分化型甲状腺癌的规范化综合治疗
摘要
目的甲状腺癌是最常见的内分泌系统的恶性肿瘤,近期的流行病学调查显示,其发病率呈上升趋势。分化型甲状腺癌(如:乳头状癌、滤泡状癌)是甲状腺癌最常见的病理类型。目前,对分化型甲状腺癌的处理还存在很多争论,因为尚无前瞻性的随机对照研究结果。由于该类肿瘤发生率相对较低且病程特别长,正在进行的随机试验结果估计要多年后才能有结果。大多数处理意见来自大宗患者的非随机对照研究,因此,对于分化型甲状腺癌的治疗存在许多争议。本研究结合我院乳腺甲状腺专科五年多积累的较完整的资料,对甲状腺癌的临床特征进行单中心、小规模的研究,并结合文献资料对甲状腺癌的流行病学和其他的治疗进行分析。
方法进行文献检索,讨论分化型甲状腺癌的流行病学的特点。回顾性分析2003年6月至2006年8月间收治的72例甲状腺癌再次手术患者的临床资料。再次手术原因主要为首次手术不当致肿瘤残留、肿瘤复发或颈淋巴结转移和~(131)I治疗前的甲状腺清除。回顾性分析2003年6月至2008年6月间,我院成立乳腺甲状腺中心后,分化型甲状腺癌患者采用双侧甲状腺全切,且病例资料完整的452例患者的临床资料以及2003年6月至2007年9月间收治的70例甲状腺微小癌的临床资料。讨论分化型甲状腺癌的手术切除范围。回顾性分析本分析中心03年6月至06年6月间行甲状腺癌根治+颈淋巴结清扫术,且颈淋巴结清扫的淋巴结数目大于8枚的83例甲状腺乳头状癌临床资料。讨论分化型甲状腺癌淋巴结的转移规律,为临床进行颈淋巴结清扫范围提供依据。通过文献检索,对分化型甲状腺癌的其他治疗方法和难治性分化型甲状腺癌的治疗进行讨论。
结果分化型甲状腺癌的发病与射线的关系密切,越年轻的患者对射线诱导的肿瘤越敏感。射线诱导的甲状腺癌几乎不受性别影响,几乎都是乳头状癌,且更具侵袭性,常合并有甲状腺自身免疫性疾病。甲状腺癌的总发病率和碘摄入并没有明确的关系,但甲状腺癌的亚型分配与碘的摄入有关,富含碘的地区,乳头状癌增多,滤泡状癌和未分化癌减少。广泛应用影像学检查,以及影像学检查的分辨率增加,使微小肿瘤的检出率增加,对甲状腺癌的发病率增加也有一定的作用。甲状腺癌与甲状腺癌家族史、自身甲状腺肿和甲状腺结节病史等均有关,部分研究显示,分化型甲状腺癌还和某些女性激素及生育有关。从本组72例再次手术的病理证实,腺体肿瘤残留率为47.1%(32/68),淋巴结肿瘤残留率为81.4%(35/43)。而本中心五年统计的病例资料完整的452例双侧甲状腺全切的患者中,66.4%的患者应采用双侧全切,70例微小癌的患者中,近50%的患者应采用双侧甲状腺全切。因此,双侧甲状腺全切应作为分化型甲状腺癌的标准手术方式。从本组83例甲状腺乳头状癌淋巴结转移的规律来看,乳头状癌最容易转移至Ⅵ区(单侧甲癌72.3%,双侧甲癌88.9%),其次是Ⅲ、Ⅳ区(单侧甲癌57.9%,双侧甲癌50-66.7%),Ⅴ区和Ⅰ区较少发生淋巴结转移(单侧甲癌0-20.1%,双侧甲癌25-33.3%)。侵犯甲状腺包膜(88%)和滤泡亚型(85.7%)甲状腺癌容易发生颈淋巴结转移。良性病变局部恶变(27.3%)和包裹型(25%)甲状腺癌,较少发生颈淋巴结转移。甲状腺上极的肿瘤可以先出现颈外侧区淋巴结转移。建议甲状腺乳头状癌常规清扫中央组Ⅵ区淋巴结,肿瘤位于甲状腺下极者需清扫对侧下极淋巴结;对于肿瘤位于甲状腺上极的患者,应增加清扫Ⅲ、Ⅳ区的淋巴结。对风险较高的滤泡亚型及侵犯包膜的PTC清扫范围要更大,应清扫Ⅱ-Ⅵ区淋巴结。碘131内照射治疗是分化型甲状腺癌的主要的治疗方法,可减少局部复发和降低死亡率,且有利于Tg的随访。甲状腺癌术后的甲状腺激素治疗,除了纠正甲状腺功能减低,维持甲状腺功能正常的作用外,还有利于防止肿瘤的复发、生长和出现隐性转移。外照射和化疗对分化型甲状腺癌的治疗作用有限。甲状腺癌的随访重点应是定期的颈部超声检查和非刺激条件下的甲状腺球蛋白(Tg)的监测,它们能有效的鉴别出患者是否有甲状腺癌的复发。全身碘131扫描和PET检查对确定转移病灶的部位也有一定的作用。
BACKGROUND AND OBJECTIVES The thyroid carcinoma is the most frequent endocrine cancer. According to the latest epidemiological survey, the incidence of thyroid cancer, mainly differentiated, is one of the most rapidly increasing human cancers. The differentiated thyroid cancer is the most common histotype in the thyroid cancer. Managing differentiated (ie, papillary, follicular) thyroid carcinoma can be a challenge, because no prospective randomized trials of treatment have been done. Results from ongoing randomized trials will not be available for many years, given the typically prolonged course and relative infrequency of these tumors. Most of the information about treatment comes from studies of large patient cohorts in which therapy has not been randomly assigned. This accounts for much of the disagreement about managing differentiated thyroid carcinoma. The aim of this study is to retrospectively evaluate the patients diagnosed with differentiated thyroid carcinoma in our department from Jun. 2003 to Jun. 2008 in terms of the clinical and histopathological features, conjugating with literature retrieval, thereby summarize the optimal treatment. To discuss the epidemiology and the other treatments for differentiated thyroid carcinoma.
