Sudan Journal of Medical Sciences Volume 15, Issue no. 3, DOI 10.18502/sjms.v15i3.7748 Production and Hosting by Knowledge E Research Article The Best Time for Completion Thyroidectomy on Differentiated Thyroid Carcinoma: A Literature Review Hyder O. Mirghani, MD, MSc Department of Internal Medicine, Faculty of Medicine, University of Tabuk, Saudi Arabia Abstract Background: Completion thyroidectomy is performed for high-risk differentiated thyroid carcinoma; however, the timing of the completion thyroidectomy is a matter of controversy. The current review aimed to assess the best time for completion thyroidectomy in patients with differentiated thyroid carcinoma. Methods: An electronic search was conducted in various databases, such as Pub Med, Google Scholar, Scopus, and Medline, for relevant articles assessing the timing of completion thyroidectomy from the first published article to October 2019. Keywords, “completion thyroidectomy” and “timing” were used. The search was limited to articles published in the English language. Among the 190 articles retrieved, only 11 fulfilled the inclusion criteria. Results: Of the 11 articles included, two were from Europe, one from Africa, one from Australia, and seven from Asia, and all were retrospective studies with the mean duration of studies being 12.71 ± 12.31 years. Five studies (45.5%) showed no effect of timing on the outcomes, two (18.2%) recommended both early and late operation, another two (18.2%) concluded that late operation is better, one (9.1%) found that early surgery is better, while one study (9.1%) stated that the timing of operation should be based on the category of the patient. Conclusions: The results were mixed with some studies recommending late completion thyroidectomy, some observing that both early and late thyroidectomy are safe, while some finding no effect of time on the completion thyroidectomy. Well- designed controlled trials will resolve the issue. Keywords: early completion thyroidectomy, late thyroidectomy, timing 1. Introduction The type of surgery in differentiated thyroid carcinoma is controversial; many authors recommend total thyroidectomy due to the rare metastatic potential, recurrence, mor- bidity of the second operation, and the effectiveness of radioactive iodine. On the other hand, a conservative approach is recommended based on the observations that the clinical course is not affected by the multifocal disease, anaplastic transformation is How to cite this article: Hyder O. Mirghani, MD, MSc (2020) “The Best Time for Completion Thyroidectomy on Differentiated Thyroid Carcinoma: A Literature Review,” Sudan Journal of Medical Sciences, vol. 15, issue no. 3, pages 324–331. DOI 10.18502/sjms.v15i3.7748 Page 324 Corresponding Author: Hyder Osman Mirghani; Associate Professor of Internal Medicine and Endocrine, Faculty of Medicine, University of Tabuk, Saudi Arabia PO Box 3378 Tabuk 51941, Saudi Arabia. email: s.hyder63@hotmail.com Received 22 June 2020 Accepted 15 August 2020 Published 30 September 2020 Production and Hosting by Knowledge E Hyder O. Mirghani. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Editor-in-Chief: Prof. Mohammad A. M. Ibnouf http://www.knowledgee.com mailto:s.hyder63@hotmail.com https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ Sudan Journal of Medical Sciences Hyder O. Mirghani very low (<1%), and radioactive iodine therapy is possible with low morbidity [1]. While there is a debate on what needs to be done in patients with lobectomy (conservative approach) during the first operation, a completion thyroidectomy is often suggested in high-risk patients [2] to remove the remaining thyroid tissue after the first surgery when malignancy is found. Due to inflammation, edema, and scarring after the first operation, the completion of thyroidectomy is thought to carry a high risk of complications including recurrent laryngeal nerve palsy and hypoparathyroidism due to loss of landmarks [3, 4]. An early completion thyroidectomy is typically the operation conducted within seven days post lobectomy, while a late operation is the one conducted after three months [5]. Although the timing of the second operation is critical, the best time remains uncertain. Thus, we conducted the current review to assess the timing of completion thyroidectomy in patients with differentiated thyroid carcinoma. 2. Materials and Methods 2.1. Eligibility criteria according to PICOS We included all articles investigating the timing of completion thyroidectomy, the par- ticipants were adult patients with differentiated thyroid carcinoma who underwent completion thyroidectomy. With regards to the outcome measures, all manuscripts that compare early and late completion thyroidectomy in terms of operation complications, recurrence rate, and mortality between the two groups were included. Manuscripts published on surgery other than completion thyroidectomy timing were excluded from the review. 