Indocyanine green (ICG) angiography-guided thyroidectomy: description of surgical technique.

Background: Postoperative hypoparathyroidism is the most common complication after total thyroidectomy and, when becomes permanent, lead to a myriad of clinical symptoms, long-term need of calcium and vitamin D supplementation and negative impact on the patient's health-related quality of life. Any surgical innovation that could reduce complications and improve outcomes of patients undergoing total thyroidectomy deserves to be considered. Angiography-Guided Thyroidectomy has been proposed as a modification of the standard technique of thyroidectomy aimed to identifying the vascular pattern of the parathyroid glands to maximize efforts for preserving functioning glands at the time of operation. Our aim is to provide a technical description of this procedure based on the use of indocyanine green (ICG) angiography to standardize this technique. Methods: The surgical steps that are followed during a total thyroidectomy are modified due to previous visualization of the feeding vessels of the parathyroid glands according to fluorescence of the vascular mapping obtained by ICG angiography prior to thyroidectomy. The first step is to perform an ICG angiography to assess anatomical features of the feeding vasculature of the parathyroid glands, which allows precise surgical dissection for preservation of the glands. Once the viability of the parathyroids has been evaluated angiographically, thyroidectomy is performed in a second step. Conclusions: ICG angiography-guided thyroidectomy may be effective to preserve the largest number of better perfused parathyroid glands, which would contribute to reduce the risk of postoperative and permanent hypoparathyroidism. It can be successfully and safely implemented in thyroid surgery and standardization of the technique is necessary to homogenize this procedure in the future, allowing a better comparation of the results to be published.

Indocyanine green angiography-guided thyroidectomy versus conventional thyroidectomy for preserving parathyroid function: study protocol for a randomized single-blind controlled trial.

Introduction: Angiography with indocyanine green (ICG) fluorescence performed before thyroidectomy would allow identification of the vascularization of parathyroid glands, maximizing efforts for preserving functioning glands intraoperatively. The rationale of the study was based on the hypothesis that showing the vascular pattern of the parathyroid glands by means of ICG angiography before performing the thyroidectomy could prevent permanent hypoparathyroidism. Methods and analysis: We propose a randomized single-blind controlled and multicenter clinical trial to assess the efficacy and safety of ICG angiography-guided thyroidectomy to identify the vascular pattern of the parathyroid glands versus conventional thyroidectomy in patients scheduled for elective total thyroidectomy. Patients will be randomized 1:1 to ICG angiography-guided thyroidectomy (experimental group) or conventional thyroidectomy (control group). Patients in the experimental group will undergo ICG angiography before thyroidectomy to identify the feeding vessels of the parathyroid glands and then, post-thyroidectomy ICG angiography to predict immediate parathyroid gland function by scoring the degree of fluorescence of the glands. Patients in the control group will undergo post-thyroidectomy ICG angiography only. The primary outcome measure will be the rate of patients with permanent hypoparathyroidism. Secondary outcome measures will be rate of postoperative hypoparathyroidism, the percentage of well vascularized parathyroid glands remaining in situ, the levels of iPTH and serum calcium after surgery and the influence of the type of vascular pattern of the parathyroid glands over these outcomes, as well as the safety profile of ICG angiography. Discussion: The results will contribute to adopt a new surgical strategy based on intraoperative ICG angiography before performing total thyroidectomy, according to which the rate of permanent hypoparathyroidism could be substantially reduced. Clinical trial registration: ClinicalTrials.gov. identifier NCT05573828.

Transoral endoscopic thyroidectomy vestibular approach: Results after 53 first cases.

INTRODUCTION: Trans Oral Endoscopic Thyroidectomy through Vestibular Approach (TOETVA) allows access to the thyroid with the best cosmetic results as there are no visible scars. METHODS: Here we present a prospective observational study of 53 patients which underwent TOETVA from July 2017 to June 2021. RESULTS: Fifty-two cases (98.1%) cases were women (median age 44 years old). Thyroid nodule was the main surgical indication accounting 73.6% of cases. We performed 42 lobectomies and 11 total thyroidectomies; 4 left Central Neck Dissection (CND) were also associated. The median surgical time for port placement was 14 min and for lobectomy, total thyroidectomy and left CND were 80, 140 and 30 min, respectively. The median of hospital stay was 2 days. Dysphonia was present in 4 patients; however, laryngoscopy only confirmed laryngeal nerve impairment in 2 cases, one of them classified as permanent (1.6%). In those patients that underwent total thyroidectomy, the rate of transient hypoparathyroidism was 18.2% whereas permanent was 0%. Regarding complications associated to the new approach, transient chin numbness appeared in all patients with a variable degree of intensity. CONCLUSTIONS: Transoral surgery is a recent approach in our Unit. Our results, based on the first 53 patients, show that it is a safe and effective approach when performed in appropriately selected patients offering the best cosmetic result. Besides, new complications associated to the approach has been shown to be transient.

