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BACKGROUND: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of sclerotherapy methods for hemorrhoidal disease (HD) over the past 40 years. METHODS: The review followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive literature search was conducted, including studies reporting the use of sclerotherapy in patients with HD. Study eligibility criteria were defined, and data were extracted independently by the authors. Random-effects meta-analyses were performed to assess outcomes of interest. RESULTS: Out of 1965 records identified, 44 studies met the inclusion criteria, involving 9729 patients. The majority of studies were conducted in Japan, followed by the UK, Italy, and Portugal. The median age of participants was 52 years, and the majority were male. The Goligher grade distribution indicated varying degrees of HD severity. Sclerotherapy was predominantly administered through anoscopy, with polidocanol being the most commonly used agent. The procedure was generally performed without pre-injection analgesia. The meta-analysis of 14 randomized controlled trials (RCTs) revealed that sclerotherapy was not inferior to control interventions in terms of success rate (risk ratio [RR] 1.00, 95% CI 0.71-1.41) and recurrence rate (RR 1.11, 95% CI 0.69-1.77), while resulting in fewer complications (RR 0.46, 95% CI 0.23-0.92). CONCLUSIONS: This systematic review highlights the safety and efficacy of sclerotherapy for HD, which yields similar success rates and fewer complications compared to other conservative or surgical approaches. Further research is warranted to optimize sclerotherapy techniques and evaluate long-term outcomes. REGISTRATION: PROSPERO 2023 CRD42023396910.
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Hemorroides , Escleroterapia , Masculino , Humanos , Femenino , Persona de Mediana Edad , Escleroterapia/efectos adversos , Hemorroides/terapia , Italia , Oportunidad Relativa , PolidocanolRESUMEN
A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and healthcare management protocol in thyroid surgery published in 2016, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 13 members of the SIUEC highly trained and experienced in thyroid surgery. The main topics concern clinical evaluation and preoperative workup, patient preparation for surgery, surgical treatment, non-surgical options, postoperative management, prevention and management of major complications, outpatient care and follow-up.
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Procedimientos Quirúrgicos Endocrinos , Enfermedades de la Tiroides , Humanos , Glándula Tiroides/cirugía , Tiroidectomía/métodos , Atención a la Salud , Italia , Enfermedades de la Tiroides/cirugíaRESUMEN
INTRODUCTION: The European Society of Cardiology (ESC) guidelines (GL) provide indications on the mode of delivery in women with heart disease. However available data suggests that the rate of Cesarean Delivery (CD) is high and widely variable among such patients. In this study, we aimed to investigate the degree of adherence to the ESC recommendations among women delivering in four tertiary maternity services in Italy and how this affects the maternal and neonatal outcomes. MATERIAL AND METHODS: Retrospective multicenter cohort study including pregnant women with heart disease who gave birth between January 2014 and July 2020. Composite adverse maternal outcome (CAM) was defined by the occurrence of one or more of the following: major postpartum hemorrhage, thrombo-embolic or ischemic event, de novo arrhythmia, heart failure, endocarditis, aortic dissection, need for re-surgery, sepsis, maternal death. Composite Adverse Neonatal outcome (CAN) was defined as cord arterial pH <7.00, APGAR <7 at 5 min, admission to the intensive care unit, and neonatal death. We compared the incidence of CAM and CAN between the cases with planned delivery in accordance (group "ESC consistent") or in disagreement (group "ESC not consistent") with the ESC GL. RESULTS: Overall, 175 women and 181 liveborn were included. A higher frequency of CAN was found when delivery was not planned accordingly to the ESC guidelines [("ESC consistent" 9/124 (7.2%) vs "ESC not consistent" 13/57 (22.8%) p = 0.002 OR 3.74 (CI 95% 1.49-9.74) , while the occurrence of CAM was comparable between the two groups. At logistic regression analysis, the gestational age at delivery was the only parameter independently associated with the occurrence of CAN (p = 0.006). CONCLUSION: Among pregnant women with heart disease, deviating from the ESC guidelines scheduling cesarean delivery does not seem to improve maternal outcomes and it is associated with worse perinatal outcomes, mainly due to lower gestational age at birth.
