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Ettore Seregni

Publications and source records attributed to Ettore Seregni.

At least 19 recordsLinked to original sources

Thyroid carcinoma associated with squamous cell carcinoma of the head and neck: which policy?

BACKGROUND: Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (HNSCC) is unusual. The clinical management of thyroid cancer in such cases has been debated. METHODS: Between 1975 and 2004, we collected 33 cases. The associated thyroid carcinoma was diagnosed either during or as a consequence of surgery planned as head and neck cancer treatment. RESULTS: The associated thyroid carcinoma was never seen to recur. Five-year overall survival was 41%. Disease-free survival after 40 and 66 months was 11.1% and 5.6%, respectively. CONCLUSIONS: We consider the treatment of thyroid cancer to be complete when the thyroid gland, either with or without lymph nodes, has been included in the specimen obtained during surgery for HNSCC. In the group of cases in which associated thyroid carcinoma was only found within the neck lymph nodes and the thyroid gland has not been treated, we discourage further surgical treatment or radioactive iodine therapy.

Adult↗

Circulating CA125 in patients with peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion.

BACKGROUND: Recent phase I/II trials report encouraging results in selected patients with peritoneal mesothelioma (PM) treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Circulating tumor markers have never been extensively investigated in the management of PM. We assessed the clinical role of markers in a large series of patients with PM undergoing CRS and IPHP. METHODS: Clinical data on 60 patients with PM operated with the intention to perform adequate CRS (residual tumor nodules <or= 2.5mm) and IPHP were prospectively collected. Marker levels were determined pre-operatively, post-operatively, and routinely during long-term follow-up. Baseline diagnostic sensitivity, accuracy in monitoring response to treatment or tumor progression and prognostic significance were determined. RESULTS: Baseline diagnostic sensitivity was 53.3% for CA125, 0 for CEA, 3.8% for CA19.9 and 48.5% for CA15.3. Forty-six patients underwent adequate cytoreduction and IPHP; gross residual tumor was left after the operation in fourteen. Postoperatively, CA125 became negative in 21/22 patients with elevated baseline levels undergoing adequate CRS and IPHP, while remained elevated in 9/9 patients with persistent macroscopic disease. CA125 became positive in 12/12 patients with elevated baseline levels developing disease progression after adequate CRS and IPHP. Baseline CA125 showed borderline prognostic significance only among patients not previously treated with systemic chemotherapy. CONCLUSIONS: CA125 was elevated in the majority of patients with PM in the present series. Serial maker measurements paralleled tumor growth or regression after CRS and IPHP, suggesting the need of further studies to assess the role of CA125 in this clinical setting.

Adult↗

Incident pain and analgesic consumption decrease after samarium infusion: a pilot study.

OBJECTIVE: The aim of this pilot study was to observe the variations of pain intensity on movement and at rest and the variation of analgesic drug consumption in patients with prostate cancer and painful bone metastases treated with a single dose of 1.0 mCi/kg of samarium-153 (153-Sm) lexidronam. DESIGN: Case series. SETTING: The Nuclear Medicine Unit and Pain Therapy and Palliative Care Unit, National Cancer Institute of Milan, Italy. PATIENTS: Thirteen outpatients with hormone refractory prostate cancer and painful multiple bone metastases. INTERVENTIONS: Infusion of a single dose of 1.0 mCi/kg of 153-Sm lexidronam, pain therapy, and the assessment of pain intensity at rest and on movement. MAIN OUTCOME MEASURES: Variation of pain intensity on movement and at rest by means of a verbal scale and the reduction of analgesic drug consumption 4 weeks after infusion of 153-Sm lexidronam. RESULTS: From baseline, 61.5% of patients reported a decrease of at least two levels of pain intensity on movement and 53.8% of patients had an improvement of pain at rest. Of the patients, 15.4% were not in pain at rest or on movement at baseline and continued to be free of pain 4 weeks after the administration of samarium. All ten patients, but one, who were on analgesic drugs before samarium infusion, reduced the regular drug administration or rescue medication. Bone marrow toxicity was mild and readily reversible in three patients. CONCLUSIONS: In patients with bone metastases, pain on movement is a frequent and often difficult clinical problem to treat and the most frequent cause of breakthrough pain. In patients with painful multiple bone metastases due to prostate cancer, the infusion of a single dose of 1.0 mCi/kg of 153-Sm lexidronam may be considered an effective and safe treatment for pain either at rest or during movement.

