Outcomes for patients with papillary thyroid cancer who do not undergo prophylactic central neck dissection.

BACKGROUND: The role of prophylactic central neck dissection (CND) in the management of papillary thyroid cancer (PTC) is controversial. This report describes outcomes of an observational approach in patients without clinical evidence of nodal disease in PTC. METHODS: All patients who had surgery between 1986 and 2010 without CND for PTC were identified. All patients had careful clinical assessment of the central neck during preoperative and perioperative evaluation, with any suspicious nodal tissue excised for analysis. The cohort included patients in whom lymph nodes had been removed, but no patient had undergone a formal neck dissection. Recurrence-free survival (RFS), central neck RFS and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. RESULTS: Of 1798 patients, 397 (22.1 per cent) were men, 1088 (60.5 per cent) were aged 45 years or more, and 539 (30.0 per cent) had pT3 or pT4 disease. Some 742 patients (41.3 per cent) received adjuvant treatment with radioactive iodine. At a median follow-up of 46 months the 5-year DSS rate was 100 per cent. Five-year RFS and central neck RFS rates were 96.6 and 99.1 per cent respectively. CONCLUSION: Observation of the central neck is safe and should be recommended for all patients with PTC considered before and during surgery to be free of central neck metastasis.

Anaplastic thyroid carcinoma: a 25-year single-institution experience.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive solid tumors accounting for 1-5 % of primary thyroid malignancies. In this retrospective review, we aim to evaluate the prognostic factors, treatment approaches, and outcomes of patients with ATC treated at a single institution. MATERIALS AND METHODS: We retrospectively identified 95 patients with ATC from an institutional database between 1985 and 2010. A total of 83 patients with sufficient records were included in this study. Patient, tumor, and treatment characteristics were recorded. Disease-specific survival (DSS) was determined by the Kaplan-Meier method, and factors predictive of outcome were determined by univariate and multivariate analysis. RESULTS: Of the 83 patients, 41 were male and 42 were female. The median age at presentation was 60 years (range 28-89 years) with a median survival of 8 months. The 1- and 2-year DSS were 33 and 23 %, respectively. On univariate analysis, age less than 60 years, clinically N0 neck, absence of clinical extrathyroidal extension (cETE), gross total resection, and multimodality treatment were statistically significant predictors of improved survival. On multivariate analysis, absence of cETE, multimodality therapy, and gross total resection were predictors of improved outcome. CONCLUSIONS: In patients with locoregional limited disease, multimodality treatment with gross total surgical resection and postoperative radiotherapy with or without chemotherapy offers the best local control and DSS.

The utility of parathyroid autofluorescence as an adjunct in thyroid and parathyroid surgery 2023.

Thyroid and parathyroid surgery requires careful dissection around the vascular pedicle of the parathyroid glands to avoid excessive manipulation of the tissues. If the blood supply to the parathyroid glands is disrupted, or the glands are inadvertently removed, temporary and/or permanent hypocalcemia can occur, requiring post-operative exogenous calcium and vitamin D analogues to maintain stable levels. This can have a significant impact on the quality of life of patients, particularly if it results in permanent hypocalcemia. For over a decade, parathyroid tissue has been noted to have unique intrinsic properties known as "fluorophores," which fluoresce when excited by an external light source. As a result, parathyroid autofluorescence has emerged as an intra-operative technique to help with identification of parathyroid glands and to supplement direct visualization during thyroidectomy and parathyroidectomy. Due to the growing body of literature surrounding Near Infrared Autofluorescence (NIRAF), we sought to review the value of using autofluorescence technology for parathyroid detection during thyroid and parathyroid surgery. A literature review of parathyroid autofluorescence was performed using PubMED. Based on the reviewed literature and expert surgeons' opinions who have used this technology, recommendations were made. We discuss the current available technologies (image vs. probe approach) as well as their limitations. We also capture the opinions and recommendations of international high-volume endocrine surgeons and whether this technology is of value as an intraoperative adjunct. The utility and value of this technology seems promising and needs to be further defined in different scenarios involving surgeon experience and different patient populations and conditions.

Anatomy of thyroid and parathyroid glands and neurovascular relations.

Historically, thyroid surgery has been fraught with complications. Injury to the recurrent laryngeal nerve, superior laryngeal nerve, or the parathyroid glands may result in profound life-long consequences for the patient. To minimize the morbidity of the operation, a surgeon must have an in-depth understanding of the anatomy of the thyroid and parathyroid glands and be able to apply this information to perform a safe and effective operation. This article will review the pertinent anatomy and embryology of the thyroid and parathyroid glands and the critical structures that lie in their proximity. This information should aid the surgeon in appropriate identification and preservation of the function of these structures and to avoid the pitfalls of the operation.

Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer.

OBJECTIVE: To describe the risk of structural disease recurrence in a cohort of patients with differentiated thyroid cancer selected for treatment with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation (RRA). DESIGN: Retrospective review. PATIENTS: A total of 289 patients were selected for either thyroid lobectomy (n = 72) or total thyroidectomy (n = 217) without RRA and followed with modern disease detection tools in a tertiary referral centre. Most patients had papillary thyroid cancer (89%) without clinically evident lymph node metastases (91%). However, 55% (156/289) of patients had primary tumours that were >1 cm and 10% (28/289) had minor extrathyroidal extension. MEASUREMENTS: The primary endpoint was detection of recurrent/persistent structural disease. RESULTS: After a 5-year median follow-up, structural disease recurrence was detected in 2·3% (5/217) of patients treated with total thyroidectomy without RRA, and in 4·2% (3/72) of patients treated with thyroid lobectomy. Size of the primary tumour, the presence of cervical lymph node metastases and American Thyroid Association risk category were all statistically significant predictors of recurrence. Changes in serum thyroglobulin were not helpful in identifying the presence of persistent/recurrent structural disease. Importantly, 88% (7/8) of the patients that had recurrent disease were rendered clinically disease free with additional therapies. CONCLUSIONS: Initial risk stratification is able to identify a cohort of patients with differentiated thyroid cancer with a very low risk of structural disease recurrence following treatment with either thyroid lobectomy or total thyroidectomy without RRA. Our data strongly support a selective approach to the initial management of thyroid cancer.

Complications of thyroid surgery: prevention and management.

The essentials of thyroid surgery include intimate knowledge of thyroid gland anatomy, sound understanding of thyroid pathology and meticulous technique. While mortality due to thyroid surgery is rare, complications can result in debilitating sequelae. Thyroid surgeons need to understand and anticipate situations when these may occur, and actively take steps to prevent them, as treatment of these complications is often difficult and frustrating. Surgeons also need to maintain an audit of their own complication rates and convey these to patients instead of quoting data from published literature, which is biased towards high-volume specialized units rather than "real world data". This review addresses the common complications that occur during thyroid surgery and the issues therein.

The role of radioactive iodine in the management of patients with differentiated thyroid cancer - An oncologic surgical perspective.

With improved understanding of the biology of differentiated thyroid carcinoma its management is evolving. The approach to surgery for the primary tumour and elective nodal surgery is moving from a "one-size-fits-all" recommendation to a more personalised approach based on risk group stratification. With this selective approach to initial surgery, the indications for adjuvant radioactive iodine (RAI) therapy are also changing. This selective approach to adjuvant therapy requires understanding by the entire treatment team of the rationale for RAI, the potential for benefit, the limitations of the evidence, and the potential for side-effects. This review considers the evidence base for the benefits of using RAI in the primary and recurrent setting as well as the side-effects and risks from RAI treatment. By considering the pros and cons of adjuvant therapy we present an oncologic surgical perspective on selection of treatment for patients, both following pre-operative diagnostic biopsy and in the setting of a post-operative diagnosis of malignancy.

Ethical issues in non-intervention trials for thyroid cancer.

In recent years, the increasing numbers of small, apparently indolent thyroid cancers diagnosed in the world have encouraged investigators to consider non-intervention as an alternative to surgical management. In the following pages, the prospect of a non-intervention trial for thyroid cancer is considered with attention to the ethical issues that such a trial might raise. Such a non-intervention trial is analyzed relative to 7 ethical considerations: the social or scientific value of the research, the scientific validity of the trial, the necessity of fair selection of participants, a favorable risk-benefit ratio for trial participants, independent review of the trial, informed consent, and allowing the study participants to withdraw from the trial. A non-intervention trial for thyroid cancer is also considered relative to the central concept of equipoise.

Differentiated and Medullary Thyroid Cancer: Surgical Management of Cervical Lymph Nodes.

Thyroid cancer metastasises to the central and lateral compartments of the neck frequently and early. The impact of nodal metastases on outcome is affected by the histological subtype of the primary tumour and the patient's age, as well as the size, number and location of those metastases. The impact of extranodal extension has recently been highlighted as an important prognosticating factor. Although clinically evident nodal disease in the lateral neck compartments has a significant impact on both survival and recurrence, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. Here we discuss the surgical management of neck metastases in well-differentiated and medullary thyroid carcinoma.

Molecular cytogenetic characterization of head and neck squamous cell carcinoma and refinement of 3q amplification.

