Laryngeal Ultrasound Detects Vocal Fold Immobility in Adults: A Systematic Review.

Laryngeal ultrasound (US) is becoming widely accepted for assessing true vocal fold immobility (TVFI), a potential complication of laryngeal and thyroid surgery. The objective of this project is to perform a systematic review and meta-analysis of pooled evidence surrounding laryngeal US as a modality for diagnosing TVFI in adults at risk for the condition in comparison to laryngoscopy as a gold standard. Medical subject heading terms were used to search MEDLINE, Embase, Google Scholar, Web of Science, and the Cochrane Library for relevant citations from January 1, 2000, to June 30, 2020. Studies were included if they involved patients 16 years and older, where laryngeal US was compared to laryngoscopy for TVFI. Studies were excluded if there were insufficient data to compute a sensitivity/specificity table after attempting to contact the authors. Case reports, and case series were also excluded. The initial search returned 1357 citations. Of these, 109 were selected for review utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty citations describing 6033 patients were included in the final meta-analysis. A bivariate random effects meta-analysis was performed, revealing a pooled sensitivity for laryngeal US of 0.95 (95% confidence interval [CI] 0.88-0.98), a specificity of 0.99 (95% CI 0.97-0.99), and a diagnostic odds ratio of 1328.2 (95% CI 294.0-5996.5). The area under the curve of the hierarchical summary receiver operating characteristic curve was 0.99 (95% CI 0.98-1.00). Laryngeal US demonstrates high sensitivity and specificity for detecting VFI in the hands of clinicians directly providing care to patients.

Health-Related Quality of Life in Asian Differentiated Thyroid Cancer Survivors.

BACKGROUND: Health-related quality of life (HRQoL) is important for differentiated thyroid cancer survivors, but data for Asian survivors is lacking. This study aimed to have an overview of, and identify any disease-or treatment-related factors associated with, HRQoL in Asian differentiated thyroid cancer survivors. PATIENTS AND METHODS: Thyroid cancer survivors were recruited from the thyroid clinics at Queen Mary Hospital, Hong Kong from February 2016 to December 2016. All adult differentiated thyroid cancer patients with stable disease more than or equal to 1 year received a survey on HRQoL using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Thyroid cancer specific quality of life (THYCA-QoL) questionnaire. Clinical information was collected retrospectively from the computerized clinical management system. To identify factors associated with poor HRQoL, univariable and stepwise multivariable regression analysis were performed. RESULTS: A total of 613 survivors completed the questionnaires (response rate: 82.1%; female: 80.1%; median survivorship: 7.4 years (range: 1.0-48.2 years)). The QLQ-C30 summary score mean was 84.4 (standard deviation (SD): 12.7) while the THYCA-QoL summary score mean was 39.9 (SD: 9.7). The 2 highest symptom subscales were fatigue (mean: 26.4, SD: 20.6) and insomnia (mean: 26.2, SD: 27.6). Factors associated with worse HRQoL included serum thyrotropin (TSH) greater than 1.0 mIU/L, unemployment, and concomitant psychiatric disorders. Concomitant psychiatric illness (n = 40/613, 6.5%) also showed significant association with most of the symptom and functional subscales. CONCLUSIONS: Fatigue and insomnia were the 2 most common symptoms experienced by our differentiated thyroid cancer survivors. Long-term survivorship care with monitoring serum TSH level, supporting return-to-work and screening for concomitant psychiatric disorders should be offered.

Vocal Cord Palsies Missed by Transcutaneous Laryngeal Ultrasound (TLUSG): Do They Experience Worse Outcomes?