Aged↗

Conservative surgical approach for thyroid and lymph-node involvement in papillary thyroid carcinoma of childhood and adolescence.

BACKGROUND: Prior to 1990s, papillary thyroid carcinomas (PTCs) in childhood/adolescence underwent a standard therapeutic approach (total thyroidectomy plus elective neck dissection, followed by radioactive iodine (RAI) ablation), with an overall survival of about 100%. The aim of this study is to outline the possibility of a conservative approach (hemithyroidectomy plus selective neck dissection of clinically involved nodes, followed by TSH-suppressive therapy) in a selected group of patients. PROCEDURE: From 1968 to 2001, 42 pediatric PTC patients were treated at our institution. Absence of distant metastases and a tumor clinically limited to one lobe were both present in 28 cases that underwent a radical (20 cases) or a conservative (8 cases) surgical approach at the thyroid level. At cervical node level, 10 patients underwent a radical and 32 a conservative surgical approach. Clinicopathologic features at onset, type of therapy (radical vs. conservative), post-operative complications, and outcome till May 31, 2004 were recorded. The impact of the type of surgery on outcome was evaluated. RESULTS: Overall and progression-free survival (PFS) curves were found to be independent of the type of therapy (radical vs. conservative) in subgroups of patients matched for extent of disease at onset. Post-operative complications occurred only with radical surgical approaches. CONCLUSIONS: Childhood and adolescence PTCs show a high rate of spread but an excellent outcome independent of the type of therapy (radical vs. conservative). Taking into account the marked responsiveness to TSH-suppression and the complications after radical therapy, in selected cases, a conservative approach should be considered, reserving more aggressive therapies in case of metastases or relapse.

Adolescent↗

Papillary thyroid carcinoma of childhood and adolescence: a 30-year experience at the Istituto Nazionale Tumori in Milan.

BACKGROUND: Survival rates are reportedly excellent for papillary thyroid carcinomas (PTCs) in childhood/adolescence, despite their strong tendency to spread. The aim of this study was to verify this assumption in a single-institution series spanning a 30-year period with a very long follow-up. PROCEDURE: From 1968 to 2001, 74 cases of thyroid carcinoma were collected. The papillary histological type was confirmed in 42 cases with available slides; we recorded the sex, age at diagnosis, age of menarche, tumor side and size, TNM/pTNM classification, multicentricity, vascular invasion, type of surgery, post-operative complications, post-surgical therapies and outcome up to May 31, 2004. RESULTS: The female/male ratio was 2.2; pT4, pN1 and M1 cases were 52%, 95%, and 12% (four in lungs and one in bone), respectively. Total thyroidectomy was performed in 33 patients, hemithyroidectomy in 8, and a biopsy in 1 inoperable case. Nine patients (21%) relapsed, six in the cervical lymph nodes and three in the lungs. After a median follow-up of 189 months, all patients were alive, two of them with evidence of disease. Overall and progression-free survival curves were independent of sex, age, TNM/pTNM classification, or type of surgery. Overall survival was also independent of recurrence. CONCLUSIONS: Unlike its adult counterpart, PTC of childhood and adolescence is a cancer with a high frequency of spread, but an excellent outcome irrespective of sex, age at diagnosis, TNM/pTNM classification, type of surgery, recurrence. Since pediatric PTCs proved highly responsive to hormone manipulation, it is worth considering a different therapeutic approach from adult cases.

Adolescent↗

Independent validation of candidate breast cancer serum biomarkers identified by mass spectrometry.

