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Agnieszka Maliszewska,
Luis J Leandro-Garcia,
Esmeralda Castelblanco,
Anna Macià,
Aguirre de Cubas,
Gonzalo Goméz-López,
Lucía Inglada-Pérez,
Cristina Alvarez-Escolá,
Leticia De la Vega,
Rocío Letón, [......],
Salud Borrego,
Mariangela Zane,
Francesca Schiavi, Isabella Merante-Boschin,
Maria R Pelizzo,
David G Pisano,
Giuseppe Opocher,
Xavier Matias-Guiu,
Mario Encinas,
Mercedes Robledo
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ABSTRACT: Medullary thyroid carcinoma accounts for 2% to 5% of thyroid malignancies, of which 75% are sporadic and the remaining 25% are hereditary and related to multiple endocrine neoplasia type 2 syndrome. Despite a genotype-phenotype correlation with specific germline RET mutations, knowledge of pathways specifically associated with each mutation and with non-RET-mutated sporadic MTC remains lacking. Gene expression patterns have provided a tool for identifying molecular events related to specific tumor types and to different clinical features that could help identify novel therapeutic targets. Using transcriptional profiling of 49 frozen MTC specimens classified as RET mutation, we identified PROM1, LOXL2, GFRA1, and DKK4 as related to RET(M918T) and GAL as related to RET(634) mutation. An independent series of 19 frozen and 23 formalin-fixed, paraffin-embedded (FFPE) MTCs was used for validation by RT-qPCR. Two tissue microarrays containing 69 MTCs were available for IHC assays. According to pathway enrichment analysis and gene ontology biological processes, genes associated with the MTC(M918T) group were involved mainly in proliferative, cell adhesion, and general malignant metastatic effects and with Wnt, Notch, NFκB, JAK/Stat, and MAPK signaling pathways. Assays based on silencing of PROM1 by siRNAs performed in the MZ-CRC-1 cell line, harboring RET(M918T), caused an increase in apoptotic nuclei, suggesting that PROM1 is necessary for survival of these cells. This is the first report of PROM1 overexpression among primary tumors.
American Journal Of Pathology 11/2012; · 4.89 Impact Factor
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ABSTRACT: BRAF mutations, the most common genetic alteration associated with papillary thyroid carcinoma (PTC), have never been associated with follicular thyroid carcinoma (FTC) except for one possible case, which, however, had some cellular features of the follicular variant of PTC. Here, we present a patient with a BRAF mutation within a FTC.
A 78-year-old man presented with a nodular lesion 8 cm in size in the right thyroid lobe, coexisting with a goiter. Fine-needle aspiration samples were obtained for cytology, immunocytology, and molecular analysis. Immunoblot analysis on thyroid tissues was performed to evaluate the most important tumor activating pathways. Cytology was consistent with "follicular neoplasia" (negative for galectin-3 immunostaining); molecular analysis on the cytology sample detected a K601E mutation in the exon 15 of the BRAF gene. After total thyroidectomy with lymph-node dissection, the diagnosis of FTC was established by histopathological examination. The BRAF(K601E) mutation was confirmed in DNA obtained from different areas of the FTC. In addition, an activating mutation (E545A) in the PKI3CA oncogene was found in the FTC. As expected, immunoblot analysis showed activation of the PI3K/Akt pathway.
This article describes what may be the first case of a classical FTC carrying a BRAF mutation. Unlike the most common BRAF mutation seen in PTC carcinoma (BRAF(V600E)), this patient's mutation was a BRAF(K601E) mutation that previously has been associated with some cases of the follicular variant of PTC. The BRAF(K601E) mutation should be included in the spectrum of genetic alterations in FTC.
