Damian Sendler Health Research News on Thyroid Diagnostics

Damian Sendler: Radiofrequency thermal ablation is a novel, less invasive treatment option for people with benign thyroid nodules or recurring thyroid malignancies who don't want surgery. Radiofrequency ablation for thyroid cancers was recommended by the Task Force Committee of the Korean Society of Thyroid Radiology (KSThR) in 2012. It was determined by KSThR that the recommendations needed to be updated in light of the growing body of relevant research. New guidelines are based on a thorough review of the existing research and the consensus of medical experts.

Damian Jacob Sendler: For benign thyroid nodules, US-guided radiofrequency ablation (RFA) may be used as an alternative to surgery; in addition, RFA can play a complementary role in the therapy of recurrent thyroid malignancies, which is a less invasive therapeutic method (1,2,3). Thyroid nodule-related aesthetic issues and pressure complaints have been successfully treated with RFA.

Dr. Sendler: An group of Korean thyroid radiologists, the Korean Society of Thyroid Radiology (KSThR), made preliminary guidelines for thyroid RFA in 2009 (13), emphasizing on indications and effectiveness for the treatment of thyroid nodules. The task force committee members of the KSThR have recommended revising prior recommendations due to recent information about RFA clinical trials in individuals with benign thyroid nodules and recurrent thyroid malignancies. Guidelines for RFA of thyroid nodules and recurring thyroid malignancies released in 2012 by a KSThR committee to amend these prior recommendations (1). All parts covering indications, pre-procedural assessments, procedures, post-procedural monitoring, effectiveness, and safety were covered by the second suggestion (1).

Damian Sendler

The KSThR intended to update the recommendations in December 2015, after the second set of recommendations was issued, due to the fast development of relevant evidence. Prior recommendations on thyroid RFA were reviewed by the task force members; they also looked at additional research released after 2001 to clarify their findings. As of May 2017, the relevant literature has yet to be examined. The terms "thyroid" and "radiofrequency ablation" or "radio-frequency ablation" or "RF ablation" or RFA" were searched in worldwide and local databases, including MEDLINE, EMBASE, and KoreaMed. Seven offline sessions and regular online discussions were used to begin the editing process.

When it came to deciding on benefits and damage, a modified version of the Delphi technique was used. Members of an expert committee with expertise in thyroid radiology and methodology assessed the data and made recommendations in nine panels. It was thought beneficial to have a median value of less than seven. Median value 3 was, on the other hand, regarded to have more negative effects than positive ones. Decisions on the recommendations were based mostly on the strength of the evidence and the net benefits (14). The clinical application and influence on patient outcomes of the recommendation's strength were addressed in further detail. As a result, despite the high Delphi score, the recommendation strength was downgraded in accordance with expert committee agreement.

In the vast majority of cases, thyroid nodules are benign and asymptomatic; nonetheless, big thyroid nodules may induce symptoms such as pain, dysphasia, a foreign body feeling, neck bulging and cough. RFA is recommended in certain situations in order to alleviate symptoms by shrinking the lesion (12). A grading system may be used to assess a patient's symptomatology or appearance. Patients may self-evaluate their symptom severity using a 10-cm visual analog scale (grades 0–10). (9,10,18). There are four possible aesthetic scores: 1, no perceptible mass, 2, no visible issue but visible mass, 3, visible difficulty while swallowing, and 4, easily visible cosmetic problem (4,9,10,18). Thyroid RFA does not have a set standard for nodule volume or size. Thyroid nodule therapy is dictated by the symptoms and/or aesthetic issues of each patient, which vary according to the size and position of the thyroid nodule on the individual's neck (1,19). When it comes to aesthetic complaints, patients with a smaller neck circumference tend to come out sooner than those with a broader neck. In addition, isthmic nodules may cause aesthetic issues even if they are less than 2 cm in diameter. This correlation seems to be based only on how large the thyroid nodule or lobe is (20,21). Patients with compressive symptoms who had their thyroid nodules or thyroid gland surgically removed reported significant relief in their symptoms (20). Based on the patient's symptoms, aesthetic and clinical concerns, and the nodules' diameters surpassing 2 cm, thyroid RFA may be an option for such patients. The moving-shot approach makes it difficult to perform RFA on thyroid nodules with significant calcifications. RFA for these nodules must thus be carefully examined.

Damian Jacob Markiewicz Sendler: It is possible to treat a thyroid nodule if it is compressing nearby tissues or causing aesthetic concerns or hyperthyroidism. Treatment options for toxic AFTN, according to the American Thyroid Association's current guidelines, include radioactive iodine (RAI) therapy and surgery (52). Surgery and RAI therapy may cause hypothyroidism in the elderly, although the treatment is controversial in young women (7,53). RAI treatment or surgery may also be rejected by some patients because of their apprehension about radiation exposure or possible side effects, such as hypothyroidism (53). RFA has emerged as an alternate treatment for AFTN in recent research (4,7,53,54,55,56,57,58,59). When surgery and RAI aren't an option or aren't desired, an Italian research team proposes that RFA may be used to treat hyperthyroidism induced by AFTN (60). The treatment of pretoxic nodules is typically suggested because they may develop into overtly toxic nodules (annual risk of around 4 percent); in addition, subclinical hyperthyroidism may have negative consequences on the skeletal system as well as the cardiovascular system over time (7,53,54,61). RFA is less effective in instances with big AFTN (those with a volume more than 20 mL) and further research should be conducted in these situations (7,54,60). As an alternative to RAI treatment, RFA is more costly, calls for RF equipment, and has a steeper learning curve (53). The cost of RFA was comparable to that of surgery when the two procedures were compared (58).