BACKGROUND: We previously selected a panel of 3 breast cancer biomarkers (BC1, BC2, and BC3) from serum samples collected at a single hospital based on their collective contribution to the optimal separation of breast cancer patients and noncancer controls by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The identities and general applicability of these markers, however, were unknown. In this study, we performed protein expression profiling on samples obtained from a second hospital, included a greater number of ductal carcinoma in situ (DCIS) cases, and performed purification and identification of the 2 confirmed markers. METHODS: Using a case-control study design, we performed protein expression profiling on serum samples from the National Cancer Institute (Milan, Italy). The validation sample cohort consisted of 61 women with locally invasive breast cancer, 32 with DCIS, 37 with various benign breast diseases (including 13 atypical), and 46 age-matched apparently healthy women (age range, 44-68 years). Validated biomarkers were purified and identified with serial chromatography, 1-dimensional gel electrophoresis, in-gel ASP-N digestion, peptide mass fingerprinting, and tandem mass peptide sequencing. RESULTS: The BC3 and BC2 expression patterns in this sample set were consistent with the first study sample set. BC3 and BC2 were identified to be complement component C3a(desArg) and a C-terminal-truncated form of C3a(desArg), respectively. CONCLUSIONS: Evaluation of biomarkers in independent sample sets can help determine the broader utility of candidate markers, and protein identification permits understanding of their molecular basis. C3a(desArg) appears to lack specificity among patients with benign diseases, limiting its utility as a stand-alone tumor marker, but it may still be useful in a multimarker panel for early detection of breast cancer.

Adolescent↗

90Y Labeling of monoclonal antibody MOv18 and preclinical validation for radioimmunotherapy of human ovarian carcinomas.

The monoclonal antibody (mAb) MOv18 binds the membrane alpha isoform of the folate receptor (FR) which is overexpressed in human ovarian carcinoma cells. Exploiting the targeting capacity of this mAb, we developed and preclinically validated a protocol for the stable labeling of the mAb with 90Y, an isotope which has shown promise in cancer radioimmunotherapy. MOv18 was derivatized with the stable macrocyclic ligand p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (Bz-DOTA). MOv18-Bz-DOTA conjugates were labeled with 90Y or 111In under metal-free and good laboratory practice conditions. At the optimal Bz-DOTA/mAb derivatization ratio of 4-5, conjugates maintained binding activity up to 6 months, were efficiently labeled with 90Y or 111In (mean labeling yield 85 and 64%, associated to a final mean specific activity of 74 and 37 MBq/mg) and displayed a mean immunoreactivity of 60 and 58%, respectively. The radiolabeled preparations were stable in human serum, with >97% radioactivity associated to mAb at 48 h after labeling. The ability of 90Y- and 111In-MOv18 to localize FR on tumors in vivo was analyzed in nude mice bearing tumors induced by isogenic cell lines differing only in the presence or absence of the relevant antigen [A431FR (FR-positive) and A431tMock (FR-negative)]. In vivo biodistribution in organs other than tumor was comparable in non-tumor-, A431tMock- and A431FR-bearing mice, whereas the median tumor uptake of the radiolabeled reagents, expressed as area under the curve (AUC) and maximum uptake (Umax), was significantly higher (sixfold to sevenfold) in A431FR than in A431tMock tumors (P=0.0465 and P=0.0332, respectively). Mean maximum uptake (% ID/g) for 90Y-MOv18 was 53.7 and 7.4 in A431FR and A431tMock respectively; corresponding values for 111In-Mov18 were 45.0 and 11.3. These data demonstrate the feasibility of 90Y-labeling of MOv18 without compromising antibody binding ability and the immunoreagent-specific localization in vivo on FR-expressing tumors, suggesting the suitability of 90Y-MOv18 for clinical studies.

Antibodies, Monoclonal↗

Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape.