Thyroid: official journal of the American Thyroid Association 12/2011; 21(12):1393-6. · 2.60 Impact Factor
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ABSTRACT: Parathyroid cancer is an uncommon malignant cancer and is associated with a poor prognosis. The staging of parathyroid cancer represents an important issue both at initial diagnosis and after surgery and medical treatment. The role of positron emission tomography/computed tomography (PET/CT) with 18F-Fluorodeoxyglucose (18F-FDG) as an imaging tool in parathyroid cancer is not clearly reported in the literature, although its impact in other cancers is well-defined. The aim of the following illustrative clinical cases is to highlight the impact of PET/CT in the management of different phases of parathyroid cancer. We describe five patients with parathyroid malignant lesions, who underwent FDG PET/CT at initial staging, restaging and post-surgery evaluation. In each patient we report the value of PET/CT comparing its findings with other common imaging modalities (e.g., CT, planar scintigraphy with 99mTc-sestamibi, magnetic resonance imaging) thus determining the complementary benefit of FDG PET/CT in parathyroid carcinoma. We hope to provide an insight into the potential role of PET/CT in assessing the extent of disease and response to treatment which are the general principles used to correctly evaluate disease status.
World journal of clinical oncology. 10/2011; 2(10):348-54.
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Caterina Mian,
Gianmaria Pennelli,
Susi Barollo,
Elisabetta Cavedon,
Davide Nacamulli,
Federica Vianello,
Isabella Negro,
Giulia Pozza, Isabella Merante Boschin,
Maria Rosa Pelizzo,
Massimo Rugge,
Franco Mantero,
Maria Elisa Girelli,
Giuseppe Opocher
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ABSTRACT: Medullary thyroid carcinoma (MTC) derives from the parafollicular C cells, being sporadic in 75% of cases and familial in 25%, due to RET proto-oncogene germinal mutations. In sporadic forms, stage at diagnosis is the most important negative prognostic factor. The aim of this study was to evaluate the prognostic impact of molecular and immunohistochemical markers in sporadic MTC.
We studied 60 patients with sporadic MTC. For each case, we sought RET somatic mutations in the primary cancer and in lymph node metastases. The primary cancer also underwent immunohistochemical examination for Ki-67.
A somatic RET mutation was found in 38% of patients, being M918T in 52% of them. We observed a statistically significant association between RET mutations and male gender (P<0.01), tumor size (P<0.05), lymph nodes (P<0.05) and distant metastases (P<0.001), advanced stage (P<0.05), increased risk of persistent disease (P=0.01), and low overall survival (P<0.01). High Ki-67 levels were similarly associated with extra-thyroid spread (P<0.05), lymph nodes (P<0.05) and distant metastases (P<0.001), advanced stage (P=0.01), and low overall survival (P=0.01). Combining somatic RET analysis with Ki-67 assessment seems to be useful for increasing the specificity of Ki-67 assessment alone and identifying patients with a more aggressive cancer: in our series, only the patients who died during the follow-up had both a somatic RET mutation and a Ki-67 expression level >50 cells/mm(2).
The combined evaluation of RET and Ki-67 could act as an adjuvant prognostic marker useful for ameliorating the initial risk stratification of patients with sporadic MTC.
European Journal of Endocrinology 03/2011; 164(6):971-6. · 3.42 Impact Factor
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Maria Rosa Pelizzo, Isabella Merante Boschin,
Susi Barollo,
Gianmaria Pennelli,
Antonio Toniato,
Laura Zambonin,
Federica Vianello,
Andrea Piotto,
Eric Casal Ide,
Costantino Pagetta,
Nadia Sorgato,
Francesca Torresan,
Maria Elisa Girelli,
Davide Nacamulli,
Franco Mantero,
Caterina Mian
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ABSTRACT: The current preoperative diagnosis of a thyroid mass relies on microscopic evaluation of thyroid cells obtained by fine needle aspiration biopsy (FNAB). More recently, FNAB has been combined with molecular analysis to increase the accuracy of the cytological evaluation. In this mono-institutional prospective study, we evaluated whether the routine introduction of BRAF testing in thyroid FNAB could help ameliorate the preoperative recognition of papillary thyroid carcinoma (PTC) in "suspended" or malignant cytological categories. Moreover, we investigated the prognostic role of the BRAFV600E mutation in PTC.
BRAFV600E analysis was performed in thyroid FNAB from 270 patients classified into one of five cytological categories THY1, THY2, THY3, THY4, THY5. All subsequently underwent thyroidectomy±node dissection, from October 2008 to September 2009 in our Department. For each cytological category, we considered the definitive histological diagnosis of PTC and the presence of the BRAFV600E mutation. In 141 patients with a final tissue diagnosis of PTC, we correlated the presence of BRAFV600E with gender, age, histotype, TNM, size of the lesion, extracapsular extension, node metastases and multifocality.