Damian Jacob Sendler

Initially, Dupuy et al. (63), in 2001, first reported RFA for recurrent papillary and follicular carcinomas in eight patients, following which other trials treating recurrent thyroid malignancies with RFA have been described, including two meta-analyses (64,65,66,67,68,69,70,71,72,73,74). Patients with recurrent thyroid cancer who were at high surgical risk or who had refused surgery but still required it clinically were mentioned as a reason for RFA in these publications. Previous surgeries, poor lung function, poor systemic health, severe cardiovascular illness, or elderly age were all associated with an increased risk of surgery. RFA might be used to remove a recurring tumor completely or only to alleviate its symptoms. A full tumor removal can only be achieved by RFA if it has been declared radiologically feasible. Aside from that, the disease should not go beyond the neck. Recurrence rates of fewer than 3 or 4 per patient and tumor diameters of less than 1.5–2 cm were favorable outcomes in previous trials utilizing RFA for curative purposes, according to a press release (64,73,74).

Symptoms of recurrent thyroid cancer include dysphagia, hoarseness, dyspnea, and aesthetic issues owing to a tumor projecting from the thyroid. Even if total radiological excision is not achievable, RFA may be used if it is determined that size reduction via RFA can relieve symptoms and enhance the patient's quality of life (68). Repeated procedures for recurring cancer may be constrained and create issues owing to postoperative scarring and normal tissue plane deformation, but RFA may typically cure the tumor without substantial complications (74).

One of the most frequent thyroid nodules is a thyroid follicular adenoma, and follicular carcinoma accounts for 10–20% of all thyroid cancers (50,85). For the treatment of follicular tumors seen on FNA or CNB, surgery is usually the only option since the presence of nodes or distant metastases helps distinguish carcinoma from an adenoma (16). RFA was originally not recommended by KSThR due to the absence of evidence that RFA was effective in treating follicular tumors (1). Before follicular neoplasms are surgically treated to rule out malignancy, it is difficult to get a definitive pathological diagnosis (50,88,89,90). One of the indicators of malignancy is the size of the follicular neoplasm (more than or equal to 2 cm) (91). A substantial percentage of follicular neoplasms are falsely diagnosed as thyroiditis or nodular goiter by FNA (22.2–35 percent) (88,89). Patients who are at high surgical risk or who are ineligible for surgery have a greater need for conservative medicinal care. Though RFA has been used to treat benign thyroid nodules as well as recurrent thyroid malignancies, there have been few published studies on the use of RFA to treat follicular neoplasms. Patients with follicular neoplasms less than 2 centimeters in diameter may benefit with RFA, as shown by a recent 5-year follow-up study (95). During the time of follow-up, no recurrences or metastatic lesions were discovered. One additional research found that RFA should not be the initial treatment option for follicular neoplasm patients. Regrowth following RFA revealed minimally invasive follicular cancer and an undetermined malignant activity in two of the six lesions graded Bethesda-3 or Bethesda-4 that measured more than 2 cm in diameter. According to the authors, RFA may be able to postpone surgery in the event of malignancy by promoting the growth of Bethesda-3- or Bethesda-4-grade tumors.

To identify nodules or recurring malignancies, as well as to assess the surrounding vital anatomical structures, ultrasound scanning is essential. Each nodule or tumor should be examined for its size, echogenicity, percentage of solid component, and internal vascularity. The volume of a nodule or tumor may be determined using the equation V = abc/6, where V represents volume, a represents the biggest diameter, and b and c represent the other two perpendicular diameters (5,9,11).

Laboratory tests include a blood count, prothrombin time, and activated partial thromboplastin time, as well as a thyroid function test (measurement of TSH, triiodothyronine [T3], and ft4]) (9,99). Thromboglobulin (Tg) and anti-Tg antibody are used to determine whether thyroid cancer has returned following complete thyroidectomy in patients with recurrent disease. Reduction or conversion to negative serologic results might serve as surrogate indicators for effective ablation (74). If a patient's platelets or blood coagulation tests come back abnormal, the doctor should note any anti-platelet or anticoagulant medicines the patient has taken, as well as any coagulopathy-causing diseases they may have.