INTRODUCTION: Transcutaneous laryngeal ultrasound (TLUSG) is an innovative, non-invasive tool in detecting post-thyroidectomy vocal cord palsy (VCP). However, TLUSG failed to detect about 6-15% laryngoscopic examination (LE)-confirmed VCP. It is unclear whether the outcome of patients with VCP missed by TLUSG [false negative (FN)] is different from those with VCP diagnosed by TLUSG [true positive (TP)]. Therefore, this study aimed to compare the clinical outcome and prognosis between patients with FN results and TP results. METHODS: Over 46 months, all consecutive patients undergoing thyroidectomy or endocrine-related neck procedure were recruited. They underwent pre-operative and post-operative voice assessments on symptoms, voice-specific questionnaire [voice handicap index questionnaire (VHI-30)], TLUSG and LE. For patients with post-operative vocal cord palsy, reassessment LE would be arranged at second, fourth, sixth and twelfth months post-operatively until VCP recovered. RESULTS: In total, 1196 patients, including 74 post-thyroidectomy VCP, were recruited. For those with assessable vocal cords (VC), 58 VCP were correctly diagnosed by TLUSG (TP) and 10 VCP were missed by TLUSG (FN). Sensitivity and specificity of detecting a VCP by TLUSG were 85.3% and 94.7%, respectively. VHI-30 score was significantly increased after operation in TP group [31 (range - 6-105), p < 0.001] but not in FN group [20 (14-99), p = 0.089]. Comparing to TP group, VCP recovered earlier (69 vs. 125 days, p < 0.001) and less patients suffered from permanent VCP in patients with FN results. (34.5% vs. 0.0%, p = 0.027). CONCLUSION: The VCP missed by TLUSG had a milder course of disease. Early recovery of VC function and non-permanent palsy were expected.

Role of surgery in pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumours (PNETs) are rare. They are generally accepted to be slow-growing and have an indolent course. These tumours can be non-functioning or functioning, consisting of a biochemically heterogeneous group of tumours including insulinomas, gastrinomas, carcinoids and glucagonomas. Although surgery remains the mainstay of treatment, controversy still exists especially for non-functioning tumours <2 cm in size. Whether these should be resected or undergo intensive surveillance remains unclear. The surgical approach depends on local expertise. Many studies have shown comparable short-term surgical outcome with laparoscopic pancreatic resection compared to open techniques, however data on long-term oncological outcome are still lacking. On the other hand, liver metastasis occurs in as high as 80% of PNET patients. Five-year survival rate is only 30% if left untreated compared to 60-80% if complete resection is achieved. Current evidence supports liver resection with an aim for symptomatic control and to improve survival in those with respectable disease and no extra-hepatic metastasis. Palliative debunking can be considered in those with intractable symptoms. This article reviews the current evidence on pancreatic resection for PNETs, in particular the role of laparoscopic resection and the management of liver metastasis.

Effect of Thyroid Remnant Volume on the Risk of Hypothyroidism After Hemithyroidectomy: A Prospective Study.

BACKGROUND: Hypothyroidism is a common sequel after a hemithyroidectomy. Although various risk factors leading to hypothyroidism have been reported, the effect of the contralateral lobe's volume has been understudied. This study aimed to examine the association between the preoperative contralateral lobe's volume and the risk of postoperative hypothyroidism. METHODS: During a 2-year period, 150 eligible patients undergoing a hemithyroidectomy were evaluated. The volume of the contralateral nonexcised lobe was estimated preoperatively by independent assessors on ultrasonography using the following formula: width (in cm) × depth (in cm) × length (in cm) × (π/6), adjusted for the body surface area (BSA). Postoperative hypothyroidism was defined as serum thyroid-stimulating hormone (TSH) exceeding 4.78 mIU/L. Any significant characteristics in the univariate analysis were entered into the multivariate analysis to determine independent factors. RESULTS: After a mean follow-up period of 53.5 ± 9.4 months, 44 patients (29.3 %) experienced postoperative hypothyroidism, and 10 of these patients required thyroxine replacement. Hypothyroidism was associated with a higher preoperative TSH level (p < 0.001), a smaller BSA-adjusted volume (p < 0.001), fewer ipsilateral nodules (p = 0.037), and the presence of thyroiditis (p = 0.050). After adjustment for thyroiditis, preoperative TSH (p < 0.001), number of ipsilateral nodules (p = 0.048), and BSA-adjusted volume (p < 0.001) were independent factors for hypothyroidism. Patients with a BSA-adjusted volume smaller than 3.2 ml had a threefold greater hypothyroidism risk than those with a BSA-adjusted volume of 3.2 ml or more (p < 0.001). CONCLUSIONS: A significant inverse association between the preoperative contralateral lobe's volume and hypothyroidism risk was observed after hemithyroidectomy. Together with a higher preoperative TSH level and fewer ipsilateral nodules, a smaller BSA-adjusted volume measured by preoperative ultrasonography independently predicted hypothyroidism.