The prevalence of the BRAFV600E mutation, among PTCs at final tissue diagnosis, was 69%. It improved the FNAB diagnostic accuracy from 88% to 91%. The BRAFV600E mutation was correlated with older age, classical variant of PTC, advanced stages in patients > 45 years.
BRAFV600E testing could play a role in improving the diagnostic accuracy of FNAB for PTC, representing a useful adjuvant tool in presurgical characterization of thyroid nodes in particular cases. There is an association between the BRAFV600E mutation and some clinico-pathological characteristics of PTC.
Clinical Chemistry and Laboratory Medicine 02/2011; 49(2):325-9. · 2.15 Impact Factor
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Susi Barollo,
Gianmaria Pennelli,
Federica Vianello,
Sara Watutantrige Fernando,
Isabella Negro, Isabella Merante Boschin,
Maria Rosa Pelizzo,
Massimo Rugge,
Franco Mantero,
Davide Nacamulli,
Maria Elisa Girelli,
Benedetto Busnardo,
Caterina Mian
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ABSTRACT: BRAF V600E is a potential marker of poor prognosis in papillary thyroid cancers (PTC). In a previous report, we showed that recurrent PTC with no radioiodine ((131)I) uptake are frequently associated with BRAF mutations, a low expression of thyroid-related genes and a high expression of glucose type-1 transporter gene.
The aim of the present study was to assess BRAF status in a large series of recurrent PTC patients, considering paired primary and recurrent cancers. The BRAF genotype was correlated with the ability to concentrate (131)I and/or 2-[(18)F]fluoro-2-deoxi-d-glucose ((18)F-FDG) in the recurrent cancers, serum markers of recurrence, and patient outcome.
We studied 50 PTC patients with recurrent cervical disease submitted to a re-intervention, followed up in median for 9 years. BRAF analysis was conducted by direct sequencing and mutant allele-specific PCR amplification. In 18 cases, molecular analysis was also assessed in the primary cancer. Out of 50 patients, 30 underwent (18)F-FDG-positron emission tomography-computed tomography.
BRAF V600E-positive recurrent patients were found (131)I-negative in 94% of cases (P<0.001); 73% of the cancers carrying BRAF V600E were both (131)I-negative and (18)F-FDG positive. In paired primary and recurrent PTC, BRAF V600E was observed in 79% of the primary cancers and 84% of their recurrences. Three patients with (131)I-negative and BRAF V600E-positive recurrent cancers deceased during follow-up.
BRAF mutations are more common in thyroid recurrences with no (131)I uptake than in (131)I-positive cases. They are correlated with the ability to concentrate (18)F-FDG, and they can appear, albeit rarely, as a de novo event in the course of PTC recurrences.
European Journal of Endocrinology 10/2010; 163(4):659-63. · 3.42 Impact Factor
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ABSTRACT: The purpose of our study was to investigate the efficacy of rapid intraoperative parathyroid hormone (rIO-PTH) analysis performed using material collected by fine needle aspiration as a parameter to distinguish anatomical structures which the surgeon is not able to identify clearly as parathyroid or lymph node during thyroid/parathyroid surgery. Before surgery, all patients gave written, informed consent.
We measured the rIO-PTH on 50 anatomical structures, 32 presumed parathyroids and 18 presumed lymph nodes from 22 patients, who underwent thyroid/parathyroid surgery between May and September 2009.
The rIO-PTH values obtained on parathyroids ranged from 85.4 pmol/L to more than 2106 pmol/L, with a rIO-PTH median of 263.25 pmol/L. Results obtained on lymph nodes ranged from <0.52 pmol/L up to 20.4 pmol/L, with a rIO-PTH median equal to 1.31 pmol/L. Results of the Mann-Whitney test showed a rIO-PTH median significantly different (p<0.0001) between samples obtained from parathyroid glands and lymph node tissue.
We demonstrated that rapid intraoperative measurement of parathyroid hormone is a good parameter for the differential diagnosis of parathyroid vs. lymph node tissue. We suggest extending the use of this technique to the field of parathyroid preservation during thyroid/parathyroid surgery in those cases where the parathyroids prove difficult to recognize on the basis of topographic or morphologic criteria.
