CLINICAL STUDY
Total Endoscopic Versus Conventional Open Thyroidectomy for Papillary Thyroid Microcarcinoma Yichao Wang, MD,* Kai Liu, MD,† Junjie Xiong, MD,‡ and Jingqiang Zhu, MD* Background: The objective of this study was to conduct a meta-analysis to assess the safety and efficacy of total endoscopic thyroidectomy (TET) versus conventional open thyroidectomy (COT) for papillary thyroid microcarcinoma with regard to short-term clinical outcomes. Methods: MEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library between January 1996 and July 2014 were searched to identify relevant comparative studies. Pooled weighted mean differences (WMD) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using either fixed or random-effects models. The perioperative outcomes were evaluated. Results: Five eligible nonrandomized studies were included, involving 1004 patients: 475 were TET and 529 were COT. Meta-analysis results revealed that TET group had a significantly longer operative time (WMD, 48.15; 95% CI, 27.54–68.75; P < 0.00001), compared with the COT group. While analyzing the number of removed lymph nodes, 4 studies were included. The TET group had a less number of removed lymph nodes (WMD, −0.68; 95% CI, −1.20 to −0.15; P = 0.01). There were no significant differences in terms of hospital stay, transient recurrent laryngeal nerve palsy, permanent recurrent laryngeal nerve palsy, transient hypocalcemia, and permanent hypocalcemia. Conclusions: Total endoscopic thyroidectomy appears to be a much feasible safe surgical procedure for papillary thyroid microcarcinoma in selected patients. Key Words: endoscopy, open, thyroidectomy, papillary thyroid microcarcinoma, meta-analysis (J Craniofac Surg 2015;26: 464–468)
ince Gagner1 reported the first endoscopic parathyroidectomy in 1996; soon afterward, in 1997, Hüscher2 performed the first endoscopic thyroidectomy (ET). At present, various endoscopic techniques
S
From the Departments of *Thyroid and Breast Surgery, †Cardiology, and ‡Pancreatic Surgery, West China Hospital, Sichuan University, Guo Xue Rd 37, Chengdu, Sichuan Province, China. Received October 14, 2014. Accepted for publication December 1, 2014. Address correspondence and reprint requests to Jingqiang Zhu, MD, Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Guo Xue Rd 37, Chengdu 610041, Sichuan Province, China; E-mail: [email protected] The author(s) received no financial support for the research, authorship, and/or publication of this article. The authors report no conflicts of interest. Author contributions: Y.W. and J.Z. designed the research. Y.W., K.L., and J.X. developed the literature search and carried out statistical analysis of the studies. Y.W. drafted the article, and all authors read and approved the final manuscript. Copyright © 2015 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001449
464
have been widely applied to thyroid surgery, which can be divided into 2 approaches: video-assisted thyroidectomy and total ET (TET).3 The advantages of ET were superior cosmetic appearance, less postoperative pain, and a better surgical view with magnification compared with conventional open thyroidectomy (COT).4–6 Nevertheless, the indication for endoscopic surgery has been limited to benign thyroid tumors.7 Along with the accumulation of experience of ET, the indication for endoscopic techniques has been expanded to thyroid cancer. In 2001, Miccoli et al8 reported minimally invasive, video-assisted thyroidectomy for papillary thyroid carcinoma. Thereafter, some researchers reported the applicability of TET for thyroid cancer with low-risk patients, which compared the early surgical outcomes of TET and COT.9–13 Currently, general application of ET for malignant thyroid tumors continues to be debated, because its oncologic outcomes and complete thyroidectomy have not yet been proved.12 Some previously published meta-analyses have reported the feasibility and safety of ET for thyroid nodules.14–17 However, no meta-analysis has systematically reviewed the differences between TET and COT for papillary thyroid microcarcinoma (PTMC). Therefore, a systematic and comprehensive analysis of the published data on TET and COT for PTMC should be undertaken to compare the short-term clinical outcomes.
