Validation study of a novel clinical algorithm in evaluating abnormal uterine bleeding using a Combination of Saline Infusion Sonohysterography (SIS) and endometrial brush biopsy (EMB).

Abnormal uterine postmenopausal blood loss is a marker for uterine
abnormalities and endometrial cancer. In case a patient presents with this
complaint further investigation is necessary. In the past, in all women
curettage was performed (preferably under general anaesthesia), to rule out
malignancies. With advancing age, the chance of malignancy is increasing. The
most common cause of the blood loss was endometrial atrophia. Based on
methodologically good studies, a new approach was introduced to reduce
unnecessary diagnostic procedures: endometrial thickness measurement. In case
of thin endometrium (below 4mm) as measured by ultrasound was small, the chance
of malignancy appeared low, atrophia was most likely and no further diagnostic
procedures were performed (2-4). Specificity and sensitivity of this
measurement was 98 and 97 % respectively. In case of recurrent bloodloss
further diagnostic evaluation was performed by hysteroscopy and histology. In
case of thickened endometrium (4mm or more), the endometrium was sampled using
micro curettage. This approach has proven to be successful and reliable.
However, the introduction of this approach has lead to an increase in
hysteroscopies (golden standard). Moreover, the number of unnecessary
hysteroscopies is increasing due to inconclusive or incomplete samples.

An alternative diagnostic method is saline infused sonography (SIS) combined
with EMB. This has proven to be a safe and reliable way to diagnose
intrauterine abnormalities (1,5,6). This ultrasound technique is able to
visualize the total endometrium and myometrium. In some aspects it is even more
reliable then hysteroscopy. (Pre) malignant abnormalities in the endometrium
can be exclusively found (in case of negative sampling results) focally in
polyps or other endometrial changes. Combination of SIS and endometrial tissue
sampling is complimentary in generally accepted existing algorithms.

Hysteroscopy, which is a costly and time-consuming procedure, can easily be
exchanged by the combined EMB and SIS approach as described by Mihm et.al (1).
Based on these data and observations, we are planning to perform a combined SIS
and EMB prior to hysteroscopy using a new algorithm.
At the end of the study we will evaluate the sensitivity and specificity of
this combined approach with the gold standard: hysteroscopy.

Primary Objective:
To assess whether the combination of Saline Infusion Sonohysterography (SIS)
and Endometrial Brush Biopsy (EMB) will create an innovative algorithm for
diagnosing corpus uteri malignancy in postmenopausal women suffering from
abnormal uterine bleeding, which may restrict diagnostic hysteroscopies to
inconclusive or failed SIS and EMB.

Secondary Objective:
To asses the experience (pain, number of visits, economic effects, efficiency
etc) of patients on the Sonosure device for combined SIS and EMB using the
questionnaire.

This study is a Prospective controlled multicentre cohort study, which will be
performed in 6 months in 6 Santeon hospitals (Canisius-Wilhelmina Hospital,
Nijmegen; Catharina Hospital, Eindhoven; Martini Hospital, Groningen; Medisch
Spectrum Twente, Enschede; Onze Lieve Vrouwen Gasthuis, Amsterdam; St. Antonius
Hospital, Nieuwegein).

We are testing a new algorithm using the golden standard (hysteroscopy) as a
control to avoid the risk of missing abnormalities. The tests done with the
Sonosure device will be performed on about 50 patients per institution, coming
from there regular cohort of women with postmenopausal uterine bleeding. We
think each institution should be able to include 50 patients in this particular
population within 6 months.

The algorithm we test includes the methods that are currently used. The use,
results and risks of these methods are well known and generally accepted. The
burden for the patients only lies within the group with a clear diagnosis who
would not have undergone a hysteroscopy in the standaard situation.