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.

Laparoscopy versus open adrenalectomy in patients with solid tumor metastases: results of a multicenter European study.

BACKGROUND: The outcome of adrenalectomy carried out by laparoscopy or open surgery for solid tumor metastases was assessed. METHODS: A total of 317 patients with histologically confirmed adrenal metastatic disease collected from 30 centres in Europe underwent adrenalectomy by laparoscopy (n=146) or open laparotomy (n=171). Differences between laparoscopic and open adrenalectomy were assessed by a single Cox analysis for both procedures. RESULTS: The median overall survival was 24.0 [95% confidence interval (CI): 21.4-26.6] months for open adrenalectomy and 45.0 (95% CI: 22.6-67.4) for laparoscopic adrenalectomy (P=0.008). Survival rates were 68%, 49%, 35% and 29% at 1, 2, 3 and 5 years for open surgery vs. 88%, 62%, 52% and 46% for laparoscopy, respectively. In the subgroup of R0 resections, the difference in survival in favor of laparoscopy (median 46 vs. 27 months) was marginally significant (P=0.073). Renal cancer [hazard ratio (HR) 0.42; 95% CI: 0.23-0.76, P=0.005], surgery of the primary tumor (HR 0.33; 95% CI: 0.19-0.54), and use of chemotherapy (HR 0.62; 95% CI: 0.43-0.88) were associated with a better survival, whereas type of resection (R1/R2 vs. R0) was associated with a worse prognosis (HR 2.29; 95% CI: 1.52-3.44, P<0.001). CONCLUSIONS: Laparoscopic adrenalectomy patients showed a longer survival than open adrenalectomy individuals, as minimally invasive approach was attempted more common in less advanced disease which led to higher number of R0 resections.

Continuous monitoring of the recurrent laryngeal nerve.

OBJECTIVE: The objective of this study was to assess the safety and utility of continuous intraoperative neuromonitoring for the prevention of recurrent laryngeal nerve injury during thyroidectomy. METHODS: A prospective cohort study was conducted in consecutive patients undergoing thyroidectomy. Variations in amplitude and distal latency of the electromyogram (EMG) were assessed. In the case of suspicious events, restorative manoeuvers were performed to attempt to recover the potentials. Associations were explored between findings in laryngoscopy 24 h after surgery and intraoperative neurophysiological events. RESULTS: In the study, 248 consecutive thyroidectomies were included, which were carried out between January 2012 and December 2015. Continuous vagal nerve monitoring was not associated with adverse cardiopulmonary events. Among the 400 at-risk recurrent laryngeal nerves (RLNs), there were eight nerves showing temporary palsy (2%). While an increase in distal latency of > 10% did not provide any relevant information, a decrease in the amplitude of the EMG of > 50% was associated with a higher risk of RLN palsy. A decrease in the amplitude of the EMG of > 50% was associated with negative and positive predictive values of 100 and 47%, respectively. Recovery manoeuvers reversed the decline in the amplitude of potentials in 80% of cases. CONCLUSIONS: Continuous vagal nerve monitoring is safe and allows us to assess nerve function intraoperatively. A decrease of more than 50% in the amplitude of the potentials from EMG baseline is a warning sign of the development of a nerve injury. Nevertheless, this decrease is reversible with restorative manoeuvers, making it possible to minimise RLN injuries.

Compliance with recommendations on surgery for primary hyperparathyroidism-from guidelines to real practice: results from an Iberian survey.

PURPOSE: Knowledge about compliance with recommendations derived from the positional statement of the European Society of Endocrine Surgeons on modern techniques in primary hyperparathyroidism surgery and the Third International Workshop on management of asymptomatic primary hyperparathyroidism is scarce. Our purpose was to check it on a bi-national basis and determine whether management differences may have impact on surgical outcomes. METHODS: An online survey including questions about indications, preoperative workup, surgical approach, intraoperative adjuncts, and outcomes was sent to institutions affiliated to the endocrine surgery divisions of the National Surgical Societies from Spain and Portugal. A descriptive evaluation of the responses was performed. Finally, we assessed the correlation between the different types of management with the achievement of optimal results, defined as a cure rate equal or greater than the median of all interviewed institutions. RESULTS: Fifty-seven hospitals (41 Spanish, 16 Portuguese) answered the survey. First-ordered imaging tests were neck ultrasound and sestamibi scan. Facing negative or non-concordant results, 44 % of surgeons ordered additional tests before first-time surgery, and 84 % before reoperations. When indicated, selective parathyroidectomy was an acceptable option for 95 % of institutions as first-time surgery and for 51 % in reoperations. Intraoperative parathormone measurements were used by 92 % of departments. The surgical outcomes were good in most institutions (median cure rate 97 %) and were influenced mostly by the presence of an endocrine surgery unit in the surgical department (p = 0.038). CONCLUSIONS: Practice of Iberian endocrine surgeons is consistent with current recommendations on surgery for primary hyperparathyroidism, with variability in some areas.

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.

Adrenalectomy for solid tumor metastases: results of a multicenter European study.