Usefulness of ICG Angiography-Guided Thyroidectomy for Preserving Parathyroid Function.

INTRODUCTION: Hypoparathyroidism is the most frequent complication after total thyroidectomy and, when permanent, it becomes a severe chronic disease. We assessed the usefulness of indocyanine green (ICG) angiography-guided thyroidectomy to reduce the postoperative hypocalcemia. METHODS: Prospective study with two consecutive cohorts of patients who underwent total thyroidectomy: historical control group (CG) and angiography-guided thyroidectomy group (AG). In all patients, ICG-angiography was performed at the end of the surgery to predict immediate parathyroid gland (PG) function. In the AG, ICG-angiography was also done after PG identification to show their vascular supply. We compared the rate of postoperative hypocalcemia (calcium supplementation needed due to hypocalcemia symptoms or calcium levels < 1.8 mmol/L on the first postoperative day) and permanent hypocalcemia (need of calcium ± vitamin D supplementation 12 months after thyroidectomy). RESULTS: We included 120 consecutive patients (84 CG; 36 AG). Thyroid cancer was the most common diagnostic (63.1% CG-69.4% AG; p = 0.646) and central neck dissection was also frequent (54.8% CG-64.3% AG; p = 0.468). The AG developed a lower rate of postoperative (26.2-5.6%; p = 0.011) and permanent hypocalcemia (11.9-0%; p = 0.032). The OR for permanent hypocalcemia was 0.673 (95% CI 0.591-0.766). A significant higher rate of well vascularized PG at the end of the surgery (score 2) in the AG (39.2-52.9%; p = 0.018) was also seen. CONCLUSION: ICG angiography-guided thyroidectomy is a useful tool to identify PG vascularization, allowing a better PG preservation and a significant decrease in hypocalcemia rates.

Transoral endoscopic thyroidectomy vestibular approach (TOETVA).

Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) is a novel technique that allows the thyroid to be approached without visible scars, as it is performed through a natural orifice. It was first described and developed in Asia where due to sociocultural reasons neck scars are considered a stigma. This technique, as we now nowadays, and its preliminary results, were first reported by Angkoon Anuwong in August 2015 at the International Association of Endocrine Surgeons (IAES) world surgery congress held in Bangkok. Here we present the TOETVA approach, step-by-step, in order it could be safely replicated, aiming also it can be spread within the therapeutic framework of endocrine surgery. However, it is important to remark that, as happens in most of remote approaches, it is only suitable for a small percentage of patients.

Lymphocytic Thyroiditis Transcriptomic Profiles Support the Role of Checkpoint Pathways and B Cells in Pathogenesis.

Background: Autoimmune thyroid diseases are the most common types of autoimmune diseases, but their physiopathology is still relatively unexplored. Genotype-tissue expression (GTEx) is a publicly available repository containing RNAseq data, including profiles from thyroid. Approximately 14.8% of these glands were affected by focal lymphocytic thyroiditis and 6.3% were annotated as Hashimoto. We interrogated these data to improve the characterization of infiltrating cells and to identify new molecular pathways active in autoimmune thyroiditis. Materials and Methods: Histological GTEx images of 336 thyroid samples were classified into three categories, that is, non-infiltrated thyroid, small focal infiltrated thyroid, and extensive lymphoid infiltrated thyroid. Differentially expressed genes among these categories were identified and subjected to in silico pathway enrichment analysis accordingly. CIBERSORTx deconvolution was used to characterize infiltrating cells. Results: As expected, most of the transcriptional changes were dependent on tissue infiltration. Upregulated genes in tissues include-in addition to lineage-specific B and T cell genes-a broad representation of inhibitory immune checkpoint receptors expressed by B and T lymphocytes. CIBERSORTx analysis identified 22 types of infiltrating cells showed that T cells predominate 3:1 over B cells in glands with small infiltrates, only by 1.7:1 in those with large infiltrates. Follicular helper and memory CD4 T cells were significantly more abundant in glands with large infiltrates (p < 0.0001), but the most prominent finding in these glands was an almost sixfold increase in the number of naive B cells (p < 0.0001). A predominance of M2 macrophages over M1 and M0 macrophages was observed in the three gland categories (p < 0.001). Conclusions: Analysis of transcriptomic RNA-seq profiles constitutes a rich source of information for the analysis of autoimmune tissues. High-resolution transcriptomic data analysis of thyroid glands indicates the following: (a) in all infiltrated glands, active autoimmune response coexists with suppressor counteracting mechanisms involving several inhibitory checkpoint receptor pairs, (b) glands with small infiltrates contain an unexpected relatively high proportion of B lymphocytes, and (c) in highly infiltrated glands, there is a distinct transcriptomic signature of active tertiary lymphoid organs. These results support the concept that the autoimmune response is amplified in the thyroid tissue.

