2023 European Thyroid Association Clinical Practice Guidelines for thyroid nodule management.

With the widespread use of sensitive imaging techniques, which include neck visualization, a conspicuous number of thyroid nodules emerge and demand attention. Most lesions are benign, asymptomatic, and do not warrant treatment. In the case of cancer diagnosis, most are small, intrathyroidal and indolent neoplasms that can safely be managed conservatively. There is a pronounced need for more cost-effective, risk-adapted approaches to the management of this highly prevalent condition, taking the wishes of the patient into consideration. Thus, the present guidelines aim at providing a clinical practice guide for the initial workup and the subsequent management of adult individuals harboring thyroid nodules. Importantly, these guidelines are not intended to cover the management of thyroid malignancy. The manuscript and the specific recommendations were developed by reconciling the best available research evidence with the knowledge and clinical experience of the panelists and updating aspects of a number of previous European Thyroid Association guidelines.

Considerable interobserver variation calls for unambiguous definitions of thyroid nodule ultrasound characteristics.

Objective: Thyroid nodule ultrasound characteristics are used as an indication for fine-needle aspiration cytology, usually as the basis for Thyroid Imaging Reporting and Data System (TIRADS) score calculation. Few studies on interobserver variation are available, all of which are based on analysis of preselected still ultrasound images and often lack surgical confirmation. Methods: After the blinded online evaluation of video recordings of the ultrasound examinations of 47 consecutive malignant and 76 consecutive benign thyroid lesions, 7 experts from 7 thyroid centers answered 17 TIRADS-related questions. Surgical histology was the reference standard. Interobserver variations of each ultrasound characteristic were compared using Gwet's AC1 inter-rater coefficients; higher values mean better concordance, the maximum being 1.0. Results: On a scale from 0.0 to 1.0, the Gwet's AC1 values were 0.34, 0.53, 0.72, and 0.79 for the four most important features in decision-making, i.e. irregular margins, microcalcifications, echogenicity, and extrathyroidal extension, respectively. The concordance in the discrimination between mildly/moderately and very hypoechogenic nodules was 0.17. The smaller the nodule size the better the agreement in echogenicity, and the larger the nodule size the better the agreement on the presence of microcalcifications. Extrathyroidal extension was correctly identified in just 45.8% of the cases. Conclusions: Examination of video recordings, closely simulating the real-world situation, revealed substantial interobserver variation in the interpretation of each of the four most important ultrasound characteristics. In view of the importance for the management of thyroid nodules, unambiguous and widely accepted definitions of each nodule characteristic are warranted, although it remains to be investigated whether this diminishes observer variation.

Dose Finding and Food Effect Studies of a Novel Abiraterone Acetate Formulation for Oral Suspension in Comparison to a Reference Formulation in Healthy Male Subjects.

Currently approved formulations of the androgen synthesis inhibitor abiraterone acetate (AA) consist of multiple tablets administered daily in a fasted state. Removing the food effect and switching to a suspension formulation is expected to improve the pharmacokinetic profile and facilitate drug administration for patients with late-stage prostate cancer. Two four-sequence, four-period randomized crossover investigations were undertaken to establish the pharmacokinetic profiles of single doses of commercially available Zytiga®, as the reference AA (R-AA), and a novel tablet for oral suspension (TOS). Four single doses of TOS (from 62.5 to 250 mg) were compared in study C01, and two single doses each of TOS (250 mg) and R-AA (1000 mg) were compared under fasted and fed (modified fasted for R-AA) conditions in C02. Plasma concentrations of abiraterone over time were measured, and pharmacokinetic parameters were calculated. Each doubling of the dose of TOS was associated with a greater than 3-fold increase in exposure. A single dose of TOS (250 mg) exhibited similar exposure over 24 h, whether given fasted (625 ng × h/mL) or fed (485 ng × h/mL). A single dose of TOS (250 mg) was associated with higher (fasted, p = 0.028) or equivalent exposure (fed) compared to 1000 mg R-AA fasted (532 ng × h/mL). Substantially higher exposures were seen with 1000 mg R-AA under modified fasted conditions compared to TOS, irrespective of prandial status (p < 0.001). TOS was generally safe and well tolerated in the study. A 250 mg dose of a novel AA formulation for oral suspension demonstrated bioequivalence to 1000 mg R-AA under fasted conditions. This novel TOS formulation also addresses some of the limitations of current AA treatment, including low bioavailability, high variability in systemic exposure and a large food effect. It may offer an alternative for patients with dysphagia or discomfort with swallowing large pills.

