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1 Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Surgery, Seoul National University Boramae Medical.

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Presentation on theme: "1 Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Surgery, Seoul National University Boramae Medical."— Presentation transcript:

1 1 Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Korea 2 Department of Surgery, Seoul National University Boramae Medical Center and College of Medicine, Seoul, Korea 3 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea 4 Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea 5 Cancer Research Institute, Seoul National University, Seoul, Korea 6 Department of Surgery, Seoul National University Hospital and College of Medicine, Seoul, Korea 7 Division of Surgery, Thyroid Center, Seoul National University Cancer Hospital, Seoul, Korea 8 Department of Surgery, National Medical Center, Seoul, Korea Youngpeck Song, 1 Do Hoon Koo, 2 Seung Hyun Ma, 3,5 Sue K. Park, 3,4,5 June Young Choi, 6,7 Kyuhyung Kim, 1 Eunyoung Kim, 6,7 Yeo-Kyu Youn, 6,7,8 Kyu Eun Lee, 6,7 Papillary Thyroid Microcarcinoma, The Significance Of 5 mm: A Meta-analysis

2 Introduction Most PTMCs are clinically indolent and have a good prognosis. Aggressive tumor features and recurrence are similar to conventional PTC Roti et al. Eur J Endocrino. 2008: Meta-analysis on PTMC characteristics for recurrence; age, incidental tumor, multifocality, LN metastasis, distant metastasis Yu et al. Ann Surg 2011;254:653–660 Ito et al. World J Surg 2010;34: Arora et al. Thyroid 2009;19: Kasai et al. Cancer 1987;60: Han et al. KATES 2006;6:63-67

3 Introduction ATA and KTA guideline: FNA only the patient with over 5 mm PTMC NCCN guideline 2012: above 1 cm or high-risk clinical features No general consensus about relationship between tumor size and aggressiveness of PTMC –No difference is in aggressiveness between patients with PTMC greater than 5 mm and smaller than 5 mm. –Significant difference is exist in the rate of LN metastasis according tumor size Pelizzo et al. Nucl Med Commun. 2004;25(6): Kasai et al. Cancer 1987;60:

4 Aim Systemically reviewing the relevant articles and evaluate tumor aggressiveness of PTMC by size: less than 5 mm vs. over 5 mm

5 Methods Search Strategy –Literature search : PUBMED, MEDLINE, EMBASE, KoMCI and KOREAMED published from May 1976 through April 2012 –Search terms Papillary thyroid microcarcinoma To find any additional published studies, a manual search was performed by checking all the references of prior meta-analysis and of all original studies.

6 Publications were identified using search word “Papillary thyroid mi crocarcinoma” (n = 689) Titles and abstracts were r eviewed (n = 505) Articles described about PTMC characteristics for any tumor size were included (n = 36) 9 relevant articles of initially sele cted articles was added by biblio graphy and full-text assessed for eligibility (n = 45) 25 articles were finally included in meta-analysis 20 articles were excluded (n) Not reported eligible risk factor for tumor size (7) No description about number of patients have risk factors for tumor size (3) Cut off point was not 5 mm (3) Review article (1) Time sequential recurrence free survival rate (1) Not pure papillary thyroid cancer (data was mixed with follicular thyroid cancer) (1) Discordance between data of tables (1) Same center and author, duplicated data (1) Different pathologic subtype between over 5 mm and less than 5 mm (1) Unable to assay due to have 0 cell (1) 20 articles were excluded (n) Not reported eligible risk factor for tumor size (7) No description about number of patients have risk factors for tumor size (3) Cut off point was not 5 mm (3) Review article (1) Time sequential recurrence free survival rate (1) Not pure papillary thyroid cancer (data was mixed with follicular thyroid cancer) (1) Discordance between data of tables (1) Same center and author, duplicated data (1) Different pathologic subtype between over 5 mm and less than 5 mm (1) Unable to assay due to have 0 cell (1) Remove duplicated records (n = 184) Selection of The Studies

7 Methods Data Extraction –Authorship, Publication year, Country, Age, Sample size, OR and 95% CI –Outcomes : Lymph node metastasis, Extrathyroidal extension, Multifocality, Bilaterality, Recurrence Statistical Analysis –Meta-analysis using STATA 9.2 Random-effects model The Cochran Q statistics : Heterogeneity Egger's regression asymmetry test : Publication bias

