Adverse Events in Thyroid Surgery. Observational Study in Three Surgical Units With High Volume/Year.

Adverse Events in Thyroid Surgery. 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Observational Study in Three Surgical Units With High Volume/Year. Paolo Del Rio, Paolo Carcoforo, Fabio Medas, Elena Bonati, Tommaso Loderer, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-113254/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Thyroid surgery, performed for benign or malignant pathologies, is one of the most frequently performed procedures and its frequency has even been increasing in recent years. Postoperative bleeding, recurrent laryngeal nerve (RLN) palsy, associated to dysphonia, dysphagia, dyspnea, and hypoparathyroidism represent the most fearful and common complications. We conducted a multicenter, observational study of retrospectively collected data in three high-volume referral centers, enrolling all patients undergone to thyroid surgery between January 2016 and December 2017 in Parma University Hospital, Cagliari University Hospital and Ferrara University Hospital. Materials Patients were divided into 5 groups, differentiated thyroid carcinoma, medullary thyroid carcinoma, non-toxic benign pathology, hyperfunctioning benign pathology and NIFTP (Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features). A follow up at 7 and 30 days was executed, evaluating the onset of paresthesia, dysphonia and dysphagia. A six-month follow-up was conducted in cases of early complications. Results Totally, 1252 patients were eligible for the study: 907 female and 345 male, with a female to male ratio of 2.6:1 and an average age of 53.428. Total thyroidectomy was performed in 1022 cases, lobectomy in 230.After 6 months we recorded paresthesia in 0.5%, dysphonia in 1.8% and dysphagia in 0.5%. Conclusion Our study confirms once again that a share of morbidity escapes the possibilities of prediction and control by the operator, depending on patient anamnestic, pathological or anatomical factors. Surgery General Surgery vocal cord palsy thyroidectomy hypocalcemia postoperative bleeding dysphonia. Figures Figure 1 Figure 2 Figure 3 Introduction Thyroid surgery, performed for benign or malignant pathologies, is one of the most frequently performed procedures and its frequency has even been increasing in recent years with the increased incidence of differentiated thyroid cancer. The incidence of post thyroidectomy complications has steadily decreased in recent decades, thanks to technical improvements and technological advances, reaching the lowest rates in high-volume referral centers. ( 1 – 3 ) Postoperative bleeding, recurrent laryngeal nerve (RLN) palsy, associated to dysphonia, dysphagia, dyspnea, and hypoparathyroidism represent the most fearful and common complications. Capsular dissection, visual identification and intraoperative nerve monitoring have reduced the incidence of RLN injury to 1–2% in tertiary referral centers, showing that sometimes, neuronal damage must be consider an inevitable complication rather than a "surgical error". ( 4 , 5 ) Therefore, permanent complications can result in a marked deterioration in the patient's quality of life, affecting personal, social and working life. This is frequently cause of surgical malpractice claims. For this reason, many studies have tried to identify predictive factors for the possible onset of complications, including characteristics of patient, of underlying disease or of surgical technique. In our study, we wanted to overcome the population variability deriving from different geographic areas and the variability in the surgical habits of different surgical teams, including patients undergoing surgery in three high-volume referral centers. Methods We conducted a multicenter, observational study of retrospectively collected data in three high-volume referral centers, enrolling all patients undergone to thyroid surgery between January 2016 and December 2017 in Parma University Hospital, Cagliari University Hospital and Ferrara University Hospital. Totally, 1252 patients were eligible for the study. Collected data included patient demographics, anamnesis and clinical-instrumental-laboratory data, such as thyroid ultrasound pattern, preoperative diagnosis by ultrasound-guided fine needle aspiration (FNA) reported according to the Bethesda System for Reporting Thyroid Cytopathology ( 6 ), preoperative TSH, PTH and calcemic, X-ray trachea / CT neck, preoperative fibroscopy. Intraoperative data included type of surgery performed (total thyroidectomy or lobectomy), number of parathyroid glands seen during surgery, lymph node dissection, use of intraoperative neuromonitoring (IONM) hemostatic agents, intraoperative administration of corticosteroids. During hospitalization, bleeding, paresthesia, dysphonia, dysphagia, dyspnea, first day calcium value, first day PTH value, hospital therapy with intravenous calcium, oral calcium or corticosteroids, length of hospitalization were recorded. Paresthesia, dysphonia, dysphagia and dyspnea are subjectively reported by the patient during the clinical visit in case, respectively, of bilateral tingling in the extremities or perioral, voice alterations, alterations in swallowing, in particular fluids and breathing difficulties. After hospitalization, we assessed any therapy with calcium and vitamin D, post-operative fibroscopy, definitive histopathological diagnosis, tumor size, angiovascular invasion, infiltration of perithyroid tissues, metastatic lymph nodes, presence of parathyroid glands in the specimen, radiometabolic therapy and speech therapy. Based on definitive histological diagnosis, patients were divided into 5 groups, differentiated thyroid carcinoma, medullary thyroid carcinoma, non-toxic benign pathology, hyperfunctioning benign pathology and NIFTP (Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features). A follow up at 7 and 30 days was executed, through an outpatient visit, evaluating the onset of paresthesia, dysphonia and dysphagia. A six-month follow-up was conducted in cases of early complications. Only adult we included and patients previously undergone to thyroid surgery or presenting vocal cords pathologies on preoperative fibroscopy, were excluded from the study, as potential confounders. Univariate analysis was conducted to evaluate the influence of demographic, preoperative, intraoperative, and pathological factors on postoperative complications, as potential effect modifier. The studied factors included, depending on the complication under consideration, age, sex, high blood pressure, use of anticoagulant/antiaggregant, type of intervention, intraoperative administration of corticosteroids, use of suction drainages, use and findings of IONM, use of hemostatic agents, pathological diagnosis, postoperative calcemic and presence of parathyroid glands in the specimen. In case of missing data, patient was excluded from the analysis. Chi-squared test and Student’s t-test were used for categorical data and for continuous variables, respectively. Variables < 0.100 in the univariate analysis were considered significant and were then included in the multivariate analysis. Logistic regression analysis was used to identify independent risk factors of postoperative complications. Results were considered statistically significant if p-value was < 0.05. All analyses were carried out using IBM SPSS Statistics, version 19. Results Patients included in the study were 1252, 907 female and 345 male, with a female to male ratio of 2.6:1 and an average age of 53.428. Considering the site of the intervention, 474 procedure were executed at Parma University Hospital, 504 at Cagliari and 274 at Ferrara University Hospital. Patients with missing data were previously excluded from the study. Medium preoperative TSH was 1.562 uU/ml and calcium was 9.425 mg/dl. Demographic and preoperative laboratory tests are reported in Table 1. Preoperative cytological examination by FNA was performed in 715 patients and the result was reported according to the Bethesda System for Reporting Thyroid Cytopathology. ( 6 ) Results are reported in Table 2. Patients without nodularity at preoperative thyroid ultrasound examination did not undergo cytological examination. Total thyroidectomy was performed in 1022 cases, lobectomy in 230; in 130 patients, a lymph node dissection was also performed. NIM was used in 958 procedures, according to the habits of the different operating units. In fact, in two centers it was routinely used while in one it was used only in complex selected cases, such as neoplasms suspected for perithyroid infiltration, voluminous goiters, reoperations or laterocervical lymphadenomies. In 24 cases a loss of signal was recorded. Overall, 8.9% of patients underwent postoperative fibroscopy, which in one center was performed routinely while in the others only in case of persistent dysphonia 30 days after surgery. Speech therapy was necessary in 3.4% of cases. Complications arising on day 1, day 7, day 30 and at 6 months were then evaluated. On day 1, bleeding was found in 3.2% of