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Cardiología , Cardiopatías , Recién Nacido , Femenino , Embarazo , Humanos , Estudios de Cohortes , Periodo Periparto , CesáreaRESUMEN
OBJECTIVE: To evaluate outcomes of dichorionic twin pregnancies undergoing early vs late selective termination of pregnancy (ST). METHODS: MEDLINE, EMBASE, CINAHL and the Web of Science databases were searched electronically up to March 2022. The primary outcome of this study was pregnancy loss prior to 24 weeks' gestation. The secondary outcomes included preterm birth (PTB) before 37, 34, and 32 weeks, preterm prelabor rupture of membranes (PPROM), gestational age (GA) at delivery, Cesarean delivery, mean birth weight, 5-min Apgar score < 7, overall neonatal morbidity and neonatal survival. Only prospective or retrospective studies reporting data on the outcome of early (before 18 weeks) vs late (at or after 18 weeks) ST in dichorionic twin pregnancies were considered suitable for inclusion. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale for cohort studies. Random-effects head-to-head meta-analysis was used to analyze the data. RESULTS: Seven studies reporting on 649 dichorionic twin pregnancies were included in this systematic review. The risk of pregnancy loss prior to 24 weeks was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST (1% vs 8%; odds ratio (OR), 0.25 (95% CI, 0.10-0.65); P = 0.004). The risk of PTB was significantly lower in dichorionic twin pregnancies undergoing early compared with late ST when considering PTB before 37 weeks (19% vs 45%; OR, 0.36 (95% CI, 0.23-0.57); P < 0.00001), before 34 weeks (4% vs 19%; OR, 0.24 (95% CI, 0.11-0.54); P = 0.0005) and before 32 weeks (4% vs 20%; OR, 0.21 (95% CI, 0.05-0.85); P = 0.03). The mean birth weight was significantly greater in the early-ST group (mean difference (MD), 392.2 g (95% CI, 59.1-726.7 g); P = 0.02), as was the mean GA at delivery (MD, 2.47 weeks (95% CI, 0.04-4.91 weeks); P = 0.049). There was no significant difference between dichorionic twin pregnancies undergoing early compared with late ST in terms of PPROM (P = 0.27), Cesarean delivery (P = 0.38), 5-min Apgar score < 7 (P = 0.35) and neonatal survival of the non-reduced twin (P = 0.54). CONCLUSIONS: The risk of pregnancy loss prior to 24 weeks and the rate of PTB before 37, 34 and 32 weeks were significantly higher in dichorionic twin pregnancies undergoing late vs early ST, thus highlighting the importance of early diagnosis of fetal anomalies in twin pregnancies. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
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Aborto Espontáneo , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Embarazo Gemelar , Nacimiento Prematuro/epidemiología , Peso al Nacer , Estudios Retrospectivos , Estudios Prospectivos , Edad Gestacional , Resultado del Embarazo/epidemiologíaRESUMEN
We report a case of a 73-year-old woman affected by Lemmel's syndrome, a rare type of obstructive jaundice caused by a periampullary duodenal diverticulum. The patient was admitted to the Emergency Department for pneumonia associated with mild epigastric pain and vomiting. While hospitalized for antibiotic treatment, the appearance of jaundice led us to discover a periampullary duodenal diverticulum by endoscopy and CT scan. The jaundice was successfully managed endoscopically with removal of food debris from the diverticulum.
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Divertículo , Enfermedades Duodenales , Ictericia Obstructiva , Ictericia , Dolor Abdominal/etiología , Anciano , Divertículo/complicaciones , Divertículo/diagnóstico por imagen , Divertículo/cirugía , Enfermedades Duodenales/complicaciones , Enfermedades Duodenales/diagnóstico por imagen , Femenino , Humanos , Ictericia Obstructiva/etiología , SíndromeRESUMEN
Duodenal follicular lymphoma (DFL) is a rare variety of non-Hodgkin's lymphoma of the gastrointestinal tract that usually carries a favorable course, recognized as a new entity in 2016. It is usually diagnosed at an early stage located predominantly in the second portion of the duodenum. We report the case of a 74-year-old male patient with epigastric pain in whom gastroscopy revealed white mucosal nodules that were pathologically diagnosed as grade 1-2 DFL. Staging investigations revealed secondary lesions in the spleen and at the base of the tongue together with latero-cervical adenopathy. The tumor was stage IV according to the Lugano staging system. We reviewed the recent (last five years) literature defining the importance of combination therapy in the advanced stage. The patient achieved complete remission of the disease through chemoimmunotherapy following the Rituximab-Bendamustine scheme.