Clinical Chemistry and Laboratory Medicine 09/2010; 48(9):1313-7. · 2.15 Impact Factor
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Iñigo Landa,
Sergio Ruiz-Llorente,
Cristina Montero-Conde,
Lucía Inglada-Pérez,
Francesca Schiavi,
Susanna Leskelä,
Guillermo Pita,
Roger Milne,
Javier Maravall,
Ignacio Ramos, [......],
Roberto Castello, Isabella Merante-Boschin,
Maria-Rosa Pelizzo,
Didac Mauricio,
Giuseppe Opocher,
Cristina Rodríguez-Antona,
Anna González-Neira,
Xavier Matías-Guiu,
Pilar Santisteban,
Mercedes Robledo
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ABSTRACT: In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30-1.70; P = 5.9x10(-9)). Functional assays of rs1867277 (NM_004473.3:c.-283G>A) within the FOXE1 5' UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/alphaCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era.
PLoS Genetics 09/2009; 5(9):e1000637. · 8.69 Impact Factor
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ABSTRACT: To compare the clinical outcome of patients with subclinical Cushing syndrome (SCS) due to an adrenal incidentaloma (the autonomous hypersecretion of a small amount of cortisol, which is not enough to cause clinically-evident disease) who underwent surgery or were managed conservatively.
The most appropriate management of SCS patients is controversial, either adrenalectomy or close follow-up being recommended for their treatment.
Over a 15-year period, 45 SCS patients were randomly selected to undergo surgery (n = 23) or conservative management (n = 22). All surgical procedures were laparoscopic adrenalectomies performed by the same surgeon. All patients were followed up (mean, 7.7 years; range, 2-17 years) clinically by 2 experienced endocrinologists 6 and 12 months after surgery and then yearly, or yearly after joining the trial, particularly monitoring diabetes mellitus (DM), arterial hypertension, hyperlipidemia, obesity, and osteoporosis. The study end point was the clinical outcome of SCS patients who underwent adrenalectomy versus those managed conservatively.
All 23 patients in the surgical arm had elective surgery. Another 3 patients randomly assigned to conservative management crossed over to the surgical group due to an increasing adrenal mass >3.5 cm. In the surgical group, DM normalized or improved in 62.5% of patients (5 of 8), hypertension in 67% (12 of 18), hyperlipidemia in 37.5% (3 of 8), and obesity in 50% (3 of 6). No changes in bone parameters were seen after surgery in SCS patients with osteoporosis. On the other hand, some worsening of DM, hypertension, and hyperlipidemia was noted in conservatively-managed patients.
Based on the results of this study, laparoscopic adrenalectomy performed by skilled surgeons appears more beneficial than conservative management for SCS patients complying with our selection criteria. This trial is registered with Australian Clinical Trials Registry number, ANZCTR12608000567325.
Annals of surgery 03/2009; 249(3):388-91. · 7.90 Impact Factor
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ABSTRACT: The spontaneous rupture of a parathyroid adenoma accompanied by extracapsular hemorrhage is a rare, potentially fatal, condition and is a cervicomediastinal surgical emergency.
This report describes an atypical two-step spontaneous rupture of an asymptomatic parathyroid adenoma in a 56-year-old Caucasian woman who presented with a painful mass in the right side of her neck.
Based on this case report and similar cases reported in the medical literature, a diagnosis of extracapsular parathyroid hemorrhage should be considered when a non-traumatic sudden neck swelling coexists with hypercalcemia and regional ecchymosis.
Journal of Medical Case Reports 01/2009; 3:7404.
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ABSTRACT: Activating mutations of the BRAF oncogene are frequently detected in papillary thyroid carcinoma (PTC) and have been associated with a worse prognosis. The amino acid substitution V600E accounts for 90% of all oncogenic BRAF mutations and is typically detected in classic PTCs, whereas other less frequent BRAF mutations seem to be associated with other PTC histotypes.
