LH, progesterone, and TSH can stimulate aldosterone in vitro: a study on normal adrenal cortex and aldosterone producing adenoma.

Endocrine factors different from ACTH or angiotensin II can stimulate aldosterone secretion and have a role in the pathophysiology of hyperaldosteronism. Aldosterone may increase in luteotropic/progestogenic and in hypothyroid states; LH and, occasionally, TSH receptors have been detected in normal adrenal cortex and aldosterone-producing adenoma. The aim of the study was to compare adrenal contents of LH and TSH receptors between normal cortex and aldosterone-producing adenoma and to evaluate the ability of LH, its product progesterone, and TSH to stimulate aldosterone secretion in vitro from primary adrenocortical cells. Surgical aldosterone-producing adenoma fragments from 19 patients and adrenal cortex fragments from 10 kidney donors were used for Western blotting and cell cultures. LH (n=26), TSH (n=19) and progesterone (n=8) receptor proteins were investigated; LH receptor-mRNA was also tested in 8 samples. Aldosterone responses in vitro to LH, progesterone, and TSH stimulation were assayed. LH and TSH receptors were more expressed in adenoma than normal cortex (p<0.01, p<0.05, respectively); progesterone receptor was observed in 6/8 samples. Aldosterone increased after in vitro stimulation with LH (5/12 adenoma, 1/7 normal cells), progesterone (4/5 adenoma, 5/6 normal cells), and TSH (3/5 adenoma and 3/5 normal cells). LH and TSH receptors were more expressed in aldosterone producing adenoma than normal adrenal cortex. LH, progesterone, and TSH can stimulate aldosterone in vitro. Similar mechanisms could participate in vivo in the aldosterone increase in lutheotropic, progestogenic, or hypothyroid states and may exist in both normal adrenal cortex and adenoma in responsive individuals.

Cervical sympathetic chain schwannoma: a case report.

Nerve sheath tumours arising from the sympathetic chain are extremely rare and are a diagnostic challenge. We report the case of a 31- year-old man who presented with an asymptomatic right cervical swelling. He was evaluated with sonography, CT, MR and angiography. Surgical excision of the lesion was performed, and histological examination revealed a schwannoma. The differential diagnosis of such tumours and their management are discussed.

Genetic markers to discriminate benign and malignant thyroid nodules with undetermined cytology in an area of borderline iodine deficiency.

BACKGROUND: Fine needle aspiration (FNA) with cytologic evaluation is the most reliable tool for malignancy prediction in thyroid nodules, but cytologic diagnosis remains undetermined for 20% of nodules. AIM: We investigated the diagnostic potential of a set of 6 marker genes to distinguish benign and malignant thyroid nodules. SUBJECTS AND METHODS: The prospective study included 153 thyroid samples obtained by FNA of thyroid nodules from 151 patients (56 benign, 43 malignant, and 54 nodules with undetermined cytology). Gene expression was evaluated by quantitative realtime PCR and statistical analysis of data was performed. All samples were analyzed for V600E BRAF mutation. RESULTS: A decrease in TTF3 and HGD1 expression was observed in malignant nodules with respect to benign ones, while an increase in PLAB expression was demonstrated in these nodules. The decision model was valid for 88 of 99 cases of benign and malignant nodules, with a total of 11 false positive or negative predictions. The obtained malignant/benign phenotype prediction was also valid for 37 of 54 cases of nodules with undetermined cytology with a total of 8 false positive and 9 false negative predictions. V600E BRAF gene mutation was demonstrated in 19/43 malignant nodules, in 0/56 benign nodules, and in 1/54 undetermined nodules. CONCLUSIONS: The expression profiles of genes (TFF3, HGD1, and PLAB) allowed a good prediction for the differentiation of benign thyroid lesions and thyroid cancer starting from cells of FNA; however, this assay showed limitations when applied to discriminate thyroid nodules with undetermined cytology.

Neck lesions mimicking thyroid pathology.