2.2. Information source and search methods Databases such as Pub Med, Scopus, Medline, and Google Scholar were searched for relevant articles including those in press starting from the first published articles to those published until October 2019. The terms used for the search were: “completion thyroidectomy” OR “thyroid reoperation” AND “timing”. In the current review, the filter was set to English language publications among adults. DOI 10.18502/sjms.v15i3.7748 Page 325 Sudan Journal of Medical Sciences Hyder O. Mirghani 2.3. Data extraction and study selection The abstracts and full articles were screened manually for relevant articles; clearly, irrelevant manuscripts were excluded according to the inclusion and exclusion criteria. The authors’ name, year of publication, country, type of study, number of patients, and the duration of the study were reported (Table 2). For the purpose of the current review, an early completion thyroidectomy is defined as an operation within the first seven days post the first operation, while a late thyroidectomy is the one conducted after three months. 2.4. Assessment of risk of bias in the included articles The Newcastle–Ottawa scale for cross-sectional studies was used to assess the quality of the selected studies (Table 1). Figure 1 shows the different phases of the systematic review. 3. Results A total of 190 studies were identified through the database search. Next, the duplicate manuscripts were removed and 20 papers were shortlisted, finally, only 11 full-text articles meeting the inclusion criteria of the review were included: (two [18.2%] papers were from Europe, one [9.1%] from Africa, one [9.1%] from Australia, and seven [63.6%] from Asia). All studies were retrospective (1616 patients included). The mean duration was 12.71 ± 12.31 years. Five studies (45.5%) showed no effect of timing on the outcomes, two (18.2%) recommended both early and late operation, another two (18.2%) concluded that late operation is better, one (9.1%) found that early surgery is better, while one study (9.1%) stated that the timing of operation should be based on the category of the patient. Table 2 depicts the details of the studied articles. 4. Discussion In the present review, the first published article retrieved [6] concluded that completion thyroidectomy should be performed as early as possible (<7 days) to prevent any permanent damage to the recurrent laryngeal nerve; a study published in Germany assessed the papillary and follicular thyroid cancer for disease-free and long-term survival, whereby a completion thyroidectomy was conducted within an interval ranging DOI 10.18502/sjms.v15i3.7748 Page 326 Sudan Journal of Medical Sciences Hyder O. Mirghani Records iden!fied through database searching (n = 190) S c r e e n in g In c lu d e d E li g ib il it y Id e n ti fi c a ti o n Addi!onal records iden!fied through other sources (n = 0); no other sources Records a#er duplicates removed (n = 20) Records screened (n = 20) Records excluded (n = 9) Full-text ar!cles assessed for eligibility (n =11 ) Full-text ar!cles excluded (n =0) because they are not randomized trials Studies included in the qualita!ve synthesis (n = 11) Figure 1: Flow diagram of the different phases of the systematic review (PRISMA flowchart). from three days to four months [7]. The authors suggest that completion thyroidectomy is better performed within seven days or after three months. Tan et al. [8] assessed 63 patients (operation time within ten days and after three months) and concluded that the timing of thyroidectomy has no impact on complications; similar findings were observed by Makay and colleagues [9] who observed 150 patients (the operation time ranged from five days to six months, followed for recurrent laryngeal nerve injury, transient, and permanent hypothyroidism). Balock et al., Kepenekçi et al., and Erbil et al. [10–12] found that the best time is after three months. Cho et al. [13] studied 522 patients with papillary thyroid carcinoma in South Korea, the American Thyroid Association [14], and DOI 10.18502/sjms.v15i3.7748 Page 327 Sudan Journal of Medical Sciences Hyder O. Mirghani TABLE 1: The quality of the selected studies determined using the Newcastle–Ottawa scale. Author Selection Compatibility and Outcome Total Score Rau et al. 4 2 6 Walgenbach et al. 4 3 7 Tan et al. 4 3 7 Makay et al. 4 3 7 Balock et al. 4 1 5 Erbil et al. 4 2 6 Kepenekçi et al. 4 2 6 Cho et al. 4 3 7 Glockzin et al. 4 3 