G Model
ANL-1806; No. of Pages 7 Auris Nasus Larynx xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer Melek Kezban Gu¨rbu¨z a,*, Mustafa Ac¸ıkalın b, Soner Tasar c, Hamdi C¸aklı a, ¨ zu¨dog˘ru a, Cem Kec¸ik a, Ertug˘rul C¸olak f, Go¨knur Yorulmaz d, Metin Erdinc¸ e, Erkan O g Suzan S¸aylısoy a
Eskisehir Osmangazi University, Faculty of Medicine, Department of Otorhinolaryngology, Turkey Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Turkey c Eskisehir Government Hospital, Turkey d Batman Regional Hospital, Turkey e Medical Park Hospital, Us¸ak, Turkey f Eskisehir Osmangazi University, Faculty of Medicine, Department of Biostatistics, Turkey g Eskisehir Osmangazi University, Faculty of Medicine, Department of Radiology, Turkey b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 November 2012 Accepted 4 October 2013 Available online xxx
Objective: The incidence of thyroid gland invasion in patients with advanced laryngeal cancer was reported to be 0–50%. However there is a controversy in necessity and extent of routine thyroidectomy in these patients due to the difficulty in diagnosis of tumor invasion to thyroid gland and the risk of possible postoperative hypothyroidism and hypocalcemia. Methods: The medical files of 47 patients who underwent thyroidectomy as part of surgical treatment for advanced laryngeal cancer were reviewed. Results: Fourty-four (93.6%) patients underwent hemithyroidectomy, 3 (6.3%) patients underwent total thyroidectomy. Thyroid gland invasion was found in 2 (4.2%) patients. Hypothyroidism occurred in 15 (31.9%) patients, and their hormone levels were regulated with medical treatment during follow-up. Hypocalcemia was not found in any patients. Conclusion: We recommend that at least a hemithyroidectomy should be performed in patients with advanced laryngeal cancer, if they have any predictive factor (subglottic extension more than 1 cm, invasion of paraglottic space, thyroid cartilage, cricoid cartilage and prelaryngeal tissue detected by radiological examination) for thyroid gland invasion. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Advanced Laryngeal cancer Thyroid gland Invasion Thyroidectomy
1. Introduction Laryngeal cancer (LC) is one of the most common malignancies of the aerodigestive system. The majorities of this malignancy are squamous cell carcinoma (SCC) and located in the glottic region. It is classified into early and advanced stages. Advanced LC can be defined either by virtue of an advanced primary tumor or by the presence of regional lymph node metastasis. In advanced primary tumor, the tumor is limited to the larynx with vocal cord fixation or invades the cricoid cartilage, thyroid cartilage and/or other tissues
* Corresponding author at: Eskisehir Osmangazi University, Faculty of Medicine, Department of Otorhinolaryngology, 26480 Meselik, Eskisehir, Turkey. Tel.: +90 533 364 55 35; fax: +90 222 239 37 74. E-mail address: [email protected] (M.K. Gu¨rbu¨z).