Methods It was discussed epidemiological characteristic of differentiated thyroid carcinoma according to the latest literature retrieval. Protocols of 72 patients undergoing reoperation for thyroid cancer from June 2003 to August 2006 were reviewed. Causes for reoperation were as follows: residue of the tumor locally as the inappropriate initial operation; local recurrence and cervical lymph node metastasis; before ~(131)I ablation which differentiated thyroid cancer with distant place metastasis. Protocols of 70 thyroid microcarcinoma patients undergoing operation from June 2003 to September 2007 and protocols of 452 differentiated thyroid carcinoma patients undergoing total thyroidectomy from June 2003 to June 2008 were reviewed. It was discussed the surgical strategy of the thyroid gland resection extent. Protocol of 83 papillary thyroid cancer patients undergoing radical thyroidectomy and modified radical neck dissection whose lymph node dissection number was over 8 in the period June 2003 to June 2006 were reviewed. To investigate the regular pattern of cervical lymph node metastases of papillary thyroid cancer, and determine the treatment of selective lymph node dissection in patients with papillary thyroid cancer. It also wanted to discuss the other treatments for the common and refractory differentiated thyroid carcinoma.
Result It was well recognized that the incidence of differentiated thyroid carcinoma was closed related with exposure to radiation. The youngest children were most sensitive to radiation-induced carcinogenesis and it became apparent that the radiation-induced thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. The overall incidence of differentiated thyroid carcinoma was generally not considered to be influenced by the iodine intake of a population, whereas the distribution of the types of thyroid carcinoma seemed to be related to the intake of iodine, with fewer of the more aggressive follicular and anaplastic carcinomas and more papillary carcinomas in iodine rich areas. That more frequent use and higher resolution of medical imaging had led to an increased detection rate of small, subclinical tumours, which in turn accounts for the higher incidence of differentiated thyroid carcinoma. Thyroid cancer was related with family history of thyroid caner and thyroid morbidity. A significantly more frequent hormone replacement therapy and contraception and more frequent miscarriages in women with thyroid cancer were noteworthy. The rate of residual in thyroid and cervical lymph node confirmed by postoperative pathology were 47.1% and 81.4% (35/43) respectively in our 72 cases of reoperation thyroid cancers. About 50% thyroid microcarcinoma in 70 cases and 66.4% differentiated thyroid carcinoma in 452 cases thyroid total thyroidectomy needed total thyroidectomy. Total thyroidectomy should be the stand surgery strategy for differentiated thyroid carcinoma. Lymph node metastasis of papillary thyroid cancer(PTC) was commonly presented in the level VI central compartment (unilateral PTC 72.3% and bilateral PTC 88.9%) , the second was in the levelIII, IV lateral compartment (unilateral PTC 57.9% and bilateral PTC 50-66.7%) .Level V and I are seldom found metastasis ( unilateral PTC 0-20.1% and bilateral PTC 25-33.3%) .Thyroid capsular invasion (88%) and follicular variant(85.7%) of PTC easy metastasis to the cervical lymph node. Focal malignant of benign thyroid diseases (27.3%) and encapsulated variant (25%) are seldom found metastasis. Metastatic lymph nodes may found in the lateral compartment of cervical lymph node and free in the central compartment in the upper pole PTC. Routine level VI central compartment LND at the time of thyroidectomy is advocated. Anus perineum of PTC need explore the opposite side level VI. The upper pole PTC should be treated by selective neck dissection (at least levels III,IV, and VI). With a higher risk PTC (capsular invasion and follicular variant) of PTC should underwent selective LND at levels II through VI. Radioactive iodine (RAI) was the major adjuvant treatment of well-differentiated papillary cancer of the thyroid, which could reduce the mortality and local recurrence of thyroid cancer. RAI was benefit for the follow-up of Tg. Thyroid hormone replace treatment after thyroid operation with the L-enantiomer of tetraiodothyronine (L-T(4)) was not only maintenance the normal thyroid hormone level but also benefit high-risk thyroid cancer patients by decreasing recurrence, growth and delitescence metastasis of tumour. The role of adjuvant external radiotherapy and chemotherapy were limited for the thyroid cancer. A follow-up strategy emphasizing routine cervical ultrasonography and unstimulated thyroglobulin was effective in identifying patients with recurrent papillary thyroid cancer. RAI whole-body scanning (WBS) and positron emission tomography (PET) computed tomography were useful in the detection of recurrence and/or metastases of differentiated thyroid carcinoma.