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Linfoma Folicular , Linfoma no Hodgkin , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Duodeno/patología , Humanos , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/patología , Masculino , Inducción de Remisión , Rituximab/uso terapéuticoRESUMEN
The new Italian cytological classification (SIAPEC 2014) of thyroid nodules, in line with those of Bethesda and BTA-RCPath, replaces the previous TIR3 class with two new classes (TIR3A and TIR3B), which correspond to different risks of malignancy and clinical actions required. The present study was conducted to evaluate the diagnostic accuracy of the new SIAPEC classification as opposed to its previous version (SIAPEC 2007). Preoperative cytology was compared with the final histology obtained from 650 consecutive patients who underwent total thyroidectomy for multinodular goiter. Of this total, 434 patients (group A) had their cytological diagnosis based on the old SIAPEC 2007 classification and 216 patients (group B) had their cytological diagnosis based on the SIAPEC 2014 classification. In group A 111 patients (25.6%) had a TIR3 diagnosis, while in group B 52 patients (24.1%) received a TIR3 diagnosis, of whom 30 had TIR3A and 22 had TIR3B. In group A, 46 (41.4%) out of the 111 patients with TIR3 diagnosis had, based on histology, a thyroid carcinoma. In group B, only 2 (6.7%) out of 30 patients with TIR3A diagnosis had a thyroid carcinoma. This rate of malignancy was significantly lower (p less than 0.001) than that observed in patients with TIR3B diagnosis, in which 12 (54.5%) out of 22 patients had a carcinoma. The observations here reported show that, in respect to the previous version, the new Italian cytological classification provides greater diagnostic accuracy for detecting thyroid nodule malignancy.
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Citodiagnóstico/normas , Bocio Nodular/clasificación , Bocio Nodular/diagnóstico , Nódulo Tiroideo/clasificación , Nódulo Tiroideo/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biopsia con Aguja Fina , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Adulto JovenRESUMEN
AIM: The continued hospitalization after total thyroidectomy is often due to the onset of hypocalcemic complications more than 24 hours after surgery. So it would be important to predict which patients will not develop the hypocalcemic complication to discharge them early. This was the aim of our study. PATIENTS AND METHODS: Our retrospective study was conducted on 327 consecutive thyroidectomized patients, operated on for benign and malignant diseases. We evaluated the values of preoperative serum calcium levels (Cal0) and of the first postoperative day (Cal1) and two new variables were calculated (dCal and dCaln). The same thing was made on a subgroup of 111 patients in whom also parathiroyd hormone (PTH) values were detected. Statistical analysis was performed with the goal of determining if we could establish a safe criterion for discharge at 24 hours after surgery and if there is a correlation between suitability for discharge and diagnosis. RESULTS: As to discharge, the predictive power of the discriminant function applied was significant both on the total of patients and in the subgroup of 111 patients, but it was clinically unacceptable because it would expose us to a 21% to 27% error rate. It is not possible to identify a threshold, below which to consider patients surely dischargeable. The diagnosis does not appear correlated with the suitability for discharge. CONCLUSION: On the basis of serum calcium and PTH levels in the first postoperative day, it is impossible to predict which patients can be discharged 24 hours after surgery without incurring in hypocalcemic complications.
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Alta del Paciente/estadística & datos numéricos , Tiroidectomía , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tiroidectomía/métodos , Factores de TiempoRESUMEN
Small Ubiquitinlike MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.
