Key PointsQuestion
Is total thyroidectomy or thyroid lobectomy associated with better longitudinal health-related quality of life (HRQOL) of patients with low to intermediate risk of recurrence of differentiated thyroid cancer?
Findings
In this cohort study of 1060 patients, those who underwent total thyroidectomy reported more HRQOL problems at 1 and 3 months postoperatively than patients who underwent thyroid lobectomy. Nearly all the differences were not found at 6 and 12 months postoperatively.
Meaning
The findings of this study suggest that HRQOL may not be an important consideration in making decisions regarding surgery; however, if better HRQOL is requested as a short-term outcome, thyroid lobectomy may be preferable.
Importance
Owing to the good prognosis of differentiated thyroid cancer (DTC), guidelines recommend total thyroidectomy (TT) or thyroid lobectomy (TL) as surgical treatment for DTC with low to intermediate risk of recurrence. However, the association of these surgeries with the health-related quality of life (HRQOL) of patients with DTC with low to intermediate risk of recurrence is unclear.
Objective
To longitudinally compare the HRQOL of patients with DTC undergoing different surgeries.
Design, Setting, and Participants
This prospective observational longitudinal cohort study enrolled patients diagnosed with DTC with low to intermediate risk of recurrence at the First Affiliated Hospital, Sun Yat-sen University, China, from October 1, 2018, to September 31, 2019. Eligible patients were categorized into TL and TT groups according to the surgery they underwent. They were evaluated preoperatively and followed up at 1, 3, 6, and 12 months postoperatively using 3 HRQOL-related questionnaires (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0; Hospital Anxiety and Depression Scale; and Thyroid Cancer–Specific Quality of Life Questionnaire); serum thyrotropin levels, complications, and patient satisfaction were also monitored. Data were analyzed to compare the HRQOL of patients undergoing different surgeries at different time points.
Exposures
Total thyroidectomy or TL.
Main Outcomes and Measures
The primary end point was HRQOL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.0; Hospital Anxiety and Depression Scale; and Thyroid Cancer–Specific Quality of Life Questionnaire) at different time points, and the secondary end points were postoperative complications, thyrotropin level, and patient satisfaction.
Results
Of the 1060 eligible patients, 563 underwent TL (438 women [77.8%]; median [IQR] age, 38 [31-45] years), and 497 underwent TT (390 women [78.5%]; median [IQR] age, 38 [32-48] years). Compared with the TL group, including the 1- to 4-cm tumor subgroup, the TT group experienced more postoperative HRQOL problems at 1 and 3 months postoperatively. However, nearly all the differences disappeared at 6 and 12 months postoperatively.
Conclusions and Relevance
Results of this study suggest that HRQOL of patients with DTC with low to intermediate risk of recurrence is not associated with the extent of surgery, and HRQOL may not be an important consideration when making surgical decisions. If better HRQOL is requested in the short term, TL may be preferred.
The incidence of thyroid cancer has increased during the past few decades. From 1975 to 2009, the incidence of thyroid cancer in the US increased from 4.9 to 14.3 per 100 000 people.1 In 2021, an estimated 44 280 new cases of thyroid cancer and 2200 deaths associated with thyroid cancer have been projected to occur in the US.2
Differentiated thyroid cancer (DTC) is the predominant pathological type of thyroid cancer, accounting for approximately 80% to 90% of all cases,3 and comprises mainly papillary and follicular thyroid cancer. The 10-year overall survival rate in patients with DTC is 92%; for disease-specific survival, 99%; and for recurrence-free survival, 98%.4 Given the good prognosis of patients with DTC, achieving better health-related quality of life (HRQOL) should be considered and concerns regarding overtreatment are increasing.
Total thyroidectomy (TT) and thyroid lobectomy (TL) are the main surgical approaches to DTC with low to intermediate risk of recurrence. An increasing number of studies have found no association between the extent of surgery and prognosis of DTC, especially DTC tumors measuring 1 to 4 cm with low to intermediate risk of recurrence.4-8 The most common complications of thyroidectomy include recurrent laryngeal nerve injury, hypoparathyroidism, hematoma, and wound infection.9 Recently, there has been increased controversy regarding the optimal management of DTC.10-12 The issue is complications related to TT vs cancer residue and recurrence risks related to TL, both of which are associated with the HRQOL of patients with DTC.