EU-TIRADS-Based Omission of Fine-Needle Aspiration and Cytology from Thyroid Nodules Overlooks a Substantial Number of Follicular Thyroid Cancers.

BACKGROUND: The classification of nodules by Thyroid Imaging Reporting and Data Systems (TIRADS) is important in guiding management. Whether sensitivity in identifying thyroid cancers varies with thyroid cancer phenotype remains unclarified. METHODS: The ultrasound (US) characteristics of nodules of 26,908 nodular goiter patients were recorded. Fine-needle aspiration cytology (FNA) was performed in all nodules >1 cm irrespective of US findings (n = 25,025) and in nodules between 5 mm and 10 mm with suspicious US characteristics (n = 1,883). Of the 3281 operated cases, 221, 30, and 23 were papillary (PTC), follicular (FTC), and medullary (MTC) cancers, respectively. The US-based indication of FNA, as defined by EU-TIRADS scores, combined with lesion size, was calculated. This study design is unique in avoiding the common selection bias when TIRADS' sensitivity is tested in a cohort selected for FNA and surgery based on the same US characteristics on which TIRADS is based. RESULTS: The EU-TIRADS score influences decision of FNA in the 10-20 mm range. In such nodules (n = 118), the number of suspicious features (marked hypoechogenicity, microcalcifications, irregular shape, and irregular border) per lesion was lower in FTC (0.7 ± 0.6) than in PTC (1.7 ± 1.0) or MTC (1.8 ± 0.7; p < 0.02), resulting in EU-TIRADS scores of 4.1 ± 0.6, 4.8 ± 0.3, and 4.9 ± 0.2, respectively (p < 0.01). The EU-TIRADS-based FNA indication rate was lower in FTC (55.5%) compared to PTC (85.0%) and MTC (88.9%) (p=0.02). CONCLUSIONS: EU-TIRADS-defined suspicious US features are less common in FTC than in PTC and MTC. Therefore, a substantial number of FTCs in the 10-20 mm range escape surgery.

Ultrasound-Based Indications for Thyroid Fine-Needle Aspiration: Outcome of a TIRADS-Based Approach versus Operators' Expertise.

BACKGROUND: Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. METHODS: Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). RESULTS: For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p < 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). CONCLUSIONS: Recommendations for FNA based on the investigators' US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.

[Percutaneous ethanol injection efficacy in the treatment of benign thyroid nodules. Ten-year follow-up of 254 patients]. / Jóindulatú pajzsmirigygöbök perkután alkoholinjekciós kezelésének hosszú távú eredményessége. 254 beteg 10 éves követésével szerzett tapasztalatok.

Introduction and aim: Although percutaneous ethanol sclerotherapy for the treatment of benign thyroid nodules (PEI) has been used for more than 30 years, there are only two studies in thyroid cysts (THCY) and 2 in autonomously functioning nodule (AFN) in which the mean follow-up reaches at least five years, while in the event of non-autonomously functioning solid nodules (NAS), there is not any study with at least 5-year mean follow-up. Our study focuses on the long-term efficacy of PEI in benign thyroid nodules. Method: We analyzed the long-term success of PEI in 254 patients treated for more than 10 years. The success was defined as 50% or greater reduction in nodule volume. In addition, the patient had to remain euthyroid without thyrostatic therapy in AFN. Results: The 10-year success rate was 79.4%, 37.1% and 69.4% in THCY, AFN and NAS, respectively. In 23.3% of unsuccessful PEIs, the failure could be revealed only after 5 years of follow-up. The mean nodule volume at 10-year follow-up related to the initial size was 29.8%, 39.6% and 48.9% in THCY, NAS and AFN, respectively. In THCY, PEI proved to be significantly more effective in older patients while other parameters (size of the nodule, amount of the injected alcohol and the ratio of these) did not correlate significantly with the success rate. Conclusions: Our study which presents the longest follow-up in all 3 types of benign thyroid nodules confirms that PEI has a minimal role in AFN, is recommendable in THCY and might have a role in NAS. The success rate decreases over time which emphasizes the importance of the long-term follow-up in the judgement of PEI. Orv Hetil. 2020; 161(6): 224-231.