8 Methods Analysis Overall analysis Subgroup analysis Outcomes Methodological quality RoBANS scale Thyroid cancer incidence Globocan 2008Publish date Subgroup analysis –Thyroid cancer incidence rate : Globocan 2008 in WHO –Two authors qualified 25 articles independently using RoBANS scale

9 Author Summery odds ratio (95%CI) CountryIncidence High & Low Study quality High & Low Lymph node metastasis Extrathyroidal extension MultifocalityBilateralityRecurrence Lee et al (0.16~3.05)Korea35.4High14High J.-C. Riss et al (1.20~6.40)France0.7Low14High Lee et al (1.63~5.91)Korea35.4High14High Chow et al (0.47~1.78)9.26 (2.74~31.28)1.47 (0.77~2.81) Hong Kong (China) 1.4Low13Low Vasileiadis et al (3.03~20.68)3.09 (1.78~5.39)5.31 (2.91~9.79)Greece1.8Low13Low Yoo et al (0.77~4.65)Korea35.4High12Low Kim et al (0.63~4.14)1.53 (0.47~5.13)Korea35.4High12Low Friguglietti et al (1.56~6.51)1.14 (0.66~1.98)1.11 (0.66~1.89)Brazil2.9Low13Low Kim et al (0.82~3.46)1.68 (0.77~3.68)1.38 (0.61~3.12)Korea35.4High14High Yoon et al (0.46~5.04)Korea35.4High11Low Cho et al (0.76~3.81)2.01 (0.79~5.07)4.05 (1.14~14.38)Korea35.4High13Low Pakdaman et al (1.53~3.56)2.08 (1.23~3.53)Canada9.4High13Low Tae et al (0.67~4.24)2.98 (1.18~7.53)1.40 (0.59~3.32)Korea35.4High13Low Kim et al (0.39~2.10)2.47 (0.54~11.33)0.78 (0.23~2.68)3.69 (0.46~29.69)Korea35.4High13Low Yu et al (1.50~99.84)China1.4Low12Low Pelizzo et al (1.09~3.24)1.23 (0.78~1.92)Italy9.1High13Low Roti et al (2.31~42.62)Italy9.1High13Low Lee et al (1.14~3.25)1.72 (0.93~3.18)1.49 (0.88~2.55)1.43 (0.74~2.75)Korea35.4High13Low Lee et al (0.68~2.39)3.76 (1.64~8.64) Korea35.4High13Low Wada et al (1.23~3.97) Japan3.1High13Low Lombardi et al (2.31~8.36) Italy9.1High13Low Kim et al (1.08~5.04) Korea35.4High13Low Han et al (1.46~12.89) Korea35.4High13Low Pelizzo et al (0.88~5.83) Italy9.1High12Low Park et al (1.85~15.94) 1.92 (1.02~3.59) Korea35.4High12Low Summary odds ratio (95% CI), incidence rate and quality of study in the present 25 articles

10 Results OutcomeN of studiesSummary OR (95% CI)p-heterogeneity a Lymph node metastasis All studies202.23( )0.004 Incidence rate High ( )0.014 Low62.02 ( )0.048 Study quality Score ≥ ( )0.476 Score < ( )0.001 Published year In 2008 and after ( )0.027 Before ( )0.031 Extrathyroidal extension All studies72.39 ( )0.038 Incidence rate High52.34 ( )0.630 Low23.02 ( )0.002 Study quality Score < ( )0.038 Published year In 2008 and after41.64 ( )0.313 Before ( )0.147 Summary odds ratio (OR) for outcomes in relation to the cut-off point tumor size (5 mm)

11 Results OutcomeN of studiesSummary OR (95% CI)p-heterogeneity a Multifocal tumors All studies ( )0.193 Incidence rate High ( )0.459 Low31.72 ( )0.028 Study quality Score ≥ ( )0.148 Score < ( )0.108 Published year In 2008 and after91.77 ( )0.175 Before ( )0.298 Bilateral tumors All studies52.12 ( )0.022 Incidence rate High41.69 ( )0.775 Low15.31 ( )0.172 Study quality Score ≥ ( )NA Score < ( )0.02 Published year In 2008 and after52.12 ( )0.022 Recurrence All studies ( )0.66

