血清甲状腺球蛋白及促甲状腺素在分化型甲状腺癌预后判断中的意义

目的探讨血清甲状腺球蛋白(thyroglobulin,Tg)及促甲状腺素(thyrotropin,TSH)在分化型甲状腺癌预后判断中的意义。方法分化型甲状腺癌患者112例,检测112例患者术前血清Tg和TSH水平。采用Kaplan-Meier生存分析和COX多因素回归模型分析不同病理参数与患者平均总生存期和平均无进展生存期的关系。结果血清Tg≥20 ng/ml和TSH≥2.5 mIU/L的患者其T分期为3/4的比例和淋巴转移率较高(P0.05),Tg≥20 ng/ml的患者其肿瘤体积显著大于Tg20 ng/ml的患者(P0.05),不同TSH水平患者之间肿瘤大小比较差异无统计学意义(P0.05)。TNM不同分期患者血清Tg和TSH水平比较差异有统计学意义(P0.05)。Tg≥20 ng/ml和TSH≥2.5 mIU/L的患者5年生存率分别为79.9%和82.8%,无进展生存率分别为71.0%和73.3%,均显著低于Tg20 ng/ml和TSH2.5 mIU/L的患者(P0.05)。肿瘤大小、T分期、淋巴转移、远处转移、Tg水平、TSH水平是分化型甲状腺癌5年生存率的独立危险因素。结论高Tg和TSH水平与分化型甲状腺癌患者不良预后有关。     

分化型甲状腺癌术后复发的处理策略

分化型甲状腺癌虽然预后良好,但常易复发,包括生化性复发和结构性复发,造成患者身心和经济上的负担,同时也给临床医师对甲状腺癌的诊治带来困难。不同于甲状腺癌的初始治疗,对复发病灶的处理需要考虑更多的因素,包括更多的原发灶及淋巴结生物学信息、患者因素、再次手术风险、其他治疗选择等各种因素。一方面我们要追求复发病灶的完全清除,使以后不再复发,另一方面又不能损害患者的生理功能和生活质量。如何在这两者间取得平衡,制定最合理的处理策略,使患者获益最大,是值得探讨的问题。     

Long-term results of reoperation and localizing studies in patients with persistent or recurrent medullary thyroid cancer

HYPOTHESIS: Reoperation benefits patients with locoregional, persistent, or recurrent medullary thyroid cancer (MTC). Currently available localizing studies have limited utility for detecting all foci of residual MTC. DESIGN: A retrospective study with a mean follow-up time of 7.5 years (median, 13 years; range, 2.2-29 years). SETTING: A tertiary referral medical center. PATIENTS: Thirty-three patients who underwent 46 reoperations for locoregional residual MTC. RESULTS: Sixty-four percent of residual MTC was located in the lateral cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by greater than 50% in 10 patients, and either increased or were not reduced by greater than 50% in the remaining patients. On reoperation, one patient had a thoracic duct injury that required reexploration and ligation. Patients who had a greater than 50% decrease in calcitonin levels after reoperation were less likely to develop distant metastases compared with patients who did not have a greater than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n = 31), computed tomographic scan (n = 16), ultrasound (n = 9), and dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively. CONCLUSIONS: Although reoperation in patients with residual MTC rarely results in biochemical cure, cervical reexploration is safe and in selected patients may limit MTC progression. Lateral cervical node dissection could be beneficial at the time of initial surgical treatment because of the high frequency of residual MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but far from perfect for guiding the reexploration for locoregional residual MTC.     