Dose Escalation Study to Assess the Pharmacokinetic Parameters of a Nano-amorphous Oral Sirolimus Formulation in Healthy Volunteers.

BACKGROUND AND OBJECTIVES: Sirolimus (Rapamune®) exhibits low bioavailability, high variability and moderate food effect following oral administration. This makes therapeutic blood monitoring of sirolimus concentrations necessary for kidney transplant patients. Furthermore, reaching therapeutic blood sirolimus concentrations in renal cancer patients was found to be challenging when the marketed drug was administered alone. A novel, nano-amorphous formulation of the compound was developed and its pharmacokinetic properties were investigated in a dose escalation study in a first-in-human clinical trial. The effect of food at the highest dose on the pharmacokinetic parameters was also assessed. METHODS: Each group received one of the escalating doses (0.5-2-10-40 mg) of sirolimus as the novel formulation in the fasted state. Following a 2- to 3-week washout period, the 40-mg group then also received another 40 mg dose in the fed state. Sirolimus whole blood concentrations were determined for up to 48 h. To avoid degradation of sirolimus in the acidic environment in the stomach, 40 mg famotidine was administered 3 h pre-dose in all regimens. The main pharmacokinetic parameters were calculated and data were compared with pharmacokinetic data reported for dose escalation studies for Rapamune®. RESULTS: Thirty-two healthy volunteers were divided into 4 cohorts of 8 volunteers. Dose increments resulted in approximately dose-proportional increases of maximal plasma concentrations (Cmax) and area under the concentration-time curve (AUC)0-48 h up to 10 mg, while less than dose-proportional increases were observed when the dose was increased from 10 to 40 mg. Mean AUCinf at the 40 mg dose in the fasted state was 4,300 ± 1,083 ng·h/ml, which is 28% higher than the AUC reported following the administration of 90 (2 × 45) mg Rapamune® and 11% higher than the exposure reported for 25 mg intravenous pro-drug temsirolimus (3,810 ng·h/ml). At the 40 mg dose, food reduced Cmax by 35.5%, but it had no statistically significant effect on AUC. Inter-individual variability of the pharmacokinetic parameters mostly fell in the 20-30% (CV) range showing that sirolimus administered as the nano-amorphous formulation is a low-to-moderate variability drug. CONCLUSION: Based on the pharmacokinetic profiles observed, the nano-amorphous formulation could be a better alternative to Rapamune® for the treatment of mammalian target of rapamycin-responsive malignancies. Therapeutically relevant plasma concentrations and exposures can be achieved by a single 40 mg oral dose. Furthermore, the low variability observed might make therapeutic blood monitoring unnecessary for transplant patients taking sirolimus as an immunosuppressant.

Preparation, Pre-clinical and Clinical Evaluation of a Novel Rapidly Absorbed Celecoxib Formulation.

Celecoxib (Celebrex®) is the only widely used NSAID that selectively inhibits the COX-2 isoenzyme. Celebrex® is absorbed slowly in the fasted state and food intake further delays absorption. In this work, an amorphous water dispersible granule formulation of celecoxib is described with in vitro characterization, preclinical and clinical data. The formulation exhibited very high passive permeability and apparent solubility, significantly outperforming the micronized celecoxib and the drug product Celebrex®. The granule formulation remained stable for at least 1 year in stability tests. In dog studies, tmax was 1 h with over 50% of Cmax reached within 15 min regardless of food intake. A phase 1 clinical trial was conducted with 12 volunteers at 100- and 200-mg doses. Celecoxib plasma concentrations reached 250 ng/ml, the effective therapeutic plasma level, in less than 15 min regardless of food or dose. The novel celecoxib formulation is rapidly absorbed, demonstrating the potential utility as an acute treatment offering advantages over the currently marketed product.

