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The Advantage of Total Thyroidectomy to Avoid Reoperation for Incidental Thyroid Cancer in Multinodular Goiter
Yasemin Giles, MD;
Harika Boztepe, MD;
Tarik Terzio lu, MD;
Serdar Tezelman, MD
Arch Surg. 2004;139:179-182.
ABSTRACT
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Hypothesis To investigate the impact of total thyroidectomy on the rate of completion thyroidectomy for incidentally found thyroid cancer in euthyroid multinodular goiter.
Design A randomized, prospective clinical trial.
Setting A tertiary referral center.
Patients Patients with euthyroid multinodular goiter without any preoperative suspicion of malignancy, history of familial thyroid cancer, or previous exposure to radiation were randomized (according to a random table) to total or near-total thyroidectomy leaving no remnant tissue or less than 1 g (group 1; n = 109) or bilateral subtotal thyroidectomy leaving 5 g or more of remnant tissue (group 2; n = 109). Patients with preoperative or perioperative suspicion of malignancy were excluded.
Main Outcome Measures We compared the complication rates and the incidence of thyroid cancer requiring radioactive iodine ablation and completion thyroidectomy between groups.
Results There were no permanent complications. The rates of temporary unilateral vocal cord dysfunction and hypoparathyroidism showed no significant difference between groups 1 and 2 (0.9% vs 0.9% and 1.8% vs 0.9%, respectively; P>.05). Papillary cancer was found in 10 group 1 patients (9.2%) and 8 group 2 patients (7.3%) (P = .80). Of the 9 patients requiring radioactive iodine ablation, reoperation was avoided in 5 group 1 patients; the remaining 4 group 2 patients underwent completion thyroidectomy (P = .007).
Conclusion We recommend total or near-total thyroidectomy in multinodular goiter to eliminate the necessity for early completion thyroidectomy in case of a final diagnosis of thyroid cancer.
INTRODUCTION
Total thyroidectomy is the procedure of choice in patients with thyroid cancer, Basedow or Graves disease, and toxic multinodular goiter. In recent years, total thyroidectomy has emerged as a surgical option to treat patients with multinodular goiter, especially in endemic iodine-deficient regions.1-11 Multinodular hyperplasia frequently involves the whole gland in endemic regions, and there is no normal tissue to leave behind. The rate of recurrence is high after subtotal resections for multinodular goiter in long-term follow-up, despite postoperative thyroid hormone supplementation.2, 6, 8, 12-15 A considerable number of patients undergoing primary treatment with subtotal resection need reoperation for recurrence, which has a higher rate of complication compared with the primary procedures.6, 16-20 The incidence of thyroid cancer varies from 7.5% to 13% in multinodular goiter.21-23 The presence of multiple nodules decreases the diagnostic value of fine-needle aspiration biopsy, and thyroid cancer is frequently an incidental postoperative histological finding in multinodular goiter. In such patients treated with subtotal thyroidectomy, completion thyroidectomy might be necessary.
The aim of this study was to investigate whether total or near-total thyroidectomy decreased the rate of completion thyroidectomy for incidentally diagnosed thyroid cancer in multinodular goiter in an endemic iodine-deficiency region.