We applied a combination of molecular cytogenetic methods, including comparative genomic hybridization (CGH), spectral karyotyping (SKY), and fluorescence in situ hybridization, to characterize the genetic aberrations in a panel of 11 cell lines derived from head and neck squamous cell carcinoma and 1 cell line derived from premalignant oral epithelium. CGH identified recurrent chromosomal losses at 1p, 3p, 4, 8p, 10p, and 18q; gains at 3q, 5p, 8q, 9q, and 14q; and high-level amplification at 3q13, 3q25-q26, 5q22-q23, 7q21, 8q24, 11q13-q14, 12p13, 14q24, and 20q13.1. Several recurrent translocations including t(1;13)(q10;q10), t(13;13)(q10;q10), t(14;14)(q10;q10), i(8)(q10), and i(9)(q10) and breakpoint clusters at 1p11, 1q21, 3p11, 5q11, 5q13, 6q23, 8p11, 8q11, 9p13, 9q13, 10q11, 11q13, 13q10, 14q10, and 15q10 were identified by SKY. There was a good correlation between the number of aberrations identified by CGH and SKY (r = 0.69), and the analyses were both confirmatory and complementary in their assessment of genetic aberrations. Amplification at 3q26-q27 was identified in 42% of cases. Although SKY defined the derivation of 3q gain, the precise breakpoint remained unassigned. Positional cloning efforts directed at the amplified region at 3q26-q27 identified three highly overlapping nonchimeric yeast artificial chromosome clones containing the apex of amplification. The use of these yeast artificial chromosome clones as a probe for fluorescence in situ hybridization analysis allowed a detailed characterization and quantification of the 3q amplification and refinement of unassigned SKY breakpoints.

Hürthle cell carcinoma: a critical histopathologic appraisal.

PURPOSE: Controversy exists over the ability of morphology to predict the biologic behavior of Hürthle cell carcinoma. The aim of this study was to conduct a critical histopathologic review of Hürthle cell carcinoma and to correlate morphologic parameters with clinical outcome. PATIENTS AND METHODS: Patients with histologically confirmed Hürthle cell carcinoma treated between 1940 and 2000 form the basis of this study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB] n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi). Minimally invasive carcinomas ([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both. The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Rates of recurrence/death were estimated by Kaplan-Meier method. The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression. RESULTS: Median follow-up was 8 years. No patients with UMB or MIC relapsed or died of disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and extent of resection did not influence outcome. Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P <.05). Both Ci and Vi were associated with worse DSS (P <.05). On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P <.05). CONCLUSION: Patients with Hürthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics. Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hürthle cell carcinoma, as does extrathyroidal extension.

Accelerated concomitant boost radiotherapy and chemotherapy for advanced nasopharyngeal carcinoma.

PURPOSE: To evaluate the feasibility and efficacy of concomitant boost radiotherapy (RT) plus cisplatin-based chemotherapy compared with standard fractionation RT for patients with advanced nasopharyngeal cancer. PATIENTS AND METHODS: From 1988 through 1999, 50 patients with American Joint Committee on Cancer stage II-IVb nasopharyngeal carcinoma were treated with 70-Gy concomitant boost RT (1.8 Gy/d, weeks 1 through 6; 1.6 Gy second daily fraction, weeks 5 through 6) and two cycles of concurrent cisplatin 100 mg/m(2) days 1 and 22. Thirty-seven patients also received three cycles of cisplatin-based adjuvant chemotherapy. These 50 patients were compared with a nonrandomized cohort of 51 patients with nasopharyngeal cancer treated with 70-Gy standard fractionation RT (1.8 Gy/d) without chemotherapy from 1988 through 1995. The groups were well matched for prognostic factors except stage, for which the concomitant boost RT/chemotherapy group was more advanced (54%, T3-4; 54%, N2-3; 44%, stage IV) compared with the standard RT group (31%, T3-4, P =.03; 22%, N2-3, P <.001; 20%, stage IV, P <.01). RESULTS: With a median follow-up of 42 months (range, 12 to 129 months), the 3-year actuarial local control, progression-free survival, and survival rates were 89% v 74% (P <.01), 66% v 54% (P =.01), and 84% v 71% (P =.04) for the concomitant boost RT/chemotherapy group and the standard RT patients, respectively. Acute grade 3 mucositis was more prevalent with combined therapy, 84% v 43% (P <.001), resulting in a higher rate of temporary gastrostomy tube placement, 46% v 20% (P <.01). CONCLUSION: Concomitant boost RT with cisplatin-based chemotherapy is feasible and improves local-regional control as well as survival for patients with advanced nasopharyngeal cancer compared with standard RT alone.