In addition to the classic end points of oncological trials, such as survival and complication rates, HRQOL is also viewed as an important end point in the evaluation of clinical therapies and interventions.13 An increasing number of studies have been performed on the HRQOL of patients with DTC,10,14,15 but, to our knowledge, no prospective studies with large sample sizes have evaluated the association of surgical extent with the HRQOL of patients with DTC, including those with low to intermediate risk of recurrence. Therefore, this study aimed to prospectively compare the HRQOL of patients with DTC with low to intermediate risk of recurrence according to the extent of thyroidectomy longitudinally with a large sample size (the QDTC Study).
We enrolled patients diagnosed with DTC with low to intermediate risk of recurrence at the First Affiliated Hospital, Guangzhou, China, from October 1, 2018, to September 31, 2019. According to the American Thyroid Association Risk Stratification System of structural disease recurrence, we defined low to intermediate risk of recurrence as DTC with all of the following characteristics: no distant metastases, no macroscopic invasion of the tumor into the perithyroidal soft tissues (gross extrathyroidal extension), no macroscopic residual tumor, pathologic category N0 or N1 without metastatic lymph nodes measuring 3 cm or more at the largest dimension, and follicular thyroid cancer with 4 or fewer foci of vascular invasion. This prospective observational cohort study was approved by the Clinical Research and Animal Trials Ethics Committees of the First Affiliated Hospital, Sun Yat-sen University. All patients gave written informed consent; no financial compensation was provided.
The inclusion criteria were as follows: age 18 years or older, biopsy or surgical pathologic findings indicative of DTC, low to intermediate risk of recurrence, ability to read and write in Chinese, and willingness to adhere to scheduled follow-up. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
The exclusion criteria included undifferentiated/medullary thyroid cancer, mixed undifferentiated or medullary carcinoma components; tall cell, columnar cell, or hobnail variants; insular carcinoma; anaplastic thyroid cancer; DTC with a high risk of recurrence accompanied by other malignant tumors; prior thyroid surgery; and cognition and behavioral impairment.
All patients with possible thyroid cancer completed preoperative surveys and were categorized into the TT or TL group according to the surgery they underwent. Data on the following factors were collected: age, sex, educational level, marital status, surgical methods, pathologic types, other thyroid diseases, comorbidities, complications, serum thyrotropin levels, insurance conditions, employment status, and receipt of radioactive iodine therapy. Because HRQOL was related to ethnic customs, ethnicity information, defined by participants, was also collected; no further ethnicity data were collected. All of the above factors were considered potential confounders. After surgeries, according to inclusion and exclusion criteria, participants enrolled were asked to complete an online or paper version of the questionnaires at 1, 3, 6, and 12 months postoperatively. All questionnaires were distributed through email, postal mail, fax, and social media. A maximum of 3 reminders were sent via the above methods to increase the response rate. All participants were followed up at the next scheduled time irrespective of whether they responded at the previous time. Surveys involved 1 patient satisfaction questionnaire and 3 questionnaires on HRQOL: Hospital Anxiety and Depression Scale16; European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, version 3.017; and Thyroid Cancer–Specific Quality of Life Questionnaire.18 These 3 questionnaires are widely applicable to HRQOL-related studies and are available in Chinese languages. A brief introduction to the above questionnaires is in the eMethods in the Supplement.