INTRODUCTION: Nodular lesions within the neck may origin from several structures. A misdiagnosed origin may expose the surgeon to inappropriate procedures. These lesions are paradoxically frequent in high specialised centre for endocrine surgery. PATIENTS AND METHODS: In the year 2006, three patients were first admitted to our department with a diagnosis of thyroid nodule (1) or lymphatic metastases of thyroid carcinoma (2). The first patient had ultrasound (US) and Tc-99-m scan orienting for thyroid nodule. The two other patients, presented with lateral neck lesion in ipsilateral sincronous and previous diagnosis of papillary thyroid carcinoma, respectively, with US and computed tomography scan confirmed lesion but with a FNA cytology negative for tumoural cells. RESULTS: All three patients underwent surgical exploration. In the first two cases, a whitish tender nodule (4 and 4.5cm), cleavable from surrounding structures, was removed with final histology of Schwannoma and Paraganglioma, respectively. Both patients experienced Bernard Horner Syndrome. In the last patients, a firm grey nodule of 5cm strictly adherent to muscular planes was removed with diagnosis of Castleman's Disease. CONCLUSIONS: Nodular neck lesions mimicking a thyroid pathology (thyroid nodules or metastatic lymph nodes) are rare but can represent a tough challenge for surgeons who might fall into incorrect surgical approaches, resulting in high morbidity. Pre-operative work-up would help the surgeon to obtain the correct diagnosis, thus, to follow the better surgical approach. Nevertheless, a careful approach would be used for that neurogenic tumour amenable of resection without jeopardising nervous structures.

Unexpected histological findings of lesions diagnosed in the adrenal region in a series of 420 patients submitted to adrenal surgery. Review of our experience.

INTRODUCTION: The incidence of adrenal incidentalomas is reported to be up to 30% in the current literature; nevertheless, in some patients undergoing surgery, a final diagnosis of non-adrenal origin of the mass is performed. In this paper we present our experience of 13 patients with unexpected histological findings of lesions diagnosed in the adrenal region. PATIENTS AND METHODS: From June 1986 to December 2004, 420 patients underwent adrenalectomy in our Department. Since the introduction of videolaparoscopic technique in 1993, 228 adrenalectomies have been performed videolaparoscopically. Pre-operative diagnosis was: incidentaloma (34.0% of patients), Conn's adenoma (29.0%), Cushing's adenoma (13.9%), pheochromocytoma (8.8%), suspicious metastasis (7.3%), Cushing's disease (6.0%), other (1.0%). RESULTS: Final histology revealed an unexpected diagnosis of non-adrenal origin of the mass in 13 patients (3.1%). Histology demonstrated a benign neurogenic tumor in 10 patients. In the other 3 patients diagnosis was respectively of lymphnode, hemangioma and a gastric metastasis of melanoma. Five patients out of 7 had a successful laparoscopic resection of the lesion. Mean operative time in this group was higher compared to laparoscopic resection for adrenal lesion (95.3 min vs 73.2 min). CONCLUSION: A small percentage of our patients (3.1%) demonstrated unexpected findings of the lesion pre-operatively misinterpreted as an adrenal mass. Despite a complete pre-operative assessment, adrenal lesions might reveal a different origin, increasing the surgical challenge as well as the morbidity for the patient.

Proteomic analysis of human thyroid fine needle aspiration fluid.

The aim of this study was to determine the protein pattern of human thyroid fine needle aspiration fluid (FNA) using a proteomic approach. FNA proteins were separated using 2-dimensional gel electrophoresis (2DE), digested and then analyzed by peptide mass fingerprinting. For the first time, we provided an image of the protein components of the FNA, in which approximately 220 protein spots can be identified. The proteome analysis revealed a specific fingerprint of FNA with proteins appertaining to various functional systems. Our preliminary results of FNA protein pattern could be a starting point in studying the presence of potential markers implicated in thyroid diseases.

Vagal paragangliomas: two case reports.

Two uncommon cases of paragangliomas arising from the vagus nerve are described. The first patient underwent surgery for suspected carotid body tumour. In the second patient, computed tomography scan and digital angiography allowed a correct pre-operative diagnosis to be made. These cases confirm the prevalence of vagal paragangliomas in female sex and middle age, and the possibility of multiple similar tumours in the same patient. Histological benign features, absence of neurological symptoms, of local invasion or intracranial extension confirm the frequent benign behaviour of these neoplasms. Lack of catecholamine secretion confirms the low incidence of functioning tumours. Contrast computed tomography and digital angiography still remain the gold standard reliable instruments for diagnosis despite the success of magnetic resonance imaging, magnetic resonance angiography and octreotide scintigraphy to detect head and neck paragangliomas. A transcervical approach, without mandibulotomy, is suitable too for large tumours but complete removal, with sparing of involved segments of the vagus nerve, is rarely possible. Post-operative neurological morbidity is still an unsolved issue and, therefore, rehabilitation of deglutition and phonation is an integral part of management.

Role of frozen section associated with intraoperative cytology in comparison to FNA and FS alone in the management of thyroid nodules.

