USEFULNESS OF INTRAOPERATIVE PARATHYROID HORMONE MONITORING DURING MINIMALLY INVASIVE VIDEO-ASSISTED PARATHYROIDECTOMY

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USEFULNESS OF INTRAOPERATIVE PARATHYROID HORMONE MONITORING DURING MINIMALLY INVASIVE VIDEO-ASSISTED PARATHYROIDECTOMY Elisabetta Stenner elisabetta.stenner@asuits.sanita.fvg.it

Introduction: primary hyperparathyroidism (PHPT) PHPT is a disease of improper calcium regulation Osteoporosis, fractures, bone pain Kidney stones GERD Atherosclerois, atrial fibrillation and palpitations, tiredness, memory loss, poor concentration chronic fatigue, higher risk of several cancers Norman Parathyroid Center

Norman Parathyroid Center Introduction: primary hyperparathyroidism NO DRUGS NO PILLS NO OTHER TREATMENTS THE ONLY CURE IS SURGERY

Introduction: MIP versus BNE FROZEN SECTION Exposure of all 4 glands Performable on all pts BNE MIP Less pain Quicker recovery Smaller PTHIO incision Better cosmetic result Shorter operative time Shorter hospital stay The current status of the postoperative transient hypoparathyroidism is about 5%, in contrast to approximately 15-25% after BNE.

Clinical question Test ordering Clinical effect POST-ANALYTICAL PRE-ANALYTICAL Sample collection Sample timing Sample preparation for analysis TTP for PTHIO Interpretation Results report Analysis and validation ANALYTICAL

Pre-analytical phase: clinical question/test ordering Areas of application of intraoperative ipth monitoring 1 To guide surgical decisions during parathyroidectomy (MIP) in one of the following clinical contexts: To confirm complete removal of all hyperfunctioning parathyroid tissue To identify patients with additional hyperfunctioning parathyroid tissue 2 To differentiate parathyroid from non-parathyroid tissue by ipth measurement in the fineneedle aspiration washout 3 To lateralize the side of the neck harboring hyperfunctioning parathyroid tissue by determination of jugular venous gradient in patients with negative or discordant preoperative imaging studies, in order to increase the number of patients eligible for unilateral neck exploration

IOPTH during MIP: recommended by American Association of Endocrine Surgeons. Pre-analytical phase: Eligibility criteria for MIP well-localized single adenoma Using IOPTH has a potential to reduce pre-operative scans < 3 cm no simultaneous thyroid disease no simultaneous malignancy no previous neck irradiation

Pre-analytical phase: sample collection COLLECTION TUBE Plasma EDTA (to reduce TAT) SAMPLING SITE CENTRAL VEIN (internal jugular vein) PERIPHERAL VEIN Venous sampling for IOPTH can be performed from a central or peripheral site but should be consistent for any individual procedure

TIMEPOINTS Pre-analytical phase: sample timing

Pre-analytical phase: sample timing

TIMEPOINTS Pre-analytical phase: sample timing

Pre-analytical phase: preparation for analysis CALIBRATION (One day before ) and CQI PREPARATION 5 min 3500 RPM SAMPLE REJECTION CRITERIA HEMOLYZED J. Moalem et al. Ann Surg Oncol (2010) 17:2963-2969 Mean PTHIO = 39% [19% 70%]

Pre-analytical phase: preparation for analysis PRE-ASPORTATION FN longer operative time unnecessary BNE POST-ASPORTATION FP failed parathyroidectomy recurrent/persistent phtp J. Moalem et al. Ann Surg Oncol (2010) 17:2963-2969

Analytical phase: PTH assays 4th generation?

Analytical phase: inter-method bias in PTH results Differences in results observed for a haemodialysis patient

Analytical phase: PTH (7-84) Assessment of recognition/cross reaction of purified PTH (7-84)

Analytical phase: PTH fragments and their recognition PTH assay harmonization is mandatory BUT since DELTA is all important during parathyroidectomy, it does t matter if the assay is 2nd / 3rd generation E. Cavalier et al. / Annales d Endocrinologie (2015)

Post-analytical phase: interpretation Most common IOPTH assay criteria used for prognostication of outcome of parathyroid surgery

Post-analytical phase: interpretation Performance of IOPTH monitoring using different criteria for cure

Post-analytical phase: interpretation IOPTH performs consistently and accurately in different clinical scenarios

Post-analytical phase: interpretation Advantages of IOPTH IOPTH guides surgical decision MIP + IOPTH improved cure rate (3-5%) of BNE without IOPTH Cure rate MIP + IOPTH > cure rate MIP IOPTH Recently, due to the ability of IOPTH to predict cure, surgeons have been considering to perform MIP in pts who do not have perfect co-localization

Post-analytical phase: interpretation FALSE POSITIVE FALSE NEGATIVE Parathyroid cancer Double adenoma Concomitant thyroid surgery Renal impairment Stringent criteria (i.e drop to normal range Halle and Rome) Excessive manipulation of adenoma Pre-incision baseline (i.e. Vienna)

Post-analytical phase: interpretation Results of studies comparing the performance of IOPTH, US and MIBI

Servizio Sanitario Regionale AZIENDA OSPEDALIERO UNIVERSITARIA Ospedale di rilievo nazionale e di alta specializzazione ( D.P.C.M. 8 aprile 1993) Servizio Sanitario Regionale AZIENDA OSPEDALIERO UNIVERSITARIA Ospedale di rilievo nazionale e di alta specializzazione ( D.P.C.M. 8 aprile 1993) OSPEDALI RIUNITI DI TRIESTE FACOLTA' DI MEDICINA OSPEDALI E CHIRURGIA RIUNITI DI TRIESTE FACOLTA' DI MEDICINA E CHIRURGIA DAI DI MEDICINA DI LABORATORIO Direttore: dott. Bruno Biasioli DAI DI MEDICINA DI LABORATORIO Direttore: dott. Bruno Biasioli ASUITS AZIENDA SANITARIA UNIVERSITARIA INTEGRATA DI TRIESTE, ITALY

8% recurrent/persistent HPT 5% 4% 2% 1% ADENOMA 88% MULTIGLANDULAR DISEASE ATYPICAL ADENOMA PARATHYROID CARCINOMA DIFFERENT NATURE 30% no IOPTH 50% IOPTH > 50% FP 20% IOPTH < 50% but frozen section confirmed adenoma and second adenoma was not found

Clinical question Test ordering Clinical effect POST-ANALYTICAL PRE-ANALYTICAL Sample collection Sample timing Sample preparation for analysis TTP for PTHIO Interpretation Results report Analysis and validation ANALYTICAL

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