BACKGROUND & AIMS: Normal and neoplastic cells release microvesicles, whose effects on the immune system still need to be elucidated. Because human colorectal cancer cells are hypothesized to escape immune recognition by expressing proapoptotic molecules, we investigated whether microvesicles bearing Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand and inducing apoptosis of activated T cells are secreted by colorectal cancer cells both in vitro and in affected patients. METHODS: Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand expression were analyzed in colorectal cancer cells and purified microvesicles by flow cytometry, Western blotting, and immunoelectron microscopy. Microvesicle tumor origin was assessed through simultaneous detection of lysosomal (CD63) and adenocarcinoma (carcinoembryonic antigen) markers. Proapoptotic activity of microvesicles was evaluated by annexin V/propidium iodide staining and caspase activation in T cells, including CD8+ T lymphocytes from colorectal cancer patients. RESULTS: Colorectal cancer cells showed a granular pattern of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand expression, suggesting a secretory behavior. These proapoptotic molecules were detected on isolated microvesicles, together with class I HLA, CD63, and carcinoembryonic antigen. Microvesicles induced Fas ligand-mediated and tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis of activated CD8+ T cells generated from colorectal cancer patients. Microvesicles with comparable phenotypes and functions were found in plasma from patients with advanced disease, whereas vesicular structures expressing Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand were also detected in colorectal cancer specimens. CONCLUSIONS: These data show that colorectal cancer induces T-cell apoptosis through the release of Fas ligand-bearing and tumor necrosis factor-related apoptosis-inducing ligand-bearing microvesicles both in vitro and in vivo. This mechanism of immune escape has potential implications as a prognostic factor and could be targeted for the development of new antitumor therapies in colorectal cancer patients.

Apoptosis↗

Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma.

BACKGROUND: The RET proto-oncogene encodes a receptor tyrosine kinase. RET oncogenes arise through sporadic and inherited gene mutations and are involved in the etiopathogenesis of medullary thyroid carcinoma, a cancer that responds poorly to conventional chemotherapy. Medullary thyroid carcinoma is a component of multiple endocrine neoplasia type 2 or MEN2 syndromes. METHODS: We investigated the cellular effects of RPI-1, a novel 2-indolinone Ret tyrosine kinase inhibitor on cells that express RET C634 oncogenic mutants common in the MEN2A syndrome: NIH3T3 fibroblasts transfected with RET(C634R) and human medullary thyroid carcinoma TT cells that express endogenous RET(C634W). RPI-1 antiproliferative activity was determined by cell proliferation and anchorage-independent growth assays. Expression and phosphorylation of Ret and of proteins involved in downstream signaling pathways were examined by immunoblotting. Antitumor activity of oral RPI-1 treatment was tested by using two dosing levels in nude mice bearing subcutaneous TT xenograft tumors. All statistical tests were two-sided. RESULTS: The RPI-1 IC50 value for cell proliferation was 3.6 microM (95% confidence interval [CI] = 1.8 to 5.4 microM) in NIH3T3 cells expressing the Ret mutant compared with 16 microM (95% CI = 12.3 to 19.7 microM) in non-transfected NIH3T3 cells, and that for colony formation in soft agar was 2.4 microM (95% CI = 0.8 to 4.0 microM) and 26 microM (95% CI = 17 to 35 microM) in RET mutant-transfected and H-RAS-transfected NIH3T3 cells, respectively. In NIH3T3 cells expressing the Ret mutant, Ret protein and tyrosine phosphorylation were undetectable after 24 hours of RPI-1 treatment. In TT cells, RPI-1 inhibited proliferation, Ret tyrosine phosphorylation, Ret protein expression, and the activation of PLCgamma, ERKs and AKT. In mice, oral daily RPI-1 treatment inhibited the tumor growth of TT xenografts by 81% (P<.001 versus control mice) and reduced the plasma levels of the specific biomarker calcitonin (P =.01 versus control mice). Twenty-five percent of RPI-1-treated mice were tumor-free. CONCLUSIONS: Ret oncoproteins represent exploitable targets for therapeutic intervention in MEN2A-associated medullary thyroid carcinoma. The antitumor efficacy and oral bioavailability of RPI-1 support its therapeutic potential.