Intraoperative Indocyanine Green Angiography of Parathyroid Glands and the Prevention of Post-Thyroidectomy Hypocalcemia.

BACKGROUND: We compared the reliability of indocyanine green (ICG) angiography and intraoperative PTH levels for predicting early post-thyroidectomy hypocalcemia. METHODS: Prospective study of 94 patients (71% women, mean age 53.7 years) undergoing total thyroidectomy. An ICG score of 2 (white) indicated a well-vascularized gland. PTH preoperative levels-PTH postresection levels divided by preoperative PTH × 100 was used to determine the PTH decline percentage. A decrease of at least 62.5% or <17.1 pg/mL in ioPTH was the criterion for predicting hypocalcemia. RESULTS: At surgery, the four parathyroid glands were identified in 50 (53.2%) patients and <4 glands in 44. Calcium supplements were needed by 22 patients (23.4%) postoperatively, 11 patients in each group of 4 and <4 parathyroid glands identified. The diagnostic accuracy of ICG angiography (0.883, 95% confidence interval [CI] 0.800-0.940) and ioPTH (0.862, 95% CI 0.775-0.92) was similar. When all four parathyroid glands were identified, ICG angiography showed a slightly higher diagnostic accuracy, specificity and positive predictive than ioPTH levels, but when < 4 glands were identified, the ioPTH showed a slightly higher diagnostic accuracy, specificity and positive predictive value. Differences were not statistically significant for any of the comparisons. CONCLUSIONS: The presence of one well-perfused parathyroid gland (ICG score 2) using ICG angiography or ioPTH decline, measured before and after completion of thyroid surgery, is both reliable methods in prediction of early post-thyroidectomy hypocalcemia independently of the number of glands identified intraoperatively.

Transoral endoscopic thyroidectomy vestibular approach (TOETVA). / Tiroidectomía endoscópica transoral por vía vestibular: TOETVA.

Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) is a novel technique that allows the thyroid to be approached without visible scars, as it is performed through a natural orifice. It was first described and developed in Asia where due to sociocultural reasons neck scars are considered a stigma. This technique, as we now nowadays, and its preliminary results, were first reported by Angkoon Anuwong in August 2015 at the International Association of Endocrine Surgeons (IAES) world surgery congress held in Bangkok. Here we present the TOETVA approach, step-by-step, in order it could be safely replicated, aiming also it can be spread within the therapeutic framework of endocrine surgery. However, it is important to remark that, as happens in most of remote approaches, it is only suitable for a small percentage of patients.

Efficacy and safety of preoperative preparation with Lugol's iodine solution in euthyroid patients with Graves' disease (LIGRADIS Trial): Study protocol for a multicenter randomized trial.

BACKGROUND: Currently, both the American Thyroid Association and the European Thyroid Association recommend preoperative preparation with Lugol's Solution (LS) for patients undergoing thyroidectomy for Graves' Disease (GD), but their recommendations are based on low-quality evidence. The LIGRADIS trial aims to provide evidence either to support or refute the systematic use of LS in euthyroid patients undergoing thyroidectomy for GD. METHODS: A multicenter randomized controlled trial will be performed. Patients ≥18 years of age, diagnosed with GD, treated with antithyroid drugs, euthyroid and proposed for total thyroidectomy will be eligible for inclusion. Exclusion criteria will be prior thyroid or parathyroid surgery, hyperparathyroidism that requires associated parathyroidectomy, thyroid cancer that requires adding a lymph node dissection, iodine allergy, consumption of lithium or amiodarone, medically unfit patients (ASA-IV), breastfeeding women, preoperative vocal cord palsy and planned endoscopic, video-assisted or remote access surgery.Between January 2020 and January 2022, 270 patients will be randomized for either receiving or not preoperative preparation with LS. Researchers will be blinded to treatment assignment. The primary outcome will be the rate of postoperative complications: hypoparathyroidism, recurrent laryngeal nerve injury, hematoma, surgical site infection or death. Secondary outcomes will be intraoperative events (Thyroidectomy Difficulty Scale score, blood loss, recurrent laryngeal nerve neuromonitoring signal loss), operative time, postoperative length of stay, hospital readmissions, permanent complications and adverse events associated to LS. CONCLUSIONS: There is no conclusive evidence supporting the benefits of preoperative treatment with LS in this setting. This trial aims to provide new insights into future Clinical Practice Guidelines recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03980132.