Systematic review and meta-analysis on intra-operative neuro-monitoring in high-risk thyroidectomy.

INTRODUCTION: Use of intra-operative neuro-monitoring (IONM) during high-risk thyroidectomy has been suggested to decrease the rate of recurrent laryngeal nerve (RLN) palsy. However, current evidences were mixed and there was no large-scale study concluding its benefit. We evaluated the role of IONM in reducing RLN palsy during high-risk thyroidectomy and identified which high-risk subgroup would be most benefited. METHODS: A systemic review was performed to identify studies comparing the use of IONM and visual identification of RLN alone (VA) during high-risk thyroidectomy, namely re-operation, thyroidectomy for malignancy, thyrotoxicosis or retrosternal goitre. Rate of RLN palsy was presented in terms of number of nerve-at-risk (NAR). Meta-analysis on overall high-risk thyroidectomy and subgroups were performed using fixed or random-effects model. RESULTS: Ten articles were eligible for final analysis. There were 4460 NARs in VA group and 6155 NARs in IONM group. Comparing to VA, IONM had lower rate of overall [4.5% vs. 2.5%, Odd ratio (OR): 1.40, 95% confidence interval (CI): 1.12-1.79, p = 0.003] and temporary [3.9% vs. 2.4%; OR: 1.47, 95% CI: 1.07-2.00, p = 0.016] RLN palsy in overall high-risk thyroidectomies. On subgroup analysis, although numbers of NARs were less than minimal numbers required for a statistical powered study (2.1%-72.7%), use of IONM decreased the rate of overall RLN palsy during re-operation (7.6% vs. 4.5%, OR: 1.32, p = 0.021) and temporary RLN palsy during thyroidectomy for malignancy (3.1% vs. 1.6%, OR: 1.90, p = 0.026). Use of IONM tended to have a lower rate of overall RLN palsy during thyroidectomy for malignancy than VA alone. (3.5% vs. 2.1%, p = 0.050). CONCLUSIONS: Selective use of IONM during high-risk thyroidectomy decreased the rate of overall RLN palsy. IONM should be applied during re-operative thyroidectomy and thyroidectomy for malignancy.

Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy.

BACKGROUND: Because the fluorescent light intensity on an indocyanine green fluorescence angiography reflects the blood perfusion within a focused area, the fluorescent light intensity in the remaining in situ parathyroid glands may predict postoperative hypocalcemia risk after total thyroidectomy. METHODS: Seventy patients underwent intraoperative indocyanine green fluorescence angiography after total thyroidectomy. Any parathyroid glands with a vascular pedicle was left in situ while any parathyroid glands without pedicle or inadvertently removed was autotransplanted. After total thyroidectomy, an intravenous 2.5 mg indocyanine green fluorescence angiography was given and real-time fluorescent images of the thyroid bed were recorded using the SPY imaging system (Novadaq, Ontario, Canada). The fluorescent light intensity of each indocyanine green fluorescence angiography as well as the average and greatest fluorescent light intensity in each patient were calculated. Postoperative hypocalcemia was defined as adjusted calcium <2.00 mmol/L within 24 hours. RESULTS: The fluorescent light intensity between discolored and normal-looking indocyanine green fluorescence angiographies was similar (P = .479). No patients with a greatest fluorescent light intensity >150% developed postoperative hypocalcemia while 9 (81.8%) patients with a greatest fluorescent light intensity ≤150% did. Similarly, no patients with an average fluorescent light intensity >109% developed PH while 9 (30%) with an average fluorescent light intensity ≤109% did. The greatest fluorescent light intensity was more predictive than day-0 postoperative hypocalcemia (P = .027) and % PTH drop day-0 to 1 (P < .001). CONCLUSION: Indocyanine green fluorescence angiography is a promising operative adjunct in determining residual parathyroid glands function and predicting postoperative hypocalcemia risk after total thyroidectomy.

Lessons Learned After 1000 Cases of Transcutaneous Laryngeal Ultrasound (TLUSG) with Laryngoscopic Validation: Is There a Role of TLUSG in Patients Indicated for Laryngoscopic Examination Before Thyroidectomy?