Duplicate questionnaire data were eliminated to make sure no patient had inadvertently completed questionnaires twice. Continuous data are described using mean (SD) and/or median (IQR) as appropriate. Nominal data are described using numbers and percentages. The Wilcoxon rank sum test was used for intergroup comparison of continuous variables because all the variables did not pass the Shapiro test of normality, and the χ2 test or Fisher exact test was used for intergroup comparison of nominal variables, as appropriate. The HRQOL scores were longitudinal continuous data that were measured before surgery and 1, 3, 6, and 12 months postoperatively. Intergroup difference of HRQOL score distribution at each time point was tested separately by the Wilcoxon rank sum test. The generalized estimating equation was used for intergroup comparison of mean of HRQOL scores at each time point with adjustment of confounders, as well as comparisons of HRQOL scores at each time point postoperatively with those before surgery. The baseline variables that were different between groups before surgery were considered confounders. The generalized estimating equation was also used to explore the association of the thyrotropin level with HRQOL. The missing completely at random hypothesis of HRQOL scores was tested. The generalized estimating equation model was built using the observed data, and then the data set, with missing values replaced by neighbor observation, was used to fit the generalized estimating equation model to explore the robustness of the results. A prespecified subgroup analysis of patients with a 1- to 4-cm DTC tumor was performed. A 2-sided P value <.05 was considered statistically significant. The false discovery rate method was used to adjust P values of multiple tests. R program, version 3.5.1 (R Foundation for Statistical Computing) was used in statistical analysis. Detailed interpretation of generalized estimating equation model, false discovery rate adjustment, missing mechanism test, missing value imputation, and statistical power assessment is presented in the eMethods in the Supplement.
A total of 1446 patients with possible thyroid cancer completed the preoperative questionnaires. Excluding patients with benign pathologic test results, 1149 patients were diagnosed with DTC. After exclusion of patients with high-risk factors or those undergoing surgical procedures by different methods, 1060 patients were enrolled in this study (828 [78.1%] women, 232 [21.9%] men) (Figure 1). Overall median age was 38 [IQR, 31-47] years. Of 1060 patients, 863 (81.4%) returned completed questionnaires at 1 month, 792 (74.7%) at 2 months, 902 (85.1%) at 6 months, and 783 (73.9%) at 12 months postoperatively. The nonresponse rates of the TT vs TL groups were 16.9% vs 22.4% (P = .03) at 1 month, 26.6% vs 24.2% (P = .41) at 3 months, 14.7% vs 15.1% (P = .92) at 6 months, and 27.4% vs 25.6% (P = .56) at 12 months postoperatively. Good prognosis of DTC and complexity of the scales may explain the high nonresponse rates. Characteristics were nearly balanced between responders and nonresponders in the 2 treatment groups at different time points (eTables 1-4 in the Supplement). None of the enrolled patients died during the follow-up period.
Of the 1060 eligible patients, 563 (53.1%) underwent TL (438 women [77.8%]; median [IQR] age, 38 [31-45] years), and 497 (46.9%) underwent TT (390 women [78.5%]; median [IQR] age, 38 [32-48] years). Further participant characteristics are summarized in Table 1. Compared with patients in the TL group, those in the TT group were more likely to be married (427 [85.9%] vs 455 [80.8%]; P = .03), have a large tumor (>4 cm: 7 [1.4%] vs 2 [0.4%]; P < .001), undergo lymph node dissection (330 [66.4%] vs 264 [46.9%]; P < .001), and receive radioactive iodine therapy (90 [18.1%] vs 13 [2.3%]; P < .001). No statistically significant differences were found between groups in other baseline characteristics.
Comparison of HRQOL Between TT and TL
The HRQOL scores of the 2 groups at each time point are shown in Figure 2 and the eFigure in the Supplement. Except for cognitive function, social function, and financial difficulties, all HRQOL dimensions were similar between the 2 groups before surgery (eTable 5 in the Supplement). At 1 month postoperatively, the TT group reported more anxiety, depression, fatigue, pain, voice change, chills, and tingling, as well as neuromuscular, psychological, and sexual symptoms, and decreased physical, emotional, and social function, than the TL group (eTable 6 in the Supplement). At 3 months postoperatively, the TT group reported more anxiety, fatigue, appetite loss, financial difficulties, and neuromuscular, voice, sympathetic, and tingling symptoms with physical, role, and social dysfunction, than the TL group. The TT group also had a lower global HRQOL score than the TL group (eTable 7 in the Supplement). None of the differences were statistically significant at 6 months postoperatively (eTable 8 in the Supplement). The same was found at 1 year, except for sleep disturbance (P = .02) (eTable 9 in the Supplement). For example, at 1 and 3 months postoperatively, the TT group reported more anxiety vs the TL group (median [IQR], 1 month: 3 [1-6] vs 2 [0-5]; P = .02; 3 months: 3 [1-6] vs 2 [0-5]; P = .03). However, there were no significant differences in the anxiety dimension between the TT and TL groups at 6 and 12 months postoperatively (median [IQR], 6 months: 2 [0-5] vs 2 [0-5]; P = .86; 12 months: 3 [0-5] vs 3 [0-5]; P = .77) (eTable 7 in the Supplement).