BACKGROUND: We assessed the results of adrenalectomy for solid tumor metastases in 317 patients recruited from 30 European centers. METHODS: Patients with histologically proven adrenal metastatic disease and undergoing complete removal(s) of the affected gland(s) were eligible. RESULTS: Non-small cell lung cancer (NSCLC) was the most frequent tumor type followed by colorectal and renal cell carcinoma. Adrenal metastases were synchronous (≤6 months) in 73 (23%) patients and isolated in 213 (67%). The median disease-free interval was 18.5 months. Laparoscopic resection was used in 46% of patients. Surgery was limited to the adrenal gland in 73% of patients and R0 resection was achieved in 86% of cases. The median overall survival was 29 months (95% confidence interval, 24.69-33.30). The survival rates at 1, 2, 3, and 5 years were 80%, 61%, 42%, and 35%, respectively. Patients with renal cancer showed a median survival of 84 months, patients with NSCLC 26 months, and patients with colorectal cancer 29 months (P = .017). Differences in survival between metachronous and synchronous lesions were also significant (30 vs. 23 months; P = .038). CONCLUSION: Surgical removal of adrenal metastasis is associated with long-term survival in selected patients.

[Surgical treatment of adrenal gland metastases: results in a series of 35 patients]. / Cirugía de las metástasis en la glándula suprarrenal: resultados de una serie de 35 pacientes.

INTRODUCTION: The objectives of this study are to present the results of adrenalectomies due to metastasis, and to analyse the prognostic factors that may help to predict long-term survival in this patient group. PATIENTS AND METHODS: A retrospective study was conducted on 35 patients who underwent adrenalectomy for metastases in the Hospital de Cruces from 1996 to January 2010. The survival analysis was performed using the Kaplan and Meier method. RESULTS: Non-small cell lung cancer (NSCLC) was the most frequent primary tumour, with 18 cases. In 15 patients the diagnosis of adrenal metastasis was synchronous with the primary tumour, and in 20 cases it was metachronous. Only 7 patients survived without disease for 12, 22, 26, 58, 60, 65 and 120 months after the adrenalectomy. The disease free survival at 5 years was 16% in the whole series, and 27% in the NSCLC sub-group. None of the prognostic factors evaluated (size greater than 4.5 cm, cell type, differentiation grade, chemotherapy, surgical technique, disease free interval) was statistically significant in the overall survival, either in the general series or in the sub-group of patients with NSCLC. However, in the general series with tumour recurrence, the difference in survival between metachronous and synchronous metastasis was statistically significant (P=.05), in favour of the former. CONCLUSIONS: Adrenalectomy improves the expected survival particularly in patients with NSCLC. Patients with metachronous metastases do not have a higher rate of disease free survival at 5 years than those with synchronous metastases, although they do have a longer survival with the disease. When there is tumour recurrence, it is usually early.

[Oesophageal endoscopic ultrasound in the accurate location of primary hyperparathyroidism (HPT)]. / Valor de la ecoendoscopia transesofágica en el diagnóstico de localización en el hiperparatiroidismo primario.

AIM: Our aim was to estimate the usefulness of oesophageal endoscopic ultrasound in the accurate location of recurrent or persistent primary hyperparathyroidism (HPT). MATERIAL AND METHOD: A total of 352 patients with primary hyperparathyroidism were operated on over the last seven years. A preoperative parathyroid 99Tc- sestamibi gammagraphy and an intraoperative PTH determination were performed routinely. Only 5 patients (1.4%) had localization problems: three with persistent HPT after parathyroid extirpation, one recurrent HPT and one HPT after a right hemithyroidectomy. An oesophageal endoscopic ultrasound was carried out before any new exploratory neck surgery in order to find the definitive location. RESULTS: The endoscopic ultrasound showed a clear image of adenoma with an accurate location in four patients. No tumour was present in one patient. All five patients were operated on. The exact location was confirmed in the four patients with positive endoscopic ultrasound images. The fifth surgical exploration revealed a parathyreosis. All five patients had a favourable post-operative period, with no nerve lesions or morbidity associated with the endoscopic ultrasound. CONCLUSIONS: Oesophageal endoscopic ultrasound is a very useful diagnostic tool in HPT patients with location problems, particularly in cases having anatomical changes due to previous surgery. It is a procedure that helps the surgeon to make a more selective and efficient exploration of parathyroid glands.

[Absence/disappearance of gallbladder in a patient diagnosed with cholelithiasis]. / Ausencia-desaparición de la vesícula biliar en un paciente diagnosticado de colelitiasis.

We report the case of a patient with preoperatively demonstrated cholecystitis due to cholelithiasis but with no presence of gallbladder at laparoscopy or on conversion to open surgery. Gallbladder ectopy was ruled out and the possibility of gallbladder agenesia was discussed. However, four preoperative ultrasound scans performed within a protocol of treatment with octreotide, in the setting of acute cholecystitis, ruled out this possibility. We discuss the possibility of gallbladder destruction and digestion after a severe inflammatory process, as well as Frey's criteria for gallbladder agenesia. We believe that this is a case of complete gallbladder lysis due to an inflammatory process.