方法进行文献检索,讨论分化型甲状腺癌的流行病学的特点。回顾性分析2003年6月至2006年8月间收治的72例甲状腺癌再次手术患者的临床资料。再次手术原因主要为首次手术不当致肿瘤残留、肿瘤复发或颈淋巴结转移和~(131)I治疗前的甲状腺清除。回顾性分析2003年6月至2008年6月间,我院成立乳腺甲状腺中心后,分化型甲状腺癌患者采用双侧甲状腺全切,且病例资料完整的452例患者的临床资料以及2003年6月至2007年9月间收治的70例甲状腺微小癌的临床资料。讨论分化型甲状腺癌的手术切除范围。回顾性分析本分析中心03年6月至06年6月间行甲状腺癌根治+颈淋巴结清扫术,且颈淋巴结清扫的淋巴结数目大于8枚的83例甲状腺乳头状癌临床资料。讨论分化型甲状腺癌淋巴结的转移规律,为临床进行颈淋巴结清扫范围提供依据。通过文献检索,对分化型甲状腺癌的其他治疗方法和难治性分化型甲状腺癌的治疗进行讨论。
结果分化型甲状腺癌的发病与射线的关系密切,越年轻的患者对射线诱导的肿瘤越敏感。射线诱导的甲状腺癌几乎不受性别影响,几乎都是乳头状癌,且更具侵袭性,常合并有甲状腺自身免疫性疾病。甲状腺癌的总发病率和碘摄入并没有明确的关系,但甲状腺癌的亚型分配与碘的摄入有关,富含碘的地区,乳头状癌增多,滤泡状癌和未分化癌减少。广泛应用影像学检查,以及影像学检查的分辨率增加,使微小肿瘤的检出率增加,对甲状腺癌的发病率增加也有一定的作用。甲状腺癌与甲状腺癌家族史、自身甲状腺肿和甲状腺结节病史等均有关,部分研究显示,分化型甲状腺癌还和某些女性激素及生育有关。从本组72例再次手术的病理证实,腺体肿瘤残留率为47.1%(32/68),淋巴结肿瘤残留率为81.4%(35/43)。而本中心五年统计的病例资料完整的452例双侧甲状腺全切的患者中,66.4%的患者应采用双侧全切,70例微小癌的患者中,近50%的患者应采用双侧甲状腺全切。因此,双侧甲状腺全切应作为分化型甲状腺癌的标准手术方式。从本组83例甲状腺乳头状癌淋巴结转移的规律来看,乳头状癌最容易转移至Ⅵ区(单侧甲癌72.3%,双侧甲癌88.9%),其次是Ⅲ、Ⅳ区(单侧甲癌57.9%,双侧甲癌50-66.7%),Ⅴ区和Ⅰ区较少发生淋巴结转移(单侧甲癌0-20.1%,双侧甲癌25-33.3%)。侵犯甲状腺包膜(88%)和滤泡亚型(85.7%)甲状腺癌容易发生颈淋巴结转移。良性病变局部恶变(27.3%)和包裹型(25%)甲状腺癌,较少发生颈淋巴结转移。甲状腺上极的肿瘤可以先出现颈外侧区淋巴结转移。建议甲状腺乳头状癌常规清扫中央组Ⅵ区淋巴结,肿瘤位于甲状腺下极者需清扫对侧下极淋巴结;对于肿瘤位于甲状腺上极的患者,应增加清扫Ⅲ、Ⅳ区的淋巴结。对风险较高的滤泡亚型及侵犯包膜的PTC清扫范围要更大,应清扫Ⅱ-Ⅵ区淋巴结。碘131内照射治疗是分化型甲状腺癌的主要的治疗方法,可减少局部复发和降低死亡率,且有利于Tg的随访。甲状腺癌术后的甲状腺激素治疗,除了纠正甲状腺功能减低,维持甲状腺功能正常的作用外,还有利于防止肿瘤的复发、生长和出现隐性转移。外照射和化疗对分化型甲状腺癌的治疗作用有限。甲状腺癌的随访重点应是定期的颈部超声检查和非刺激条件下的甲状腺球蛋白(Tg)的监测,它们能有效的鉴别出患者是否有甲状腺癌的复发。全身碘131扫描和PET检查对确定转移病灶的部位也有一定的作用。
BACKGROUND AND OBJECTIVES The thyroid carcinoma is the most frequent endocrine cancer. According to the latest epidemiological survey, the incidence of thyroid cancer, mainly differentiated, is one of the most rapidly increasing human cancers. The differentiated thyroid cancer is the most common histotype in the thyroid cancer. Managing differentiated (ie, papillary, follicular) thyroid carcinoma can be a challenge, because no prospective randomized trials of treatment have been done. Results from ongoing randomized trials will not be available for many years, given the typically prolonged course and relative infrequency of these tumors. Most of the information about treatment comes from studies of large patient cohorts in which therapy has not been randomly assigned. This accounts for much of the disagreement about managing differentiated thyroid carcinoma. The aim of this study is to retrospectively evaluate the patients diagnosed with differentiated thyroid carcinoma in our department from Jun. 2003 to Jun. 2008 in terms of the clinical and histopathological features, conjugating with literature retrieval, thereby summarize the optimal treatment. To discuss the epidemiology and the other treatments for differentiated thyroid carcinoma.
