Prior to the late 1800’s, the function of endocrine glands was unknown. Surgeons excised the thyroid gland for severe goiters, but operative mortality was over 40% due to massive hemorrhage.¹ Outcomes for patients who survived the operation were ambiguous, but as neither antisepsis nor the existence of parathyroid glands was recognized, it was unclear whether postoperative mortality reflected infection or organ failure.²

Major advances in the mid-19th century, namely, the advent of effective anesthesia, adoption of aseptic technique, and the invention of hemostatic forceps, enabled significant strides in thyroid surgery. Swiss surgeon Theodor Kocher (1841–1917) refined the operation over the course of his 40-year career and approximately 5000 thyroidectomies, reducing mortality rates to 0.5%.³ Crucially, Kocher also characterized the vital role of the thyroid gland in metabolism and organ function. At the behest of a referring physician, Kocher reexamined a girl he had previously performed a total thyroidectomy on 9 years earlier, and found her to be cretinoid. This prompted him to initiate follow-up on 102 of his postthyroidectomy patients (the largest reported single-surgeon series at the time) and review an additional 134 cases collected from 15 colleagues in Germany and Switzerland. He catalogued in detail the clinical features and outcome of each patient, and coined the term cachexia strumipriva (decay resulting from lack of goiter).² His work represents a milestone in surgery, as a classic example of a surgical audit and investigation into the long-term effects of a procedure. For his groundbreaking work on the physiology, pathology, and surgery of the thyroid gland, Kocher was awarded the Nobel Prize in 1909, and is considered the father of endocrine surgery.

Thyroid and parathyroid surgery today boasts very low complication rates in experienced hands. The more common disease entities requiring surgical interventions, such as well-differentiated thyroid cancer and primary hyperparathyroidism, have excellent long-term survival and cure rates.^4,5 A comparison of different treatment approaches in a prospective randomized controlled fashion would, therefore, require a prohibitively high number of subjects, as demonstrated by Carling et al in a feasibility study concerning prophylactic central lymph node dissection for papillary thyroid cancer.⁶ Given these considerations, as well as the rarity of many endocrine disorders, the majority of published reports in the field of endocrine surgery are retrospective in nature. Without good randomized clinical trials, surgeons rely on clinical practice guidelines developed and endorsed by reputable professional societies such as the American Thyroid Association, American Association of Endocrine Surgeons, and American Association of Clinical Endocrinologists. We will review several of these guidelines in this chapter.

The modern age of clinical practice guidelines began in 1992 with an Institute of Medicine report advocating for “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific circumstances.”⁷ Clinical practice guidelines aim to create consistent practice patterns based on the best available evidence. Guidelines are formulated according to a structured process. A panel of “expert” stakeholders convenes to vet and summarize the total weight of evidence on a specific subject area or clinical question, taking into consideration the quality and strength of the data. The summarized evidence is then categorized according to its susceptibility to bias. When conclusive evidence is absent, expert opinion is relied on to interpret or extrapolate the evidence and derive recommendations. This subjectivity is an inherent weakness of practice guidelines. Recommendations are typically graded in terms of strength, indicating the panel’s level of confidence that the guidelines will produce the desired outcome. In general, recommendation grades are a reflection of research methodology ranging from strong (randomized controlled trials), to weak (cross-sectional studies, case reports), to anecdotal (opinion, consensus, or review). After critical review of the quality of evidence, various subjective factors are incorporated, such as risk–benefit analysis, cost-effectiveness, clinical relevance, and dissenting opinions. A final recommendation grade is then established, with grade A and B representing strong recommendations, grade C weaker recommendations, and grade D expert opinion.⁸

The guidelines then undergo external review to ensure content validity, clarity, and applicability.⁹ Thus, while tremendously practical and informative, it is wise when reading guidelines to keep in mind that they are (1) derived only in part from randomized trials, (2) reliant on the expertise and judgment of the appointed task force, and (3) meant to be customized to the individual patient rather than prescriptively applied.

Some of the greatest surgeon scientists of all time have been endocrine surgeons: Theodor Kocher, Theodor Billroth, William Stewart Halsted, and Charles Mayo, to name only a few. Their contributions and impact far transcend the subspecialty of endocrine surgery. In their relentless pursuit of technical excellence, optimal surgical outcomes, and scientific progress, they revolutionized the world of surgery in their day. Their legacy has served as an inspiration and model for countless young surgeons through the generations to this day.

Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer.

SYNOPSIS

Takeaway Point: In contrast to guidelines published by American Thyroid Association (ATA) in 2006, the revised 2009 guidelines advise total or near-total thyroidectomy for differentiated thyroid carcinoma (DTC) > 1 cm, and central lymph node dissection (CLND) for any cN1 disease. The glaring paucity of level I studies to guide the surgical management of thyroid cancer remains apparent in these guidelines.

Commentary: In 2006, the ATA issued an updated set of management guidelines for thyroid nodules and DTC, advising “routine central compartment (level VI) neck dissection for patients with papillary thyroid carcinoma and suspected Hurthle cell carcinoma.” This sparked heated controversy due to its susceptibility to varying interpretations and the absence of strong supporting data. Proponents of prophylactic central lymph node dissection (pCLND) cite the high incidence of cervical lymph node metastasis¹⁰ and possible attendant increase in recurrence and decrease in survival.^11,12,13 Preoperative ultrasound and intraoperative assessment have low sensitivity for microscopic lymph node involvement.^14,15 In addition, central neck dissection during the initial surgery affords valuable staging information to determine the need for and dosing of adjuvant radioactive iodine.¹⁶ Arguments against pCLND focus on the unproven benefit^17,18 and concern for increased surgical morbidity. Neck dissection carries a low complication rate in experienced hands;¹⁹ however, studies have shown that the majority of thyroid surgeries in the United States are performed by low-volume surgeons—a group that has been associated with higher complication rates.^20,21

In light of the limited and conflicting data regarding the initial management of the central compartment lymph nodes in clinically node-negative papillary thyroid cancer, the ATA revised and clarified their stance in 2009, as detailed in the following summary. Prophylactic CLND may be considered, especially for advanced primary tumors, but with the acknowledgment that this approach can be associated with increased morbidity, especially among low-volume surgeons. Following publication of the 2009 guidelines, several large-volume trials were conducted to further investigate the role of central compartment neck dissection in DTC, two of which are discussed later in this chapter (see b and c, below).

Although it has been shown that care in accordance with guidelines for DTC is associated with improved patient outcomes, a wide variability in the degree of adherence to the revised ATA recommendations has been noted among practitioners.²²

ANALYSIS

Introduction: Differentiated thyroid cancer (DTC), which includes papillary and follicular cancer, occurs in 5–10% of thyroid nodules, and represents 90% of all thyroid cancers. Incidence is increasing, and surgery is essential for management. In 1996, the American Thyroid Association (ATA) published its first treatment guidelines for patients with thyroid nodules and DTC. These guidelines were updated in 2006, and a surge of high-quality studies led to another update in 2009.

Methods

A task force of 13 experts on short- and long-term medical and surgical management of thyroid nodules and thyroid cancer reviewed the previously published ATA guidelines from 2006 in light of new data and produced updated consensus guidelines. Given the paucity of randomized controlled trials in the treatment of DTC, the panel relied on all available published evidence. When evidence was judged to be insufficient, the task force members relied on their personal experience and judgment.

Results

In keeping with the previous version, the revised guidelines cover the management of thyroid nodules and DTC, including diagnostic approach and algorithms for initial and long-term medical and surgical management. Of particular interest to surgeons, the updated guidelines address controversial topics, including extent of thyroidectomy based on tumor size, and prophylactic central neck dissection:

Discussion

Conclusion: Total or near-total thyroidectomy should be performed for DTC > 1 cm. Patients with cN1 disease should undergo therapeutic CLND. Prophylactic CLND may be considered in patients with cN0 disease, especially for advanced primary tumors.

Limitations: The majority of data informing the guidelines are derived from retrospective, single-institution studies. In addition, the recommendations may reflect the bias of the experts on the task force.

A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer.

SYNOPSIS

Takeaway Point: Routine central lymph node dissection (CLND) in papillary thyroid carcinoma (PTC) is associated with lower postoperative thyroglobulin levels and reduces the need for reoperation in the central compartment.

Commentary: The authors evaluated the impact of routine CLND after total thyroidectomy in the management of patients with cN0 PTC in three international endocrine surgery centers over a 14-year period. The authors demonstrated that patients who underwent CLND with thyroidectomy had statistically lower postoperative thyroglobulin (Tg) levels (prior to radioiodine ablation) and lower reoperation rates compared with thyroidectomy alone. In addition, there was no significant difference in complication rates between those who underwent CLND versus those who did not. While this study indicates that routine prophylactic CLND is associated with positive outcomes without an increase in morbidity, it is limited by its retrospective nature and the use of data from high-volume centers, which restricts generalizability.

