Total thyroidectomy for occult familial medullary carcinoma of the thyroid in children

Experience with 17 children in one kindred with familial medullary carcinoma of the thyroid and pheochromocytoma has demonstrated the utility and validity of periodic provocative testing by calcium infusion or pentagastrin injection in the identification of children with early medullary carcinoma of the thyroid or its premalignant precursor, C-cell hyperplasia. In these 17 patients with two consecutive elevations of calcitonin levels greater than 0.55 ng/ml after stimulation all but one have had MTC or CCH at operation. Total thyroidectomy has been well tolerated and can be performed with an acceptably low incidence of complications in this group of patients.     

Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2

Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Completion thyroidectomy for thyroid carcinoma

We have reviewed the charts of 149 patients who underwent completion thyroidectomies for cancer of the thyroid. The purpose of the study was to evaluate extent of residual disease in the thyroid, and morbidity and mortality of the operation. Residual cancer was found in 58% of the cases, the morbidity was low, and there was no operative mortality.     

Completion thyroidectomy for differentiated thyroid carcinoma

Completion thyroidectomy is performed because of a deferred diagnosis of differentiated carcinoma of the thyroid or a significant thyroid remnant after initial operation. During a period of 6 years, data from 40 patients with differentiated thyroid carcinoma undergoing completion thyroidectomy were retrospectively reviewed. There were 4 men and 36 women (1:9), and the average age was 39.6 ± 1.9 years (range, 20 to 62 years). The indications for the initial surgery were a solitary thyroid nodule in 36 (90%) patients, multinodular goiter in 3 (7.5%) patients, and Graves’ disease in 1 (2.5%) patient. Three patients underwent completion thyroidectomy during the same hospital stay. In the remaining 37 patients, completion thyroidectomy was performed 4 to 252 days (44.1 ± 7.8 days) after the initial operation. The length of hospital stay for the initial operation was not different from that for completion thyroidectomy (5.1 ± 0.3 days vs. 5.2 ± 0.3 days). The length of time needed to accomplish the initial operation was not different from that required for the completion thyroidectomy (122 ± 7.5 minutes vs. 110.8 ± 5.9 minutes). There was no 30-day perioperative mortality. The postoperative morbidity in completion thyroidectomy consisted of transient hypoparathyroidism in 3 (7.5%) patients, permanent hypoparathyroidism in 1 (2.5%) patient, transient recurrent laryngeal nerve palsy in 1 (2.5%) patient, and permanent recurrent laryngeal nerve palsy in 1 (2.5%) patient. On the other hand, one transient recurrent laryngeal nerve palsy and one transient hypoparathyroidism occurred at the initial operation. Completion thyroidectomy is a safe procedure to remove the thyroid remnant. (Otolaryngol Head Neck Surg 1998;118:896-9.)     

Video-assisted thyroidectomy for papillary thyroid carcinoma

Background: In patients with small papillary thyroid carcinomas (PTC), we evaluated the operative feasibility and safety of video-assisted thyroidectomy (VAT) and the completeness of the surgical resection. Methods: Video-assisted thyroidectomy was attempted in 24 patients with thyroid malignancy. Total thyroid resection for PTC was achieved completely by VAT in 20 of them, who were included in this study. Results: In this study, 12 total thyroidectomies and 8 lobectomies followed by completion thyroidectomies were performed. Eight patients also underwent central neck lymph node dissection. Mean postoperative serum thyroglobulin was 0.2 ng/ml for patients receiving LT4 suppressive treatment and 4.2 ng/ml for patients after LT4 withdrawal. Postoperative ultrasonography showed no residual thyroid tissue. The mean radioiodine uptake at postoperative scintiscan was 2.2%. Conclusions: In the case of PTC, VAT is feasible and safe. The completeness of the surgical resection seems comparable with that reported for conventional surgery. Nevertheless, larger series and longer follow-up evaluation are necessary for definitive conclusions to be drawn about its oncologic validity. This article is based on a communication at the 10th European Association for Endoscopic Surgery (E.A.E.S.) Annual Congress, Lisbon Portugal, 2–5 June 2002     