AIMS: The utilization of fine needle aspiration (FNA) biopsy is an accurate and cost-effective method in the diagnosis of thyroid diseases. However, the non-diagnostic cases and cases of suspicious carcinoma remain a dilemma, and in these cases thyroidectomy is usually recommended, even if only 15-20% of these patients really need a thyroidectomy. To avoid unnecessary surgical treatment, frozen section (FS) is usually performed. This method is well recognized, but is not useful for the diagnosis of follicular lesions. Therefore, many authors have tried to increase the specificity and sensibility of intraoperative examination, supporting it with an intraoperative cytological technique (IC). To clarify the role of intraoperative exam (FS and IC), also comparing to FNA, we have reviewed our own experiences. METHODS: In a period covering 6 years (2000-2005), FS was performed in 1,472 cases out of 11,420 total thyroidectomy operations. FS diagnosis and definitive diagnosis, were reviewed and confirmed, moreover, FNA diagnosis and definitive diagnosis were also considered and all intraoperatory cytological slides were reviewed. Diagnostic accuracy was assessed for FNA and FS with or without intraoperative cytology. We compared 1,472 FS diagnoses with their definitive histological diagnosis; 728 FNA out of 1,472 patients with definitive histological diagnosis, and 564 FS associated with IC out of 1,472 patients with definitive diagnosis. RESULTS: The diagnostic accuracy of these three methods were, respectively, 88.8%, 88.8% and 95.7%. CONCLUSION: We can assert that FS associated with IC remains the most accurate technique in the surgical management of thyroid nodules.

Radiation damage induced by krypton ions in sintered alpha-Al2O3.

Alpha-alumina is a useful thermoluminescence (TL) dosemeter. The knowledge of its behaviour under irradiation is thus of primary importance. The purpose of this paper is to characterise the radiation damage produced by swift krypton ions using various experimental methods, namely TL, optical absorption, fluorescence and electron paramagnetic resonance (EPR). After ion irradiation, the TL intensity is shown to decrease, whereas the optical absorption rises in the whole studied wavelength range. These two phenomena seem to be related to one another. Furthermore, optical absorption measurements highlight the appearance of new absorption bands probably owing to oxygen vacancies. Induced defects are also observed in the EPR spectra of irradiated pellets. They are likely related to electronic holes trapped on oxygen ions. The concentration of these defects increases with ion fluence and fluorescence measurements indicate that some pre-existing defects such as F2(2+) centres follow the same trend up to approximately 4.1 x 10(13) ions cm(-2).

Thermoluminescence properties of CVD diamond for clinical dosimetry use.

The application of diamond to dosimetry is desirable because of its tissue equivalence, chemical inertness and small size, but this has not been commercially viable owing to the non-reproducible response of natural diamond. The chemical vapour deposition (CVD) of diamond permits controlled, reproducible and large-scale production of this material at potentially low cost. An investigation of some clinically relevant features like the depth-dose distribution as well as the absorbed dose profile, obtained using thermoluminescence (TL), is reported for several CVD diamond films. The TL characterisation presented here shows that CVD diamond films should be excellent TL-mode detectors in instances of radiotherapy and in vivo radiation dosimetry.

Peripheral type benzodiazepine receptor in human parathyroid glands: up-regulation in adenoma.

In this study we report the presence of peripheral benzodiazepine receptors (PBRs) in human parathyroid glands and describe the effect of their benzodiazepine type ligands on parathyroid cell function. PBR binding features in normal parathyroid tissue were characterized and compared to parathyroid adenoma, using a specific and selective ligand for PBR, [3H] 1-(2-chlorophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline-carboxamide ([3H]PK11195). Affinity and density of [3H]PK11195 binding sites in homogenate membrane preparations from adenomatous and normal tissues were determined. Parathyroid adenoma showed a statistically significant 2.2 fold increase of [3H]PK11195 binding sites, while the affinity remained unchanged. Our results represent the first evidence of PBRs in parathyroid glands and suggest for them a role in influencing PTH release. A clear trend of PBR up-regulation in parathyroid adenoma was also found.

Angiogenesis in human normal and pathologic adrenal cortex.

The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 +/- 27.8) than in N (336.6 +/- 14.5), APA (322.8 +/- 19.1), CPA (288.5 +/- 14.3), and NFA (274.2 +/- 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 +/- 2.1) than in APA (56.5 +/- 7.5), CPA (38.5 +/- 7.0), N (33.1 +/- 6.1), and NFA (0.76 +/- 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found. In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.

Characterisation of thermoluminescent LiF:Mg,Ti (MTS-N) detectors in the 85-550 K temperature range.