patients, paresthesia in 6.4%, dysphonia in 4.8%. Calcemic in the first postoperative day showed an average value of 8.47 mg / dl, ranging from a minimum of 5 mg / dl to a maximum of 12 mg / dl. On the 7th day, paresthesia were found in 1.7% of cases, dysphonia in 4.4%, dysphagia in 0.9%. On day 30, paresthesia were found in 1.3% of patients, dysphonia in 3.8% and dysphagia in 0.3%. After 6 months we recorded paresthesia in 0.5%, dysphonia in 1.8% and dysphagia in 0.5%. The relationship between the type of surgery (lobectomy or total thyroidectomy) and the onset of complications at the various established follow-up steps (1st, 7th, 30th day and 6 months) was analyzed. (Table 3) Bleeding on day 1 occurred in 1.9% of patients undergoing lobectomy and in 3.7% of patients undergoing total thyroidectomy, with no statistically significant difference. Paresthesia occurred on day 1 in 0.9% of patients undergoing lobectomy, while in patients undergoing total thyroidectomy they occurred in 8%, thus showing a statistically significant correlation (p = 0.000). The correlation between dysphonia in day 1 and type of intervention also proved to be statistically significant, occurring in 5.9% of patients who underwent total thyroidectomy (5.9%), while only in 1.9% of lobectomy cases. Regarding the complications arising on day 7, 30 and after 6 months (paresthesia, dysphonia, dysphagia) no significant correlations emerged; however, there is a higher percentage of dysphonia among lobectomies (6.3%) compared to total thyroidectomies (3.7%), in all follow-up phases. Nevertheless, among patients undergoing lobectomy who presented dysphonia on day 7, a loss of NIM signal was recorded in 76.9%, there was no loss of IONM signal in 7.7% and the IONM has not been used in 15.4% As this is a retrospective study, it was not possible to trace which of these patients were originally enrolled for a total thyroidectomy and therefore how many procedures became lobectomies due to intraoperative NIM signal loss, according to the indications of the two stage thyroidectomy. ( 7 ) In the pre-IONM era, these cases would have relapsed into the group of patients undergoing total thyroidectomy. Considering the loss of NIM signal and the onset of dysphonia on the entire sample of patients, only one patient presented this association on the 1st postoperative day, while we found a statistically significant association on the 7th (p = 0.000) and 30th day (p = 0.000) and after 6 months (p < 0.001). It was then assessed whether the onset of paresthesia could correlate with the calcemic values detected on the 1st postoperative day. Paresthesia were recorded in 6.48% of cases in the first postoperative day. In patients without paresthesia on day 1, the calcium has an average value of 8.53 mg / dl, with a minimum of 7 mg / dl and a maximum 12 mg / dl, while in patients who presented paresthesia the average calcium is attests to a significantly lower value of 7.59 mg / dl on average, with a minimum value of 5 mg / dl and a maximum of 9 mg / dl. A correlation between the calcemic value in the first day and the development of paresthesia was highlighted in all the stages considered (p = 0.000 in the 1st, 7th and 30th day, p = 0.004 at 6 months). A correlation was sought between the onset of paresthesia and the presence of parathyroid glands in the surgical specimen. However, no statistically significant relationships emerged. In fact, only 9.2% of patients with presence of parathyroid glands at the definitive histological examination, presented paresthesia on the first day, on the 7th day 2.5% and on the 30th day 1.7%; on the other hand, among patients negative for the presence of parathyroid glands, paresthesia were recorded in 1.6% in day 7 and in 1.3% in 30th. After 6 months, among patients in whom the presence of parathyroid glands was found, there was not even one case of paresthesia, while 0.6% of those who did not have parathyroid glands accidentally removed at the final histological examination were recorded. The mean length of hospitalization was 2.459 days, showing a minimum of 1 day and a maximum of 14 days. Patients who experienced bleeding on day 1 had a hospital stay of 4.174 days while those who did not have bleeding reported a mean hospital stay of 2.076 days. Even the onset of paresthesia in the first day minimally prolonged hospitalization, with an average duration of 2.625 days compared to 2.265 days for patients without paresthesia. Similarly, the development of dysphonia in day 1 led to an average hospital stay of 3.730 days compared to 2.062 days for patients without dysphonia. Analyzing data with the Kruskall-Wallis test, a statistically significant difference was highlighted between the hospitalization of patients who presented at least one of the complications considered in the 1first day and the duration of hospitalization (p < 0.000 in all cases). Finally, we evaluated the possible association between thyroid disease, divided into 5 diagnostic categories (differentiated carcinoma, medullary carcinoma, non-hyperfunctioning benign disease, hyperfunctioning benign disease, NIFTP) and the onset of complications. The analysis found only a statistically significant correlation between the hyperfunctioning benign disease and the onset of bleeding and paresthesia in first postoperative day. Full results are shown in Table 4. At multivariate analysis, intraoperative corticosteroid administration (OR = 5.682; CI: 1.2329–26.1859; p = 0.025) and the use of haemostatic agent during surgery (OR = 2,928; CI: 1.1383–7.5345; p = 0.025) were found as independent risk factors for postoperative dysphonia (Fig. 1 ). Male sex (OR = 4.606; CI: 1.8132–11,7053; p = 0.001) was found as independent predictive factor for postoperative bleeding (Fig. 2 ); and a postoperative calcemia < 8.0 mg/dl (OR = 7.994; CI: 3.555–17.9763; p < 0.001) was identified as independent predictive factor for paraesthesia (Fig. 3 ). Discussion Thyroid surgery, although with a low incidence, can present some specific postoperative complications that have a strong impact on the patient's quality of life and are often a source of medico-legal dispute. The incidence rates reported in the literature are highly variable and primarily influenced by the surgeon's experience and by the volume of the center. All studies agree that operations performed by experienced surgeons and in high volume centers (> 100 thyroidectomies / year) show a lower complication rate and a shorter hospital stay. ( 8 ) In particular, it has been shown that the length of stay and complications are more determined by the surgeon experience than by hospital volume, which does not have a consistent association with the results. ( 3 ) Some study described also a threshold (> 25 total thyroidectomies/y) that identify a high-volume thyroid surgeon and it is associated with improved patient outcomes. ( 9 ) In our multicenter study, Parma, Cagliari and Ferrara University Hospital are high-volume referral centers and high-volume thyroid surgeons have executed all procedures included. This led to the finding of a low complication rate, uniform among the three centers despite differences in surgical practice, first in the use of the IONM. In particular, the average incidence of definitive dysphonia settles at 1.8% in our series, with literature reported rate from 0.7 to 5.65%. ( 10 – 13 ) Direct visualization of the RLN still remains the cornerstone of avoiding damage, while the non-visualization during dissection causes the highest risk for nerve palsy occurrence. No consensus exist regarding the utility of IONM. In particular, different studies have compared neural visualization and dissection alone to identification plus intraoperative use of NIM, without the evidence of any statistically significant difference. ( 14 – 17 ) Anaway, the routinary use of NIM has the enormous advantage to avoid bilateral palsy in case of loss of signal on the initial site, forcing to stop the operation. ( 18 – 20 ) After RLN palsy, the recovery of the nerve at one year is expected to be as high as 95% when the anatomic integrity is confirmed during the procedure. Consequently, the non-visualization of the nerve during dissection represents a striking risk factor for permanent damage. ( 10 ) Additionally, it has been reported that a large thyroid mass predicts a poor recovery after RLN injury, but this do not represent an independent risk factor for complications. ( 17 ) In our study, the use of hemostatic agents during surgery was found as independent risk factors for postoperative dysphonia, probably due to a greater use of coagulation instruments too in a more bloody operating field during procedure, with greater risk of thermal nerve injury, or due to the development of postoperative adhesions, which alter normal pharyngo-laryngeal mobility. The development of muscle adhesions, which impair mobility, can also causes an associated dysphagia. This complication has a more complex pathogenesis, related to trauma from orotracheal intubation, postoperative tissue swelling and presence of pre-existing functional gastroesophageal