Management of Recurrent Well-Differentiated Thyroid Carcinoma in the Neck: A Comprehensive Review.

Surgery has been historically the preferred primary treatment for patients with well-differentiated thyroid carcinoma and for selected locoregional recurrences. Adjuvant therapy with radioactive iodine is typically recommended for patients with an intermediate to high risk of recurrence. Despite these treatments, locally advanced disease and locoregional relapses are not infrequent. These patients have a prolonged overall survival that may result in long periods of active disease and the possibility of requiring subsequent treatments. Recently, many new options have emerged as salvage therapies. This review offers a comprehensive discussion and considerations regarding surgery, active surveillance, radioactive iodine therapy, ultrasonography-guided percutaneous ablation, external beam radiotherapy, and systemic therapy for well-differentiated thyroid cancer based on relevant publications and current reference guidelines. We feel that the surgical member of the thyroid cancer management team is empowered by being aware and facile with all management options.

Robotic total thyroidectomy with modified radical neck dissection via unilateral retroauricular approach.

BACKGROUND: Traditionally, total thyroidectomy was performed through an open transcervical incision; in cases where there was evident nodal metastasis, the conventional surgical approach was to extend the incision into a large single transverse incision to complete the required neck dissection. However, recent innovation in the surgical technique of thyroidectomy has offered the opportunity to reduce the patient's burden from these prominent surgical scars in the neck. Minimally invasive surgical techniques have been developed and applied by many institutions worldwide, and more recently, various techniques of remote access surgery have been suggested and actively applied.1-6 Since the advent of robotic surgical systems, some have adopted the concept of remote access surgery into developing various robotic thyroidectomy techniques. The more former and widely acknowledged robotic thyroidectomy technique uses a transaxillary (TA) approach, which has been developed by Chung et al. in Korea.7,8 This particular technique has some limitations in the sense that accessing the lymph nodes of the central compartment is troublesome. Terris et al. realized some shortcomings of robotic TA thyroidectomy, especially in their patients in the United States, and developed and reported the feasibility of robotic facelift thyroidectomy.9-13 In cases of thyroid carcinomas with lateral neck node metastases, most abandoned the concept of minimally invasive or remote access surgery and safely adopted conventional open surgical methods to remove the tumor burden. However, Chung et al. have attempted to perform concomitant modified radical neck dissection (MRND) after robotic thyroidectomy through the same TA port.14 This type of robot-assisted neck dissection (RAND) had some inherent limitations, due to fact that lymph nodes of the upper neck were difficult to remove. Over the past few years, we have developed a RAND via modified facelift (MFL) or retroauricular (RA) approach and reported the feasibility and safety of this technique.15, 16 Since then, we have actively applied such RAND techniques in various head and neck cancers. In our country, almost all cases of robotic total thyroidectomy utilize the TA approach. According to the reports made by Terris et al., robotic facelift thyroidectomy technique has been solely applied for ipsilateral hemithyroidectomy. For total thyroidectomy, Terris et al. performed the robotic surgery with bilateral RA incisions. Here, we intend to introduce our novel surgical method after successfully attempting simultaneous robotic total thyroidectomy and RAND via a single RA approach without an axillary incision. To our knowledge, this is the first to report in the medical literature. METHODS: We present four cases of our surgical experience since the beginning of 2013. All patients received robotic total thyroidectomy with MRND via single RA port without axillary incision after approval from the institutional review board at Severance Hospital, Yonsei University College of Medicine. The inclusion criteria for this operation were as follows: (1) patients with malignant carcinomas of the thyroid gland with evident cervical lymph node metastasis on preoperative imaging studies which are indicated for surgery; (2) patients with no previous history of treatment for thyroid carcinoma. The exclusion criteria were as follows: (1) patients with recurred thyroid tumors; (2) patients with thyroid carcinomas that showed gross invasion to local structures or extensive extrathyroidal capsular spread; (3) patients with clinically evident neck nodal metastasis with extracapsular spread; (4) patients with past history of neck surgery of any kind. In order to assess the extent of disease, neck ultrasonography with fine needle aspiration, neck CT or MRI and PET-CT were performed as preoperative evaluation. All patients were given full information of the possible treatment options for their thyroid cancer comprising of open transcervical approach and robotic surgery via RA approach, including the advantages and disadvantages of each treatment choice and provided written, informed consents