Surgical approaches to thyroid. / Abordajes en cirugía tiroidea.

Thyroidectomy is the most frequent procedure in endocrine surgery. The conventional approach through a collar incision, as described by Kocher in XIXth century, has become the "gold standard". It is continuously evolving in spite of, many years ago, it showed to be safe and efficient with quality standards difficult to beat. Endoscopic and robotic surgery have developed "new approaches" to thyroid in order to improve the cosmetic results, looking even for invisible scars. We have done a thoughtful review of most of them trying to understand their benefits and drawbacks. Currently none of these "new approaches" have been shown to be better than conventional open thyroidectomy beyond offering a better cosmetic result. Besides, only a small percentage of patients can benefit of them. However, most of these approaches will remain if they treat the diseased thyroid and also improve the quality of life of our patients.

Diagnostic Accuracy of 18F-FDG PET/CT in Patients With Biochemical Evidence of Recurrent, Residual, or Metastatic Medullary Thyroid Carcinoma.

OBJECTIVE: Medullary thyroid carcinoma (MTC) is a rare malignancy. Location of residual, recurrent, or metastatic disease is crucial to treatment management and outcome. We aimed to evaluate the use of F-FDG PET/CT in localizing MTC foci in patients with biochemical relapse. METHODS: This is a retrospective cohort study. Review of 51 FDG PET/CT studies of 45 patients referred to restage MTC due to increased calcitonin (Ctn) and carcinoembryonic antigen (CEA) values at follow-up. FDG PET/CT diagnostic accuracy was determined through a patient-based analysis, using histology as criterion standard when available, or other imaging studies and clinical follow-up otherwise (mean, 4 years). RESULTS: There were 25 positive scans. Sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and positive likelihood ratio were 66.7%, 83.3%, 88.0%, 57.7%, 72.5%, and 4.0, respectively. Using a Ctn cutoff of 1000 pg/mL, sensitivity increased to 76.9%. There were significant differences of Ctn and CEA values between positive and negative FDG PET/CT (P < 0.05). Regarding true-positive studies, average SUVmax comparing locoregional and metastatic disease was at the limit of significance (P = 0.046). CONCLUSIONS: PET/CT can be useful to restage patients with biochemical relapse of MTC, with a better performance in higher Ctn levels. Its high positive predictive value (88%) may impact in the therapeutic management, although its low negative predictive value (57.7%) makes strict follow-up mandatory in examinations without pathologic findings.

Mortality after thyroid surgery, insignificant or still an issue?

BACKGROUND: Thyroidectomy is considered to be a safe procedure. Although very uncommon, death may occur after thyroid resection. The aim of this study was to investigate the prevalence and causes of death after thyroidectomy and the associated risk factors in the modern era of thyroid surgery. PATIENTS AND METHODS: A structured questionnaire was sent to all endocrine surgery units in Spain to report all deaths that occurred after thyroidectomy in recent years. RESULTS: Twenty-six surgical units, encompassing 30.495 thyroidectomies, returned the questionnaire. A total of 20 deaths (0.065%) were recorded: 12 women (60%) and 8 men (40%) with a median age of 65 years (range 32-86). Half of the patients had a retrosternal goiter with a median weight of 210 g. The median operative time was 185 min. Histological diagnoses were benign goiter (35%) or thyroid carcinoma (65%): differentiated (30%), medullary (20%), poorly differentiated/anaplastic (10%), and colorectal cancer metastasis (5%). Causes of death were cervical hematoma (30%), respiratory distress/pneumonia due to prolonged endotracheal intubation (25%), tracheal injury (15%), heart failure (15%), sepsis (wound infection/esophageal perforation) (10%) and mycotic aneurysm (5%). The median time from surgery to death was 14 days (range 1-85). CONCLUSIONS: Death after thyroidectomy is very uncommon, and most often results from a combination of advanced age, giant goiters, and upper airway complications.

Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study.

