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E Bombardieri

Publications and source records attributed to E Bombardieri.

At least 37 records · Page 2Linked to original sources

Diagnostic and prognostic tumor markers in the gastrointestinal tract.

The gastrointestinal tract is the most common site of malignancies of any anatomic system in the body. An early detection of primary tumors of the bowel, pancreas, liver, stomach, and esophagus is often difficult in asymptomatic patients and for this reason these tumors are often detected at a relatively advanced stage, when symptoms lead to a diagnostic evaluation. Furthermore, gastrointestinal tract tumors have an extremely variable prognosis; thus, the identification of new prognostic parameters may be useful for selecting patients to more tailored therapies. In this work, the main molecular, genetic, tissular, and circulating tumor markers proposed for diagnosis and prognosis of gastrointestinal malignancies are reviewed and discussed.

Biomarkers, Tumor↗

Nuclear medicine imaging of neuroendocrine tumours.

Different tracers have been proposed in nuclear medicine to visualize neuroendocrine tumours: the majority are based on specific uptake mechanisms while some are aspecific. Among the most important gamma-emitting tracers, radiolabelled metaiodobenzylguanidine (123I or 121I-MIBG) and 111In-pentetreotide should be mentioned. In particular. good results can be obtained with 111In-pentetreotide scanning, which visualizes more than 70% of all neuroendocrine tumours and in some indications, as in gastro-entero-pancreatic (GEP) tumours, has a diagnostic sensitivity superior to that of conventional radiological imaging. Radiolabelled monoclonal antibodies have at present only a storical value, while a series of new peptides represent interesting subjects in areas currently being regarded. Positron emission tomography (PET) is a successful modality to detect cancer and recent years, has demonstrated a great diagnostic value in a large series of tumour types. 18F-deoxyglucose (FDG)-PET has also been used to diagnose tumours of neuroendocrine origin. Even if 18F-FDG has been successfully and widely employed in oncology, it has not demostrated a significant uptake in well differentiated neuroendocrine tissues. On the contrary, other positron emitter tracers seem to be more promising. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. This uptake seems to be selective and some clinical evidence has demonstrated that it allows the detection of more lesions with PET than with CT or octreotide scintigraphy. Another radiopharmaceutical in development for PET is 11C L-DOPA, which seems to be useful in visualizing endocrine pancreatic tumours. This Review summarizes the potential of several nuclear medicine techniques in the diagnosis of neuroendocrine tumours and stresses the renewed role of nuclear -medicine in the management of this disease.

3-Iodobenzylguanidine↗

Clinical significance of blood chromogranin A measurement in neuroendocrine tumours.

BACKGROUND: Tumour marker measurement gives clinicians useful information for the follow-up and management of patients with neuroendocrine tumours (NETs). The currently used tumour markers for NETs are neuron-specific enolase (NSE) and chromogranin A (CgA). The clinical accuracy of these biomarkers depends on histotype and disease extent. CgA is thought to be the optimal marker for most NETs, as it is independent of the biological characteristics of the tumour. AIM OF THE STUDY: In this study we investigated the value of CgA assessment with respect to the other biomarkers in the diagnosis and follow-up of patients with different types of NETs. PATIENTS AIND METHODS: We measured CgA, NSE, carcinoembryonic antigen (CEA) and urine 5-hydroxy-3-indoleacetic acid (5-HIAA) in 290 patients with 127 gastroenteropancreatic (GEP) tumours, 49 neuroblastomas, 36 lung tumours, 24 medullary thyroid carcinomas (MTCs). 15 pNETs, 12 paragangliomas. 7 Merkel's cell carcinomas (MCCs) and 20 NETs of unknown origin. CgA and 5-HIAA were quantitated by immunoenzymatic assays, while NSE and CEA were determined by radioimmunoassays. RESULTS: The biomarkers' specificity in GEP tumours was 86% for CgA, 100% for NSE, 91% for CEA and 100% for 5-HIAA. The corresponding sensitivity was 68% for CgA, 33% for NSE, 15.4% for CEA and 35% for 5-HIAA. The sensitivity of CgA largely depends on disease extent or presence of functioning tumours and is highest in metastatic and syndromic patients. CgA determination in GEP tumour monitoring is useful to evaluate the response to therapy and to follow up patients with liver metastases. In neuroblastomas the overall specificity of NSE and CgA was 50%, and 83%, respectively. In these tumours NSE sensitivity was close to 90% in all clinical stages, while the sensitivity of CgA depended on clinical stage (50% for stage I and II, 60% for stage III and 100% for stage IV tumours). Also in this type of tumour changes in CgA levels correlated with objective response. In paragangliomas CgA measurement may provide useful clinical information. Measurement of CgA is of use in the diagnosis of lung carcinoids, while its value in MTCs, pNETs and MCCs is very limited. CONCLUSIONS: CgA was confirmed to be the best tumour marker currently available for identifying patients suffering from NETs of the GEP system, lung carcinoids and neuroblastomas. CgA evaluation is recommended in the follow-up of patients with such tumours.