12 Summary odds ratio (OR) for outcomes in papillary thyroid microcarcinoma patients without heterogeneity 1.Analysis about study of high quality 2.Analysis about all study 3.Analysis about study in high incidence rate NOTE: Weights are from random effects analysis.. Recurrence 2 Kim et al,2009 Lee et al,2010 Subtotal (I-squared = 24.8%, p = 0.193) Subtotal (I-squared = 0.0%, p = 0.663) Tae et al,2008 Pelizzo et al,2007 J.-C. Riss et al,2012 Cho et al,2006 Kim et al,2008 Pelizzo et al,2006 Multifocal tumors 2 Author et al Tae et al,2008 Lee et al,2006 Lee et al,2008 Subtotal (I-squared = 0.0%, p = 0.630) Lymph node metastasis 1 Kim et al,2008 Pakdaman et al,2008 Subtotal (I-squared = 0.0%, p = 0.476) Kim et al,2010 Vasileiadis et al,2011 Lee et al,2010 Kim et al,2009 Extrathyroidal extension 3 Han et al,2006 Cho et al,2006 Friguglietti et al,2010 Kim et al, (0.93, 3.62) 1.04 (0.16, 3.05) 1.72 (1.39, 2.11) 3.06 (1.56, 6.01) 1.40 (0.59, 3.32) 1.23 (0.78, 1.92) 2.70 (1.20, 6.40) 4.05 (1.14, 14.38) 2.34 (1.08, 5.04) 2.26 (0.88, 5.83) OR (95% CI) 2.98 (1.18, 7.53) 3.76 (1.64, 8.64) 3.11 (1.63, 5.91) 2.34 (1.60, 3.43) 0.78 (0.23, 2.68) 2.34 (1.53, 3.56) 2.34 (1.58, 3.46) 1.61 (0.63, 4.14) 3.09 (1.78, 5.39) 1.49 (0.88, 2.55) 1.68 (0.77, 3.68) 4.34 (1.46, 12.89) 1.11 (0.66, 1.89) 3.69 (0.46, 29.69) 2.47 (0.54, 11.33) Outcome Kim et al, (0.79, 5.07) Lee et al, (0.93, 3.18) Chow et al, (0.77, 2.81) Park et al, (1.02, 3.59) Subtotal (I-squared = 0.0%, p = 0.775) Lee et al,2010 Kim et al,2010 Pakdaman,2008 Bilateral tumors 3 Kim et al, (1.19, 2.40) 1.43 (0.74, 2.75) 1.38 (0.61, 3.12) 2.08 (1.23, 3.53) 1.53 (0.47, 5.13)

13 AuthorTotal number of patients Ratio of LN metastasis less than 5 mm (%)over 5 mm (%) Lee et al /26 (3.8)15/26 (57.7) J.-C. Riss et al /62 (16.1)36/98 (36.7) Lee et al /125 (12.8)72/220 (32.7) Chow et al /70 (25.7)32/133 (24.7) Vasileiadis et al /202 (3.5)16/74 (21.6) Yoo et al /62 (12.9)22/103 (21.4) Friguglietti et al /173 (5.8)45/275 (16.4) Kim et al /52 (36.5)56/109 (51.4) Yoon et al /32 (21.9)16 (40.0) Cho et al /39 (28.2)38/95 (40.0) Tae et al /62 (12.9)16/80 (20.0) Kim et al /72 (12.5)21/182 (11.5) Yu et al /12 (8.3)39/74 (52.7) Pelizzo et al /258 (8.1)47/329 (14.3) Roti et al /86 (2.3)30/157 (19.1) Lee et al /106 (27.4)71/169 (42.0) Lee et al /62 (25.8)73/238 (30.7) Wada et al /61 (50.8)135/198 (68.2) Lombardi et al /459 (2.6)50/474 (10.5) Park et al /71 (5.6)36/147 (24.5) Sum of patients /2092 (11.5)866/3221 (26.9) Results Summary patient ratio for LN metastasis in the group of less than 5 mm and over 5 mm

14 Limitation Our search was restricted to studies published in indexed journals. Only four articles provided adjusting odds ratio. Others were calculated crudely. Heterogeneity was high in each literatures, so subgroup analysis was performed.

15 Conclusion PTMC over 5 mm has more aggressive character than PTMC less than 5mm in terms of LN metastasis, ETE, multifocality, bilaterality and recurrence. However even PTMC less than 5 mm do shows aggressiveness in terms of LN metastasis, ETE, bilaterality, multiplicity, and recurrence. We need further evidence to justify the avoidance of further study for the PTMC less than 5 mm.


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