beyond the larynx (e.g. trachea, thyroid gland, soft tissues of the neck, esophagus) [1,2]. The present study deals with thyroid gland invasion (TGI) and routine thyroidectomy in patients with advanced LC, which is a subject of controversy. Theoretically, invasion of laryngeal cancer to thyroid gland can occur by three pathways that are direct extension, lymphatic spread and hematogenous spread. However, direct extension is mainly mechanism due to the close anatomical relationship of the thyroid gland to the laryngeal framework. It is clear that the prognosis of patients with LC having TGI is worse than that of patients without invasion [3]. Therefore it is important to diagnose thyroid gland involvement in treatment planning to determine which patients must undergo thyroidectomy. In this work, we described our experience of management of thyroid gland in patients with advanced LC by sharing our results obtained by a retrospective review. In addition, we presented a
0385-8146/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.anl.2013.10.004
Please cite this article in press as: Gu¨rbu¨z MK, et al. Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.10.004
G Model
ANL-1806; No. of Pages 7 M.K. Gu¨rbu¨z et al. / Auris Nasus Larynx xxx (2013) xxx–xxx
2
literature review including the rates and types of TGI in patients with advanced LC. 2. Materials and methods This retrospective study was performed in accordance with local laws, and approval was obtained from the University’s Ethics Committee. The study consisted of patients who underwent thyroidectomy as part of surgical treatment for advanced LC during 2006–2011. Seven patients who had not regular follow-up were excluded from the study. A total of 47 patients were included in the study. Data were collected from the medical files of patients. A data collection form used to record the clinicopathological characteristics of patients is shown in Table 1. Subglottic extension more than 1 cm, invasion of paraglottic space, thyroid cartilage, cricoid cartilage and prelaryngeal tissue identified by contrast-enhanced computerized tomography (CT) were considered as predictive factors for TGI. Lymph nodes were considered to be metastatic on CT scans if central necrosis or extracapsular spread was present irrespective of size, if their shortest axial diameter reached 11 mm in the jugulodigastric region and 10 mm in other cervical regions, or if there was a group of 3 or more nodes that were borderline in
Table 1 Data collection form. I. Demograhic characteristics a. Age b. Gender II. History of preoperative radiotherapy (RT) III. Characteristics of the tumor a. Histopathology b. Origin c. Stage IV. Findings of contrast-enhanced computerized tomography (CT) of the head and neck performed preoperatively a. Radiologic evidence for TGI b. Predictive factors for thyroidectomy -Subglottic extension more than 1 cm -The invasion of paraglottic space -The invasion of thyroid cartilage -The invasion of cricoid cartilage -The invasion of prelaryngeal tissue V. Operation notes a. Types of laryngectomy b. Neck dissections (unilateral/bilateral) c. Extent of thyroidectomy VI. Results of frozen section of thyroid tissue VII. Results of postoperatively histopathologic examination a. Thyroid gland invasion b. Pimer thyroid gland malignancy c. Tumor invasion to subglottic region d. Tumor invasion to paraglottic space e. Tumor invasion to thyroid cartilage f. Tumor invasion to prelaryngeal tissue g. Cervical lymph node metastasis h. Perineural invasion i. Vascular invasion VIII. Laboratuary a. Preoperative -Serum calcium level -Serum thyroid hormone level b. Postoperative -Serum calcium level -Serum thyroid hormone level IX. Postoperatif follow-up -History of RT -Disease-free survival