Administration, Oral↗

Circulating tumour markers in breast cancer.

A large number of markers have been proposed for breast cancer, but among them only CA 15.3, CEA and cytokeratins (i.e. TPA, TPS and Cyfra 21.1) are currently used in clinical practice. Serum marker levels reflect tumour burden and for this reason they are not sensitive enough to be used for screening and early diagnosis of primary breast cancer. By contrast, the role of tumour markers is established in the diagnosis of recurrent disease and in the evaluation of response to treatment. In the former case, however, prospective randomised studies are required to demonstrate any survival benefit when earlier therapeutic interventions are instituted upon elevation of serum markers. In the second case, tumour marker evaluation represents a simple, objective method for monitoring of therapeutic response that seems to offer significant advantages over conventional imaging methods (e.g. objectivity, modifications in tumour biology). Furthermore, research studies are ongoing to identify and validate new biochemical parameters which can be of use not only in advanced disease but also in other stages of the diagnostic work-up of breast cancer.

Biomarkers, Tumor↗

The estrogen suppression after sequential treatment with formestane in advanced breast cancer patients.

In postmenopausal patients, estrogens have an important role in breast cancer growth and aromatase inhibitors (AI) suppress the aromatase enzyme system which converts androgens into estrogens. The aim of this study was to evaluate the effect on estrogen suppression of formestane 250 mg i.m. fortnightly, given immediately after the failure of a previous treatment with non-steroidal AI. Twenty-two advanced breast cancer patients progressing on letrozole, anastrozole and aminoglutethimide entered the study. At the beginning of the study, the serum estrogen levels were suppressed by the previous treatment with non-steroidal AI, and the following treatment with formestane moderately maintained this suppression; in four patients serum estrogen levels increased fivefold after 10 weeks. Neither complete nor partial responses were observed; 11 patients (50%) showed a stable disease lasting > or = 6 months, and the median time to progression was 6 months (range 3-9 months). No correlation was observed between clinical responses and serum estrogen suppression. Tolerability was satisfactory, and no patient withdrew from the study due to adverse events. In conclusion, formestane has demonstrated a moderate activity in estrogen suppression, and there is evidence that, at the failure of a previous treatment with non-steroidal AI, the sequential use of steroidal AI is feasible. This approach can be used in clinical practice in order to offer a disease control with a satisfactory quality of life.

Adult↗

Feasibility of somatostatin receptor scintigraphy in the detection of occult primary gastro-entero-pancreatic (GEP) neuroendocrine tumours.

The aim of this study was to assess the feasibility of somatostatin receptor scintigraphy (SRS) for the detection of the site of unknown primary neuroendocrine neoplasms in patients in whom clinical examination and conventional radiological imaging had failed to do so. From 1996 to 2000, 36 patients were referred with gastro-entero-pancreatic (GEP) neuroendocrine tumours. In these patients, no clinical, radiological or endoscopic diagnostic modalities had been able to identify the primary tumour. Twenty-nine patients had liver metastases. Of the others, one had skin and one had lymph node metastases, three had diffuse metastatic involvement and two had carcinoid syndrome. SRS was carried out with both whole-body and single-photon emission tomography (SPET) acquisition, 24 and 48 h after the intravenous administration of In-pentetreotide. SRS findings were suggestive of the possible site of the primary lesion in 14 patients (39%). Six patients underwent surgery on the basis of the SRS findings and, therefore, the final, i.e. pathological, diagnosis was reached. In two patients, the final diagnosis was obtained within 6 months of SRS by means of a follow-up computed tomography (CT) scan. In the remaining six patients, the final diagnosis was reached after at least 2 years of follow-up by means of clinical, radiological and/or nuclear medicine findings. In all eight patients, the primary site identified during follow-up was consistent with the SRS findings. It can be concluded that SRS modified management in the six patients who had surgery. However, the most important finding was that SRS prompted surgical management in 17% of cases.