MATERIALS AND METHODS Systematic Literature Search The literature was systematically searched in MEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library between the time period of January 1996 and July 2014. The following MeSH (Medical Subject Headings) terms and key words were used: “laparoscopy” or “endoscopy” or “minimally invasive” and “thyroidectomy” and “papillary thyroid microcarcinoma” or “thyroid cancer.” Only human studies published in English language with full-text descriptions were considered for inclusion. Reference lists from retrieved articles were also searched for relevant studies. Final inclusion of articles was determined by consensus from 2 reviewers; when this failed, a third author was adjudicated.
Inclusion Criteria Two reviewers independently identified and screened eligible studies. Study had to fulfill the following criteria: (1) articles with comparison of the outcomes of TET and COT for patients with PTMC; (2) clear documentation of the operative techniques as “total endoscopic” or “conventional open”; (3) articles with clear indication of TET for thyroid cancer; (4) studies reported on at least 1 of the outcomes mentioned in Outcome Measures; (5) studies reported in English language; and (6) multiple studies published by the same institution and/or authors, either the one of higher quality or the most recent publication.
Exclusion Criteria Studies were excluded from the analysis on the basis of (1) abstracts, case reports, letters, editorials, expert opinions, reviews;
The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015
Endoscopic vs Open Thyroidectomy
by using odds ratio (OR) with corresponding 95% confidence interval (CI). For continuous variables, pooled effects were expressed as weighted mean difference (WMD) with corresponding 95% CI. Meta-analysis was performed using fixed- or random-effects model, depending on the heterogeneity. Heterogeneity was measured using the χ2 and I2, with a P < 0.1 considered as significant.20 Random-effects analysis was performed if the I2 statistic was greater than 50%. Sensitivity analysis was also conducted by removing individual studies from the data set and analyzing the effect on the overall results to identify statistical heterogeneity. Funnel plots were created to evaluate the potential publication bias.
RESULTS Description of Included Trials in the Meta-analysis FIGURE 1. Flow diagram for the search strategy and selection process.
(2) studies lacking control groups and clearly reported outcomes of interest; and (3) studies including patients with benign lesions of the thyroid.
Outcome Measures Intraoperative and postoperative outcomes were used to compare TET with COT. Intraoperative outcomes included operative time and number of removed lymph nodes. Postoperative outcomes were transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcemia, permanent hypocalcaemia, and hospital stay.
Data Extraction and Quality Assessment Two reviewers independently extracted data from all eligible studies using standardized forms. Data extracted from each report included first author and year of publication, number of patients, study design, participant characteristics, operative details, and postoperative outcomes. Quality of the nonrandomized study was assessed using the Newcastle-Ottawa Scale with some modifications to match the need of this study. The quality was evaluated by using the following items: patient selection, comparability of the 2 groups, and assessment of outcome. Studies achieving 6 or more stars were considered as higher quality.18,19
Statistical Analysis The meta-analysis was performed by using Review Manager software, version5.0 (The Cochrane Collaboration, Oxford, United Kingdom). For categorical variables, pooled effects were performed
Five hundred forty-four potentially relevant articles were identified according to the search strategy. Twelve articles were selected for further investigation. Of these, 7 studies21–27 were reported on benign and malignant tumors without comparison. Finally, a total of 5 nonrandomized studies9–13 matched the inclusion criteria and were included. A flowchart of reference selection is illustrated in Figure 1.
Study and Patient Characteristics The general characteristics and pathologic details are summarized in Tables 1 and 2. One thousand four patients were included, of whom 475 underwent TET, and 529 underwent COT. The surgical approaches of the 5 studies were bilateral axilla-breast with insufflation of CO2,9 axilla without gas insufflation,10 unilateral axilla-breast without gas insufflation.11 unilateral axilla-breast or axilla without gas insufflation,12 and axilla with insufflation of CO2,13 respectively. All except 1 study9 reported the central compartment neck dissection. Three studies10–13 revealed the multiplicity, bilateralism, and extrathyroidal extension of the tumor. All these studies had been performed in Korea.