before the surgery. General clinical information of the patients is outlined in Table 1. The skin incision for the operation was designed just like the approach for robotic facelift thyroidectomy by Terris et al. and RAND, which has been first reported by our institution.11 (,) 16 The operation was performed by the following sequence. Initially, the skin-subplatysmal flap was elevated after making the skin incision to create sufficient working space. During this process, the elevated skin flap was retracted and maintained by retractors held by the assistant. After application of the self-retaining retractor (Sangdosa Inc., Seoul), neck dissection of the upper neck levels was performed under gross vision. Next, RAND through the RA incision was conducted followed by ipsilateral thyroidectomy with central compartment neck dissection (CCND) via the same approach. Finally, contralateral thyroidectomy with CCND was performed via the single RA port. During these steps, the operator is aided by the bedside assistant with long-suction tips to manipulate and direct the dissected specimen to maintain optimal surgical view or to suck out the fume created by the thermocoagulation from the Harmonic shears. The da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced via the RA port with a facedown 30° dual-channel endoscopic arm placed in the center, and two instrument arms equipped at either side with 5-mm Maryland forceps and Harmonic curved shears. During the step of robotic contralateral thyroidectomy, a ProGrasp forceps was utilized at times, instead of 5-mm Maryland forceps. The rest of the surgery was completed with the robotic system (see Video for demonstration of operation for patient 2). Table 1 Clinical characteristics of the patients Patient Sex/age (yr) BMI Side(a) Approach Pathology(b) Tumor size(c) (cm) CCND(d) MRND(d) Drain removal day Drainage amount (ml) Hospital stay (days) 1 F/38 23.8 L RA PC 0.7 2/5 8/23 8 788 11 2 F/18 18.3 L RA PC 0.8 2/8 7/35 6 398 9 3 F/44 23.1 L RA PC 0.9 5/12 5/27 6 607 9 4 F/26 32.9 L RA PC 1.4 3/14 9/48 7 476 15 BMI body mass index, RA retroauricular approach, PC papillary carcinoma, CCND central compartment neck dissection, MRND modified radical neck dissection (a)Side refers to the site of main lesion (b)Pathology refers to the primary tumor within the thyroid gland (c)Tumor size refers to the diameter of the largest tumor in the thyroid gland (d)For each type of lymph node dissection, the number of positive nodes/total number of retrieved nodes is stated RESULTS: For all of the patients, robotic total thyroidectomy with MRND (levels II, III, IV, V) via unilateral RA approach was successfully completed without any significant intraoperative complications or conversion to open or other approach methods. The total operation time was defined as the time from initial skin incision to removal of the final specimen, which was an average 306.1 ± 11.1 min (Table 2). This included the time for skin flap elevation and neck dissection under gross vision (87 ± 2.8 min), setting up the robotic system for RAND (6.8 ± 2.4 min), console time using the robotic system for RAND (59.3 ± 2.2 min), flap elevation for thyroidectomy (11.3 ± 2.5 min), robotic arms docking for ipsilateral thyroidectomy (6.3 ± 2.5 min), console time for ipsilateral thyroidectomy (61.3 ± 2.1 min), robotic arms docking for contralateral thyroidectomy (6.3 ± 2.5 min), and console time for contralateral thyroidectomy (61.8 ± 2.1 min). The working space created from RA incision was sufficient, and manipulations of the robotic instruments through this approach were technically feasible and safe without any mutual collisions throughout the entire operation. It also allowed for an excellent magnified surgical view enabling visualization of important local anatomical structures. There was no postoperative vocal cord palsy due to recurrent laryngeal nerve injury. However, two patients developed transient hypoparathyroidism, which resolved in the end without the need for calcium or vitamin D supplementation after certain period of medical management (Table 3). Also, there was no incidence of postoperative hemorrhage or hematoma formation, although a single patient developed a postoperative seroma on postoperative day 9, which was managed conservatively without the need for further surgical intervention. On average, the wound catheter was removed 6.8 ± 1 days after surgery and the patient was discharged from the hospital at an average 11 ± 2.8 days from admission (Table 1). Final surgical pathology confirmed the diagnosis of papillary carcinoma for every patient. The total number of cervical nodes retrieved from CCND and MRND was 9.8 ± 4 and 33.1 ± 11 respectively, and the number of positive metastatic nodes was 3 ± 1.4 and 7.3 ± 1.7 respectively (Table 1). In three patients (patients 2, 3, and 4), the presence of one parathyroid gland was each verified in the pathology specimen. All four patients have received high-dose (150 mCi) radioiodine ablation (RAI) therapy after the operation and are being followed up (average 11.3 months, range 9-13 months) on a regular basis with no evidence of recurrence (post-RAI, most recent, nonsuppressed thyroglobulin range 0.1-0.4 ng/ml, antithyroglobulin antibody range 13.7-147.5 IU/ml). (ABSTRACT TRUNCATED)

What is the best definitive treatment for Graves' disease? A systematic review of the existing literature.