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Biomarcadores de Tumor/biosíntesis , Carcinoma/metabolismo , Carcinoma/mortalidad , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Sumoilación , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Carcinoma/terapia , Carcinoma Papilar , Niño , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/terapiaRESUMEN
The three members of the Aurora kinase family, Aurora-A, -B and -C, regulate several aspects of the mitotic process, and their aberrant expression and/or function causes mitotic abnormalities leading either to cell death or aneuploidy. They are found overexpressed in several human malignancies, including the papillary thyroid carcinoma (PTC). In the present study, we sought to establish whether Aurora kinase inhibition could be of any therapeutic value in the treatment of aggressive forms of PTC, enduring to radioactive iodide (RAI) ablation. To this end, the effects of selective inhibitors of Aurora-A (MLN8237) and Aurora-B (AZD1152) were analyzed on 3 human PTC cell lines expressing either wild-type (K1 and TPC1) or mutant p53 (BCPAP). The two inhibitors were capable of reducing cell proliferation in a time- and dose-dependent manner, with IC50 comprised between 65.4 and 114.9 nM for MLN8237, and between 26.6 and 484.6 nM for AZD1152. Immunofluorescence experiments confirmed that AZD1152 inhibited Aurora-B phosphorylation of histone H3 on Ser10, however, it did not affect Aurora-A autophosphorylation. MLN8237 inhibited Aurora-A autophosphorylation as expected, but at concentrations required to achieve the maximum antiproliferative effects it also abolished H3 (Ser10) phosphorylation. Time-lapse videomicroscopy evidenced that both inhibitors prevented the completion of cytokinesis, and cytofluorimetric analysis showed accumulation of cells in G2/M phase and/or polyploidy. Apoptosis was induced in all the cells by both inhibitors independently from the p53 status. In conclusion, in the present preclinical study MLN8237 and AZD1152 have emerged as promising drug candidates for RAI-insensitive PTC.
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Aurora Quinasas/antagonistas & inhibidores , Carcinoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias de la Tiroides/tratamiento farmacológico , Azepinas/uso terapéutico , Carcinoma/patología , Carcinoma Papilar , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Organofosfatos/uso terapéutico , Pirimidinas/uso terapéutico , Quinazolinas/uso terapéutico , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/patologíaRESUMEN
Elastofibroma Dorsi (EFD) is a rare pseudo-tumor characterized by the overgrowth of elastic fibers mixed to adipose and connective tissues typically growing in the subscapular region. This can be bilateral but only rarely synchronous affecting different anatomical sites at the same time. Hereby we present a case of a 42-year-old male patient found with three different metachronous elastofibromas: bilateral EFD and a further third localization by the right elbow. The two EFs in the subscapular region were resected. After surgery pain reoccurred on the right side. This required the implantation of a spinal electro-stimulator. The elbow lesion was not excised as it was asymptomatic.
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Fibroma/patología , Neoplasias Primarias Múltiples/patología , Neoplasias de los Tejidos Blandos/patología , Adulto , Fibroma/cirugía , Humanos , Masculino , Neoplasias Primarias Múltiples/cirugía , Neoplasias de los Tejidos Blandos/cirugíaRESUMEN
The anaplastic thyroid cancer (ATC) is among the most aggressive human tumors which fail to respond to all the currently available therapeutic approaches. As a consequence most patients die within a few months from diagnosis. In the present preclinical study, the effects of the ZM447439, a functional inhibitor of Aurora kinases, on the growth and tumorigenicity of a panel of ATC derived cell lines (CAL-62, 8305C, 8505C and BHT-101) were evaluated. The treatment of the different ATC cells with ZM447439 inhibited proliferation in a time- and dose-dependent manner, with IC50 comprised between 0.5 mM and 5 mM. Moreover, the drug remarkably impaired the formation of colonies in soft agar of all the cell lines. Consistently with Aurora inhibition, immunofluorescence and immunoblotting experiments demonstrated that Aurora auto-phosphorylation following drug treatment was completely abrogated, and treated cells were characterized by the presence of multiple spindles with short microtubules. In the same experiments we observed the loss of histone H3 phosphorylation on Ser10, specifically due to Aurora-B, after ZM447439 treatment. Time-lapse videomicroscopy and flow cytometric analysis demonstrated that in presence of ZM447439 the cells were able to enter mitosis but not to complete it, becoming polyploid. Almost all the ATC cell lines studied showed increased apoptosis after only 48 h of treatment. In conclusion, our data demonstrate that ZM447439 is effective in reducing cell growth and tumorigenicity of different ATC derived cell lines, and further investigations are needed to exploit its potential therapeutic value for ATC treatment.