Complications of thyroid surgery performed by residents.

The purpose of this report is to study the incidence of complications in thyroid surgery performed by the residents in a surgical training program. This is a report of complications in 200 consecutive thyroidectomies performed by residents with attending surgeons' assistance. There were 128 female and 72 male patients, ranging in age from 16 to 89 years. Ten patients had undergone previous thyroid surgery. There were 40 total thyroidectomies, 38 subtotal thyroidectomies, and 122 lobectomies with isthmusectomy. Preoperative and postoperative evaluation of the vocal cords was a standard routine. Identification of the recurrent laryngeal nerve was routine except in patients with large goiters, who underwent intracapsular subtotal thyroidectomy. An attempt was made to identify and preserve all four parathyroid glands. Even in lobectomy procedures, the ipsilateral parathyroids were identified and preserved. Parathyroid autotransplantation into the sternomastoid muscle was performed in thirteen instances, whenever any of the parathyroids was devascularized. Complications included superior laryngeal nerve palsy (one case) and temporary recurrent laryngeal nerve palsy (one case). There was only one patient in whom temporary hypoparathyroidism developed. In three patients hematomas developed in the recovery room and reexploration was required. Two diabetic patients had wound infections develop that required drainage. Seromas and minor wound collections were noted in 6% of the patients. The incidence of major postoperative complications of thyroidectomy is low, even when residents are the primary surgeons. Thyroidectomy appears to be a safe operation in the hands of residents with close supervision and assistance by the attending surgeons.

Completion thyroidectomy: a critical appraisal.

BACKGROUND: Completion thyroidectomy can most accurately be described as reexploration of the neck to remove the contralateral thyroid lobe. This procedure has commonly been performed when the histopathologic condition of the ipsilateral thyroid lobe reveals papillary or follicular carcinoma of the thyroid. Because of a definitely increased risk of complications with completion thyroidectomy, avoiding its routine use is important. The purpose of this paper is to define the specific indications for completion thyroidectomy. METHODS: Over the past 9 years, we have performed 400 thyroidectomies; the patients ranged in age from 18 to 88 years. Although we have routinely used preoperative needle biopsy and intraoperative frozen section, decisions regarding the extent of thyroidectomy have been based on the gross findings at operation, taking into consideration such prognostic factors as patient age, tumor grade and size, the presence of extracapsular spread or distant metastasis, and associated risk factors. The minimal procedure for solitary thyroid nodule has been lobectomy with isthmusectomy. If the contralateral lobe is grossly normal, lobectomy with isthmusectomy has also been the maximal operation in most of patients. Very few specific indications exist for removal of the opposite lobe. RESULTS: Only three patients underwent completion thyroidectomy. All three patients had aggressive follicular carcinoma requiring radioactive iodine ablation, and all were referred after the initial surgery. We have not performed completion thyroidectomy on any of the patients on whom we initially operated. CONCLUSIONS: The most common indication considered for completion thyroidectomy is a frozen section diagnosis of a benign follicular adenoma that is subsequently changed on permanent pathologic condition to follicular carcinoma based on the presence of capsular and/or vascular invasion. However, if minimal invasion has occurred, no difference exists in survival related to the extent of the thyroidectomy. Local recurrence in the contralateral lobe occurs in less than 10% of the time. Because completion thyroidectomy carries more risks, it should be avoided in most patients when possible. The definitive decision should be made during the initial operation based on gross findings, prognostic factors, and frozen section, and this plan should only be changed to mandate completion thyroidectomy in select circumstances.

Acute airway distress due to thyroid pathology.

Patients with multinodular goiter or related thyroid disorders rarely have acute airway distress due to tracheal deviation or compression. However, our institution cares for a large number of patients with untreated multinodular goiters, and in the progression of this disorder, tracheal deviation and airway problems are relatively common. During the past 4 years, we have cared for 24 patients who were admitted with acute, life-threatening airway distress that required emergency intervention. Nine patients had emergency intubation, the remaining 15 had stridor on admission and underwent emergency operations. The series consists of 19 females and five males whose ages ranged from 37 to 89 years. Only four patients had malignant thyroid lesions (two papillary-follicular, two anaplastic), and two of these had multiple pulmonary metastases. Fifteen of the patients with multinodular goiters had a mediastinal extension that led to marked tracheal deviation. Three patients had recurrent multinodular goiters decades after previous surgery. Twenty-one patients underwent surgery at our institution, and all did well. Only one patient required sternotomy for thyroidectomy. Two patients required tracheostomy procedures, one because of tracheomalacia and the other because of poor pulmonary reserve. Interestingly, two patients had acute symptoms when in their third trimester of pregnancy. We have routinely used the laryngoscope (fiberoptic rigid or flexible) for preoperative and postoperative evaluation of the vocal cords and for determination of the condition of the larynx. On the basis of our experience with acute airway distress, we strongly advocate elective surgery for patients with multinodular goiter at the first sign of tracheal compression, especially if they have mediastinal extension.

