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PURPOSE: To characterize patients with APS and to propose a new approach for their follow-up. Query ID="Q1" Text="Please check the given names and familynames." METHODS: Monocentric observational retrospective study enrolling patients referred to the Outpatients clinic of the Units of Endocrinology, Diabetology, Gastroenterology, Rheumatology and Clinical Immunology of our Hospital for Autoimmune diseases. RESULTS: Among 9852 patients, 1174 (11.9%) [869 (73.9%) female] were diagnosed with APS. In 254 subjects, the diagnosis was made at first clinical evaluation (Group 1), all the other patients were diagnosed with a mean latency of 11.3 ± 10.6 years (Group 2). Group 1 and 2 were comparable for age at diagnosis (35.7 ± 16.3 vs. 40.4 ± 16.6 yrs, p = .698), but different in male/female ratio (81/173 vs 226/696, p = .019). In Group 2, 50% of patients developed the syndrome within 8 years of follow-up. A significant difference was found after subdividing the first clinical manifestation into the different outpatient clinic to which they referred (8.7 ± 8.0 vs. 13.4 ± 11.6 vs. 19.8 ± 8.7 vs. 7.4 ± 8.1 for endocrine, diabetic, rheumatologic, and gastroenterological diseases, respectively, p < .001). CONCLUSIONS: We described a large series of patients affected by APS according to splitters and lumpers. We propose a flowchart tailored for each specialist outpatient clinic taking care of the patients. Finally, we recommend regular reproductive system assessment due to the non-negligible risk of developing premature ovarian failure.
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Enfermedades Autoinmunes , Endocrinología , Poliendocrinopatías Autoinmunes , Insuficiencia Ovárica Primaria , Humanos , Femenino , Masculino , Estudios Retrospectivos , Poliendocrinopatías Autoinmunes/diagnósticoRESUMEN
Context: Hypothyroidism and iron deficiency are among the most common pathologies in population. Therefore, there are a lot of patients assuming both iron salt supplements and levothyroxine therapy. Objective: To evaluate the effect of iron salt intake on L-T4 absorption among different L-T4 formulations. Materials and methods: A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Original studies and reviews written in English and published online up to 21 December 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review. Results: The data show an impaired absorption of L-T4 in tablets formulation when taken concomitantly with iron salt supplements. These phenomena seem to be circumvented by new L-T4 formulations. Conclusion: Liquid L-T4 formulations can be ingested with iron salts, with no impairment of absorption. More studies are necessary to confirm these data for soft-gel capsules L-T4.
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OBJECTIVE: The purpose of this study is to verify the effectiveness and complications occurrence of radiofrequency ablation (RFA) in the treatment of osteoid osteoma (OO) in non-operating room anesthesia (N.O.R.A.). PATIENTS AND METHODS: From 2014 to 2017, 61 patients affected by OO (40 men and 21 women) with an age of 20.7 years on average (range, 4-51 years; 12 patients aged 20 years or younger) underwent computed tomography-guided percutaneous radiofrequency ablation (RFA) in N.O.R.A. (Non-Operating Room Anesthesia). Lesion sites treated were: femur (27), tibia (22), pelvis (2), talar bone (3), distal radius (1), and humerus (6). Mean follow-up time was 36 months. In each case, anesthesiologic support followed a new protocol (N.O.R.A. protocol), approved by our Institute. Primary success rate, complications, symptom-free intervals, and follow-up results were evaluated. RESULTS: Pain relief (evaluated with Visual Analogue Scale - VAS) was significant in 97% of patients; it disappeared within 24 hours of the procedure in 44 patients, within 3 days in 10 patients, and within 7 days in 7 patients. After 6 months of observation time, 60 of 61 patients were successfully treated and had no more complaints. In 2 patients, two major complications were found: infection of the site treated, healed with antibiotics, and a nerve lesion, healed with steroid therapy. No other complications were observed. CONCLUSIONS: RFA is a highly effective, efficient, minimally invasive and safe method for the treatment of OO following N.O.R.A.