size. Round nodes were also more likely to harbor metastases than oval nodes. The patients were staged according to the TNM classification published in 2002 by the American Joint Committee on Cancer (AJCC). The evaluation of computerized tomography (CT) scans and pathologic specimens was performed by experienced radiologist and pathologist, respectively. 2.1. Statistical analysis The dependence between TGI and predictive factors for thyroidectomy obtained by CT scan was analyzed using Fisher Exact test. To analyze the accuracy of tumor spread obtained by CT scan, radiological and histopathological evaluation of tumor invasion (invasion to the subglottic area, thyroid cartilage, cricoid cartilage, paraglottic space, thyroid gland and prelaryngeal soft tissue) were compared using McNamer Chi-square test. The specificity, sensitivity, accuracy of CT scan and the 95% confidence interval of these values were also calculated. The dependence between the tumor spread and the degree of differentiation of the tumor was analyzed using Pearson Chi-square Exact test. Survival rate was calculated using the Kaplan–Meier method. All of the statistical analyses were performed using IBM SPSS Statistics 20. P value of 1cm on the contralateral lobe
Palpated nodule (-) on the contralateral lobe
Ipsilateral Hemithyroidectomy
Due to risk of synchronous primary thyroid cancers Frozen section examination
Positive
Total thyroidectomy
Negative
Waiting for final histopathological
in the remaining thyroid tissue
examination
Malignancy (-)
Due to the risk of occult invasion
Malignancy (+)
Follow- up
the dependence between TGI and predictive factors was analyzed in the present study: the most frequently detected predictive factors were the invasion of paraglottic space, prelaryngeal tissue, thyroid cartilage and subglottic area, respectively, and the majority of patients had at least one predictive factor that verified histopathologically. However the evidence of histopathological TGI had been observed in only 2 (4.2%) patients and we did not find a correlation between TGI and predictive factors statistically. In accordance with these results, it is possible to say that TGI is not a commonly noted phenomenon and it may be perceived that we have made unnecessarily hemithyroidectomy in most patients and so that we have placed extra burden on patients by causing hypothyroidism. However we do not agree with this judgement because of 4 reasons: firstly, the removal of half of the thyroid gland alone mostly does not cause hypothyroidism. Secondly, hypothyroidism may be an inevitable fate in patients with advanced LC, even if thyroid lobes have been preserved, because conventional treatment for advanced LC generally consists of the surgery and postoperative external beam radiation, and also
radiotherapy can lead to hypothyroidism in these patients by corrupting the function and vascularization of thyroid gland. Thirdly, the consequent hypothyroidism can be effectively managed medically. Lastly, the involvement of thyroid gland in patients with LC cannot be diagnosed still accurately today with radiologic imaging techniques. The removal of half of the thyroid gland facilitates the identification of thyroid gland involvement. Thus, patients with TGI will not be omitted and their surgical treatment will be complete. Our results also support all these ideas: hypothyroidism was found in 15 (31.9%) patients. Three (20%) of them were the patients that underwent total thyroidectomy, 2 (13.3%) of them had a history of preoperative RT and 7 (46.6%) of them received postoperative RT. Eighteen (38.2%) patients out of 47 patients had not a history of RT, and hypothyroidism occurred only in 3 (16.6%) patients out of them. In other words, the removal of half of the thyroid gland alone leads to hypothyroidism only in 3 patients. Thyroid hormone levels of all 15 patients were precisely regulated during follow up. The patients that had histopathologic evidence for TGI had not radiologic evidence for thyroid
Please cite this article in press as: Gu¨rbu¨z MK, et al. Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.10.004
G Model
ANL-1806; No. of Pages 7 M.K. Gu¨rbu¨z et al. / Auris Nasus Larynx xxx (2013) xxx–xxx
gland involvement, and these patients were detected thanks to thyroidectomy. Additionally, there are studies that show presence of thyroid gland invasion is associated with a poor prognosis and local recurrence [3,9,13]. Unfortunately, distant metastases and deaths may have to be inevitable in these patients despite total thyroidectomy as in the present study. However, we are in the opinion that the results of this small number of patients should not be used to arrive at conclusions. We also believe that total thyroidectomy may minimize the risk of local recurrence and may improve the prognosis of these patients, at any rate, by providing surgical margin. Otherwise, in the