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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 55  |  Issue : 1  |  Page : 23-32
 

Surgical outcomes of thyroid cancer patients in a tertiary cancer center in India


1 Department of Head and Neck Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
2 Department of Nuclear Medicine, Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
3 Clinical Research Secretariat, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication23-Aug-2018

Correspondence Address:
Dr. Anuja Deshmukh
Department of Head and Neck Surgical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijc.IJC_528_17

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 » Abstract 


Background: Surgery is the mainstay in the management of thyroid cancer. Surgical outcomes need to be tempered against the excellent prognosis of the disease. Aims: This study aims to study the surgical outcomes including the 30-day morbidity and 5-year survival of thyroid cancer patients. Settings and Design: Retrospective analysis of a prospectively maintained surgical database in a tertiary cancer center in India. Materials and Methods: We analyzed 221 surgically treated patients in the year 2012. Statistical Analysis: Used IBM SPSS 24.0 (Armonk, NY) with p < 0.05. Results: The median age was 40 years with predominantly papillary thyroid carcinoma (55%). Localized disease in 47% of cases, locoregional disease in 42.5% and distant metastasis in 10.2% of cases at presentation was noted. Treatment naïve patients were 71% and revision surgeries were done in 29% patients. Extended thyroidectomy constituted 11% of the surgeries. Temporary hypocalcemia was seen in 30.8% of patients, 5% requiring intravenous calcium supplementation. Vocal cord palsy as per nerve at risk and chyle leak were seen in 4.5% and 3.1%, respectively. Aggressive histology, extended thyroidectomy, and inadvertent parathyroidectomy were significant factors associated with complications. Five year estimated overall survival with median follow-up of 50 months was 98%, and event-free survival was 84.8%. Advanced age, distant metastasis at presentation and aggressive histology connoted poor outcomes. Conclusion: Thyroid cancer, irrespective of the extent of disease, has good prognosis. Aggressive histology, the extent of thyroid surgery, distant metastasis and age are important factors, which should be factored in the algorithm of thyroid cancer management.


Keywords: Complication, surgery, survival, thyroid cancer


How to cite this article:
Deshmukh A, Gangiti K, Pantvaidya G, Nair D, Basu S, Chaukar D, Pai P, Nair S, Hawaldar R, Dusane R, Chaturvedi P, D'Cruz A. Surgical outcomes of thyroid cancer patients in a tertiary cancer center in India. Indian J Cancer 2018;55:23-32

How to cite this URL:
Deshmukh A, Gangiti K, Pantvaidya G, Nair D, Basu S, Chaukar D, Pai P, Nair S, Hawaldar R, Dusane R, Chaturvedi P, D'Cruz A. Surgical outcomes of thyroid cancer patients in a tertiary cancer center in India. Indian J Cancer [serial online] 2018 [cited 2018 Dec 17];55:23-32. Available from: http://www.indianjcancer.com/text.asp?2018/55/1/23/239602





 » Introduction Top


The spectrum of thyroid cancer ranges from one of the most indolent cancers to one of the most virulent cancers. A surge in the incidence of thyroid cancer has been observed in the last few decades. In the western world, most of the newly diagnosed cancers are microcarcinomas. However, in India, we see a combination of both early and advanced presentation of thyroid cancers.

Globally, the annual estimated incidence of thyroid cancer is 298,102 in the year 2012. In India, the incidence is 3960 for men and 9944 for women. The incidence of age-standardized ratio is 0.7 for males (World 1.7) and 1.7 for females (World 6.1).[1]

Surgery is the mainstay in the management of thyroid cancer. The dilemma faced by the clinician is how to appropriately treat this cancer while balancing the indolent nature of the disease with the posttreatment sequelae and complications. In this study, we present the surgical data extracted from a prospectively maintained database.


 » Materials and Methods Top


We retrospectively reviewed the prospectively maintained database of 30-day morbidity of thyroid surgeries performed between January 2012 and December 2012.

The demographic pattern, clinical presentation, treatment details, 30-day morbidity, mortality and survival outcomes at 5 years were analyzed. A majority of the patients were from Mumbai and rest of Maharashtra (30.7%), followed by those from West Bengal 63 (28%).

Physical examination and diagnostic workup

All patients were evaluated by clinical examination. Thyroid-specific investigations were done as per the institution policy.[2] These included serum T3, T4, thyroid-stimulating hormone, ultrasound of the neck, fine-needle aspiration cytology (FNAC) of thyroid nodule, computed tomography (CT) with contrast and positron emission tomography with CT when indicated. All patients underwent vocal cord examination before surgery.

