Comparison of two methods to improve the outcome of a ultrasound assisted fine needle aspiration biopsy (FNAB) of the thyroid gland.

To cytopathologically diagnose a thyroidal gland nodule the golden standard is
to perform a (ultrasound guided) fine needle aspiration biopsy (FNAB) [4] [5].
At the laboratory the cytological material will be interpreted and classified
according to the Bethesda system [3] [4]. Within this classification there are
six categories (figure 1).


This research mainly concerns the category Bethesda 1, *non diagnostic*. As can
be seen in figure 1, the risk of malignancy in this group is small, but it is
recommended to repeat the ultrasound examination and perform a new FNAB [4]
[6]. This leads to having to repeat an unpleasant examination for the patient,
extra procedure-related risks, uncertainty about the results and possible
consequences, not to forget also new appointments in the hospital (internist
and radiology) are made. In addition to the adverse consequences for the
patient, there are also additional costs, such as costs for the ultrasound
guided thyroid FNAB, pathological examination and an appointment with referring
specialist(s). If the 'non-diagnostic' percentage could be reduced, this is not
only a huge benefit for the patient, but also in favour of healthcare costs.
In 2012, an inventory was made among healthcare professionals regarding the
thyroid carcinoma guideline in the Netherlands. In this inventory 53 out of 116
respondents indicated that they experienced the ultrasound with FNAB as a
bottleneck. Of these 53 respondents, 18 considered this the most important
hindrance [7]. Indirectly you can say that cytology is part of this hindrance.

According to literature, you can assume a variation in 'non-diagnostic yield'
of approximately 5-25% for a FNAB of the thyroid gland [6] [8] [9] [10] [11]
[12] [13] [14] [15]. In the Jeroen Bosch hospital approximately 50% of thyroid
biopsies are performed by a PA radiology with a non-diagnostic yield of
approximately 13-18% over n=700 patients. This corresponds to literature.

In the Jeroen Bosch hospital, an agreement has been made between radiologists,
internists and pathologists to perform a fine needle aspiration biopsy of every
thyroid nodule twice in order to minimize the chance of a non-diagnostic
result. A thyroid FNAB is done under ultrasound guidance on the radiology
department. During the biopsy, the nodule is punctured twice with a 25 Gauge
needle. When the needle is in position in the thyroid, the present laboratory
technician applies vacuum to the needle and at the same time the doctor/PA
moves the needle gently up and down in the thyroid nodule with a rotating
movement.

A device has been developed in America, the Cytocore, which provides vacuum to
the needle and needle rotation in one act. The preliminary results show a clear
improvement in the diagnostic yield of the biopsy (appendix 1). The cytological
material contains more assessable cells and does not create any additional risk.

There is currently no literature available on the possible gain in yield for
cytological biopsies of the thyroid gland by using the CytoCore. There is
however a 'CytoCore white paper' on cytological biopsy of a pig liver, in which
the use of the CytoCore caused less blood loss and increased cellularity of the
cytological material (appendix 1). In addition, manufacturer Praxis, mentions
that clinical feedback shows that 100% of the material was adequate for
diagnosis (appendix 1). This sounds to good to be through and therefore before
to introduce this promising device in clinical practice we would like to
investigate its technical and diagnostic efficacy.

Primary objective:
- obtain an comparison in diagnostic results of two methods of ultrasound
assisted fine needle aspiration biopsies (FNAB) of the thyroidal gland in the
Jeroen Bosch hospital (JBZ).
Secondary objective:
- can the cytological thyroid material obtained with the CytoCore (method B) be
better assessed under the microscope in comparison with the material obtained
manually (method A)?

This is a randomized prospective cohort study. With an ultrasound guided
thyroid FNAB, the thyroid nodule is standard biopsied twice with a 25 Gauge
needle. The intervention consists of replacing 1 standard biopsy (method A) by
a biopsy with the CytoCore (method B). In both cases the same standard 25 Gauge
needle is used. Randomization determines with which method the first and second
biopsy is performed, this creates 2 possibilities. The first possibility is a
standard biopsy (method A) at first followed by a CytoCore biopsy (method B).
The second possibility is at first a biopsy with CytoCore (method B) followed
by a standard biopsy (method A). Randomization is performed for the 140
participants via http://www.randomization.com (appendix 2). The randomization
is divided into 7 blocks of 20 participants so that after the first 20
participants method A and B are equally distributed for an additional
assessment. If the randomization table shows an 'A' the first biopsy is done in
the standard way (method A), if the table shows a 'B' the first biopsy is done
with the CytoCore (method B). All cytological material is assessed according to
the Bethesda criteria [3].

The intervention consists of replacing one out of two standard thyroid FNAB*s
(method A) with a thyroid FNAB using the CytoCore (method B).

No additional measures have been taken for the use of the CytoCore. The product
meets the requirements set by the JBZ. A prospective risk assessment for
medical devices (PRS) has been performed, which indicated that no further risk
analysis is required.
The standard 25 Gauge needle is used during the biopsy and there is no reason
to believe that using the CytoCore would increase the risk of patients. The
same kind of technique (rotating needle and negative pressure) is now also
used. The CytoCore is used as intended and European approved.