Methods It was discussed epidemiological characteristic of differentiated thyroid carcinoma according to the latest literature retrieval. Protocols of 72 patients undergoing reoperation for thyroid cancer from June 2003 to August 2006 were reviewed. Causes for reoperation were as follows: residue of the tumor locally as the inappropriate initial operation; local recurrence and cervical lymph node metastasis; before ~(131)I ablation which differentiated thyroid cancer with distant place metastasis. Protocols of 70 thyroid microcarcinoma patients undergoing operation from June 2003 to September 2007 and protocols of 452 differentiated thyroid carcinoma patients undergoing total thyroidectomy from June 2003 to June 2008 were reviewed. It was discussed the surgical strategy of the thyroid gland resection extent. Protocol of 83 papillary thyroid cancer patients undergoing radical thyroidectomy and modified radical neck dissection whose lymph node dissection number was over 8 in the period June 2003 to June 2006 were reviewed. To investigate the regular pattern of cervical lymph node metastases of papillary thyroid cancer, and determine the treatment of selective lymph node dissection in patients with papillary thyroid cancer. It also wanted to discuss the other treatments for the common and refractory differentiated thyroid carcinoma.
Result It was well recognized that the incidence of differentiated thyroid carcinoma was closed related with exposure to radiation. The youngest children were most sensitive to radiation-induced carcinogenesis and it became apparent that the radiation-induced thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. The overall incidence of differentiated thyroid carcinoma was generally not considered to be influenced by the iodine intake of a population, whereas the distribution of the types of thyroid carcinoma seemed to be related to the intake of iodine, with fewer of the more aggressive follicular and anaplastic carcinomas and more papillary carcinomas in iodine rich areas. That more frequent use and higher resolution of medical imaging had led to an increased detection rate of small, subclinical tumours, which in turn accounts for the higher incidence of differentiated thyroid carcinoma. Thyroid cancer was related with family history of thyroid caner and thyroid morbidity. A significantly more frequent hormone replacement therapy and contraception and more frequent miscarriages in women with thyroid cancer were noteworthy. The rate of residual in thyroid and cervical lymph node confirmed by postoperative pathology were 47.1% and 81.4% (35/43) respectively in our 72 cases of reoperation thyroid cancers. About 50% thyroid microcarcinoma in 70 cases and 66.4% differentiated thyroid carcinoma in 452 cases thyroid total thyroidectomy needed total thyroidectomy. Total thyroidectomy should be the stand surgery strategy for differentiated thyroid carcinoma. Lymph node metastasis of papillary thyroid cancer(PTC) was commonly presented in the level VI central compartment (unilateral PTC 72.3% and bilateral PTC 88.9%) , the second was in the levelIII, IV lateral compartment (unilateral PTC 57.9% and bilateral PTC 50-66.7%) .Level V and I are seldom found metastasis ( unilateral PTC 0-20.1% and bilateral PTC 25-33.3%) .Thyroid capsular invasion (88%) and follicular variant(85.7%) of PTC easy metastasis to the cervical lymph node. Focal malignant of benign thyroid diseases (27.3%) and encapsulated variant (25%) are seldom found metastasis. Metastatic lymph nodes may found in the lateral compartment of cervical lymph node and free in the central compartment in the upper pole PTC. Routine level VI central compartment LND at the time of thyroidectomy is advocated. Anus perineum of PTC need explore the opposite side level VI. The upper pole PTC should be treated by selective neck dissection (at least levels III,IV, and VI). With a higher risk PTC (capsular invasion and follicular variant) of PTC should underwent selective LND at levels II through VI. Radioactive iodine (RAI) was the major adjuvant treatment of well-differentiated papillary cancer of the thyroid, which could reduce the mortality and local recurrence of thyroid cancer. RAI was benefit for the follow-up of Tg. Thyroid hormone replace treatment after thyroid operation with the L-enantiomer of tetraiodothyronine (L-T(4)) was not only maintenance the normal thyroid hormone level but also benefit high-risk thyroid cancer patients by decreasing recurrence, growth and delitescence metastasis of tumour. The role of adjuvant external radiotherapy and chemotherapy were limited for the thyroid cancer. A follow-up strategy emphasizing routine cervical ultrasonography and unstimulated thyroglobulin was effective in identifying patients with recurrent papillary thyroid cancer. RAI whole-body scanning (WBS) and positron emission tomography (PET) computed tomography were useful in the detection of recurrence and/or metastases of differentiated thyroid carcinoma.
引文
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7.Pacini F,Elisei R,Capezzone M,et al.Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in lowand high-risk patients.Thyroid,2001,11:877-881.
8.Machens A,Hinze R,Lautenschlager C,et al.Prophylactic completion thyroidectomy for differentiated thyroid carcinoma:prediction of extrathyroidal soft tissue infiltrates.Thyroid.2001;11:381-384.
9.黄耿文,杨连粤.甲状腺癌的再次手术治疗.中国实用外科杂志,2004,24:589-590.
10.何文亮,麦沛成,周冬仙,等.甲状腺癌再次手术62例临床分析.现代肿瘤医学,2004,12:225-226.
11.卢增红,杨安奎,宋明,等.cN_0期甲状腺乳头状癌Ⅵ区淋巴结处理探讨78例报告.中国肿瘤,2006,15:58-60.
12.Hay ID,McConahey WM,Goellner JR.Managing patients with papillary thyroid carcinoma:insights gained from the Mayo Clinic's experience of treating 2512consecutive patients during 1940 through 2000.Trans Am Clin Climatol Assoc,2002,113:241-260.
13.王虎,张燕萍,张世文,等.甲状腺癌的再手术治疗.中国耳鼻咽喉头颈外科,2005.12:680-682.
14.Management of low-risk differentiated thyroid cancer.Mazzaferri EL.Endocr Pract.2007,13(5):498-512.
15.Extent of surgery affects survival for papillary thyroid cancer.Bilimoria KY,Bentrem DJ,Ko CY,et al.Ann Surg.2007,246(3):375-381.