Surgery

In 2012, the Head and Neck Oncology Department followed the ATA 2009 guidelines[3] and the 7th edition of AJCC TNM staging system.[4] The FNAC, frozen section and final histopathologic diagnosis were used to decide the extent of the surgery.

Patients with low-risk disease underwent a hemithyroidectomy, whereas high-risk patients underwent total thyroidectomy. Intermediate risk patients were treated by hemithyroidectomy or total thyroidectomy depending on various factors. Most of the surgeries were done without any optical magnification.

The treatment decisions regarding neck dissection and central compartment clearance were taken based on the findings of clinico-radiology, intraoperative assessment, frozen section diagnosis and poor prognostic features of the thyroid cancer. Being a tertiary referral cancer center, the majority of our patients had advanced tumors and underwent a prophylactic central compartment clearance. Any devascularized gland was autotransplanted into the sternocleidomastoid muscle.

Morbidity and mortality data collection

The 30-day morbidity was documented in the surgical audit. Major complications were defined as any patient developing vocal cord palsy, who required intravenous calcium supplementation, or surgical reexploration under general anesthesia. Minor complication was defined as any patient who required only oral calcium supplementation or conservative management for any complication without a prolonged hospital stay.

Patients symptomatic for hypocalcemia were classified as those requiring intravenous calcium preparation or oral supplements alone depending on the severity of symptoms along with corrected calcium levels. None of the patients were given calcium preoperatively as a prophylaxis or treated empirically with oral calcium supplements. None of the patients were given any vitamin D supplementation preoperatively. Ionized calcium or parathyroid hormone assay was not done to assess hypocalcemia. All patients were postoperatively assessed for vocal cord mobility.

Histopathology assessment

Histopathology was reported for all patients.

Adjuvant treatment

Radioiodine ablation, radiotherapy and chemotherapy were used as adjuvant treatment as per the risk stratification and protocol. Radioiodine scanning and treatment were offered to intermediate and high-risk patients. Adjuvant radiotherapy to the primary and metastatic sites was offered on a case-to-case basis.

Statistical methods

Data were presented as mean ± (standard deviation), median (range) and frequency (percentage). Categorical data were analyzed using the Chi-square test or Fisher's Exact test (for binary data). Logistic regression was used as multivariate technique. Survival plot was calculated using Kaplan–Meier and compared between groups using log-rank test. For multivariate survival analysis, we used Cox multiple regression was employed. p <0.05 was considered statistically significant. Statistical Package for Social Sciences, version 24.0 (SPSS v 24.0) (Armonk, NY, USA: IBM Corp) was used for analysis.

The overall survival (OS) is defined as the duration from the date of surgery until death from any cause. The event-free survival (EFS) was calculated by Kaplan–Meier method. Any recurrence or progression of distant metastasis to new anatomical site or death was considered as an event. The EFS was calculated as the duration from the surgery date to the event date.


 » Results Top


A total of 619 patients were registered in the Head and Neck Oncology Department of Tata Memorial Hospital in 2012. A total of 262 surgeries were performed from January to December 2012. Of 262 surgical procedures, 35 surgeries (13 benign histology, 6 synchronous or metachronous squamous second primaries, 1 inoperable poorly differentiated locally invasive disease and 15 with incomplete information) were excluded from the final analysis. Thus, a total of 227 surgical procedures were analyzed for surgical morbidity. Six patients underwent hemithyroidectomy followed by completion total thyroidectomy (due to high-risk factors on histopathology) as a second procedure. For survival analysis, 221 patients were considered. The demographic details of the patients are shown in [Table 1].
Table 1: Demographics (n=221)

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Bony distant metastasis was the most common presentation followed by lung metastases. Six patients had hypothyroidism and one patient was on medication for hyperthyroidism. Forty patients had medical comorbidities at presentation.

