Additional value of integrated 18F-choline PET/4D contrast-enhanced CT in the localization of hyperfunctioning parathyroid glands and correlation with molecular profile.

PURPOSE: The localization of hyperfunctioning parathyroid gland(s) (HPTG) in patients with primary hyperparathyroidism (PHPT) with negative or inconclusive first-line imaging is a significant challenge. This study aimed to evaluate the role of integrated 18F-choline PET/4D contrast-enhanced computed tomography (4DCeCT) in these patients, compare its detection rate and sensitivity with those of 18F-choline PET/CT and (4DCeCT), and analyse the association between choline metabolism and morphological, biochemical and molecular parameters of HPTG. METHODS: We prospectively enrolled 44 PHPT patients with negative or inconclusive first-line imaging. 18F-Choline PET/CT and 4DCeCT were performed at the same time, and integrated 18F-choline PET/4DCeCT images were obtained after coregistration. Experienced physicians examined the images. The SUVratio and degree of contrast enhancement were recorded for each positive finding. Histopathology, laboratory and multidisciplinary follow-up were used as the standard of reference. Both the detection rates and sensitivities of the three imaging modalities were calculated retrospectively. Immunohistochemistry was performed to evaluate the molecular profile of HPTGs. RESULTS: 18F-Choline PET/4DCeCT was positive in 32 of 44 patients with PHPT (detection rate 72.7%), and 31 of 31 surgically treated patients (sensitivity 100%). These results were significantly (p < 0.05) better than those of 18F-choline PET/CT (56.8% and 80%, respectively) and those of 4DCeCT (54.5 and 74%, respectively). A significant correlation between SUV and calcium level was found. In a multivariate analysis, only calcium level was significantly associated with 18F-choline PET/4DCeCT findings. SUVratio and Ki67 expression were significantly correlated. CONCLUSION: Integrated 18F-choline PET/4DCeCT should be considered as an effective tool to detect PHPT in patients with negative or inconclusive first-line imaging. Choline metabolism is correlated with both calcium level and Ki67 expression in HPTG.

Bayesian analysis of hybridization and introgression between the endangered european mink (Mustela lutreola) and the polecat (Mustela putorius).

Human-mediated global change will probably increase the rates of natural hybridization and genetic introgression between closely related species, and this will have major implications for conservation of the taxa involved. In this study, we analyse both mitochondrial and nuclear data to characterize ongoing hybridization and genetic introgression between two sympatric sister species of mustelids, the endangered European mink (Mustela lutreola) and the more abundant polecat (M. putorius). A total of 317 European mink, 114 polecats and 15 putative hybrid individuals were collected from different localities in Europe and genotyped with 13 microsatellite nuclear markers. Recently developed Bayesian methods for assigning individuals to populations and identifying admixture proportions were applied to the genetic data. To identify the direction of hybridization, we additionally sequenced mtDNA and Y chromosomes from 78 individuals and 29 males respectively. We found that both hybridization and genetic introgression occurred at low levels (3% and 0.9% respectively) and indicated that hybridization is asymmetric, as only pure polecat males mate with pure European mink females. Furthermore, backcrossing and genetic introgression was detected only from female first-generation (F1) hybrids of European mink to polecats. This latter result implies that Haldane's rule may apply. Our results suggest that hybridization and genetic introgression between the two species should be considered a rather uncommon event. However, the current low densities of European mink might be changing this trend.

Low thyroglobulin concentrations after thyroidectomy increase the prognostic value of undetectable thyroglobulin levels on levo-thyroxine suppressive treatment in low-risk differentiated thyroid cancer.

DESIGN: Recombinant human TSH-stimulated thyroglobulin (Tg) levels (rhTSH-Tg) are sufficient for early follow-up of low-risk differentiated thyroid cancer (DTC) patients after thyroidectomy and radioiodine (131I) remnant ablation (RAI). Serum Tg levels at the time of remnant ablation (ablation-Tg) is thought to be related with rhTSH-Tg and may be predictive of recurrent disease. During long-term follow-up, Tg levels on levo-T4 (L-T4) suppressive treatment (suppressive-Tg) is sufficiently sensitive to avoid further evaluations in patients with undetectable rhTSH-Tg. The aim of our study was to verify whether, in a subgroup of low-risk DTC patients, the association of low ablation-Tg levels (<10 microg/l) with undetectable suppressive-Tg concentrations has a sufficient negative predictive value (NPV) for recurrence of disease, leading to avoid rhTSH testing. METHODS: We enrolled 169 low-risk DTC patients treated by thyroidectomy + RAI and undetectable suppressive-Tg at 12-month followup. In all patients, we retrospectively evaluated ablation-Tg and rhTSH-Tg. For all patients, 2-yr follow-up was available. RESULTS: Based on rhTSH-Tg>2 microg/l, relapsing disease was histologically proven in 2 patients. rhTSH-Tg levels between 0.6-2.0 microg/l, with no evidence of disease, was observed in 10 patients (6%). One hundred and fifty-seven patients showed undetectable rhTSH-Tg. The NPV of undetectable suppressive- Tg was 92.8%. The ablation-Tg level was <10 microg/l in 140 patients. In this group, the NPV of undetectable suppressive- Tg was 100%. CONCLUSION: Our data indicate that undetectable suppressive-Tg value, combined with ablation- Tg levels <10 microg/l, may avoid a significant number of high-cost rhTSH-Tg test.