Investigations of the mechanism behind the rapid absorption of nano-amorphous abiraterone acetate.

Abiraterone acetate is indicated for patients with metastatic castration resistant prostate cancer. The marketed drug product (Zytiga®) exhibits very low bioavailability in the fasted state and a substantial positive food effect. We recently developed a nano-amorphous formulation of this drug which exhibited higher apparent solubility and dissolution rate, and significantly improved absorption and bioavailability in the fasted state in beagle dogs and in a phase I clinical study. One surprising finding, however, was the very rapid absorption observed both in dogs and in humans with median tmax values in the 0.5-0.75 h range. This could not be explained by the improved dissolution characteristics alone. A recent study showed that following the administration of Zytiga® abiraterone acetate is converted to abiraterone in the intestinal lumen yielding supersaturated abiraterone concentrations, which is believed to be the driving force of the absorption process. In our work we found that the enzymatic hydrolysis of abiraterone acetate profoundly changes the pharmacokinetics of the nano-amorphous formulation in the fasted state and it is the most probable reason for the unexpectedly high absorption rate. Our primary candidate for the isoenzyme involved is pancreatic cholesterol esterase. Furthermore, we identified orlistat as a potent inhibitor of cholesterol esterase and found it to be an ideal compound for the study of the enzymatic process in vivo. The observed inhibition could result in a clinically significant modification of abiraterone pharmacokinetics, which might make a drug interaction warning necessary for abiraterone acetate containing drugs. The mathematical and experimental tools presented in this work might be suitable for the study of the contribution of other intestinal enzymatic processes to the absorption process of other prodrugs as well.

Development of an abiraterone acetate formulation with improved oral bioavailability guided by absorption modeling based on in vitro dissolution and permeability measurements.

Particle size reduction of drug crystals in the presence of surfactants (often called "top-down" production methods) is a standard approach used in the pharmaceutical industry to improve bioavailability of poorly soluble drugs. Based on the mathematical model used to predict the fraction dose absorbed this formulation approach is successful when dissolution rate is the main rate limiting factor of oral absorption. In case compound solubility is also a major factor this approach might not result in an adequate improvement in bioavailability. Abiraterone acetate is poorly water soluble which is believed to be responsible for its very low bioavailability in the fasted state and its significant positive food effect. In this work, we have successfully used in vitro dissolution, solubility and permeability measurements in biorelevant media to describe the dissolution characteristics of different abiraterone acetate formulations. Mathematical modeling of fraction dose absorbed indicated that reducing the particle size of the drug cannot be expected to result in significant improvement in bioavailability in the fasted state. In the fed state, the same formulation approach can result in a nearly complete absorption of the dose; thereby, further increasing the food effect. Using a "bottom-up" formulation method we improved both the dissolution rate and the apparent solubility of the compound. In beagle dog studies, this resulted in a ≫>10-fold increase in bioavailability in the fasted state when compared to the marketed drug and the elimination of the food effect. Calculated values of fraction dose absorbed were in agreement with the observed relative bioavailability values in beagle dogs.

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

PURPOSE: Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. METHODS: The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. RESULTS: The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. CONCLUSION: The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

The Clinical and Pathological Presentation of Thyroid Nodules in Children and the Comparison with Adult Population: Experience of a Single Institution.

The clinical and pathological presentation of thyroid nodules among younger and adult patients was compared in an iodine-deficient (ID) region. Data of 3,010 consecutive patients younger than 20 years and 3,010 patients older than 20 years were compared. The proportion of nodular goiters (22.8% versus 39.3%), the ratio of surgically treated nodules (33.2% versus 15.2%), and the proportion of malignant nodules (4.3% versus 2.1%) among diseased patients differed significantly between the two groups (younger versus adult). Nine papillary and 1 medullary carcinoma were found among children, while 15 papillary, 2 follicular, 1 insular, 1 anaplastic, and 1 medullary carcinomas occurred among adults. The ratio of follicular adenoma to hyperplastic nodules (3 : 1 to 1 : 1.67), the proportion of follicular variant (77.8% versus 26.7%), T4 tumors (77.8% versus 33.3%), and tumors with lymph node metastasis (88.9% versus 66.7%) were significantly higher among younger papillary carcinoma patients. No malignancies occurred among spongiform and central type cysts. Similarly to iodine-sufficient regions, more nodules are malignant and carcinomas have a clinically more aggressive presentation in children in comparison with adult patients in ID. Taking the significantly greater proportion of adenomas and the lack of follicular carcinoma into account, a conservative approach has to be considered in follicular tumors among children.