Screening for activating BRAF mutations in a series of 83 PTCs identified the most common V600E mutation in 39 cases (histologically, 38 classic PTCs and 1 sclerosing variant PTC) and a complex in-frame mutation involving amino acids V600-S605 in a stage III multicentric follicular variant PTC, occurring in a 50-year-old female patient, who was affected by hypothyroidism in autoimmune thyroiditis and had a family history of PTC and autoimmune thyroiditis. Since the identified BRAF mutation was novel in the literature, bioinformatic modeling was performed to predict its impact on BRAF activity. Although the mutation resulted in loss of a phosphorylation site in the activation loop of BRAF, it was predicted to increase BRAF kinase activity by mimicking an activating phosphorylation.
This study, which reports a new BRAF mutation, highlights the usefulness of bioinformatic modeling in the prediction of functional effects of new mutations and indicates that mutation-specific screening tests might miss some rare BRAF mutations. These facts should be taken into consideration in the molecular diagnosis of thyroid cancer and in the design of therapeutic protocols based on inhibitors of the BRAF pathway.
European Journal of Endocrinology 08/2008; 159(1):77-80. · 3.42 Impact Factor
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ABSTRACT: The aim of this prospective study was to identify patients at high risk of developing hypocalcemia after thyroidectomy on the basis of the parathyroid hormone (PTH) level on the first postoperative day.
We included 160 patients undergoing total thyroidectomy in a period of 6 months by the same surgical team in this study. In all patients the PTH level was measured before surgery on the day of surgery (PTH1), and on the first postoperative day (PTH2), whereas serum calcium level was measured daily until discharge. Patients were classified as hypocalcemic if they had a serum calcium level less than the normal range on the first postoperative day, independently of symptoms of hypocalcemia.
At an average follow-up period of 5.9 months (range, 4-9 mo), 66 patients were considered hypocalcemic, 57 patients (35.6%) had a transient hypocalcemia, and 9 patients (5.6%) required calcium-vitamin D supplementation for persistent hypocalcemia. The mean PTH1 value was 54.4 +/- 17.2 pg/mL (median, 53.85 pg/mL), the mean PTH2 value was 22.8 +/- 13.3 pg/mL (median, 21 pg/mL). The mean PTH decrease in value was 51.54% +/- 27.4% (median, 51.83%; range, 4%-94%) and 43.7% of patients presented a PTH decrease of more than 50%. The presence of a postoperative hypocalcemia was statistical correlated both with the PTH2 level and with the PTH drop percent value (P < .001 and P = .002, respectively). With the use of the receiver operating characteristic curve, the maximum sum of the sensitivity and specificity for the correlation of PTH2 levels and hypocalcemia occurred at a PTH2 level of 9.6 pg/mL.
The PTH measurement on the first postoperative day may be considered a useful method to predict postthyroidectomy hypocalcemia, thus avoiding prolonged hospitalization. Moreover, PTH dosage at first postoperative day is more reliable and less expensive than intraoperative quick PTH assay.
American journal of surgery 08/2008; 196(2):285-8. · 2.36 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the factors influencing morbidity after total thyroidectomy for carcinoma, such as the histotype, the extension of surgery, the primary surgery versus reoperation, and the surgeon's experience.
We performed a retrospective analysis on inferior laryngeal nerve (ILN) injury and permanent hypoparathyroidism (HPT) rates in 504 consecutive patients with thyroid carcinoma who were operated on by the same surgeon from 1999 to 2006. The following parameters were assessed at univariate analysis: histotype, total thyroidectomy with or without central node dissection (level VI), primary surgery versus reoperation, and early (group 1: 1999-2002, 143 patients) and late (group 2: 2003-2006, 361 patients) experience.
The global incidence rates of ILN palsy and permanent HPT were 2.18% and 6.3%, respectively. The incidence of ILN damage after total thyroidectomy plus node dissection versus total thyroidectomy without node excision was 2.87% vs. 0.36% (p = 0.029). The incidence of permanent HPT in group 1 was 13.2% vs. 3.6% in group 2 (p = 0.0001). Moreover, the incidence rate of ILN palsy resulted higher in group 1 (2.8%) and in reoperation (3.4%), while the permanent HPT resulted higher in thyroidectomy with node dissection (6.8%) and reoperation (6.9%), although the difference was not significant.
The complications after total thyroidectomy were progressively reduced as a result of a more accurate technique. Nevertheless, our study showed that the incidence of complications is mostly related to the dissection of central lymph node (level VI) and the surgeon's experience.