INTRODUCTION: Patients with hoarseness of voice, previous neck operation, or suspicion of malignancy are at high risk of having pre-thyroidectomy vocal cord (VCP) palsy. Therefore, vocal cord (VC) functions should be evaluated before surgery. This study aimed to evaluate the accuracy of hoarseness, a voice-related questionnaire (Voice Handicap Index [VHI]-30), and transcutaneous laryngeal ultrasound (TLUSG) in diagnosing VCP, as well as the role of TLUSG in the evaluation of high-risk patients. METHODS: A total of 1000 patients undergoing thyroidectomy or other endocrine-related neck procedures were prospectively included. Symptoms of hoarseness, the VHI-30 score, and TLUSG were evaluated. Validation laryngoscopies were performed by a separate endoscopist after performing TLUSG. All the assessments were performed one to seven days before surgery. The findings of hoarseness, the VHI-30 score, and TLUSG were correlated with laryngoscopic findings to evaluate the diagnostic accuracy. RESULTS: Of 1000 patients, nine preoperative VCP were diagnosed with laryngoscopy. Sensitivity in detecting VCP by hoarseness, the VHI-30 score, and TLUSG were 33.3%, 62.5%, and 88.9%, respectively. A total of 342 patients were considered as high risk, and eight preoperative VCP were confirmed with laryngoscopy. Despite it not being possible to visualize the VCs in 26 (7.7%) patients, TLUSG had a higher accuracy in detecting VCP than the VHI-30 did (96.8% vs. 74.2%; p < 0.001). If patients had been selected who were unassessable or who had had VCP on assessment for confirmatory laryngoscopy, TLUSG saved more patients from laryngoscopic examinations than the VHI-30 did (87.7% vs. 71.3%; p < 0.001). A history of neck operation and suspicion of malignancy did not affect the assessment by TLUSG (p > 0.05). CONCLUSION: TLUSG is a feasible, non-invasive, and sensitive tool in detecting VCP in high-risk patients. It has safely precluded 87.7% high-risk patients from laryngoscopy. TLUSG should be incorporated as a part of the ultrasound examination of the thyroid.

The Association of Discolored Parathyroid Glands and Hypoparathyroidism Following Total Thyroidectomy.

BACKGROUND: It remains uncertain whether a parathyroid gland (PG) that appears darkened or severely bruised but still has an attached vascular pedicle should be left in situ or taken out and auto-transplanted following total thyroidectomy. Our study aimed to examine the impact of discolored PGs (DPGs) on short- and long-term hypoparathyroidism. METHODS: One hundred and three patients who underwent total thyroidectomy with 4 clearly identified PGs were analyzed. Location (superior/inferior) and color of each PG were recorded. Patients without DPG were grouped into I while those with 1-2 DPGs and ≥3 DPGs were grouped into II and III, respectively. Transient hypoparathyroidism meant adjusted Ca <2.00 mol/L 24 h after surgery and/or need for supplements. Protracted hypoparathyroidism meant a subnormal PTH at 4-6 weeks and/or supplements >6 weeks. Permanent hypoparathyroidism meant supplements ≥1 year. RESULTS: Relative to I, group III had greater adjusted Ca drop at postoperative 1-h (p = 0.012), 24-h (p < 0.001) and lower day-1 PTH (p = 0.015). Having ≥3 DPGs (OR 14.00, 95 % CI 1.575-124.474, p = 0.018) was an independent factor of transient hypoparathyroidism. However, permanent hypoparathyroidism rate was higher than in group I than II (p = 0.019). Eight patients (25.8 %) in group I had undetectable day-1 PTH, while none in group III had undetectable day-1 PTH. Graves' disease/toxic goiter (OR 15.166, 95 % CI 2.594-88.661, p = 0.003) and excised gland weight (OR 1.028, 95 % CI 1.010-1.046, p = 0.003) were independent factors of ≥3 DPGs. CONCLUSIONS: PG discoloration is associated with transient hypoparathyroidism while normal colored PG with seemingly adequate blood supply does not always imply functionally normal gland. These findings highlights the need for a real-time intraoperative method to assess PG viability.

Using Transcutaneous Laryngeal Ultrasonography (TLUSG) to Assess Post-thyroidectomy Patients' Vocal Cords: Which Maneuver Best Optimizes Visualization and Assessment Accuracy?

