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.

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.

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.

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.

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.

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.

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.

A systematic review and meta-analysis comparing surgically-related complications between robotic-assisted thyroidectomy and conventional open thyroidectomy.

BACKGROUND: Despite gaining popularity, robotic-assisted thyroidectomy (RT) remains controversial. This systematic review and meta-analysis is aimed at comparing surgically-related complications between RT and conventional open thyroidectomy (OT). METHODS: A systematic review of the literature was performed to identify studies comparing surgically-related outcomes between RT and OT. Studies that compared ≥ 1 surgically-related outcomes between RT and OT were included. Outcomes included operating time, blood loss, complications, and hospital stay. Meta-analysis was performed using a fixed-effects model. RESULTS: Eleven studies were eligible but none were randomized controlled trials. Of the 2,375 patients, 839 (35.3 %) underwent RT, while 1,536 (64.7 %) underwent OT. RT was significantly associated with longer operating time (p < 0.001), hospital stay (p = 0.023) and higher temporary recurrent laryngeal nerve (RLN) injury (p = 0.016). Although there was no correlation between the number of RTs reported in the study and the rate of temporary RLN injury (p = -0.486, p = 0.328, respectively), routine perioperative laryngoscopy was performed in only 2 of 11 studies. Blood loss (p = 0.485), temporary (p = 0.333) and permanent (p = 0.599) hypocalcemia, hematoma (p = 0.602), and overall morbidity (p = 0.880) appeared comparable. Two (0.2 %) brachial plexus injuries in RT were reported in one study. CONCLUSIONS: Relative to OT, RT was associated with significantly longer operating time, longer hospital stay, and higher temporary RLN injury rate but comparable permanent complications and overall morbidity. Given some of the limitations with the literature and the potential added surgical risks and morbidity in RT, application of the robot in thyroid surgery should be carefully and thoroughly discussed before one decides on the procedure.

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.

Evaluating the cost-effectiveness of laryngeal examination after elective total thyroidectomy.

BACKGROUND: Although routine laryngeal examination (RLE) after thyroidectomy may cost more than selective laryngeal examination (SLE), it permits earlier detection and treatment of vocal cord palsy (VCP) and so may be cost-saving in the longer term. We compared the 2-year cost-effectiveness between RLE and SLE with RLE performed at 2 weeks (SLE-2w), 1 month (SLE-1m), and 3 months (SLE-3m) after thyroidectomy in the institution's perspective. METHODS: Our case definition was a hypothetical 50-year-old woman who underwent an elective total thyroidectomy for a benign multinodular goiter. A decision-analytic model was constructed to compare the estimated cost-effectiveness between RLE, SLE-2w, SLE-1m, and SLE-3m after a 2-year period. Outcome probabilities, utilities, and costs were estimated from the literature. The threshold for cost-effectiveness was set at US$50,000/quality-adjusted life-year. Sensitivity and threshold analyses were used to examine model uncertainty. RESULTS: RLE was not cost-effective because its incremental cost-effectiveness ratio to SLE-2w, SLE-1m, and SLE-3m were US$302,755, US$227,883 and US$247,105, respectively. RLE was only cost-effective when the temporary VCP rate increased >42.7 % or when the cost of RLE equaled zero. Similarly, SLE-2w was only cost-effective to SLE-3m when dysphonia for temporary VCP at 3 months increased >39.13 %, dysphonia for permanent VCP at 3 months increased >50.29 %, or dysphonia without VCP at 3 months increased >42.69 %. However, none of these scenarios appeared clinically likely. CONCLUSIONS: In the institution's perspective, RLE was not cost-effective against the other three SLE strategies. Regarding to the optimal timing of SLE, SLE-3m appears to be a reasonable and acceptable strategy because of its relative low overall cost.

A systematic review and meta-analysis comparing outcomes between robotic-assisted thyroidectomy and non-robotic endoscopic thyroidectomy.

