Transthyretin Amyloidosis Cardiomyopathy in Greece: Clinical Insights from the National Referral Center.

BACKGROUND: Clinical characteristics and outcomes of patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) vary by region, necessitating the acquisition of country-specific evidence for proper management. METHODS: This is an observational study including sequential patients presenting in the Amyloidosis Reference Center of Greece, from 01/2014 to 12/2022. ATTR-CM was diagnosed by positive scintigraphy and exclusion of light-chain amyloidosis or positive biopsy typing. Genetic testing was performed in all cases. RESULTS: One-hundred and nine ATTR-CM patients were included (median age, 81 years) of which 15 carried TTR mutations (27% Val30Met). Most patients (82%) presented with heart failure and 59% with atrial fibrillation, while 10% had aortic stenosis. Importantly, 78 (71.6%) had clinically significant extracardiac manifestations (45% musculoskeletal disorder, 40% peripheral neuropathy and 33% gastrointestinal symptoms). Sixty-five (60%) received disease-specific treatment with tafamidis. Estimated median survival was 48 months; advanced NYHA class, National Amyloidosis Center stage, eGFR<45 ml/kg/1.73m2, NT-pro-BNP>5000 pg/mL were associated with worse survival, while tafamidis treatment was associated with improved survival in patients with IVS≥ 12 mm. DISCUSSION: These are the first data describing the characteristics, management, and outcomes of patients with ATTR-CM in Greece, which could influence local guidelines. SHORT TITLE: Transthyretin cardiomyopathy in Greece.

The Emerging Role of the Gut Microbiome in Cardiovascular Disease: Current Knowledge and Perspectives.

The collection of normally non-pathogenic microorganisms that mainly inhabit our gut lumen shapes our health in many ways. Structural and functional perturbations in the gut microbial pool, known as "dysbiosis", have been proven to play a vital role in the pathophysiology of several diseases, including cardiovascular disease (CVD). Although therapeutic regimes are available to treat this group of diseases, they have long been the main cause of mortality and morbidity worldwide. While age, sex, genetics, diet, tobacco use, and alcohol consumption are major contributors (World Health Organization, 2018), they cannot explain all of the consequences of CVD. In addition to the abovementioned traditional risk factors, the constant search for novel preventative and curative tools has shed light on the involvement of gut bacteria and their metabolites in the pathogenesis of CVD. In this narrative review, we will discuss the established interconnections between the gut microbiota and CVD, as well as the plausible therapeutic perspectives.

Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by accumulation in the heart interstitium of amyloid fibrils formed by misfolded proteins. Most common CA types are light chain amyloidosis (AL) caused by monoclonal immunoglobulin light chains and transthyretin amyloidosis (ATTR) caused by either mutated or wild-type transthyretin aggregates. Previously considered a rare disease, CA is increasingly recognized among patients who may be misdiagnosed as undifferentiated heart failure with preserved ejection fraction (HFPEF), paradoxical low-flow/low-gradient aortic stenosis, or otherwise unexplained left ventricular hypertrophy. Progress in diagnosis has been due to the refinement of cardiac echocardiographic techniques (speckle tracking imaging) and magnetic resonance (T1 mapping) and mostly due to the advent of bone scintigraphy that has enabled noninvasive diagnosis of ATTR, limiting the need for endomyocardial biopsy. Importantly, proper management of CA starts from early recognition of suspected cases among high prevalence populations, followed by advanced diagnostic evaluation to confirm diagnosis and typing, preferentially in experienced amyloidosis centers. Differentiating ATTR from other types of amyloidosis, especially AL, is critical. Emerging targeted ATTR therapies offer the potential to improve outcomes of these patients previously treated only palliatively.

Imaging of cardiac amyloidosis by (99m)Tc-PYP scintigraphy.