METHODS
From September 1, 2001, to December 31, 2002, we undertook a prospective study to compare the rates of completion thyroidectomy for incidentally found thyroid cancer after total or near-total and subtotal thyroidectomy in multinodular goiter. Two hundred eighteen patients with multinodular goiter were included in the study. All patients were euthyroid and had no history of hyperthyroidism, radiation exposure, or familial thyroid cancer. Thyroid scanning and ultrasonography revealed multinodular hyperplasia of the thyroid gland in all patients. Patients were selected according to the number on the random table for 2 different extensions of surgical procedures. The total amount of remnant thyroid tissue was intended to be none or less than 1 g in group 1 and 5 g or more in group 2. Near-total thyroidectomy was performed by the capsular dissection method, leaving less than 1 g of remnant tissue. The amount of remnant tissue was estimated as 1 cm3 equals 1 g. Any patient with preoperative or perioperative suspicion of malignancy was excluded. Postoperative complications, thyrotropin (TSH) values, and the incidence of thyroid cancer were assessed in both groups. We investigated whether there was a significant difference in the rate of thyroid cancer requiring radioactive iodine (RAI) ablation and completion thyroidectomy between groups. Histological criteria for RAI therapy included tumor size greater than 1.5 cm, any size of tumor with thyroid capsule or extrathyroidal invasion, or multicentricity ( 3 tumor foci). The departments of general surgery and endocrinology collaborate to maintain the treatment of patients with thyroid cancer at Istanbul Medical Faculty, Istanbul, Turkey. The histological criteria for postoperative RAI ablation (100 mCi [3700 MBq]) was established as a result of this cooperative work and has been our policy for the past 2 decades. The TSH values were required to be more than 30 mIU/L to refer the patient to RAI ablation therapy. Patients who were treated with RAI were verified to have undetectable levels of serum thyroglobulin and no uptake at the thyroid bed or distant sites by iodine I131 (131I)–labeled thyroid and whole body scans after the treatment. These patients received suppressive doses of thyroid hormone, and serum thyroglobulin assays were performed at 6-month intervals. Thyroid and whole body scans labeled with 131I were repeated if serum thyroglobulin levels increased during further follow-up. Patients with noninvasive microcarcinoma who did not receive RAI ablation received suppressive doses of thyroid hormone after thyroidectomy. The follow-up schedule of these patients was similar to that of patients undergoing operation for benign goiter (neck examination and determination of serum TSH values every 6 months for the initial 2 years and then annually). Linear correlation, paired t test, and Fisher exact test were used for statistical analysis, and P<.05 was accepted as significant. The ethics committee of our institution approved of the study, and informed consent was obtained from all patients participating in the trial.
RESULTS
PREOPERATIVE FINDINGS
The mean ± SD age was found to be significantly higher in group 1 (50.3 ± 12.5 years) compared with group 2 (45.7 ± 12.1 years) (P = .02). The male-female ratio was 15:94 and 17:92 in groups 1 and 2, respectively (P = .70). A coexistent dominant nodule was found in 39 patients (17.9%), including 20 in group 1 and 19 in group 2.
PERIOPERATIVE FINDINGS
Total and near-total thyroidectomy was performed in 19 (17.4%) and 90 (82.6%) patients, respectively, in group 1. Bilateral subtotal thyroidectomy was performed in all 109 patients in group 2. The total amount of remnant tissue was estimated to be 5 g in 77 patients (70.6%), 6 g in 26 (23.9%), and 7 g in 6 (5.5%).
POSTOPERATIVE FINDINGS
Permanent hypoparathyroidism and vocal cord paralysis were not encountered in either group of patients. The rate of temporary unilateral vocal cord dysfunction was the same (0.9%) in both groups. Although not statistically significant, the incidence of temporary hypoparathyroidism was slightly higher in group 1 than in group 2 (1.8% vs 0.9%).
The mean ± SD value of the TSH value at the first postoperative month was significantly higher in group 1 compared with group 2 (45.3 ± 17.3 vs 11.5 ± 6.5 mIU/L) (P<.001). Papillary cancer was detected in 18 patients (8.2%), of whom 13 (72%) had papillary microcarcinoma (<1 cm). Of 39 patients with a coexistent dominant nodule, papillary cancer was found in only 1. This patient had a papillary microcarcinoma not originating from the dominant nodule and without local invasion or multicentricity. The incidence of papillary cancer was 9.2% (10/109) in group 1 and 7.3% (8/109) in group 2 (P = .80) (Table 1). Of 18 patients with papillary cancer, 9 (50%) had microcarcinoma with no local invasion or multicentricity. These patients were scheduled for follow-up only. The remaining 9 patients were found to have the histological criteria for RAI ablation (Table 1). Of these 9 patients, 5 were in group 1 and 4 in group 2. Five patients in group 1 received RAI ablative therapy directly. The TSH values of the 4 patients in group 2 were below 30 mIU/L, and these patients underwent completion thyroidectomy before ablative therapy. Thus, of 9 patients requiring RAI ablation, reoperation was avoided in 5 group 1 patients; however, 4 patients in group 2 underwent completion thyroidectomy (P = .007). There were no complications after completion thyroidectomy in those 4 patients.