Measurement of serum thyroglobulin is of value in detecting tumour recurrence following treatment of differentiated thyroid carcinoma by lobectomy

Serum thyroglobulin was measured in 243 samples from 84 patients (20 men and 64 women, with a mean age of 48.9(14) years) with differentiated thyroid carcinoma treated by lobectomy, and in 58 patients treated by total thyroidectomy. Both groups were given thyroxine to suppress thyroid stimulating hormone (TSH). Three patients in the lobectomy group and eight in the thyroidectomy group had evidence of tumour recurrence. Serum thyroglobulin concentration was elevated in the presence of known recurrent tumour (P less than 0.001) irrespective of the type of operation, and in its absence tended to be higher in the lobectomy than in the thyroidectomy group (median 4 micrograms/l versus 2 micrograms/l, P less than 0.05). Serum thyroglobulin levels of less than 10 micrograms/l could confirm the absence of otherwise known tumour recurrence in both groups with a specificity of 100 per cent, and sensitivities of 80 per cent and 86 per cent in the lobectomy and thyroidectomy groups respectively. Exclusion of samples liable to spurious elevation of thyroglobulin improved the sensitivity in the lobectomy group to 92 per cent. Despite the presence of residual thyroid tissue, measurement of serum thyroglobulin can exclude the presence of significant metastases in most patients following lobectomy for thyroid carcinoma.     

Preservation of recurrent laryngeal nerve invaded by differentiated thyroid cancer.

OBJECTIVE: This study was undertaken to determine whether the recurrent laryngeal nerve involved in differentiated thyroid carcinoma could be preserved. SUMMARY BACKGROUND DATA: Few investigations have provided definitive results concerning preservation of the recurrent laryngeal nerve involved in thyroid cancer. Complete excision with resection of the recurrent laryngeal nerve reportedly did not improve survival over incomplete excision in differentiated thyroid carcinoma. METHODS: A retrospective study was performed with the medical records of 50 patients with differentiated carcinoma and preoperative normal vocal cord function to investigate outcomes of recurrent laryngeal nerve preservation including local recurrence, prognosis, and postoperative vocal cord function. The recurrent laryngeal nerves on 1 or both sides were preserved in 23 patients (the preserved group), whereas the involved recurrent laryngeal nerve of the other 27 patients was resected (the resected group). RESULTS: Backgrounds of patients were similar between the resected and preserved groups. The number of patients with recurrences in each group was similar, and incidence of local, regional, and distant metastatic recurrences were not different between the groups. Postoperative overall survival of the preserved group was similar to that of the resected group (p = 0.1208). More than 60% of patients or of nerve at risk in the preserved group restored normal vocal cord function within 6 months. Some functional vocal cord movement was recognized in 80% of patients or of nerve at risk. All patients in the resected group including patients with nerve anastomosis showed permanent paralysis of the ipsilateral vocal cord. CONCLUSIONS: These results suggested that the recurrent laryngeal nerve, even if infiltrated by differentiated thyroid cancer, is worthwhile to preserve for maintenance of postoperative vocal cord function without affecting the incidence of local recurrence or prognosis.     

Utility of fluorine-18-fluorodeoxyglucose positron emission tomography in differentiated thyroid carcinoma with negative radioiodine scans and elevated serum thyroglobulin levels

BACKGROUND: This study aimed to determine the role of fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up of patients who underwent total thyroidectomy and iodine-131 ((131)I) ablation therapy for differentiated thyroid cancer and presented increased thyroglobulin levels with negative (131)I and thallium-201 ((201)Tl) scans. METHODS: Two patients with follicular carcinoma and eight with papillary tumors underwent total thyroidectomy and (131)I therapy until the (131)I scan was negative. (131)I and (201)Tl scans were performed with negative results in all cases, while serum thyroglobulin measurements were all positive with negative thyroglobulin autoantibodies. One week after the (131)I scans, all the patients underwent FDG-PET whole-body scans. RESULTS: The FDG-PET scan detected in 4 patients, a single focal increase of FDG uptake in one lymph node metastasis (subsequently confirmed histologically); in 1 patient, multiple pathological focal uptakes in brain, neck, and chest; and in 1 patient, two mild focal uptakes in the mediastinum, close to the tracheal branch. In 2 other patients, pathological FDG uptakes in cervical spine and mediastinum were not confirmed by other imaging techniques, and in the 2 remaining patients the scan results were inconclusive. The sensitivity of FDG-PET whole-body scan for detecting metastatic thyroid cancer was 60%. CONCLUSIONS: This study indicates that the FDG-PET whole-body scan is a useful tool in the follow-up of patients with differentiated thyroid cancer, negative (131)I and (201)Tl scans and elevated serum thyroglobulin levels. The FDG-PET scan detects metastatic disease in 60% of patients with differentiated thyroid cancer, enabling surgical therapy to be performed on accessible lesions.     