The details and extent of the surgery performed are shown in [Table 2]. Central compartment clearance done for 81% of patients of which 47.6% had bilateral clearance. The mean number of nodes retrieved was 4.98 (1–29). In 14 (6.2%) patients, the recurrent laryngeal nerve (RLN) was sacrificed for disease clearance. Ten patients had mobile vocal cord before surgery, however RLN was sacrificed.
Table 2: Treatment details (procedures, n=227)

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[Table 3] shows the histopathological characteristics. Aggressive histology (tall cell variant, poorly differentiated thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer) was seen in 23 (10%) patients. Number of disconnected parathyroids included intentional devascularized parathyroid disconnection for autotransplantation and inadvertent parathyroid glands found in the final histopathological examination. [Table 4] shows the pathological staging and risk stratification.
Table 3: Histopathological characteristics

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Table 4: Pathological staging and risk stratification

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Surgical morbidity

There was no 30-days mortality [Table 5]. The major complications included patients who required intravenous calcium supplement (5%), RLN palsy (4.5%), or procedure under general anesthesia (1.3%). Patients requiring only oral calcium supplementation (25.6%) and conservative management without any surgical intervention for chyle leak and infection (3.1%) were considered as minor complications. Ten (4.4%) patients had more than one complication. Forty-three patients without any clinical symptoms of hypocalcemia were not included in the study.
Table 5: Surgical complication - 30-day morbidity (n=227)

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The patients with prior vocal cord palsy (n = 15) and any intentional RLN resection (n = 14) were not considered as complications of the procedure.

Only mobile cords preoperatively and not resected ones were considered for 'nerve at risk' calculation, which amounted to a total of 379 nerves (unilateral exploration in 37 and bilateral exploration in 171 patients), which were at risk. Vocal cord palsy was detected in 17 (4.5%)(16 patients). One patient had bilateral vocal cord palsy due to handling of both RLNs for multiple central compartment nodal clearance. The other patient had intentional RLN resection on one side and extensive dissection on other side. Thus, out of 16 patients, two patients had bilateral vocal cord paresis. Both were managed conservatively.

Chyle leak was seen in 3.1% of patients. One patient required cervical exploration for surgical ligation of thoracic duct, and this was considered as a major complication. The remaining 2.6% were managed conservatively and were considered as a minor complication.

Three patients had other surgical complications. Two major complications-bleeding and surgical emphysema following intentional resection of tracheal ring required exploration under general anesthasia. One patient had a minor infection around the suture line that was managed conservatively.

Various factors affecting the complications were studied in detail and are listed in [Table 6] (univariate analysis) and [Table 7] (multivariate analysis).
Table 6: Factors affecting the complication on univariate analysis with p value on Chi-square test

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Table 7: Factors affecting the complication on multivariable analysis with p value and odds ratio on logistic regression

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Aggressive histology and inadvertent parathyroidectomy were significant factors for hypocalcemia. Bilateral central compartment clearance was significantly associated with hypocalcemia (p = 0.019) [Figure 1] and RLN palsy (p = 0.050). The presence of extrathyroidal extension (ETE) was significantly associated with hypocalcemia (p = 0.006) [Figure 2]. Extended thyroid surgery was a significant factor for RLN palsy. Distant metastasis at presentation and inadvertent parathyroidectomy were significant factors associated with the overall complication. Inadvertent parathyroidectomy had a significant association with ETE (p = 0.006).
Figure 1: Bilateral central compartment clearance and hypocalcemia occurrence (p = 0.019)

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Figure 2: Presence of extrathyroidal extension and hypocalcemia occurrence (p = 0.006)

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Adjuvant treatment

Of 221 patients, 194 were differentiated thyroid cancers. Out of these 136 (70.1%) received radioiodine therapy. About 55.2% received a single dose of RAI and 83.1% received <200 mci cumulative doses. [Table 8] shows the details about the radioiodine treatment.
Table 8: Radioiodine dosage received in mci (total 194 differentiated thyroid cancer)

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Fourteen patients received radiotherapy to the neck and superior mediastinum for aggressive histology, and six patients received radiotherapy to a distant metastatic site.

Thyroxin supplementation

Of 12 patients who underwent a hemithyroidectomy, 7 required thyroxine supplementation (58%). However, long-term results for 5 patients were not available.

Outcomes

Twenty-six (11.8%) patients had progression of disease or appearance of new lesions or death as an event. The most common event was the distant metastasis progression or appearance (57.7%). Eleven (42.3%) were surgically salvageable locoregional recurrences. Details are given in [Table 9]. Median follow-up was 50 months. Five years estimated EFS was 84.8%.
Table 9: Pattern of events and death (n=26)

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Four patients died due to disease progression due to distant metastasis. Five years estimated OS was 98%. The Kaplan–Meier survival graphs for OAS and EFS are shown in [Figure 3] and [Figure 4]. Various factors affecting the OS and EFS are listed in [Table 10].
Figure 3: Five years overall survival 98% (IQR 36-57 months)

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Figure 4: Five years event free survival 84.8% (IQR 36-57 months)