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Anestesia Local/métodos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Osteoma Osteoide/diagnóstico por imagen , Osteoma Osteoide/cirugía , Ablación por Radiofrecuencia/métodos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
The objective is to reconstruct the subchondral bone after curettage of benign tumors located in the epiphysis, a relevant topic in oncological orthopedics. Several bones substituted are commercially available, yet none of these are suitably moldable to repair or be placed in the bone defect; although autologous bone for little defects and homologous for bigger defects are still considered the standard in reconstruction, we verify the ability to adapt and support articular cartilage through the application of Plexur M (Registered Trademark), a newly engineered biomaterial bone. In the present study, we enrolled the first ten consecutive cases referred to our department, where patients were affected by a benign epiphyseal tumor destroying the subchondral bone through to the articular cartilage. Every patient underwent curettage of the disease, apposition of a newly engineered biomaterial bone and filling with homologous morselized bone. The quality of reconstruction was evaluated by two surgeons and by a radiologist based on the achievement of surgical objectives and comparing pre and postoperative imaging. In seven out of eight cases of lesions located in the lower limbs the quality of reconstruction was considered good, restoring an adequate support to the articular cartilage. The quality of the remaining case was considered poor probably due to the extent of the spread of the disease, which destroyed the entire proximal tibial epiphysis. In the two cases where the disease was located in the upper limbs, the Plexur M application restored support to the articular cartilage sufficiently well. However, in the case of a giant cell tumor of the distal radial epiphysis there was a slight reabsorption of the morselized homologous bone. Our series suggest that Plexur M should be considered a valid option for orthopedic surgeons in restoring adequate mechanical support to the articular cartilage; nevertheless, considering its high cost, its use might be reserved to selected cases until further studies can verify the integration process, the effects on the survival of the articular cartilage and on the prevention of premature osteoarthritis.
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Neoplasias Óseas/cirugía , Procedimientos de Cirugía Plástica/métodos , Ingeniería de Tejidos , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Human oncogenes involved in the development of hematological malignancies have been widely used to model experimental leukemia. However, models of myeloid leukemia rarely reproduce the human disease in full, due to genetic complexity or to difficulties in targeting leukemia initiating cells. Here, we used a zebrafish genetic model to induce the expression of oncogenic RAS in endothelial cells, including the hemogenic endothelium of the dorsal aorta that generates hematopoietic cells, and observed the development of a myelo-erythroid proliferative disorder. In larvae, the phenotype is characterized by disruption of the vascular system and prominent expansion of the caudal hematopoietic tissue. In few surviving juveniles, increased number of immature hematopoietic cells and arrest of myeloid maturation was found in kidney marrow. Peripheral blood showed increased erythroblasts and myeloid progenitors. We found that the abnormal phenotype is associated with a downregulation of the Notch pathway, whereas overexpressing an activated form of Notch together with the oncogene prevents the expansion of the myelo-erythroid compartment. This study identifies the downregulation of the Notch pathway following an oncogenic event in the hemogenic endothelium as an important step in the pathogenesis of myelo-erythroid disorders and describes a number of potential effectors of this transformation.
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Linaje de la Célula , Proliferación Celular , Transformación Celular Neoplásica/patología , Endotelio Vascular/patología , Células Precursoras Eritroides/patología , Células Mieloides/patología , Proteínas Proto-Oncogénicas/genética , Receptor Notch1/metabolismo , Proteínas ras/genética , Animales , Apoptosis , Western Blotting , Diferenciación Celular , Endotelio Vascular/metabolismo , Células Precursoras Eritroides/metabolismo , Técnica del Anticuerpo Fluorescente , Hematopoyesis , Humanos , Células Mieloides/metabolismo , Proteína Proto-Oncogénica c-fli-1 , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas p21(ras) , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Notch1/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Pez Cebra/genética , Pez Cebra/metabolismo , Proteínas ras/metabolismoRESUMEN
Glioblastoma is a deadly cancer with intrinsic chemoresistance. Understanding this property will aid in therapy. Glucosylceramide synthase (GCS) is associated with resistance and poor outcome; little is known about glioblastomas. In glioblastoma cells, temozolomide and paclitaxel induce ceramide increase, which in turn promotes cytotoxicity. In drug-resistant cells, both drugs are unable to accumulate ceramide, increased expression and activity of GCS is present, and its inhibitors hinder resistance. Resistant cells exhibit cross-resistance, despite differing in marker expression, and cytotoxic mechanism. These findings suggest that GCS protects glioblastoma cells against autophagic and apoptotic death, and contributes to cell survival under chemotherapy.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Dacarbazina/análogos & derivados , Glioblastoma/tratamiento farmacológico , Glucosiltransferasas/metabolismo , Paclitaxel/farmacología , Antineoplásicos Alquilantes/farmacología , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/metabolismo , Ceramidas/metabolismo , Dacarbazina/farmacología , Resistencia a Antineoplásicos/fisiología , Glioblastoma/metabolismo , Humanos , TemozolomidaRESUMEN
In patients with osteosarcoma several causative factors are implicated in the occurrence of osteoporosis, such as no weight-bearing, pre- and post-surgical immobilization, and neoadjuvant and adjuvant chemotherapy. Nevertheless, osteoporotic fractures are a rare complication in young patients. We report the case of a spontaneous greenstick fracture of the distal tibia occurring during adjuvant chemotherapy in a 12-year-old Caucasian girl. Among the various drugs, the main role of methotrexate was investigated. A review of the literature is also presented along with a discussion about the role of preventive agents able to reduce the occurrence of osteopenia and/or osteoporosis following cancer treatment.
