THE VALUE OF FROZEN SECTION EXAMINATION IN PLANNING SURGERY FOR FOLLICULAR THYROID NEOPLASMS

Frozen section examination of follicular neoplasms of the thyroid has been claimed to be of little value in planning the extent of surgery. Clinical factors such as age, sex and tumour size are said to be more accurate predictors of malignancy. The aim of this study was to examine the respective value of clinical factors and frozen section in the surgical management of follicular thyroid neoplasms. A retrospective study of 735 patients with follicular neoplasms treated at Royal North Shore Hospital was undertaken. Factors assessed included clinical features, such as age and sex of the patients and tumour size, as well as findings at frozen section examination. No significant difference in sex distribution was demonstrated when comparing follicular adenoma with follicular carcinoma. There was a significant difference with respect to patient age between the two groups, but the large overlap in the distribution made this difference of no clinical value. In addition, there was no significant difference in tumour size when comparing follicular adenoma with carcinoma. On the other hand, review of frozen section results showed that 40% of patients with follicular carcinoma were positively identified by frozen section examination at initial surgery, with a false positive rate of less than 0.2%. It appears that clinical factors, such as age, sex and tumour size, are of little assistance in differentiating benign from malignant follicular neoplasms. Frozen section examination remains the most definitive tool in planning intra-operatively the extent of surgery for follicular neoplasms of the thyroid.     

Management of hyperfunctioning single thyroid nodules in the era of minimally invasive thyroid surgery

Both surgical excision and radioiodine ablation are effective modalities in the management of hyperfunctioning thyroid nodules. Minimally invasive thyroid surgery (MITS) using the lateral mini‐incision approach has previously been demonstrated to be a safe and effective technique for thyroid lobectomy. As such MITS may offer advantages as a surgical approach to hyperfunctioning thyroid nodules without the need for a long cervical incision or extensive dissection associated with formal open hemithyroidectomy. The aim of the present study was to assess the safety and efficacy of MITS for the treatment of hyperfunctioning thyroid nodules. This is a retrospective case study. Data were obtained from the University of Sydney Endocrine Surgical Unit Database from 2002 to 2007. There were 86 cases of hyperfunctioning thyroid nodules surgically removed during the study period, of which 10 (12%) were managed using the MITS approach. The ipsilateral recurrent laryngeal nerve was identified and preserved in all cases with no incidence of temporary or permanent nerve palsy. The external branch of the superior laryngeal nerve was visualized and preserved in eight cases (80%). There were no cases of postoperative bleeding. There was one clinically significant follicular thyroid carcinoma in the series (10%). In nine of 10 cases (90%) normalization of thyroid function followed surgery. MITS is a safe and effective procedure, achieving the benefits of a minimally invasive procedure with minimal morbidity. As such it now presents an attractive alternative to radioiodine ablation for the management of small hyperfunctioning thyroid nodules.     

THYROID FROZEN SECTION: FLAWED BUT HELPFUL

The role of frozen section (FS) thyroid histology is controversial, some finding it helpful and others finding it inaccurate and of little assistance. The FS and subsequent permanent histology diagnosis were analysed retrospectively in 241 patients, 23 of whom were subsequently shown to have carcinoma. FS correctly identified five (22%) of these, deferred the diagnosis in three (13%) and made an incorrect benign diagnosis in 15 (65%). This impaired accuracy was attributed to the high proportion (13/23) of follicular neoplasms, which are difficult to categorize on FS. No false positive diagnoses were made in the 218 patients with benign disease. The possibility of a benign FS diagnosis being converted to malignant was 6.2%. The result of the FS affected management in that all five patients with the diagnosis of cancer underwent immediate contralateral surgery, but only seven of 18 in the negative FS group had further surgery when permanent histology demonstrated carcinoma, despite equivalent risk factors for poor prognosis in each group. This study suggests that the interpretation of FS and risk factors, in particular the tendency to interpret most follicular neoplasms as benign rather than defer decision, may be improved if pathologists and surgeons interested in thyroid disease are involved in the management of patients with thyroid nodules. Although FS remains flawed it is helpful in a small proportion of cases where it allows immediate contralateral surgery.     