Prophylactic antibiotics in children at risk for urinary tract infection

The outcome of using prophylactic antibiotics in children considered at risk for a urinary tract infection (UTI) was documented in 66 children during the period of suppressive antibiotics and for a follow-up period of 3.7+/-2.2 years (range 0.92-9.83 years). A breakthrough UTI occurred in 13 girls but none of the boys during the initial course of prophylactic antibiotics. During the follow-up period, 33 girls and 5 boys had no recurrence of infection, while 25 girls and 3 boys had UTIs. Statistical analysis of the data using chi-square and risk estimate relating factors for infection to the occurrence of a UTI showed that during the period of initial prophylactic antibiotic there was significant risk of infection among children with voiding dysfunction and abnormal kidneys and during the follow-up there was increased risk of infection among those with voiding dysfunction and vesicoureteric reflux (VUR) of grade 3 or greater severity. Lesser grades of VUR and constipation did not significantly increase the risk of UTI. These observations should be useful in developing a study to define the risks and benefits of prophylactic antibiotic in "at-risk" children.     

Nonfamilial medullary thyroid carcinoma

On the basis of this report and the current literature, we conclude that the familial type of medullary thyroid carcinoma can be diagnosed early using basal and poststimulation levels of calcitonin. However, most of the patients with sporadic disease present with a neck mass later in life. The tumor has a tendency to invade locally and metastasize to lymph nodes early in its course. Prognosis is negatively influenced by the extent of disease, lymph node involvement and elderly age. The surgical procedures of choice should be total thyroidectomy with clearance of central nodes of the neck as well as neck dissection when indicated. All parathyroid glands should be inspected. For patients treated for cure, the determinant 10 year survival is 48 percent, and 20 year survival is 33 percent. Recurrence of local disease should be treated aggressively, as important palliation and prolongation of life can be achieved. Radiotherapy may be helpful in the management of residual tumor or recurrent disease. Basal calcitonin assays and poststimulation studies are useful in diagnosing residual or recurrent disease. In the familial cases, the existence of other endocrinopathies has to be considered in the management of the patients.     

Near-total thyroidectomy for carcinoma of the thyroid

There is controversy about the most appropriate treatment for patients with thyroid cancer. This study analyses our experience with 206 cases of thyroid cancer from an endemic goiterous area. There were 100 males and 106 females; patients presented at an earlier age with a short history. Thyroid cancers demonstrated an aggressive biological behaviour with an advanced stage at presentation (overt cancers in 51 per cent) and a relentless course with a mortality rate of 24.2 per cent for the well-differentiated tumours. Near-total thyroidectomy was performed in 126 patients. Multicentric foci of tumour were seen in 17.2 per cent of the well-differentiated cancers and 25.2 per cent of the cases of well-differentiated cancers who underwent near-total thyroidectomy developed loco-regional recurrence. Hemithyroidectomy was performed in 35 patients who refused completion total thyroidectomy at a second stage; 16.7 per cent of these patients developed a recurrence in the remaining contralateral lobe. Thus in our patients from an endemic goiterous area, near-total thyroidectomy is the treatment of choice particularly because of the frequent occurrence of follicular and anaplastic cancers (in 44.2 per cent) and because the course of the disease is more virulent.     

Prophylactic thyroidectomy in pediatric carriers of multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma: mutation in C620 is associated with Hirschsprung's disease

Purpose

Prophylactic total thyroidectomy is now recommended after having confirmed RET mutations in children of parents with multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma. We reviewed our experience to determine the incidence of medullary thyroid carcinoma with respect to age at surgery, the location of the mutation, and its association with Hirschsprung's disease (HD).

Methods

A retrospective review from 1996 to 2005 revealed 20 children with genetic screening for multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma who underwent a prophylactic total thyroidectomy with parathyroid gland preservation.