Intermediate-risk group for differentiated carcinoma of thyroid.

BACKGROUND: We have previously described prognostic factors in differentiated carcinoma of the thyroid gland relating to age, size and extrathyroid extension of the tumor, histologic grade, gender, and distant metastasis. These factors have identified patients in the low-risk group with excellent prognosis and the high-risk group with significant mortality. However, some patients fall within the intermediate-risk category where due deliberation in decision making is required for selection of appropriate treatment. METHODS: A retrospective review of a consecutive series of 1038 previously untreated patients with differentiated carcinoma of thyroid treated during a period of 55 years was undertaken. Data gathered from review of the charts were subjected to univariate and multivariate analysis to assess prognostic factors. On the basis of the patient's age, presence of distant metastasis, and size, grade, and histologic characteristics of the tumor they could be classified into low-, intermediate-, and high-risk categories. Thus 403 (39%) patients were in the low-risk group, 232 (22%) patients in the high-risk category, and 403 (39%) patients in the intermediate-risk category. RESULTS: With a median follow-up of 20 years, 99% survival was achieved in the low-risk group, whereas only 57% survived in the high-risk group. Interestingly, in the intermediate-risk category of 403 patients, the 20-year survival was only 85%. Our results clearly identify a distinct intermediate-risk category that includes low-risk patients with high-risk tumor or high-risk patients with low-risk tumor. CONCLUSION: Patients in the intermediate-risk category should be considered for an aggressive treatment approach based on individual prognostic factors.

Intraoperative decision making during thyroid surgery based on the results of preoperative needle biopsy and frozen section.

Prognostic factors in well-differentiated thyroid cancer are age of the patient and grade, size, distant metastasis, and extracapsular spread of the disease. However, the surgeon is often not sure about the pathologic diagnosis of thyroid nodules. The accuracy of preoperative studies, such as ultrasonography and thyroid scanning, is limited. The most cost-effective test is fine-needle aspiration, the accuracy of which exceeds 80% in most series. However, a large group of nodules exist for which aspiration cytologic studies are considered to be either suspicious or indeterminate. The decision about the extent of thyroidectomy may be difficult in these patients. Intraoperative frozen section may help the surgeon to distinguish benign from malignant lesions, but as in fine-needle aspiration, the major problem is the distinction between follicular adenoma and follicular carcinoma. The frozen section diagnosis of follicular adenoma was changed to follicular carcinoma in one third of the cases (13 of 38 cases). The decision about the extent of thyroidectomy in patients with follicular adenomas was based on other prognostic factors, such as age and sex of the patient and the size of the nodule. The accuracy of frozen section diagnosis was 95%. Our experience suggests that decisions regarding the extent of thyroidectomy can best be made by preoperative fine-needle aspiration with confirmation by frozen section diagnosis in equivocal cases.

Prognostic factors and risk group analysis in follicular carcinoma of the thyroid.

BACKGROUND: The understanding of prognostic factors has facilitated stratification of risk groups in differentiated carcinoma of the thyroid. The prognostic factors have clearly identified the risk groups as low, intermediate, and high risk. Risk group categorization has facilitated a selective surgical approach for thyroid carcinoma. METHODS: A retrospective review of 228 patients with follicular carcinoma of the thyroid was undertaken. Various prognostic factors and risk groups were analyzed. Univariate and multivariate analyses were performed, and the survival curves were plotted by the Kaplan-Meier method. Fifty-nine (26%) patients presented with Hürthle cell histology. The risk groups revealed 62 patients in the low, 84 in the intermediate, and 82 in the high risk groups. RESULTS: The 10-year survival for low, intermediate, and high risk groups was 98%, 88%, and 56%, respectively, and the 20-year survival for the same groups was 97%, 87%, and 49%, respectively. Adverse prognostic factors included age older than 45 years (p < 0.001), Hürthle cell variety (p = 0.05), extrathyroidal extension, tumor size exceeding 4 cm, and the presence or absence of distant metastasis (p < 0.001). Gender, focality, and presence of lymph node metastasis had no significant impact on prognosis. CONCLUSIONS: Patients in the low risk group have excellent survival, whereas the high risk group behaves poorly. Appropriate selection of treatment for the primary disease and adjuvant therapy should be considered on the basis of the prognostic factors and risk group analysis.