OBJECTIVE: Cardiac amyloidosis (CA) is an underestimated and underdiagnosed cause of cardiac insufficiency. Despite being often considered as a solitary entity attributable to extracellular deposition of fibrillary proteins, there exist at least two different pathophysiologic backgrounds, with different clinical course and treatment. a) In light-chain cardiac amyloidosis (immunoglobulin light-chain amyloidosis-AL) the fibrils consist of light-chain immunoglobulins produced by a clonal plasma cell population in bone marrow. b) In CA related to transthyretin (transthyretin-related amyloidosis - ATTR), whether familial amyloid cardiomyopathy or senile systemic amyloidosis, monomers or dimers of the normally tetrameric protein of transthyretin are deposited in the myocardium. Today, definitive diagnosis of cardiac amyloid disease is based on endomyocardial biopsy in conjunction with immunohistochemical parameters or, in ambiguous cases, with mass spectroscopy. Several radiotracers have been hitherto tried in the detection of CA. SUBJECTS AND METHODS: In this pilot study technetium-99m pyrophosphate ((99m)Tc-PYP) was administered to patients suffering from CA, aiming to differentiate scintigraphically between AL and ATTR. Twelve patients (8 males, aged [mean±SD] 70,6±13,2y; 4 females, aged 65,7±9,9y) were enrolled for the discrimination between AL and ATTR. Diagnosis was confirmed by biopsy combined with the clinical and laboratory evaluation of the patients. Myocardial scintigraphy (planar and tomographic imaging) was conducted at 1, 2 and/or 3h after intravenous administration of 555-925MBq (99m)Tc-PYP. Myocardial radiotracer uptake was evaluated optically and also by a semiquantitative method. Two regions of interest (ROI) were drawn: one over the heart and another over the contralateral hemithorax, to calculate the corresponding heart-to-contralateral (H/CL) count ratio. According to established reference standards, a cut-off H/CL value of 1.5 best discriminates between the two conditions. (99m)Tc-PYP scintigraphy revealed diffuse intense myocardial uptake upon visual evaluation that was also verified semi-quantitatively in 6 patients, all of which had ATTR. Faint or no myocardial tracer uptake was found in 4 patients who were diagnosed with AL. Two AL patients had a borderline positive scan on visual evaluation but their H/CL ratios did not exceed the value of 1.5. In three patients, we also attempted scintigraphy with the tracer pentavalent (99m)Tc-dimercaptosuccinic acid. Results and possible mechanisms of uptake are discussed. The sensitivity and specificity of scintigraphy with (99m)Tc-PYP was high, albeit the small number of patients. IN CONCLUSION: These preliminary results are compatible with current international literature, and demonstrate that scintigraphy with (99m)Tc-PYP may prove a simple, non-invasive and widely available method in the identification of patients with the ATTR subtype, thus optimizing therapeutic decisions.

Technetium-99m labelled red blood cells scintigraphy and not iminodiacetic acid cholescintigraphy facilitates the discrimination of hepatic cirrhosis from fibrosis.

OBJECTIVE: This pilot study was designed to investigate the efficacy of technetium-99m labelled red blood cells ((99m)Tc-RBC) compared with (99m)Tc-mebrofenin cholescintigraphy ((99m)Tc-MHS), in the diagnosis of hepatic dysfunction at early stages. SUBJECTS AND METHODS: Twenty four patients, 8 with hepatic fibrosis and 16 with cirrhosis, at Child-Pugh stage A to C and 20 age-matched controls were examined by (99m)Tc-RBC and by (99m)Tc-MHS. Dynamic acquisition and static images were semiquantitatively analused by studying the liver-to-heart (L/H) ratio estimated by both the (99m)Tc-RBC and (99m)Tc-MHS methods. The L/H ratios were compared between fibrosis, cirrhotic stages and controls, by Student's t test. Linear regression analysis of the L/H ratios for both methods has been applied in the whole study population. RESULTS: Labelled RBC could statistically differentiate fibrotic from normal liver parenchyma (P<0.001), whereas the (99m)Tc-MHS could not (P: 0.13). The L/H ratios of cirrhotic lesions using both methods were significantly lower than those in controls: (P<0.000001 for (99m)Tc-RBC and P<0.0001 for (99m)Tc-MHS). Statistically significant difference was demonstrated by both modalities between fibrotic and cirrhotic lesions ((99m)Tc-RBC: P: 0.003 and (99m)Tc-MHS: P: 0.024). CONCLUSION: Our study although in a limited number of patients suggested that as opposed to (99m)Tc-MHS, scintigraphic evaluation by (99m)Tc-RBC could be useful in the discrimination of patients with liver fibrosis, cirrhosis and normal controls.

Towards the optimization of nuclear medicine procedures for better spatial resolution, sensitivity, scan image quality and quantitation measurements by using a new Monte Carlo model featuring PET imaging.

