Pulmonary alveolar macrophages from patients with active sarcoidosis express type IV collagenolytic proteinase. An enzymatic mechanism for influx of mononuclear phagocytes at sites of disease activity.

Alveolar macrophages (AMs) recovered from the bronchoalveolar lavage (BAL) of 44 patients with sarcoidosis were evaluated for their ability to release type IV collagenolytic metalloproteinase (IV-Case). This enzyme, which is produced by peripheral blood monocytes (PBMs) but not by tissue macrophages, degrades type IV collagen, the major structural component of vessel wall basement membranes, and helps to promote the migration of PBMs from the blood compartment to peripheral tissues. Our results demonstrated that AMs from patients with active sarcoidosis released significantly increased levels of IV-Case with respect to patients with inactive disease and control subjects. After in vitro culture, sarcoid AMs secreted IV-Case during the first 24 h of collection; after that time, AMs progressively lost their ability to release IV-Case. Exposition of both sarcoid and normal AMs to recombinant IL 2 or gamma IFN did not influence their property to release IV-Case. The immunoblot analysis of IV-Case demonstrated complete identity between IV-Case released by AMs and the degradative enzyme obtained from PBMs. The increased property to release IV-Case was significantly related to the increase of the absolute number of AMs and, in particular, of AMs bearing two determinants that are usually expressed by most PBMs (CD11b and CD14). Selective depletion of CD11b+/CD14+ AMs from the entire macrophagic population was associated with the recovery of the IV-Case activity to normal values. A positive correlation was also found between the increase in the absolute number of lung T cells and the enhanced CD4/CD8 pulmonary ratio. A 6-mo follow-up study indicated a significant association between the positivity for the 67Gallium scan and the increased property of AMs to release IV-Case. Our data are consistent with the hypothesis that a IV-Case mediated influx of peripheral monocytes takes place in the lung of sarcoid patients. Furthermore, the correlation found between the IV-Case release and disease activity suggests that this assay could represent a useful tool in sarcoidosis disease staging.

99mTc-sestamibi radio-guided surgery of loco-regional 131Iodine-negative recurrent thyroid cancer.

AIM: We report here our experience in a larger series of differentiated thyroid cancer (DTC) patients who had been treated by (99m)Tc-sestamibi radio-guided surgery (RGS) for (131)Iodine ((131)I)-negative loco-regional recurrent disease. METHODS: Fifty-eight patients with loco-regional (131)I-negative recurrent disease from DTC were studied with (99m)Tc-sestamibi directed RGS using a hand-held 11-mm gamma probe as an intra-operative detector. Patients were selected for RGS on the basis of (a) progressive increase of serum thyroglobulin (Tg) levels after first treatment during follow-up, (b) negative high dose (100 mCi, 3.7 GBq) (131)I whole-body scan, and (c) positive pre-operative (99m)Tc-sestamibi scintigraphy for the presence of loco-regional recurrent disease. There were 41 papillary (1 "tall" cell variant), 13 follicular and 4 Hürthle cells tumours. In 14 patients thyroid cancer recurred in the thyroid bed while cervical lymph node metastases were found in 37 patients, and 7 patients had recurrent disease both in the thyroid bed and in cervical lymph nodes. RESULTS: At bilateral neck exploration, 147 metastatic foci ranging from 4 mm to 51 mm in largest diameter (mean tumour diameter=17.3+/-9.5mm) were removed. Eighty-five of them (58%) had been pre-operatively identified at (99m)Tc-sestamibi scintigraphy. After RGS, serum Tg levels normalised in 43 of 58 patients (serum Tg<2 ng/ml--they were considered disease-free), serum Tg remained slightly increased in 12 patients without evidence of metastatic disease at scintigraphic and radiologic imaging (serum Tg<10 ng/mg--they were considered living with microscopic disease), while serum Tg significantly increased up to values>900 ng/ml in 3 patients who developed lung metastases. The mean lesion to background (99m)Tc-sestamibi uptake ratios decreased in all 58 patients (p<0.0001). Post-surgical follow-up ranged 6-72 months (mean+/-SD=29.6+/-13.5 months). The operating surgeon assessed RGS as very useful in 14 patients in whom metastatic foci were embedded in fibrotic tissues or located behind blood vessels, useful in 22 patients, moderately useful 17 patients and not useful in 5 patients. CONCLUSION: Our data suggest that a (99m)Tc-sestamibi intra-operative gamma probe can be used to identify and guide resection of recurrent loco-regional tumour in DTC patients with (131)I-negative loco-regional metastatic foci.