Miniature LiF:Mg,Ti (MTS-N) pellets, specially designed for dosimetry in proton radiotherapy, were studied in the 85-550 K temperature range. TL glow curves for differently Mg- or Ti-doped detectors were recorded, showing the preponderant influence of Mg concentration on the intensity of peak 5. The presence of a three-peak complex was also confirmed near 140 K; spectral emission of this peak consists of two bands whose maxima occur at 290 and 420 nm. TSEE glow curves above 300 K similar to those of TL were observed. The behaviour of TSEE and TL peak 5 following an X ray exposure from 33 to 500 Gy was studied: its intensity is a linear function of air kerma in both cases.

Thermoluminescent properties of Ni and Co doped synthetic, high pressure, high temperature diamonds: application to ionising radiation dosimetry.

An investigation of the thermoluminescence (TL) properties of high pressure, high temperature (HPHT) synthetic diamond crystals grown under diluted nickel or cobalt as solvent catalysts is reported. After a study of TL properties of 6 different samples, it is shown that a crystal grown with Ni+2%Ti and annealed at 2100 K presents an intense glow peak at around 490 K. This peak is characterised by a broad emission band centred at 530 nm (2.34 eV). This crystal presents a significant, reproducible and linear TL response relative to the absorbed dose up to an X ray air kerma of 10 Gy. All these features make this material suitable for ionising radiation dosimetry. A similar study is made on another crystal grown from pure Co, and a comparative review of the results does show that for dosimetry work, Ni-containing diamonds are more appropriate than those grown from Co catalyst.

Apoptosis control and proliferation marker in human normal and neoplastic adrenocortical tissues.

We evaluated by immunohistochemistry the expression of the Bcl-2 and p53 proteins, as markers of apoptosis control, and of MIB-1, as a marker of cell proliferation, in a series of normal and neoplastic adrenocortical tissues. The specimens were 13 normal adrenals, 13 aldosterone-producing adenomas, 13 non-functioning adenomas and 16 carcinomas. Results were calculated as percentage of immunostained cells by using specific antibodies. No p53 protein was detected in any of the adrenocortical adenomas (functioning and non functioning) or normal adrenals, while p53 was overexpressed in 15 out of 16 carcinomas. In particular, 10 adrenal cancer specimens (62.5%) showed strong staining in a high percentage (range 10-50%) of the malignant cells. The percentage of Bcl-2 positive cells was higher (P<0.05 or less) in non-functioning adenomas (8.1+/-1.9%) and in carcinomas (14.9+/-5.6%) than in normals (2.9+/-0.9%) and aldosterone-producing adenomas (5.3+/-1.3%) since four specimens of the non-functioning adenomas-group (30.7%) and six of the carcinomas-group (37.5%) showed over 10% positivity (cut-off for normal values, set at 90th percentile of our controls). MIB-1 positivity was 0.50+/-0.36% in normals, 0.54+/-0.08% in non-functioning adenomas and 0.54+/-0.08% in aldosterone-producing adenomas. MIB-1 was expressed in all carcinomas with values (13.7+/-3.1%) significantly (P<0.0006) higher than in the other groups. In conclusion, the present data indicate that the apoptosis control and proliferation activity evaluated by the p53 and MIB-1 proteins are impaired in adrenal carcinomas but preserved in adenomas, independently of their functional status. Therefore, these immunohistochemical markers, overexpressed in carcinomas only, may be useful in the diagnosis of malignancy in adrenocortical tumours. Whether Bcl-2 positivity found in some carcinomas and non-functioning adenomas may constitute, in the latter, a negative prognostic marker is still unknown.

Complete salvage surgical cytoreduction improves further survival of patients with late recurrent ovarian cancer.

OBJECTIVE: The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with late recurrent ovarian cancer. METHODS: Thirty patients with recurrent ovarian cancer who underwent salvage surgical cytoreduction were retrospectively reviewed. All had been initially treated by primary surgery and platinum-based chemotherapy and had a period of clinical remission of at least 6 months. Median time to recurrence was 17.5 months (range, 6-76 months). RESULTS: A macroscopically complete salvage cytoreduction was obtained in 17 (56.7%) patients, whereas 8 patients were left with macroscopic residual disease <2 cm and 5 patients with a larger residuum. Logistic regression showed that the probability of achieving a complete cytoreduction was significantly related to the residual disease after initial surgery (<2 cm versus >2 cm, P = 0.0027, odds ratio = 36.000, 95% confidence interval = 3. 473-373.176), but not to FIGO stage, tumor grade, histologic type, patient age at recurrence, and time to recurrence. In the whole series median survival following salvage surgery was 21 months. Survival was significantly longer in patients who were completely cytoreduced compared to those who were not (median: 37 months versus 19 months, P = 0.04). Moreover, survival was significantly related to time to recurrence (>17.5 months versus <17.5 months, median: 25 months versus 15 months, P = 0.039), number of recurrence sites (single versus multiple, median: 40 months versus 19 months, P = 0. 009), and residual disease after initial surgery (<2 cm versus >2 cm, median: 37 months versus 19 months, P = 0.01), but not to patient age, recurrence site with the largest size, FIGO stage, tumor grade, and histologic type. CONCLUSIONS: The present data seem to show that complete salvage surgical cytoreduction significantly improves further survival of ovarian cancer patients who recur at least 6 months after the completion of primary therapy.