ANALYSIS

Introduction: The role of routine, or prophylactic, central lymph node dissection (CLND) for papillary thyroid cancer (PTC) remains controversial.

Objectives: The aim of this study was to evaluate the impact of routine CLND after total thyroidectomy (TTx) in the management of patients with PTC who were clinically node negative at presentation with emphasis on stimulated thyroglobulin (Tg) levels and reoperation rates.

Methods

Trial Design: Retrospective, multicenter cohort study.

Participants

Inclusion Criteria: Age ≥ 16 years with PTC >1 cm without preoperative evidence of lymph node disease (cN0).

Exclusion Criteria: Papillary microcarcinoma, subtotal or hemithyroidectomy as definitive procedure, preoperative evidence of nodal disease, lateral neck dissection performed at original surgery, distant metastatic disease.

Intervention: Thyroidectomy alone (group A) or CLND (group B). Of note, the study did not distinguish between ipsilateral and bilateral CLND; both were included in group B.

Sample Size: 606 patients from three centers in Australia, the United States, and England underwent surgery between 1995 and 2009, including 347 without CLND (group A) and 259 with CLND (group B).

Statistical Analysis: Fisher’s exact test, Student’s t-test, number needed to treat.

Results

Baseline Data: Group A was significantly older (mean age 48 vs. 44, p 0.002), and had significantly longer follow-up time (50 vs. 32 months, p <0.001). Group B had significantly higher rates of vascular invasion (50% vs. 36%, p 0.002). Tumor size was similar between the two groups.

Outcomes: Stimulated Tg values were lower in group B before initial radioiodine ablation (15.0 vs. 6.6 ng/mL; p 0.025). There was a trend toward a lower Tg at final follow-up in group B (1.9 vs. 7.2 ng/mL; p 0.110). The rate of reoperation in the central compartment was lower in group B (1.5% vs. 6.1%; p 0.004). Though there was no difference in the incidence of permanent hypoparathyroidism or recurrent laryngeal nerve (RLN) palsy, group B had a significantly greater number of parathyroid autotransplantation (0.88 vs. 1.2; p 0.006) and temporary hypocalcemia (4.1% vs. 9.7%; p 0.026). Twenty CLND procedures were required to prevent one central compartment reoperation.

Discussion

Conclusion: The addition of routine CLND in cN0 papillary thyroid carcinoma is associated with lower postoperative Tg levels and reduces the need for reoperation in the central compartment.

Limitations: Retrospective study design with variable follow-up time, and lack of multivariate analysis. The data are from tertiary referral centers with high surgeon volume, which limits generalizability to lower-volume practices. The groups were not balanced for preoperative characteristics.

A meta-analysis of the effect of prophylactic central compartment neck dissection on locoregional recurrence rates in patients with papillary thyroid cancer.

SYNOPSIS

Takeaway Point: This meta-analysis demonstrated a trend toward lower recurrence rates in patients with clinically node-negative PTC undergoing total thyroidectomy with prophylactic central node dissection (pCLND) compared to those undergoing total thyroidectomy alone.

Commentary: Most of the studies examining the effectiveness of prophylactic CLND are single-institution retrospective studies, and a prospective randomized trial is likely not feasible as it would require a prohibitively large sample size.⁶ For these reasons, meta-analyses such as this study are important for evaluating optimal management algorithms for patients with DTC. The authors performed a meta-analysis of 11 studies involving more than 2300 patients to determine the impact of prophylactic CLND on recurrence rates after total thyroidectomy in the management of adult patients with PTC who are clinically node-negative. The authors showed a trend toward lower recurrence rate in patients undergoing prophylactic CLND for PTC compared to patients undergoing total thyroidectomy alone, although the difference did not reach statistical significance. The study is the first of its kind to exclude pediatric patients, those who underwent lobectomies, and those with microcarcinomas. However, it is limited by extent of follow-up data and exclusion of data regarding postoperative radioactive iodine administration. A subsequent consensus report by the European Society of Endocrine Surgeons²⁴ provides a critical appraisal of the studies and meta-analyses regarding prophylactic CLND to date and identifies a comprehensive list of bias sources. They conclude that prophylactic dissections should be risk-stratified and performed only by surgeons with the available expertise and experience.