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Antimetabolitos Antineoplásicos/efectos adversos , Neoplasias Óseas/tratamiento farmacológico , Rodilla , Metotrexato/efectos adversos , Osteoporosis/inducido químicamente , Osteosarcoma/tratamiento farmacológico , Fracturas de la Tibia/inducido químicamente , Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Óseas/diagnóstico por imagen , Niño , Femenino , Humanos , Metotrexato/administración & dosificación , Osteoporosis/diagnóstico por imagen , Osteoporosis/terapia , Osteosarcoma/diagnóstico por imagen , Radiografía , Fracturas de la Tibia/diagnóstico por imagen , Fracturas de la Tibia/terapiaRESUMEN
PURPOSE: To evaluate the safety, local effectiveness, and long-term results of laser thermal ablation (LTA) in the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ninety-two biopsies proved small HCCs (range, 0.8-4.0 cm) in 74 patients who were treated percutaneously with LTA in an outpatient clinic. A laser at a power of 5.0 W was coupled with one to four fibers that were advanced through 21-gauge needle(s) for 6-12 minutes. All lesions were evaluated with computed tomography (CT) for changes in size and vascular pattern, recurrence rates, and cumulative survival rates. Patients were examined for complications. RESULTS: No major complications occurred in 117 LTA sessions, with an average of 1.3 sessions per tumor. At 3 months, CT scans showed a nonenhancing area (complete necrosis) in 89 (97%) of 92 lesions. During follow-up (range, 6-66 months; mean, 25.3 months), 84 tumors (91%) decreased in size. The local recurrence rates (range, 1-5 years) ranged from 1.6% to 6.0%. Recurrence rates (range, 12-60 months) in other liver segments ranged from 24% to 73%. Cancer-free survival rates (range, 1-4 years) ranged from 73% to 24%. Overall survival rates were 99%, 68%, and 15% at 1, 3, and 5 years, respectively. Twenty-one patients (28%) died. CONCLUSION: LTA is a safe and effective treatment for small HCC.
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Carcinoma Hepatocelular/cirugía , Coagulación con Láser , Neoplasias Hepáticas/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Coagulación con Láser/efectos adversos , Coagulación con Láser/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
PURPOSE: To determine the potential long-term effectiveness of laser thermal ablation (LTA) followed by transcatheter arterial chemoembolization (TACE) in the percutaneous ablation of large hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty large HCCs 3.5-9.6 cm in diameter (mean diameter, 5.2 cm) and 15 small HCCs 0.8-3.0 cm (mean diameter, 1.9 cm) were treated with ultrasonographically guided LTA with TACE and with LTA alone, respectively, in 30 patients: 19 with a solitary large HCC, and 11 with one to three additional synchronous small HCCS: A 1.064-microm neodymium yttrium-aluminium-garnet (Nd-YAG) laser at a power of 5.0 W was coupled with one to four quartz optic fibers that were advanced through 21-gauge needles. Segmental TACE was performed 30-90 days after LTA. All lesions were evaluated for change in size at computed tomography (CT), alpha-fetoprotein (AFP) levels, recurrence rates, and cumulative survival rates. RESULTS: No major complications occurred in 127 LTA sessions. CT showed complete tumor necrosis in 27 (90%) of 30 large HCCS: Twenty-eight patients were followed up for 6-41 months (mean, 17.1 months). In 25 patients, all lesions appeared stable or smaller at CT. AFP levels decreased to the normal range in all patients with high pretreatment values. The 1-, 2-, and 3-year local recurrence rate was 7% in large HCCS: Complete tumor necrosis was achieved in all 15 (100%) small HCCs; none of them recurred locally. The 1-, 2-, and 3-year cumulative survival rates were 92%, 68%, and 40%, respectively. CONCLUSION: LTA followed by TACE is an effective palliative therapy in treating large HCCS:
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Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Terapia por Láser , Neoplasias Hepáticas/terapia , Anciano , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/mortalidad , Terapia Combinada , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Tasa de Supervivencia , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