[Papillary thyroid microcarcinoma. Long-term outcome in 587 cases compared with published data]. / Il microcarcinoma papillare della tiroide: nostra esperienza e letteratura a confronto.

AIM: Papillary thyroid microcarcinoma (PTMC), a tumor measuring =or<1 cm according to the World Health Organization (WHO) histologic classification, is the most common histologic variant of thyroid cancer. The aim of this study was to evaluate the long-term outcome of surgical treatment for PTMC at a single institution with a view to differentiate therapy options based on risk of progression of disease by comparing our results with those reported in the literature. METHODS: The study sample was a total of 587 cases of PTMC treated surgically at our institution between 1990 and 2006. PTMC was an incidental finding (PTMC-I) in 325 (55.4%) cases, diagnosed preoperatively (PTMC-D) at echography and needle-aspiration biopsy in 229 (39%), and occult with metastasis (PTMC-O) in 33 (5.6%). Patients were grouped into two classes (PTMC diameter =or>5 mm or <5 mm) and compared against prognostic factors: sex, age, type of PTMC (PTMC-I, PTMC-D, PTMC-O), extent of surgery, lymph node dissection, lymph node metastasis, iodine-131 (131-I) therapy, state of disease, relapses. These parameters were then compared against tumor size (PTMC diameter =or>5 mm or <5 mm), excluding cases of PTMC-O with metastasis. RESULTS: Comparison of the two groups divided by tumor size, across the entire sample and after PTMC-O cases were excluded, revealed significant differences in the type of PTMC, frequency of partial thyroidectomy, presence of lymph node metastasis, iodine-131 therapy, life status and recurrence rate. CONCLUSION: Published PTMC studies were analyzed for definition of the disease, incidence, therapy, prognosis, and follow-up results and compared with our data. The results of our analysis argue against use of the term ''microcarcinoma'' in the wider sense since the three PTMC categories (PTMC-I, PTMC-D, PTMC-O) present different behaviour patterns. When cases of PTMC-O with clinically manifest metastasis were excluded, none of the patients with PTMC <5 mm in diameter were reoperated for tumor recurrence and all are currently free of disease. In conclusion In PTMC <5 mm in diameter, whether PTMC-I and PTMC-D, and without evidence of lymph node involvement, partial thyroidectomy may be a viable approach to treatment. By contrast, occult PTMC with metastasis is prognostically important and should therefore be treated like tumors =or>5 mm in diameter.

The role of sentinel lymph node biopsy in patients with differentiated thyroid carcinoma.

AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN) biopsy procedure in patients affected by differentiated thyroid carcinoma. METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma patients was the vital blue dye technique. This technique had some disadvantages as: (a) risk of disruption of the lymphatic channels deriving from the thyroid cancer; (b) difficulty in disclosing SLN lying outside the central compartment; (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as lymph nodes. Some of the above cited disadvantages were overcome by using the lymphoscintigraphy and intraoperative gamma probe technique. A combination of the blue dye and gamma probe technique has also been proposed with synergic results. CONCLUSION: The reported advantages of the SLN biopsy in small differentiated thyroid carcinoma patients can be resumed as follows: (a) better selection of patients who would benefit from compartment oriented nodal dissection; (b) more accurate lymph node staging; (c) better selection of patients who can require (131)I treatment after surgery (SLN positive for metastasis); (d) better identification of SLN located out of the central compartment.

Sentinel node mapping and biopsy in thyroid cancer: a surgical perspective.