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Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa B/antagonistas & inhibidores , Benzamidas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Quinazolinas/farmacología , Neoplasias de la Tiroides/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides/patologíaRESUMEN
Thyroid Paragangliomas are exceptionally rare tumors and only 35 documented cases have been reported in the literature. We report an additional unusual male case of thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma. A 45-year-old man presented with a solitary thyroid nodule. Physical examination revealed a smooth, well-circumscribed, firm, mobile, painless thyroid nodule in the right lobe measuring 3 cm. Ultrasound examination showed a 40 mm hypoechoic, non-homogeneous nodule with peri- and intra-nodular vascular flow. An ultrasound-guided fine needle aspiration biopsy was performed showing the presence of atypical cells (Thy 3). He underwent a total thyroidectomy associated to VI level lymphectomy. Histology showed a thyroid Paraganglioma associated to a chronic lymphocytic thyroiditis and a papillary microcarcinoma measuring 0.3 cm in the greatest dimension. Thyroid Paraganglioma is an elusive tumor. It is difficult to diagnose and should be included in the differential diagnosis of all neuroendocrine tumors of the thyroid, even those arising in men or behaving in a locally aggressive fashion.
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Carcinoma Papilar/patología , Neoplasias Primarias Múltiples/patología , Paraganglioma/patología , Neoplasias de la Tiroides/patología , Biopsia con Aguja Fina , Carcinoma Papilar/complicaciones , Carcinoma Papilar/diagnóstico por imagen , Carcinoma Papilar/cirugía , Diagnóstico Diferencial , Enfermedad de Hashimoto/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Primarias Múltiples/complicaciones , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias Primarias Múltiples/cirugía , Paraganglioma/complicaciones , Paraganglioma/diagnóstico por imagen , Paraganglioma/cirugía , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
Thyroid cancer is not very common, accounting for 1-2% of all cancers, with a population incidence of about 0.004%. Currently, the ability to discriminate between follicular adenoma and carcinoma represents the major challenge in preclinical diagnosis of thyroid proliferative lesions. Better discrimination between the two would help avoid unnecessary thyroidectomy and save valuable resources. Over the years, galectin-3 (Gal-3) has been proposed as a diagnostic marker with varied success. In this paper, we used Environmental Scanning Electron Microscopy Immunogold Labelling (ESEM-IGL) to investigate the expression of Gal-3 on Thin-Prep fine needle aspiration cytology (FNAC). We optimized the ESEM-IGL method on thyroid cell lines (RO-82 and FTC-133) comparing our membrane Gal-3 labeling data with Western blot. We evaluated 183 thyroid FNAC from Italian patients with a uncertain pre-surgical diagnosis. ESEM-IGL method marker sensitivity is 71.2%, while specificity is 53.3% and diagnostic efficacy is 61.2%. Our results confirmed that Gal-3 expression is associated with situations of hypertrophy and/or cellular hyperproliferation, pathophysiological situations common both to adenomas and to thyroid carcinomas. The innovation of thyroid FNAC Thin-Prep ESEM-IGL shows the levels of Gal-3 immunolabeling clearly, even through the individual cells of a thyroid nodule. However, Gal-3 alone, as a molecular marker of thyroid cancer, can still have a limited application in pre-surgery diagnosis.
