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.