PURPOSE: To evaluate percutaneous interstitial laser photocoagulation (ILP) as a palliative treatment of recurrent thyroid carcinoma untreatable with surgery or radioiodine administration. MATERIALS AND METHODS: By using 18 resected thyroid glands, the volume and histologic pattern of ILP-induced thyroid damage were assessed. In vivo treatment feasibility was evaluated by using a low-energy laser in two volunteers before thyroidectomy for huge autonomously functioning nodules. With ultrasonographic (US) monitoring, a 21-gauge spinal needle was inserted into the thyroid nodules. A 300-microm quartz fiberoptic guide was inserted through the needle lumen, and the fiber tip was placed in direct contact with the tissue. Laser irradiation was performed with a 1.064-nm Nd:YAG laser in surgically resected glands, which were treated with 2, 3, 5, or 7 W. RESULTS: Tissue ablation was well-defined histologically, and its area was related to laser irradiation parameters (range, 0-26 mm). No correlation was found between US images and the actual extent of laser-induced lesions. Large colloid or fluid collections did not permit regular heat diffusion within the tissue. In vivo low-energy ILP was performed without technical difficulties or complications. CONCLUSION: ILP induces well-defined tissue ablation correlated with energy parameters in thyroid glands devoid of cystic areas. ILP could be a therapeutic tool for highly selected problems in thyroid tumor treatment.
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Coagulación con Láser/métodos , Glándula Tiroides/cirugía , Análisis de Varianza , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Análisis de Regresión , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/patología , UltrasonografíaRESUMEN
The aim of this work was to study the vascularization of hepatocellular carcinoma (HCC) by means of dynamic CT and to demonstrate the existence of optimal temporal windows for visualization of HCC in order to develop new protocols for helical CT of the liver. We studied, by means of dynamic CT, 42 histologically proved HCCs in 30 patients after injecting contrast medium (100 ml, 3 ml/s). We performed a time-density analysis of the aorta, liver, portal vein, spleen and lesion. We identified three temporal curves of attenuation of the neoplastic tissue. Curve 1 was three-phasic: hyperattenuation, isoattenuation and hypoattenuation; curve 2 was two-phasic: hyperattenuation and isoattenuation; curve 3 was two-phasic: isoattenuation and hypoattenuation. Thirty-two lesions were homogeneous (curve 1 in 22 cases, 68.7 %; curve 2 in 7 cases, 21.8 %; curve 3 in 3 cases, 9.4 %), whereas 10 lesions were non-homogeneous. Two optimal temporal windows were identified: the first, with predominantly hyperattenuating lesions (range 29-65 s, 90.4 % sensitivity); the second, with predominantly hypoattenuating lesions (range 132.1-360 s, 76.1 %). There is an interposed time range of reduced visualization (range 62-127 s, 54.7 %) in which lesions are isoattenuating. Combined CT study during the first and second temporal windows improves the detection of HCCs especially for homogeneous and small lesions. The intermediate isoattenuation time range does not increase lesion detection rate.
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Aorta Abdominal/diagnóstico por imagen , Carcinoma Hepatocelular/irrigación sanguínea , Neoplasias Hepáticas/irrigación sanguínea , Vena Porta/diagnóstico por imagen , Bazo/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste/administración & dosificación , Estudios de Evaluación como Asunto , Femenino , Humanos , Infusiones Intravenosas , Yohexol/administración & dosificación , Yohexol/análogos & derivados , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neovascularización Patológica/diagnóstico por imagen , Intensificación de Imagen Radiográfica , Estudios Retrospectivos , Bazo/irrigación sanguíneaRESUMEN
Interstitial laser photocoagulation (ILP) causes tumor necrosis with local hyperthermia produced by laser light energy. We treated with US-guided ILP 14 patients (7 men and 7 women; mean age: 67 years) and 20 metastases: 9 of them were < 3 cm in max. diameter and 11 were > 3 cm (mean diameter: 2.9 cm); 14 metastases were from colon carcinoma, 5 from breast cancer and 1 from lung cancer. ILP was performed with 300 and 600 microns quartz fiberoptic guides advanced in 21-18G Chiba needles and a continuous-wave Nd: YAG laser with 1064 nm wavelength. We used single expositions of 5-6 minutes with an irradiation power of 5 watts and scheduled 3 treatment sessions, performing CT scans and biopsies at the end of each session. The extent of induced necrosis was classified as follows on the basis of CT findings: grade 1 = 100% necrosis; grade 2 = necrosis > 50%; grade 3 = necrosis < 50%. The average follow-up was 6 months. After the 3 scheduled treatment sessions, CT showed grade 1 necrosis in all the lesions < 3 cm in diameter and in 4/9 (44%) lesions > 3 cm and grade 2 and 3 necrosis in the remaining cases (necrosis > 50% in 95% of the lesions and 92% of the patients). The cytologic findings were in agreement with CT results in all grade 2 and 3 cases, but in one grade 1 necrosis cytology showed residual viable tumor. To conclude, ILP is a safe and well-tolerated procedure. Maximum efficacy was observed in the lesions < 3 cm, while lesion volume was markedly reduced in the lesions > 3 cm. US is a useful tool in the real-time monitoring of this procedure and CT is the most accurate imaging technique to assess treatment efficacy.
