Abstract
Background
Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. The incidence of PTC is rising in tandem with an obesity epidemic. Associations have been demonstrated between increased body mass index (BMI) and worse oncological outcomes in a number of malignancies. However, research on this topic in PTC to date has been inconsistent, often due to limited data. This study aimed to measure the association between BMI and potentially adverse clinicopathological features of PTC.
Methods
A meta-analysis of studies reporting outcomes after surgical treatment of PTC was performed. PubMed, Embase and the Cochrane Library were searched systematically to identify studies which provided data on BMI and clinicopathologic features of PTC. Relevant data were extracted and synthesis performed using adjusted odds ratios where available and crude values when not. Data were analysed by inverse variance using random and fixed effects models.
Results
Data on 35,237 patients from 15 studies met the criteria for inclusion. Obesity was associated with larger tumour size (MD = 0.17 cm [0.05, 0.29]), increased rates of multifocality (OR = 1.41 [1.16, 1.70]), extrathyroidal extension (OR = 1.70 [1.39, 2.07]) and nodal spread (OR = 1.18 [1.07, 1.30]). Associations were more pronounced as BMI increased. There was no association between BMI and bilaterality, vascular invasion or metastatic spread.
Conclusion
Increased BMI is significantly associated with multiple potentially adverse features of PTC. The effect on long-term oncological outcomes requires further evaluation.
Similar content being viewed by others
References
Smittenaar CR, Petersen KA, Stewart K, Moitt N (2016) Cancer incidence and mortality projections in the UK until 2035. Br J Cancer 115:1147–1155
Davies L, Welch HG (2014) Current thyroid cancer trends in the United States. JAMA Otolaryngol Neck Surg 140:317
Sipos JA, Mazzaferri EL (2010) Thyroid cancer epidemiology and prognostic variables. Clin Oncol 22:395–404
Kitahara CM, Sosa JA (2016) The changing incidence of thyroid cancer. Nat Rev Endocrinol 12:646–653
Bertagna F, Treglia G, Piccardo A, Giubbini R (2012) Diagnostic and clinical significance of F-18-FDG-PET/CT thyroid incidentalomas. J Clin Endocrinol Metab 97:3866–3875
Wiltshire JJ, Drake TM, Uttley L, Balasubramanian SP (2016) Systematic review of trends in the incidence rates of thyroid cancer. Thyroid 26:1541–1552
Kitahara CM, Platz EA, Freeman LE et al (2011) Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomark Prev 20:464–472
Lengyel E, Makowski L, DiGiovanni J, Kolonin MG (2018) Cancer as a matter of fat: the crosstalk between adipose tissue and tumors. Trends cancer 4:374–384
Vucenik I, Stains JP (2012) Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci 1271:37–43
Ackerman SE, Blackburn OA, Marchildon F, Cohen P (2017) Insights into the link between obesity and cancer. Curr Obes Rep 6:195–203
Freedland SJ, Aronson WJ, Kane CJ et al (2004) Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the shared equal access regional cancer hospital database study group. J Clin Oncol 22:446–453
Hahn KME, Bondy ML, Selvan M et al (2007) Factors associated with advanced disease stage at diagnosis in a population-based study of patients with newly diagnosed breast cancer. Am J Epidemiol 166:1035–1044
Chung YS, Lee JH, Lee YD (2017) Is body mass index relevant to prognosis of papillary thyroid carcinoma? A clinicopathological cohort study. Surg Today 47:506–512
Choi JS, Kim EK, Moon HJ, Kwak JY (2014) Higher body mass index may be a predictor of extrathyroidal extension in patients with papillary thyroid microcarcinoma. Endocrine 48:264–271
Kim SK, Woo J-W, Park I et al (2016) Influence of body mass index and body surface area on the behavior of papillary thyroid carcinoma. Thyroid 26:657–666
Kwon H, Kim M, Choi YM et al (2015) Lack of associations between body mass index and clinical outcomes in patients with papillary thyroid carcinoma. Endocrinol Metab 30:305
Yu S-T, Chen W, Cai Q et al (2017) Pretreatment BMI is associated with aggressive clinicopathological features of papillary thyroid carcinoma: a multicenter study. Int J Endocrinol 2017:5841942
Zhao Q, Ming J, Liu C et al (2013) Multifocality and total tumor diameter predict central neck lymph node metastases in papillary thyroid microcarcinoma. Ann Surg Oncol 20:746–752