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The Histological Feature of Papillary Cancer in Groups 1 and 2
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COMMENT
In the present study, the incidence of incidental thyroid cancer was found to be 8.2% in patients undergoing operation for multinodular euthyroid goiter without any preoperative or perioperative suspicion of malignancy. We documented that performance of total or near-total thyroidectomy instead of subtotal resection as the primary procedure significantly reduced the rate of completion thyroidectomy for incidentally found thyroid cancer in multinodular goiter. Total or near-total thyroidectomy was associated with a slightly higher risk for temporary hypoparathyroidism, but this was not statistically significant.
The goal of surgical treatment in thyroid disease should be to eliminate the disease with low complication rates and to minimize the necessity for reoperative procedures. Reoperations are undertaken for postoperative histological evidence of thyroid cancer or recurrent goiter during further follow-up and are associated with higher complication rates compared with primary procedures.1, 6-20,24-25
Multinodular goiter is the most common indication for thyroidectomy in endemic iodine-deficient regions. Preoperative evaluation for thyroid cancer by means of fine-needle aspiration biopsy is difficult in multinodular goiter owing to the presence of multiple nodules, and thyroid cancer is frequently an unexpected postoperative finding. The risk for malignancy was thought to be lower in multinodular goiter compared with solitary cold nodules. Recent studies, however, documented that this was not the case. The incidence of thyroid cancer showed no significant difference in solitary cold nodules and in cold nodules of multinodular goiter, and patients with thyroid cancer frequently presented with multinodular goiter.21, 26-27 Reoperation should be performed in patients with incidentally found thyroid cancer if the histological criteria mandate RAI ablation and there is a large volume of thyroid remnant. In the present study, of 9 patients scheduled for RAI ablation, tumor size was smaller than 1.5 cm in 7. Although these patients were considered to be at low risk according to MACIS (Metastasis, Age, Curative resection, Invasion, Size) classification, histological examination revealed multifocality, thyroid capsule invasion, or extrathyroidial spread. Low-risk patients have a favorable prognosis, but multifocality, thyroid capsule invasion, and extrathyroidial invasion were shown to adversely affect the prognosis.28-31 Baudin et al31 analyzed the data of 281 patients with thyroid microcarcinoma (<1 cm) and documented that patients with more than 1 tumor focus had a significantly higher rate of recurrence compared with those with unifocal tumors, and multifocality significantly influenced the prevalence of RAI treatment. The RAI ablation was found to be an important factor in prolonging the disease-free interval and survival in patients with well-diffferentiated thyroid cancer, even low-risk patients.32 In Turkey, a considerable number of patients undergoing operation for thyroid cancer adher to the postoperative follow-up program; however, patient noncompliance still constitutes a major problem, and some patients undergoing surgery for thyroid cancer delay seeking medical help until the development of serious complications. We prefer to take unfavorable histological findings into account when deciding on RAI treatment, despite the low-risk score. The preferred TSH level is higher than 30 mIU/L for effective RAI ablation.33 Despite interfering with proper RAI ablation, remnant tissue may contain residual carcinoma in 11% to 53% of patients who undergo subtotal thyroidectomy with no difference in the frequency in high- and low-risk patients.17, 34-39 Thyroid cancer might be detected in approximately 10% of thyroidectomy specimens of recurrent goiter, although the preceding operations were performed for benign goiter.40 Menegaux et al40 documented that 20% of such patients had multifocal cancer, lymph node metastasis, or distant metastasis.