The aim of this study was to develop a Monte-Carlo model that can be used for the optimization of positron emission tomography (PET) procedures and image quality metrics. This model was developed using the Monte Carlo package of Geant4 application for tomographic emission (GATE) and the software for tomographic image reconstruction (STIR) with cluster computing to obtain reconstructed images. The PET scanner used in this study was the General Electric Discovery-ST (US). The GATE model was validated by comparing results obtained in accordance with the National Electrical Manufacturers Association NEMA-NU-2-2001 protocol [Mawlawi et al (2004) and Bettinardi et al (2004)]. All images were reconstructed with the commonly used 2D filtered back projection and the 3D reprojection algorithms. We found that the simulated spatial resolution in terms of full width at half maximum (FWHM) agreed within less than 3.29% in 2D and less than 2.51% in 3D with published data of others, respectively. The 2D values for the sensitivity, scatter fraction and count-rate were found to agree within less than 0.46%, 4.59% and 7.86%, respectively with these published values. Accordingly, our study showed that the corresponding 3D values were found to agree to less than 1.62%, 2.85% and 9.13%, respectively with Mawlawi et al (2004) published values. Sensitivity, which was also estimated without the presence of attenuation material by simulating an ideal source, showed differences between the extrapolated and the ideal source values (with and without attenuation) ranging in 2D from 0.04% to 0.82% (radial location R=0cm) and 0.52% to 0.67% in 3D mode (radial locations R=10cm). The simulated noise equivalent count rate was found to be 94.31kcps in 2D and 66.9kcps in 3D at 70 and 15kBq/mL respectively, compared to 94.08kcps in 2D and 70.88kcps in 3D at 54.6kBq/mL and 14kBq/mL respectively, from the published by others values. The simulated image quality was found in excellent agreement with these published values. In conclusion, our study showed that our Monte Carlo model can be used to assess, optimize, simplify and reduce the simulation time for the quality control procedure of PET scanners. By using this model, sensitivity can be obtained in a more simplified procedure. Reconstructed images by STIR can be also used to obtain radiopharmaceutical distribution of images and direct dose maps, quite useful to nuclear medicine practitioners.

[Is major depression in middle-aged men correlated with bone density decrease? A study on Greek population].

During the last 10 years there has been an increasing interest in studying the coexistence of osteoporosis and depression in the male population, due to the increased morbidity and mortality in the patients' life. The present retrospective study evaluates the effect of major depression on the bone density of Greek middle-aged men. By using the method of dual-energy X-rays absorptiometry (DEXA) we reviewed the bone mineral density (BMD) studies performed in the lumbar spine (LS) and/or femoral neck, in 97 men of the white race, aged 55 years with mean age±standard deviation (SD)= 65±10.6 years, and body mass index (BMI) 30.2±4. The patients were divided in two groups, based on the coexistence (Group A) or absence of major depression (Group B). In group A men, the incidence of osteoporosis was 34.8% and osteopenia 39.5%, while in group B the corresponding percentages were 9.3% and 42.6%. Statistically significant difference was observed in mean BMD between Group A (0.876±0.170) and Group B (0.961±0.136) at the level of P=0.008, and also in mean T score (-1.72±1.57 versus -1.06±1.17) at the level of P value: 0.02 in both groups, while the diagnosis of osteoporosis between the two groups was statistically significantly different too (P=0.001. Pearson R: 0.3, P=0.004). Furthermore, the model of multiple linear regression and ANOVA table revealed statistically significantly depression of 0.252 and 0.575 units in mean BMD value and mean T score respectively in man with major depression in comparison to a mentally healthy man of the same age and BMI (regression coefficient b, P< 0.02). In conclusion, we observed statistically significant difference in mean BMD and mean T score values between major depression and mentally healthy men. Moreover, almost triple relative risk for the development of osteoporosis was shown in men with depression as compared to mentally healthy men (RR: 3.8, P=0.02). Cortisone intake, hypertension and smoking were statistically independent factors for male depression and BMD. The clarification of the underlying interactive mechanism between major depression, sympathetic system activation, age and bone resorption is important.

Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

Breast density, scintimammographic (99m)Tc(V)DMSA uptake, and calcitonin gene related peptide (CGRP) expression in mixed invasive ductal associated with extensive in situ ductal carcinoma (IDC + DCIS) and pure invasive ductal carcinoma (IDC): correlation with estrogen receptor (ER) status, proliferation index Ki-67, and histological grade.