To assess vocal cord (VC) movement with transcutaneous laryngeal ultrasound (TLUSG), three maneuvers, namely passive (quiet respiration), active (phonation), and Valsalva maneuvers have been described. It remains unclear which maneuver or using more maneuvers provides better visualization and assessment accuracy. We prospectively evaluated 342 post-thyroidectomy patients from two centers. They underwent TLUSG with direct laryngoscopic (DL) validation afterwards. During TLUSG, patients were instructed to perform all three maneuvers (passive, active, and Valsalva). VC visualization rate and accuracy between three maneuvers were compared. Visualization rate tended to be higher in Valsalva maneuver than that in other two maneuvers (92.1% vs. passive: 91.5%; active: 89.8%). While 19 patients had post-operative VC palsy, passive maneuver had lower test specificity than active (94.3 vs. 97.6%, p = 0.01) and Valsalva maneuvers (94.3 vs. 97.4%, p = 0.02). In assessable VCs, passive maneuver has a higher ability to differentiate between mobile VCs and VC palsy (Area under ROC curve--passive: 0.942, active: 0.863, Valsalva: 0.893). TLUSG with more maneuvers did not improve sensitivity or specificity. On applying TLUSG as a screening tool (i.e., only selected patient with "unassessable" VCs or VCP on TLUSG for DL), Valsalva maneuver (85.96%) saved more patients from DL than passive (81.87%) or active (84.81%) maneuver. Passive maneuver has a higher ability to differentiate VC palsy from normal. Using TLUSG as a screening tool, Valsalva was the preferred maneuver as it was more specific, had high visualization rate, and saved more patients from DL.

Determining the Learning Curve of Transcutaneous Laryngeal Ultrasound in Vocal Cord Assessment by CUSUM Analysis of Eight Surgical Residents: When to Abandon Laryngoscopy.

Transcutaneous laryngeal ultrasonography (TLUSG) is a promising alternative to laryngoscopy in vocal cords (VCs) assessment which might be challenging in the beginning. However, it remains unclear when an assessor can provide proficient TLUSG enough to abandon direct laryngoscopy . Eight surgical residents (SRs) without prior USG experience were recruited to determine the learning curve. After a standardized training program, SRs would perform 80 consecutive peri-operative VCs assessment using TLUSG. Performances of SRs were quantitatively evaluated by a composite performance score (lower score representing better performance) which comprised total examination time (in seconds), VCs visualization, and assessment accuracy. Cumulative sum (CUSUM) chart was then used to evaluate learning curve. Diagnostic accuracy and demographic data between every twentieth TLUSG were compared. 640 TLUSG examinations had been performed by 8 residents. 95.1% of VCs could be assessed by SRs. The CUSUM curve showed a rising pattern (learning phase) until 7th TLUSG and then flattened. The curve declined continuously after 42nd TLUSG (after reaching a plateau). Rates of assessable VCs were comparable in every twentieth cases performed. It took a longer time to complete TLUSG in 1st-20th than 21st-40th examinations. (45 vs. 32s, p = 0.001). Although statistically not significant, proportion of false-negative results was higher in 21st-40th (2.5%) than 1(st)-20th (0.6%), 41(st)-60th (0.7%), and 61(st)-80th (0.7%) TLUSG performed. After a short formal training, surgeons could master skill in TLUSG after seven examination and assess vocal cord function consistently and accurately after 40 TLUSG.

Bilateral Pheochromocytomas in MEN2A Syndrome: A Two-Institution Experience.

BACKGROUND: Bilateral pheochromocytoma (PHEO) is more frequently found in patients with multiple endocrine neoplasia 2A carrying a RET germline mutation located in codon 634 (C634). However, it is unclear whether different amino acid substitutions within C634 cause differences in bilateral PHEOs expression. We aimed to answer this by pooling data from two Asian institutions. METHODS: Sixty-seven patients had confirmed C634 germline mutation. Age-dependent penetrance of bilateral PHEO was calculated from date of birth to the date when bilateral PHEO was first diagnosed or when the contralateral gland became a PHEO (if the patient already had one adrenal gland removed). Age-dependent penetrance was estimated by the Kaplan-Meier method and compared by log-rank test. RESULTS: The 4 different amino acid substitutions included C634R (arginine) (n = 19, 28.4 %), C634Y (tyrosine) (n = 36, 38.8 %), C634G (glycine) (n = 4, 6.0 %), and C634W (tryptophan) (n = 8, 11.9 %). The age-related penetrance of PHEO was similar between C634R, C634Y, C634G, and C634W (by age 40, 69.8, 55.2, 25.0, and 56.2 %, respectively) (p = 0.529). However, the age-related penetrance of bilateral PHEO in C634R was significantly higher than C634Y (by age of 40, 59.3 % vs. 25.2 %, p = 0.046) or C634Y, C634G, and C634W combined (59.3 % vs. 21.5 %, p = 0.024). Nevertheless, the accumulative risk of bilateral PHEOs across all four C634 mutations almost approached 100 % over time. CONCLUSION: The accumulative risk of bilateral PHEOs almost reached 100 % but its onset was significantly earlier in C634R mutation. These findings implied that those with C634R mutation might benefit from earlier screening of contralateral PHEO than other C634 mutations after an unilateral adrenalectomy.