16.Donald E.Yarbrough MD,Geoffrey B.et al.Intraoperative electromyographic monitoring of the recurrent laryngeal nerve in reoperative thyroid and parathyroid surgery Surgery.2004.136(6).1107-1115.
17.Robert L.Witt。Recurrent Laryngeal Nerve Electrophysiologic Monitoring in Thyroid Surgery:The Standard of Care? Journal of Voice 2005.19(3).497-500.
18.Shindo M,Wu JC,Park EE,et al.The importance of central compartment elective lymph node excision in the staging and treatment of papillary thyroid cancer.Arch Otolaryngol Head Neck Surg.2006,132(6):650-654.
19.Caron NR,Tan YY,Ogilvie JB,et al.Selective Modified Radical Neck Dissection for Papillary Thyroid Cancer-Is Level Ⅰ,Ⅱ and Ⅴ Dissection Always Necessary? World J Surg.2006,30(5):833-840.
20.Wang TS,Dubner S,Sznyter LA,et al.Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes.Arch Otolaryngol Head Neck Surg.2004,130(1):110-113.
21.Rosario PW,de Faria S,Bicalho L,et al.Ultrasonographic differentiation between metastatic and benign lymph nodes in patients with papillary thyroid carcinoma.J Ultrasound Med.2005,24(10):1385-1389.
22.Pingpank JF Jr,Sasson AR,Hanlon AL,et al.Tumor above the spinal accessory nerve in papillary thyroid cancer that involves lateral neck nodes:a common occurrence.Arch Otolaryngol Head Neck Surg.2002,128(11):1275-1278.
23.Shindo M,Wu JC,Park EE,et al.The importance of central compartment elective lymph node excision in the staging and treatment of papillary thyroid cancer.Arch Otolaryngol Head Neck Surg.2006,132(6):650-654.
24.Goropoulos A,Karamoshos K,Christodoulou A,et al.Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma.World J Surg.2004,28(12):1275-1281.
25.徐本义,李凤婉.分化型甲状腺癌颈淋巴结转移的规律.肿瘤防治研究,1999.26(3).266-268.
26.方国恩,陈琳.甲状腺癌颈淋巴结清扫术的评价.中国实用外科杂志,2004,24(10),587-589.
27.张艳,刘素香.甲状腺乳头状癌病理分性和淋巴结转移与预后的关系.中华普通外科杂志,2005,20(7),422-424.
28.Uruno T,Miyauchi A,Shimizu K,et al.Usefulness of Thyroglobulin Measurement in Fine-needle Aspiration Biopsy Specimens for Diagnosing Cervical Lymph Node Metastasis in Patients with Papillary Thyroid Cancer.World J Surg.2005,29(4):483-485.
29.Watkinson JC,Franklyn JA,Olliff JF.Detection and surgical treatment of cervical lymph nodes in differentiated thyroid cancer.Thyroid.2006,16(2):187-194.
30.Park HM,Perkins OW,Edmondson JW,et al.Influence of diagnostic radioiodines on the uptake of ablative dose of 131 Ⅰ.Thyroid,1994,4:49-54.
31.Huic D,Medvedec M,Dodig D,et al.Radioiodine uptake in thyroid cancer patients after diagnostic application of low-dose Ⅰ-131.Nucl Med Commun.1996,17:839-842,.
32.Leger FA,Izembart M,Dagollsset F,et al.Decreased uptake of therapeutic doses of 131 Ⅰ after 185 MBq 131 Ⅰ imaging for thyroid carcinoma.Eur J Nucl Med,1998,25:242-246.
33.Silberstein EB.Comparison of outcomes after(123)Ⅰ versus(131)Ⅰ pre-ablation imaging before radioiodine ablation in differentiated thyroid carcinoma.J Nucl Med.2007,48(7):1043-1046.
34.Sawka AM,Thephamongkhol K,Brouwers M,et al.Clinical review 170:A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer.J Clin Endocrinol Metab.2004,89(8):3668-3676.
35.Woodrum DT,Gauger PG.Role of 131Ⅰ in the treatment of well differentiated thyroid cancer.J Surg Oncol.2005,89(3):114-121.
36.Lin JD,Hsieh SH,Chang HY,et al.Outcome after treatment for papillary thyroid cancer.Head Neck.2001,23(2):140-146.
37.Kouvaraki MA,Shapiro SE,Lee JE,et al.Surgical management of thyroid carcinoma.J Natl Compr Canc Netw.2005,3(3):458-466.
38.余永利;罗全勇;陈立波,等.分化型甲状腺癌术后^131Ⅰ治疗生存率分析.中华核医学杂志2006;26(5):261-263.
39.Handkiewicz-Junak D,Wloch J,Roskosz J,et al.Total thyroidectomy and adjuvant radioiodine treatment independently decrease locoregional recurrence risk in childhood and adolescent differentiated thyroid cancer.J Nucl Med.2007,48(6):879-888.
40.Podnos YD,Smith DD,Wagman LD,et al.Survival in patients with papillary thyroid cancer is not affected by the use of radioactive isotope.J Surg Oncol.2007 Jul 1;96(1):3-7.
41.Verburg FA,de Keizer B,Lam MG,et al.Persistent disease in patients with papillary thyroid carcinoma and lymph node metastases after surgery and iodine-131 ablation.World J Surg.2007,31(12):2309-2314.
42.Ish-Shalom S, Durleshter L, Segal E, et al. Sialochemical and oxidative analyses in radioactive 1131-treated patients with thyroid carcinoma. Eur J Endocrinol.2008,158(5):677-681.