After adjustment for marital status, tumor size, extent of lymph node dissection, and radioactive iodine treatment by the generalized estimating equation model, intergroup comparison of HRQOL showed similar results to those without adjustment (eTable 10 in the Supplement). When preoperative HRQOL was adjusted as a confounder in the generalized estimating equation model, results of intergroup comparisons were also similar (Table 2). Using a data set with missing values filled by neighbor observation, generalized estimating equation modeling still gave similar results (eTable 11 in the Supplement).
A total of 429 patients had tumor sizes of 1 to 4 cm; of these, 261 patients (60.8%) underwent TT and 168 patients (39.2%) underwent TL. Except for cognitive function, no difference was seen in the preoperative HRQOL among the TT and TL groups (median [IQR], 100 [88.33-100] vs 88.33 [66.67-100], P = .04) (eTable 12 in the Supplement). At 1 and 3 months postoperatively, patients undergoing TT reported significantly poorer HRQOL scores than those undergoing TL (eg, median [IQR] postoperative scores of anxiety at 1 month: 3 [1-6] vs 2 [0-4]; P = .007; 3 months: 3 [1-6] vs 2 [0-5]; P = .04) (eTable 13 and eTable 14 in the Supplement). All the variations in the HRQOL measures disappeared at 6 and 12 months postoperatively (eTable 15 and eTable 16 in the Supplement).
Longitudinal Evaluation of HRQOL
Every HRQOL dimension score measured at 1, 3, 6, and 12 months postoperatively was compared with that before surgery using the generalized estimating equation model. Within 12 months postoperatively, some HRQOL dimensions remained significantly different from preoperative levels (eg, anxiety [coefficient <0; P < .001] and depression [coefficient <0; P < .001]), and others recovered to preoperative levels (eg, physical function and voice) (Figure 2; the eFigure, eTable 17 in the Supplement).
Postoperative Complications, Thyrotropin Level, and Patient Satisfaction
Transient hypoparathyroidism and hoarseness (within 3 months postoperatively) were more prevalent in the TT group than in the TL group (hypoparathyroidism: 32.2% vs 6.2%; P < .001; hoarseness: 30.8% vs 21.1%; P = .002) (eTable 18 in the Supplement). There was no difference in the incidence of recurrent laryngeal nerve paralysis, hemorrhage, lymphatic leakage, and long-term hoarseness between the groups. The rates of well-controlled thyrotropin levels were higher in the TL group than in the TT group within 1 year postoperatively (1 month: 58.9% vs 45.5%; 3 months: 57.5% vs 40.1%; 6 months: 58.8% vs 35.9%; 12 months: 68.6% vs 38.8%; P < .001) (eTable 19 in the Supplement). Scores of some HRQOL dimensions were associated with thyrotropin level in the TT and TL groups (eTable 20 in the Supplement). There was no significant difference in patient satisfaction between TT and TL at 1 year postoperatively (eTable 21 in the Supplement).
Differentiated thyroid cancer is the predominant pathological type of thyroid cancer, accounting for approximately 80% to 90% of all cases.3 It is characterized by a good prognosis, with 10-year overall survival of 92% and disease-specific survival of 99%.4 Studies published in 2005 and thereafter found no difference in survival among patients with DTC undergoing TT or TL.5-8 An increasing number of studies also showed no prognostic advantage for TT over TL in DTC tumors measuring 1 to 4 cm5-7; thus, the 2015 revised American Thyroid Association guidelines adopted TL as an initial management option for low- to intermediate-risk DTC tumors measuring 1 to 4 cm,19 which is an alternative to TT or near-TT.