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Table 10: Overall survival and event free survival univariate analysis by log-rank test and multivariate analysis on Cox multiple regression

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For EFS, the presence of distant metastasis, age >45 years, nodal positivity with age >45 years [Figure 5], aggressive histology, intentional recurrent nerve resection, and extended total thyroidectomy [Figure 6] were significant factors on univariate analysis.
Figure 5: Effect of age over 45 with node positivity and Event free survival (p = 0.044)

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Figure 6: Effect of perprimum surgery versus extended and revision on event free survival (p = 0.001)

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Except aggressive histology and nodal positivity with age >45 years years, all other aforementioned significant factors for EFS were also significant for OS on univariate analysis.

Aggressive histology (p = 0.006) was the significant negative factor on multivariate analysis for EFS. [Figure 7] shows the effect of aggressive histopathology on EFS.
Figure 7: Effect of aggressive histology on event free survival (p = 0.0001)

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The presence of distant metastasis at presentation (hazard ratio [HR] 44.04, 95% confidence interval [CI] 2.85–680.67, p = 0.007), and age (HR 1.2, 95% CI 1.00–1.439, p = 0.05) were the significant factors on multivariate analysis for OS. [Figure 8] shows the negative effect of age >45 years on OS. The presence of distant metastasis at presentation and intentional RLN resection had worse OS as seen in [Figure 9] and [Figure 10].
Figure 8: Effect of age over 45 and overall survival (p = 0.004)

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Figure 9: Effect of distant metastasis at presentation on overall survival (p = 0.0001)

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Figure 10: Effect of intentional recurrent laryngeal nerve resection on overall survival (p = 0.0001)

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 » Discussion Top


Thyroid surgery is precise due to the presence of crucial anatomic structures, namely, the RLN and the parathyroid glands. The damage to these structures during surgery can lead to dreadful long-term consequences that cannot be justified taking into consideration the indolent nature of disease. The surgeon has to strike a delicate balance between the adequacy of the surgery vis-a-vis overtreatment.

The present study had only 6.8% microcarcinomas and 30% patients presented with tumor size >4 cm, 52% with nodal metastasis and 10.4% had distant metastasis at presentation. Various studies have documented about 1%–7% patients presenting with distant metastasis at the time of initial diagnosis.[5],[6]

Age is an important prognostic factor in thyroid cancer so much so that it is factored into the staging system. Age >45 years is known for recurrences and mortality.[7] About 35% of our patients were over 45 years of age. The OS of this age group was 94.8% compared to a 100% survival in those <45 years of age (p = 0.004). Our study, in keeping with the other studies, has shown the presence of nodal metastasis in patients more than 45 years of age had a significantly worse recurrence-free survival.[8],[9]

Thyroid cancers have the potential to invade the strap muscles, RLN, trachea, esophagus, great vessels, larynx and prevertebral space in that order of frequency. In spite of local invasion, surgery remains the mainstay of treatment to achieve an R0 resection status even if this means sacrificing surrounding structures. Mayo clinic data reported about 6.1% RLN infiltration.[10] The present study had similar rates (6.3%). Price et al.[11] have reported poorer outcomes with locally invasive thyroid cancer. Extended total thyroidectomy patients had more complications and more events in our study, which is also well documented in literature.[11],[12]

ETE is a poor prognostic factor.[13] It has a higher rate of nodal metastases. Residual disease is more common with ETE. In our study, it was a significant factor for overall complications and hypocalcemia. Aggressive histologies connote poor outcomes.[14],[15] The EFS for this group was significantly low.

In our study, there was no 30-day mortality emphasizing the safe nature of this specialized surgery in the present era. Despite higher rate of poor tumor characteristics and elderly patients, the OS was 98% in this series.[16],[17] Mortality is due to the progression of distant metastasis or dedifferentiation of tumor with loss of radioiodine avidity. In the 5-year follow up period, four patients died due to metastatic disease.

Revision surgery poses a challenge because of the scarring and nonavailability of usual anatomical landmarks for parathyroid gland identification.[18],[19] In our study, about one-third were revision cases. The revision surgery in our series did not correlate with higher complication rates.

The hypocalcemia rates depend on various factors and reporting methods.[20] Transient hypocalcemia rates have been reported up to 46% in the literature.[20] Our study had a hypocalcemia rate of 30.8%. The factors identified for hypocalcemia in various studies are malignancy, unintentional parathyroidectomy[21],[22] and devascularization of parathyroid glands.[23] The risk increases with the extent of thyroidectomy[11] and reoperative procedures.[18],[19] In addition, central compartment neck dissection increases the risk of hypocalcemia[24],[25],[26] which concurs with the findings of the present study.

