For unavailable or cannot be afforded. [3] Many

For decades,
endometrial tissue sampling was routinely performed by reproductive surgeons before
proceeding to hysterectomy to recognize any asymptomatic pathology and to
design an effective management plan. 1 Since dilatation and
curettage (D&C) was first described by Recamier in 1943, it became
the key technique for routine endometrial sampling and a frequently used diagnostic
procedure worldwide. 2 Modern techniques are now available for
uterine cavity visualization as hysteroscopy and endometrial sampling like
Pippelle suction curette, but D&C still has a role where these modalities
are unavailable or cannot be afforded. 3

Many authors
adopted D&C as the “gold standard” procedure for endometrial sampling addressing
its accuracy in the endometrial cancer detection. 4, 5 On the
other hand, others considered it as inefficient diagnostic tool for
intrauterine pathologies. They reported frequently missed focal uterine lesions
as endometrial polyps as well as hyperplasia by preoperative D&C. 6,
7 Furthermore, limitations of the routine D&C are that it
necessitates anesthesia administration, prolongs the hospital stay with
subsequent increase of costs and the procedure specific morbidities such as infection,
uterine perforation or cervical tears. 6, 8

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As the
debate of obtaining an endometrial sample before hysterectomy by which
technique remains unsolved and the efficacy of D&C is still questionable, the
aim of the current study was to examine the validity of performing the
pre-hysterectomy D&C. In addition, we investigated the agreement between
the histopathological examination results of the D&C and hysterectomy
specimens.

Methods

This
cohort study included the retrospective charts of all women who underwent a
hysterectomy for various indications at the department of obstetrics and gynecology,
Benha University, between January 2010 and June 2017 after getting the
legitimate ethical approvals from the local ethics committee. Eight-hundred twenty-nine women were enrolled in this study. Specimens collected from 531 premenopausal and
298 postmenopausal women were studied after excluding the incomplete medical
records and endometrial samples obtained by an interval of two months or more before
getting the hysterectomy specimen examined.

The
hysterectomy indications had a wide range of complaints such as abnormal
uterine bleeding, chronic pelvic pain, myomas, endometriosis, adenomyosis,
cervical, endometrial and ovarian cancers. The histopathological diagnosis of
the D&C samples was compared with the postoperative hysterectomy one without
considering the hysterectomy type or indication.

All the
endometrial samples were collected by the traditional D&C technique performed
by certified physicians under general anesthesia. After the woman was placed in
the lithotomy position, the vagina and perineum were cleaned by betadine. After
urinary bladder catheterization, bimanual pelvic examination was carried out to
identify the size, mobility and position of the uterus Then, Hegar dilators were
used to gradually dilate the cervix before starting curettage of the uterine
cavity walls.

Formalin, embedded
in paraffin, was used to fix all endometrial samples before cutting them into sections
of (4-?m) thickness. Also, hematoxylin and eosin was the standard stain for
histopathological testing which was carried by an experienced gynecological
histopathologist who evaluated the sections by using (Leica RM2125 / RM2125RT
Rotary microtome, Leica Biosystems©, Nussloch GmbH, Germany).

Endometrial
lesions were evaluated with reference to the World Health Organization (WHO)
classification of female reproductive organs tumors (2014) that stratify
endometrial epithelial lesions into; tumor-like lesions, precursors of endometrial
carcinoma, leiomyoma and endometrial carcinomas. WHO considered endometrial
polyp, Arias-Stella reaction and metaplasias as tumor-like lesions, while endometrial
hyperplasias (hyperplasia without atypia and atypical hyperplasia) as precursors
of endometrial carcinoma.

In order
not to miss other categories of endometrial lesions we divided the samples into
three groups. Firstly,
the benign pathology group included the normal and benign endometrial pathology
such as atrophic endometrium, chronic endometritis, endometrial polyps,
submucous myomas, glandular-Stromal breakdown and disordered proliferative
endometrium. Secondly, the premalignant (precursor) endometrial pathology group
that reported samples of simple, complex and atypical endometrial hyperplasia
and lastly, malignant endometrial
pathology (adenocarcinoma or others) were also included.