The clinical role of sentinel node biopsy (SNB) in thyroid cancer remains an open matter in literature. The main reason of this fact is that nodal disease is considered a non-relevant prognostic factor by some authors in differentiated thyroid cancer (DTC). Aim of this study was to investigate the efficacy of radiocolloid lymphoscintigraphy and of hand held gamma probe procedure for SNB in patients with DTC and its potential clinical role. Forty-one consecutive pts with a small thyroid nodule highly suspected for malignancy at fine-needle aspiration cytology (FNAC) and without clinical and ultrasonographic (US) evidence of lymph node involvement entered the study. All patients underwent lymphoscintigraphy 3 hours before intervention using a 99mTc-nanocolloid solution. One single intratumoral injection of 4-9 MBq in 0.1-02 ml normal saline was obtained under US-guidance followed by a dynamic lymphoscintigraphy. After total thyroidectomy central and lateral compartments of the neck were scanned with a hand held gamma probe. The hottest node and any lymph node with a count rate of more than 10% of the hottest node were removed. SLNs were sent to frozen section analysis and a surgical enlargement of corresponding compartment was performed when at least one SLN was positive at histology. Preoperative lymphoscintigraphy was able to identify one node in six cases, two nodes in five cases, three nodes in 14 cases, four or more nodes in 16 cases. A papillary thyroid carcinoma (PTC) was diagnosed in 39 cases, a mixed papillary-medullary carcinoma in one case and a micro-follicular adenoma in one case. In 21/40 patients (pts) positive lymph nodes were found: in 16/21 patient one node showed micrometastasis only, in 5/21 patients more nodes were metastatic. In particular in 11 cases the first hottest node was involved (true SLN), in 10 cases a second or third hot lymph node was involved. In our preliminary experience lymphoscintigraphy with 99mTc-nanocolloid resulted highly sensitive: in fact at least one lymph node was visualized in all cases and the surgeon was able to detect by means of hand held probe during intervention al least one hot SLN in all cases. In 21/40 pts (more than 50% of cases) metastatic lymph nodes were found despite preoperative clinical and US examination negative for lymph node involvement. In prospective SLN technique might be proposed as a relevant tool in lymphoadenectomy decision in DTC patients with a small tumor.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

Axillary sentinel lymph nodes in breast cancer: a single lymphatic pathway drains the entire mammary gland.

AIM: To report the pattern of lymphatic mapping following intrasubdermal injections of radiocolloid and of blue dye in different sites of the breast. METHODS: Prior to surgery 137 breast cancer patients underwent intrasubdermal injection of 30-50 MBq 99mTc-colloidal albumin over the tumour site (ISI group). Ten minutes before surgery, 2 ml patent blue was injected in the subareolar area (SAI group) in 117/137 patients, while 20 patients received intrasubdermal blue-dye in the quadrant opposite the tumour site (OQI group). The different injection routes were considered concordant when the hottest sLN was also blue. RESULTS: In 134/137 patients radiocolloid drained to one or more axillary nodes, while blue nodes were found in 98/117 SAI patients and in 17/20 OQI patients. Multiple hot nodes were found in 63/134 cases and multiple blue nodes in 35/115. In patients in whom both tracers reached the axilla, the hottest node was also blue in 108/115 cases (93/98 SAI and 15/17 OQI patients). In the seven discordant cases, the hottest node was not blue, but in two cases the blue node was also radioactive. CONCLUSIONS: Superficial lymphatic drainage from the breast most frequently merges to a single axillary lymph node, irrespective of the site of tracer injection. In a few cases different injection sites identify different, often closely interconnected sLNs.

Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications.