course of time, additional serious problems would be not inevitable and the comfort of patients can get worse. For instance, esophago-cutaneous fistulas that are difficult to deal with would be occurred by invasion of cancer cells into the esophagus due to the close anatomical relationship. Therefore it is a great importance to identify TGI accurately in patients with LC prior to treatment planning. Lastly, despite the low incidence, we would like to highlight the possibility of association of squamous cell carcinoma of the larynx with primary thyroid cancer [22,23]. This topic is recently noteworthy especially in patients with LC who are candidates for open laryngectomy. The reason is that the prognosis of patients having synchronous laryngeal and thyroid cancer would be worse if the diagnosis of primary thyroid cancer is omitted, because required surgery for thyroidectomy would be more difficult owing to the adhesions around thyroid gland formed due to laryngectomy. Of course, it may be more important in patients who are candidates for adjuvant RT postoperatively that might lead to increased adhesions around surgical field and might aggravate primary thyroid cancer. For all these reasons, some authors advocated that thyroid gland should also be evaluated in respect to synchronous thyroid tumors in patients with LC, and they encourage using ultrasonography (USG) for this purpose [24]. Due to concern of loss of time and additional cost in treatment process that may be caused by ultrasonographic evaluation, we prefered intraoperative palpation as a simple method so far. However we also agree with widely adopted opinion that USG is more useful than intraoperative palpation for detecting synchronous thyroid tumors, especially in patients with diffuse goiter in whom detecting tumor by palpation is sometimes difficult. In conclusion, it is obvious that patients with advanced LC have a risk of the invasion of the tumor to thyroid gland even though the rate is low according to the literature review. It is important to get an accurate diagnosis of thyroid gland involvement preoperatively to select patients for thyroidectomy. However it is unfortunately difficult to diagnose thyroid gland involvement still accurately today. Radiological errors are inevitable as in the present study. New scientific and technological advances are needed for more accurately diagnosis of thyroid gland involvement in patients with LC. Therefore we recommend using some radiologic clues to predict the involvement of thyroid gland and routine hemithyroidectomy in patients with advanced LC if they have any of these radiologic clues. So, potential thyroid gland involvement can be diagnosed through frozen section examination of removed part of thyroid
7
gland. We also believe that the removal of half of thyroid gland does not give rise to extra burden on patients. Conflict of interest None. References [1] Sinard RJ, Netterville JL, Garrett CG, Ossoff RH. Cancer of the larynx. In: Myers EN, Suen JY, editors. Cancer of the head and neck. 3th ed., Philadelphia, PA: W.B. Saunders Company; 1996. p. 381–422. [2] Carew JF. The larynx: advanced stage disease. In: Shah JP, editor. Atlas of clinical oncology, cancer of the head and neck. Hamilton/London: BC Decker Inc.; 2001. p. 156–68. [3] Kim JW, Han GS, Byun SS, Lee DY, Cho BH, Kim YM. Management of thyroid gland invasion in laryngopharyngeal cancer. Auris Nasus Larynx 2008;35: 209–12. [4] Brennan JA, Meyers AD, Jafek BW. The intraoperative management of the thyroid gland during laryngectomy. Laryngoscope 1991;101:929–34. [5] Al-Khatib T, Mendelson AA, Kost K, Zeitouni A, Black M, Payne R, et al. Routine thyroidectomy in total laryngectomy: is it really indicated? J Otolaryngol Head Neck Surg 2009;38:564–7. [6] Fagan JJ, Kaye PV. Management of the thyroid gland with laryngectomy for cT3 glottic carcinomas. Clin Otolaryngol Allied Sci 1997;22:7–12. [7] Dadas B, Uslu B, Cakir B, Ozdog˘an HC, Calis¸ AB, Turgut S. Intraoperative management of the thyroid gland in laryngeal cancer surgery. J Otolaryngol 2001;30:179–83. [8] Gurunathan RK, Panda NK, Das A, Karuppiah S. Thyroid gland in carcinoma of the larynx and hypopharynx: analysis of factors indicating thyroidectomy. J Otolaryngol Head Neck Surg 2008;37:435–9. [9] Elliot MS, Odell EW, Tysome JR, Connor SEJ, Siddiqui