Data were
analyzed using IBM SPSS Statistics version 23 (IBM© Corp., Armonk, NY, USA).
Contingency tables were constructed in which the result of hysterectomy biopsy
(gold-standard test) was cross-tabulated against that of D&C biopsy. The
following diagnostic indices together with their 95% confidence intervals (95%
CI) were calculated: sensitivity, specificity, positive and negative predictive
values (PPV and NPV). Overall accuracy or correct classification rate was also
documented.

The
accuracy of D&C biopsy was evaluated using the whole study population as
well as subgroup analysis was conducted for premenopausal and postmenopausal
women separately. Inter-method agreement was examined using the weighted kappa
coefficient.

Results

Eight-hundred twenty-nine legible specimens were tested for the
conformity of D&C endometrial samples and the more conclusive hysterectomy
specimens regarding their histopathological examination reports.

 There were 179(21.6%) women who had
“insufficient tissue samples” for appropriate pathological reporting. inadequate
endometrial tissue samples was more frequent in 147 postmenopausal than 32
premenopausal women. The histological findings of most of the “insufficient
tissue” group were atrophic endometrium (90 cases, 61.2%) among postmenopausal
women and normal endometrium (22 cases, 68.75%) in premenopausal women. (Table
1)

The cross-tabulation
of the histopathological results for the study group with sufficient samples
(n=650) as well as the subgroups of premenopausal (n=499) and postmenopausal
(n=151) women are compared in Tables (2, 3 and 4). Comparing the findings
showed that endometrial polyps and atrophic endometrium were the commonly
missed lesions for premenopausal and postmenopausal women respectively.

Sensitivity,
specificity, PPV, NPV and correct classification rate (accuracy) with their 95%
confidence limits of the sufficient curettage samples of all the recorded
endometrial lesions collectively and separately are listed in Tables (5&6)
respectively.

Table (7)
shows a good agreement between D&C biopsy and hysterectomy diagnoses
regarding the ultimate classification of women in the whole study population
(weighted ? = 0.756, 95% CI = 0.692-0.819) and postmenopausal women
(weighted ? = 0.834, 95% CI = 0.761-0.906). However, the agreement is
moderate in the premenopausal group (weighted ? = 0.568, 95% CI =
0.433-0.704).

Discussion

Preoperative
endometrial tissue sampling is a crucial step in the work-up of women with
different clinical presentations before proceeding to hysterectomy. Curettage
is the classic routine diagnostic and sometimes curative tool over years. Thus,
it was described as “the most expensive test in the whole medical field” by
Mengert and Slate. 9

Our hypothesis
in the current study was to determine the accuracy of the curettage specimen
pathological examination and its similarity to the more definitive hysterectomy
specimen. We did not compare the curettage procedure to any other diagnostic
modality such as hysteroscopy, 3 Pippelle endometrial sampling 10
or endometrial brush cytology 11 as theses are not available in
every medical centre worldwide especially in the developing countries where the
curettage seems to be the affordable alternative to an expensive equipment or
disposable catheters.

The efficacy
of curettage was tested and evaluated. Multiple studies revealed the inaccuracy
of curettage procedure and they considered D&C as a poor diagnostic tool
for endometrial cancer, as presented with high frequency of false-negative findings.
6, 8 On the contrast, adequate sensitivity, specificity and
accuracy for the use of preoperative D&C biopsies had been reported. 12-15

Although D&C
is proven effective for detecting endometrial lesions, it is still considered
as a poor alternative for detecting the focal ones. 12 Endometrial
polyps, submucous myomas and focal endometrial malignancy may be undiagnosed. 7
In our study the commonly missed lesions were endometrial polyps for the whole
study group, in addition, to atrophic endometrium for the postmenopausal women.
These findings were similarly reported by other researchers. 7, 14

Inadequate
uterine cavity evaluation and improper targeted biopsies of endometrium are the
most challenging points with obtaining endometrial samples blindly. Thus, D&C
could miss focal premalignant or malignant endometrial pathologies as mentioned
in previous articles. 2, 17 Stovall et al. reported that in
5.7% of their study group of 407 women, endometrial hyperplasia or carcinoma were
missed. 2 Furthermore, D&C missed two cases with cervical
intraepithelial neoplasia and one woman with endometrial carcinoma in 411 women
as described by Möller and Berget. 17

