Experience of sorafenib treatment in differentiated thyroid cancer from Taiwan.

BACKGROUND: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan. METHODS: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018. RESULTS: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II. CONCLUSION: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib.

Traction Injury of Recurrent Laryngeal Nerve During Thyroidectomy.

BACKGROUND: Loss of the neuromonitoring signal (LOS) during thyroidectomy signifies recurrent laryngeal nerve (RLN) injury, which is one of the common complications, especially by traction injury. Transient intraoperative LOS means spontaneous recovery of nerve function during surgery or within 6-month post-surgery. Few articles discuss intraoperative recovery time and transient LOS, and there is no consensus on the risk factors for RLN traction injury and its recovery course; thus, we wanted to determine the maximum intraoperative recovery time. MATERIALS AND METHODS: This retrospective study included patients who had undergone thyroidectomies at Tainan National Cheng Kung University Hospital between January 2015 and August 2018. A total of 775 patients (with 1000 nerves at risk) who underwent intermittent intraoperative neuromonitoring during thyroidectomy were included in this study. The LOS nerves were divided into 4 groups based on the LOS subtype and the intraoperative status of the recovery. The postoperative vocal cord function was determined by thyroid ultrasound and/or laryngoscope. All the patients would be followed up postoperatively in 2-3 days, 1 week, 2 weeks, and 4-6 weeks. RESULTS: LOS occurred in 67 of 775 (8.6%) patients and in 70 of 1000 nerves at risk (7.0%). There were 2 in 70 nerves (2.9%) with LOS type 1 (segmental nerve traction injury) with intraoperative recovery (Group 1), 5 (7.1%) with LOS type 1 without intraoperative recovery (Group 2), 47 (67.1%) with LOS type 2 (global injury) with intraoperative recovery (Group 3), and 16 (22.8%) with LOS type 2 without intraoperative recovery (Group 4). All LOS type 1 (segmental nerve injury) nerves had pathologic lesions near the RLN or vagus nerve, but none had invaded the nerves (p < 0.05). The resolving time intraoperatively in the 2 patients in Group 1 was 5 min and 10 min, respectively. The resolving time intraoperatively in Group 3 was 1-20 min, and the average time was 4.8 min. In Group 2, 3 injured nerves recovered within 6 weeks postoperatively, and 2 nerves in 12 weeks. In Group 4, all the 16 injured nerves recovered within 6 weeks postoperatively. CONCLUSION: Applying intermittent intraoperative neuromonitoring during thyroidectomy, traction recurrent laryngeal nerve injury still happened in 7.0%. 70% of the injured nerves recovered the function intraoperatively after releasing the traction, and the longest duration of recovery is 20 min.

Is Partial or Total Thyroidectomy Associated with Risk of Long-Term Osteoporosis: A Nationwide Population-Based Study.

BACKGROUND: Whether thyroidectomy contributes to osteoporosis (OP) and osteoporotic fracture (OF) is a subject of debate. This study aimed to determine the effect of thyroidectomy on the risk of OP and OF. METHODS: This retrospective cohort study is based on patient data between January 2000 to December 2005 from the National Health Insurance Research Database. Patients who underwent thyroidectomy were enrolled in the thyroidectomy cohort, and the control cohort was selected by propensity score matching at a ratio of 1:4. Incident OP and OF cases were identified until the end of 2013. The thyroidectomy cohort to control cohort adjusted hazard ratio (aHR) for OP/OF was assessed through multivariable Cox proportional hazard regression analysis. RESULTS: Totals of 1426 and 5704 patients were included in the thyroidectomy and control cohorts, respectively. The incidence density of OP was higher in the thyroidectomy cohort (7.91/1000 person-years) than in the control cohort (5.98/1000 person-years), with an aHR of 1.43 (95% CI 1.16-1.77, p < 0.05). Younger patients, women, and patients with comorbidities were at a higher risk. The risks of postoperative OP/OF were significantly increased in patients who received thyroxine treatment for more than 1 year, both in the partial thyroidectomy group and in the total and subtotal thyroidectomy group (aHR: 2.47, 95% CI: 1.42-2.31 vs. aHR: 1.84, 95% CI: 1.22-2.76). CONCLUSION: Thyroidectomy significantly increased the long-term risk of OP. Younger patients, women, patients with comorbidities, and patients receiving chronic thyroxin treatment should be monitored for changes in postoperative bone density.

Application of Tissue Aspirate Parathyroid Hormone Assay for Imaging Suspicious Neck Lesions in Patients with Complicated Recurrent or Persistent Renal Hyperparathyroidism.

BACKGROUND: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios. METHODS: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists. RESULTS: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value. CONCLUSIONS: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.

Leukoaraiosis and risk of intracranial hemorrhage and outcome after stroke thrombolysis.

BACKGROUND: The impact of leukoaraiosis on the risk of symptomatic intracerebral hemorrhage (SICH) after stroke thrombolysis is conflicting, and the data on Asian populations are lacking. Therefore, in this study, we assessed the association between leukoaraiosis and SICH, and the association between leukoaraiosis and the 90-day functional outcome in the Asian population. METHODS: Data were collected from a two-center prospective registry of acute ischemic stroke patients given intravenous tissue plasminogen activator between 2006 and 2014. A total of 614 pretreatment brain CT and 455 posttreatment MRI were retrospectively assessed using two different rating scales for the presence of leukoaraiosis. Outcome measures were the occurrence of SICH with three definitions and any hemorrhage after thrombolysis and functional outcome at 3 months. RESULTS: Of the 614 patients assessed, 30.3% showed severe leukoaraiosis on the baseline brain CT. The SICH rate was 4.6% - 7.2% based on different definitions, and overall, 24.9% of patients showed any post-tPA hemorrhage. No association was observed between the severity of leukoaraiosis and SICH, regardless of having used different leukoaraiosis rating scales or as assessment using different imaging modalities. However, severe leukoaraiosis was independently associated with poor functional outcome at 3 months (OR 1.96, 95% C1 1.24-3.11, P = 0.004) after adjustment for confounders. CONCLUSIONS: Our results showed no association between leukoaraiosis and the risk of SICH. Although the presence of severe leukoaraiosis predicted a poor functional outcome after stroke, IV thrombolysis might not be withheld in acute ischemic stroke patients solely based on the presence of severe leukoaraiosis on pre-thrombolytic CT scans.