高频彩色多普勒超声和血清甲状腺球蛋白在分化型甲状腺癌131I清除残余甲状腺后随访中的应用

目的探讨高频彩色多普勒超声检查和血清甲状腺球蛋白(Tg)检测在分化型甲状腺癌(DTC)131I清除残余甲状腺后随访中的临床应用价值。方法回顾性分析92例接受甲状腺近全或全切除术联合131I清除残余甲状腺治疗的DTC患者资料。根据血清Tg水平分为血清Tg2ng/ml组、2~10ng/ml组及10ng/ml组,比较各组间DTC复发转移率的差异。以临床随访131I全身扫描或病理结果为金标准,评价高频彩色多普勒超声、血清Tg检测及二者联合应用诊断DTC复发转移的效能。结果 92例中,39例DTC复发转移。血清Tg2ng/ml组、2~10ng/ml组及10ng/ml组复发转移率分别为14.81%(8/54)、41.67%(5/12)及100%(26/26),组间差异有统计学意义(P0.05)。高频彩色多普勒超声诊断DTC复发转移的敏感度、特异度、准确率、阳性预测值、阴性预测值分别为89.74%(35/39)、90.57%(48/53)、90.22%(83/92)、87.50%(35/40)、92.31%(48/52),血清Tg检测分别为79.49%(31/39)、86.79%(46/53)、83.70%(77/92)、81.58%(31/38)及85.19%(46/54),二者联合应用分别为94.87%(37/39)、86.79%(46/53)、90.22%(83/92)、84.09%(37/44)、95.83%(46/48)。结论高频彩色多普勒超声检查和血清Tg检测均可用于DTC患者131I清除残余甲状腺后的随访,二者联合应用有利于及早发现复发转移。     

Prognostic value of postsurgical stimulated thyroglobulin levels after initial radioactive iodine therapy in well-differentiated thyroid carcinoma

BACKGROUND: In well-differentiated thyroid carcinoma, predictors of future positivity of stimulated thyroglobulin (>2 microg/L) after initial radioactive iodine treatment are not known. METHODS: In a retrospective study, we used logistic regression analysis to determine whether postoperative stimulated thyroglobulin measurements and pathologic stage independently predict future stimulated thyroglobulin positivity. RESULTS: We followed 141 patients with well-differentiated thyroid carcinoma for a median of 35 months; follow-up stimulated thyroglobulin measurements were positive in 20.6% (29/141). The natural logarithm of the postsurgical stimulated thyrogolobulin was independently associated with a positive stimulated thyroglobulin at long-term follow-up (odds ratio [OR], 4.44; 95% confidence interval [CI], 2.33-8.45; p < .001); there was a trend for a positive association of TNM stage with positive follow-up stimulated thyroglobulin (p = .054). Lymph node positivity predicted a positive stimulated thyroglobulin in papillary cancer. CONCLUSIONS: Stimulated thyroglobulin measurements prior to initial radioactive iodine treatment independently predict future stimulated thyroglobulin positivity in well-differentiated thyroid carcinoma.     

Positron emission tomography with F-18-deoxyglucose in patients with differentiated thyroid carcinoma, elevated thyroglobulin levels, and negative iodine scans