Therapeutic Strategies and Clinical Outcome in Papillary Thyroid Microcarcinoma: A Multicenter Observational Study.

PURPOSE: Papillary thyroid microcarcinoma (MPTC) has an excellent prognosis. We aimed to evaluate the evolution of therapeutic strategies over time and the clinical outcome of MPTC. METHODS: In this retrospective multicenter observational study in a northwest Italian region, patients with intrathyroidal, unifocal tumor ≤1 cm in size, incidentally found at histology or preoperative cytology diagnosis, were included. Exclusion criteria were a previous head-and-neck irradiation and/or node metastases. RESULTS: From 1985 to 2012, 437 patients had an MPTC diagnosis, which was incidental in 85% and preoperative in 15%. Patients with a preoperative diagnosis were younger at the time of diagnosis (47.6 ± 12.7 years, p < 0.01) and had a larger tumor (7.0 ± 2.5 mm, p < 0.0001) than patients with an incidental diagnosis (age 52 ± 13.5 years, size 4.4 ± 2.8 mm), but there were no differences in clinical outcome between both groups. We observed a significant (p < 0.001) reduction in radioiodine remnant ablation during the years. TSH levels were: <0.1 mIU/l in 27.5%, 0.1-0.5 mlU/l in 33.7%, 0.5-2.5 mlU/l in 32.6%, 2.5-4.2 mlU/l in 3.9%, and >4.2 mlU/l in 2.3% of patients. Six patients (1.37%) had nodal recurrence; 5 of them were cured after therapy. MPTC-linked mortality was null. CONCLUSIONS: We confirmed the favorable clinical outcome of MPTC. Despite the reduction in radioiodine ablation, overtreatment of MPTC is still observed.

Thyroid nodules with indeterminate cytology: prospective comparison between 18F-FDG-PET/CT, multiparametric neck ultrasonography, 99mTc-MIBI scintigraphy and histology.

PURPOSE: To evaluate the role of (18)F-flurodeoxiglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in predicting malignancy of thyroid nodules with indeterminate cytology. PATIENTS AND METHODS: We analysed 87 patients who have been scheduled to undergo surgery for thyroid nodule with indeterminate cytology. All patients underwent (18)F-FDG-PET/CT, multiparametric neck ultrasonography (MPUS), and (99m)Tc-methoxyisobutylisonitrile scintigraphy ((99m)Tc-MIBI-scan). Histopathology was the standard of reference. We compared the sensitivity (SE), specificity (SP), accuracy (AC), positive (PPV) and negative predictive (NPV) values of (18)F-FDG-PET/CT with those of (99m)Tc-MIBI-scan and MPUS in detecting cancer. Univariate and multivariate analyses evaluated the association between each diagnostic tool and histopathology. RESULTS: On histopathology, 69 out of 87 nodules were found to be benign and 18 to be malignant. The SE, SP, AC, PPV and NPV of (18)F-FDG-PET/CT were 94, 58, 66, 37 and 98% respectively. The SE, AC and NPV of (18)F-FDG-PET/CT were significantly higher than those of MPUS and (99m)Tc-MIBI-scan. The association of both positive (18)F-FDG-PET/CT and MPUS (FDG+/MPUS+) showed significantly lower SE (61% vs 94%) and NPV (88% vs 98%) than (18)F-FDG-PET/CT alone, but significantly higher SP (77% vs 58%). On univariate analysis, (18)F-FDG-PET/CT and the combination of FDG+/MPUS+ and of FDG+/MIBI- were all significantly associated with histopathology. On multivariate analysis, only FDG+/MIBI- was significantly associated with histopathology. CONCLUSION: The AC of (18)F-FDG-PET /CT in detecting thyroid malignancy is higher than that of (99m)Tc-MIBI-scan and MPUS. A negative (18)F-FDG-PET/CT correctly predicts benign findings on histopathology. The association of FDG+/MPS+ is significantly more specific than (18)F-FDG-PET/CT alone in identifying differentiated thyroid cancer. A positive (18)F-FDG-PET/CT is significantly associated with malignancy when qualitative (99m)Tc-MIBI-scan is rated as negative.