High False Positivity in Positron Emission Tomography is a Potential Diagnostic Pitfall in Patients with Suspected Adrenal Metastasis.

BACKGROUND: Although 18F-fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) is a potentially powerful, non-invasive imaging tool in differentiating adrenal metastasis from benign disease, some adenomas also exhibit high FDG uptake, therefore mimicking metastasis (i.e., false positives). We aimed to evaluate the accuracy of FDG-PET/CT based exclusively on histology and to identify risk factors for adrenal metastasis. METHODS: Among the 289 consecutive patients who underwent adrenalectomy, 39 (78.0%) patients had suspected solitary adrenal metastasis and had a positive preoperative FDG-PET/CT. The FDG-PET/CT findings were correlated with the histology of the excised adrenal gland. To identify risk factors for adrenal metastasis, characteristics were compared between patients with histologically proven adrenal metastasis and those without. Youden's index was used to calculate the optimal cut-off value for predicting adrenal metastasis. RESULTS: Histology of the excised adrenal tumor confirmed adrenal metastasis in 28/39 (71.8%) patients while non-metastatic lesions comprised mostly benign adrenal cortical adenoma (n=10) and one non-functional pheochromocytoma. Therefore, the overall false-positive rate of FDG-PET/CT was 28.2%. History of primary lung malignancy [odds ratio (OR) (95% CI) 20.00 (1.01-333.3), p=0.049] and SUVmax>2.65 [OR (95% CI) 31.606 (2.46-405.71), p=0.008] were independent risk factors for adrenal metastasis. CONCLUSIONS: Single adrenal uptake on FDG-PET/CT in suspected solitary adrenal metastasis was associated with a high false-positive rate (28.2%). Risk factors associated with adrenal metastasis included a history of known primary lung malignancy and a SUVmax>2.65 at the adrenal lesion of interest on FDG-PET/CT. Based on these findings, a new algorithm was constructed.

Long-term outcomes for older patients with papillary thyroid carcinoma: should another age cutoff beyond 45 years be added?

BACKGROUND: Although an age cutoff of 45 years has often been adopted to stratify cancer risk in papillary thyroid carcinoma (PTC), both cancer-specific survival (CSS) and disease-specific survival (DFS) continue to worsen beyond this cutoff. This study aimed to determine whether advanced age (i.e., >60 years) at diagnosis was an independent predictor of CSS and DFS in older (≥45 years) patients. METHODS: This study analyzed 407 PTC patients with a minimal follow-up period of 7 years. Standard protocol was followed. Both CSS and DFS were estimated using the Kaplan-Meier method and compared with the log-rank test. Variables shown to be significant by the log-rank test were entered into the Cox regression analysis. RESULTS: During a median follow-up period of 15.1 years, 51 patients (12.5 %) died of PTC, whereas 80 (20.5 %) experienced at least one recurrence. For CSS, age beyond 60 years (hazard ratio [HR], 3.027; 95 % confidence interval [CI] 1.369-6.690; p = 0.006), tumor size greater than 4 cm (HR 2.043; 95 % CI 1.141-4.255; p = 0.049), central nodal metastases (HR 2.726; 95 % CI 1.198-6.200; p = 0.017), lateral nodal metastases (HR 5.247; 95 % CI 2.987-9.216; p < 0.001), and distant metastases (HR 4.297; 95 % CI 1.726-2.506; p = 0.002) were independent predictors. For DFS, only tumor size greater than 4 cm (HR 1.733; 95 % CI 1.030-3.058; p = 0.049), central nodal metastases (HR 2.362; 95 % CI 1.010-5.523; p = 0.047), and lateral nodal metastases (HR 4.383; 95 % CI 2.388-8.042; p < 0.001) were independent predictors. CONCLUSIONS: Advanced age was an independent predictor of CSS, and cancer-related death risk showed a continuing increase beyond the age of 60 years. However, advanced age was not an independent predictor of DFS. Therefore, having another age cutoff appears justifiable for stratifying risk of cancer-related death but less justifiable for disease recurrence. Tumor size as well as central and lateral nodal metastases independently predicted CSS and DFS.