Shah JP, Loree TR, Dharker D et al (1992) Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 164:658–661
Gardner RE, Tuttle RM, Burman KD et al (2000) Prognostic importance of vascular invasion in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg 126:309–312
Lin J-D, Hsueh C, Chao T-C (2016) Soft tissue invasion of papillary thyroid carcinoma. Clin Exp Metastasis 33:601–608
Scheumann GF, Gimm O, Wegener G et al (1994) Prognostic significance and surgical management of locoregional lymph node metastases in papillary thyroid cancer. World J Surg 18:559–67
Shamseer L, Moher D, Clarke M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ 349:g7647–g7647
Wells G, Shea B, O’Connell D et al (2009) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 21 May 2019
Feng JW, Yang XH, Wu BQ et al (2019) Influence of body mass index on the clinicopathologic features of papillary thyroid carcinoma. Ann Otol Rhinol Laryngol. https://doi.org/10.1177/0003489419834314
Wu C, Wang L, Chen W et al (2017) Associations between body mass index and lymph node metastases of patients with papillary thyroid cancer: A retrospective study. Med 96:e6202
Liu Z, Maimaiti Y, Yu P et al (2015) Correlation between body mass index and clinicopathological features of papillary thyroid microcarcinoma. Int J Clin Exp Med 8:16472–16479
Kim SH, Park HS, Kim KH et al (2015) Correlation between obesity and clinicopathological factors in patients with papillary thyroid cancer. Surg Today 45:723–729
Trésallet C, Seman M, Tissier F et al (2014) The incidence of papillary thyroid carcinoma and outcomes in operative patients according to their body mass indices. Surg 156:1145–1152
Kim HJ, Kim NK, Choi JH et al (2013) Associations between body mass index and clinico-pathological characteristics of papillary thyroid cancer. Clin Endocrinol 78:134–140
Harari A, Endo B, Nishimoto S et al (2012) Risk of advanced papillary thyroid cancer in obese patients. Arch Surg 147:805–811
Li CL, Dionigi G, Zhao YS et al (2020) Influence of body mass index on the clinicopathological features of 13,995 papillary thyroid tumors. J Endocrinol Invest. https://doi.org/10.1007/s40618-020-01216-6
Zhao S, Jia X, Fan X et al (2019) Association of obesity with the clinicopathological features of thyroid cancer in a large, operative population: a retrospective case-control study. Med. https://doi.org/10.1097/MD.0000000000018213
Jin QF, Fang QG, Qi JX, Li P (2019) Impact of BMI on complications and satisfaction in patients with papillary thyroid cancer and lateral neck metastasis. Cancer Control. https://doi.org/10.1177/1073274819853831
Calle EE, Thun MJ (2004) Obesity and cancer. Oncogene 23:6365–6378
Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults N Engl J Med 348:1625–1638
Han JM, Kim TY, Jeon MJ et al (2013) Obesity is a risk factor for thyroid cancer in a large, ultrasonographically screened population. Eur J Endocrinol 168:879–886
Xu L, Port M, Landi S et al (2014) Obesity and the risk of papillary thyroid cancer: a pooled analysis of three case-control studies. Thyroid 24:966–974
Renehan AG, Tyson M, Egger M et al (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578
Marcello MA, Cunha LL, Batista FA, Ward LS (2014) Obesity and thyroid cancer. Endocr Relat Cancer 21:T255–T271
Engeland A, Tretli S, Akslen LA, Bjørge T (2006) Body size and thyroid cancer in two million Norwegian men and women. Br J Cancer 95:366–370
Zhao ZG, Guo XG, Ba CX et al (2012) Overweight, obesity and thyroid cancer risk: a meta-analysis of cohort studies. J Int Med Res 40:2041–2050
Kwon H, Han KD, Park CY (2019) Weight change is significantly associated with risk of thyroid cancer: a nationwide population-based cohort study. Sci Rep 9:1546
Strom SS, Wang X, Pettaway CA et al (2005) Obesity, weight gain, and risk of biochemical failure among prostate cancer patients following prostatectomy. Clin Cancer Res 11:6889–6894
Marcello MA, Cunha LL, Batista FA, Ward LS (2014) Obesity and thyroid cancer. Endocr Relat Cancer 21:255–271
Fox CS, Pencina MJ, D’Agostino RB et al (2008) Relations of thyroid function to body weight. Cross-sectional and longitudinal observations in a community-based sample. Arch Intern Med 168(6):587