Megatherapy combining I(131) metaiodobenzylguanidine and high-dose chemotherapy with haematopoietic progenitor cell rescue for neuroblastoma.

Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has very poor prognosis which is estimated at 25%. Metabolic radiotherapy with I(131) MIBG appears a feasible option to enhance the effects of chemotherapy. Seventeen patients having MIBG-positive residual disease received 4.1-11.1 mCi/kg of I(131) MIBG 7-10 days before initiating the high-dose chemotherapy cycle consisting of busulphan 16 mg/kg and melphalan 140 mg/m(2) followed by PBSC infusion. We compared the toxicity in these patients to that seen in 15 control subjects with neuroblastoma who underwent a PBSC transplant without MIBG therapy. We observed greater toxic involvement of the gastrointestinal system in children treated with I(131) MIBG: grade 2 or 3 mucositis developed in 13/17 patients treated with I(131) MIBG and in 9/15 treated without it. Grade 1-2 gastrointestinal toxicity occurred in 12/17 children given MIBG and in 5/15 of the controls. One child receiving I(131) MIBG developed transient interstitial pneumonia. Another child who also received I(131) MIBG after PBSC rescue developed fatal pneumonia after the third course of metabolic radiotherapy. Our experience indicates that MIBG can be included in the high-dose chemotherapy regimens followed by PBSC rescue for children with residual neuroblastoma taking up MIBG. Attention should be paid to avoiding lung complications. Prospective studies are needed to demonstrate the real efficacy of this treatment.

99mTc-white cell scanning to detect gut inflammation in children with inflammatory bowel diseases or spondyloarthropathies.

OBJECTIVE: Gut inflammation is a common feature shared by inflammatory bowel diseases (IBD) and the spondyloarthropathies (SpA). The aim of the present study was to compare the reliability of a number of non-invasive investigations for the detection of an inflammatory process of the intestine. METHODS: Forty-two children were studied: (i) patients with a previous diagnosis of IBD (group A); (ii) patients with suspected IBD (group B); and (iii) patients with predominantly rheumatological manifestations associated with gastrointestinal symptoms (group C). All the patients were studied using 99mTechnetium-HMPAO labelled white cell scanning (99mTc-WCS), and abdominal ultrasound (US). In addition the ESR, serum class A immunoglobulins, faecal occult blood (OB) and faecal alpha 1-antitripsin level (F alpha 1-AT) were determined. Colonoscopy plus multiple biopsies and radiological study of the intestine were used as gold standards. RESULTS: 99mTc-WCS showed the highest sensitivity (85%) and specificity (100%) in detecting the presence of gut inflammation. This was followed by ESR and faecal occult blood (63% sensitivity, 44% specificity), F alpha 1-AT (43% sensitivity, 44% specificity) and IgA (42% sensitivity, 88% specificity). Ultrasound was informative in 28% of the active/affected patients, with a specificity of 75%. CONCLUSION: Although ileo-pancolonscopy remains the gold standard for the histological characterisation of gut inflammation, 99mTc-WCS represents the most reliable non-invasive test for its detection.

PET/CT imaging in neuroblastoma.

123Iodine-metaiodobenzylguanidine (123I-MIBG) scintigraphy is currently the tracer of choice for neuroblastoma (NB). It has high diagnostic accuracy and prognostic value for the assessment of patients after chemotherapy. A positive 123I-MIBG scan is also used for the basis of targeted radionuclide therapy with 131I-MIBG. I-123 MIBG scan however has some limitations which should be taken into account. Moreover the reasons for false negative MIBG results have not been entirely elucidated. Meticulous correlation with radiological examinations and recognition of the normal distribution pattern of 123I-MIBG in children is vital to obtain optimal results. With its technical superiorities, positron emission tomography/computed tomography (PET/CT) can be successfully introduced into the diagnostic workup of NB. Different PET tracers have been offered for imaging in patients with NB, and the efficacy of this modality has been compared with that of 123I-MIBG scan. Our review aims to analyze the present role of PET/CT imaging and radiopharmaceuticals in NB.

Radioguided occult lesion localization of cervical recurrences from differentiated thyroid cancer: technical feasibility and clinical results.