The potential impact of needle biopsy on surgery for thyroid nodules

Current techniques with fine and cutting needle biopsies permit greatly improved selection of patients with thyroid nodules for operation. A diagnosis of definite or probable carcinoma was confirmed in 95% of 76 patients, and the addition of the category of indeterminate cellular nodule resulted in an overall frequency of carcinoma in 86%. Therefore, the frequency of operations for benign thyroid nodules was dramatically decreased. Critical for the use of needle biopsy of the thyroid is experience in obtaining an adequate and representative sample of the nodule, as well as in cytologic and histologic interpretation of the tissue. Results of needle biopsy of thyroid nodules should be correlated with clinical findings even though the latter criteria provide a much less accurate index of the need of operation. The frequency of carcinoma in patients selected for operation can be increased from the 15% to 30% experienced in the past to a level of approximately 85% by needle biopsy. Thyroid nodules that are recognized as cellular by needle biopsy, but in which carcinoma cannot be ruled out should be treated surgically. Improved selectivity for operation for thyroid nodules has not yet significantly reduced the total number of patients undergoing operation in our practice. Some thyroid nodules that would have been treated nonoperatively in the past are now recognized as needing surgery. Operative eradication of nodules that have been considered clinically benign and managed as such in the past, but which are now recognized as being actual or possible carcinoma by needle biopsy conceivably will reduce the frequency of anaplastic or invasive carcinoma in the future. Falsenegative results have been recognized in 1% or less of patients. A preoperative diagnosis of thyroid carcinoma by needle biopsy permits an immediate, definitive surgical procedure, and changes the operative approach for such patients. Needle biopsy of thyroid nodules can reduce procrastination in making a decision for a surgical or medical approach to the management of thyroid nodules.     

甲状腺结节手术范围合理选择——美国及我国相关指南解读

甲状腺结节是甲状腺外科最常见的疾病,其外科治疗一直存在争议。近年来甲状腺结节的发病率在全球范围内呈持续增长趋势。标准的甲状腺手术方式联合规范化的颈淋巴结清扫,对于改善病人的预后,具有至关重要的意义。2015年,美国甲状腺协会（ATA）将发布新版《ATA甲状腺结节和分化型甲状腺癌诊治指南》。该指南内容主要涉及良性甲状腺结节和分化型甲状腺癌（DTC）的初始超声、细针穿刺细胞学检查（FNA）及分子标记物的评估以及甲状腺癌的危险分层、外科治疗、131I治疗和TSH抑制治疗。新版ATA指南将甲状腺结节和DTC外科治疗的基本原则、概念更为科学化、精准化,为今后的临床实践提供了重要的指导作用。     

Thyroid disease and surgery

Thyroid disease remains a common disorder worldwide. In the UK thyrotoxicosis has a prevalence of 2% in women and 0.2% in men. Thyroid diseases affect the function of the thyroid gland. It is associated with thyroid hormone dysfunction and/or thyroid gland enlargement, which may be either benign (nodules or a goitre) or malignant. Thyroid function is divided into normal thyroid hormone activity (euthyroid), reduced thyroid activity (hypothyroidism), and increased thyroid activity, over activity (hyperthyroidism, which if uncontrolled can lead to thyrotoxicosis). These patients are frequently encountered in anaesthesia and an understanding of the pathophysiology of thyroid disease and its associated signs, symptoms and associated complications is essential. In the article we will consider thyroid anatomy, pathophysiology and anaesthetic management.     

机器人甲状腺切除术在韩国将成为一种新的规范术式?