Assessing the Validity of Transcutaneous Laryngeal Ultrasonography (TLUSG) After Thyroidectomy: What Factors Matter?

INTRODUCTION: Although transcutaneous laryngeal ultrasound (TLUSG) is an excellent, noninvasive way to assess vocal cord (VC) function after thyroidectomy, some patients simply have "un-assessable" or "inaccurate" examination. Our study evaluated what patient and surgical factors affected assessability and/or accuracy of postoperative TLUSG. METHODS: Five hundred eighty-one consecutive patients were analyzed. All TLUSGs were done by one operator using standardized technique, whereas direct laryngoscopies (DL) were done by an independent endoscopist to confirm TLUSG findings. Their findings were correlated. TLUSG was "unassessable" if ≥1 VC could not be clearly visualized, whereas it was "inaccurate" if the TLUSG and DL findings were discordant. Demographics, body habitus, neck anthropometry, and position of incision were correlated with assessability and accuracy of TLUSG. RESULTS: Twenty-nine (5.0 %) patients had "unassessable" VCs; among the "assessable" patients, 29 (5.3 %) patients had "inaccurate" TLUSG. More than one-third (38.5 %) of VC palsies (VCPs) were "inaccurate." Older age (odds ratio [OR] = 1.055, 95 % confidence interval [CI] 1.016-1.095, p = 0.005), male sex (OR = 13.657, 95 % CI 2.771-67.315, p = 0.001), taller height (OR = 1.098, 95 % CI 1.008-1.195, p = 0.032), and shorter distance from cricoid cartilage to incision (OR = 0.655, 95 % CI 0.461-0.932, p = 0.019) were independent factors for "unassessable" VCs, whereas older age (OR = 1.028, 95 % CI 1.001-1.056, p = 0.040) was the only factor of incorrect assessment. CONCLUSIONS: Older age, male sex, tall in height, and incision closer to the thyroid cartilage were independent contributing factors for unassessable VCs, whereas older age was the only contributing factor for inaccurate postoperative TLUSG. Because more than one-third of VCPs were actually normal, patients labeled as such on TLUSG would benefit from laryngoscopic validation.

Pain and surgical outcomes with and without neck extension in standard open thyroidectomy: a prospective randomized trial.

BACKGROUND: The purpose of this study was to compare surgical outcomes between those patients who underwent open thyroidectomy with and without neck extension. METHODS: One hundred eighty patients were randomized into 2 groups, with neck extension (group I) and without neck extension (group II). Outcomes included pain score on postoperative day 0, day 1, and the first clinic visit, operating time, blood loss, recurrent laryngeal nerve (RLN) injury, and hypoparathyroidism. RESULTS: Pain scores in group II were significantly lower on postoperative day 1 (2.38 vs 3.08; p = .022) and at the first clinic visit (0.57 vs 0.78; p = .026). There was a significant direct correlation between degree of neck extension and pain score on day 1 (p = .159 and p = .033). Other outcomes seemed comparable. However, the overall RLN injury rate was not significantly different between the 2 groups (5.3% vs 2.0%; p = .212). CONCLUSION: Compared to group I, pain on postoperative day 1 and at the first visit in group II were significantly less, but both groups had similar overall RLN injury rate.

The importance of sonographic landmarks by transcutaneous laryngeal ultrasonography in post-thyroidectomy vocal cord assessment.