AIM: We explored the feasibility of radioguided occult lesion localization (ROLL) for radioiodine-negative cervical recurrences from differentiated thyroid cancer (DTC). METHODS: The procedure was performed in 32 patients (3 patients being operated twice); 15/32 patients had had multiple prior lymph node dissections ("hostile" anatomy). 99mTc-albumin macro-aggregates (99mTc-MAA) were injected intra-lesionally under ultrasound guidance; 2 to 18 hours later, a hand-held gamma-probe helped to localize the lesions intraoperatively and to ascertain removal of the radiolabeled lesions. Mini-invasive excision of the radiolabelled lesions was performed in 12 cases (m-ROLL), while a modified radical neck dissection was performed in 23 cases after radioguided lymphadenectomy (d-ROLL). Fifty-nine lesions were radiolabelled (mean size 11±4.5 mm). RESULTS: Radioguidance allowed to identify/remove 56/59 lesions (95%). Some leakage of 99mTc-MAA in the surrounding tissues hampered detection of 3 lesions, which were removed anyway (100% overall localization). Histopathology confirmed metastatic involvement of the radiolabeled lesions and some additional metastases in other nodes. Neither nerve injury nor hypoparathyroidism occurred. After a median follow-up of 29 months, 19 patients were disease-free, 12 patients developed loco-regional recurrences, 1 patient had distant metastases and 1 patient had both loco-regional and distant metastases. Recurrences rates were 33% for m-ROLL and 40% for d-ROLL. CONCLUSIONS: The ROLL technique is feasible in selected patients with loco-regional recurrence from DTC, proving to be particularly useful also in patients already submitted to cervical dissections and/or with small lesions located in surgically difficult sites. It can therefore have a clinical role in the management of cervical DTC recurrences.

Role of low-cost thyroid follow-up in children treated with radiotherapy for primary tumors at high risk of developing a second thyroid tumor.

AIM: Differentiated thyroid cancer (DTC) is uncommon in childhood and data on its prevalence as a second malignant neoplasm (SNM) after radiotherapy (RT) for malignancies are limited. We evaluated: 1) the incidence DTC in pediatric-oncologic patients treated with RT; 2) the relationship between DTC, RT and the features of the first malignancy; 3) the usefulness of thyroid follow-up in irradiated oncological patients. METHODS: We have followed up 252 patients treated with RT out of 966 oncologic pediatric patients. Thyroid follow-up included TSH level evaluation and neck ultrasonography. In the presence of thyroid nodule/s ≥1 cm and/or with ultrasonography suspicious for malignancy, fine needle aspiration biopsy (FNAB) was performed. When papillary/follicular lesions were detected by cytology, thyroidectomy was performed. If DTC was confirmed, patients underwent radioactive iodine (RAI) treatment. RESULTS: At least one thyroid nodule was detected in 106 irradiated patients (42%): 45 patients underwent FNAB and 27 underwent thyroidectomy. Seventeen DTC (6.7%) were found on histology. A higher incidence of DTC was seen in patients with neuroblastoma (38%) or Wilms' tumor (18%). One third of DTC showed capsule invasion, and one fourth node involvement. Eleven patients, treated with a single RAI treatment, showed undetectable thyroglobulin levels after rh-TSH-stimulation. Five patients underwent at least two RAI treatments: four patients showed complete remission and one patient partial remission. CONCLUSION: A high rate of DTC, often with invasive features, was observed in children treated with RT for primary tumors. This finding underlines the usefulness of thorough low-cost thyroid follow-up in this high-risk population.

Could [18]F-fluorodeoxyglucose PET/CT change the therapeutic management of stage IV thyroid cancer with positive (131)I whole body scan?

AIM: Stage-IV differentiated thyroid cancer (DTC) patients may present elevated serum thyroglobulin (Tg) levels associated with positive [(131)I] whole-body-scan (WBS). Nevertheless some patients in whom WBS does not reveal new sites of disease show increased Tg levels. This finding prompts thorough restaging in order to exclude the presence of metastases unable to concentrate iodine. The aim of our study was to evaluate the impact of [(18)F]FDG-PET/CT in both the assessment of overall extent of the disease and the therapeutic management in a group of stage-IV DTC patients. METHODS: On suspicious of non-iodine concentrating additional metastases, 20 stage-IV DTC patients with increasing Tg levels and stable positive post-therapy WBS were enrolled. Conventional imaging (CI) procedures, including neck ultrasonography, bone-scintigraphy and computed tomography (CT) were performed before [(18)F]FDG-PET/CT. RESULTS: [(18)F]FDG-PET/CT was positive in 16 out of 20 patients (80%). In 9 patients (45%) [(18)F]FDG PET/CT detected a larger number of tumour recurrences/metastatic sites than WBS+CI. [(18)F]FDG PET/CT findings prompted modification of the management of 11 patients (55%), in whom surgery or external radiotherapy were eventually considered more appropriate than radioactive iodine therapy. These further therapies improved the quality of life in several patients but did not change their survival rate. CONCLUSION: Our results showed that [18F]FDG-PET/CT can detect new radioiodine-negative metastases in advanced DTC patients with unchanged positive WBS and increasing Tg levels. [(18)F]FDG-PET/CT may constitute a useful tool in the choice of the best therapeutic strategy in such difficult cases.