Percutaneous Ethanol Sclerotherapy of Symptomatic Nodules Is Effective and Safe in Pregnant Women: A Study of 13 Patients with an Average Follow-Up of 6.8 Years.

Background. Because of the increased risk of surgery, thyroid nodules causing compression signs and/or hyperthyroidism are concerning during pregnancy. Patients and Methods. Six patients with nontoxic cystic, four with nontoxic solid, and three with overt hyperthyroidism caused by toxic nodules were treated with percutaneous ethanol injection therapy (PEI). An average of 0.68 mL ethanol per 1 mL nodule volume was administered. Mean number of PEI treatments for patients was 2.9. Success was defined as the shrinkage of the nodule by more than 50% of the pretreatment volume (V0) and the normalization of TSH and FT4 levels. The average V0 was 15.3 mL. Short-term success was measured prior to labor, whereas long-term success was determined during the final follow-up (an average of 6.8 years). Results. The pressure symptoms decreased in all but one patient after PEI and did not worsen until delivery. The PEI was successful in 11 (85%) and 7 (54%) patients at short-term and long-term follow-up, respectively. Three patients underwent repeat PEI which was successful in 2 patients. Conclusions. PEI is a safe tool and seems to have good short-term results in treating selected symptomatic pregnant patients. Long-term success may require repeat PEI.

Sirolimus formulation with improved pharmacokinetic properties produced by a continuous flow method.

The oral bioavailability of Sirolimus is limited by poor dissolution of the compound in the gastrointestinal tract resulting in a low bioavailability and large inter-individual differences in blood levels. Several different formulation approaches were applied to overcome these disadvantageous pharmacokinetic properties including the marketed oral solution and a tablet form containing wet milled nanocrystals. These approaches deliver improved pharmacokinetics, yet, they share the characteristics of complex production method and composition. We have developed a nanostructured Sirolimus formulation prepared by the controlled continuous flow precipitation of the compound from its solution in the presence of stabilizers. We have shown that contrary to the batch production the process could be easily intensified and scaled up; apparently the uniformity of the precipitation is heavily dependent on the production parameters, most likely the mixing of the solvent and antisolvent. We compared the physicochemical and pharmacokinetic properties of the nanostructured formula with the marketed nanoformula. We found that our method produces particles in the size range of less than 100nm. The solid form redispersed instantaneously in water and in biorelevant media. Both the solid form and the redispersed colloid solution showed excellent stability even in accelerated test conditions. The oral administration of the nanostructured formula resulted in faster absorption, higher exposure and higher trough concentrations when compared to the marked form. These advantageous properties could allow the development of solid oral Sirolimus formulae with lower strength and gel based topical delivery systems.

Novel continuous flow technology for the development of a nanostructured aprepitant formulation with improved pharmacokinetic properties.

The oral bioavailability of Aprepitant is limited by poor dissolution of the compound in the gastrointestinal tract which is more prominent in the fasted state resulting in significant positive food effect. Due to the low aqueous solubility of the active substance the product development has been focused on decreasing the particle size of the active compound down to the submicron range in order to overcome this disadvantageous pharmacokinetic property. The marketed drug consisting of wet-milled nanocrystals exhibits significantly higher oral bioavailability in the fasted state and reduced food effect when compared to the unformulated compound. We have developed a novel process for the production of a nanostructured Aprepitant formulation in which the generation of the nanosized particles takes place at molecular level. The process relies on controlled continuous flow precipitation of the compound from its solution in the presence of stabilizers. The precise control of the production parameters (mixing geometry, flow rates, temperature, etc.) allows to tailor the physicochemical properties and biological performance of the active compound. We have prepared a novel nanostructured Aprepitant formulation using this method and compared its physicochemical and pharmacokinetic properties with the reference compound and the marketed nanoformula. We found that our method produces a stable amorphous solid form comprising novel nanostructured particles having a particle size of less than 100 nm with instantaneous redispersibility characteristics and improved apparent solubility and permeability. In vivo beagle dog pharmacokinetic studies showed that the novel formula exhibited greatly improved pharmacokinetic characteristics when compared to the reference compound, while serum blood concentrations for the nanostructured formula and the wet-milled formula were similar. The marked food effect observed for the reference compound was practically eliminated by our formulation method. These results indicate that the novel continuous flow precipitation technology is a suitable tool to prepare nanostructured formulations with similar, or even superior in vitro and in vivo characteristics when compared to the industrial standard milling technology.