Introduction: In patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin (hTg) may occur in spite of otherwise negative diagnostic procedures and in particular in spite of a negative iodine-131 scan. Positron emission tomography with F-18-deoxyglucose (FDG-PET) is a potentially useful method for the detection of metastatic lesions or the recurrence of thyroid cancer. We aimed to investigate whether FDG-PET is capable of detecting metastastic lesions or recurrence in patients with differentiated thyroid carcinoma, elevated serum levels of thyroglobulin, and otherwise negative diagnostic procedures, including the iodine-131 scan. Methods: From a group of 500 patients with differentiated thyroid carcinoma, a subgroup of 32 patients had elevated serum hTg-levels, negative iodine-131 scans, negative cervical and abdominal ultrasound, and negative X-ray of the chest. In 12 of these patients (hTg 77.8±94.3 ng/ml, range 1.5 – 277 ng/ml, median 20 ng/ml), FDG-PET was performed. All but one FDG-PET study was performed in a state of hypothyroidism (TSH 75.8±32.2 μIU/ml, range 31 – 116 μIU/ml, median 74.6 μIU/ml). Results: In 6 of the 12 patients investigated, the FDG-PET was positive. In three of the patients, the diagnosis was confirmed by computed tomography or magnetic resonance imaging. In patients with a positive FDG-PET finding, the hTg level was 146.7±90.1 ng/ml (23 – 277 ng/ml, median 144.5 ng/ml). In contrast, in patients with a negative finding the hTg level was only 9.0±7.6 ng/ml (range 1.5 – 17 ng/ml, median 8.1 ng/ml), P = 0.01. Conclusion: These preliminary results show that in patients with differentiated thyroid carcinoma, elevated hTg levels, and otherwise negative “conventional” diagnostic procedures, FDG-PET is helpful in detecting metastatic lesions. Received: 15 November 1997     

Radio-guided surgery for persistent differentiated papillary thyroid cancer: case presentations and review of the literature

Background and aims Persistent differentiated papillary thyroid cancer following radical locoregional surgery with metastases is an indication for limited reoperation or radioiodine therapy. Following injection of radioiodine, radio-guided surgery with application of an intraoperative gamma probe offers detection of metastases not seen by conventional imaging and control of completeness of resection.Patients/methods We demonstrate four patients with locoregional metastases, two of them with additional distant metastases of papillary thyroid cancer following radical neck surgery. Postoperative radioiodine scans demonstrated persistent ipsilateral or contralateral cervical and mediastinal lymph node and isolated rib metastases.Results Radio-guided surgery (RGS) leads to complete clearance of persistent lymph node metastases by limited recurrent neck surgery, resection of metastases not seen by conventional imaging and control of complete mediastinal lymph node dissection. Post-RGS scans allowed early diagnosis of occult diffuse or nodal pulmonary metastases in two patients. At last follow-up, 23 to 48 months following RGS and radioiodine therapy, there was no evidence of disease.Conclusions Radio-guided surgery is an additive surgical technique with low morbidity in selected patients with persistent thyroid cancer individualizing tumor therapy options in multimode oncological therapy.Presented at the International Symposium "Modern Technologies in Thyroid Surgery", 10–11 February 2006, Halle/Saale, Germany     

Results of reoperations for persistent or recurrent secondary hyperparathyroidism in hemodialysis patients

Among 258 patients operated on for secondary hyperparathyroidism (HPT II) from 1971 to 1988, a total of 33 had one or more reoperations for persistent or recurrent HPT II. These reoperations did not induce any mortality or significant morbidity. After inadequate parathyroidectomy (25 cases), 15 patients were reoperated. Twelve of these had undergone initial surgery at another institution. Three patients died of causes unrelated to their HPT II. The other 12 patients are disease-free. After successful subtotal parathyroidectomy (79 cases), 2 patients (2.5%) had a recurrence 5 and 6 years later, respectively. Currently, the 2 patients remain disease-free. After total parathyroidectomy with autotransplantation (152 cases), 16 patients (10.5%) had reoperations on the grafts. The mean time before reoperation was 2 1/2 years. Hypertrophy of grafted fragments was observed in 4 cases (2.6%), but only 2 of these 4 patients were cured by removal of the grafts. Residual parathyroid tissue or a supernumerary gland in the neck or the mediastinum was suspected in 5 patients, but this could not be confirmed because one had already been reoperated on in the neck without success, another still refuses reoperation, and 3 died. In 6 other patients, the recurrence was debatable and HPT II was not confirmed. In the last 3 patients, the diagnosis was incorrect and aluminium intoxication was proved later. Results of reoperations for persistent or recurrent HPT II depend, first, on a correct diagnosis. After Successful subtotal parathyroidectomy, reoperations are rare and simple. After total parathyroidectomy and transplantation, it must be kept in mind that recurrences can occur on the grafts and/or on residual tissue in the neck or mediastinum.