Biomarkers, Tumor↗

Bone scintigraphy and the added value of SPECT (single photon emission tomography) in detecting skeletal lesions.

Skeletal metastases are one of the major clinical problems for the oncologist. Over the last several decades bone scintigraphy has been used extensively in detecting bone involvement since it can provide information about disease location, prognosis and the effectiveness of treatment. Bone scan offers the advantage of total body examination, and images bone lesions earlier than other techniques. In this paper the main clinical problems related to the most common applications of bone scan in breast, prostate, lung cancer and other tumours are discussed. The experience carried out at the National Cancer Institute of Milan by using bone SPECT to detect single bone metastases is reported. One hundred and eighteen patients with bone metastases (from different tumour types: breast, lung, prostate, lymphomas, etc.) were studied by planar scintigraphy, SPECT and other radiological modalities (CT, MRI or X-rays). The overall performances of bone SPECT were sensitivity: 90.5% (19/21), specificity 92.8% (90/97), positive predictive value 73% (19/26), negative predictive value 97.8% (90/92), accuracy 92.4% (109/118). Considering breast cancer, the most frequent pathology in our series, and the lumbar spinal tract, the most common skeletal segment involved, the figures of merit of SPECT were: sensitivity 100% (4/4), specificity 95.3% (41/43), positive predictive value 66.7% (4/6), negative predictive value 100% (41/41), accuracy 95.7% (45/47). In conclusion bone SPECT showed very good performances, in particular improving the predictive value of planar scan in the diagnosis of vertebral metastases.

Bone Neoplasms↗

Clinical utility of biochemical marker of bone remodelling in patients with bone metastases of solid tumors.

Bone turnover is characterized both by the formation of new bone by the osteoblasts and the resorption of old tissue by the osteoclast. This process takes place only on the surface of bone and can be described in terms of spatio-temporal events that are the bone metabolic unit and the bone remodelling cycle. The former consists of a discrete group of cells (osteoblasts and osteoclasts) involved in a particular remodelling event while the latter represents the succession of resorption and formation. In a typical remodelling cycle, resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is regulated either by local or systemic factors, including electrical and mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids, calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and cytokines. Recently different circulating biochemical markers have been proposed for the investigation of bone turnover. In addition to classical parameters such as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers have gained clinical attention because of their accuracy in assessing the dynamic changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline, pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the recent advances in this field and the clinical application of markers of bone turnover in patients with bone metastases from solid tumors. Also the cellular and molecular bases of bone remodelling are reported with details.

Acid Phosphatase↗

[Radioisotopic imaging of neuroendocrine tumours. Which radiopharmaceutical and which diagnostic procedure?].