BACKGROUND: Little is known about the clinical, diagnostic, and prognostic aspects of upper-extremity deep vein thrombosis (UEDVT). OBJECTIVES: To identify the clinical and laboratory parameters associated with this disease, to assess the diagnostic accuracy of ultrasonographic methods for its detection, and to establish the frequency of both early and late complications. PATIENTS AND METHODS: After a careful history was taken, 58 consecutive patients with signs and symptoms that were clinically suggestive of UEDVT underwent the determination of antithrombin III and protein C and S levels and resistance to activated protein C and lupuslike anticoagulants. Compression ultrasonography, color flow Doppler imaging, and Doppler ultrasonography were performed prior to venography. Patients with confirmed UEDVT underwent objective tests to detect a pulmonary embolism and were followed up prospectively to record recurrent thromboembolic events and postthrombotic sequelae. RESULTS: Findings from venography confirmed UEDVT in 27 patients (47%). Central venous catheters, thrombophilic states, and a previous leg vein thrombosis were statistically significantly associated with UEDVT. Sensitivity and specificity of compression ultrasonography (96% and 93.5%, respectively) and color flow Doppler imaging (100% and 93%, respectively) were comparable and better than those of Doppler ultrasonography (81% and 77%, respectively). Objective findings suggestive of a pulmonary embolism were recorded in 36% of the patients with UEDVT. After a mean follow-up of 2 years, 2 patients with UEDVT experienced recurrent thromboembolic events, and 4 had postthrombotic sequelae. CONCLUSIONS: Symptomatic UEDVT is associated with central venous catheters, thrombophilic states, and a previous leg vein thrombosis. Both compression ultrasonography and color flow Doppler imaging are accurate methods for its detection. A pulmonary embolism is a common complication of the disease. Finally, this disorder may recur and may be followed by postthrombotic sequelae.

A rare case of paraneoplastic cerebellar degeneration discovered by whole-body F-18 FDG PET.

A rare case of paraneoplastic cerebellar degeneration (PCD) in a 36-year-old woman is reported. She developed hyposthenia of the inferior limbs, diplopia, and disequilibrium in July 2001. Routine blood tests, tumoral markers, brain MRI, evoked potentials, and cerebrospinal fluid (CSF) examination were substantially normal. The clinical syndrome rapidly worsened in the following 2 months; she was wheelchair-bound with marked limb ataxia. CSF showed an increase of the IgG index with oligoclonal bands; brain MRI remained negative. The patient's serum and CSF were analyzed to detect antineuronal antibodies; anti-Yo antibodies were found that is typical of PCD. No tumor was found until April 2003; repeated CT scan, ultrasound, and mammographic examinations were negative. A further worsening in clinical symptoms was observed with a complete loss of autonomy (Rankin score 5) despite the performance of immunosuppressive therapy. In April 2003, an F-18 FDG PET scan visualized an area of abnormal uptake in the upper outer quadrant of the left breast. Interestingly, brain F-18 FDG uptake was normal. Suspicious microcalcifications were found on a new mammography and malignant cells were disclosed at cytology. The patient was operated on and final histologic examination revealed an infiltrating ductal breast cancer. In the reported case, F-18 FDG PET played a crucial role in detecting the unknown primary tumor in a young patient with PCD.

Sentinel node biopsy and ultrasound scanning in cutaneous melanoma: clinical and technical considerations.

1.5 mm and in all cases with two metastatic SNs, further positive additional nodes were found. The mean counts per 10 s (CP10S) ratio for SN and non-SN values was 5.62 (1.29-23.51) and 3.09 (1.03-10.99) in the intra-operative and extra-operative phases, respectively. US scanning and preoperative lymphoscintigraphy associated with PBD allows preoperative patient selection and accurate SN(s) identification. Breslow thickness and the number of metastatic SN(s), but not their type, are correlated with disease spread; CP10S contributed to the differentiation amongst the nodes and the determining of procedure's completion.

Clinical meaning of circulating antithyroglobulin antibodies in differentiated thyroid cancer: a prospective study.