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Resumen Entre 258 pacientes operados por hiperparatiroidismo secundario (HPT II) entre 1971 y 1988, un total de 33 tenían historia de una o más reoperaciones por HPT II persistente o recurrente. Estas operaciones no produjeron mortalidad ni morbilidad significativa.De 25 pacientes con paratiroidectomía inadecuada, 15 pacientes fueron reoperados. Doce habían sido operados inicialmente en otra institución. Tres murieron por causas no relacionadas con su HIPT II; los otros 12 pacientes se encuentran libres de enfermedad.De 79 pacientes sometidos a paratiroidectomía subtotal exitosa, 2 (2.5%) tuvieron recurrencia a los 5 y 6 años, respectivamente. Actualmente los 2 están libres de enfermedad.De 152 pacientes sometidos a paratiroidectomía con autotrasplante, 16 (10.5%) requirieron reoperaciones sobre los injertos. El promedio del intervalo a la reoperación fue de 2 1/2 años. Se observó hipertrofia de los fragmentos injertados en 4 casos (2.6%), pero sólo 2 fueron curados con la remoción de los injertos. Se sospechó la presencia de tejido paratiroideo residual o de una glándula supernumeraria ubicada en el cuello o en el mediastino en 5 casos, pero ésto no pudo ser confirmado puesto que uno ya había sido reoperado sobre el cuello sin éxito, otro aún rehusa operación, y 3 han muerto.En otros 6 pacientes, la recurrencia apareció dudosa y el HPT II no pudo ser confirmado.El diagnóstico fue incorrecto en los últimos 3 pacientes, y en ellos se comprobó, más tarde, intoxicación por aluminio.Los resultados de la reoperación por HPT II dependen, en primer lugar, de un diagnóstico correcto. Después de paratiroidectomia total y trasplante, debe tenerse en cuenta que las recurrencias pueden presentarse en el trasplante y/o el tejido residual en el cuello o el mediastino.

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Résumé Sur 258 patients opérés pour hyperparathyroïdie secondaire (HPT II) entre 1971 et 1988, 33 ont eu une ou plusieurs réinterventions pour HPT II persistante ou récidivante. Ces réinterventions n'ont été suivie ni d'une mortalité ni d'une morbidité significative.Après parathyroïdectomie incomplète (25 cas), 15 patients ont été réopérés. Douze d'entre eux avaient déjà été opérés dans un autre établissement. Trois patients sont morts pour des causes sans rapport avec leur HPT II. Les 12 autres patients sont guéris.Après parathyroïdectomie subtotale réussie (79 cas), 2 patients (2.5%) ont eu une récidive, respectivement 5 et 6 ans plus tard. Actuellement les 2 patients sont guéris.Après parathyroïdectomie totale avec autotransplantation (152 cas), 16 patients (10.5%) ont dû être réopérés á cause des greffons. Le délai moyen avant la réintervention fut de 2 1/2 ans. Une hypertrophie des fragments greffés fut observés dans 4 cas (2.6%) mais 2 seulement de ces 4 patients ont été guéris après ablation des greffons. Chez 5 patients du tissu parathyroïdien résiduel ou une glande surnuméraire au cou ou dans le médiastin ont été suspectés, mais ceci n'a pas été confirmé: un patient a été à nouveau cervicotomisé sans succès, un autre refuse toujours la réopération, et 3 sont morts. Chez 6 autres patients la récidive était discutable et l'HPT II n'a pas été confirmée.Quant aux 3 derniers patients, le diagnostic était incorrect et une intoxication à l'aluminium fut démontre utérieurement. Les résultats d'une réintervention pour HPT II persistante ou récidivante dépendent avant tout d'un bon diagnostic. Après parathyroïdectomie subtotale réussie, les réinterventions sont rares et simples. Après parathyroïdectomie totale et transplantation, on ne doit pas oublier que les récidives peuvent survenir sur les greffons et/ou sur le tissu résiduel au cou ou au médiastin.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Total thyroidectomy does not enhance disease control or survival even in high-risk patients with differentiated thyroid cancer.