BACKGROUND: Parathyroid carcinoma (PC) is an uncommon disease that generally is detected postoperatively and traditionally is associated with a poor prognosis. Our purpose was to evaluate treatment outcomes, prognostic factors, and usefulness of some proposed staging systems for this disease. METHODS: A multicenter review of patients with surgically resected PC was performed, led by the Spanish Association of Surgery. All surgical units affiliated with its endocrine surgery section were invited to answer a questionnaire that collected several hospital-related, clinical, biochemical, operative, pathologic, and follow-up data. Their relationships with prognosis were assessed by both univariate and multivariate analysis, as well as the effectiveness of three staging systems for parathyroid carcinoma. RESULT: Of the 6,863 patients undergoing parathyroidectomy, 62 (0.9%) had PC. Of them, 12 (19.3%) died, in 5 cases (8%) because of disease, and 14 (22.6%) suffered recurrence, after a median follow-up of 55 months. The most predictive independent variables on tumor recurrence were intraoperative tumor rupture (hazard ratio [HR] 6.22; 95% confidence interval [CI] 1.19-32.36; P = .030); the presence of mitotic figures within tumor parenchyma cells (HR 4.76; 95% CI 1.24-18.21; P = .022); and allocation in class III according to Schulte differentiated staging classification (HR 5.23; 95% CI 1.41-19.31; P = .013). As to disease-specific survival, poor outcomes were associated with intraoperative tumor rupture (HR 58.71; 95% CI 2.39-1,439.96; P = .013) and distant recurrence (HR 38.74; 95% CI 3.44-435.62; P = .003). CONCLUSION: In addition to factors associated with tumor histopathology and stage, prognosis of PC is greatly influenced by surgeon's performance, which emphasizes the importance of preoperative diagnosis.

[Adrenal surgery in Spain: final results of a national survey]. / Cirugía suprarrenal en España: resultados finales de una encuesta nacional.

INTRODUCTION: The indications for adrenalectomy could be changing by the availability of laparoscopy and the growing detection of incidentalomas. The Endocrine Surgery Section of the Spanish Association of Surgeons conducted a survey to analyse the current indications for adrenalectomy and their results in Spanish surgical departments. MATERIAL AND METHODS: Data was gathered as regards the type of hospital and department, volume of procedures, localisation studies and pre-surgical preparations, indications, surgical approach, and results in terms of morbidity and hospital stay. The results of the centres were compared as regards their volume of activity using the Mann-Whitney Test for the quantitative variables and chi squared for the qualitative ones. RESULTS: Thirty-six centres completed the questionnaire and 301 adrenalectomies were reported to be performed in 2008. Most frequent indications were pheochromocytoma (25.2%), non-functioning adenoma (16.2%), aldosteronoma (15.9%), Cushing adenoma (11.2%), metastasis (10.3%), myelolipoma (5.6%), and carcinoma (4.9%). Laparoscopic adrenalectomy was performed in 83.7% of cases (6.7% required conversion to laparotomy). The mean hospital stay was 3.9 days for laparoscopic adrenalectomy and 7.4 days for laparotomy. High-volume units (more than 10 per year) used more frequently the laparoscopic approach (P=.019), and had a shorter overall hospital stay (P<.0001). Laparoscopic adrenalectomy was also associated with a shorter hospital stay (P<.0001). CONCLUSIONS: Laparoscopy for adrenalectomy has become the standard practice in Spain, with good results in terms of morbidity and hospital stay. High volume centres have better results as regards the use of minimally invasive surgery and hospital stay.

[Laparoscopic adrenalectomy for suspected isolated adrenal metastasis]. / Adrenalectomía laparoscópica por sospecha de metástasis adrenal solitaria.

INTRODUCTION: Isolated adrenal metastasis is uncommon. Both resection and the laparoscopic approach in this entity are controversial. The aim of this study was to evaluate the indications, diagnosis and utility of laparoscopic adrenalectomy (LA) in patients with isolated adrenal metastasis. PATIENTS AND METHOD: A prospective study was conducted in patients with current or previous tumoral disease and with isolated adrenal metastasis. RESULTS: Sixteen patients, with a mean age of 58 years, were selected. Fifteen LA were performed (one patient was found to have an inoperable tumor at surgery). Histopathological analysis revealed non-tumoral disease in two patients. The most common metastatic disease was non-small cell lung carcinoma (NSCLC) (10 patients), followed by colorectal cancer metastasis (two patients). The mean tumor size was 4.7 cm and was 3.8 cm on computed tomography (p = 0.09). The disease-free interval (DFI) in the NSCLC group was shorter than that in the remaining tumors (p = 0.17). The mean length of follow-up was 39 months, with a mean survival of 39.7 months. The mean actuarial survival at 2 and 5 years was 61% and 17%. At the end of the study, five patients were alive: two were disease free, one had recurrent disease, one had margin involvement and one was awaiting resection of the primary tumor. Eight patients died. One patient survived 9 years after surgery. CONCLUSIONS: LA for metastasis can be performed without oncological disadvantage and should be offered to patients with resectable disease, a DFI > 6 months, and a tumoral size that allows laparoscopic resection.