Damien Sendler: Prior to RFA, hormone replacement therapy may be recommended if the blood TSH concentration is high. Doctors should note whether a patient is receiving thyroid hormone therapy or has hyperthyroidism when the TSH levels in the blood drops. Hyperthyroidism may be diagnosed with the use of a technetium 99mTc pertechnetate pertechnetate or a 123I thyroid scan (8,55). After chemical or thermal ablation of thyroid nodules, hypothyroidism has seldom been documented, and the reason is unknown (100,101,102). Patients with thyroid antibodies should be warned about the risk of hypothyroidism prior to therapy, since hypothyroidism seems to be the most likely cause of autoimmune thyroiditis development and related with preexisting thyroid antibodies. Routinely checking for thyroid antibodies, such as anti-Tg antibody or anti-microsomal antibody, before to RFA of a benign thyroid nodule is still contentious, however; this (64,103,104).

There must be enough lidocaine injected into the skin puncture site and thyroid capsule during RFA to decrease discomfort (1,107). Rather of employing general anesthesia or drowsiness, perithyroidal lidocaine injection is advised for pain management during ablation. Thyroid glands lack sensory nerves, which are typically found near the thyroid capsule. The thyroid capsule should be punctured with the lidocaine needle and put into the midline of the anterior neck, just above the thyroid isthmus (108).

There are risks associated with general anesthesia and sedation during ablation procedures (109).

In 2012, the KSThR recommended RFA of benign thyroid nodules using the trans-isthmic approach and the moving-shot method (1). Using a trans-isthmic technique, an RF electrode is introduced through the isthmus to reach the target nodule in either the right or left thyroid gland (99,110). Individuals who are doing this operation should think that they are dealing with a target nodule that can be broken down into a series of smaller and smaller ablation units, and then begin ablation unit-by-unit, working from deepest and remotest to smallest and closest (107,111). Preventing thermal injury to nearby cervical tissues is best accomplished by continually monitoring the placement of the RF electrode tip using real-time ultrasound during the operation (107,111). To prevent marginal regrowth, vascular ablation procedures have recently been established (108).

When using RFA to treat an AFTN or cancerous thyroid nodule, a safety margin must also be taken into consideration; otherwise, the treatment will not be effective.

In most studies, the VRR or improvements in symptoms or aesthetic issues after six to twelve months following treatment are used to evaluate the effectiveness of RFA. Safe and successful results are documented in the majority of short-term treatments (138,139). As reported by Deandrea et al. (132), 2 of 40 treated nodules failed to achieve a 50% decrease in volume in the short term six months following RFA. In certain studies, more than two RFA treatments were required in 24.1–57.9 percent of instances in order to sustain long-term volume decrease (5,94,116).

Damian Jacob Markiewicz Sendler

More treatment sessions were needed for bigger nodules (> 20 mL) to obtain the same VRR as smaller nodules at 4-year follow-up (116). Nodule volumes of 20 mL or more were more likely to respond favorably to two RFA treatments, according to the results of an earlier randomized study and Bayesian network meta-analysis (137). According to these research, RFA's ability to have a long-term impact is limited, particularly if the index nodule volume is big.

In both long-term and short-term follow-up studies, the need for more therapy is often mentioned, although the precise timing of such treatment remains uncertain. Additional therapy is indicated when the condition is not entirely cured after treatment, the VRR is less than 50%, and the tumor develops again, as mentioned above (5,110,135).

Sim and colleagues (94), who studied the time of follow-up therapy based on US, split the ablated nodule into two parts: RFA-ablated low-echoic region, and the remaining viable area, which is frequently isoechoic and positioned on the edge of the ablation zone. Volume of the viable region increases during regeneration whereas the ablation zone shrinks with time. In order to show regrowth and hence time the subsequent ablation, it may be more advantageous to trace the volume of the viable region than trace the volume of the whole nodule (94).

Because of the large quantity of untreated tissue near the thyroid nodule boundary, the broad range of treatment effects may be the result of an inadequate volume decrease, which explains the persistence of hyperthyroidism (7,53,54). AFTN patients in an RCT who were given either one RAI dosage or one LA session had lower TSH levels after LA than those who received RAI treatment (141), and these results might be explained by the fact that the untreated nodule margin was so large after LA. Additionally, the internally cooled electrode may be better suited for usage in the moving-shot approach and be a safer manner of ablating the nodule edge.

Dr. Sendler

On the other hand, moving a multi-tined, expandable electrode in LA could be problematic, and simultaneous US surveillance of several expanding prongs throughout the ablation may be difficult (53,54,116). There was an 81.7 percent VRR, an 81.8 percent normalized TSH rate, a 79.5 percent normalized scan rate in an RFA investigation by qualified radiologists utilizing the moving-shot approach and comparable electrodes (modified straight internally cooled electrodes) (53). RFA was less successful in treating big AFTN (often more than 20 mL) (7,54,60).

Large AFTN may benefit from a therapeutic approach that combines LA with RAI therapy. The combo treatment is more effective at treating local symptoms and biochemical hyperthyroidism than RAI therapy alone, while also reducing RAI activity (60,142). Despite the fact that it hasn't been extensively studied, the combination of RFA and RAI therapy may be examined in the near future. RFA is a successful non-surgical therapy for AFTN that improves thyrotoxic symptoms, hormone levels, and scintigraphic results without the need for surgical intervention.