43.Burns, J A, Morgenstern, KE, Cahill, KV, et al. Nasolacrimal Obstruction Secondary to 1131 Therapy. Ophthal Plast Reconstr Surg. 2004,20(2): 126-129.
44.Biondi B, Filetti S, Schlumberger M. Thyroid-hormone therapy and thyroid cancer: a reassessment. Nat Clin Pract Endocrinol Metab. 2005,l(l):32-40.
45.Biondi B, Fazio S, Carella C,et al. Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine. J Clin Endocrinol Metab.1993,77(2):332-333.
46.Khanna CM, Dubey YS, Shankar R, et al. Effects of long-term thyroid hormone suppressive treatment on the cardiac functions. Indian Heart J. 1997,49(3):289-292.
47.Fazio S, Biondi B, Carella C,et al. Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: beneficial effect of beta-blockade. J Clin Endocrinol Metab. 1995,80(7):2222-2226.
48.Eulry F, Bauduceau B, Lechevalier D, et al. Bone density in differentiated cancer of the thyroid gland treated by hormone-suppressive therapy. Study based on 51 cases.Rev Rhum Mal Osteoartic. 1992,59(4):247-252.
49.Krausz Y,Uziely B,Nesher R,et al. Recombinant thyroid-stimulating hormone in differentiated thyroid cancer. Isr Med Assoc J. 2001,3(11):843-849.
50.Girelli ME, Busnardo B, Amerio R,et al. Critical evaluation of serum thyroglobulin (Tg) levels during thyroid hormone suppression therapy versus Tg levels after hormone withdrawal and total body scan: results in 291 patients with thyroid cancer. Eur J Nucl Med. 1986,11(9):333-335.
51.David A, Blotta A, Bondanelli M,et al. Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone. J Nucl Med. 2001 Oct;42(10):1470-1475.
52.Gholamrezanezhad A, Saghari M, Mirpour S,et al. On-levothyroxine measurement of thyroglobulin is not a reliable test for the follow-up of patients at high risk for remnant/recurrent differentiated thyroid carcinoma. Endokrynol Pol.2007,58(2):100-104.
53.Barzon L, Boscaro M, Pacenti M, et al. Evaluation of circulating thyroid-specific transcripts as markers of thyroid cancer relapse. Int J Cancer. 2004,110(6):914-920.
54.Pellegriti G, Scollo C, Regalbuto C,et al.The diagnostic use of the rhTSH/thyroglobulin test in differentiated thyroid cancer patients with persistent disease and low thyroglobulin levels.Clin Endocrinol (Oxf). 2003,58(5):556-561.
55.Huang SH, Wang PW, Huang YE,et al. Sequential follow-up of serum thyroglobulin and whole body scan in thyroid cancer patients without initial metastasis. Thyroid.2006,16(12).1273-1278.
56.Gutiérrez Cardo AL, Rodríguez Rodriguez JR, Borrego Dorado I,et al. Patients treated for differentiated thyroid cancer with negative 131I whole-body scans and elevated thyroglobulin levels: a possible course. Rev Esp Med Nucl.2007,26(3):138-145.
57.Roberts M, Maghami E, Kandeel F, et al. The role of positron emission tomography scanning in patients with radioactive iodine scan-negative, recurrent differentiated thyroid cancer. Am Surg. 2007,73(10):1052-1056.
58.Cabrera Martin MN, Pasamontes Pingarrón JA, Carreras Delgado JL,et al. Diagnostic accuracy of 18F-FDG PET in residual or recurrent differentiated thyroid carcinoma with high thyroglobulin and negative 131-I whole-body scan. Rev Esp Med Nucl.2007,26(5):263-269.
59.Yamaga LY, Cunha ML, Wagner J, et al. Diagnostic value of positron emission tomography/computed tomography with fluorine-18 fluordeoxyglucose in patients with differentiated thyroid gland carcinoma, high thyroglobulin serum levels and negative iodine whole body scan. Arq Bras Endocrinol Metabol. 2007,51(4):581-586.
60.Salvatore B, Paone G, Klain M,et al. Fluorodeoxyglucose PET/CT in patients with differentiated thyroid cancer and elevated thyroglobulin after total thyroidectomy and (131)I ablation. Q J Nucl Med Mol Imaging. 2008,52(1):2-8.
61.Kloos RT. Approach to the patient with a positive serum thyroglobulin and a negative radioiodine scan after initial therapy for differentiated thyroid cancer. J Clin Endocrinol Metab.2008, 93(5):1519-1525.
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63.Mittendorf EA, Wang X, Perrier ND,et al. Followup of patients with papillary thyroid cancer: in search of the optimal algorithm. J Am Coll Surg. 2007,205(2):239-247.
64.Argiris A, Agarwala SS, Karamouzis MV,et al. A phase II trial of doxorubicin and interferon alpha 2b in advanced, non-medullary thyroid cancer. Invest New Drugs.2008,26(2): 183-188.
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1.Mazzaferri EL,Jhiang SM.Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer.American Journal of Medicine.97(5):418-428.
2.Esnaola NF,Cantor SB,Sherman SI,et al.Optimal treatment strategy in patients with papillary thyroid cancer:A decision analysis.Surgery,2001,130(6):921-930.
3.Hay ID,Grant CS,Bergsstralh EJ,et al.Unilateral lobectomy:is it sufficient surgical treatment for patients with AMES low risk papillary thyroid carcinoma?.Surgery,1998,124:958-966.