Subtotal resections (unilateral or bilateral) have been the preferred surgical treatment for multinodular goiter.6, 23, 41 A conservative surgical approach followed by thyroid hormone supplementation has been claimed to efficiently prevent recurrence.41-42 Reoperation rate for recurrence was low (2%) when all nodules were removed during thyroidectomy, but multinodular goiter was documented to be a risk factor for recurrence.42 Anderson et al41 found that postoperative thyroid hormone therapy reduced the rate of recurrence, but that limited unilateral procedures were associated with a high rate of recurrence. Recent studies, however, have documented that the recurrence rate after subtotal resections is high, and that the preventive effect of postoperative thyroxine treatment is highly questionable.12-15,43-44 The incidence of recurrence has been directly related to a long postoperative follow-up and to large amounts of remnant tissue.13, 41, 43-45 Most of the recurrences developed 10 to 20 years after the previous surgery, although some authors recommend 30 years of follow-up to determine the actual outcome.3, 6, 13, 41-42 Subtotal thyroidectomy in multinodular goiter has resulted in reoperation for recurrence in 13% to 20% of patients, reaching a peak incidence 13 years after the primary operation.6
The performance of total thyroidectomy in multinodular disease has been reserved for exceptionally large goiters. Opponents of total thyroidectomy claim that the procedure is not justified in multinodular disease, as the risk for malignancy is low but associated complication rates are high.46-47 It has been documented that total thyroidectomy can be performed safely in benign nodular goiter, but that reoperations carry greater risk.5-6,8-9,16 In addition, the relative risk for permanent complications has been found to be higher in reoperations for recurrent disease than in primary operations with extensive resection.48
CONCLUSIONS
The incidence of thyroid cancer in multinodular goiter without any previous suspicion of malignancy was found to be 8.2%. Subtotal thyroidectomy resulted in a significantly higher rate of completion thyroidectomy for incidentally diagnosed thyroid cancer compared with total or near-total thyroidectomy. No permanent complications occurred, and the extent of surgical resection had no significant effect on the rate of temporary complications. We recommend total or near-total thyroidectomy in multinodular goiter to eliminate the need for completion thyroidectomy in case of a final diagnosis of thyroid cancer.
AUTHOR INFORMATION
Corresponding author and reprints: Yasemin Giles, MD, Istanbul Tip Fakültesi, Genel Cerrahi ABD, Çapa, Topkapi, Istanbul, Turkey 34390 (e-mail: ygiles{at}ixir.com).
Accepted for publication August 7, 2003.
From the Departments of Surgery (Drs Giles, Terzio lu, and Tezelman) and Endocrinology (Dr Boztepe), Istanbul Medical Faculty, Istanbul, Turkey.
REFERENCES
1. Siragusa G, Lanzara P, Di Pace G. Subtotal thyroidectomy or total thyroidectomy in the treatment of benign thyroid disease: our experience [in Italian]. Minerva Chir. 1998;53:233-238.
PUBMED
2. Zaraca F, Di Paola M, Gossetti F, et al. Benign thyroid disease: 20-year experience in surgical therapy [in Italian]. Chir Ital. 2000;52:41-47.
PUBMED
3. Visset J, Lumingu K, Le Bodic MF, Paineau J, Letessier E. Total thyroidectomy to prevent recurrence of benign thyroid goiter [in French]. Chirurgie. 1991;117:37-40.
PUBMED
4. Peix JL, Van Box Som P. Role of total thyroidectomy in the treatment of benign thyroid diseases [in French]. Ann Endocrinol (Paris). 1996;57:502-507.
PUBMED
5. Reeve TS, Delbribge L, Cohen A, Crummer P. Total thyroidectomy: the preferred option for multinodular goiter. Ann Surg. 1987;206:782-786.
ISI
| PUBMED
6. Delbridge L, Guinea AI, Reeve TS. Total thyroidectomy for bilateral benign multinodular goiter: effect of changing practice. Arch Surg. 1999;134:1389-1393.
FREE FULL TEXT
7. Jacobs JK, Aland JW Jr, Ballinger JF. Total thyroidectomy: a review of 213 patients. Ann Surg. 1983;197:542-549.
PUBMED
8. Pappalardo G, Guadalaxara A, Frattaroli FM, Illomei G, Falaschi P. Total compared with subtotal thyroidectomy in benign nodular disease: personal series and review of published reports. Eur J Surg. 1998;164:501-506.
FULL TEXT
|
ISI
| PUBMED
9. Liu Q, Djuricin G, Prinz RA. Total thyroidectomy for benign thyroid disease. Surgery. 1998;123:2-7.
ISI
| PUBMED
10. Mishra A, Agarwal A, Agarwal G, Mishra SK. Total thyroidectomy in benign thyroid disorders in an endemic region. World J Surg. 2001;25:307-310.