SUMMARY BACKGROUND DATA: The extent of primary thyroidectomy for differentiated thyroid cancer is controversial. There are strong proponents for total thyroidectomy based on its presumed and theoretical disease control benefits. In contrast, there are equally strong advocates of less aggressive thyroidectomy with its lower hazard of parathyroid and recurrent nerve injury. The authors have addressed whether total thyroidectomy has a survival benefit justifying its use in patients with high-risk primary cancer. The major risk factors include age and the following the pathologic determinants follicular histology, vascular invasion, and extracapsular extension. MATERIALS AND METHODS: The clinical pathologic, therapeutic, prognostic, and outcome data were reviewed in 347 patients with well-differentiated thyroid cancer. Seventy-five percent were women, 216 patients were in the younger age group (low-risk) (21-50 years), 103 were in the intermediate-risk group (51-70 years), and 28 were in the high-risk group (>70 years). Included in the high-risk pathologic category were 158 patients who had follicular histology (55), extracapsular extension (107), or vascular invasion (119). Total thyroidectomy was performed in 56 patients, near or subtotal thyroidectomy in 47 patients and lobectomy in 55 patients. The 10-year disease specific survival in the overall patient group was 82% in patients with total thyroidectomy, 78% in patients with subtotal thyroidectomy, and 89% in patients with lobectomy (p = 0.30). There was no significant survival difference according to extent of thyroidectomy in the intermediate or high-risk groups either by age or in patients who had high-risk pathologic feature. CONCLUSIONS: Total thyroidectomy in high-risk patients with differentiated thyroid cancer (containing follicular histology, vascular invasion, or extracapsular extension) showed no benefit over partial thyroidectomy. This suggests that the general use of total thyroidectomy is not indicated, except in highly selected patients.     

Total thyroidectomy: the treatment of choice for patients with differentiated thyroid cancer.

There is considerable controversy about the most appropriate treatment of patients with thyroid cancer. This report concerns the author's experience with 82 consecutive patients having total thyroidectomy from January 1977 through December 1981. The age of the patients ranged from 21 to 86 years (mean age 44 years). There were 44 women and 38 men. Twenty-four patients (29%) had had previous thyroid operations; ten patients (11%) had coexistent parathyroid adenomas removed; and seven patients (8.5%) had modified radical neck dissections. Thirty-four patients (41%) had a history of radiation to the head and neck, and 12 (35%) of the 34 irradiated patients and 51 (63%) of the entire group of 82 patients had thyroid cancer (45 papillary, five follicular, one medullary). Coexistent lesions in the patients with papillary cancer included Hashimoto's thyroiditis, five patients; parathyroid adenomas, four patients; Graves' disease, one patient; Hurthle cell neoplasm, one patient; and amyloid struma, one patient. If less than total thyroidectomy had been performed, 26 (51%) of the 51 patients with thyroid cancer would have had cancer left in the residual thyroid lobe, and focal cancers in the lobe opposite to the one containing the nodule for which the operation was performed would have been missed in five patients (10%). Five of the 20 patients with unilateral cancer had follicular cancer. Complications included one case of permanent hypoparathyroidism and two cases of transient bilateral recurrent laryngeal nerve palsy. Ninety-six per cent of the patients were discharged within four days of thyroidectomy, 94% by three days, and 79% by two days. Uptake of radioactive iodine was not above background levels in nine (26%) of the 35 patients studied after operation and was less than 1% in the remainder. These data suggest that total thyroidectomy is the treatment of choice for patients with thyroid cancer because residual cancer would persist in the remaining thyroid tissue in at least 61% of patients if only lobectomy had been performed. Total thyroidectomy can be done with minimal permanent disability in patients with benign and malignant thyroid tumors, in patients who have had previous thyroid operations, and in patients with coexistent hyperparathyroidism.