BACKGROUND: Despite its feasibility, using the da Vinci robot in remote-access thyroidectomy remains controversial. This meta-analysis compared surgical and oncological outcomes between robotic-assisted thyroidectomy (RT) and non-robotic endoscopic thyroidectomy (ET). METHODS: A systematic review was performed to identify studies comparing outcomes between RT and ET. Outcomes included operating time, drain output, complications, number of central lymph nodes retrieved, and preablation stimulated thyroglobulin level. A random-effects model was used. RESULTS: Six studies were eligible. Of the 3510 patients, 2167 (61.7%) underwent RT whereas 1343 (38.3%) underwent ET. Despite a higher drain output (185.8 mLs versus 173.3 mLs, P = 0.019), RT had fewer temporary recurrent laryngeal nerve injury (2.6% versus 3.3%, P = 0.035) and shorter length of hospital stay (3.4 d versus 3.5 d, P = 0.030). In terms of oncological outcomes, despite higher incidence of multicentricity and larger tumors, the number of central lymph nodes retrieved during unilateral central neck dissection in RT was significantly greater than ET (4.5 ± 2.6 and 3.4 ± 2.5, P < 0.001) whereas the preablation stimulated thyroglobulin was comparable (0.8 ng/mL versus 1.1 ng/mL, P = 0.456). However, follow-up data were relatively scarce. CONCLUSIONS: Adding the robot in remote-access thyroidectomy was associated with a significantly lower risk of temporary recurrent laryngeal nerve injury and shorter length of hospital stay. However, despite achieving a comparable level of surgical completeness for low-risk differentiated thyroid carcinoma between RT and ET, this study highlighted the limitations with the current literature and the need for more prospective studies with adequate follow-up.

High pre-operative urinary norepinephrine is an independent determinant of peri-operative hemodynamic instability in unilateral pheochromocytoma/paraganglioma removal.

BACKGROUND: Peri-operative hemodynamic instability (HDI) may increase peri-operative morbidity in pheochromocytoma/paraganglioma (PPGL) patients. OBJECTIVE: This study aimed to determine which tumor-related risk factors could lead to peri-operative HDI in unilateral or single PPGL removal. METHODS: Before surgery, 66 PPGL patients had at least two sets of 24 h urine collected for fractionated catecholamine analysis. At surgery, an arterial line was inserted to record systolic blood pressure (SBP), diastolic BP, and mean arterial BP (MAP). Peri-operative HDI was defined as hypertension (SBP > 160 mmHg) and/or hypotension (SBP < 90 mmHg and/or MAP < 60 mmHg) for >10 consecutive minutes either intra-operatively or within the first 12 h after surgery. Urinary fractionated catecholamines and other variables were compared between those with peri-operative HDI (group I) and those without (group II). RESULTS: A total of 15 (22.7 %) patients belonged to group I, while 51 patients belonged to group II. One (1.5 %) patient died 9 days after surgery. Relative to group II, group I had significantly higher urinary norepinephrine (NE) (5,488.0 vs. 1,980.0 nmol/L, p < 0.001), urinary normetanephrine (5,130.9 vs. 3,853.4 nmol/L, p = 0.045), maximum SBP at operation (188.2 vs. 167.4 mmHg, p = 0.037), but lower MAP after operation (78.9 vs. 91.8 mmHg, p = 0.026). Urinary NE (OD 1.02, 95 % confidence interval [CI] 1.01-1.03, p = 0.046) was an independent risk factor for peri-operative HDI. The urinary NE level significantly correlated with maximum intra-operative SBP and MAP (r 0.692, p < 0.001; and r 0.669, p < 0.001, respectively) and inversely correlated with maximum post-operative MAP (r -0.305, p = 0.040). CONCLUSIONS: High pre-operative urinary NE was an independent tumor-related factor for peri-operative HDI and significantly correlated with sustained intra-operative hypertension and post-operative hypotension.