BACKGROUND: The management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists for Graves' disease (GD) include any of the following modalities: (131)I therapy, antithyroid medication, or thyroidectomy. No in-depth analysis has been performed comparing the treatment options, even though a single treatment option seems to be universally accepted. METHODS: A systematic review of the literature was performed to examine contemporary literature between 2001 and 2011 evaluating the management options of GD. We compiled retrospective and prospective studies analyzing surgery and radioactive iodine. Outcomes of interest included postoperative hypothyroidism, euthyroidism, and persistent or recurrent hyperthyroidism without supplementation. Success was defined as postoperative euthyroidism or hypothyroidism. Failure was defined as persistent or recurrent hyperthyroidism. RESULTS: Of the 14,245 patients, 4,546 underwent surgery [3,158 patients had subtotal thyroidectomy (STT) and 1,388 had total thyroidectomy (TT)] and 9,699 had radioactive iodine. The radioactive iodine group consisted of 2,383 patients receiving 1-10 mCi, 1,558 patients receiving 11-15 mCi, 516 patients receiving >15 mCi, and 5,242 patients receiving an unspecified amount. Surgery was found to be 3.44 times more likely to be successful than radioactive iodine (p < 0.001). STT and TT were found to be 2.33 and 94.45 times more likely to be successful than radioactive iodine (p < 0.001), respectively. CONCLUSIONS: On the basis of the outcomes analyzed, surgery appears to be the most successful in the management of GD, with TT being the preferred surgical option.

Reoperative central compartment dissection for patients with recurrent/persistent papillary thyroid cancer: efficacy, safety, and the association of the BRAF mutation.

OBJECTIVES/HYPOTHESIS: The aims of this study were to present our experience with reoperative central compartment dissection (RCCD) for recurrent/persistent papillary thyroid cancer (PTC), and to explore the association between the BRAF mutation status and the clinicopathologic characteristics and outcomes of a large cohort of PTC patients who have undergone RCCD. STUDY DESIGN: Case series with chart review. METHODS: This is a retrospective study. One hundred twenty consecutive patients between July 2001 and June 2010 who underwent RCCD for recurrent/persistent PTC performed by a single surgeon (r.p.t.) were reviewed. Data reviewed included demographic information; records from previous operations, RCCD, and any other concurrent procedures; pre- and postoperative serum and ionized calcium levels; pre- and postoperative fiberoptic laryngoscopic examination reports; postoperative notes; and pathology reports. V600E mutations in the BRAF gene were detected by performing pyrosequencing for the 107 patients deemed evaluable for the BRAF mutation. RESULTS: The median time to tumor recurrence (TTR) was 36 months (range, 6-791 months). All recurrent laryngeal nerves (RLNs; 161/161) that were at risk were successfully identified. There were seven new findings of abnormal post-RCCD vocal fold (VF) motion that were the result of intentional RLN resection. Among them, six were because of the need for resection of a local recurrence, and one was because of bulky lymph nodes circumferentially involving the RLN. There were no findings of unexpected RLN injury or VF paralysis. Fifteen patients developed hypocalcemia as a result of RCCD that improved with oral calcium and vitamin D supplementation. Among them, 12 cases developed only post-RCCD transient hypocalcemia (≤6 months), and three patients developed permanent hypocalcemia. No patient exhibited central compartment recurrent/persistent PTC in the post-RCCD period based on semiannual high-resolution neck ultrasound examination with a median follow-up of 41.5 months (range, 6-123 months). Eighty (74.8%) of 107 cases demonstrated the BRAF V600E mutation. The presence of the BRAF mutation was significantly associated with a shorter TTR (P = .015) compared with the BRAF mutation-negative group. The BRAF mutation-positive group had a higher incidence of concurrent lateral lymph node metastases (P = .0064) than the BRAF mutation-negative group. CONCLUSIONS: Recurrent/persistent PTC in the central compartment typically harbors the BRAF mutation. The time to central neck recurrence from initial treatment is significantly shorter in the BRAF-positive population of patients compared to the BRAF-negative group, making it more likely that a recurrence will be identified early in the surveillance period. Although we have demonstrated that RCCD can be performed safely and effectively for nodal metastases, there is still risk involved, and this must be carefully weighed by the multidisciplinary team and the patient in optimizing a tailored plan for management.

A safe and cost-effective short hospital stay protocol to identify patients at low risk for the development of significant hypocalcemia after total thyroidectomy.