World Journal of Surgery 05/2008; 32(4):572-5. · 2.36 Impact Factor
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American journal of surgery 03/2008; 195(2):277. · 2.36 Impact Factor
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ABSTRACT: Papillary thyroid carcinoma (PTC) is universally regarded as a curable malignancy with a favorable prognosis. However, a minority of patients may present, or subsequently develop, locoregional and distant metastases that may adversely affect survival. The value of the various staging methods is complicated by different approaches to diagnostic, therapeutic and follow-up strategies. We aimed at assessing the prognostic factors and survival rate in a large cohort of patients treated and followed up in the same center.
A total of 1858 patients with PTC operated on by the same surgeon, and followed in the same center over a period of 35 years, were included. Total thyroidectomy was performed in the majority of patients after I-131 diagnostic scans and thyroglobulin assays. When the latter 2 were positive, therapy with I-131 was given. Follow-up was performed periodically and further therapy doses were administered when necessary. All patients were maintained on life-long thyroxine.
Ninety-three patients (5%) developed evidence of locoregional or distant metastases after an average follow-up period of 7.9 years (range 1.53-30.5 years). Univariate analysis showed all variables (except for gender) to be significantly correlated with disease recurrence and survival. Multivariate analysis showed 4 variables to be significant and independent prognostic factors: patient age at first treatment, extent of disease, extent of surgery, and the presence of I-131 positive metastases.
Our data agree with other scoring systems in that patient age at first treatment and the extent of disease are significant and independent prognostic factors. However, and at variance with other methods, we found that the extent of primary surgery and the presence of I-131 positive or negative metastases have similar prognostic significance. In high risk patients, total thyroidectomy and lymphadenectomy followed by I-131 treatment and TSH-suppressive hormonal therapy are recommended.
Clinical Nuclear Medicine 07/2007; 32(6):440-4. · 3.67 Impact Factor
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ABSTRACT: It is a matter of controversy whether prophylactic lymph node dissection improves prognosis and survival in papillary thyroid carcinoma (PTC) patients without suspicion of lymph node metastases either clinically or on ultrasonography. It is possible that in such patients the use of lymphatic mapping and sentinel lymph node (SLN) biopsy, as are employed for other tumours, will be of assistance. The aim of this study was to evaluate the feasibility of preoperative 99mTc-nanocolloid lymphoscintigraphy and an intra-operative SLN procedure in the management of PTC patients.
Twenty-five consecutive patients were entered in the study between April 2005 and October 2005. All had a preoperative diagnosis of malignancy obtained by fine-needle aspiration cytology (FNAC), without clinical or ultrasonographic evidence of loco-regional lymph node involvement. Patients underwent preoperative lymphoscintigraphy after the injection of 99mTc-nanocolloid [median 6 MBq (range 4-9 MBq) in 0.1-0.2 ml saline injected intratumorally under ultrasound guidance] and an intra-operative SLN procedure using a hand-held gamma probe. Surgery was performed by the same surgeon in all patients.
Preoperative lymphoscintigraphy identified at least one SLN in all patients. During surgery, using the gamma probe, the surgeon was able to find at least one SLN in all cases. A good correlation was found between preoperative imaging and probe results. Metastasis was found in at least one SLN in 12 (48%) patients. In seven (28%) patients the involved SLN was the most radioactive SLN, while in five (20%) patients a less radioactive SLN was involved by malignancy. Ten of these 12 patients had only micrometastases (<2 mm). Micrometastases were found in the most radioactive SLN in six cases and in less radioactive SLNs in four cases, while in two patients more lymph nodes visualised at lymphoscintigraphy ipsilateral to the primary tumour were sites of metastasis.
The rate of nodal involvement was very high in our series: in 48% of patients at least one metastatic lymph node was found. From a technical point of view the intra-operative SLN procedure in PTC patients was easy to perform, without major intra-operative complications. Our promising preliminary experience needs to be confirmed in larger series of patients series with longer follow-up.