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Adenoma/diagnóstico , Carcinoma/diagnóstico , Galectina 3/metabolismo , Neoplasias de la Tiroides/diagnóstico , Biopsia con Aguja Fina , Citodiagnóstico , Diagnóstico Diferencial , Regulación Neoplásica de la Expresión Génica , Humanos , Microscopía Electrónica de Rastreo , Glándula Tiroides/citología , Glándula Tiroides/patología , Neoplasias de la Tiroides/patologíaRESUMEN
Fine needle aspiration cytology (FNAC) is the more accurate diagnostic method for cervical lymph node (CLN) metastasis from differentiated thyroid cancers (DTC). However, FNAC diagnosis of cystic CLN is, in most cases, uninformative due to inadequate cellularity. Recently, thyroglobulin (Tg) detection in FNAC needle washout fluid has been shown to improve the diagnostic accuracy of FNAC, and its routine association with cytology is recommended. We here describe the case of a 20 yr old girl complaining of the recent appearance of palpable non-painful laterocervical nodes in the neck. Ultrasound examination revealed the presence of 3 cystic CLNs and 2 mixed thyroid nodules, with the larger one showing irregular margins. On the latter, and on 2 larger CLNs, FNAC was performed, and both Tg protein and mRNA were determined in the needle washout. The cytological analysis was not diagnostic for the two CLNs, while that of the thyroid nodule reported the presence of colloid and groups of thyrocytes with normal morphology. Both CLNs showed, however, high levels of Tg protein and were positive for Tg mRNA, suggestive of metastatic DTC. Based on these findings, the FNAC analysis was performed on the second smaller thyroid nodule suggesting (Tir4) the presence of PTC. The patient was then subjected to total thyroidectomy with lymph nodes resection of the central and homolateral compartments. The histological diagnosis confirmed the presence of a PTC in the small nodule and metastatic lymph nodes. In conclusion, this case confirms that the cytological diagnosis of cystic lymph nodes is challenging, and that the measurement of Tg protein and/or mRNA in the needle washout may overcome this limitation.
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Biopsia con Aguja Fina , Carcinoma Papilar/química , Carcinoma Papilar/diagnóstico , Cuello/patología , Tiroglobulina/análisis , Neoplasias de la Tiroides/química , Neoplasias de la Tiroides/diagnóstico , Adulto , Biomarcadores/análisis , Carcinoma Papilar/secundario , Carcinoma Papilar/cirugía , Femenino , Estudios de Seguimiento , Humanos , Escisión del Ganglio Linfático , Cuello/cirugía , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Neoplasias de la Tiroides/secundario , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Resultado del Tratamiento , Ultrasonografía IntervencionalRESUMEN
The urokinase plasminogen activator (uPA) system (uPAS) comprises the uPA, its cell membrane receptor (uPAR) and two specific inhibitors, the plasminogen activator inhibitor 1 (PAI-1) and 2 (PAI-2). The uPA converts the plasminogen in the serine protease plasmin, involved in a number of physiopathological processes requiring basement membrane (BM) or extracellular matrix (ECM) remodelling, including tumor progression and metastasis. The tumor-promoting role of PAS is not limited to the degradation of ECM and BM required for local diffusion and spread to distant sites of malignant cells, but widens to tumor cell proliferation, adhesion and migration, intravasation, growth at the metastatic site and neoangiogenesis. The relevance of uPAS in cancer progression has been confirmed by several studies which documented an increased expression of uPA, uPAR and PAI-1 in different human malignancies, and a positive correlation between the levels of one or more of them and a poor prognosis. For these reasons, the uPAS components have aroused considerable interest as suitable targets for anticancer therapy, and several pharmacological approaches aimed at inhibiting the uPA and/or uPAR expression or function in preclinical and clinical settings have been described. In the present manuscript, we will first glance at uPAS biological functions in human cancer progression and its clinical significance in terms of prognosis and therapy. We will then review the main findings regarding expression and function of uPAS components in thyroid cancer tissues along with the experimental and clinical evidence suggesting its potential value as molecular prognostic marker and therapeutic target in thyroid cancer patients.
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Neoplasias de la Tiroides/etiología , Activador de Plasminógeno de Tipo Uroquinasa/fisiología , Progresión de la Enfermedad , HumanosRESUMEN
OBJECTIVES: Aim of the study was to identify, in 59 operated patients affected by medullary thyroid carcinoma (MTC), the recurrence rate, survival, mortality and incidences of surgically derived hypoparathyroidism and recurrent laryngeal nerve injury (RLNI). MATERIALS AND METHODS: Based on pre-surgical diagnosis of the 59 patients included in the study, 35 underwent total thyroidectomy with central neck dissection (Group A), 14 total thyroidectomy, central neck dissection and monolateral functional neck dissection (Group B) and 10 total thyroidectomy central neck dissection, bilateral functional neck dissection (Group C). Overall survival, recurrences, incidence of hypoparathyroidism and RLNI were evaluated. RESULTS: The survival and recurrences were not statistically different among the three Groups. In Group B there was major probability of re-operation (p=0.042). The mortality rate was clearly major in Group C (p=0.003) due to the stage of pathology. Group C showed a high number of hypoparatiroidism compared to Group B, and B compared to A. In Group A there was only one unexpected RLNI; in 5 cases, 3 in Group B and 2 in Group C, there were a necessity laringeal section due to nerve tumor involvement. CONCLUSIONS: From our data it appears clearly that disease outcome following the different surgical approaches is mainly determinated by the stage of the disease at diagnosis. However, the finding that patients in Group A and B showed a high rate of local-regional recurrences may suggest that homolateral lymphadenectomy in Group A patients and bilateral lymphadenectomy in Group B patients should be always performed.
