DISCUSSION
In our study, we aimed to investigate the differences in cure rate and
operative time, using IOPTH. We have shown, in a large cohort, that
there is no statistical difference in cure rate with or without IOPTH
assay, and that using IOPTH significantly increases operative time.
This study was conducted as a follow-up to a previous study we performed
in 2010.(6) Following the 2010 study, our department
has changed its practice and stopped using IOPTH routinely in every
parathyroidectomy, but only in selected clinical scenarios, as outlined
above.
IOPTH assay is performed routinely by 74% of parathyroid surgeons in
the US.(12) However, its routine use in all
parathyroidectomies is long debated.
There is a wide consensus amongst most parathyroid surgeons and the
literature that several scenarios necessitate its use, such as
unconcordant pre-operative localization studies or multiglandular
disease, and both the ESES (European Society of Endocrine Surgeons) and
the AAES (American Association of Endocrine Surgeons) agree on its use
in such circumstances.
Whilst the clinical scenarios are agreed upon, the routine use of IOPTH
in every parathyroidectomy, regardless of the scenario, is widely
debated. Two main approaches in the literature that represent this
debate, are the ESES and the AAES: the ESES recommends that ”when
preoperative localization with MIBI and US is concordant for
single-gland disease, the use of IOPTH is of little added value”; on the
other hand, the AAES recommends that when image-guided focused
Parathyroidectomy is planned, IOPTH should be used to avoid higher
operative failure rates.(13,15)
Another noteworthy approach is that of J. Norman et al. who advocated to
abandon unilateral parathyroidectomies and perform a bilateral
exploration in every parathyroidectomy.(21) However,
it should be emphasized, that their group does not use US at all, but
rather Sestamibi as the single pre-operative localization modality.
At Rabin Medical Center, we follow the ESES recommendation, with a 99%
success rate without the routine use of IOPTH. Our approach for primary
hyperparathyroidism due to a single adenoma with two concordant imaging
modalities for pre-operative localization, is minimally invasive
surgery, performed by experienced surgeons and a frozen section
confirmation.
According to the literature, the sensitivity and PPV of pre-operative
localization using both Sestamibi and US, ranges from 78.7-91.9% and
89.8-100% respectively.(24) Our results are on the
lower side of these ranges (sensitivity: 74.17%, PPV: 90.06%), and are
lower than the rates we have shown in a previous study conducted at our
center. We speculate that several factors contributed to these rates:
(1) Regarding the low sensitivity, whenever the two modalities were
unconcordant, even if one of them showed no adenoma while the other
predicted the location of the adenoma correctly, we labeled it as ”False
Negative”; (2) Not all US and Sestamibi tests were performed by the same
operator, and many of them were not performed by experts specialized
solely in head & neck imaging. In a previous study performed at our
center, we included mainly patients who underwent US and Sestamibi by a
specialized head & neck operator. Sensitivity and PPV were 93% and
99% respectively.(6)
Regarding operative time analysis, we decided to divide our control
group into two subgroups as outlined in the ”Methods” section. We wanted
to examine the hypothesis that because many patients who underwent
parathyroidectomy with IOPTH monitoring had unconcordant pre-operative
localization, their operative time would be longer a priori, thus
leading to a bias when comparing operative time between the study and
control group. We have shown, that regardless of pre-operative
localization studies concordance, operative time with IOPTH monitoring
is significantly longer compared to operative time without IOPTH
monitoring.
Economically, the IOPTH assay affects operative financial costs,
primarily in two manners: the first is the cost of operating room time,
which was significantly shorter in our No IOPTH group compared
individually to both IOPTH subgroups; the second is the direct cost of
the assay itself.
In a study conducted L. Morris et al(23), the authors
performed a cost-benefit analysis of IOPTH use. For them, when
considering the cost-benefit of routine IOPTH use, the most important
factor to weigh, is the rate of multi-glandular disease, which varies
substantially amongst different institutions and countries. They argue
that when pre-operatively unrecognized multi-glandular disease exceeds
6%, it is reasonable to perform IOPTH in all Parathyroidectomies. In
our cohort only 3.7% (17/452) of patients had a multi-glandular disease
discovered intra-operatively. Additionally, the authors argue that IOPTH
use becomes cost-saving when the probability of cure without IOPTH
monitoring decreases below 94%. In our study we reached a 98.8% cure
rate in the No IOPTH group.
Likewise, as shown in a study by Badii B et al. from 2017, when IOPTH is
not used routinely in every parathyroidectomy, but only in selected
patients, a substantial amount of money can be saved - up to \euro678
per patient.(25)
Moreover, as health-economics become a substantial consideration in
modern medical centers, a protocol to reduce costs, without diminishing
the success rates of a commonly performed procedure, is paramount.
Based on this study, we would like to propose that using our protocol
for parathyroidectomies is non-inferior to parathyroidectomies performed
with IOPTH assay, while also saving operating room time.
The present study is limited by its retrospective nature and the fact
that the data had been collected over almost two decades. Nevertheless,
the study timeline reflects the natural evolution of IOPTH and the
transition to a minimally invasive approach. Furthermore, the importance
of continuous report from a single high-volume center cannot be
overstated, since practice change needs to be reviewed respectively to
assure quality.