Mcleod DSA, Cooper DS, Ladenson PW et al (2014) Prognosis of differentiated thyroid cancer in relation to serum thyrotropin and thyroglobulin antibody status at time of diagnosis. Thyroid 24:35–42
Fiore E, Rago T, Provenzale MA et al (2009) Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 16:1251–1260
Cao R, Brakenhielm E, Wahlestedt C et al (2001) Leptin induces vascular permeability and synergistically stimulates angiogenesis with FGF-2 and VEGF. Proc Natl Acad Sci U S A 98:6390–6395
Cheng S-P, Chi C-W, Tzen C-Y et al (2010) Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma. Surgery 147:847–853
Ukkola O, Santaniemi M (2002) Adiponectin: a link between excess adiposity and associated comorbidities? J Mol Med 80:696–702
Cheng SP, Liu CL, Hsu YC et al (2013) Expression and biologic significance of adiponectin receptors in papillary thyroid carcinoma. Cell Biochem Biophys 65:203–210
Mitsiades N, Pazaitou-Panayiotou K, Aronis KN et al (2011) Circulating adiponectin is inversely associated with risk of thyroid cancer: in vivo and in vitro studies. J Clin Endocrinol Metab 96:E2023–E2028
Wang ZV, Scherer PE (2016) Adiponectin, the past two decades. J Mol Cell Biol 8:93–100
Lai X, Xia Y, Zhang B et al (2017) A meta-analysis of Hashimoto’s thyroiditis and papillary thyroid carcinoma risk. Oncotarget 8:62414–62424
Harvey AE, Lashinger LM, Hursting SD (2011) The growing challenge of obesity and cancer: an inflammatory issue. Ann N Y Acad Sci 1229:45–52
Johnson DE, O’Keefe RA, Grandis JR (2018) Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol 15:234–248
Cunha LL, Marcello MA, Ward LS (2014) The role of the inflammatory microenvironment in thyroid carcinogenesis. Endocr Relat Cancer 21:R85–R103
Choi JS, Lee HS, Kim EK et al (2015) The influence of body mass index on the diagnostic performance of pre-operative staging ultrasound in papillary thyroid carcinoma. Clin Endocrinol 83:550–555
Haakinson DJ, Leeds SG, Dueck AC et al (2012) The impact of obesity on breast cancer: a retrospective review. Ann Surg Oncol 19:3012–3018. https://doi.org/10.1245/s10434-012-2320-8
Kim MR, Kim SS, Huh JE et al (2013) Neck circumference correlates with tumor size and lateral lymph node metastasis in men with small papillary thyroid carcinoma. Korean J Intern Med 28:62–71. https://doi.org/10.3904/kjim.2013.28.1.62
Cespedes Feliciano EM, Kroenke CH, Caan BJ (2018) The obesity paradox in cancer: how important is muscle? Annu Rev Nutr 38:357–379
Perros P, Boelaert K, Colley S et al (2014) Guidelines for the management of thyroid cancer. Clin Endocrinol 81:1–122
Haugen BR, Alexander EK, Bible KC et al (2016) 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 26:1–133
Bilimoria KY, Bentrem DJ, Ko CY et al (2007) Extent of surgery affects survival for papillary thyroid cancer. Ann Surg 246:375–384
Farag M, Ibraheem K, Garstka ME et al (2019) Thyroid surgery and obesity: cohort study of surgical outcomes and local specific complications. Am J Surg 217:142–145
Blanchard C, Bannani S, Pattou F et al (2019) Impact of body mass index on post-thyroidectomy morbidity. Head Neck. https://doi.org/10.1002/hed.25773
Meltzer C, Hull M, Sundang A, Adams JL (2019) Association between annual surgeon total thyroidectomy volume and transient and permanent complications. JAMA Otolaryngol Head Neck Surg. https://doi.org/10.1001/jamaoto.2019.1752
Adam MA, Thomas S, Youngwirth L et al (2017) Is there a minimum number of thyroidectomies a surgeon should perform to optimize patient outcomes? Ann Surg 265:402–407
Aspinall S, Oweis D, Chadwick D (2019) Effect of surgeons’ annual operative volume on the risk of permanent hypoparathyroidism, recurrent laryngeal nerve palsy and haematoma following thyroidectomy: analysis of United Kingdom registry of endocrine and thyroid surgery (UKRETS). Langenbeck’s Arch Surg 404:421–430
Keane E, Francis EC, Catháin EO, Rowley H (2017) The role of race in thyroid cancer: systematic review. J Laryngol Otol 131:480–486
Funding
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
O’Neill, R.J., Abd Elwahab, S., Kerin, M.J. et al. Association of BMI with Clinicopathological Features of Papillary Thyroid Cancer: A Systematic Review and Meta-Analysis. World J Surg 45, 2805–2815 (2021). https://doi.org/10.1007/s00268-021-06193-2
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00268-021-06193-2