European journal of nuclear medicine and molecular imaging 07/2007; 34(6):934-8. · 4.99 Impact Factor
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ABSTRACT: Laparoscopic adrenalectomy has become the gold standard for removing adrenal masses, but several authors still debate the role of laparoscopic adrenalectomy in pheochromocytoma. The purpose of this study was to evaluate the short- and long-term outcomes of laparoscopic versus open adrenalectomy for pheochromocytomas and to compare the feasibility and safety of laparoscopic adrenalectomy for neoplasms that are smaller than 6 cm versus those that are larger than 6 cm.
From January 1990 to December 2005, the same team in our department carried out 221 adrenalectomies in 211 patients. A total of 64 of these patients underwent 71 adrenalectomies for pheochromocytoma, 24 patients (37%) had open adrenalectomy, and 40 patients (63%) had laparoscopic adrenalectomy. Sex, age, side and size of lesion, operating time, duration of hospital stay, need for intensive care, intraoperative blood pressure variations, blood loss, postoperative analgesia, return to oral nutrition, and complications were compared among groups.
An advantage of laparoscopic adrenalectomy over open adrenalectomy was observed in mean operating time, hospital stay, need for intensive care, intraoperative hypertension, intraoperative blood loss, postoperative analgesia, and return to oral nutrition (P <or= .035 in all). The analysis of tumor size (<or=6 vs >6 cm) in laparoscopic adrenalectomy showed that none of the variables differed significantly, except for intraoperative blood loss, which was greater for the larger neoplasms (P = .007).
Laparoscopic adrenalectomy, when performed by experienced laparoscopic surgeons, is preferable to open adrenalectomy for the majority of pheochromocytomas, and as long as there is no evidence of invasion of surrounding structures, tumor size does not appear to have a profound effect on surgical outcome.
Surgery 06/2007; 141(6):723-7. · 3.10 Impact Factor
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Surgery 10/2006; 140(3):482-3; author reply 483. · 3.10 Impact Factor
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Giuseppe Opocher,
Francesca Schiavi,
Maurizio Iacobone,
Antonio Toniato,
Sabina Sattarova,
Zoran Erlic,
Maddalena Martella,
Caterina Mian, Isabella Merante Boschin,
Laura Zambonin,
Paola De Lazzari,
Alessandra Murgia,
Maria Rosa Pelizzo,
Gennaro Favia,
Franco Mantero
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ABSTRACT: Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2+43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.
Annals of the New York Academy of Sciences 09/2006; 1073:149-55. · 3.15 Impact Factor
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Maria Rosa Pelizzo,
Antonio Toniato, Isabella Merante Boschin,
Andrea Piotto,
Paolo Bernante,
Costantino Pagetta,
Margherita Palazzi,
Anna Maria Guolo,
Paolo Preo,
Otello Nibale,
Domenico Rubello
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ABSTRACT: Debate exists in the literature about the optimal treatment to be adopted in patients with locally advanced differentiated thyroid carcinoma. We aimed to better define the most appropriate diagnostic and therapeutic protocol for this type of tumour.
The clinical and histopathological records of 280 consecutive patients with locally advanced differentiated thyroid carcinoma, studied and operated on by the same surgical team in the period between 1967 and 2002, were reviewed.
With regard to overall survival, at univariate statistical analysis, the patient's age at diagnosis (threshold, 45 years), primary tumour size, local cancer extension at diagnosis (subtypes of T4), extent of thyroidectomy, performance of lymph node dissection and performance of post-surgical external radiotherapy were found to be significant prognostic variables. With regard to the appearance of recurrent disease during follow-up, at univariate statistical analysis, the patient's age at initial diagnosis (threshold, 45 years), primary tumour size, local cancer extension at diagnosis (subtypes of T4), extent of thyroidectomy, performance of lymph node dissection, presence of metastatic lymph nodes, performance of post-surgical 131I therapy and performance of post-surgical external radiotherapy were found to be significant prognostic variables. At multivariate statistical analysis, the patient's age at initial diagnosis, extent of tumour, extent of thyroidectomy and performance of lymph node dissection were the only independent prognostic variables.
In our experience, an aggressive surgical approach at first diagnosis appears to offer a better prognosis in terms of both overall survival and disease-free time interval in patients with locally advanced differentiated thyroid carcinoma, especially those over 45 years of age.
Nuclear Medicine Communications 12/2005; 26(11):965-8. · 1.40 Impact Factor
