush sampler using a liquid-based preparation method for detection of endometrial cancer and atypical hyperplasia, the sensitivity and specificity were 95% and 66%. The results of the current study demonstrate that the SAP-1 sampler combined with the liquid-based SurePath preparation method is a reliable diagnostic method. The overall accuracy for detecting endometrial cancer, complex hyperplasia with atypia and EIN was 92.4%, with a sensitivity of 73%, a specificity of 95.8%, a PPV of 75%, and a NPV of 95.3%.
Although the findings of current studies were informative, there were some limitations. Almost all patients enrolled into this study received the ECT for screening, so women with positive cytologic results or persistent bleeding underwent hysteroscopic biopsy or D & C. In the current study, patients with carcinoma that was subsequently confirmed by histology were initially diagnosed with atypical endometrial cells or suspected carcinoma using cytology. The main reasons that the accuracy of this study was lower than that in previously studies are as follows: Patients with positive results including atypical cells underwent hysteroscopic biopsy and D & C, and some of them were subsequently diagnosed as normal or benign. In addition, other methods, including enlarging the sample quantity to collect more information to correctly distinguish focal atypical endometrial lesions from benign lesions, should be investigated using immunohistochemistry and biochemistry to improve the accuracy of endometrial cytology.
In conclusion, the SAP-1 sampler combined with SurePath preparation may become a reliable method for screening endometrial carcinoma and its precursor, especially in postmenopausal and asymptomatic women. If this screening procedure can be used in the high risk-factor women, some unnecessary D & C may be avoided, and asymptomatic women with the precursor may benefit from early detection and management.
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Edited by: Jian Gao
Source of Support: Nil.
Conflict of Interest: None declared.
Keywords:© 2015 Chinese Medical Association
Diagnostic Accuracy; Endometrial Carcinoma; Liquid-based Cytology; Specimen Adequacy