近年来,日新月异的医学技术新发明为外科技术带来了巨大发展。当今,甲状腺手术技术的趋势在韩国也正逐渐发生着改变。因为机器人手术较腔镜手术具有更好的术后美容效果及在人体工程学上的巨大优势,机器人在甲状腺手术中的应用日益增加。此外,机器人甲状腺手术可能成为治疗甲状腺疾病的新规范术式,尤其是在青少年患者的甲状腺恶性肿瘤中。常规机器人及机器人辅助甲状腺手术有多种方法。本文对经双侧腋窝和乳晕入路法(bilateral axillo-breast approach,BABA)在首尔国立大学医学院的运用进行介绍,并讨论其优势。     

Aspiration biopsy cytology in diagnosis of thyroid cancer

Aspiration biopsy cytology (ABC) is a diagnostic method that has been used extensively in Sweden for a quarter of a century. The technical steps involved in this biopsy procedure are described, and the differences from large needle biopsy techniques are pointed out. An overview is given of the different pathologic conditions that present as thyroid nodules and are recognizable by ABC. The accuracy of the method as a preoperative diagnostic tool has been shown to be superior to other clinical methods. ABC enables the surgeon not only to better select patients with thyroid nodules for surgery, but also to plan a definite operative strategy in papillary, medullary, and anaplastic neoplasms. In follicular neoplasms, however, the method cannot distinguish with certainty between adenoma and carcinoma. ABC has drastically reduced the number of diagnostic surgical operations for benign lesions. It requires no anesthesia. It has no complications and there is good patient acceptance, even in children.     

Predicting malignancy in thyroid nodules: molecular advances

Over the last several years, a clearer understanding has developed of the genetic alterations underlying thyroid carcinogenesis. This knowledge can be used to tackle 1 of the challenges facing thyroidologists: management of the indeterminate thyroid nodule. Despite the accuracy of fine-needle aspiration cytology, many patients undergo surgery to diagnose malignancy and better diagnostic tools are required. A number of biomarkers have recently been studied and show promise in this setting. In particular, BRAF, RAS, PAX8-PPARγ, microRNAs, and loss of heterozygosity have each been demonstrated as useful molecular tools for predicting malignancy and can potentially guide decisions regarding surgical management of nodular thyroid disease. This review summarizes the current literature surrounding each of these markers, highlights our institution's prospective analysis of these markers, and describes the subsequent incorporation of molecular markers into a management algorithm for thyroid nodules.     

腔镜甲状腺癌手术后复发特点及处理

腔镜甲状腺手术是指采用颈部或颈外入路在腔镜辅助或完全腔镜下进行的甲状腺手术。随着腔镜技术的完善、手术经验的积累和器械的研发，目前腔镜甲状腺手术适应证已扩大到早期甲状腺乳头状癌。腔镜甲状腺手术有成像放大和术后美容的优势，但也存在一些不足，如腔镜甲状腺癌手术清扫淋巴结时，可能会存在操作盲区，为肿瘤复发和转移留下隐患。腔镜甲状腺癌手术后复发的主要因素是术前评估不到位、手术操作不规范和腔镜经验不足。肿瘤或淋巴结残留是腔镜甲状腺癌手术后复发较常见的情况。腔镜甲状腺癌手术后复发时需要认真评估，多需要再次手术，多主张开放手术，处理原则同开放手术后复发灶的处理。     

Carbonic anhydrase 4 and crystallin alpha-B immunoreactivity may distinguish benign from malignant thyroid nodules in patients with indeterminate thyroid cytology

Background

Thyroid nodules are present in 19%–67% of the population and carry a 5%–10% risk of malignancy. Unfortunately, fine-needle aspiration biopsies are indeterminate in 20%–30% of patients, often necessitating thyroid surgery for diagnosis. Numerous DNA microarray studies including a recently commercialized molecular classifier have helped to better distinguish benign from malignant thyroid nodules. Unfortunately, these assays often require probes for >100 genes, are expensive, and only available at a few laboratories. We sought to validate these DNA microarray assays at the protein level and determine whether simple and widely available immunohistochemical biomarkers alone could distinguish benign from malignant thyroid nodules.