A, Jeannon JP, et al. Role of thyroidectomy in advanced laryngeal and pharyngolaryngeal carcinoma. J Otolaryngol Head Neck Surg 2010;142:851–5. [10] Harrison DF. Laryngectomy for subglottic lesions. Laryngoscope 1975;85: 1208–10. [11] Pittam MR, Carter RL. Framework invasion by laryngeal carcinomas. Head Neck Surg 1982;4:200–8. [12] Bahadur S, Iyer S, Kacker SK. The thyroid gland in the management of carcinoma of the larynx and laryngopharynx. J Laryngol Otol 1985;99: 1251–3. [13] Biel MA, Maisel RH. Indications for performing hemithyroidectomy for tumors requiring total laryngectomy. Am J Surg 1985;150:435–9. [14] Gilbert RW, Cullen RJ, van Nostrand AW, Bryce DP, Harwood AR. Prognostic significance of thyroid gland involvement in laryngeal carcinoma. Arch Otolaryngol Head Neck Surg 1986;112:856–9. [15] Gal RL, Gal TJ, Klotch DW, Cantor AB. Risk factors associated with hypothyroidism after laryngectomy. Otolaryngol Head Neck Surg 2000;123:211–7. [16] Ceylan A, Ko¨ybas¸iog˘lu A, Yilmaz M, Uslu S, Asal K, Inal E. Thyroid gland invasion in advanced laryngeal and hypopharyngeal carcinoma. Kulak Burun Bogaz Ihtis Derg 2004;13:9–14. [17] Sparano A, Chernock R, Laccourreye O, Weinstein G, Feldman M. Predictors of thyroid gland invasion in glottic squamous cell carcinoma. Laryngoscope 2005;115:1247–50. [18] Garas J, McGuirt Sr WF. Squamous cell carcinoma of the subglottis. Am J Otolaryngol 2006;27:1–4. [19] Gaillardin L, Beutter P, Cottier JP, Arbion F, Morinie`re S. Thyroid gland invasion in laryngopharyngeal squamous cell carcinoma: prevalence, endoscopic and CT predictors. Eur Ann Otorhinolaryngol Head Neck Dis 2012;129:1–5. [20] Timon CV, Toner M, Conlon BJ. Paratracheal lymph node involvement in advanced cancer of the larynx, hypopharynx, and cervical esophagus. Laryngoscope 2003;113:1595–9. [21] Hoover LA, Calcaterra TC, Walter GA, Larrson SG, Preoperative CT. scan evaluation for laryngeal carcinoma: correlation with pathological findings. Laryngoscope 1984;94:310–5. [22] Shih C, Wang CP, Lou PJ, Hu YL, Yang TL, Ko JY, et al. Thyroid cancer incidentally found in radical surgery for laryngeal/hypopharyngeal cancer. Otolaryngol Head Neck Surg 2009;141:343–6. [23] Iqbal FR, Sani A, Gendeh BS, Aireen I. Triple primary cancers of the larynx, lung and thyroid presenting in one patient. Med J Malaysia 2008;63:417–8. [24] Ashraf MJ, Alavi MS, Azarpira N, Khademi B. Simultaneous laryngeal squamous cell carcinoma and papillary thyroid carcinoma. Middle East J Cancer 2011; 2:87–90.
Please cite this article in press as: Gu¨rbu¨z MK, et al. Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.10.004
ANL-1806; No. of Pages 7 Auris Nasus Larynx xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer Melek Kezban Gu¨rbu¨z a,*, Mustafa Ac¸ıkalın b, Soner Tasar c, Hamdi C¸aklı a, ¨ zu¨dog˘ru a, Cem Kec¸ik a, Ertug˘rul C¸olak f, Go¨knur Yorulmaz d, Metin Erdinc¸ e, Erkan O g Suzan S¸aylısoy a
Eskisehir Osmangazi University, Faculty of Medicine, Department of Otorhinolaryngology, Turkey Eskisehir Osmangazi University, Faculty of Medicine, Department of Pathology, Turkey c Eskisehir Government Hospital, Turkey d Batman Regional Hospital, Turkey e Medical Park Hospital, Us¸ak, Turkey f Eskisehir Osmangazi University, Faculty of Medicine, Department of Biostatistics, Turkey g Eskisehir Osmangazi University, Faculty of Medicine, Department of Radiology, Turkey b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 26 November 2012 Accepted 4 October 2013 Available online xxx
Objective: The incidence of thyroid gland invasion in patients with advanced laryngeal cancer was reported to be 0–50%. However there is a controversy in necessity and extent of routine thyroidectomy in these patients due to the difficulty in diagnosis of tumor invasion to thyroid gland and the risk of possible postoperative hypothyroidism and hypocalcemia. Methods: The medical files of 47 patients who underwent thyroidectomy as part of surgical treatment for advanced laryngeal cancer were reviewed. Results: Fourty-four (93.6%) patients underwent hemithyroidectomy, 3 (6.3%) patients underwent total thyroidectomy. Thyroid gland invasion was found in 2 (4.2%) patients. Hypothyroidism occurred in 15 (31.9%) patients, and their hormone levels were regulated with medical treatment during follow-up. Hypocalcemia was not found in any patients. Conclusion: We recommend that at least a hemithyroidectomy should be performed in patients with advanced laryngeal cancer, if they have any predictive factor (subglottic extension more than 1 cm, invasion of paraglottic space, thyroid cartilage, cricoid cartilage and prelaryngeal tissue detected by radiological examination) for thyroid gland invasion. ß 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Advanced Laryngeal cancer Thyroid gland Invasion Thyroidectomy