disorders. For the most part, however, these are transient disturbances, which recede spontaneously. ( 21 – 23 ) Minor surgical trauma and reduced postoperative pain could be responsible in part for the better vocal and swallowing outcomes found in patients operated with MIVAT technique. ( 24 , 25 ) Thyroiditis on pathology specimen is not associated with increased postoperative complications in our study, while the presence of thyroid hyperfunction is associated with both an increased rate of bleeding and transient hypoparathyroidism with paresthesia, as confirmed in literature. ( 26 – 29 ) Paraesthesias is the most frequent postoperative complication, related to the lowering of serum calcium levels in the postoperative period. It can be attributed to a number of causes, which can also coexist, such as hemodilution associated with surgical stress, decreased renal tubular reabsorption, vitamin D deficiency and acute increase in calcitonin levels. The main cause of hypocalcemia after thyroidectomy appears to be hypoparathyroidism. ( 30 – 32 ) Lymph node dissection and female gender are associated with this complication, as previously suggested in case series, but parathyroid function recovery is not affected by these factors. ( 33 – 36 ) Considering the lack of association between the accidental removal of parathyroid glands and the onset of paresthesias, which however correlate with the levels of calcium in the first postoperative day, our study seems to suggest that postoperative hypocalcemia depends on numerous surgical and personal factors of the patient, difficult to predict. Conclusions The possible complications resulting from thyroid surgery have a strong impact on patients and are frequently the cause of medico-legal disputes. Despite the technological improvement, the volume of the dedicated thyroid surgeon and the meticulous dissection and visualization of the intraoperative RLN, remain the gold standards for decreasing the incidence of complications. In our study, compared to an equal volume of centers involved and equal experience of surgeons, the different technologies or protocols routinely applied did not influence the outcomes. Overall, low complication rates were recorded, however not zero. This confirms once again that a share of morbidity escapes the possibilities of prediction and control by the operator, depending on patient anamnestic, pathological or anatomical factors. Declarations Ethics approval, guidelines and consent to participate : authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Institutional ethics board of Area Vasta Emilia Nord (AVEN) approved the study (NO.: 1155/2018/OSS/AOUPR, protocol number 2881 on 21/01/2019). The authors have produced the manuscript according to STROBE reporting check-list. An informed consent to participate in the study has been approved by the same institutional ethic board and obtained from participants. Consent for publication : not applicable. Availability of data and materials : the datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing interests : the authors have no competing interests to declare. Funding : none. Authors' contributions: (I) Conception and design: Del Rio P, PG Calò, Carcoforo P. (II) Administrative support: Bonati E. (III) Provision of study materials or patients: Bonati E, Koleva Radica M, Medas F (IV) Collection and assembly of data: Loderer T, Koleva Radica M, Medas F (V) Data analysis and interpretation: Bonati E, Medas F (VI) Manuscript writing: All authors (VII) Final approval of manuscript: All authors Acknowledgements : not applicable. 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Radio-guided selective compartment neck dissection improves staging in papillary thyroid carcinoma: A prospective study on 345 patients with a 3-year follow up. Surgery 2014;156(1):147–57. Del Rio P, Rossini M, Montana CM. et al. Postoperative hypocalcemia: analysis of factors influencing early hypocalcemia development following thyroid surgery. BMC Surg. 2019 Apr 24;18(Suppl 1):25. Tables Table 1. Demographic and preoperative laboratory tests. Mean Std Error 95% Confidence Interval for Mean 5% Trimmed Mean Median Std Deviation Minimum Maximum Lower Bound Upper Bound Age 53.428 0.4012 52.641 54.215 53.579 54.000 14.1954 18.00 89.00 Preoperative TSH 1.562 0.0396 1.484 1.639 1.452 1.309 1.2442 0.0 7.0 Preoperative serum calcium 9.425 0.0144 9.397 9.453 9.412 9.400 0.4517 8.0 12.1 Table 2. Preoperative cytological examination by fine needle aspiration (FNA), reported according to Bethesda System. Frequency Percent FNA Thyr 1 26 2.1 Thyr 2 195 15.6 Thyr 3 89 7.1 Thyr 4 205 16.4 Thyr 5 63 5.0 Thyr 6 137 10.9 Total 715 57.1 Non executed 537 42.9 Total 1252 100.0 Table 3. Postoperative complication and type of intervention. Hemithyroidectomy Total Thyroidectomy P value Bleeding Day 1 1.9% 3.7% 0.214 Parestesia Day 1 0.9% 8.0% 0.000 Day 7 1.4% 1.9% 0.700 Day 30 1.4% 1,3% 0.269 6 Months 0.5% 0.6% 0.900 Dysphonia Day 1 1.9% 5.9% 0.021 Day 7 6.3% 3.7% 0.129 Day 30 5.8% 3.0% 0.052 6 Month 2.9% 1.3% 0.139 Dysphnea Day 7 1.0% 0.9% 0.273 Day 30 0.5% 0.2% 0.483 6 Month 1.0% 0.4% 0.320 Table 4. Postoperative complication and histological diagnosis. CDT CM NT-BTD T-BTD NIFTP P value Bleeding Day 1 3.4% 0.0% 2.0% 15.8% 0.0% 0.014 Parestesia Day 1 8.4% 0.0% 4.0% 16.4% 0.0% 0.001 Day 7 2.2% 0.0% 1.3% 0.0% 0.0% 0.856 Day 30 1.9% 0.0% 0.8% 0.0% 0.0% 0.936 6 Months 0.3% 0.0% 0.5% 0.0% 0.0% 0.991 Dysphonia Day 1 4.3% 0.0% 5.3% 10.5% 0.0% 0.717 Day 7 4.7% 0.0% 4.4% 0.0% 0.0% 0.867 Day 30 3.1% 0.0% 4.4% 0.0% 0.0% 0.951 6 Month 1.3% 0.0% 2.1% 0.0% 0.0% 0.877 Dysphnea Day 7 0.9% 0.0% 0.5% 5.9% 0.0% 0.555 Day 30 0.3% 0.0% 0.0% 0.0% 0.0% 0.862 6 Month 0.3% 0.0 0.5% 0.0% 0.0% 0.990 CDT: differentiated thyroid carcinoma; CM: medullary carcinoma; NT-BTD: non-toxic benign thyroid disease, T-BTD: toxic benign thyroid disease; NIFTP: Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 12 May, 2021 Reviews received at journal 10 May, 2021 Reviews received at journal 17 Jan, 2021 Reviewers agreed at journal 03 Jan, 2021 Reviewers agreed at journal 09 Dec, 2020 Reviewers invited by journal 03 Dec, 2020 Editor assigned by journal 03 Dec, 2020 Editor invited by journal 03 Dec, 2020 Submission checks completed at journal 03 Dec, 2020 First submitted to journal 21 Nov, 2020 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-113254","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":5781722,"identity":"041e6bee-573d-4286-bb00-d3029515be33","order_by":0,"name":"Paolo Del Rio","email":"","orcid":"","institution":"University Hospital of Parma","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paolo","middleName":"Del","lastName":"Rio","suffix":""},{"id":5781723,"identity":"bf89cdf3-680b-4138-9751-e7fb4266ce2c","order_by":1,"name":"Paolo Carcoforo","email":"","orcid":"","institution":"University Hospital of Ferrara","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paolo","middleName":"","lastName":"Carcoforo","suffix":""},{"id":5781724,"identity":"6267401a-2a4b-48db-b693-d76c2da0aa62","order_by":2,"name":"Fabio Medas","email":"","orcid":"","institution":"University Hospital of Cagliari","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fabio","middleName":"","lastName":"Medas","suffix":""},{"id":5781725,"identity":"982ba04f-693a-46b9-84bd-fcc01720c3c9","order_by":3,"name":"Elena Bonati","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYDACdjB5AEJ+YGDgQXBxAWa4FmaGgzNgWvDqQdbCzAMTxaeFn5n52IMfDHfkzNnPHzxs23ZHxlz6AOPhD3i0SDazpRv2MDwztuxJZjic2/aMx7IvAb/DDA7zmEnwMBxO3HAArOUwj8EZAn6xP8z/TfIPSMv5xwyHLYnRYsDMwyYNtuUG0BZGYrRIHGYzk5YxeGZscOOxwcGec4d5LHsYGw6cwaOFv735meSbijtyBucTH3/4UXbY3pyH+fCHCjxaoM5DYTM2ENSAW/soGAWjYBSMAhAAABruUXLUp/xNAAAAAElFTkSuQmCC","orcid":"","institution":"University Hospital of Parma","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Bonati","suffix":""},{"id":5781726,"identity":"c53941c5-a5c3-438b-91b3-392c49bd1869","order_by":4,"name":"Tommaso Loderer","email":"","orcid":"","institution":"University Hospital of Parma","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tommaso","middleName":"","lastName":"Loderer","suffix":""},{"id":5781727,"identity":"88834ef9-c14a-41c2-8418-0602e50ffacc","order_by":5,"name":"Margherita Koleva Radica","email":"","orcid":"","institution":"University Hospital of Ferrara","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Margherita","middleName":"Koleva","lastName":"Radica","suffix":""},{"id":5781728,"identity":"cce34811-6eba-4911-aa07-35dd6d09872b","order_by":6,"name":"Piergiorgio Calò","email":"","orcid":"","institution":"University Hospital of Cagliari","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Piergiorgio","middleName":"","lastName":"Calò","suffix":""}],"badges":[],"createdAt":"2020-11-21 12:14:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-113254/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-113254/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":4068840,"identity":"e484c5a2-028e-4cde-9bcb-12a8ac301dd3","added_by":"auto","created_at":"2020-12-07 15:26:23","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":448640,"visible":true,"origin":"","legend":"Forest plot reporting results of multivariate analysis considering postoperative dysphonia as dependent variable.