FULL TEXT
|
ISI
| PUBMED
11. Gough IR, Wilkinson D. Total thyroidectomy for management of thyroid disease. World J Surg. 2000;24:962-965.
PUBMED
12. Berglund J, Bondesson L, Christensen SB, Larsson AS, Tibblin S. Indications for thyroxine therapy after surgery for nontoxic benign goitre. Acta Chir Scand. 1990;156:433-438.
PUBMED
13. Rojdmark J, Jarhult J. High long term recurrence rate after subtotal thyroidectomy for nodular goitre. Eur J Surg. 1995;161:725-727.
PUBMED
14. Geerdsen JP, Frolund L. Thyroid function after surgical treatment of nontoxic goitre: a randomized study of postoperative thyroxine administration. Acta Med Scand. 1986;220:341-345.
PUBMED
15. Geerdsen JP, Frolund L. Recurrence of nontoxic goitre with and without postoperative thyroxine medication. Clin Endocrinol (Oxf). 1984;21:529-533.
PUBMED
16. Reeve TS, Delbridge L, Brady P, Crummer P, Smyth C. Secondary thyroidectomy: a twenty-year experience. World J Surg. 1988;12:449-453.
FULL TEXT
|
ISI
| PUBMED
17. Pezzullo L, Delrio P, Losito NS, Caraco C, Mozzillo N. Post-operative complications after completion thyroidectomy for differentiated thyroid cancer. Eur J Surg Oncol. 1997;23:215-218.
PUBMED
18. Bergamaschi R, Becouarn G, Ronceray J, Arnaud JP. Morbidity of thyroid surgery. Am J Surg. 1998;176:71-75.
FULL TEXT
|
ISI
| PUBMED
19. Wilson DB, Staren ED, Prinz RA. Thyroid reoperations: indications and risks. Am Surg. 1998;64:674-678.
PUBMED
20. Beahrs OH, Vandertoll DJ. Complications of secondary thyroidectomy. Surg Gynecol Obstet. 1963;117:535-539.
PUBMED
21. McCall A, Jarosz H, Lawrence AM, Paloyan E. The incidence of thyroid carcinoma in solitary cold nodules and in multinodular goiters. Surgery. 1986;100:1128-1132.
ISI
| PUBMED
22. Koh KBH, Chang KW. Carcinoma in multinodular goitre. Br J Surg. 1992;79:266-267.
PUBMED
23. Lopez LH, Herrera MF, Gamino R, et al. Surgical treatment of multinodular goiter at the Instituto Nacional de nutricion Salvador Zubiran [in Spanish]. Rev Invest Clin. 1997;49:105-109.
PUBMED
24. Chao TC, Jeng LB, Lin JD, Chen MF. Reoperative thyroid surgery. World J Surg. 1997;21:644-647.
FULL TEXT
|
ISI
| PUBMED
25. Calabro S, Auguste LJ, Attie JN. Morbidity of completion thyroidectomy for initially misdiagnosed thyroid carcinoma. Head Neck Surg. 1988;10:235-238.
PUBMED
26. Sachmechi I, Miller E, Varatharajah R, et al. Thyroid carcinoma in single cold nodules and in cold nodules of multinodular goiters. Endocr Pract. 2000;6:5-7.
PUBMED
27. Mato A, Gippini A, Peino R, Gayosso P, Uriel B. Differentiated carcinoma of the thyroid gland in an area of endemic goiter: clinical study and prognostic correlation [in Spanish]. An Med Interna. 1996;13:537-540.
PUBMED
28. Hay ID, Bergstralh EJ, Goellner JR, Ebersold JR, Grant CS. Predicting outcome in papillary thyroid carcinoma: development of a reliable prognostic scoring system in a cohort of 1779 patients surgically treated at one institution during 1940 through 1989. Surgery. 1993;114:1050-1058.
ISI
| PUBMED
29. Mazzaferri EL. Papillary thyroid carcinoma: factors influencing prognosis and current therapy. Semin Oncol. 1987;14:315-322 [published correction appears in Semin Oncol. 1988;15(3):x].
ISI
| PUBMED
30. Shah JP, Loree TR, Dharker D, Strong EW, Begg C, Vlamis V. Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg. 1992;164:658-661.