1. Introduction Laryngeal cancer (LC) is one of the most common malignancies of the aerodigestive system. The majorities of this malignancy are squamous cell carcinoma (SCC) and located in the glottic region. It is classified into early and advanced stages. Advanced LC can be defined either by virtue of an advanced primary tumor or by the presence of regional lymph node metastasis. In advanced primary tumor, the tumor is limited to the larynx with vocal cord fixation or invades the cricoid cartilage, thyroid cartilage and/or other tissues
* Corresponding author at: Eskisehir Osmangazi University, Faculty of Medicine, Department of Otorhinolaryngology, 26480 Meselik, Eskisehir, Turkey. Tel.: +90 533 364 55 35; fax: +90 222 239 37 74. E-mail address: [email protected] (M.K. Gu¨rbu¨z).
beyond the larynx (e.g. trachea, thyroid gland, soft tissues of the neck, esophagus) [1,2]. The present study deals with thyroid gland invasion (TGI) and routine thyroidectomy in patients with advanced LC, which is a subject of controversy. Theoretically, invasion of laryngeal cancer to thyroid gland can occur by three pathways that are direct extension, lymphatic spread and hematogenous spread. However, direct extension is mainly mechanism due to the close anatomical relationship of the thyroid gland to the laryngeal framework. It is clear that the prognosis of patients with LC having TGI is worse than that of patients without invasion [3]. Therefore it is important to diagnose thyroid gland involvement in treatment planning to determine which patients must undergo thyroidectomy. In this work, we described our experience of management of thyroid gland in patients with advanced LC by sharing our results obtained by a retrospective review. In addition, we presented a
0385-8146/$ – see front matter ß 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.anl.2013.10.004
Please cite this article in press as: Gu¨rbu¨z MK, et al. Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.10.004
G Model
ANL-1806; No. of Pages 7 M.K. Gu¨rbu¨z et al. / Auris Nasus Larynx xxx (2013) xxx–xxx
2
literature review including the rates and types of TGI in patients with advanced LC. 2. Materials and methods This retrospective study was performed in accordance with local laws, and approval was obtained from the University’s Ethics Committee. The study consisted of patients who underwent thyroidectomy as part of surgical treatment for advanced LC during 2006–2011. Seven patients who had not regular follow-up were excluded from the study. A total of 47 patients were included in the study. Data were collected from the medical files of patients. A data collection form used to record the clinicopathological characteristics of patients is shown in Table 1. Subglottic extension more than 1 cm, invasion of paraglottic space, thyroid cartilage, cricoid cartilage and prelaryngeal tissue identified by contrast-enhanced computerized tomography (CT) were considered as predictive factors for TGI. Lymph nodes were considered to be metastatic on CT scans if central necrosis or extracapsular spread was present irrespective of size, if their shortest axial diameter reached 11 mm in the jugulodigastric region and 10 mm in other cervical regions, or if there was a group of 3 or more nodes that were borderline in