Thomusch et al.[27] reported that the presence of two functioning parathyroid glands is essential to avoid hypocalcemia. Implanted glands have more predictable survival than leaving devascularized gland in the paratracheal area.[28],[29] Careful examination of specimen is crucial to identify a parathyroid gland that has been inadvertently removed.

Although devascularized glands are autotransplanted, they take time to regain function.[30] Various studies have shown that the rate of inadvertent parathyroidectomy during thyroid surgery is between 5.2% and 21.6%.[26],[27],[28],[29] In our study, there was a significant correlation of inadvertent parathyroidectomy and aggressive histology (p = 0.016) with subsequent hypocalcemia (p = 0.007) on multivariate analysis. The presence of ETE was a significant factor with inadvertent parathyroidectomy (p = 0.006). A number of studies have shown the effectiveness of the use of parathyroid hormone to evaluate the function of the parathyroid gland and selective use of oral calcium and vitamin D after thyroidectomy before clinical manifestation.[23],[30],[31],[32] However, Proye et al.[33] argued against the utility of vitamin D in thyroid surgery. We treat our patients by the reactive approach, i.e., only symptomatic patients are treated with calcium and vitamin D supplement.

We have reported our results of morbidity of central compartment clearance with respect to lesser versus complete clearance during the same study period. The rate of hypocalcemia was 40.2% in bilateral and 17.4% in lesser clearance group.[34]

Various studies have reported vocal cord palsy rates of 2%–15%.[35],[36],[37],[38] Vocal cord palsy is under-reported in the literature because many do not document the palsy in asymptomatic patients with undetected injury of RLN.[35] The knowledge of anatomy and surgical maneuvers are important factors for RLN preservation.[36] The role of RLN monitoring has been variably reported in the literature.[35],[36],[37],[38] Bilateral thyroidectomy, malignancy, extended total thyroidectomy, revision surgery, exploration for hemorrhage; significant central compartment lymph nodal resection and lack of RLN identification[37],[38],[39],[40] are a few known factors for vocal cord palsy in the literature. In this study, we found extended total thyroidectomy as a significant factor on multivariate analysis for vocal cord palsy (p = 0.052). These were patients with advanced tumors, who were subjected to extensive central compartment exploration. In most of the cases, although nerve was anatomically saved, it was handled extensively for disease clearance. Being a referral center, we had one-third revision cases with malignancy. The use of intraoperative nerve monitoring may be a useful tool to preserve the RLN,[39] although this was not used during this study.

In the present study, out of 379 recurrent nerves at risk, 17 vocal cords were impaired. Rate of RLN at risk was 4.5%, for all thyroid surgery performed during the year 2012, which is comparable to that reported in various studies.[35],[36],[37],[38],[39],[40],[41]

Infection following thyroid surgery is reported in <2% cases. This is attributed to a breach in sterile technique or contamination. The present study had only one patient with minor infection.[41]

Hemorrhage and hematoma formation occur in <2% of cases. Meticulous hemostasis is key towards avoiding this complication. Apart from age and gender, malignancy with bilateral surgical procedure and patients on antiplatelet and anticoagulant medication may be risk factors.[42],[43] In our study, only one patient required surgical exploration for hemorrhage.

The incidence of postoperative hypothyroidism following lobectomy ranges from 21.1% to 64.2% in the literature.[44] In this study, 58% of the patients had postoperative hypothyroidism despite undergoing hemithyroidectomy.

The strength of this study is that we have analyzed the prospective data and the detailed information about the surgery in association with histopathological parameters, surgical morbidity and survival information.

The limitation of this study is that we have not reported long-term result for survival and complications including permanent hypocalcemia. No parathyroid assay was employed for assessment of hypoparathyroidism.


 » Conclusion Top


Thyroid cancer, even with advanced disease, is eminently treatable, with surgery being the mainstay of treatment. The complications of thyroid surgery and treatment can be severe for this indolent disease and minimized with meticulous dissection and attention to various details. Aggressive histology, the extent of thyroid surgery, distant metastasis and age are important factors, which should be factored in the algorithm of thyroid cancer management.

Acknowledgment

The authors would like to acknowledge Mr. Nilesh N Ganthade, Officer in charge of Medical Graphics, Tata Memorial Centre, Mumbai for his assistance in graphics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]



 

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