OBJECTIVE: The objective of this retrospective chart review was to determine if serial postoperative serum calcium levels early after total thyroidectomy can be used to develop an algorithm that identifies patients who are unlikely to develop significant hypocalcemia and can be safely discharged within 24 hours after surgery. METHODS: Records of 135 consecutive patients who underwent total/completion thyroidectomy and were operated on by the senior author from 2001 to 2005 have been reviewed. For the entire study group, reports of the early postoperative serum calcium levels (6 hours and 12 hours postoperatively), final thyroid pathology, preoperative examination, inpatient course, and postoperative follow up were reviewed. An endocrine medicine consultation was obtained for all patients while in the hospital after surgery. For patients who developed significant hypocalcemia, reports of their management and the need for readmission or permanent medications for hypoparathyroidism were reviewed. According to the change in serum calcium levels between 6 hours and 12 hours postoperatively, patients were divided into two groups: 1) positive slope (increasing) and 2) nonpositive (nonchanging/decreasing). RESULTS: All patients with a positive slope (50/50) did not develop significant hypocalcemia in contrast to only 59 of 85 patients (69.4%) with a nonpositive slope (P < .001, positive predictive value of positive slope in predicting freedom from significant hypocalcemia = 100%, 95% confidence interval = 92.9-100). In the nonpositive slope group, 61 patients had a serum calcium level > or =8 mg/dL at 12 hours postoperatively (< or =0.5 mg/dL below the low end of normal), and 53 (87%) of these patients remained free of significant hypocalcemia in contrast to only 6 (25%) of 24 patients with serum calcium level <8 mg/dL at 12 hours postoperatively (sensitivity = 90%, positive predictive value = 87%). In addition, of the eight patients who developed significant hypocalcemia in the nonpositive slope group with a serum calcium level > or =8 mg/dL at 12 hours postoperatively, 7 (88%) patients developed the signs and symptoms during the first 24 hours after total thyroidectomy. Readmission and permanent need for calcium supplementation happened in two patients, respectively, all with serum calcium levels <8 mg/dL at 12 hours after total thyroidectomy. The compressive and/or symptomatic large multinodular goiter as an indication for thyroidectomy was associated with developing significant hypocalcemia (P < .05). There was no statistically significant correlation between the development of significant hypocalcemia and gender, age, thyroid pathology other than goiter, or neck dissection. CONCLUSION: Patients with a positive serum calcium slope (t = 6 and 12 hours) after total thyroidectomy are safe to discharge within 24 hours after surgery with patient education with or without calcium supplementation. In addition, patients with a nonpositive slope and a serum calcium level > or =8 mg/dL at 12 hours postoperatively (< or =0.5 mg/dL below the low end of normal) are unlikely to develop significant hypocalcemia, especially beyond 24 hours postoperatively, and therefore can be safely discharged within 24 hours after total thyroidectomy with patient education and oral calcium supplementation. Our management algorithm identifies those patients at low risk of developing significant hypocalcemia early in the postoperative course after total thyroidectomy to allow for a short hospital stay and safe discharge.

The role of positron emission tomography/computed tomography in the management of recurrent papillary thyroid carcinoma.

OBJECTIVES/HYPOTHESIS: The aim of the study was to evaluate the role of combined positron emission tomography/computed tomography (PET/CT) fusion imaging in the detection and management of recurrent papillary thyroid cancer. STUDY DESIGN: A retrospective analysis of 33 patients with suspected recurrent papillary thyroid carcinoma who had undergone PET/CT was performed. PET/CT was compared with standard imaging techniques in each patient to determine whether PET/CT contributed to the therapeutic management plan. Histopathological findings were correlated to PET/CT in patients who underwent surgery. METHODS: The senior author reviewed the charts of 33 patients with recurrent papillary thyroid carcinoma to determine the impact PET/CT had on management. PET/CT was compared with conventional imaging results. In surgical patients, PET/CT was compared with histopathological findings to determine its sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. RESULTS: In 67% of the cases (22 of 33), PET/CT supplied additional information that altered or confirmed the management plan. Twenty of 33 patients underwent surgery with 36 sites assessed by histopathological analysis. PET/CT correlated with histopathological findings in 25 of 36 distinct anatomical sites, with an accuracy of 70%. The sensitivity of PET/CT in identifying recurrence was found to be 66%, with a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 27%. CONCLUSION: Combined PET/CT fusion scanning was most useful in the detection and management of recurrent papillary thyroid cancer in patients who had average thyroglobulin levels greater than 10 ng/mL and when the tumor no longer concentrated radioactive iodine. In 100% of the cases in which PET/CT localized a region suspicious for malignancy, histopathological analysis confirmed the results. When PET/CT is positive, it is a powerful tool for predicting exact locations of recurrent papillary thyroid cancer, thus making it a reliable guide for surgical planning. PET/CT is a supplement to conventional imaging and fine-needle aspiration in the workup of recurrent papillary thyroid cancer. A negative finding on PET/CT is not sufficiently reliable to preclude further investigation and treatment.