Table 1 Data collection form. I. Demograhic characteristics a. Age b. Gender II. History of preoperative radiotherapy (RT) III. Characteristics of the tumor a. Histopathology b. Origin c. Stage IV. Findings of contrast-enhanced computerized tomography (CT) of the head and neck performed preoperatively a. Radiologic evidence for TGI b. Predictive factors for thyroidectomy -Subglottic extension more than 1 cm -The invasion of paraglottic space -The invasion of thyroid cartilage -The invasion of cricoid cartilage -The invasion of prelaryngeal tissue V. Operation notes a. Types of laryngectomy b. Neck dissections (unilateral/bilateral) c. Extent of thyroidectomy VI. Results of frozen section of thyroid tissue VII. Results of postoperatively histopathologic examination a. Thyroid gland invasion b. Pimer thyroid gland malignancy c. Tumor invasion to subglottic region d. Tumor invasion to paraglottic space e. Tumor invasion to thyroid cartilage f. Tumor invasion to prelaryngeal tissue g. Cervical lymph node metastasis h. Perineural invasion i. Vascular invasion VIII. Laboratuary a. Preoperative -Serum calcium level -Serum thyroid hormone level b. Postoperative -Serum calcium level -Serum thyroid hormone level IX. Postoperatif follow-up -History of RT -Disease-free survival
size. Round nodes were also more likely to harbor metastases than oval nodes. The patients were staged according to the TNM classification published in 2002 by the American Joint Committee on Cancer (AJCC). The evaluation of computerized tomography (CT) scans and pathologic specimens was performed by experienced radiologist and pathologist, respectively. 2.1. Statistical analysis The dependence between TGI and predictive factors for thyroidectomy obtained by CT scan was analyzed using Fisher Exact test. To analyze the accuracy of tumor spread obtained by CT scan, radiological and histopathological evaluation of tumor invasion (invasion to the subglottic area, thyroid cartilage, cricoid cartilage, paraglottic space, thyroid gland and prelaryngeal soft tissue) were compared using McNamer Chi-square test. The specificity, sensitivity, accuracy of CT scan and the 95% confidence interval of these values were also calculated. The dependence between the tumor spread and the degree of differentiation of the tumor was analyzed using Pearson Chi-square Exact test. Survival rate was calculated using the Kaplan–Meier method. All of the statistical analyses were performed using IBM SPSS Statistics 20. P value of 1cm on the contralateral lobe
Palpated nodule (-) on the contralateral lobe
Ipsilateral Hemithyroidectomy
Due to risk of synchronous primary thyroid cancers Frozen section examination
Positive
Total thyroidectomy
Negative
Waiting for final histopathological
in the remaining thyroid tissue
examination
Malignancy (-)
Due to the risk of occult invasion
Malignancy (+)
Follow- up
the dependence between TGI and predictive factors was analyzed in the present study: the most frequently detected predictive factors were the invasion of paraglottic space, prelaryngeal tissue, thyroid cartilage and subglottic area, respectively, and the majority of patients had at least one predictive factor that verified histopathologically. However the evidence of histopathological TGI had been observed in only 2 (4.2%) patients and we did not find a correlation between TGI and predictive factors statistically. In accordance with these results, it is possible to say that TGI is not a commonly noted phenomenon and it may be perceived that we have made unnecessarily hemithyroidectomy in most patients and so that we have placed extra burden on patients by causing hypothyroidism. However we do not agree with this judgement because of 4 reasons: firstly, the removal of half of the thyroid gland alone mostly does not cause hypothyroidism. Secondly, hypothyroidism may be an inevitable fate in patients with advanced LC, even if thyroid lobes have been preserved, because conventional treatment for advanced LC generally consists of the surgery and postoperative external beam radiation, and also
radiotherapy can lead to hypothyroidism in these patients by corrupting the function and vascularization of thyroid gland. Thirdly, the consequent hypothyroidism can be effectively managed medically. Lastly, the involvement of thyroid gland in patients with LC cannot be diagnosed still accurately today with radiologic imaging techniques. The removal of half of the thyroid gland facilitates the identification of thyroid gland involvement. Thus, patients with TGI will not be omitted and their surgical treatment will be complete. Our results also support all these ideas: hypothyroidism was found in 15 (31.9%) patients. Three (20%) of them were the patients that underwent total thyroidectomy, 2 (13.3%) of them had a history of preoperative RT and 7 (46.6%) of them received postoperative RT. Eighteen (38.2%) patients out of 47 patients had not a history of RT, and hypothyroidism occurred only in 3 (16.6%) patients out of them. In other words, the removal of half of the thyroid gland alone leads to hypothyroidism only in 3 patients. Thyroid hormone levels of all 15 patients were precisely regulated during follow up. The patients that had histopathologic evidence for TGI had not radiologic evidence for thyroid