Methods

A tissue microarray (TMA) composed of 26 follicular thyroid carcinomas (FTCs) and 53 follicular adenomas (FAs) from patients with indeterminate thyroid nodules was stained with 17 immunohistochemical biomarkers selected based on prior DNA microarray studies. Antibodies used included galectin 3, growth and differentiation factor 15, protein convertase 2, cluster of differentiation 44 (CD44), glutamic oxaloacetic transaminase 1 (GOT1), trefoil factor 3 (TFF3), Friedreich Ataxia gene (X123), fibroblast growth factor 13 (FGF13), carbonic anhydrase 4 (CA4), crystallin alpha-B (CRYAB), peptidylprolyl isomerase F (PPIF), asparagine synthase (ASNS), sodium channel, non-voltage gated, 1 alpha subunit (SCNN1A), frizzled homolog 1 (FZD1), tyrosine related protein 1 (TYRP1), E cadherin, type 1 (ECAD), and thyroid hormone receptor associated protein 220 (TRAP220). Of note, two of these biomarkers (GOT1 and CD44) are now used in the Afirma classifier assay. We chose to compare specifically FTC versus FA rather than include all histologic categories to create a more uniform immunohistochemical comparison. In addition, we have found that most papillary thyroid carcinoma could often be reasonably distinguished from benign disease by morphological cytology findings alone.

Results

Increased immunoreactivity of CRYAB was associated with thyroid malignancy (c-statistic, 0.644; negative predictive value [NPV], 0.90) and loss of immunoreactivity of CA4 was also associated with malignancy (c-statistic, 0.715; NPV, 0.90) in indeterminate thyroid specimens. The combination of CA4 and CRYAB for discriminating FTC from FA resulted in a better c-statistic of 0.75, sensitivity of 0.76, specificity of 0.59, positive predictive value (PPV) of 0.32, and NPV of 0.91. When comparing widely angioinvasive FTC from FA, the resultant c-statistic improved to 0.84, sensitivity of 0.75, specificity of 0.76, PPV of 0.11, and NPV of 0.99.

Conclusions

Loss of CA4 and increase in CRYAB immunoreactivity distinguish FTC from FA in indeterminate thyroid nodules on a thyroid TMA with an NPV of 91%. Further studies in preoperative patient fine needle aspiration (FNAs) are needed to validate these results.     

COMPLETION TOTAL THYROIDECTOMY IN THE MANAGEMENT OF DIFFERENTIATED THYROID CARCINOMA

Background: Completion thyroidectomy is the removal of any thyroid tissue that remains after a less than total thyroidectomy. This procedure has been commonly performed when the final histopathology of the excised ipsilateral thyroid lobe reveals papillary or follicular carcinoma of the thyroid. Complete thyroidectomy carries little morbidity if performed by experienced surgeons using a lateral approach. The purpose of this study is to reinforce the usefulness of a lateral approach. Methods: A retrospective analysis over a 5 year period at the Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS) yielded 19 patients who underwent completion thyroidectomy. This group represents 23% of 82 patients who underwent total thyroidectomy for differentiated thyroid cancer (DTC) during that period. The residual thyroid tissue was excised through a lateral approach and could be resected safely, preserving the recurrent laryngeal nerve (RLN) and the parathyroid glands. Results: A lateral approach dissection could be performed with ease in a virgin area. Excision of residual thyroid tissue could be performed safely even in cases with prior partial lobectomy or bilateral subtotal resection. Tumour was found in 52% of the re-operative specimens: in three out of four of those after a previous partial lobectomy, in six out of 12 of those after a total lobectomy, and in one out of three of those after a prior bilateral (although incomplete) thyroid resection. Postoperative complications included transient RLN palsy (n = 2) and transient hypoparathyroidism (n = 4). Conclusions: Completion thyroidectomy using a lateral approach is safe in re-operative thyroid surgery.     

分化甲状腺癌手术治疗进展

分化甲状腺癌发病率近年来虽然有逐年升高的趋势,但随着诊治水平不断提高,病死率却呈逐年下降趋势.病死率的降低很大程度与进一步规范了甲状腺癌治疗有关,尤其是外科手术治疗不断发展及完善.甲状腺癌手术治疗还没有达到共识,在很多领域尚存在争议.本文将对分化甲状腺癌手术切除范围,甲状腺癌的再次手术,颈淋巴结清扫,术后辅助放射性I131消融治疗及术后内分泌治疗等问题进行综述.     

