1. Minimally Invasive Parathyroidectomy for Primary Hyperparathyroidism Joint Hospital Surgical Grand Round 18 April 2009 Dr. David KW Leung United Christian Hospital

2. Outline  Primary hyperparathyroidism  Surgical treatment  Bilateral neck exploration  Minimally invasive parathyroidectomy (MIP)  Conclusion

3. Definition Primary hyperparathyroidism - A sporadic or familial disorder associated with hyperCa, elevated or inappropriately raised PTH levels and parathyroid gland enlargement Bailey & Love’s Short Practice of Surgery

4. Parathyroidectomy Conventional bilateral cervical exploration Minimally invasive/ Limited parathyroidectomy

5. Bilateral neck exploration  ‘Gold standard’  Pre-op localization of abnormal parathyroid gland not mandatory  The success is based on a thorough knowledge of the anatomy and embryological evolution of the glands  Success rate – 95-98%

6. Bilateral neck exploration  To identify all 4 parathyroid glands  Only enlarged glands are removed whether single- or multiple- gland disease found  If 4 glands are enlarged, subtotal parathyroidectomy is performed; leaving a single vascularized gland remnant no larger than a normal parathyroid

7. Limited/minimal invasive parathyroidectomy  The need for routine bilateral neck exploration being challenged because:  Pathology of the disease  Improvement of pre-op localization studies  Introduction of quick parathyroid hormone assay (QPTH)  Confirm removal of all hyper-functioning parathyroid tissue

8. Pathology Adenoma 85% Hyperplasia14% Carcinoma<1%

9. Imaging and pre-op localization Ultrasound technetium-99M sestamibi scan (MIBI) CT scan MRI parathyroid angiography/ selective venous sampling

10. Ultrasound  Sensitivity 70-80%  Lower sensitivity in re-operative cases  False-positive (15-20%) due to muscle, vessels, thyroid nodules, LN and oesophageal pathology  has difficulty locating abnormalities in the retro-oesophageal, retrosternal, retrotracheal and deep cervical areas

11. Technetium-99M sestamibi scan (MIBI)  technetium-99M sestamibi concentrated in abnormal parathyroid glands

12. Technetium-99M sestamibi scan (MIBI)  Sensitivity 80-100%  drawbacks  Not always identify patients with multiple adenomas or four-gland hyperplasia  Failed to localized small adenomas

13. Limited/minimal invasive parathyroidectomy  General/ local anaesthesia  Accurate pre-op localization is a prerequisite  Targeted on one specific parathyroid gland  Procedure carried out through a small incision Parathyroid gland Thyroid

14. Limited/minimal invasive parathyroidectomy  Exclusion  Suspected multiple - gland disease on imaging studies  History of familial hyperparathyroidism or multiple endocrine neoplasia

15. Evidence-based?

16. 1. Miccoli et al. Video-assisted vs. conventional parathyroidectomy in primary hyperparathyroidism: a prospective randomized study. Surgery 1999;126:1117-1122 2. Bergenfelz A. et al. Unilateral vs. bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial. Ann Surg. 2002;236:543-551. 3. Westerdahl et al. Unilateral vs. bilateral neck exploration for primary hyperparathyroidism: Five-year Follow-up of a randomized controlled trial. Ann Surg. 2007;246:976-981. 4. Bergenfelz A et al. Conventional bilateral cervical exploration vs. open minimally invasive parathyroidectomy under local anaesthesia for primary hyperparathyroidism. Br. J Surg. 2005;92:190-197 5. Russell CF et al. Randomized clinical trial comparing scan-directed unilateral vs. bilateral cervical exploration for primary hyperparathyroidism due to solitary adenoma. Br. J Surg. 2006;93:418-421

17. Patients with sporadic primary hyperparathyroidism Minimally invasive parathyroidectomy - Unilateral - focused - video-assisted Bilateral cervical exploration Compare - Cure rate - early post-op hypoCa/ Ca level - Operative time - cost - pain - Cosmetic results - Complication/ vocal cord palsy Study design - overall