Neuroendocrine tumours can be visualized by several nuclear medicine modalities based on different mechanisms of cellular uptake. The most widely used radiopharmaceutical are the metaiodobenzylguanidine (123I/131I MIBG) and pentetreotide (111In pentetreotide). The first tracer follows the metabolic pathway of norephinephrine while the second one binds to somatostatin receptors which are expressed with high intensity on the neuroendocrine tissue. Some radiopharmaceuticals (Anti-CEA, Anti-CgA, Anti-GD2 monoclonal antibodies) have today only an experimental value, others such as 99mTc(V)DMSA had in the past very limited indications (medullary thyroid cancer) but at present their production is going to be stopped. An interesting series of new peptides showing a great affinity for the receptors/structures expressed by the neuroendocrine tissue is under evaluation in order to obtain a better tumour specificity. Among the positron-emitting radiopharmaceuticals, the 18F-fluorodeoxyglucose (FDG), in spite it is considered the most widely used tracer for clinical PET in oncology, did not show a satisfactory uptake in the well differentiated neuroendocrine tissues. On the contrary 18F-FDG is the best radiopharmaceutical to visualize those rare poorly differentiated neurondocrine tumours with a high proliferative index. For this reason also in this area, new radiopharmaceuticals have been studies and developed. A serotonin precursor 5-hydroxytryptophan (5-HTP) labelled with 11C has shown an increased uptake in carcinoids. Another radiopharmaceutical in development for PET is 11C L-DOPA which seems to be useful in visualizing endocrine pancreatic tumours. 18F-DOPA whole body PET may be a more promising imaging approach. Aim of this review is to summarize the potential of nuclear medicine techniques in the diagnosis of neuroendocrine tumours and to stresses the renewed role of nuclear medicine in the management of this disease.

Endocrine Gland Neoplasms↗

PET imaging in breast cancer.

The basis of tumour imaging with PET is a specific uptake mechanism of positron emitting radiopharmaceuticals. Among the potential tracers for breast cancer (fluorodeoxyglucose, methionine, tyrosine, fluoro-estradiol, nor-progesterone), 2-deoxy-2-fluoro-D-glucose labelled with fluorine (FDG) is the most widely used radiopharmaceutical because breast cancer is particularly avid of FDG and 18F has the advantages of a relatively long physical half-life. Mammography is the first choice examination in studying breast masses, due to its very good performances, an excellent compliance and the best value regarding the cost/effectiveness aspects. However FDG-PET revealed to be effective in the study of patients with ambiguous mammographies. The FDG uptake in tissue correlates with the histological grade and potential aggressiveness of breast cancer and this may have prognostic consequences. Besides the evaluation of breast lesions, FDG-PET shows a great efficacy in staging lymph node involvement prior surgery and this could have a great value in loco-regional staging. Whole body PET provides also information with regard to metastasis localizations both in soft tissue and bone, and plays an important clinical role mainly in detecting recurrent metastatic disease. In fact for its metabolic characteristics PET visualizes regions of enhanced metabolic activity and can complements other imaging modalities based on structural anatomic changes. Even though CT and MRI show superior resolution characteristics, it has been demonstrated that PET provides more accurate information in discriminating between viable tumour, fibrotic scar or necrosis. Several clinical evidences demonstrated that FDG-PET is also able to predict wether cancer will respond to the therapy, or, when applied at the end of the treatment, it can assess the response to the therapy. These statements are coming from the examination of more than 2000 breast cancer patients included in 88 articles or abstracts on studies in which FDG-PET was used for breast cancer detection.

Axilla↗

The luteinising hormone-releasing hormone analogue triptorelin with or without the aromatase inhibitor formestane in premenopausal breast cancer: effects on bone metabolism markers.