[Effectiveness and safety of total thyroidectomy in the management of benign multinodular goiters]. / A total thyreoidectomia hatásossága és biztonságossága a jóindulatú multinodularis golyvák kezelésében.

BACKGROUND: The appropriate surgical procedure for benign multinodular goiters is debated. We report our clinical experience of performing total thyroidectomy for multinodular goiters, focusing on the outcome and complications to evaluate the efficacy and safety. MATERIAL AND METHODS: The medical records of 264 patients who underwent total thyroidectomy for multinodular goiter between 2000 and 2006 were reviewed retrospectively. We examined the indications for operation, average hospital stay, early and late postoperative complications, the results of the final pathology in particular the frequency of incidental thyroid cancers and the recurrence rates after an average 6.2 years follow-up. The results were compared to literature data. RESULTS: The indications for surgery were compression and/or dislocation of the trachea in 174 (65.9%) patients, hyperthyreodism in 74 (28%) and cosmetic problems in others. The mean hospital stay was 4 days. Thirty-one patients (11.7%) had transient hypocalcaemia, but only 1 (0.3%) was symptomatic, and only 4 (1.5%) had permanent hypocalcaemia. Other complications included hematoma 4 (1.5%), temporary unilateral recurrent laryngeal nerve palsy 7 (2.6%), permanent unilateral laryngeal nerve palsy 2 (0.75%), and seroma in 8 (3%) cases. Incidental thyroid carcinomas were found on hystology in 9 (3.5%) patients. No recurrence was observed during the follow-up. CONCLUSION: Total thyroidectomy may be the procedure of choice for the surgical management of benign multinodular goiter.

Twenty years of experience with the preoperative diagnosis of medullary cancer in a moderately iodine-deficient region.

Background. There is a current debate in the medical literature about plasma calcitonin screening in patients with nodular goiter (NG). We decided on analyzing our 20-year experience with patients in an iodine-deficient region (ID). Patients and Methods. 22,857 consecutive patients with NG underwent ultrasonography and aspiration cytology (FNAC). If FNAC raised suspicion of medullary cancer (MTC), the serum calcitonin was measured. Results. 4,601 patients underwent surgery; there were 23 patients among them who had MTC (0.1% prevalence). Significantly more MTC cases were diagnosed cytologically in the second decade than in the first: 11/12 and 6/11, respectively. The frozen section was of help in 2 cases out of 3. Two patients suffered from a 3-year delay in proper therapy, and reoperation was necessary in 1 case. FNAC raised the suspicion of MTC in 20 cases that were later histologically verified and did not present MTC. The diagnostic accuracy of FNAC in diagnosing MTC was 99.2%. Two false-positive serum calcitonin tests (one of them in a hemodialyzed patient) and one false-negative serum calcitonin test occurred in 40 cases. Conclusion. Regarding the low prevalence of MTC in ID regions, calcitonin screening of all NG patients does not only appear superfluously but may have more disadvantages than advantages.

Minimally invasive video-assisted thyroidectomy and conventional thyroidectomy: a prospective randomized study.