Results

The median age of the 20 patients (9 boys and 11 girls) included in this study was 8.2 years (range, 3.7-16.9 years) at the time of their surgery. Final pathology revealed normal thyroid tissue (n = 3; median age, 5.9 years), C-cell hyperplasia (n = 13; median age, 10 years), or medullary thyroid carcinoma (n = 4; median age, 8 years). Four children, all with mutations in C620, had a previous diagnosis of HD. At a median follow-up of 3.7 years (range, 1 month to 8.4 years), all patients were well and cancer free.

Conclusions

There is no correlation between histologic findings and median age at surgery. Hirschsprung's disease was found in 50% of the patients with the RET mutation in C620. In children of C620 parents, symptoms of HD should be actively sought, and if such are found, rectal biopsies should be performed even if mutation results are not yet available. Based on the age of the earliest cancer and the safety of total thyroidectomy, children should promptly undergo surgery after genetic screening and before their fifth year of life.     

甲状腺癌患者甲状腺全切手术安全性探讨

目的 探讨甲状腺癌患者行甲状腺全切除手术的安全性.方法 回顾性分析1986年1月至2006年12月因甲状腺癌行甲状腺全切除(全切组)以及次全或近全切除术(双叶手术组)的患者资料,比较两组间喉返神经损伤和继发性甲状旁腺功能低下的发生率.结果 双叶切除手术组433例:13例发生暂时性单侧喉返神经损伤,5例发生永久性单侧喉返神经损伤;11例发生暂时性甲状旁腺功能低下,无永久性甲状旁腺功能下病例.甲状腺全切手术组共70例:4例发生暂时性单侧喉返神经损伤(P>0.05),1例发生永久性单侧喉返神经损伤(P>0.05);7例发生暂时性甲状旁腺功能低下(P<0.01),2例永久性甲状旁腺功能低下(P<0.05).结论 甲状腺全切除术并不增加喉返神经损伤的概率,但手术后甲状旁腺功能低下发生率增加,因此应该有选择的施行甲状腺全切除手术.     

Cyclooxygenase-2 expression in medullary thyroid carcinoma

BACKGROUND: Recent studies have demonstrated that cyclooxygenase-2 (COX-2) expression is associated with the carcinogenesis of numerous neoplasms. The aim of this study was to evaluate the role of COX-2 in medullary thyroid carcinoma (MTC). METHODS: Tissue specimens of thyroid neoplasms were obtained from 22 patients with MTC and 15 control subjects with nonmalignant thyroid specimens. RESULTS: This immunohistochemical study confirms the presence of COX-2 in a significant number of MTCs. A large area of staining was noted in only 2 patients in the control group (13%) compared with 18 (82%) in the medullary carcinoma group. On a scale of 0 to 3, the average area of positive staining measured 2.35 in the study group and 0.9 in the control group (p < .0001). The average intensity of staining on a scale of 0 to 5 (deep brown) was 2.15 and 0.8 mm, respectively (p < .001). CONCLUSION: COX-2 is expressed significantly in MTC including a larger area of staining and greater intensity than in nonmalignant thyroid tissue. These findings may have important treatment implications for the use of COX-2 inhibitors in patients with MTC.     