7 K𝚤saoğlu et al. 4 2 6 Salem et al. 4 3 7 the National Comprehensive Cancer Network (NCCN) [15] were followed for the extent of surgery the authors compared early surgery (within three months) and follow-up groups without immediate surgery, the patients were observed for central and lateral recurrences. Based on the observation that no differences were found between groups, the authors concluded that the timing of completion thyroidectomy should be based on the patient’s risk category. Cho and colleagues’ [13] study was limited due to the short period of follow-up (3.5 years) that may not be enough for metastasis evaluation, and also the fact that four surgeons conducted the operations should be considered, since it is well-known that the access to an experienced surgeons is among the predictive factors of the outcome [16]. Moreover, while Glockzin et al. [17] concluded that the best time is within three days or after three months, K𝚤saoğlu et al. [1] found no effect of timing on morbidity. On the contrary, a relatively recent study conducted in Egypt [18] concluded that the best timing is at least six months after the first surgery. 5. Conclusion The time of completion thyroidectomy is better within seven days or after three months. However, some studies found no effect of timing on the outcome. Declaration Section DOI 10.18502/sjms.v15i3.7748 Page 328 Sudan Journal of Medical Sciences Hyder O. Mirghani TABLE 2: The timing of completion thyroidectomy and complications. Author Year Country Type Patients Study Period Result Rau et al. 1998 Germany Retrospective 60 10 years Time > 7 days is associated with permanent damage to the recurrent laryngeal nerve Walgenbach et al. 2002 Germany Retrospective 81 16.25 years Within seven days or after three months Tan et al. 2002 Australia Retrospective 63 45 years Timing has no impact on complications Makay et al. 2006 Turkey Retrospective 150 6.5 years Timing has no impact on complications Balock et al. 2007 Pakistan prospective 141 6.75 years Timing does not influence the complications rate Erbil et al. 2008 Turkey Retrospective 60 – 90 days after Kepenekçi et al. 2009 Turkey Retrospective 241 5.67 years Can be undertaken at any time Cho et al. 2012 South Korea Retrospective 522 4 years Should be based on the patient’s risk category Glockzin et al. 2012 Germany Retrospective 128 17 years Within three days or after three months K𝚤saoğlu et al. 2014 Turkey Retrospective 52 8 years Timing of surgery does not affect morbidity Salem et al. 2017 Egypt Retrospective 118 8 The operation should be performed at least six months after the primary surgery Acknowledgements The author would like to acknowledge Ibrahin Eltedlawi, Professor of Oncology Surgery, University of Tabuk, Saudi Arabia for revising this manuscript. Ethical Considerations The current study has been approved by the ethical committee of the Medical College, University of Tabuk, Saudi Arabia. DOI 10.18502/sjms.v15i3.7748 Page 329 Sudan Journal of Medical Sciences Hyder O. Mirghani Competing Interests The author declares that there are no conflicts of interest Availability of Data and Material The data included in this manuscript are available upon request Funding The manuscript is self-funded and not supported by any institute or organization References [1] K𝚤saoğlu, A., Özoğul, B., Akçay, M.N., et al. (2014). Completion thyroidectomy in differentiated thyroid cancer: when to perform? Turkish Journal of Surgery, vol. 30, pp. 18–21. [2] Akcan, A., Sözüer, E., Aky𝚤ld𝚤z, H., et al. (2008). Completion thyroidectomy in well-differentiated thyroid cancers-Retrospective clinical study. Turkish Journal of Surgery, vol. 24, no. 83, pp. 88. [3] Pironi, D., Pontone, S., Vendettuoli, M., et al. (2014). 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[17] Glockzin, G., Hornung, M., Kienle, K., et al. (2012). Completion thyroidectomy: effect of timing on clinical complications and oncologic outcome in patients with differentiated thyroid cancer. World Journal of Surgery, vol. 3, no. 5, pp. 1168–1173. DOI: 10.1007/s00268-012-1484-5. [18] Salem, M. A., Ahmed, B. M., and Elshoieby, M. H. (2017). Optimum timing and complication of completion thyroidectomy for differentiated thyroid cancer. Journal of Cancer Therapy, vol. 8, pp. 518–526. DOI: 10.4236/jct.2017.85044. DOI 10.18502/sjms.v15i3.7748 Page 331 Introduction Materials and Methods Eligibility criteria according to PICOS Information source and search methods Data extraction and study selection Assessment of risk of bias in the included articles Results Discussion Conclusion Declaration Section Acknowledgements Ethical Considerations Competing Interests Availability of Data and Material Funding References