In recent studies of patients with differentiated thyroid cancer (DTC), an association between the persistence of tumor and the presence of circulating anti-thyroglobulin antibodies (TgAbs) have been described. The aim of the present study was to evaluate TgAb variations before and after total thyroid ablation and to correlate TgAb levels to the outcome of disease. Forty-three patients with DTC were studied (35 female, 8 male; 33 patients had papillary cancer and 10 follicular cancer). Tumor was intrathyroid in 20 cases, had spread to the lymph nodes in 19 and to the lungs in 4. All patients underwent total thyroidectomy and 131I therapy, and were then treated by suppressive doses of L-thyroxine. After a mean follow-up of 3.55 yr, TgAbs became undetectable in 24 patients (all were considered tumor-free), whereas TgAbs remained elevated in 19 cases. In 5 of these 19 patients, disease progression or persistence was documented (to the lymph nodes in three and to the lungs in two). TgAb levels were higher in patients with persistent disease in comparison with those tumor-free. Serum thyroglobulin (S-Tg) results were only elevated in the two patients with persistent disease in the lungs. Our data suggest that TgAbs determination may give some additional information to the follow-up of patients with DTC: the disappearance of TgAbs after therapy seems to represent a favorable prognostic factor, while the persistence of circulating TgAbs, particularly at high levels and in the absence of detectable S-Tg, may be representative of disease.

Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables.

We studied 134 patients with differentiated thyroid cancer and pulmonary metastases. All were treated with total or near total thyroidectomy, radioiodine and L-thyroxine. The prognostic value of the following variables in three groups of patients were evaluated by univariate and multivariate analysis: age at diagnosis, sex, histologic type, tumor extension, cervical lymph node metastases, mediastinic metastases, presence of metastases in distant sites other than lungs (multiple distant metastases) and morphological (chest x-rays) and functional (131I uptake) features of lung metastases. Univariate analysis identified patient age (p < 0.0001), morphological and functional features of lung metastases (p < 0.0001), presence of multiple distant metastases (p < 0.0001) and histologic type (p = 0.04) as significant prognostic factors. Multivariate analysis showed only morphological (p = 0.0014) and functional (p < 0.0001) features of lung metastases and the presence of multiple distant metastases (p = 0.01) as significant and independent variables. The data show that early (pre-radiological) scintigraphic diagnosis and 131I therapy of lung metastases appear to be the most important elements in obtaining both a significant improvement in survival rate and a prolonged disease-free time interval in these patients.

Serum lipids, "double pre-beta lipoproteinemia," and distribution of the apo-very-low density (VLDL) lipoprotein peptides in hypothyroid patients before and after substitution therapy.

Thirty-six hypothyroid patients had total thyroidectomy for cancer. Thirty of them were studied before and during hormone replacement therapy, 1-1 .1 microgram/kg triiodothyronine (T3) per day. Mean treatment period was 90 days. During treatment mean serum total cholesterol (TC), triglycerides (TG), the ratio of TC to TG in very-low-density lipoprotein and the prevalence of the "double pre-beta VLDL lipoproteinemia" (Double-PBL) were significantly reduced as compared to the pretreatment values. The VLDL peptides were separated bysoelectric focusing (IEF) in polyacrylamide gel. The relative content of apolipoprotein E (arginine-rich apoprotein) and the E/C-peptides ratio were significantly reduced after T3 therapy. On the contrary, the content of C11 peptide was significantly increased. Apoprotein E was positively correlated with serum TC. The proportion of the intermediate density lipoprotein fraction, evaluated by agarose gel electrophoresis, consistently decreased after treatment. The results of our study suggest that thyroid hormones affect the metabolism of remnant lipoproteins.

Sentinel node biopsy in breast cancer.

Axillary lymph node dissection (ALND) is an important tool in staging patients with breast cancer. However, this procedure has several sequelae and complications and improvement in early diagnosis has led to an increasing number of cases of ALND in which axillary nodes are found to be negative. Sentinel node (SN) biopsy appears to be a less invasive alternative to ALND. The aim of the present study was to assess whether SN is a reliable indicator for axillary staging. We studied 126 consecutive patients with T1-T2 breast cancer and clinically negative axilla. In each case, 30-70 MBq of 99mTC-labelled colloidal albumin was injected subdermally close to the tumour and SN was visualised by lymphoscintigraphy. Surgery was performed 24 h after injection and the SN was removed under the guidance of a gamma ray-detecting probe. ALND was then undertaken in all cases. A histopathologic examination of the SNs was then made and the findings compared with the status of the other axillary nodes. SNs were identified and biopsied in 115/126 patients (91.3%) and correctly predicted the axillary status in 110/115 cases (95.6%). In five cases (4.4%), SNs were found to be negative, but other axillary nodes were positive. Our data confirm that SN biopsy is a good method for staging the axilla in patients with breast cancer. However, before SN biopsy can replace ALND in daily clinical practice, some technical aspects must be standardized, and clinical trials are required in order to clarify the prognostic impact of false-negative cases.