Use of surgical gamma probe for the detection of lymph node metastases in differentiated thyroid cancer.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) after total or near-total thyroidectomy require 131I therapy. After surgery the persistence of lymph node metastases in our series of patients was frequent (30%). Such patients are preferentially treated with radioiodine and shifted to surgical reintervention when the nodal lesions persist after two 131I treatments. AIM: Use of an intraoperative radioactive probe (C-TraK) to allow a more radical surgical approach in thyroid cancer patients submitted to surgery for lymph node metastases. METHODS AND RESULTS: After adequate withdrawal of L-thyroxine suppressive therapy six patients were given high 131I doses followed by post-therapy WBS which demonstrated cervical activity in 5 patients and peri-jugular activity in 1. Surgery with the help of a gamma probe allowed to detect and remove all metastatic nodes. After excision all surgical specimens showed higher radioactive counts with respect to the background. The post-surgical scan showed the disappearance of all areas of 131I uptake. Histology confirmed the presence of metastatic lesions from papillary thyroid cancer. CONCLUSIONS: We conclude that the use of a gamma probe can be successful in patients with metastatic neck lesions resistant to 131I treatment, particularly in patients with nonpalpable lesions.

Cyclin D1 overexpression in thyroid carcinomas: relation with clinico-pathological parameters, retinoblastoma gene product, and Ki67 labeling index.

Cyclin D1 is a G1 cyclin participating in the control of cell cycle progression through interaction with the retinoblastoma gene product (pRB). The overexpression of positive regulators (such as cyclin D1) has been reported in a variety of neoplasms, but their role in thyroid tumorigenesis is yet to be established. In our series of 54 thyroid carcinomas, cyclin D1 overexpression (detected by both immunohistochemistry and by Northern blotting) was correlated with prognostic variables, proliferative activity and pRB. Cyclin D1 overexpression was observed in 35% of thyroid carcinomas with a significantly higher expression of this cyclin in neoplastic tissues than in matched normal parenchyma. In well-differentiated carcinomas, the cyclin D1 mRNA overexpression was inversely correlated with nodal status (p = 0.03), while the protein product was higher in tumors from patients less than 40 than patients over 40 years of age. Inversely, there was no significant correlation with gender and tumor status, pRB and with proliferative activity.

Surgical cytoreduction during second-look laparotomy in patients with advanced ovarian cancer.

BACKGROUND: The impact of surgical cytoreduction performed during second-look on the survival of patients with advanced ovarian cancer is still under debate. MATERIALS AND METHODS: The present retrospective investigation assessed 81 patients with advanced ovarian cancer who underwent second-look laparotomy after initial cytoreductive surgery and six cycles of platinum-based chemotherapy. RESULTS: At the beginning of the second-look, 31 patients were in pathological complete response, 7 had microscopic residual disease, 22 had macroscopic residual disease < 2 cm and 21 had a larger residuum. Twenty-two (51.2%) of the 43 patients with macroscopic disease underwent surgical cytoreduction during the second-look: 11 patients were completely cytoreduced, whereas 11 were debulked from residuum > 2 cm to macroscopic residuum < 2 cm. Patients with microscopic residual disease after the second-look had improved survival when compared to those with macroscopic residuum after re-exploration (median survival, 43 months versus 19.5 months, p = 0.002). Among the former, no difference in survival was detected between the patients who had microscopic disease at the beginning of the second-look and those who were surgically cytoreduced to microscopic disease. Moreover, the patients with macroscopic residuum < 2 cm after the second-look had a better survival than those with a larger residuum after re-exploration (median survival, 24 months versus 10 months, p = 0.0001). Among the former, no difference in survival was seen between the patients who had residual disease < 2 cm at the beginning of the second-look and those who were surgically cytoreduced to < 2 cm. However, ovarian cancer recurred in all the patients with small or large macroscopic residuum after the second-look. CONCLUSION: The complete resection of macroscopic persistent tumor seems to give ovarian cancer patients the highest likelihood of long-term survival and should represent the goal of surgical cytoreduction during second-look laparotomy.