Meta-analysis Results Intraoperative Outcomes Results of the analyses are summarized in Table 3. All studies explicitly reported operative time. Meta-analysis of the pooled data revealed that operative time was significantly longer in the TET group than in the COT group (WMD, 48.15; 95% CI, 27.54–68.75; P < 0.00001), with significant heterogeneity between the studies (I2 = 90%; Fig. 2A). The number of removed lymph nodes was reported in 4 studies,10–13 which was found to be significantly less in
TABLE 1. General Characteristic of Studies Included in the Meta-analysis Reference
Year Country Group Patients, n
Chung et al9 2007
Korea
Jeong et al10 2009
Korea
Koh et al11
2010
Korea
Tae et al12
2011
Korea
Lee et al13
2012
Korea
TET COT TET COT TET COT TET COT TET COT
103 198 275 224 29 30 31 36 37 41
Age, y 38.2 ± 8.2 47.2 ± 10.2 39.6 ± 8.8 49.5 ± 10.2 36.5 ± 5.1 38.3 ± 4.5 36.2 ± 9.9 44.6 ± 11.8 42.3 ± 7.6 49.0 ± 10.8
Male/Female, n Study Quality* 1/102 25/173 7/268 35/189 3/26 6/24 1/30 11/25 0/37 3/38
Surgical Approach
******
Bilateral axillo-breast approach with insufflation of CO2
*****
Axillary approach without gas insufflation
******
Unilateral axillo-breast approach without gas insufflations
*******
Unilateral axillo-breast or axillary approach without gas insufflation
******
Axillary approach with insufflation of CO2
*Based on Newcastle-Ottawa Scale with maximum of *** for selection, **** for comparability, and ** for outcome.
© 2015 Mutaz B. Habal, MD
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
465
The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015
Wang et al
TABLE 2. Pathologic Details in 2 Groups
Study
Chung et al9 Jeong et al10 Koh et al11 Tae et al12 Lee et al13
No. Patients
TET COT
TET COT
Tumor Size, mm
Multiplicity, n
Bilaterality, n (%)
Extrathyroidal Extension, n (%)
Tumor Size, mm
Multiplicity, n
Bilaterality, n (%)
Extrathyroidal Extension, n (%)
103 275 29 31 37
Total Endoscopic Versus Conventional Open Thyroidectomy for Papillary Thyroid Microcarcinoma Yichao Wang, MD,* Kai Liu, MD,† Junjie Xiong, MD,‡ and Jingqiang Zhu, MD* Background: The objective of this study was to conduct a meta-analysis to assess the safety and efficacy of total endoscopic thyroidectomy (TET) versus conventional open thyroidectomy (COT) for papillary thyroid microcarcinoma with regard to short-term clinical outcomes. Methods: MEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library between January 1996 and July 2014 were searched to identify relevant comparative studies. Pooled weighted mean differences (WMD) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using either fixed or random-effects models. The perioperative outcomes were evaluated. Results: Five eligible nonrandomized studies were included, involving 1004 patients: 475 were TET and 529 were COT. Meta-analysis results revealed that TET group had a significantly longer operative time (WMD, 48.15; 95% CI, 27.54–68.75; P < 0.00001), compared with the COT group. While analyzing the number of removed lymph nodes, 4 studies were included. The TET group had a less number of removed lymph nodes (WMD, −0.68; 95% CI, −1.20 to −0.15; P = 0.01). There were no significant differences in terms of hospital stay, transient recurrent laryngeal nerve palsy, permanent recurrent laryngeal nerve palsy, transient hypocalcemia, and permanent hypocalcemia. Conclusions: Total endoscopic thyroidectomy appears to be a much feasible safe surgical procedure for papillary thyroid microcarcinoma in selected patients. Key Words: endoscopy, open, thyroidectomy, papillary thyroid microcarcinoma, meta-analysis (J Craniofac Surg 2015;26: 464–468)
ince Gagner1 reported the first endoscopic parathyroidectomy in 1996; soon afterward, in 1997, Hüscher2 performed the first endoscopic thyroidectomy (ET). At present, various endoscopic techniques
S
From the Departments of *Thyroid and Breast Surgery, †Cardiology, and ‡Pancreatic Surgery, West China Hospital, Sichuan University, Guo Xue Rd 37, Chengdu, Sichuan Province, China. Received October 14, 2014. Accepted for publication December 1, 2014. Address correspondence and reprint requests to Jingqiang Zhu, MD, Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Guo Xue Rd 37, Chengdu 610041, Sichuan Province, China; E-mail: [email protected] The author(s) received no financial support for the research, authorship, and/or publication of this article. The authors report no conflicts of interest. Author contributions: Y.W. and J.Z. designed the research. Y.W., K.L., and J.X. developed the literature search and carried out statistical analysis of the studies. Y.W. drafted the article, and all authors read and approved the final manuscript. Copyright © 2015 by Mutaz B. Habal, MD ISSN: 1049-2275 DOI: 10.1097/SCS.0000000000001449