Role of scintigraphy with tumor-seeking agents in the diagnosis and preoperative staging of malignant thyroid nodules.

The commonly used procedure for the diagnosis of thyroid nodule malignancy is based on high resolution thyroid ultrasonography (US) combined with US-guided fine needle aspiration cytology (FNAC). The other imaging procedures have a limited role in malignancy diagnosis. However, nuclear medicine procedures, particularly scintigraphy with tumor-seeking agents such as 201-thallium (201-TI), 99mTc-methoxy-isobutyl-isonitrile (99mTc-MIBI) and 99mTc-tetrofosmin may play an important role in the differential diagnosis between benign and malignant thyroid nodules in cases of non-diagnostic or inadequate FNAC. This type of scintigraphy can also be used in the follow-up of patients with cytologically 'high'-risk thyroid nodules such as Hurtle cell adenomas and follicular adenomas. Furthermore, scans with tumor-seeking agents can be helpful in determining the preoperative staging of thyroid carcinoma patients with locally advanced disease, and in accurately evaluating the extent, and consequently, the surgical management of the disease.

Nuclear medicine imaging procedures in differentiated thyroid carcinoma patients with negative iodine scan.

Radioiodine treatment following surgery is an effective therapy in differentiated thyroid carcinoma (DTC) patients. However, in DTC patients with metastases characterized by very low or absent iodine uptake, total thyroidectomy and radical loco-regional lymphoadenectomy is the only effective therapeutic approach. In the present article, we have discussed the most recently available nuclear medicine techniques utilized for the detection of DTC metastases that have lost the capacity to trap radioiodine. A review of the data published in the literature has been presented, and a comparative analysis made of the results obtained by other imaging modalities such as high resolution neck ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). In our experience, the most sensitive and accurate imaging procedure is represented by the combination of neck US and whole body 99mTc-methoxy-isobutylisonitrile (99mTc-MIBI) scintigraphy; this combination might be proposed as a first-line diagnostic approach in DTC patients with increased serum thyroglobulin (Tg) levels and negative high dose 131I scans.

The role of external beam radiotherapy in the management of differentiated thyroid cancer.

Well differentiated thyroid cancers (DTC), usually having an indolent course, are generally treated by surgery, i.e., total or near total thyroidectomy, followed by radioiodine and TSH suppressive therapy with thyroid hormone. The beneficial effect of external beam radiotherapy (EBRT) in the treatment of selected metastatic sites (i.e., brain and bone) or for palliation in cases of locally advanced inoperable disease is widely accepted. In contrast, its efficacy in improving postoperative locoregional disease control is still controversial. A better definition of subgroups of patients at high risk of local failure is mandatory. At present, patients older than 40-45 years affected by papillary cancers with macro- or microscopic postoperative residual disease and with extensive extrathyroid invasion appear to benefit from EBRT performed in addition to surgery and radioiodine. The role of EBRT in patients with radioiodine non-responsive progressive disease will also be discussed.

Renal involvement in subjects with peripheral atherosclerosis.