BACKGROUND: the combination of a luteinising hormone-releasing hormone (LH-RH) analogue and an aromatase inhibitor (AI) induces greater oestrogen suppression than the analogue alone in premenopausal breast cancer. However, very few data on the biological effects of such a combination are currently available. AIM OF THE STUDY: the short-term effects of treatment with the LH-RH analogue triptorelin alone or in association with the AI formestane on bone metabolism were investigated in premenopausal breast cancer. Circulating levels of the bone formation markers carboxy-terminal and amino-terminal propeptides of type I procollagen (PICP and PINP) and the bone resorption marker cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. In addition, serum levels of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 and interleukin 6 (IL-6) were evaluated. PATIENTS AND METHODS: twenty-one patients with advanced breast cancer were randomly given triptorelin monthly alone (n=10, arm A) or in combination with formestane fortnightly (n=11, arm B). Blood samples were collected over a 3-month period. RESULTS: serum PICP and PINP levels increased significantly over time (P=0.0065 and 0.0197 in arm A and B, respectively); no change in ICTP levels was observed. A rise in IGF-I and IGFBP-3 levels was seen in each treatment group, but only the increase in IGF-I was significant (P=0.0138, always). The on-treatment levels of the bone turnover markers and IGF-system components were inversely correlated with serum oestrogens. Neither treatment modalities significantly affected serum IL-6 levels over time. No difference in the behaviour of any of the assessed biomarkers was observed between patients with or without skeletal metastases. CONCLUSION: it is worth noting that complete oestrogen depletion, at least in our case series, seems to increase only osteoblastic activity markers. The observed modifications appear to be related to oestrogen depletion per se rather than the degree of oestrogen suppression or the different therapeutic regimen administered.

Adult↗

Positron-emission tomography with [18F]fluorodeoxyglucose. Part I. Biochemical uptake mechanism and its implication for clinical studies.

Over the past decades, Positron Emission Tomography has opened a new field of imaging. Nowadays, this technique is being used for diagnosing, staging disease as well as for prognostic stratification and monitoring therapy. In this respect, [18F]fluorodeoxyglucose (FdGlc) is by far the most commonly used PET agent. Many factors have been identified being responsible for a high uptake of this agent in malignancy. However, additional factors such as tumour treatment may interfere with the uptake mechanism. Knowledge of all these factors is a prerequisite for an optimal interpretation of PET studies and, consequently, for a reliable judgement of tumour status. In this article, a review is given of the factors influencing FdGlc uptake and the implications for clinical studies.

Citric Acid Cycle↗

Results and potential of somatostatin receptor imaging in gastroenteropancreatic tract tumours.

BACKGROUND: Somatostatin receptor imaging with 111In-pentetreotide is widely accepted as an essential step in the management of patients affected by neuroendocrine tumours of the gastro-entero-pancreatic tract. Many data are already available on the high sensitivity of this technique. METHODS: We present a review of the published data together with the results of a study involving 253 patients submitted to somatostatin receptor imaging in three Italian hospitals. The patients were divided into two groups treated with different acquisition and processing protocols. RESULTS: The overall sensitivity was as high as (169/176) 96% in both groups, while the specificity was higher in the group in which semi-quantitative evaluation of somatostatin receptor density was performed: (23/26) 88% vs (39/51) 76%. The use of this method is recommended to increase the specificity of 111In-pentetreotide imaging. CONCLUSIONS: Our results with somatostatin receptor imaging in neuroendocrine tumours of the gastro-entero-pancreatic tract demonstrate that all figures of merit are excellent when imaging is accurately performed and analysed by experienced operators.

Adolescent↗

Role of 131I-metaiodobenzylguanidine (MIBG) in the treatment of neuroendocrine tumours. Experience of the National Cancer Institute of Milan.