Digestive System Neoplasms↗

Could exemestane affect insulin-like growth factors, interleukin 6 and bone metabolism in postmenopausal advanced breast cancer patients after failure on aminoglutethimide, anastrozole or letrozole?

Postmenopausal hormone-sensitive breast cancer is currently treated with either antioestrogens or aromatase inhibitors (AIs), due to the clinical efficacy and safety of these drugs. Today's challenge is the sequential use of AIs with different structure and no cross-resistance to improve the therapeutic outcome. The present study describes the biological action of the steroidal structure (SS)-AI exemestane (EXE), in patients progressing on aminoglutethimide (AG) or other non-steroidal structure (NSS)-AIs (letrozole or anastrozole). Thirteen patients were evaluated for serum insulin-like growth factor (IGF) components [total IGF-1, IGF-2 and IGF binding protein (IGFBP)-3], interleukin (IL)-6 system [IL-6 and soluble IL-6 receptor (sIL-6-R)] and bone metabolism markers [bone gla protein/osteocalcin (BGP), bone-specific isoform of alkaline phosphatase (BAP) and carboxy-telopeptide of type I procollagen (ICTP)]. IGF system components show a trend to increase both in patients progressing on AG and in patients progressing on other NSS-AIs. Such an increase depends on the wash-out length from the previous treatment and is strictly linked to the circulating oestrogen levels. Serum IL-6 and sIL-6-R are mainly related to the patients' clinical outcome. Bone formation (BGP and BAP) and bone resorption (ICTP) markers seem to be at equilibrium with oestrogen levels when starting EXE and do not appear to be uncoupled over treatment. The observed variations seem to be mainly linked to the circulating oestrogen levels rather than directly to the way of action of the AI employed.

Aged↗

Recombinant human thyrotropin (rhTSH) in the follow-up and treatment of patients with thyroid cancer.

The follow-up of thyroid cancer is based on the detection of residual and recurrent thyroid carcinoma. This is traditionally done by means of measurements of serum thyroglobulin (Tg) combined with various imaging techniques (131I-whole body scan, ultrasound and other modalities). Tg serum levels and the uptake of 131I on a whole body scan (WBS) depend on TSH stimulation, which in thyroidectomized patients can be obtained either by withdrawal of thyroid hormone treatment (thyroxine) or by administration of exogenous TSH. At present exogenous human TSH is obtained by means of recombinant DNA technology, (recombinant human TSH (rhTSH), Thyrogen). Even if the administration of rhTSH and withdrawal of thyroid hormone are not completely equivalent, the use of rhTSH has already entered the clinical routine (rhTSH Tg test and rhTSH WBS) because with rhTSH the morbidity and discomfort associated with the withdrawal of thyroid hormone can be avoided. At a recent International Consensus Conference on the follow-up of differentiated thyroid carcinoma it was proposed to carry out only Tg measurement after rhTSH stimulation; moreover, it was stated that 131I whole body scan has to be discouraged in patients submitted to radical surgery and radioiodine ablation with no clinical evidence of residual tumor and with undetectable levels of Tg during hormonal suppression of TSH. Similar strategies in this respect tend to eliminate the 131I WBS and propose only the rhTSH Tg test combined with head and neck ultrasound (US). This is still a matter of debate, also because it is not valid for all risk groups and not all patients undergo the same clinical management (radical surgery or not, thyroid ablation with 131I or not). However, the availability of rhTSH will definitely change the management of papillary and follicular thyroid carcinoma, also with regard to iodine treatment. In fact, rhTSH can be used during radioiodine treatment to enhance the 131I uptake by the cancer cells in particular groups of patients. Patients who could benefit from this approach can be divided into three subgroups: 1) patients in whom thyroxine withdrawal may be dangerous because of the effects of long-term TSH stimulation on the tumor mass (brain metastases, vertebral metastases, presence of neurological signs, heart diseases); 2) patients affected by tumors with marked biological aggressiveness and a low iodine uptake (variants of follicular carcinoma, insular carcinoma, tall and columnar cell variants of papillary thyroid carcinoma, Hürthle cell carcinoma); 3) patients with hypothalamic-pituitary alterations. The potential efficiency of rhTSH in radiometabolic treatment is an important issue that has been studied in a limited number of patients, but is worthy of further investigations in large perspective. A recent clinical prospective trial has been proposed by the Thyroid Cancer Study Group of the Istituto Nazionale Tumori and is now ongoing.

