11/8/2014 LOCALIZATION STUDIES FOR Disclosures: none PRIMARY HYPERPARATHYROIDISM Marika Russell, MD, FACS Assistant Professor UCSF Otolaryngology-Head and Neck Surgery Overview Background: Overview � Shift over last 10-15 years � Background � Four gland exploration -> minimally invasive/targeted � Review of imaging techniques parathyroidectomy � Ultrasound � Drivers: � Sestamibi (MIBI) � Decrease operative time � SPECT � Decrease morbidity � SPECT/CT � Improve cosmesis � 4D CT � Effectors: � Diagnostic efficacy � ioPTH � Improved imaging techniques � Adjunctive localization measures 1
11/8/2014 Background: Case Example Background: Case Example � 44 yo M, incidental finding elevated Ca++ � w/u reveals primary hyperparathyroidism � Sestamibi: “area of persistent focal uptake inferior to left thyroid lobe suggestive of parathyroid adenoma” � Radiology U/S: “1.9 cm right parathyroid adenoma candidate inferior to the left thyroid lobe. Recommend correlation with nuclear medicine sestamibi scan” Background: Case Example Ultrasound 2
11/8/2014 Ultrasound: Advantages Ultrasound: Limitations � Non-invasive � Obese patient, short neck � No ionizing radiation � Concurrent thyroid � Inexpensive pathology � Readily repeatable � Intrathyroidal adenoma � Surgeon performed US: direct, real-time interpretation of images; instrumental component � Ectopic glands obscured of physical exam by bone or air columns � Mediastinal � Surgeon performed US enhances understanding of � Retrotracheal anatomy and informs surgical plan � retroesophageal Terris et al. Am J Otolaryngol 2007;28:408-14 Schenk et al. Am Surg 2013 79(7):681-5 US: Imaging Characteristics US: Imaging Characteristics � Normal parathyroid glands not typically visualized R superior PT adenoma: transverse R superior PT adenoma: longitudinal � PT adenoma � homogenous, hypoechoic nodule � Well circumscribed � Ovoid, biolobed, longitudinal � Rate of detection increases with size; threshhold ~4- 8mm � Hyperplastic glands difficult to detect unless marked increase in size Lee and Steward Otolaryngol Clin N Am 2010;43:1229-39 3
11/8/2014 US: Imaging Characteristics L inferior PT adenoma: transverse L inferior PT adenoma: longitudinal Lee and Steward Otolaryngol Clin N Am 2010;43:1229-39 Sestamibi (MIBI) � First reported in 1989 Parathyroid Scintigraphy � Utilizes 99m Tc sestamibi (MIBI) � Concentrates in thyroid and parathyroid; washes out more rapidly in thyroid � Dual phase methadology � Planar imaging 4
11/8/2014 SPECT (Single Photon Emission Sestamibi (MIBI) Computed Tomography) � Advantages � Limitations � 3D imaging of MIBI uptake � Simple, easy to � Smaller size perform � Less sensitive for � Localization � Single injection MIBI multiglandular disease, � thyroid vs. parathyroid hyperplastic PT � Posterior adenoma � False positives with (descended superior thyroid nodule or PT) carcinoma � Anatomic location ectopic PT adenoma Palestro CJ, Tomas MB, Tronco GG. Semin Nucl Med 2005;35:266-76. SPECT SPECT/CT � Fuses SPECT and CT images for more precise anatomic localization � Typically acquired at single time interval (early vs. late) � Radiation dose associated with CT scan Gayed et al. J Nucl Med 2005;46:248-52 Lavely et al. Semin Nucl Med 2005;35:266-76 5
11/8/2014 4D CT � Utilizes time (contrast 4D CT washout) as “4 th dimension (≥2 contrast phases) � Parathyroid adenoma � Peak enhancement on arterial phase � Washout in delayed phase � Low attenuation in non- contrast images Diagnostic Efficacy: Ultrasound Diagnostic Efficacy � Sensitivity: 27-95% � Wide range � Varies with experience � Specificity: 92-97% Meilstrup JW. Otolaryngol Clin North Am 2004:27:763-78 Khati N et al. Ultrasound Q 2003;19:162-76 6
11/8/2014 Diagnostic Efficacy: Surgeon- Diagnostic Efficacy: Surgeon- performed US performed US Side (Left vs right) and Quadrant (Superior vs. Inferior) Side (Right vs. Left) Side and Quadrant (Superior vs. n Inferior) US MIBI P-value n US MIBI p-value US MIBI P-value 103 87% 58% < 0.001 29 90% 71% 0.0578 83% 61% 0.0522 Laryngoscope 2006;116:1380-4 Laryngoscope 2008;118:243-46 Diagnostic Efficacy: Surgeon- Diagnostic Efficacy: Surgeon- performed US performed US � 392 patients with PHPT underwent SUS � 32/392 (8%) were FN � Deep tracheoesophageal groove (9) � 357/392 (91%) with positive finding � Thyrothymic ligament below clavicle (5) � 342/392 (87%) were TP � Concurrent thyroid goiter (4) � Sensitivity 91% � Thyroid cancer (1) � PPV 96% � Normal location, missed (13) J Am Coll Surg 2011;212(4):522-9 J Am Coll Surg 2011;212(4):522-9 7