BACKGROUND: 45 patients with neuroendocrine tumours (22 neuroblastomas, 10 phaeochromocytomas, 3 para-gangliomas, 6 medullary thyroid carcinomas and 4 carcinoids) underwent 131I-MIBG therapy. METHODS: All patients, with the exception of 5 phaeochromocytoma cases with nonoperable disease, had previously been treated with conventional therapies. Patients had a previous diagnostic scintigraphy with 131I-MIBG (activity 20-44.4 MBq) or with 123I-MIBG (activity 74-222 MBq). The therapeutic activity for adults ranged from 3.7 to 7.4 GBq of 131I-MIBG; for children from 2.7 to 5.5 GBq. All treatments were repeated at not less than 4-weekly intervals. The neuroblastoma patients were divided into two groups: the first included 14 patients with advanced metastatic disease not responding to previous treatments; the second included 8 patients with documented residual neuroblastoma tissue that could not be surgically removed after first-line therapy. RESULTS: In neuroblastoma patients with advanced disease resistant to previous therapies 2 out of 14 showed a partial response, 9 stable disease and 3 progression of cancer. In neuroblastoma patients with residual disease (7 evaluable out of 8) we obtained 3 partial responses; a stable response was observed in 3 patients. The results of MIBG therapy in the group of phaeochromocytoma patients (9 evaluable out of 10) consisted of 3 partial responses, 5 stable disease and 1 progression. Evaluation of the response carried out on the basis of biochemical parameters increased the responses and MIBG therapy showed good effectiveness in controlling the functional symptoms. In the group of paraganglioma patients we observed 1 complete, 1 partial and 1 stable response. In patients with medullary thyroid carcinoma a partial response was observed in 1 patient with mediastinal metastases and 2 disease stabilisations were seen in another 2 patients. Patients with carcinoids who underwent MIBG therapy showed 3 disease stabilisations. The overall toxicity was acceptable, especially considering that the majority of our patients had had previous myelotoxic treatments (chemotherapy and/or radiotherapy, alone or in combination). CONCLUSIONS: On the basis of our experience we can conclude that 131I-MIBG therapy is effective and also well tolerated.

3-Iodobenzylguanidine↗

Which kinds of lymph node metastases can FDG PET detect? A clinical study in melanoma.

UNLABELLED: The purposes of this study were to establish the diagnostic accuracy of FDG PET for lymph node metastases and to determine the smallest detectable volume of disease. METHODS: Using FDG PET, we preoperatively studied 56 lymph node basins in 38 patients with a clinical or instrumental diagnosis of lymph node metastases from melanoma. All lymph node basins underwent node dissection. The FDG PET results were compared with the postoperative histopathology results. PET images were obtained using a GE 4096 WB scanner, after injection of a mean activity of 496 MBq (range, 366-699 MBq) of FDG. RESULTS: The efficacy of FDG PET in the diagnosis of involved lymph node basins was good. Sensitivity was 95% (35/37); specificity, 84% (16/19); accuracy, 91% (51/56); positive predictive value, 92% (35/38); and negative predicative value, 89% (16/18). Metastases were shown histologically in 114 of 647 surgically removed lymph nodes. FDG PET detected 100% of metastases > or = 10 mm, 83% of metastases 6-10 mm, and 23% of metastases < or = 5 mm. Moreover, FDG PET had high sensitivity (> or = 93%) only for metastases with more than 50% lymph node involvement or with capsular infiltration. CONCLUSION: Our study shows that FDG PET has a reasonable sensitivity and specificity for detecting the presence or absence of lymph node metastases in patients with melanoma. However, even if able to detect small volumes of subclinical macroscopic disease, FDG PET cannot detect subclinical microscopic disease with acceptable sensitivity. The specificity of FDG PET is good, but some false-positive results may occur.

Adult↗

Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors.

BACKGROUND: Chromogranin A (CgA), neuron specific enolase (NSE), carcinoembryonic antigen (CEA), and urinary 5-hydroxyindole-3-acetic acid (5-HIAA) are the markers currently used in the diagnosis, prognosis, and follow-up of patients with neuroendocrine tumors (NETs). The authors examined the role of such biomarkers in a large series of patients with NETs. METHODS: One hundred and twenty-seven patients entered the study. Multiple blood and 24-hour urine specimens were assayed for biomarker quantitation. RESULTS: The accuracy of each marker was assessed in patients with (n = 106) and without (n = 21) disease. CgA proved to be the best marker (specificity of 85.7% and sensitivity of 67.9%). Patients with disease had significantly higher CgA and NSE levels compared with disease free patients (P = 0.00003 and P = 0.00240, respectively). NSE and 5-HIAA determination showed a very high specificity (100%) but a rather low sensitivity (32.9% and 35.1%, respectively). CEA was found to have little diagnostic value (sensitivity of 15.4%). CgA was the most sensitive marker for detecting patients with disseminated disease and 5-HIAA displayed the highest sensitivity in identifying syndromic patients. Tumor marker modifications were studied during follow-up. In particular, rises in CgA were associated with progressive disease in 83.3% of cases and stable CgA was associated with stable disease in 53.8% of cases. The relation between CgA modifications and liver lesions during follow-up also was studied; increases in CgA levels were associated with local progression in 100% of cases and stable marker levels were found in 68.7% of the patients with unchanged lesions. CONCLUSIONS: The results of the current study demonstrate that CgA has the highest accuracy and is the most reliable biomarker reflecting the clinical evolution of NETs.