BACKGROUND: Ischemic nephropathy is an important cause of renal failure in western countries. Subclinical renal function abnormalities may exist in patients with extrarenal atherosclerosis, and may precede the onset of overt ischemic nephropathy. METHODS: To assess the impact of extrarenal atherosclerosis on the kidney, we evaluated renal function in 89 subjects with differing degrees of peripheral atherosclerosis, without manifest clinical or laboratory signs of ischemic nephropathy and renovascular hypertension. All laboratory testing, ultrasonography with Doppler analysis for the localization of peripheral vascular disease (carotid and lower limb arteries), and non-invasive evaluation of renal function by radionuclide studies of renal plasma flow (MAG3 clearance) and glomerular filtration (DTPA clearance), as well as total, LDL and HDL cholesterol, and triglycerides were determined; smoking habit was recorded. By combining sonographic data on arterial tree stenosis (ATS), the subjects were grouped according to the atherosclerotic vascular damage (ATS involvement). RESULTS: Despite no change in plasma creatinine and DTPA clearance (from 91.58+/-26.53 mL/min/1.73 m2 to 93.47+/-24.82), MAG3 clearance progressively declined with the severity of vascular damage (from 244.86+/-60.60 mL/min/1.73 m2 to 173.59+/-58.74). Stepwise multiple regression analysis indicated that MAG3 clearance was best explained by ATS involvement (standardized beta coefficient -0.40; p<0.001), smoking habit (-0.34; p= 0.004), and serum LDL-cholesterol (-0.24; p<0.035). CONCLUSIONS: The renal hemodynamic profile in atherosclerotic patients might constitute functional evidence of the silent phase of ischemic renal disease. The findings suggest that renal function should be carefully assessed in patients with extrarenal atherosclerosis, particularly in those with classic cardiovascular risk factors.

Recent advances in preoperative and intraoperative nuclear medicine procedures in patients with primary hyperparathyroidism.

Although bilateral neck exploration is traditionally considered as the treatment of choice in patients with primary hyperparathyroidism (HPT), several surgical techniques of limited neck exploration have been proposed over the last 10 years in primary HPT patients with a high probability to be affected by a solitary parathyroid adenoma. The availability in recent years of highly sensitive and accurate preoperative imaging modalities, particularly the parathyroid scintigraphy with 99mTc-MIBI and high resolution neck ultrasonography, allowed to increase the rate of primary HPT patients as candidates to a selective parathyroidectomy. One of the most innovative techniques for limited surgery is the minimally invasive radio-guided parathyroidectomy that is based on the intraoperative detection of the parathyroid adenoma under the guidance of a gamma probe allowing the removal of the parathyroid adenoma through a small 2-cm skin incision. However, if a minimally invasive parathyroidectomy is taken into consideration, accurate preoperative imaging is mandatory not only to distinguish patients with a solitary parathyroid adenoma from those with multi-glandular disease but also to diagnose patients with concomitant thyroid nodule(s) that can cause false-positive results at radio-guided surgery. In the present study the most recent advances reached with preoperative localizing imaging of parathyroid adenomas are reviewed and the techniques proposed to perform a minimally invasive radio-guided surgery are discussed with particular regard to the therapeutic efficacy and cost-effectiveness analysis.

Clinical role of positron emission tomography (PET) in endocrine tumours.

Positron emission tomography (PET) is considered one of the most effective nuclear medicine imaging modality in oncology. In many types of malignant tumours PET has proven to be high sensitive in detecting both primary neoplasm and metastatic disease both before therapy for staging purposes and after surgery, radiotherapy and chemotherapy during follow-up. In particular, PET showed high accuracy in differentiating post-treatment scar from viable tumoural tissue and high sensitivity in visualising very small metastatic foci as those in normal-sized (less than 1 cm in diameter) lymph nodes. A large variety of positron emitter tracers have been produced for PET imaging: the most widely used tracer in clinical oncology is 18F-fluoro-2-deoxy-D-glucose (18F-FDG). Deoxy-glucose (DG) is a glucose analog that enters the cell using specific transmenbrane carrier proteins (especially GLUT-1). Once within the cytoplasm, DG is phosphorylated to FG-6-phosphate but does not appear to be further metabolised. In most malignant tumours there is an increase of the glycolityc metabolism which accounts for an increase of the FDG uptake. However, the metabolic cellular activity can be only slightly increased or even normal in well differentiated and slow growing tumours as some endocrine neoplasms. In the present review, the clinical usefulness and limits of PET imaging are discussed in the management of patients with endocrine tumors.