甲状腺癌外科治疗术式选择

甲状腺结节是外科医生最常见的甲状腺疾病,其中有5．0％～15．0％最终会诊断为甲状腺癌。如果针吸活检后病理结果提示为阳性或高度怀疑为恶性肿瘤,则外科手术是必须的。在过去十年中,外科医生为了追求切口小型化和创伤最小化,将腔镜技术引入到甲状腺手术中,统称为“甲状腺微创手术”,包括颈部小切口甲状腺手术、腔镜辅助下小切口甲状腺手术,简称Miccoli术式,和颈部无瘢痕存留的全腔镜下甲状腺手术,以及最近开展的机器人辅助下全腔镜甲状腺手术。所有这些手术方式都必须遵循相同的肿瘤外科手术操作原则。本文列举了目前国内关于分化型甲状腺癌的术式选择,同时还列举了国内外各种主流手术方法,并说明其优缺点,以期望对临床工作有所帮助。     

Cytological diagnosis of thyroid disease

Fine needle aspiration biopsy cytology (ABC) is a morphological method, which may be used as an "office" procedure for all palpable lesions. Hyperplastic and inflammatory conditions of the thyroid and various types of neoplasms produce readily recognizable features in cytological smears. About 90% of all thyroid cancers may be diagnosed by aspiration cytology. The method bridges the diagnostic gap between initial palpatory examination and histological diagnosis and can greatly reduce the need for diagnostic surgery. The accuracy of the method has been shown to be superior to that of other non-invasive clinical methods. ABC enables the surgeon not only to better select patients with thyroid nodules who might benefit from surgery, but also to plan a definite operative strategy in papillar medullary and anaplastic cancer. In follicular neoplasms the method can not distinguish with certainty between adenoma and carcinoma. Fine needle aspiration requires no anesthesia. It has no complications and there is good patient acceptance and biopsies can therefore be repeated whenever needed.     

Thyroid carcinoma associated with squamous cell carcinoma of the head and neck: Which policy?

BACKGROUND: Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (HNSCC) is unusual. The clinical management of thyroid cancer in such cases has been debated. METHODS: Between 1975 and 2004, we collected 33 cases. The associated thyroid carcinoma was diagnosed either during or as a consequence of surgery planned as head and neck cancer treatment. RESULTS: The associated thyroid carcinoma was never seen to recur. Five-year overall survival was 41%. Disease-free survival after 40 and 66 months was 11.1% and 5.6%, respectively. CONCLUSIONS: We consider the treatment of thyroid cancer to be complete when the thyroid gland, either with or without lymph nodes, has been included in the specimen obtained during surgery for HNSCC. In the group of cases in which associated thyroid carcinoma was only found within the neck lymph nodes and the thyroid gland has not been treated, we discourage further surgical treatment or radioactive iodine therapy.     

Unusual Malignant Thyroid Tumours - a Clinical Study of 20 Cases

The aim of this study is to assess late results of surgical treatment for primary non-Hodgkin lymphoma (PNHL), thyroid sarcomas (TS) and tumour metastases (TM) of the thyroid gland.

Materials and methods : Between January 1^st, 1990 and December 31^st, 2005, 12725 patients were surgically treated for various types of goitre. Malignant tumour was diagnosed in 617 (4.9%) cases, consisting of 597 (96.8%) patients with thyroid carcinoma and 20 (3.2%) with other tumours, which included 9 (1.5%) cases of PNHL, 9 (1.5%) cases of TM and 2 (0.2%) patients who showed TS.