ISI
| PUBMED
31. Baudin E, Travagli JP, Ropers J, et al. Microcarcinoma of the thyroid gland: the Gustave-Roussy Institute experience. Cancer. 1998;83:553-559.
FULL TEXT
|
ISI
| PUBMED
32. Samaan NA, Schultz PN, Hickey RC, et al. The results of various modalities of treatment of well differentiated thyroid carcinoma: a retrospective review of 1599 patients. J Clin Endocrinol Metab. 1992;75:714-720.
ABSTRACT
33. Logue JP, Tsang RW, Brierley JD, Simpson WJ. Radioiodine ablation of residual tissue in thyroid cancer: relationship between administered activity, neck uptake and outcome. Br J Radiol. 1994;67:1127-1131.
ABSTRACT
34. Rodriguez-Cuevas S, Labastida-Almendaro S, Briceno-Ancona N, Gonzalez-Rodriguez D. Reintervention to complete the surgical treatment of thyroid cancer: indications and histopathological findings [in Spanish]. Gac Med Mex. 1998;134:677-683.
PUBMED
35. Wax MK, Briant DR. Completion thyroidectomy in the management of well-differentiated thyroid carcinoma. Otolaryngol Head Neck Surg. 1992;107:63-68.
PUBMED
36. Pacini F, Elisei R, Capezzone M, et al. Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in low- and high-risk patients. Thyroid. 2001;11:877-881.
FULL TEXT
|
ISI
| PUBMED
37. Sarda AK, Kapur MM. Thyroid carcinoma: a report of 206 cases from an area with endemic goitre. Acta Oncol. 1990;29:863-867.
PUBMED
38. Alzahrani AS, Mandil AL, Chaudhary MA, Ahmed M, Mohammed GE. Frequency and predictive factors of malignancy in residual thyroid tissue and cervical lymph nodes after partial thyroidectomy for differentiated thyroid cancer. Surgery. 2002;131:443-449.
PUBMED
39. Machens A, Hinze R, Lautenschlager C, Thomusch O, Dralle H. Prophylactic completion thyroidectomy for differentiated thyroid carcinoma: prediction of extrathyroidal soft tissue infiltrates. Thyroid. 2001;11:381-384.
PUBMED
40. Menegaux F, Turpin G, Dahman M, et al. Secondary thyroidectomy in patients with prior thyroid surgery for benign disease: a study of 203 cases. Surgery. 1999;126:479-483.
PUBMED
41. Anderson PE, Hurley PR, Rosswick P. Conservative treatment and long term prophylactic thyroxine in the prevention of recurrence of multinodular goiter. Surg Gynecol Obstet. 1990;171:309-314.
PUBMED
42. Kraimps JL, Marechaud R, Gineste D, et al. Analysis and prevention of recurrent goiter. Surg Gynecol Obstet. 1993;176:319-322.
PUBMED
43. Piraneo S, Vitri P, Galimberti A, Salvaggio A, Bastagli A. Ultrasonographic surveillance after surgery for euthyroid goitre in patients treated or not with thyroxine. Eur J Surg. 1997;163:21-26.
PUBMED
44. Piraneo S, Vitri P, Galimberti A, Guzzetti S, Salvaggio A, Bastagl A. Recurrence of goiter after operation in euthyroid patients. Eur J Surg. 1994;160:351-356.
PUBMED
45. Zelmanovitz T, Zelmanovitz F, Genro S, Gus P, de Azevedo MJ, Gross JL. Analysis of the factors associated with the recurrence of postthyroidectomy goiter[in Portuguese]. Rev Assoc Med Bras. 1995;41:86-10.
46. Gould EA, Hirsch E, Brecher I. Complications arising in the course of thyroidectomy. Arch Surg. 1965;90:81-85.
47. Foster RS Jr. Morbidity and mortality after thryoidectomy. Surg Gynecol Obstet. 1978;146:423-429.
PUBMED
48. Thomusch O, Machens A, Sekulla C, et al. Multivariate analysis of risk factors for postoperative complications in benign goiter surgery: prospective multicenter study in Germany. World J Surg. 2000;24:1335-1341.
FULL TEXT
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ISI
| PUBMED
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