Other
pitfall that can occur with endometrial sampling is the inability to obtain
adequate tissue sample sizable enough for optimum pathological examination or
what is termed “insufficient sample”. In a recent meta-analysis, authors
included 12 reports over 1029 postmenopausal women and reported a weighted
endometrial sampling failure rate of 11%, while “insufficient samples” were
detected in 31% of cases. An endometrial cancer or premalignant lesions were
found in 7% of these women with insufficient or failed samples. 16

Throughout179
“insufficient samples” in our study group, no premalignant or malignant
endometrial pathology was encountered for the premenopausal group during the
hysterectomy specimens’ evaluation; while five premalignant (3.4%) and two
malignant (1.4%) pathologies were detected in postmenopausal women. This limitation
seems to be more common and misleading among postmenopausal women due to
atrophic inactive endometrium. Thus, it is recommended for these women to use
more advanced and detailed techniques for proper diagnosis. 14, 16

The
calculation of D sensitivity, specificity and accuracy from most of
published work cannot be considered conclusive owing to inadequate information
as well as the wide heterogeneity of choosing different sample sizes,
techniques, procedures and outcomes. Some used the missed diagnosed samples
without sub-grouping them as benign or malignant or sub-classifying their study
groups according to the age or symptoms. Thus, the usefulness and validity of
performing any routine D before hysterectomy remains questionable.

Studies
comparing D with hysterectomy are not entirely accurate, as invasive
techniques such as D may alter the uterine cavity. If endometrial polyps,
for example, are totally removed during curettage, the rate of false-positive
results may be overestimated. 18

We
reported that D, apart from low sensitivity for detection of premalignant
lesions, has high sensitivity, specificity, PPV, NPV and accuracy in detecting
different endometrial lesions for the whole study group. Also, the weighted
kappa coefficient proved a good agreement between D and hysterectomy regarding
diagnoses among the whole study population and postmenopausal women and showed
a moderate agreement in the premenopausal women group. The ability of D
to diagnose the malignant lesions effectively was demonstrated.

In agreement
with our results, Sayg?l? reported positive correlation between D
endometrial findings and hysterectomy specimens’ reports. 12 Others
concluded that D&C had a high accuracy (92.1%) for endometrial hyperplasia
and carcinoma. 13 Also, in a meta-analysis, the weighted
endometrial sampling sensitivity using D&C as a reference for the diagnosis
of endometrial cancer and atypical hyperplasia were 100% and 92% respectively. 16

In
contrary, when D&C accuracy was evaluated on the basis of histological
findings or symptoms persistence in a cohort of 397 women, in 248 women (62.5%)
D&C was unable to determine intrauterine lesions, having a sensitivity of 46%, 100% specificity,
100% PPV, and 7.1% NPV. 6 Furthermore, others reported false-positive
rate of 5.6% and false-negative rate of 11.9%. 8

D&C is
not a satisfactory therapeutic procedure as by comparing D&C and
hysterectomy histological findings, the entire endometrial lesions could still
be identified in the removed uterus. However, Bettocchi et al.
considered D&C as a rare therapeutic option as they were still able to recognize
the endometrial disorders after hysterectomy. Also, they reported that neither
endometrial hyperplasia (simple, complex or atypical) nor endometrial
carcinomas were entirely curetted. 8

To our
knowledge, this is the first study that calculated the sensitivity,
specificity, PPV, NPV and accuracy of each type of endometrial pathologies that
could be frequently encountered during management of women undergoing
hysterectomy for any indication.

 

Conclusions 

In
conclusion, D&C remains an efficient diagnostic tool for preoperative
diagnosis of women undergoing hysterectomy for different indications in the
absence of other advanced diagnostic techniques. Preoperative D&C biopsy
offers acceptable accuracy regarding the diagnosis of most of endometrial disorders,
especially the premalignant and malignant lesions in postmenopausal women, when
compared to hysterectomy diagnoses. 

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