Is vocal cord asymmetry seen on transcutaneous laryngeal ultrasonography a significant predictor of voice quality changes after thyroidectomy?

BACKGROUND: Vocal cord asymmetry (VCA) on laryngoscopic examination (LE) may suggest voice impairment after thyroidectomy, but LE may cause patient discomfort. We aimed to correlate the presence of postoperative VCA assessed by noninvasive transcutaneous laryngeal ultrasonography (TLUSG) with voice quality changes after thyroidectomy. METHODS: A total of 169 patients scheduled for thyroidectomy completed two validated voice symptoms questionnaires-the GRBAS (grade, roughness, breathiness, asthenia, strain) scale and the voice impairment score (VIS)-and underwent TLUSG and LE at 1 day before and 7-10 days after thyroidectomy. Postoperative VCA was apparent in 51 patients on TLUSG (group I), whereas there was no VCA in the other 118 patients (group II, controls). The GRBAS scale and VIS results were compared between the groups. RESULTS: Before operation, the two groups had comparable preoperative GRBAS and VIS status. After operation, the "grade" and "roughness" components on the GRBAS scale were significantly worse in group I than in group II: 0.24 versus 0.07 (p = 0.016) and 0.33 versus 0.14 (p = 0.022), respectively. "Grade" and "roughness" in the GRBAS scale significantly worsened after the operation in group I: from 0.04 to 0.24 (p = 0.008) and from 0.02 to 0.33 (p = 0.001), respectively. They did not change in group II. Also, the overall VIS was significantly worse after thyroidectomy in group I: 4.97 versus 12.97 (p < 0.001). CONCLUSIONS: VCA seen on TLUSG significantly correlated with "grade" and "roughness" components on the GRBAS scale and the overall VIS. Thus, VCA might be used as a surrogate of postoperative voice changes.

Evaluating the incidence, clinical significance and predictors for vocal cord palsy and incidental laryngopharyngeal conditions before elective thyroidectomy: is there a case for routine laryngoscopic examination?

BACKGROUND: Routine preoperative laryngeal examination remains controversial. We aimed to assess the utility of preoperative routine flexible laryngoscopy (FL) by looking at the incidence, clinical significance and predictors for preoperative vocal cord paresis (VCP) and incidental laryngopharyngeal conditions (LPC) in our consecutive cohort. METHODS: A total of 302 patients underwent laryngeal examination by an independent otorhinolaryngologist and were specifically asked about voice/swallowing symptoms suggestive of VCP 1 day before surgery. As well as vocal cord (VC) mobility, the naso-pharynx and larynx were examined using FL. Any VCP and/or LPC was recorded. VCP was defined as reduced or absent movement in one or more VC. An LPC was considered clinically significant if the ensuing thyroidectomy was changed or deferred. RESULTS: Seven (2.3 %) patients had preoperative VCP, while an additional seven patients had an incidental LPC. Of the seven VCPs, five were caused by previous thyroidectomy, while two were caused by a benign goitre. The incidence of asymptomatic VCP in a previously non-operated cohort was 1/245 (0.41 %). Voice/swallowing symptoms (p = 0.033) and previous thyroidectomy (p < 0.001) were the two significant predictors for VCP. The seven incidental LPCs were vallecular cyst (n = 1), VC scar and polyp (n = 2), nasopharyngeal cyst and polyp (n = 3) and redundant arytenoid mucosa (n = 1); however, as they were benign, all seven patients proceeded to thyroidectomy as planned. CONCLUSIONS: Given the low incidence (0.41 %) of asymptomatic VCP in a previously non-operated cohort and that none of the seven LPCs were considered clinically significant, routine preoperative laryngoscopic examination should be reserved for those with previous thyroidectomy and/or voice/swallowing symptoms.

Does preoperative neutrophil lymphocyte ratio predict risk of recurrence and occult central nodal metastasis in papillary thyroid carcinoma?