464
have been widely applied to thyroid surgery, which can be divided into 2 approaches: video-assisted thyroidectomy and total ET (TET).3 The advantages of ET were superior cosmetic appearance, less postoperative pain, and a better surgical view with magnification compared with conventional open thyroidectomy (COT).4–6 Nevertheless, the indication for endoscopic surgery has been limited to benign thyroid tumors.7 Along with the accumulation of experience of ET, the indication for endoscopic techniques has been expanded to thyroid cancer. In 2001, Miccoli et al8 reported minimally invasive, video-assisted thyroidectomy for papillary thyroid carcinoma. Thereafter, some researchers reported the applicability of TET for thyroid cancer with low-risk patients, which compared the early surgical outcomes of TET and COT.9–13 Currently, general application of ET for malignant thyroid tumors continues to be debated, because its oncologic outcomes and complete thyroidectomy have not yet been proved.12 Some previously published meta-analyses have reported the feasibility and safety of ET for thyroid nodules.14–17 However, no meta-analysis has systematically reviewed the differences between TET and COT for papillary thyroid microcarcinoma (PTMC). Therefore, a systematic and comprehensive analysis of the published data on TET and COT for PTMC should be undertaken to compare the short-term clinical outcomes.
MATERIALS AND METHODS Systematic Literature Search The literature was systematically searched in MEDLINE, EMBASE, Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials in the Cochrane Library between the time period of January 1996 and July 2014. The following MeSH (Medical Subject Headings) terms and key words were used: “laparoscopy” or “endoscopy” or “minimally invasive” and “thyroidectomy” and “papillary thyroid microcarcinoma” or “thyroid cancer.” Only human studies published in English language with full-text descriptions were considered for inclusion. Reference lists from retrieved articles were also searched for relevant studies. Final inclusion of articles was determined by consensus from 2 reviewers; when this failed, a third author was adjudicated.
Inclusion Criteria Two reviewers independently identified and screened eligible studies. Study had to fulfill the following criteria: (1) articles with comparison of the outcomes of TET and COT for patients with PTMC; (2) clear documentation of the operative techniques as “total endoscopic” or “conventional open”; (3) articles with clear indication of TET for thyroid cancer; (4) studies reported on at least 1 of the outcomes mentioned in Outcome Measures; (5) studies reported in English language; and (6) multiple studies published by the same institution and/or authors, either the one of higher quality or the most recent publication.
Exclusion Criteria Studies were excluded from the analysis on the basis of (1) abstracts, case reports, letters, editorials, expert opinions, reviews;
The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015
Endoscopic vs Open Thyroidectomy
by using odds ratio (OR) with corresponding 95% confidence interval (CI). For continuous variables, pooled effects were expressed as weighted mean difference (WMD) with corresponding 95% CI. Meta-analysis was performed using fixed- or random-effects model, depending on the heterogeneity. Heterogeneity was measured using the χ2 and I2, with a P < 0.1 considered as significant.20 Random-effects analysis was performed if the I2 statistic was greater than 50%. Sensitivity analysis was also conducted by removing individual studies from the data set and analyzing the effect on the overall results to identify statistical heterogeneity. Funnel plots were created to evaluate the potential publication bias.
RESULTS Description of Included Trials in the Meta-analysis FIGURE 1. Flow diagram for the search strategy and selection process.
(2) studies lacking control groups and clearly reported outcomes of interest; and (3) studies including patients with benign lesions of the thyroid.
Outcome Measures Intraoperative and postoperative outcomes were used to compare TET with COT. Intraoperative outcomes included operative time and number of removed lymph nodes. Postoperative outcomes were transient recurrent laryngeal nerve (RLN) palsy, permanent RLN palsy, transient hypocalcemia, permanent hypocalcaemia, and hospital stay.