Biomarkers↗

Accuracy evaluation of fusion of CT, MR, and spect images using commercially available software packages (SRS PLATO and IFS).

PURPOSE: A problem for clinicians is to mentally integrate information from multiple diagnostic sources, such as computed tomography (CT), magnetic resonance (MR), and single photon emission computed tomography (SPECT), whose images give anatomic and metabolic information. METHODS AND MATERIALS: To combine this different imaging procedure information, and to overlay correspondent slices, we used commercially available software packages (SRS PLATO and IFS). The algorithms utilize a fiducial-based coordinate system (or frame) with 3 N-shaped markers, which allows coordinate transformation of a clinical examination data set (9 spots for each transaxial section) to a stereotactic coordinate system. The N-shaped markers were filled with fluids visible in each modality (gadolinium for MR, calcium chloride for CT, and 99mTc for SPECT). The frame is relocatable, in the different acquisition modalities, by means of a head holder to which a face mask is fixed so as to immobilize the patient. Position errors due to the algorithms were obtained by evaluating the stereotactic coordinates of five sources detectable in each modality. RESULTS: SPECT and MR position errors due to the algorithms were evaluated with respect to CT: deltax was < or = 0.9 mm for MR and < or = 1.4 mm for SPECT, deltay was < or = 1 mm and < or = 3 mm for MR and SPECT, respectively. Maximal differences in distance between estimated and actual fiducial centers (geometric mismatch) were in the order of the pixel size (0.8 mm for CT, 1.4 mm for MR, and 1.8 mm for SPECT). In an attempt to distinguish necrosis from residual disease, the image fusion protocol was studied in 35 primary or metastatic brain tumor patients. CONCLUSIONS: The image fusion technique has a good degree of accuracy as well as the potential to improve the specificity of tissue identification and the precision of the subsequent treatment planning.

Algorithms↗

Nuclear medicine procedures in lung cancer.

Although radiography, computed tomography and magnetic resonance imaging are still the methods of choice for the study of lung cancer, they have certain limitations in the determination of the nature of suspicious lung nodules, the evaluation of mediastinal involvement, the assessment of the viability of previously treated lesions and the diagnosis of tumour relapse. There is a wide range of current oncological requirements related to lung cancer: detection of malignant lesions at the earliest stage and in the most effective way; the definition of the biological characteristics of a lesion (proliferation, aggressiveness, differentiation, etc.); the need to define the operability of the patient (function of residual lung and staging); and the need to evaluate the behaviour of the tumour (response to therapy, early detection of recurrences, metastatic spread). Most of the efforts of the nuclear medicine community have been focussed on diagnosis, staging, restaging and therapy monitoring of lung cancer. Many radiopharmaceuticals have been employed for this, including gallium, monoclonal antibodies, somatostatin analogues, lipophilic cations and positron emission tracers. There is ample evidence that nuclear medicine techniques may provide complementary information with respect to anatomical imaging, for example in the assessment of preoperative function by means of ventilation and perfusion scintigraphy, or in tumour localisation by means of specific tumour-seeking agents. However, clinical data suggest that, when properly used, nuclear medicine procedures in some cases may be not only complementary to radiology but essential for the clinical management of lung cancer. An example of such a procedure is fluorodeoxyglucose positron emission tomography (FDG PET) the introduction of which has greatly contributed to confirmation of the clinical value of nuclear medicine in this field. FDG PET has proved of great help in lung cancer management and its cost-effectiveness in lung cancer staging is firmly established. In this review the results of the most important nuclear medicine techniques are summarised and their value in clinical practice is discussed. General, updated information is provided about the epidemiology, biology and clinical management of lung cancer, and about the role of nuclear medicine in these areas.

Female↗