Association of the Genomic Profile of Medullary Thyroid Carcinoma with Tumor Characteristics and Clinical Outcomes in an International Multicenter Study.

Purpose: The prognostic importance of RET and RAS mutations and their relationship to clinicopathologic parameters and outcomes in medullary thyroid carcinoma (MTC) need to be clarified. Experimental Design: A multicenter retrospective cohort study was performed utilizing data from 290 patients with MTC. The molecular profile was determined and associations were examined with clinicopathologic data and outcomes. Results: RET germ line mutations were detected in 40 patients (16.3%). Somatic RET and RAS mutations occurred in 135 (46.9%) and 57 (19.8%) patients, respectively. RETM918T was the most common somatic RET mutation (n = 75). RET somatic mutations were associated with male sex, larger tumor size, advanced American Joint Committee Cancer (AJCC) stage, vascular invasion, and high International Medullary Thyroid Carcinoma Grading System (IMTCGS) grade. When compared with other RET somatic mutations, RETM918T was associated with younger age, AJCC (eighth edition) IV, vascular invasion, extrathyroidal extension, and positive margins. RET somatic or germ line mutations were significantly associated with reduced distant metastasis-free survival on univariate analysis, but there were no significant independent associations on multivariable analysis, after adjusting for tumor grade and stage. There were no significant differences in outcomes between RET somatic and RET germ line mutations, or between RETM918T and other RET mutations. Other recurrent molecular alterations included TP53 (4.2%), ARID2 (2.9%), SETD2 (2.9%), KMT2A (2.9%), and KMT2C (2.9%). Among them, TP53 mutations were associated with decreased overall survival (OS) and disease-specific survival (DSS), independently of tumor grade and AJCC stage. Conclusions: RET somatic mutations were associated with high-grade, aggressive primary tumor characteristics, and decreased distant metastatic-free survival but this relationship was not significant after accounting for tumor grade and disease stage. RETM918T was associated with aggressive primary tumors but was not independently associated with clinical outcomes. TP53 mutation may represent an adverse molecular event associated with decreased OS and DSS in MTC, but its prognostic value needs to be confirmed in future studies.

Thyroidectomy in Australia 2022: lessons from 21,000 consecutive cases.

In this article, we aim to describe our modern-day approach to total thyroidectomy, detailing the subtle refinements of our technique, as it has evolved over three decades and 21 000 cases. Since Delbridge's seminal paper in 2003, the major changes to our approach include a retrograde approach to the recurrent laryngeal nerve that allows dissection of the distal RLN from fascial bands within the ligament of Berry before medialisation of the thyroid lobe. Routine use of intraoperative nerve monitoring systems has increased our awareness of temporary neuropraxia, facilitated a reduction in the risk of bilateral RLN palsy and improved our identification and preservation of the external branch of the superior laryngeal nerve. The increasing use of advanced energy devices has been associated with a reduction in post-operative haematoma rates. We adopt a low threshold to parathyroid auto-transplantation, unless all glands are assessed to be clearly not at risk, and routinely supplement patients with Caltrate in the immediate post-operative period to minimize the risk of symptomatic hypocalcaemia. Ultimately, when we reflect on the subtle refinements that have contributed to improved outcomes, the fundamental principles of exposure and dissection that have evolved over decades remain the basis of our surgical approach and must continue to do so.