18. Study design - 1 Patients with sporadic primary hyperparathyroidism Minimally invasive parathyroidectomy Bilateral cervical exploration Sestamibi scan/ USG +ve Randomization - ve Excluded 1. Miccoli et al. Surgery 1999 4. Bergenfelz et al. Br. J. Surg. 2005 5. Russell et al. Br. J. Surg. 2006 Expose all 4 glands Gross morphology Frozen section Drop in ioPTH

19. Study design - 2 Patients with sporadic primary hyperparathyroidism Minimally invasive parathyroidectomy Bilateral cervical exploration Sestamibi scan +ve Randomization - ve Explore +ve side Explore left side first If no enlarged gland on first explored side Stop if one enlarged gland found + drop in ioPTH 2. Bergenfelz et al. Ann. Surg. 2002 3. Westerdahl et al. Ann. Surg. 2007

20. Study design - summary Miccoli et al.Bergenfelz et al. Westerdahl et al. Bergenfelz et al.Russell et al. Surgery 1999 Annals of Surg. 2002 Annals of Surg. 2007 Br. J Surgery 2005 Br. J Surg. 2006 Type of studyRCT No. of patient (MIP + BCE = Total) 20 + 18 = 3847 + 44 = 9138 + 33 = 7125 + 25 = 50 54 + 46 = 100 mode of explorationVAP vs. BCEunilateral vs. bilateral targeted (MIP) vs. bilateral unilateral vs. bilateral Anaesthesia GA except 2 in VAP group GA LA in MIP/ GA in BCE GA Pre-op localization modality USGsestamibi Use of ioPTH in MIP gp.Yes No

21. Results - 1 Miccoli et al.Bergenfelz et al. Westerdahl et al. Bergenfelz et al.Russell et al. Surgery 1999 Annals of Surg. 2002 Annals of Surg. 2007 Br. J Surgery 2005 Br. J Surg. 2006 Cure rateAll (up to 6 months)Same up to 5 year Same up to 6 months All (mean FU 23 months) Early post-op hypoCa Higher in BCE (NS) Higher in BCE (p < 0.05) / Higher in BCE (p = NA) Nil Post-op Ca level / lower in BCE on D2 (2.15 vs. 2.26; p < 0.01) Same at 1and 5 years slightly lower in BCE on Day 3 (0.022) / OT time (MIP vs. BCE) shorter (57 vs. 70 mins; p < 0.05) shorter (72 vs. 82 min.; p = 0.22) shorter (41 vs. 63mins; p = 0.024) shorter (65.6 vs. 79.7 mins; p = 0.007) NA = Not available in the paper NS = not significant

22. Results - 2 Miccoli et al.Bergenfelz et al.Westerdahl et al.Bergenfelz et al.Russell et al. Surgery 1999 Annals of Surg. 2002 Annals of Surg. 2007 Br. J Surgery 2005 Br. J Surg. 2006 CostSimilar slightly higher in MIP (US$2258 vs. 2097; p = 0.13) // Pain less in VAP (p < 0.05) /Similar/ ComplicationSimilar (p = NA) higher in BCE (laryngeal edema, bleeding; p = 0.27) Higher in BCE (wound seroma; p = NA) Nil Vocal cord palsy 1 patient in VAP (p not calculated) higher in unilateral gp. (temporary; 2 vs. 1; p = 0.99) 1 patient in MIP (temporary); p = NA) 2 patients in BCE (permanent;p = NA) Cosmetic results Superior in VAP (p = NA) /Same/ NA = Not available in the paper NS = not significant

23. Conclusion  MIP is as effective as conventional bilateral neck exploration for primary hyperparathyroidism  Advantage  Less early post-operative hypoCa  Can be done under LA  Shorter operative time

24. Thank you Questions?