BACKGROUND: We evaluated the variation of calcitonin gene related peptide (CGRP) expression in patients with mixed invasive with extensive in situ ductal carcinomas (IDC + DCIS) and pure IDC, in relation to mammographic breast density (%BD), proliferation-seeking radiotracer (99m)Tc(V) dimercaptosuccinic acid (DMSA) uptake (scintimammographic-SMM), proliferation index Ki-67, and estrogen receptor (ER) status. We also assessed CGRP expression with histological grade. METHODS: We studied retrospectively 24 women with suspicious findings on mammography who were evaluated preoperatively with (99m)Tc(V)DMSA scintimammography. Histology revealed 12 IDC (grade II in 8, grade III in 4 patients; mean size ± SD, 2.6 ± 1.3 cm; mean age ± SD, 66.5 ± 13.1 years) and 12 IDC + DCIS (grade II in 6, grade III in 6 patients; DCIS component mean size ± SD, 5.3 ± 1.8 cm; IDC component mean size ± SD, 2.5 ± 1.1 cm; mean age ± SD, 58.5 ± 15.1 years). Immunohistochemistry for CGRP, Ki-67, and ER status was performed in all 24 surgical specimens. BD and SMM were calculated by computer-assisted methods and were statistically correlated with CGRP expression. BD, SMM, Ki-67, and ER were statistically compared between IDC and IDC + DCIS, whereas CGRP, Ki-67, and ER were compared between patients with BD >25 and <25%. CGRP was also compared (t test) between grade II and grade III in both groups. RESULTS: Overall positive correlation was found between BD and CGRP (r = 0.577, P < 0.001). Positive correlation was established between SMM and CGRP only in IDC + DCIS (r (SMM(IDC+DCIS)-CGRP) = 0.634, P < 0.05). CGRP and Ki-67 were significantly higher in patients with BD >25% compared with <25% BD patients (P = 0.00008 and P = 0.014, respectively). BD and SMM were significantly higher in CGRP(+) than in CGRP(-) patients as well as in IDC + DCIS compared with IDC. Ki-67 was significantly higher, whereas ER was significantly lower, in IDC + DCIS than in IDC. In all patients, CGRP was significantly higher in grade II as compared with grade III (P = 0.005). In the mixed group (IDC + DCIS), grade II cancers had also significantly higher CGRP values as compared with grade III ones (P = 0.004). In pure IDC, no statistical difference was found between grade II and III (P = 0.4). CONCLUSIONS: ΒD, SMM, CGRP, and Ki-67 were significantly increased, whereas ER was significantly decreased, in IDC + DCIS as compared with IDC, indicating that IDC + DCIS is an entity that is more aggressive, ER independent, and possibly associated with a pathway linked to stromal involvement and CGRP activity.

[Cutaneous melanoma; diagnostic procedures and their evaluation in diagnosing and mapping sentinel nodes. Part 2].

The second part of this review describes the advantages, and evaluates the radionuclide-guided methods for sentinel lymph node localization and also evaluates the intraoperative application of the blue dye technique in melanoma. By combining the two techniques, the detection rate rises to 96%-98%. The presence of cancer cells in the sentinel node is histopathologically shown by using hematoxylin-eosin and by using sensitive techniques for the detection of micrometastases. Immunohistochemical tech-niques specific for epithelial markers and polymerase chain reaction examination are also applied. Sentinel lymph node biopsy suggests whether regional elective lymphade-nectomy shall be performed.

Ibuprofen induces reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA uptake in severe epithelial breast hyperplasia without atypia.

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n  =  4) and without atypia (n  =  4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p  =  .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p  =  .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

Reduced uptake of the proliferation-seeking radiotracer technetium-99m-labelled pentavalent dimercaptosuccinic acid in a 47-year-old woman with severe breast epithelial hyperplasia taking ibuprofen: a case report.

INTRODUCTION: Recent studies have reported a risk reduction in the progression of benign breast disease to breast carcinoma through COX-2 pathways. CASE PRESENTATION: We present a case of severe epithelial hyperplasia in a 47-year-old woman with increased breast density submitted to scintimammography by the proliferation-imaging tracer Technetium-99m-labelled pentavalent dimercaptosuccinic acid, before and after an oral ibuprofen treatment for 4 weeks. The radiotracer uptake after ibuprofen intake was significantly reduced, both visually and by semi-quantitative analysis, based on a calculation of lesion-to-background ratios. CONCLUSION: In proliferating breast lesions, scintigraphically displayed reduction in Technetium-99m-labelled pentavalent dimercaptosuccinic acid uptake may indicate inhibition by ibuprofen in the pathway of malignant epithelial cell transformation.

[Cutaneous malignant melanoma; diagnostic procedures and their evaluation in diagnosing and mapping sentinel nodes].