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Coagulación con Láser , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Anciano , Anciano de 80 o más Años , Protocolos Clínicos , Femenino , Estudios de Seguimiento , Humanos , Coagulación con Láser/efectos adversos , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Ultrasound-guided ethanol injection (PEI) is an effective treatment of autonomously functioning thyroid nodules (AFTN) but little is known about the tissue lesions induced by alcohol. We report morphological changes of an AFTN which was removed after successful PEI treatment. At histological evaluation, the adenoma showed multiple areas of coagulative necrosis with eosinophilic ghost follicles, hemorrhages, small vessel thrombosis and a wedge-shaped hemorrhagic infarction. The peripheral adenomatous tissue and the surrounding thyroid parenchyma were free of regressive changes and/or lympho-monocytic inflammatory reactions. Enzyme histochemistry confirmed the hyperfunctioning character of the lesion and showed reduction of succinic dehydrogenase and cytochrome-c-oxydase activity in the viable tissue surrounding the central necrotic areas. By electron microscopy, the hyperfunctioning follicular epithelium showed submicroscopical alterations of the adenomatous cells surrounding the areas of coagulative necrosis. These results suggest that control of hyperthyroidism, after PEI, is due to: a) directly induced, irreversible damage (coagulative necrosis and vascular thrombosis with hemorrhagic infarction) in the central areas of the lesion; b) potentially reversible damage (reduction of intracellular enzyme activity and ultrastructural changes) in the peripheral areas.
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Adenoma/enzimología , Adenoma/patología , Etanol/farmacología , Neoplasias de la Tiroides/enzimología , Neoplasias de la Tiroides/patología , Fosfatasa Ácida/análisis , Adenoma/tratamiento farmacológico , Anciano , Complejo IV de Transporte de Electrones/análisis , Etanol/administración & dosificación , Etanol/uso terapéutico , Femenino , Histocitoquímica , Humanos , Inyecciones Subcutáneas , Microscopía Electrónica , Succinato Deshidrogenasa/análisis , Neoplasias de la Tiroides/tratamiento farmacológicoRESUMEN
The authors describe the technique used in the treatment of autonomously functioning thyroid nodules by percutaneous ethanol injection (PEI). They illustrate the free-hand technique followed in their hospital from January 1990 to October 1992 in a group of 25 patients. Results, advantages and disadvantages of this technique are reported and compared with the ultrasound-guided technique. In the latter, widely used, the needle is positioned in the target nodule by means of an ultrasound probe with a specially designed guiding device which forces the needle in the correct direction. This makes the manoeuver rapid and safe as the needle tip can be easily visualized. In this case, the most important drawback lies in the impossibility of changing the ultrasound scanning plane during the ethanol injection as the probe and the needle are fast together. So the correct spreading modality of ethanol inside the tissue is not completely checked. Another disadvantage is the cost of disposable guiding device necessary in order to avoid contamination. On the other side, in the free-hand technique the needle is aimed at the nodule and inserted during an ultrasound examination without restrain on the probe movements. In this way, it is possible to focus the attention on the critical structures to prevent their damage stopping ethanol injection as soon as a seepage outside the thyroid occurs. Furthermore, this technique is particularly inexpensive as a standard probe is used and the risk of contamination can be avoided by just wrapping the probe with a sterline plastic film.(ABSTRACT TRUNCATED AT 250 WORDS)