Please cite this article in press as: Gu¨rbu¨z MK, et al. Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.10.004
G Model
ANL-1806; No. of Pages 7 M.K. Gu¨rbu¨z et al. / Auris Nasus Larynx xxx (2013) xxx–xxx
gland involvement, and these patients were detected thanks to thyroidectomy. Additionally, there are studies that show presence of thyroid gland invasion is associated with a poor prognosis and local recurrence [3,9,13]. Unfortunately, distant metastases and deaths may have to be inevitable in these patients despite total thyroidectomy as in the present study. However, we are in the opinion that the results of this small number of patients should not be used to arrive at conclusions. We also believe that total thyroidectomy may minimize the risk of local recurrence and may improve the prognosis of these patients, at any rate, by providing surgical margin. Otherwise, in the course of time, additional serious problems would be not inevitable and the comfort of patients can get worse. For instance, esophago-cutaneous fistulas that are difficult to deal with would be occurred by invasion of cancer cells into the esophagus due to the close anatomical relationship. Therefore it is a great importance to identify TGI accurately in patients with LC prior to treatment planning. Lastly, despite the low incidence, we would like to highlight the possibility of association of squamous cell carcinoma of the larynx with primary thyroid cancer [22,23]. This topic is recently noteworthy especially in patients with LC who are candidates for open laryngectomy. The reason is that the prognosis of patients having synchronous laryngeal and thyroid cancer would be worse if the diagnosis of primary thyroid cancer is omitted, because required surgery for thyroidectomy would be more difficult owing to the adhesions around thyroid gland formed due to laryngectomy. Of course, it may be more important in patients who are candidates for adjuvant RT postoperatively that might lead to increased adhesions around surgical field and might aggravate primary thyroid cancer. For all these reasons, some authors advocated that thyroid gland should also be evaluated in respect to synchronous thyroid tumors in patients with LC, and they encourage using ultrasonography (USG) for this purpose [24]. Due to concern of loss of time and additional cost in treatment process that may be caused by ultrasonographic evaluation, we prefered intraoperative palpation as a simple method so far. However we also agree with widely adopted opinion that USG is more useful than intraoperative palpation for detecting synchronous thyroid tumors, especially in patients with diffuse goiter in whom detecting tumor by palpation is sometimes difficult. In conclusion, it is obvious that patients with advanced LC have a risk of the invasion of the tumor to thyroid gland even though the rate is low according to the literature review. It is important to get an accurate diagnosis of thyroid gland involvement preoperatively to select patients for thyroidectomy. However it is unfortunately difficult to diagnose thyroid gland involvement still accurately today. Radiological errors are inevitable as in the present study. New scientific and technological advances are needed for more accurately diagnosis of thyroid gland involvement in patients with LC. Therefore we recommend using some radiologic clues to predict the involvement of thyroid gland and routine hemithyroidectomy in patients with advanced LC if they have any of these radiologic clues. So, potential thyroid gland involvement can be diagnosed through frozen section examination of removed part of thyroid
7
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Please cite this article in press as: Gu¨rbu¨z MK, et al. Clinical effectiveness of thyroidectomy on the management of locally advanced laryngeal cancer. Auris Nasus Larynx (2013), http://dx.doi.org/10.1016/j.anl.2013.10.004