Asunto(s)
Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Carcinoma Neuroendocrino , Femenino , Humanos , Masculino , Persona de Mediana Edad , Disección del Cuello , Recurrencia Local de Neoplasia/epidemiología , Tasa de Supervivencia , Neoplasias de la Tiroides/mortalidad , Tiroidectomía/efectos adversosRESUMEN
OBJECTIVES: Anaplastic thyroid carcinomas (ATC) are highly aggressive tumours unresponsive to any available radio- or chemotherapeutic protocol, with a median survival rate of 4-5 months from the time of diagnosis. We previously demonstrated that ATC are characterized by increased expression of the kinases Aurora-A, -B and -C, involved in the regulation of multiple steps of the mitotic phase. In this study, the in vitro effects of SNS-314 mesylate, a pan-inhibitor of the Aurora kinases, on growth and tumorigenicity of ATC cells were evaluated. MATERIALS AND METHODS: The effects of SNS-314 mesylate were assessed on the ATC derived cell lines CAL-62, 8305C, 8505C and BHT-101 by means of cell proliferation assay, immunofluorescence, cytofluorimetry, time lapse microscopy, and colony formation in soft agar. RESULTS: Treatment of the different ATC cells with SNS-314 mesylate inhibited proliferation in a time- and dose-dependent manner, with IC(50) comprised between 2.6 nM and 26.6 nM. CAL-62 cells exposed for 24 h to SNS-314 mesylate 100 nM evidenced a significant augmentation of the apoptotic index. Time-lapse video-microscopy of CAL-62 cells showed that SNS-314 mesylate prevents the completion of mitosis leading to polyploidy. Western blot experiments demonstrated that the auto-phosphorylation of the Aurora kinases as well as histone H3 phosphorylation in CAL-62 treated cells was inhibited. Finally, the drug inhibited colony formation in soft agar of all cell lines. CONCLUSIONS: Our results demonstrated that SNS-314 mesylate is capable to efficiently reduce cell growth and tumorigenicity of different ATC derived cell lines suggesting its potential therapeutic value for ATC treatment.
Asunto(s)
Compuestos de Fenilurea/farmacología , Tiazoles/farmacología , Neoplasias de la Tiroides/patología , Células Tumorales Cultivadas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Mesilatos , Carcinoma Anaplásico de TiroidesRESUMEN
Genetic instability, a hallmark of solid tumors including thyroid cancers, is thought to represent the mean by which premalignant cells acquire novel functional capabilities responsible for cancer cell growth and tumour progression. Over the last few years, the knowledge of the molecular processes controlling the mitotic phase of the cell cycle has increased considerably, and different mitotic proteins, whose expression or function has been found altered in human cancer tissues, have been associated to tumour genetic instability and aneuploidy. These include the three members of the Aurora kinase family (Aurora-A, -B and -C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. The genes encoding the Aurora kinases have been shown to induce cell malignant transformation, and their overexpression has been detected in several tumor derived cell lines and tissues, being often associated with a poor prognosis. Over the last decade, specific inhibitors of Aurora kinases exhibited in preclinical and early phase clinical studies a good therapeutic efficacy against several tumour types, including the highly aggressive anaplastic thyroid cancer and the medullary thyroid cancer. In the present review we'll first focus on the Aurora mitotic functions in normal cells; then we shall describe the main implications of their overexpression in the onset of genetic instability and consequent aneuploidy. We shall finally discuss on the effects of the functional inhibition of Aurora kinases on thyroid cancer cells growth and tumorigenicity.