11/8/2014 Diagnostic Efficacy: Surgeon- Diagnostic Efficacy: Surgeon- performed US performed US � 156 pts with SUS before MIBI � 226 patients with PHPT � PT candidate in 140/156 (90%) � 173/226 (77%) localized with SUS � TP SUS 131/156 (84%) � 53/226 not localized with SUS � No parathyroid gland (32) � 144/156 (92%) no additional info from MIBI � Failed to recognize multiglandular disease (5) � Strategy to reserve MIBI for unclear or negative SUS � Incorrect location of abnormal gland (16) J Am Coll Surg 2011;212(4):522-9 J Am Coll Surg 2006;202:18-24 Diagnostic Efficacy: Surgeon- Summary: Surgeon-performed US performed US � Inexpensive, non-invasive � Highly effective in hands of surgeon � May be more sensitive than MIBI � Limited in: � Ectopic/extra-cervical disease � 30/53 (57%) negative SUS localized with MIBI � Concomitant thyroid disease � 203/226 (90%) localized with both studies � Multiglandular disease � 223/226 (99%) with successful surgery � Argument for SUS as primary localizing study; MIBI � ioPTH as adjunct � 88% unilateral exploration J Am Coll Surg 2006;202:18-24 8
11/8/2014 Sensitivity: MIBI vs. US MIBI vs. SPECT vs. SPECT/CT � SPECT generally purported to have better detection Author Year N US (%) Tc-Mibi (%) Combined (%) capability than planar imaging Casas 1993 22 67 100 � Studies with mixed results Light 1996 21 57 87 Mazzeo 1996 73 85 82 � Most utilize single SPECT Sofferman 1996 33 89 91 � SPECT/CT offers theoretical advantages over MIBI, Ishibashi 1998 20 78 83 SPECT Ammori 1998 72 80 100 Purcell 1999 61 57 54 78 � Few large series with direct comparisons Joshua 2004 319 86 70 Hajioff 2004 48 64 83 96 Mekel 2005 146 61 74 83 Terris DJ et al. Am J Otolaryngol 2007; Nov- Dec;28(6):408-14. MIBI vs. SPECT vs. SPECT/CT MIBI vs. SPECT vs. SPECT/CT � Early and late images obtained for every patient � Planar � SPECT � SPECT/CT � Every combination of study was generated � Lavely et al., 2007 � 2 reviewer groups examined all combinations for � Prospective comparison adenoma localization � 210 pts submitted to protocol � Level of certainty measured � 98 with single adenomas at surgery included in analysis � compared against surgical localization Lavely et al. J Nucl Med 2007;48:1084-9 Lavely et al. J Nucl Med 2007;48:1084-9 9
11/8/2014 MIBI vs. SPECT vs. SPECT/CT MIBI vs. SPECT vs. SPECT/CT � Better agreement on certainty for dual-phase studies compared with single-phase studies � Planar: dual-phase more sensitive than single-phase (early or delayed) � SPECT: dual-phase more sensitive than single-phase (early or delayed) � SPECT/CT: dual-phase SPECT/CT more sensitive than single-phase (early or delayed) � Early more sensitive than late Lavely et al. J Nucl Med 2007;48:1084-9 Lavely et al. J Nucl Med 2007;48:1084-9 MIBI vs. SPECT vs. SPECT/CT MIBI vs. SPECT vs. SPECT/CT � SPECT vs. Planar: � SPECT/CT vs. SPECT � SPECT (single- or dual-phase) not significantly better � Dual-phase SPECT/CT more sensitive than dual-phase than dual-phase planar SPECT � SPECT/CT vs Planar: � Early-phase SPECT/CT with delayed SPECT more � Single-phase SPECT/CT not significantly better than sensitive than dual-phase SPECT dual-phase planar � Dual-phase SPECT/CT more sensitive than dual-phase planar � Early SPECT/CT with delayed planar imaging more sensitive than dual-phase planar Lavely et al. J Nucl Med 2007;48:1084-9 Lavely et al. J Nucl Med 2007;48:1084-9 10
11/8/2014 MIBI vs. SPECT vs. SPECT/CT 4D CT � Conclusion: � Kelly et al., 2014 � Early SPECT/CT in combination with any delayed � Retrospective series, 208 pts imaging (planar, SPECT or SPECT/CT) more sensitive � 155 initial; 53 re-operations than dual-phase planar � 233/284 lesions (82%) correctly localized with 4D-CT � 46/48 (95.8%) re-operative cases correctly localized unilateral vs. bilateral Lavely et al. J Nucl Med 2007;48:1084-9 Kelly et al. AJNR 2014 4D CT 4D CT vs. US vs. SPECT � Hunter et al., 2012 � Cheung et al., 2012 � Retrospective study, 143 patients � Meta-analysis � Single adenoma � 43 studies � Accuracy of side and quadrant � Initial parathyroidectomy for PTHP � Laterality 93.7% Modality Sensitivity PPV � Quadrant 86.6% US 76.1% 93.2% � Median weight 417 mg SPECT 78.9% 98.7% 4D CT 89.4% 93.5% Cheung et al. 2012 Ann Surg Oncol 11
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