Cutaneous malignant melanoma represents 4% of all the malignant neoplasms. Nevertheless, 79% of the fatal malignant skin diseases are attributed to melanoma. In melanoma patients, the most important prognostic factor is the regional lymph node invasion. The present article describes the classical diagnostic, staging and therapeutic strategies in melanoma patients. In the realm of cutaneous melanoma, pre-operative lymphoscintigraphy and the intra-operative gamma-probe detection, removal and biopsy of the sentinel lymph node(s), comprise convenient, procedures, virtually lacking morbidity. The definition of sentinel includes the first lymph node or nodes, draining the lymph from the primary lesion, thereby attributed with the highest probability of harbouring migrating metastatic cells. A sentinel lymph node negative for malignancy accurately "predicts" the absence of melanoma cell invasion in all the rest regional and distant lymphatic basins. The method aims in the best discrimination of high-risk patients, as candidates for selective lymphadenectomy, with or without adjunctive treatment. Radionuclide-guided lymphatic mapping and surgery is based on the phagocytosis of colloidal-based radiopharmaceuticals by the macrophages encountered in functional tumour-infiltrated sentinel nodes. The nuclear methods successfully add to the staging and the potential surgical treatment of the disease.

[Lymphatic system and lymphoscintigraphy].

Starting from Hippocrates era, the lymphatic system has been an interesting area of study for its anatomy, physiology, pathophysiology and imaging. The present review describes the history of the lymphatic system and lymphoscintigraphy. Lymphoscintigraphy comprises a simple, non-invasive imaging method of the lymphatic system and the sentinel lymph node or nodes. Additionally the intra-operative gamma-probe detection and the blue dye technique are also presented. The nuclear methods have been incorporated in the algorithm of the diagnostic approach and the therapeutic treatment of cutaneous melanoma and breast cancer, while further experience is warranted in other solid malignancies.

Erdheim-Chester disease: symmetric uptake in the (99m)Tc-MDP bone scan.

Erdheim-Chester disease (E-C D) is a rare clinicopathologic entity with nearly pathognomonic radiographic features. About half of the affected exhibit extraskeletal manifestations, including involvement of the hypothalamus-pituitary axis, lung, heart, retroperitoneum, skin, liver, kidneys, spleen and orbit. This disease usually affects individuals in their fifties to their seventies and has a male preponderance. The lesions of E-C D consist of lipid-storing CD68 (+) and CD1a (-) non-Langerhans cell histiocytes, either localized to the bone or involving multiple systems of the body as well. Skeletal involvement is characteristically bilateral and symmetric, exhibiting an osteosclerotic pattern in the metaphysis and diaphysis of the long bones, usually sparing epiphysis. We recently had a 68 years old male patient with E-C D, with a mild and persistent knee pain, who was subjected to a 3-phase technetium-99m methylene diphosphonate ((99m)Tc-MDP) bone-scan and subsequently to gallium-67 citrate ((67)Ga-C) whole body scan. The characteristic symmetric pattern of these scans raised the question of E-CD disease. The patient showed an excellent symptomatic response to high-dose steroids. However, the symptoms recurred after discontinuation of treatment.

The potential role of Calcitonin Gene-Related Peptide (CGRP) in breast carcinogenesis and its correlation with 99mTc-(V)DMSA scintimammography.

OBJECTIVES: Experimental data suggest a role for calcitonin gene-related peptide (CGRP) in normal breast development and angiogenesis. This pilot study correlated CGRP with neoangiogenesis and the uptake of the tumor-seeking, proliferation-imaging radiotracer pentavalent technetium-99m dimercaptosuccinate (99mTc-(V)DMSA) in invasive and preinvesive breast lesions. METHODS: Among women evaluated preoperatively by 99mTc-(V)DMSA scintimammography, 29 invasive ductal carcinomas (IDCs) were retrospectively studied: 15 isolated (Group I); 14 mixed with preinvasive pathologies (ductal carcinoma in situ [DCIS] and/or epithelial hyperplasia [EH]; Group M). CGRP staining and neoangiogenesis were compared between invasive and DCIS/EH regions and were correlated. 99mTc-(V)DMSA displayed a diffusely increased uptake pattern corresponding to DCIS/EH; its lesion-to-background (L/B) ratio was compared between images acquired at 10 and 60 minutes and its retention ratio (RR) was correlated with CGRP. RESULTS: Seven of 15 group I and 10 of 14 group M patients (58.6% of the population) were CGRP-positive. CGRP was prevalent in the DCIS/EH component of mixed-lesions (even in the surrounding normal epithelium of nearly half), with declining intensity as advancing from DCIS/EH to high-grade IDC. Similarly, neoangiogenesis was considerably higher in DCIS/EH than in group I pure IDCs. A significant CGRP-neoangiogenesis correlation was verified only in group I. The diffuse 99mTc-(V)DMSA uptake exhibited significant, time-related L/B increase and a RR positively correlating with CGRP. CONCLUSIONS: CGRP expression and neoangiogenesis are intensified in mixed invasive-preinvasive breast lesions; an underlying relation may exist, requiring further investigation. CGRP also appears associated with 99mTc-(V)DMSA's propensity to depict preinvasive pathologies. This relationship could denote an additional proliferative role for CGRP.