BACKGROUND: Preoperative neutrophil to lymphocyte ratio (NLR) might be prognostic in papillary thyroid carcinoma (PTC). Given the controversy of prophylactic central neck dissection (pCND) in clinically nodal-negative (cN0) PTC, our study evaluated whether preoperative NLR predicted disease-free survival (DFS) and occult central nodal metastasis (CNM) in cN0 PTC. METHODS: A total of 191 patients who underwent pCND were analyzed. Complete blood counts with differential counts were taken before operation. NLR was calculated by dividing preoperative neutrophil count with lymphocyte count. Patients were categorized into NLR tertiles: first (NLR < 1.93; n = 63), second (NLR = 1.93-2.79; n = 64), and third tertile (NLR > 2.79; n = 64). Four other patient types, namely, benign nodular goiter, clinically nodal-positive (cN1) PTC, poorly differentiated thyroid carcinoma, and anaplastic thyroid carcinoma (ATC), were used as references. RESULTS: Age at operation (p < 0.001) and tumor size (p = 0.037) significantly increased with higher NLR. First tertile had significantly more TNM stage I tumors (p = 0.01) and lowest MACIS score (p = 0.002). Tumor size [hazard ratio (HR) 1.422, 95% confidence interval (CI) 1.119-1.809, p = 0.004] and multicentricity (HR = 2.545, 95% CI 1.073-6.024, p = 0.034) independently predicted DFS, whereas old age [odds ratio (OR) 1.026, 95% CI 1.006-1.046, p = 0.009), male (OR 2.882, 95% CI 1.348-6.172, p = 0.006), and large tumor (OR 1.567, 95% CI 1.209-2.032, p = 0.001) independently predicted occult CNM. NLR was not significantly associated with DFS or occult CNM. ATC had significantly higher NLR than cN1 PTC (7.28 vs. 2.74, p < 0.001). CONCLUSIONS: Although a higher NLR may imply a poorer tumor profile, it was not significantly associated with a worse DFS or higher risk of occult CNM in cN0 PTC. Perhaps, future research should focus on the prognostic value in other thyroid cancer types with a poorer prognosis.

A comparison of surgical morbidity and scar appearance between gasless, transaxillary endoscopic thyroidectomy (GTET) and minimally invasive video-assisted thyroidectomy (VAT).

BACKGROUND: The gasless, transaxillary endoscopic thyroidectomy (GTET) and minimally invasive video-assisted thyroidectomy (VAT) are both well-recognized endoscopic thyroid procedures, but how their postoperative outcomes are compared remains unclear. The present study was designed to compare surgical morbidities/complications and scar appearance between GTET and VAT at our institution. METHODS: Of the 141 patients eligible for endoscopic thyroidectomy, 96 (68.1 %) underwent GTET and 45 (31.9 %) underwent VAT. Patient demographics, indications, operative findings, pain scores on days 0 and 1, and surgical morbidities were compared between the two groups. At 6 months after surgery, all patients were asked about their satisfaction on the cosmetic result by giving a score (Patient Satisfaction Score or PSS) and their scar appearance was assessed by the 11 domains in the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: GTET was associated with a significantly longer operating time (84 vs. 148 min, p = 0.005), higher pain scores on days 0 and 1 (2.9 vs. 2.3, p = 0.042 and 2.2 vs. 1.7, p = 0.033, respectively), overall recurrent laryngeal nerve (RLN) injury (6.3 vs. 0 %, p = 0.043), and overall morbidity rates (12.5 vs. 2.2 %, p = 0.049) than VAT. The actual individual score for the 11 domains in POSAS and for PSS remained similar between the two groups. They remained similar even when patients with morbidity were excluded. CONCLUSIONS: GTET was a technically more challenging procedure and was associated with longer hospital stay, longer operating time, more immediate pain, and increased overall RLN injury and morbidity than VAT. The 6-month POSAS and PSS were similar between the two procedures.