Genetic screening in hereditary medullary thyroid carcinoma

Summary Background: Medullary thyroid carcinoma (MTC) is sporadic in the great majority of cases but is the sine qua non of multiple endocrine neoplasia type 2 (MEN 2), an autosomal dominantly inherited cancer syndrome. Depending on the tissues affected, MEN 2 is divided into 3 subtypes. MEN 2A is characterized by the presence of MTC, pheochromocytoma and hyperparathyroidism. MEN 2B is characterized by MTC, pheochromocytoma and typical stigmata. FMTC comprises MTC as the only disease feature. Germline mutations in theRET protooncogene, which encodes a receptor tyrosine kinase, have been shown to cause all 3 subtypes of MEN 2. Methods: Analyses utilize PCR-based protocols targeted at exons 10, 11, 13, 14 and 16: target exonic sequences are amplified either for direct sequencing and/or restriction endonuclease digestion where mutations would create or cause loss of specific sites. Results: Mutations in one of codons 609, 611, 618, 620 (exon 10) and 634 (exon 11) are associated with MEN 2A while mutation in codon 916 (codon 16) causes MEN 2B. Recently mutations in codons 768 and 804 were shown to be associated with FMTC only. Conclusions: These findings have made accurate DNA-based genetic testing possible, thus targettingRET mutation positive individuals for prophylactic surgery and/or surveillance while mutation negative individuals can be reassured.      

Early thyroidectomy for medullary thyroid carcinoma in children and young adults with the multiple endocrine neoplasia type 2A (MEN 2A) syndrome.

A South African family, at risk for the multiple endocrine neoplasia type 2A (MEN 2A) syndrome, was identified. The Bloemfontein MEN Study Group was founded, inter alia, to study the effects of early detection of medullary carcinoma of the thyroid (MTC) and treatment by total thyroidectomy in children and young adults with MEN 2A. Genotypes were identified by DNA probe and MTC diagnosed by basal and stimulated calcitonin levels. Between 1986 and 1989, 10 members of the family underwent total thyroidectomy and central lymph node dissection for MTC. There were 6 female and 4 male patients (mean age 22,0 years; range 10 - 35 years). Histological examination of the resected thyroid revealed MTC in all patients; 8 had bilateral disease and 2 unilateral. Lymph nodes were negative for MTC in all patients. None of the patients suffered injury to the recurrent nerve, while 1 experienced transient hypoparathyroidism postoperatively. Replacement therapy is maintaining thyroid hormone levels in all patients. Screening should probably begin at the age of 1 year, and total thyroidectomy should be performed when an elevated calcitonin level is observed.     

Surgical therapy of medullary thyroid carcinoma

This study describes the findings of a retrospective study of 57 medullary thyroid cancer patients observed at the main Sicilian centres for endocrine surgery. Six of these patients were observed locally in order to add a further dimension to the discussion of surgical therapies for medullary thyroid carcinoma. A review of the literature on sporadic forms of medullary thyroid carcinoma and hereditary neoplastic syndromes is followed by presentation of the authors' series. Diagnostic protocols, surgical therapies and pathological observations are discussed. Particular attention is paid to patterns of metastases of medullary thyroid carcinoma and to the differing opinions regarding the extent of lymph-node dissection required and the treatment of recurrent disease. Total extracapsular thyroidectomy with lymph-node dissection is identified as the gold standard of surgical therapies for this form of cancer.     

Treatment of familial medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy, which is familial in 25-29% of cases. Familial MTC is due to germ-line mutations in the RET proto-oncogene. It can occur either alone or as the thyroid manifestation of MEN 2 syndromes; the disease is inherited in an autosomal dominant fashion with age-related penetrance. The treatment of choice is surgery. Early diagnosis and an adeguate initial operation provide the best chance of cure. Hence, the diagnosis should be made preoperatively. Genetic testing can identify almost all affected individuals with hereditary disease and permits prophylactic/early thyroidectomy in gene carriers. Total thyroidectomy and lymphadenectomy of the cervicocentral compartment is mandatory in all patients. In addition, bilateral dissection of the cervicolateral compartment should be done in all cases with more than microscopic disease. Plasma calcitonin is an excellent marker for postoperative follow-up. Treatment of persistent/recurrent disease is primarily surgical. Hence, a reoperative cervical lymphadenectomy should be considered in patients with persistently elevated calcitonin levels and no signs of distant metastases. Chemotherapy and external radiotherapy have little impact on the course of avanced disease; more promising is metabolic radiotherapy with Y90-DOTATOC in patients with somatostatin receptor-positive tumours.