BACKGROUND: Since the first description of the minimally invasive totally gasless video-assisted thyroidectomy (MIVAT) technique in 1998, relatively few studies have evaluated the outcome of this procedure. The authors review their experiences based on a prospective randomized trial comparing the potential advantages of MIVAT over conventional thyroidectomy. METHODS: Patients undergoing surgery for either thyroid nodule or diffuse thyroid disease with hyperthyroidism were randomly selected for either MIVAT or conventional thyroidectomy. The exclusion criteria specified nodules larger than 35 mm, thyroid lobe volume greater than 20 ml, thyroiditis, and previous neck irradiation or surgery. Operative time, postoperative complications, and cosmetic results were evaluated using both a verbal response scale and a numeric scale. RESULTS: Both the MIVAT group and the conventional thyroidectomy group included 15 patients. No significant differences were noted between the two groups in terms of age, sex, or indication for operation. The mean operative times were 65.5 +/- 18 min. for MIVAT and 43.3 +/- 14 min. for conventional thyroidectomy (P = 0.001). No postoperative complications were detected in either group. The cosmetic results, evaluated by both verbal response and numeric scales, were respectively as follows: MIVAT (3.7 +/- 0.2 and 7.9 +/- 1.2) and conventional thyroidectomy (2.3 +/- 0.7 and 4.9 +/- 1.3). The differences significantly favored MIVAT (P = 0.028 and P = 0.015, respectively) despite the small number of patients enrolled in this study, and consequently, its limited statistical power. CONCLUSION: Although the complications are comparable between the two approaches, conventional thyroidectomy involves less operative time. However, MIVAT offers distinct advantages to selected patients in terms of very good to exellent cosmetic results and reduced postoperative distress.

[Minimally invasive video-assisted thyroidectomy (MIVAT)]. / Minimálisan invazív video-asszisztált thyreoidectomia (MIVAT).

Minimally invasive video-assisted thyroidectomy (MIVAT) was published in 1998. In this paper authors describe their initial experiences with this new technique, which is the first publication in their country on this topic based on authors knowledge. Ten patients were selected for MIVAT. Selection criteria were nodule size less than 30 mm, thyroid lobe volume less than 20 ml, no thyroiditis, no previous neck surgery or irradiation. The procedure was carried out through a 20-25 mm central incision above the sternal notch. Dissection was performed under endoscopic vision, using endoscopic, some special and conventional instruments. Authors performed 1 total thyroidectomy, 6 lobectomies, 2 lobectomies with subtotal resection on the opposite side, and 1 resection of thyroid isthmus. Mean operative time was 77 minutes. No conversion to open procedure was performed. No recurrent laryngeal nerve palsy or postoperative hypocalcemia were observed postoperatively. The mean hospital stay was 2 days. The cosmetic result and the postoperative distress were considered very good by the patients. The authors conclude that MIVAT is a safe and feasible procedure. The indications are limited, but in this small group of patients offer excellent cosmetic results with less postoperative distress.

Treatment of recurrent nodular goiters with percutaneous ethanol injection: a clinical study of twelve patients.

Twelve patients who had previously undergone thyroid surgery received percutaneous ethanol injection (PEI) treatment because of recurrent nodular goiter (3 with a toxic [TN], 2 with a nontoxic cystic [NCN], and 7 with a nontoxic solid nodule [NSN]). Two of the 12 had recurrent nerve palsy contralateral to the nodule. Each patient received a mean total dose of 0.88 mL of ethanol per milliliter of nodular volume. Ethanol was injected in a mean of 3.5 sessions for solid and 3 sessions for NCN. In most cases, a slight to moderate burning pain was experienced during and for 12-48 hours after PEI treatment, and one patient experienced temporary hoarseness. One patient with TN and 2 patients with NSN became hypothyroid, 7 patients with nontoxic nodules remained euthyroid, 1 with TN became euthyroid, and a previously hyperthyroid patient with TN became subclinically hyperthyroid 1-year posttherapy. The nodule shrank by more than 50% of the pretreatment volume in all patients (8.6 +/- 2.6 vs. 2.9 +/- 1.2 mL in TN, and 12.3 +/- 4.9 vs. 4.16 +/- 2.54 mL in nontoxic nodules, pretreatment vs. 1 year posttreatment volume, respectively). With regard to the increased risk of reoperation, PEI treatment can be proposed for patients with recurrent nodular goiter requiring surgery.