\nOR: odds ratio; HBP: high blood pressure; IO: intraoperative; ACT/AAG: anticoagulant/antiaggregant; LND: lymph node dissection; LOS: loss of signal; IONM: intraoperative nerve monitoring; DTC: differentiated thyroid carcinoma. X axis is reported in logarithmic scale.","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-113254/v1/d78bf5992110ba756eaf21d9.jpg"},{"id":4068841,"identity":"eed791f4-520f-42c9-946b-149c5ea79a75","added_by":"auto","created_at":"2020-12-07 15:26:24","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":379545,"visible":true,"origin":"","legend":"Forest plot reporting results of multivariate analysis considering postoperative bleeding as dependent variable.\nOR: odds ratio; HBP: high blood pressure; ACT/AAG: anticoagulant/antiaggregant; IO: intraoperative; LND: lymph node dissection. X axis is reported in logarithmic scale.","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-113254/v1/ae509c28198c28dae4a97670.jpg"},{"id":4068842,"identity":"73cbd22e-f269-4e6e-8442-296be6a29659","added_by":"auto","created_at":"2020-12-07 15:26:24","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":484248,"visible":true,"origin":"","legend":"Forest plot reporting results of multivariate analysis considering postoperative paraesthesia as dependent variable.\nOR: odds ratio; HBP: high blood pressure; ACT/AAG: anticoagulant/antiaggregant; LND: lymph node dissection; POD1: postoperative day 1; PG: parathyroid glands. X axis is reported in logarithmic scale.","description":"","filename":"figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-113254/v1/5c2ddaea94437363d170bc38.jpg"},{"id":13623998,"identity":"ef122f79-69c1-47c6-9415-ab5d5f3419c3","added_by":"auto","created_at":"2021-09-17 07:20:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":546516,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-113254/v1/c1d9461b-9c55-4520-b017-0280171d0aa3.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eAdverse Events in Thyroid Surgery. Observational Study in Three Surgical Units With High Volume/Year.\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eThyroid surgery, performed for benign or malignant pathologies, is one of the most frequently performed procedures and its frequency has even been increasing in recent years with the increased incidence of differentiated thyroid cancer.\u003c/p\u003e \u003cp\u003eThe incidence of post thyroidectomy complications has steadily decreased in recent decades, thanks to technical improvements and technological advances, reaching the lowest rates in high-volume referral centers. (\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003ePostoperative bleeding, recurrent laryngeal nerve (RLN) palsy, associated to dysphonia, dysphagia, dyspnea, and hypoparathyroidism represent the most fearful and common complications. Capsular dissection, visual identification and intraoperative nerve monitoring have reduced the incidence of RLN injury to 1\u0026ndash;2% in tertiary referral centers, showing that sometimes, neuronal damage must be consider an inevitable complication rather than a \"surgical error\". (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eTherefore, permanent complications can result in a marked deterioration in the patient's quality of life, affecting personal, social and working life. This is frequently cause of surgical malpractice claims.\u003c/p\u003e \u003cp\u003eFor this reason, many studies have tried to identify predictive factors for the possible onset of complications, including characteristics of patient, of underlying disease or of surgical technique. In our study, we wanted to overcome the population variability deriving from different geographic areas and the variability in the surgical habits of different surgical teams, including patients undergoing surgery in three high-volume referral centers.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eWe conducted a multicenter, observational study of retrospectively collected data in three high-volume referral centers, enrolling all patients undergone to thyroid surgery between January 2016 and December 2017 in Parma University Hospital, Cagliari University Hospital and Ferrara University Hospital.\u003c/p\u003e \u003cp\u003eTotally, 1252 patients were eligible for the study. Collected data included patient demographics, anamnesis and clinical-instrumental-laboratory data, such as thyroid ultrasound pattern, preoperative diagnosis by ultrasound-guided fine needle aspiration (FNA) reported according to the Bethesda System for Reporting Thyroid Cytopathology (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), preoperative TSH, PTH and calcemic, X-ray trachea / CT neck, preoperative fibroscopy.\u003c/p\u003e \u003cp\u003eIntraoperative data included type of surgery performed (total thyroidectomy or lobectomy), number of parathyroid glands seen during surgery, lymph node dissection, use of intraoperative neuromonitoring (IONM) hemostatic agents, intraoperative administration of corticosteroids.\u003c/p\u003e \u003cp\u003eDuring hospitalization, bleeding, paresthesia, dysphonia, dysphagia, dyspnea, first day calcium value, first day PTH value, hospital therapy with intravenous calcium, oral calcium or corticosteroids, length of hospitalization were recorded. Paresthesia, dysphonia, dysphagia and dyspnea are subjectively reported by the patient during the clinical visit in case, respectively, of bilateral tingling in the extremities or perioral, voice alterations, alterations in swallowing, in particular fluids and breathing difficulties.\u003c/p\u003e \u003cp\u003eAfter hospitalization, we assessed any therapy with calcium and vitamin D, post-operative fibroscopy, definitive histopathological diagnosis, tumor size, angiovascular invasion, infiltration of perithyroid tissues, metastatic lymph nodes, presence of parathyroid glands in the specimen, radiometabolic therapy and speech therapy.\u003c/p\u003e \u003cp\u003eBased on definitive histological diagnosis, patients were divided into 5 groups, differentiated thyroid carcinoma, medullary thyroid carcinoma, non-toxic benign pathology, hyperfunctioning benign pathology and NIFTP (Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features).\u003c/p\u003e \u003cp\u003eA follow up at 7 and 30 days was executed, through an outpatient visit, evaluating the onset of paresthesia, dysphonia and dysphagia. A six-month follow-up was conducted in cases of early complications.\u003c/p\u003e \u003cp\u003eOnly adult we included and patients previously undergone to thyroid surgery or presenting vocal cords pathologies on preoperative fibroscopy, were excluded from the study, as potential confounders.\u003c/p\u003e \u003cp\u003eUnivariate analysis was conducted to evaluate the influence of demographic, preoperative, intraoperative, and pathological factors on postoperative complications, as potential effect modifier. The studied factors included, depending on the complication under consideration, age, sex, high blood pressure, use of anticoagulant/antiaggregant, type of intervention, intraoperative administration of corticosteroids, use of suction drainages, use and findings of IONM, use of hemostatic agents, pathological diagnosis, postoperative calcemic and presence of parathyroid glands in the specimen. In case of missing data, patient was excluded from the analysis. Chi-squared test and Student\u0026rsquo;s t-test were used for categorical data and for continuous variables, respectively. Variables\u0026thinsp;\u0026lt;\u0026thinsp;0.100 in the univariate analysis were considered significant and were then included in the multivariate analysis. Logistic regression analysis was used to identify independent risk factors of postoperative complications. Results were considered statistically significant if p-value was \u0026lt;\u0026thinsp;0.05. All analyses were carried out using IBM SPSS Statistics, version 19.\u003c/p\u003e "},{"header":"Results","content":" \u003cp\u003ePatients included in the study were 1252, 907 female and 345 male, with a female to male ratio of 2.6:1 and an average age of 53.428. Considering the site of the intervention, 474 procedure were executed at Parma University Hospital, 504\u0026nbsp;at Cagliari and 274\u0026nbsp;at Ferrara University Hospital. Patients with missing data were previously excluded from the study.\u003c/p\u003e \u003cp\u003eMedium preoperative TSH was 1.562 uU/ml and calcium was 9.425\u0026nbsp;mg/dl. Demographic and preoperative laboratory tests are reported in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003ePreoperative cytological examination by FNA was performed in 715 patients and the result was reported according to the Bethesda System for Reporting Thyroid Cytopathology. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) Results are reported in Table\u0026nbsp;2. Patients without nodularity at preoperative thyroid ultrasound examination did not undergo cytological examination.