Humans↗

Critical aspects of immunoradiometric thyroglobulin assays.

BACKGROUND AND AIM OF THE STUDY: Thyroglobulin (Tg) evaluation is currently used in the follow-up of patients with differentiated thyroid carcinoma (DTC), but the measurement methods are flawed by analytical inaccuracy. In this paper we describe the results of a comparison between seven different immunoradiometric assays (IRMAs) for Tg determination. MATERIAL AND METHODS: Tg was measured in 50 patients with DTC by means of the following commercially available IRMA kits: HTGK-2 (DiaSorin), Tg IRMA (Schering-CIS bio international), ELSA-hTG (Schering-CIS bio international), Tg IRMA C.T. (ICN Pharmaceuticals), SELco Tg (Medipan Diagnostica), Tg Bridge IRMA (Adaltis) and IRMA-mat Tg (BYK-Sangtec Diagnostica). The distribution of the Tg values measured by the different IRMAs was compared and a correlation analysis was performed. RESULTS: The Tg values were widely dispersed and the classification of patients according to Tg concentrations of clinical relevance varied depending on the IRMA used. CONCLUSION: Despite efforts to develop standardized Tg assays, the measurement of this biomarker is still affected by a considerable degree of analytical inaccuracy. Tg values vary widely between assays and the classification of patients according to Tg values with clinical relevance is still dependent on the assay used.

Biomarkers, Tumor↗

Diagnostic and therapeutic aspects of iatrogenic hypoparathyroidism.

Postsurgical hypoparathyroidism is the most common cause of chronic hypocalcemia. This condition may occur after removal of all parathyroid glands or after interruption of the blood supply to the parathyroid glands during thyroidectomy and radical neck dissection. The severity of the clinical presentation of hypocalcemia may vary from an asymptomatic laboratory finding to a severe life-threatening condition. Persistent hypoparathyroidism requires treatment that must be maintained throughout the patient's lifetime, and for this reason care is required to avoid complications. In this review the most relevant aspects of calcium homeostasis and its alteration in hypoparathyroidism are briefly discussed. In addition, the main approaches to treatment of the hypocalcemic state are presented.

Calcium↗

Prophylactic thyroidectomy in MEN 2A syndrome.

Genetic testing is the appropriate procedure in MEN 2A syndrome for the early diagnosis of medullary carcinoma even at a preclinical stage. Prophylactic total thyroidectomy represents the standard preventive and therapeutic surgical approach in the treatment of medullary thyroid carcinoma in MEN 2A syndrome. Our experience has confirmed the presence of CCH and medullary thyroid carcinoma even in clinically negative patients, in agreement with reports in the literature.

Adult↗

Diagnostic procedures in the follow-up of patients affected by MEN type 2.

Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disease caused by germline mutations in the RET proto-oncogene. The most distinctive MEN 2 variants are MEN 2A, MEN 2B and familial medullary thyroid cancer (FMTC). The hallmark of these syndromes is the development of medullary thyroid carcinoma (MTC), which occurs in almost all patients with MEN 2 syndromes. Other endocrinopathies are variably expressed. Pheochromocytoma and hyperparathyroidism occur in patients with MEN 2A with a frequency of about 50% and 30%, respectively. In this paper we summarize the most relevant diagnostic methods to detect and monitor MTC, pheochromocytoma and hyperparathyroidism.

3-Iodobenzylguanidine↗