4.Hundahl SA,Cady Blake,Cunningham M P,et al.Initial results from a prospective cohort study of 5 583 cases of thyroid carcinoma treated in the United States during 1996.Cancer,2000,89:202 -217.
5.Machens A,Holzhausen H J,Dralle H.The prognostic value of primary tumor size in papillary and follicular thyroid carcinoma.Cancer,2005,103:2269-2273.
6.Gardner RE,Yuttle RM,Burman KD,et al.Prognostic importance of vascular invasion in papillary thyroid carcinoma.Arch Otolaryngol Head Neck Surg,2000,126:309-312.
7.Pacini F,Elisei R,Capezzone M,et al.Contralateral papillary thyroid cancer is frequent at completion thyroidectomy with no difference in lowand high-risk patients.Thyroid,2001,11:877-881.
8.Machens A,Hinze R,Lautenschlager C,et al.Prophylactic completion thyroidectomy for differentiated thyroid carcinoma:prediction of extrathyroidal soft tissue infiltrates.Thyroid.2001;11:381-384.
9.黄耿文,杨连粤.甲状腺癌的再次手术治疗.中国实用外科杂志,2004,24:589-590.
10.何文亮,麦沛成,周冬仙,等.甲状腺癌再次手术62例临床分析.现代肿瘤医学,2004,12:225-226.
11.卢增红,杨安奎,宋明,等.cN_0期甲状腺乳头状癌Ⅵ区淋巴结处理探讨78例报告.中国肿瘤,2006,15:58-60.
12.Hay ID,McConahey WM,Goellner JR.Managing patients with papillary thyroid carcinoma:insights gained from the Mayo Clinic's experience of treating 2512consecutive patients during 1940 through 2000.Trans Am Clin Climatol Assoc,2002,113:241-260.
13.王虎,张燕萍,张世文,等.甲状腺癌的再手术治疗.中国耳鼻咽喉头颈外科,2005.12:680-682.
14.Management of low-risk differentiated thyroid cancer.Mazzaferri EL.Endocr Pract.2007,13(5):498-512.
15.Extent of surgery affects survival for papillary thyroid cancer.Bilimoria KY,Bentrem DJ,Ko CY,et al.Ann Surg.2007,246(3):375-381.
16.Donald E.Yarbrough MD,Geoffrey B.et al.Intraoperative electromyographic monitoring of the recurrent laryngeal nerve in reoperative thyroid and parathyroid surgery Surgery.2004.136(6).1107-1115.
17.Robert L.Witt。Recurrent Laryngeal Nerve Electrophysiologic Monitoring in Thyroid Surgery:The Standard of Care? Journal of Voice 2005.19(3).497-500.
18.Shindo M,Wu JC,Park EE,et al.The importance of central compartment elective lymph node excision in the staging and treatment of papillary thyroid cancer.Arch Otolaryngol Head Neck Surg.2006,132(6):650-654.
19.Caron NR,Tan YY,Ogilvie JB,et al.Selective Modified Radical Neck Dissection for Papillary Thyroid Cancer-Is Level Ⅰ,Ⅱ and Ⅴ Dissection Always Necessary? World J Surg.2006,30(5):833-840.
20.Wang TS,Dubner S,Sznyter LA,et al.Incidence of metastatic well-differentiated thyroid cancer in cervical lymph nodes.Arch Otolaryngol Head Neck Surg.2004,130(1):110-113.
21.Rosario PW,de Faria S,Bicalho L,et al.Ultrasonographic differentiation between metastatic and benign lymph nodes in patients with papillary thyroid carcinoma.J Ultrasound Med.2005,24(10):1385-1389.
22.Pingpank JF Jr,Sasson AR,Hanlon AL,et al.Tumor above the spinal accessory nerve in papillary thyroid cancer that involves lateral neck nodes:a common occurrence.Arch Otolaryngol Head Neck Surg.2002,128(11):1275-1278.
23.Shindo M,Wu JC,Park EE,et al.The importance of central compartment elective lymph node excision in the staging and treatment of papillary thyroid cancer.Arch Otolaryngol Head Neck Surg.2006,132(6):650-654.
24.Goropoulos A,Karamoshos K,Christodoulou A,et al.Value of the cervical compartments in the surgical treatment of papillary thyroid carcinoma.World J Surg.2004,28(12):1275-1281.
25.徐本义,李凤婉.分化型甲状腺癌颈淋巴结转移的规律.肿瘤防治研究,1999.26(3).266-268.
26.方国恩,陈琳.甲状腺癌颈淋巴结清扫术的评价.中国实用外科杂志,2004,24(10),587-589.
27.张艳,刘素香.甲状腺乳头状癌病理分性和淋巴结转移与预后的关系.中华普通外科杂志,2005,20(7),422-424.
28.Uruno T,Miyauchi A,Shimizu K,et al.Usefulness of Thyroglobulin Measurement in Fine-needle Aspiration Biopsy Specimens for Diagnosing Cervical Lymph Node Metastasis in Patients with Papillary Thyroid Cancer.World J Surg.2005,29(4):483-485.
29.Watkinson JC,Franklyn JA,Olliff JF.Detection and surgical treatment of cervical lymph nodes in differentiated thyroid cancer.Thyroid.2006,16(2):187-194.
30.Park HM,Perkins OW,Edmondson JW,et al.Influence of diagnostic radioiodines on the uptake of ablative dose of 131 Ⅰ.Thyroid,1994,4:49-54.