\u003c/p\u003e \u003cp\u003eTotal thyroidectomy was performed in 1022 cases, lobectomy in 230; in 130 patients, a lymph node dissection was also performed.\u003c/p\u003e \u003cp\u003eNIM was used in 958 procedures, according to the habits of the different operating units. In fact, in two centers it was routinely used while in one it was used only in complex selected cases, such as neoplasms suspected for perithyroid infiltration, voluminous goiters, reoperations or laterocervical lymphadenomies. In 24 cases a loss of signal was recorded. Overall, 8.9% of patients underwent postoperative fibroscopy, which in one center was performed routinely while in the others only in case of persistent dysphonia 30 days after surgery. Speech therapy was necessary in 3.4% of cases.\u003c/p\u003e \u003cp\u003eComplications arising on day 1, day 7, day 30 and at 6 months were then evaluated. On day 1, bleeding was found in 3.2% of patients, paresthesia in 6.4%, dysphonia in 4.8%. Calcemic in the first postoperative day showed an average value of 8.47\u0026nbsp;mg / dl, ranging from a minimum of 5\u0026nbsp;mg / dl to a maximum of 12\u0026nbsp;mg / dl. On the 7th day, paresthesia were found in 1.7% of cases, dysphonia in 4.4%, dysphagia in 0.9%. On day 30, paresthesia were found in 1.3% of patients, dysphonia in 3.8% and dysphagia in 0.3%. After 6 months we recorded paresthesia in 0.5%, dysphonia in 1.8% and dysphagia in 0.5%.\u003c/p\u003e \u003cp\u003eThe relationship between the type of surgery (lobectomy or total thyroidectomy) and the onset of complications at the various established follow-up steps (1st, 7th, 30th day and 6 months) was analyzed. (Table\u0026nbsp;3)\u003c/p\u003e \u003cp\u003eBleeding on day 1 occurred in 1.9% of patients undergoing lobectomy and in 3.7% of patients undergoing total thyroidectomy, with no statistically significant difference. Paresthesia occurred on day 1 in 0.9% of patients undergoing lobectomy, while in patients undergoing total thyroidectomy they occurred in 8%, thus showing a statistically significant correlation (p\u0026thinsp;=\u0026thinsp;0.000). The correlation between dysphonia in day 1 and type of intervention also proved to be statistically significant, occurring in 5.9% of patients who underwent total thyroidectomy (5.9%), while only in 1.9% of lobectomy cases. Regarding the complications arising on day 7, 30 and after 6 months (paresthesia, dysphonia, dysphagia) no significant correlations emerged; however, there is a higher percentage of dysphonia among lobectomies (6.3%) compared to total thyroidectomies (3.7%), in all follow-up phases. Nevertheless, among patients undergoing lobectomy who presented dysphonia on day 7, a loss of NIM signal was recorded in 76.9%, there was no loss of IONM signal in 7.7% and the IONM has not been used in 15.4%\u003c/p\u003e \u003cp\u003eAs this is a retrospective study, it was not possible to trace which of these patients were originally enrolled for a total thyroidectomy and therefore how many procedures became lobectomies due to intraoperative NIM signal loss, according to the indications of the two stage thyroidectomy. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) In the pre-IONM era, these cases would have relapsed into the group of patients undergoing total thyroidectomy.\u003c/p\u003e \u003cp\u003eConsidering the loss of NIM signal and the onset of dysphonia on the entire sample of patients, only one patient presented this association on the 1st postoperative day, while we found a statistically significant association on the 7th (p\u0026thinsp;=\u0026thinsp;0.000) and 30th day (p\u0026thinsp;=\u0026thinsp;0.000) and after 6 months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eIt was then assessed whether the onset of paresthesia could correlate with the calcemic values detected on the 1st postoperative day. Paresthesia were recorded in 6.48% of cases in the first postoperative day.\u003c/p\u003e \u003cp\u003eIn patients without paresthesia on day 1, the calcium has an average value of 8.53\u0026nbsp;mg / dl, with a minimum of 7\u0026nbsp;mg / dl and a maximum 12\u0026nbsp;mg / dl, while in patients who presented paresthesia the average calcium is attests to a significantly lower value of 7.59\u0026nbsp;mg / dl on average, with a minimum value of 5\u0026nbsp;mg / dl and a maximum of 9\u0026nbsp;mg / dl. A correlation between the calcemic value in the first day and the development of paresthesia was highlighted in all the stages considered (p\u0026thinsp;=\u0026thinsp;0.000 in the 1st, 7th and 30th day, p\u0026thinsp;=\u0026thinsp;0.004\u0026nbsp;at 6 months).\u003c/p\u003e \u003cp\u003eA correlation was sought between the onset of paresthesia and the presence of parathyroid glands in the surgical specimen. However, no statistically significant relationships emerged. In fact, only 9.2% of patients with presence of parathyroid glands at the definitive histological examination, presented paresthesia on the first day, on the 7th day 2.5% and on the 30th day 1.7%; on the other hand, among patients negative for the presence of parathyroid glands, paresthesia were recorded in 1.6% in day 7 and in 1.3% in 30th.\u003c/p\u003e \u003cp\u003eAfter 6 months, among patients in whom the presence of parathyroid glands was found, there was not even one case of paresthesia, while 0.6% of those who did not have parathyroid glands accidentally removed at the final histological examination were recorded.\u003c/p\u003e \u003cp\u003eThe mean length of hospitalization was 2.459 days, showing a minimum of 1\u0026nbsp;day and a maximum of 14 days. Patients who experienced bleeding on day 1 had a hospital stay of 4.174 days while those who did not have bleeding reported a mean hospital stay of 2.076 days. Even the onset of paresthesia in the first day minimally prolonged hospitalization, with an average duration of 2.625 days compared to 2.265 days for patients without paresthesia. Similarly, the development of dysphonia in day 1 led to an average hospital stay of 3.730 days compared to 2.062 days for patients without dysphonia. Analyzing data with the Kruskall-Wallis test, a statistically significant difference was highlighted between the hospitalization of patients who presented at least one of the complications considered in the 1first day and the duration of hospitalization (p\u0026thinsp;\u0026lt;\u0026thinsp;0.000 in all cases).\u003c/p\u003e \u003cp\u003eFinally, we evaluated the possible association between thyroid disease, divided into 5 diagnostic categories (differentiated carcinoma, medullary carcinoma, non-hyperfunctioning benign disease, hyperfunctioning benign disease, NIFTP) and the onset of complications.\u003c/p\u003e \u003cp\u003eThe analysis found only a statistically significant correlation between the hyperfunctioning benign disease and the onset of bleeding and paresthesia in first postoperative day. Full results are shown in Table\u0026nbsp;4.\u003c/p\u003e \u003cp\u003eAt multivariate analysis, intraoperative corticosteroid administration (OR\u0026thinsp;=\u0026thinsp;5.682; CI: 1.2329\u0026ndash;26.1859; p\u0026thinsp;=\u0026thinsp;0.025) and the use of haemostatic agent during surgery (OR\u0026thinsp;=\u0026thinsp;2,928; CI: 1.1383\u0026ndash;7.5345; p\u0026thinsp;=\u0026thinsp;0.025) were found as independent risk factors for postoperative dysphonia (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMale sex (OR\u0026thinsp;=\u0026thinsp;4.606; CI: 1.8132\u0026ndash;11,7053; p\u0026thinsp;=\u0026thinsp;0.001) was found as independent predictive factor for postoperative bleeding (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e); and a postoperative calcemia\u0026thinsp;\u0026lt;\u0026thinsp;8.0\u0026nbsp;mg/dl (OR\u0026thinsp;=\u0026thinsp;7.994; CI: 3.555\u0026ndash;17.9763; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) was identified as independent predictive factor for paraesthesia (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eThyroid surgery, although with a low incidence, can present some specific postoperative complications that have a strong impact on the patient's quality of life and are often a source of medico-legal dispute.\u003c/p\u003e \u003cp\u003eThe incidence rates reported in the literature are highly variable and primarily influenced by the surgeon's experience and by the volume of the center. All studies agree that operations performed by experienced surgeons and in high volume centers (\u0026gt;\u0026thinsp;100 thyroidectomies / year) show a lower complication rate and a shorter hospital stay. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn particular, it has been shown that the length of stay and complications are more determined by the surgeon experience than by hospital volume, which does not have a consistent association with the results. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSome study described also a threshold (\u0026gt;\u0026thinsp;25 total thyroidectomies/y) that identify a high-volume thyroid surgeon and it is associated with improved patient outcomes. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our multicenter study, Parma, Cagliari and Ferrara University Hospital are high-volume referral centers and high-volume thyroid surgeons have executed all procedures included. This led to the finding of a low complication rate, uniform among the three centers despite differences in surgical practice, first in the use of the IONM. In particular, the average incidence of definitive dysphonia settles at 1.8% in our series, with literature reported rate from 0.7 to 5.65%. (\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDirect visualization of the RLN still remains the cornerstone of avoiding damage, while the non-visualization during dissection causes the highest risk for nerve palsy occurrence. No consensus exist regarding the utility of IONM. In particular, different studies have compared neural visualization and dissection alone to identification plus intraoperative use of NIM, without the evidence of any statistically significant difference. (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) Anaway, the routinary use of NIM has the enormous advantage to avoid bilateral palsy in case of loss of signal on the initial site, forcing to stop the operation. (\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) After RLN palsy, the recovery of the nerve at one year is expected to be as high as 95% when the anatomic integrity is confirmed during the procedure. Consequently, the non-visualization of the nerve during dissection represents a striking risk factor for permanent damage. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAdditionally, it has been reported that a large thyroid mass predicts a poor recovery after RLN injury, but this do not represent an independent risk factor for complications. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn our study, the use of hemostatic agents during surgery was found as independent risk factors for postoperative dysphonia, probably due to a greater use of coagulation instruments too in a more bloody operating field during procedure, with greater risk of thermal nerve injury, or due to the development of postoperative adhesions, which alter normal pharyngo-laryngeal mobility.\u003c/p\u003e \u003cp\u003eThe development of muscle adhesions, which impair mobility, can also causes an associated dysphagia. This complication has a more complex pathogenesis, related to trauma from orotracheal intubation, postoperative tissue swelling and presence of pre-existing functional gastroesophageal disorders. For the most part, however, these are transient disturbances, which recede spontaneously. (\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMinor surgical trauma and reduced postoperative pain could be responsible in part for the better vocal and swallowing outcomes found in patients operated with MIVAT technique. (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThyroiditis on pathology specimen is not associated with increased postoperative complications in our study, while the presence of thyroid hyperfunction is associated with both an increased rate of bleeding and transient hypoparathyroidism with paresthesia, as confirmed in literature. (\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eParaesthesias is the most frequent postoperative complication, related to the lowering of serum calcium levels in the postoperative period. It can be attributed to a number of causes, which can also coexist, such as hemodilution associated with surgical stress, decreased renal tubular reabsorption, vitamin D deficiency and acute increase in calcitonin levels. The main cause of hypocalcemia after thyroidectomy appears to be hypoparathyroidism. (\u003cspan additionalcitationids=\"CR31\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eLymph node dissection and female gender are associated with this complication, as previously suggested in case series, but parathyroid function recovery is not affected by these factors. (\u003cspan additionalcitationids=\"CR34 CR35\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eConsidering the lack of association between the accidental removal of parathyroid glands and the onset of paresthesias, which however correlate with the levels of calcium in the first postoperative day, our study seems to suggest that postoperative hypocalcemia depends on numerous surgical and personal factors of the patient, difficult to predict.\u003c/p\u003e "},{"header":"Conclusions","content":" \u003cp\u003eThe possible complications resulting from thyroid surgery have a strong impact on patients and are frequently the cause of medico-legal disputes. Despite the technological improvement, the volume of the dedicated thyroid surgeon and the meticulous dissection and visualization of the intraoperative RLN, remain the gold standards for decreasing the incidence of complications. In our study, compared to an equal volume of centers involved and equal experience of surgeons, the different technologies or protocols routinely applied did not influence the outcomes. Overall, low complication rates were recorded, however not zero.\u003c/p\u003e \u003cp\u003eThis confirms once again that a share of morbidity escapes the possibilities of prediction and control by the operator, depending on patient anamnestic, pathological or anatomical factors.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval, guidelines and consent to participate\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eauthors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Institutional ethics board of Area Vasta Emilia Nord (AVEN) approved the study (NO.: 1155/2018/OSS/AOUPR, protocol number 2881 on 21/01/2019). The authors have produced the manuscript according to STROBE reporting check-list. An informed consent to participate in the study has been approved by the same institutional ethic board and obtained from participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003ethe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003ethe authors have no competing interests to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(I) Conception and design: Del Rio P, PG Cal\u0026ograve;, Carcoforo P.\u003c/p\u003e\n\u003cp\u003e(II) Administrative support: Bonati E.\u003c/p\u003e\n\u003cp\u003e(III) Provision of study materials or patients: Bonati E, Koleva Radica M, Medas F\u003c/p\u003e\n\u003cp\u003e(IV) Collection and assembly of data: Loderer T, Koleva Radica M, Medas F\u003c/p\u003e\n\u003cp\u003e(V) Data analysis and interpretation: Bonati E, Medas F\u003c/p\u003e\n\u003cp\u003e(VI) Manuscript writing: All authors\u003c/p\u003e\n\u003cp\u003e(VII) Final approval of manuscript: All authors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003enot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eConzo G, Avenia N, Bellastella G. et al. The role of surgery in the current management of differentiated thyroid cancer. Endocrine. 2014;47:380\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiddings AE. The history of thyroidectomy. J R Soc Med. 1998;91(Suppl 33):3\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSosa JA, Bowman HM, Tielsch JM, Powe NR, Gordon TA, Udelsman R. The importance of surgeon experience for clinical and economic outcomes from thyroidectomy. Ann Surg. 1998;228:320\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGambardella C, Polistena A, Sanguinetti A. et al. Unintentional recurrent laryngeal nerve injuries following thyroidectomy: Is it the surgeon who pays the bill? Int J Surg. 2017 May;41 Suppl 1:S55-S59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eN.J. Hayward, S. Grodski, M. Yeung, W.R. Johnson and J. Serpell. Recurrent laryngeal nerve injuryin thyroid surgery: a review. ANZ J. 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Ann Surg. 2017 Feb;265(2):402\u0026ndash;407.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaher R, Lifante JC, Voirin N. et al; CATHY Study Group. Is it possible to limit the risks of thyroid surgery? Ann Endocrinol (Paris). 2015 Feb;76(1 Suppl 1):1S16-26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChiang FY, Wang LF, Huang YF, Lee KW, Kuo WR. Recurrent laryngeal nerve palsy after thyroidectomy with routine identification of the recurrent laryngeal nerve. Surgery. 2005 Mar;137(3):342\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosato L, Avenia N, Bernante P. et al.Complications of thyroid surgery: analysis of a multicentric study on 14,934 patients operated on in Italy over 5 years. World J Surg. 2004 Mar;28(3):271\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomusch O, Machens A, Sekulla C. et al.. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg. 2000 Nov;24(11):1335\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShindo ML, Wu JC, Park EE. Surgical anatomy of the recurrent laryngeal nerve revisited. Otolaryngol Head Neck Surg. 2005 Oct;133(4):514\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbadin SS, Kaplan EL, Angelos P. Malpractice litigation after thyroid surgery: the role of recurrent laryngeal nerve injuries, 1989\u0026ndash;2009. Surgery. 