Results : In the group of patients diagnosed with PNHL, variant B-cell lymphoma predominated (77.8%), and in cases of patients with TM renal cell carcinoma prevailed (77.8%). In all cases, hypo-echogenic nodules were observed in ultrasonography and cold nodules in scintigraphy. All patients were surgically treated with possible complementary chemotherapy and/or radiotherapy. At present, 5 patients with PNHL are alive - 43–93 (average of 63.8) months after the operation. Others have died within a period of 2 days to 3 months after the operation. Two patients with TM are alive - 19 and 46 (median 32.5) months after the operation. Others have died within a period of 3 to 62 (median 21) months after the operation. Patients with TS have died respectively 19 days and 13 months after the operation. Conclusions :

1. Patients with primary thyroid lymphomas should be approached individually using all available methods of treatment, including surgery and radiotherapy and/or chemotherapy.

2. Diagnosis of cold nodules in patients with oncological history should always arouse suspicion of metastases to the thyroid gland.

3. Diagnosis of non-thyroid cancer prior to surgery is difficult to obtain.

4. The need for surgery is usually based on local compression.     

Does frozen section have a role in the intraoperative management of thyroid nodules?

Background: Frozen section in thyroid surgery is used to make an intraoperative pathological diagnosis of malignancy in a thyroid nodule at the time of hemithyroidectomy. A positive diagnosis allows completion of thyroidectomy, thus avoiding reoperation. However, the use of fine needle aspiration cytology in making a preoperative diagnosis of cancer has resulted in the lack of a defined role for frozen section. We examined the role of frozen section as an adjunct to fine needle aspiration cytology in determining which cytological subset will benefit from frozen section. Methods: All patients who underwent thyroidectomy between 1992 and 2000 by a single endocrine surgeon were reviewed. Results: Two hundred and nine frozen sections were performed, of which 144 underwent preoperative fine needle aspiration cytology. Frozen sections reported 135 benign nodules, 59 follicular neoplasms, five specimens with suspicious histology and 10 cancers. Ten out of 20 thyroid cancers were correctly identified by frozen section (sensitivity: 50%; specificity: 100%), eight cancers were reported on frozen section as indeterminate and two benign. Of 144 fine needle aspiration cytological procedures, frozen section on seven suspicious aspirates identified two cancers, and frozen section on 70 follicular aspirates identified four cancers, allowing intraoperative conversions to total thyroidectomy. Frozen section on seven malignant aspirates confirmed four cancers but resulted in reoperation for three because of the indeterminate frozen section reports. There were no cancers found on 135 benign aspirates. Conclusions: Frozen section on benign aspirates is unhelpful in the management of thyroid nodules. It need not be performed for cytologically proven malignant thyroid nodules. Selective use of frozen section complements fine needle aspiration cytology findings of suspicious or follicular lesions, especially in the subset with papillary cancer, allowing one-stage total thyroidectomy.     

腔镜技术在甲状腺结节治疗中的应用与评价

甲状腺结节是甲状腺外科的常见病,为了切除病灶或明确诊断,大多数甲状腺结节需外科手术治疗。腔镜技术在甲状腺外科的应用缩小或避免了开放手术对颈部外观的不良影响。随着手术技术的进步,腔镜下已能完成几乎所有方式的甲状腺手术,其中腔镜下甲状腺次全切除术是应用最多的手术方式。常用的手术入路包括经颈前小切口的腔镜辅助甲状腺手术以及经胸乳入路或经腋窝入路的完全腔镜下甲状腺手术。对于低危的分化型甲状腺癌,腔镜下甲状腺近全切除术代替甲状腺全切除,疗效确切,安全性高,但腔镜下颈淋巴结清扫的效果尚有争议。     

Thyroidectomy

Thyroidectomy is performed for several indications including thyrotoxicosis, nodules showing equivocal/suspicious cytology, thyroid cancer and thyroids causing compression symptoms. The procedure has evolved over time and is now considered a safe procedure in experienced hands. The risks of surgery are, however, serious and therefore meticulous surgery is required. Thyroidectomy in retrosternal goitre may require an extra-cervical approach that the surgeon and patient need to be aware of. Recent changes to thyroid surgery include the increasing use of intraoperative nerve monitoring and pre- and postoperative laryngoscopy to accurately assess damage to the recurrent laryngeal nerve.