31.Huic D,Medvedec M,Dodig D,et al.Radioiodine uptake in thyroid cancer patients after diagnostic application of low-dose Ⅰ-131.Nucl Med Commun.1996,17:839-842,.
32.Leger FA,Izembart M,Dagollsset F,et al.Decreased uptake of therapeutic doses of 131 Ⅰ after 185 MBq 131 Ⅰ imaging for thyroid carcinoma.Eur J Nucl Med,1998,25:242-246.
33.Silberstein EB.Comparison of outcomes after(123)Ⅰ versus(131)Ⅰ pre-ablation imaging before radioiodine ablation in differentiated thyroid carcinoma.J Nucl Med.2007,48(7):1043-1046.
34.Sawka AM,Thephamongkhol K,Brouwers M,et al.Clinical review 170:A systematic review and metaanalysis of the effectiveness of radioactive iodine remnant ablation for well-differentiated thyroid cancer.J Clin Endocrinol Metab.2004,89(8):3668-3676.
35.Woodrum DT,Gauger PG.Role of 131Ⅰ in the treatment of well differentiated thyroid cancer.J Surg Oncol.2005,89(3):114-121.
36.Lin JD,Hsieh SH,Chang HY,et al.Outcome after treatment for papillary thyroid cancer.Head Neck.2001,23(2):140-146.
37.Kouvaraki MA,Shapiro SE,Lee JE,et al.Surgical management of thyroid carcinoma.J Natl Compr Canc Netw.2005,3(3):458-466.
38.余永利;罗全勇;陈立波,等.分化型甲状腺癌术后^131Ⅰ治疗生存率分析.中华核医学杂志2006;26(5):261-263.
39.Handkiewicz-Junak D,Wloch J,Roskosz J,et al.Total thyroidectomy and adjuvant radioiodine treatment independently decrease locoregional recurrence risk in childhood and adolescent differentiated thyroid cancer.J Nucl Med.2007,48(6):879-888.
40.Podnos YD,Smith DD,Wagman LD,et al.Survival in patients with papillary thyroid cancer is not affected by the use of radioactive isotope.J Surg Oncol.2007 Jul 1;96(1):3-7.
41.Verburg FA,de Keizer B,Lam MG,et al.Persistent disease in patients with papillary thyroid carcinoma and lymph node metastases after surgery and iodine-131 ablation.World J Surg.2007,31(12):2309-2314.
42.Ish-Shalom S, Durleshter L, Segal E, et al. Sialochemical and oxidative analyses in radioactive 1131-treated patients with thyroid carcinoma. Eur J Endocrinol.2008,158(5):677-681.
43.Burns, J A, Morgenstern, KE, Cahill, KV, et al. Nasolacrimal Obstruction Secondary to 1131 Therapy. Ophthal Plast Reconstr Surg. 2004,20(2): 126-129.
44.Biondi B, Filetti S, Schlumberger M. Thyroid-hormone therapy and thyroid cancer: a reassessment. Nat Clin Pract Endocrinol Metab. 2005,l(l):32-40.
45.Biondi B, Fazio S, Carella C,et al. Cardiac effects of long term thyrotropin-suppressive therapy with levothyroxine. J Clin Endocrinol Metab.1993,77(2):332-333.
46.Khanna CM, Dubey YS, Shankar R, et al. Effects of long-term thyroid hormone suppressive treatment on the cardiac functions. Indian Heart J. 1997,49(3):289-292.
47.Fazio S, Biondi B, Carella C,et al. Diastolic dysfunction in patients on thyroid-stimulating hormone suppressive therapy with levothyroxine: beneficial effect of beta-blockade. J Clin Endocrinol Metab. 1995,80(7):2222-2226.
48.Eulry F, Bauduceau B, Lechevalier D, et al. Bone density in differentiated cancer of the thyroid gland treated by hormone-suppressive therapy. Study based on 51 cases.Rev Rhum Mal Osteoartic. 1992,59(4):247-252.
49.Krausz Y,Uziely B,Nesher R,et al. Recombinant thyroid-stimulating hormone in differentiated thyroid cancer. Isr Med Assoc J. 2001,3(11):843-849.
50.Girelli ME, Busnardo B, Amerio R,et al. Critical evaluation of serum thyroglobulin (Tg) levels during thyroid hormone suppression therapy versus Tg levels after hormone withdrawal and total body scan: results in 291 patients with thyroid cancer. Eur J Nucl Med. 1986,11(9):333-335.
51.David A, Blotta A, Bondanelli M,et al. Serum thyroglobulin concentrations and (131)I whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone. J Nucl Med. 2001 Oct;42(10):1470-1475.
52.Gholamrezanezhad A, Saghari M, Mirpour S,et al. On-levothyroxine measurement of thyroglobulin is not a reliable test for the follow-up of patients at high risk for remnant/recurrent differentiated thyroid carcinoma. Endokrynol Pol.2007,58(2):100-104.
53.Barzon L, Boscaro M, Pacenti M, et al. Evaluation of circulating thyroid-specific transcripts as markers of thyroid cancer relapse. Int J Cancer. 2004,110(6):914-920.
54.Pellegriti G, Scollo C, Regalbuto C,et al.The diagnostic use of the rhTSH/thyroglobulin test in differentiated thyroid cancer patients with persistent disease and low thyroglobulin levels.Clin Endocrinol (Oxf). 2003,58(5):556-561.
55.Huang SH, Wang PW, Huang YE,et al. Sequential follow-up of serum thyroglobulin and whole body scan in thyroid cancer patients without initial metastasis. Thyroid.2006,16(12).1273-1278.
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