Data Extraction and Quality Assessment Two reviewers independently extracted data from all eligible studies using standardized forms. Data extracted from each report included first author and year of publication, number of patients, study design, participant characteristics, operative details, and postoperative outcomes. Quality of the nonrandomized study was assessed using the Newcastle-Ottawa Scale with some modifications to match the need of this study. The quality was evaluated by using the following items: patient selection, comparability of the 2 groups, and assessment of outcome. Studies achieving 6 or more stars were considered as higher quality.18,19
Statistical Analysis The meta-analysis was performed by using Review Manager software, version5.0 (The Cochrane Collaboration, Oxford, United Kingdom). For categorical variables, pooled effects were performed
Five hundred forty-four potentially relevant articles were identified according to the search strategy. Twelve articles were selected for further investigation. Of these, 7 studies21–27 were reported on benign and malignant tumors without comparison. Finally, a total of 5 nonrandomized studies9–13 matched the inclusion criteria and were included. A flowchart of reference selection is illustrated in Figure 1.
Study and Patient Characteristics The general characteristics and pathologic details are summarized in Tables 1 and 2. One thousand four patients were included, of whom 475 underwent TET, and 529 underwent COT. The surgical approaches of the 5 studies were bilateral axilla-breast with insufflation of CO2,9 axilla without gas insufflation,10 unilateral axilla-breast without gas insufflation.11 unilateral axilla-breast or axilla without gas insufflation,12 and axilla with insufflation of CO2,13 respectively. All except 1 study9 reported the central compartment neck dissection. Three studies10–13 revealed the multiplicity, bilateralism, and extrathyroidal extension of the tumor. All these studies had been performed in Korea.
Meta-analysis Results Intraoperative Outcomes Results of the analyses are summarized in Table 3. All studies explicitly reported operative time. Meta-analysis of the pooled data revealed that operative time was significantly longer in the TET group than in the COT group (WMD, 48.15; 95% CI, 27.54–68.75; P < 0.00001), with significant heterogeneity between the studies (I2 = 90%; Fig. 2A). The number of removed lymph nodes was reported in 4 studies,10–13 which was found to be significantly less in
TABLE 1. General Characteristic of Studies Included in the Meta-analysis Reference
Year Country Group Patients, n
Chung et al9 2007
Korea
Jeong et al10 2009
Korea
Koh et al11
2010
Korea
Tae et al12
2011
Korea
Lee et al13
2012
Korea
TET COT TET COT TET COT TET COT TET COT
103 198 275 224 29 30 31 36 37 41
Age, y 38.2 ± 8.2 47.2 ± 10.2 39.6 ± 8.8 49.5 ± 10.2 36.5 ± 5.1 38.3 ± 4.5 36.2 ± 9.9 44.6 ± 11.8 42.3 ± 7.6 49.0 ± 10.8
Male/Female, n Study Quality* 1/102 25/173 7/268 35/189 3/26 6/24 1/30 11/25 0/37 3/38
Surgical Approach
******
Bilateral axillo-breast approach with insufflation of CO2
*****
Axillary approach without gas insufflation
******
Unilateral axillo-breast approach without gas insufflations
*******
Unilateral axillo-breast or axillary approach without gas insufflation
******
Axillary approach with insufflation of CO2
*Based on Newcastle-Ottawa Scale with maximum of *** for selection, **** for comparability, and ** for outcome.
© 2015 Mutaz B. Habal, MD
Copyright © 2015 Mutaz B. Habal, MD. Unauthorized reproduction of this article is prohibited.
465
The Journal of Craniofacial Surgery • Volume 26, Number 2, March 2015
Wang et al
TABLE 2. Pathologic Details in 2 Groups
Study
Chung et al9 Jeong et al10 Koh et al11 Tae et al12 Lee et al13
No. Patients
TET COT
TET COT
Tumor Size, mm
Multiplicity, n
Bilaterality, n (%)
Extrathyroidal Extension, n (%)
Tumor Size, mm
Multiplicity, n
Bilaterality, n (%)
Extrathyroidal Extension, n (%)
103 275 29 31 37