2010 Oct;148(4):718 \u0026ndash; 22; discussion 722-3. doi: 10.1016/j.surg.2010.07.019. Epub 2010 Aug 14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePisanu A, Porceddu G, Podda M, Cois A, Uccheddu A. Systematic review with meta-analysis of studies comparing intraoperative neuromonitoring of recurrent laryngeal nerves versus visualization alone during thyroidectomy. J Surg Res. 2014 May 1;188(1):152 \u0026ndash; 61. doi: 10.1016/j.jss.2013.12.022. Epub 2013 Dec 25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCal\u0026ograve; PG, Pisano G, Medas F. et al. Identification alone versus intraoperative neuromonitoring of the recurrent laryngeal nerve during thyroid surgery: experience of 2034 consecutive patients. J Otolaryngol Head Neck Surg. 2014 Jun 18;43(1):16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu CW, Sun H, Zhang G, Kim HY, Catalfamo A, Portinari M, Carcoforo P, Randolph GW, Chai YJ, Dionigi G. Staged Thyroidectomy: A Single Institution Perspective. Laryngoscope Investig Otolaryngol. 2018 Aug 9;3(4):326\u0026ndash;332.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCal\u0026ograve; PG, Medas F, Gordini L.et al.. Interpretation of intraoperative recurrent laryngeal nerve monitoring signals: The importance of a correct standardization. Int J Surg. 2016 Apr;28 Suppl 1:S54-8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDel Rio P, Cozzani F, Puteo N, Loderer T, Rossini M, Bonati E. IONM and thyroidectomy in benign thyroid disease. Analysis of adverse events. G Chir. 2019 May-Jun;40(3):174\u0026ndash;181.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGalluzzi F, Garavello W. Dysphagia following uncomplicated thyroidectomy: a systematic review. Eur Arch Otorhinolaryngol. 2019 Oct;276(10):2661\u0026ndash;2671. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00405-019-05599-y\u003c/span\u003e\u003c/span\u003e. Epub 2019 Aug 14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScerrino G, Tudisca C, Bonventre S et al.. Swallowing disorders after thyroidectomy: What we know and where we are. A systematic review. Int J Surg. 2017 May;41 Suppl 1:S94-S102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLombardi CP, D'Alatri L, Marchese MR. Et al.. Prospective electromyographic evaluation of functional postthyroidectomy voice and swallowing symptoms. World J Surg. 2012 Jun;36(6):1354\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDel Rio P, Cozzani F, Nisi PC, Loderer T, Piva G, Bonati E. IONM and minimally invasive videoassisted thyroidectomy. G Chir. 2018 Sep-Oct;34(5):291\u0026ndash;296.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiccoli P, Fregoli L, Rossi L. et al. Minimally invasive video-assisted thyroidectomy (MIVAT). Gland Surg. 2020 Jan;9(Suppl 1):S1-S5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J, Sun W, Dong W, et al. Risk factors for post-thyroidectomy haemorrhage: a meta-analysis. Eur J Endocrinol. 2017;176(5):591\u0026ndash;602.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEdafe O, Antakia R, Laskar N, Uttley L, Balasubramanian SP. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg. 2014;101(4):307\u0026ndash;320.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHallgrimsson P, Nordenstr\u0026ouml;m E, Bergenfelz A, Almquist M. Hypocalcaemia after total thyroidectomy for Graves' disease and for benign atoxic multinodular goitre. Langenbecks Arch Surg. 2012;397(7):1133\u0026ndash;1137.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWelch KC, McHenry CR. Total thyroidectomy: is morbidity higher for Graves' disease than nontoxic goiter?. 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Int J Endocrinol. 2020 Jul 22;2020:5162496.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSitges-Serra A, Ruiz S, Girvent M, Manj\u0026oacute;n H, Due\u0026ntilde;as JP, Sancho JJ. Outcome of protracted hypoparathyroidism after total thyroidectomy. Br J Surg. 2010 Nov;97(11):1687\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaek SH, Lee YM, Min SY, Kim SW, Chung KW, Youn YK. Risk factors of hypoparathyroidism following total thyroidectomy for thyroid cancer. World J Surg. 2013 Jan;37(1):94\u0026ndash;101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarcoforo P.,Portinari M.,Feggi L.,et al. Radio-guided selective compartment neck dissection improves staging in papillary thyroid carcinoma: A prospective study on 345 patients with a 3-year follow up. Surgery 2014;156(1):147\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDel Rio P, Rossini M, Montana CM. et al. Postoperative hypocalcemia: analysis of factors influencing early hypocalcemia development following thyroid surgery. BMC Surg. 2019 Apr 24;18(Suppl 1):25.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Demographic and preoperative laboratory tests.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable id=\"Tabb\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMean\u003c/div\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eStd Error\u003c/div\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e95% Confidence Interval for Mean\u003c/div\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5% Trimmed Mean\u003c/div\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMedian\u003c/div\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eStd Deviation\u003c/div\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMinimum\u003c/div\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eMaximum\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eLower Bound\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eUpper Bound\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eAge\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e53.428\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.4012\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e52.641\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e54.215\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e53.579\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e54.000\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e14.1954\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e18.00\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e89.00\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreoperative TSH\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.562\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0396\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.484\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.639\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.452\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.309\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.2442\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e7.0\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePreoperative serum calcium\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.425\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0144\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.397\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.453\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.412\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e9.400\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.4517\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e8.0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e12.1\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cbr /\u003eTable 2. Preoperative cytological examination by fine needle aspiration (FNA), reported according to Bethesda System.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabd\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFrequency\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003ePercent\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"7\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eFNA\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eThyr 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e26\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.1\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eThyr 2\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e195\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e15.6\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eThyr 3\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e89\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e7.1\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eThyr 4\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e205\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e16.4\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eThyr 5\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e63\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.0\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eThyr 6\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e137\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10.9\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e715\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e57.1\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNon executed\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e537\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e42.9\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTotal\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1252\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e100.0\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u0026nbsp;\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Postoperative complication and type of intervention.