INTRODUCTION: During examination of the vocal cords (VC) using transcutaneous laryngeal ultrasonography (TLUSG), 3 sonographic landmarks (namely, false VC [FC], true VC [TC], and arytenoids [AR]) are often seen. However, it remains unclear which landmark provides a more reliable assessment and whether seeing more landmarks improves the diagnostic accuracy and reliability. METHODS: We evaluated prospectively 245 patients from 2 centers. One assessor from each center performed all TLUSG examinations and their findings were validated by direct laryngoscopy. All 3 sonographic landmarks were routinely visualized whenever possible. The rate of visualization and diagnostic accuracy between the 3 landmarks were compared. RESULTS: Eighteen patients suffered postoperative VC palsy (VCP). Both centers had comparable visualization or assessability rate of ≥ 1 sonographic landmark (94.9 and 95.3%; P = 1.000) and 100% sensitivity on postoperative TLUSG. The rates of FC, TC, and AR visualization were 92.7%, 36.7%, and 89.8%, respectively. The sensitivity, specificity, and diagnostic accuracy and the proportion of true positives, false positives, and true negatives between using 1, 2, landmarks and 3 landmarks were comparable (P > .05). CONCLUSION: Each sonographic landmark had similar reliability and diagnostic accuracy. Identifying all 3 sonographic landmarks was not mandatory and visualizing normal movement in one of the sonographic landmarks would be sufficient to exclude VCP.

Evaluating the efficacy of primary treatment for graves' disease complicated by thyrotoxic periodic paralysis.

Objective. Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of Graves' disease (GD). The present study compared the long-term efficacy of antithyroid drugs (ATD), radioactive iodine (RAI), and surgery in GD/TPP. Methods. Sixteen patients with GD/TPP were followed over a 14-year period. ATD was generally prescribed upfront for 12-18 months before RAI or surgery was considered. Outcomes such as thyrotoxic or TPP relapses were compared between the three modalities. Results. Eight (50.0%) patients had ATD alone, 4 (25.0%) had RAI, and 4 (25.0%) had surgery as primary treatment. Despite being able to withdraw ATD in all 8 patients for 37.5 (22-247) months, all subsequently developed thyrotoxic relapses and 4 (50.0%) had ≥1 TPP relapses. Of the four patients who had RAI, two (50%) developed thyrotoxic relapse after 12 and 29 months, respectively, and two (50.0%) became hypothyroid. The median required RAI dose to render hypothyroidism was 550 (350-700) MBq. Of the 4 patients who underwent surgery, none developed relapses but all became hypothyroid. Conclusion. To minimize future relapses, more definitive primary treatment such as RAI or surgery is preferred over ATD alone. If RAI is chosen over surgery, a higher dose (>550 MBq) is recommended.

Predictive factors and pattern of locoregional recurrence after prophylactic central neck dissection in papillary thyroid carcinoma.

BACKGROUND: Prophylactic central neck dissection (pCND) at the time of the total thyroidectomy (TT) remains controversial in clinically nodal-negative (cN0) papillary thyroid carcinoma. Our study was designed to examine the predictive factors and pattern of locoregional recurrence (LRR) after pCND in the context of the postoperative stimulated Tg (sTg) level. METHODS: A total of 341 patients who underwent TT and unilateral pCND were analyzed. Patients with an identifiable lesion on ultrasonography or whole-body scan within 6 months of surgery were excluded. LRR was defined as an identifiable lesion on USG, which was later confirmed by cytology/histology. Preablation sTg level was taken 2 months after surgery, whereas postablation sTg level was taken 8 months after surgery. Cox regression was used in the univariate and multivariate analyses to identify significant independent factors for LRR. RESULTS: After a follow-up of 66.6 ± 38.6 months, 14 (4.1 %) suffered from LRR. The duration to first LRR was 36.4 ± 21.7 months. The estimated 5- and 10-year LRR rates were 5.1 and 6.1 %, respectively. Of these 14 LRR, 3 (21.4 %) involved the central compartment alone, 9 (64.3 %) involved the lateral compartment alone, and 2 (14.3 %) involved both central and lateral compartments. After adjusting for other clinicopathological factors, postablation sTg level ≥ 1 µg/L (hazard ratio 265.109, 95 % confidence interval 1.132-62075.644, p = 0.045) was the only independent predictor of LRR. CONCLUSIONS: Annualized risk of LRR after pCND was approximately 1 % in the first 5 years and 0.2 % in the subsequent 5 years. Most (78.6 %) LRRs involved the lateral compartment. Postablation sTg ≥ 1 µg/L significantly predicted risk of LRR.