[Indications and instructions to patients for a positron emission tomography-PET scan. The importance of the hybridic PET/CT-computerised tomography scan and which specialty should be responsible for its function].

Indications and instructions to patients for performing a positron emission tomography - PET scan are mentioned. Although PET camera was developed in 1970 its clinical indications were established in about 1998. The hybridic PET/CT- computerized tomography scanner appeared in 2001 and its clinical indications are still under discussion. These discussions refer to both the use of PET/CT as an acquisition correction and anatomic localization device for PET images (AC/A) and to its use as a diagnostic CT scan (dCT). Most of the patients submitted for a PET scan have already done a dCT scan. This was the case in 286 out of the first 300 patients referred to "Evangelismos" hospital in Athens for a PET scan. These two scans can be matched electronically. Extra cost, space, personnel and radiation absorption dose especially in children, are additional factors to be considered in using the PET/CT scanner. The specialty of Nuclear Medicine is now based on the PET camera, its best part and main equipment for molecular imaging. It is very much easier and faster for a Nuclear Medicine physician who routinely reports tomographic PET and SPET images, to be familiar with the CT images than for a Radiologist to get to "know how" about the PET camera and the whole Nuclear Medicine Department. Nuclear Medicine is about open radiation sources, molecular imaging, specific radio-pharmacology, radiobiology, radiation protection etc, while on the other hand in some countries, Nuclear Physicians have already spent, as part of their official training, six months in a Radiology Department whose function is considered to be at least 25% about the CT scanner. We come to the conclusion that the PET/CT scanner should be under the responsibility of the Nuclear Medicine Department and the Radiologist should act as an advisor.

Scintimammographic detection of usual ductal breast hyperplasia with increased proliferation rate at risk for malignancy.

OBJECTIVES: To estimate whether breast uptake of (99m)Tc-(V)DMSA and (99m)Tc-sestamibi in usual ductal epithelial breast hyperplasia (UDH) and apocrine metaplasia is related to cell proliferation rate (Ki-67) and oestrogen receptor (ER) expression, both of which are associated with the potential risk of evolving to malignancy. METHODS: Among patients referred for suspicious breast findings on palpation and/or mammography and evaluated preoperatively with both radiopharmaceuticals, we retrospectively studied 17 (10 with UDH: group I; and seven with apocrine metaplasia: group II). Lesion-to-background (L/B) ratios in early and late acquisitions were calculated for both radiotracers in both groups, as well as their retention ratios. Ki-67 and oestrogen receptor expression were determined immunohistochemically. The late L/B ratios between the two tracers were compared, as were the late ratios for each tracer between Ki-67 < or = 3% and > 3%, and between ER < or = 15% and > 15%. Linear regression analysis was also performed between L/B and retention ratios and Ki-67 expression. RESULTS: There was a significant increase of the (99m)Tc-(V)DMSA L/B ratio in late images as compared to the early images in group I (P<0.05), while in group II it was not significantly increased (P=0.084). (99m)Tc-sestamibi ratios did not demonstrate variability over time in either group (P=0.156 and 0.274, respectively). Significant coefficient correlation was found between the (99m)Tc-(V)DMSA L/B(late) ratios and retention ratios and Ki-67 levels only for group I (r=0.889, P<0.001 and r=0.802, P<0.01, respectively). The (99m)Tc-(V)DMSA L/B(late) ratios in group I were significantly higher when Ki-67 > 3% than when Ki-67 < or = 3% (P=0.016) but did not differ considerably between ER > 15% and < or = 15% (P=0.732). CONCLUSION: (99m)Tc-(V)DMSA uptake in UDH correlates with Ki-67 expression. This could prove useful in identifying women with benign but high-risk breast pathologies who might benefit from chemoprophylaxis.