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable id=\"Taba\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eHemithyroidectomy\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eTotal Thyroidectomy\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eP value\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBleeding\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.7%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.214\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eParestesia\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e8.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.000\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.700\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1,3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.269\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6 Months\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.5%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.6%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.900\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDysphonia\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.021\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.7%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.129\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.8%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.052\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6 Month\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.139\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDysphnea\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.273\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.5%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.2%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.483\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6 Month\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.320\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Postoperative complication and histological diagnosis.\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tabc\" border=\"1\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCDT\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eCM\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNT-BTD\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eT-BTD\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eNIFTP\u003c/div\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eP value\u003c/div\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eBleeding\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e15.8%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.014\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eParestesia\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e8.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e16.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.001\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.2%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.856\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.8%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.936\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6 Months\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.5%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.991\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDysphonia\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 1\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e10.5%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.717\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.7%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.867\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e3.1%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e4.4%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.951\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6 Month\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e1.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e2.1%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.877\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDysphnea\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 7\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.5%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e5.9%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.555\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eDay 30\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.862\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e6 Month\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.3%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.5%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.0%\u003c/div\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cdiv class=\"SimplePara\"\u003e0.990\u003c/div\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eCDT: differentiated thyroid carcinoma; CM: medullary carcinoma; NT-BTD: non-toxic benign thyroid disease, T-BTD: toxic benign thyroid disease; NIFTP: Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features.\u003c/p\u003e\n\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"vocal cord palsy, thyroidectomy, hypocalcemia, postoperative bleeding, dysphonia.","lastPublishedDoi":"10.21203/rs.3.rs-113254/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-113254/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eThyroid surgery, performed for benign or malignant pathologies, is one of the most frequently performed procedures and its frequency has even been increasing in recent years. Postoperative bleeding, recurrent laryngeal nerve (RLN) palsy, associated to dysphonia, dysphagia, dyspnea, and hypoparathyroidism represent the most fearful and common complications. We conducted a multicenter, observational study of retrospectively collected data in three high-volume referral centers, enrolling all patients undergone to thyroid surgery between January 2016 and December 2017 in Parma University Hospital, Cagliari University Hospital and Ferrara University Hospital.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMaterials\u003c/strong\u003e Patients were divided into 5 groups, differentiated thyroid carcinoma, medullary thyroid carcinoma, non-toxic benign pathology, hyperfunctioning benign pathology and NIFTP (Non-invasive Follicular Thyroid neoplasm with Papillary-like nuclear features). A follow up at 7 and 30 days was executed, evaluating the onset of paresthesia, dysphonia and dysphagia. A six-month follow-up was conducted in cases of early complications.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eTotally, 1252 patients were eligible for the study: 907 female and 345 male, with a female to male ratio of 2.6:1 and an average age of 53.428. Total thyroidectomy was performed in 1022 cases, lobectomy in 230.After 6 months we recorded paresthesia in 0.5%, dysphonia in 1.8% and dysphagia in 0.5%.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eOur study confirms once again that a share of morbidity escapes the possibilities of prediction and control by the operator, depending on patient anamnestic, pathological or anatomical factors.\u003c/p\u003e","manuscriptTitle":"Adverse Events in Thyroid Surgery. Observational Study in Three Surgical Units With High Volume/Year.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-07 15:26:22","doi":"10.21203/rs.3.rs-113254/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-05-12T08:32:22+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-05-10T17:49:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-01-17T11:52:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"f0e07b4f-5546-4350-9d78-b5c049670480","date":"2021-01-03T08:57:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6d0a6118-861e-4ed0-8b08-e1acda6a5974","date":"2020-12-09T07:37:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-12-03T15:59:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-12-03T15:56:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-12-03T12:11:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-12-03T11:51:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Surgery","date":"2020-11-21T12:05:10+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bsur","sideBox":"Learn more about [BMC Surgery](http://bmcsurg.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bsur/default.aspx","title":"BMC Surgery","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5c284a3c-7dd3-4e8c-a392-8b0b4575add4","owner":[],"postedDate":"December 7th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":1356046,"name":"Surgery"},{"id":1356047,"name":"General Surgery"}],"tags":[],"updatedAt":"2021-08-28T21:44:03+00:00","versionOfRecord":[],"versionCreatedAt":"2020-12-07 15:26:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-113254","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-113254","identity":"rs-113254","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}