Health-related quality of life is defined as individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns.20 Given the similarly excellent prognosis in patients with DTC who undergo TT and TL, HRQOL has taken on greater importance. Thus, this prospective cohort study aimed to compare the HRQOL in patients with DTC with low to intermediate risk of recurrence undergoing different methods of thyroid surgeries longitudinally. Because debates have centered on the extent of surgery of patients with DTC tumors measuring 1 to 4 cm, this prespecified subgroup was further analyzed in our study. According to our findings, the TL group displayed better HRQOL in the short term than the TT group, and differences in nearly all HRQOL domains resolved in long-term follow-up. These findings also existed in the 1-cm to 4-cm DTC subgroup. Thus, long-term HRQOL may not help determine the best type of surgical procedure for these patients, including those in the 1- to 4-cm DTC subgroup. If better HRQOL is needed in the short term postoperatively, TL may be a better choice.
Our study indicated that scores on the questionnaires addressing neuromuscular symptoms, voice, chills, and tingling were higher in the TT group than those in the TL group in the short term after surgery. This difference may be associated with the higher incidence of complications in the TT group, such as transient hypoparathyroidism and hoarseness. Previous studies have found that transient hypocalcemia and vocal cord paralysis were significantly more prevalent after TT than after TL.9,21 Similarly, in our study, transient hypoparathyroidism and hoarseness were more common in the TT group than in the TL group, which may partially explain the reason why thyroid-specific symptoms were more common in the TT group than TL group in the short term. However, almost all the HRQOL differences disappeared at 6 and 12 months postoperatively. In examining this resolution, studies showed that the incidences of transient hypocalcemia and recurrent laryngeal nerve paralysis were much higher than those of permanent changes, and most of the complications resolved within 6 months postoperatively.22-25 The intergroup differences of HRQOL disappeared at 6 and 12 months after surgery, along with the complications. Thus, hoarse voice, chills, tingling, and neuromuscular symptoms caused by these complications may also regress.
Within a short period postoperatively, compared with those with TL, patients undergoing TT had more psychological burden, including anxiety and depression. One of the reasons for this increased burden may be that patients undergoing TT have higher rates of surgical complications,9,21 resulting in a decline in the belief that rehabilitation will be successful, which might be related more to emotional disorders. Another reason may be related to the fluctuation of serum thyrotropin levels after thyroidectomy. It was reported that thyroxine deficiency was related to emotional disorders,26,27 which could be eased by levothyroxine therapy.28,29 In the present study, the severity of anxiety, depression, and psychological problems was associated with the thyrotropin level, and more patients in the TL group had satisfactory thyrotropin levels than those in the TT group; thus, the fluctuation of thyrotropin levels may be partly responsible for the differences of psychological well-being between the 2 groups. In our study, patients displayed worse emotional status (eg, higher levels of anxiety) before surgery than after surgery. Because of the good prognosis, patients with DTC may experience a process of gradual psychological acceptance and a reduction in psychological stress. However, this assumption requires verification.
Patients with DTC undergo a time-consuming process to restore HRQOL to the preoperative level, but some domains cannot be reinstated to preoperative levels within 1 year. An increasing number of studies have reported similar findings on the change in postoperative HRQOL in patients with different cancers. In patients with laryngeal cancer, different surgical cohorts showed a general pattern of initial deterioration of most symptoms, followed by gradual recovery at 6 or 12 months after surgery.30-32 A similar HRQOL change tendency was also observed in patients with breast cancer,33 newly diagnosed ovarian cancer,34 or gynecological cancer.35 It is hypothesized that the differences between patients with DTC in the TT and TL groups may be narrowed or disappear with further follow-up; a longer follow-up period is needed for verification.
Previous studies compared the HRQOL of patients with DTC undergoing different thyroid surgeries and did not reach a consistent conclusion.10,14,15 A retrospective study suggested that HRQOL issues were more prevalent among patients with DTC undergoing TT than those undergoing TL.10 This study applied oral inquiry and summarized responses, which may result in the inducement bias and false-positive results. Similar to our results, a prospective study with a small sample size found that the HRQOL of patients with thyroid cancer was not affected by surgery methods at the 1-year follow-up.14 These 2 studies did not dynamically observe the HRQOL of participants. A prospective longitudinal cohort study with a small sample size of patients with papillary thyroid carcinoma revealed significant differences in HRQOL between the TT and TL groups in the short term, but the differences disappeared in the long-term follow-up,15 consistent with our conclusions. None of these 3 studies considered the association of complications and postoperative thyrotropin levels with HRQOL and patient satisfaction with surgical methods.
To our knowledge, this is the first prospective cohort study to focus on the HRQOL of patients with DTC with low to intermediate recurrence risk longitudinally. Compared with previous studies, the advantages of this study were the prospective design and large sample size, which provided sufficient statistical power and make our findings more reliable. In addition, comorbidities, complications, and patient satisfaction with a nonnegligible impact on HRQOL, were also adequately evaluated in different thyroid surgeries. We first attempted to focus on patient satisfaction, explain HRQOL by combining it with comorbidities and thyrotropin levels at different time points. In addition to global HRQOL and emotion instruments, we used the disease-specific scale, Thyroid Cancer–Specific Quality of Life Questionnaire, providing a more general and comprehensive assessment of HRQOL among patients with DTC with low to intermediate recurrence risk. Early detection of HRQOL-related symptoms empowers health care professionals to provide timely humanistic care, nursing intervention, and medical treatment, allowing for better medical service and better HRQOL for patients.
The study has limitations. First, this was a single-center study from a teaching hospital, resulting in enrollment of patients with more serious disease, with worse HRQOL at baseline and potentially limiting external validity. Second, a percentage of patients did not respond to questionnaires. The missing observations might induce attrition bias. However, via statistical tests, missing completely at random questionnaires were not rejected in most HRQOL dimensions, which could limit attrition bias. Third, the follow-up duration was relatively short, and long-term follow-up is required.
The findings of this study suggest the HRQOL of patients with DTC with low to intermediate risk of recurrence, including those with tumor size 1 to 4 cm, is not associated with the extent of surgery. Thus, postoperative HRQOL should not be considered when making decisions regarding surgery for patients with DTC. Longer-term HRQOL beyond 1 year requires further observational study with additional follow-up. If better HRQOL is needed in the short term postoperatively, TL may be preferred.
Accepted for Publication: October 5, 2021.
Published Online: December 22, 2021. doi:10.1001/jamasurg.2021.6442
Corresponding Authors: Weiming Lv, MD, Department of Breast and Thyroid Surgery (lvwm@mail.sysu.edu.cn), and Haipeng Xiao, PhD, Department of Endocrinology (xiaohp@mail.sysu.edu.cn), First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhong Shan Er Lu, Guangzhou, 510080, China.
Author Contributions: Drs Chen and Lv had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Chen, Li, Peng, Hong, Xu, and B. Lin contributed equally to this study.
Concept and design: Chen, Li, Hong, X. Liang, J. Liang, Xiao, Lv.
Acquisition, analysis, or interpretation of data: Chen, Peng, Hong, Xu, B. Lin, X. Liang, Y. Liu, J. Liang, Zhang, Ye, F. Liu, C. Lin, Xiao, Lv.
Drafting of the manuscript: Chen, Li, Hong, Xu, X. Liang, Y. Liu, J. Liang, Zhang, Ye, F. Liu, C. Lin, Lv.
Critical revision of the manuscript for important intellectual content: Chen, Li, Peng, Hong, B. Lin, X. Liang, J. Liang, Xiao, Lv.
Statistical analysis: Chen, Xu, B. Lin, X. Liang, J. Liang, Zhang, Lv.
Obtained funding: Li, Lv.
Administrative, technical, or material support: Chen, Li, Peng, Hong, X. Liang, Y. Liu, J. Liang, Ye, F. Liu, C. Lin, Xiao, Lv.
Supervision: Chen, Li, Hong, X. Liang, Xiao, Lv.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by the Guangdong Provincial Science and Technology Department Research Projects 2017A010105029 (Dr Lv) and 2016A040403049.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Xiaofeng Huang, BM (Clinical Trial Unit, First Affiliated Hospital, Sun Yat-sen University), and Fenghua Lai, MD (Department of Endocrinology, First Affiliated Hospital, Sun Yat-sen University), helped with the collection of questionnaires. Compensation was provided for their assistance.
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