Uncommon association of germline mutations of RET proto-oncogene and CDKN2A gene.

INTRODUCTION: Calcitonin measurement is advised in the diagnosis of thyroid nodules, as it is an accurate marker of medullary thyroid carcinoma (MTC). C-cell hyperplasia (CCH)-induced hypercalcitoninemia cannot be distinguished from that induced by MTC, unless surgery is performed. CASE: We report the clinical and biological features of a patient with a family history of cancer, including melanoma and pancreatic cancer, who had previously undergone surgery for melanoma. He presented the unusual association of papillary thyroid carcinoma (PTC), normocalcemic hyperparathyroidism, and hypercalcitoninemia with a pathological response to pentagastrin, which was histologically deemed secondary to CCH. Multiple endocrine neoplasia (MEN) 2A was diagnosed. RET gene analysis showed a p.V804M missense mutation in exon 14, a low- but variably penetrant defect found in both sporadic and MEN2A-associated MTC/CCH, and a p.G691S polymorphism in exon 11. Furthermore, the germline P48T mutation was found in the CDKN2A gene exon 1, which is known to be associated with melanoma and pancreatic cancer. The patient showed the uncommon coexistence of a germline mutation in two suppressor genes, RET and CDKN2A; this finding, deemed to be a mere coincidence, did not modify the phenotype expected by each single mutation. CCH associated with V804M RET mutation is a precancerous condition and surgery is recommended. In order to exclude MTC, surgery is advised in patients with a pathological calcitonin response to pentagastrin, in the absence of thyroid autoimmunity. CCH-induced hypercalcitoninemia can be associated with thyroid cancers other than MTC (e.g., PTC). Family history is important in scheduling specific genetic screening in high-risk patients and their relatives.

Conservation genetics and population history of the threatened European mink Mustela lutreola, with an emphasis on the west European population.

In species of great conservation concern, special attention must be paid to their phylogeography, in particular the origin of animals for captive breeding and reintroduction. The endangered European mink lives now in at least three well-separated populations in northeast, southeast and west Europe. Our aim is to assess the genetic structure of these populations to identify 'distinct population segments' (DPS) and advise captive breeding programmes. First, the mtDNA control region was completely sequenced in 176 minks and 10 polecats. The analysis revealed that the western population is characterized by a single mtDNA haplotype that is closely related to those in eastern regions but nevertheless, not found there to date. The northeast European animals are much more variable (pi = 0.012, h = 0.939), with the southeast samples intermediate (pi = 0.0012, h = 0.469). Second, 155 European mink were genotyped using six microsatellites. The latter display the same trends of genetic diversity among regions as mtDNA [gene diversity and allelic richness highest in northeast Europe (H(E) = 0.539, R(S) = 3.76), lowest in west Europe (H(E) = 0.379, R(S) = 2.12)], and provide evidences that the southeast and possibly the west populations have undergone a recent bottleneck. Our results indicate that the western population derives from a few animals which recently colonized this region, possibly after a human introduction. Microsatellite data also reveal that isolation by distance occurs in the western population, causing some inbreeding because related individuals mate. As genetic data indicate that the three populations have not undergone independent evolutionary histories for long (no phylogeographical structure), they should not be considered as distinct DPS. In conclusion, the captive breeding programme should use animals from different parts of the species' present distribution area.

Semiquantitative evaluation of regional cerebral flow by means of SPECT with 99mTc-hexamethyl-propylene amine oxime in hypertensive patients under treatment.

Cerebral SPECT with 99mTc-HM-PAO allows a semiquantitative evaluation of regional cerebral blood flow (rCBF). Using this method we studied 25 patients affected by slight-to-moderate degree hypertension, in effective pharmacological treatment, and a control group of normotensives. On the cross-sections symmetrical ROIs were traced at the level of the cerebral lobes and the cerebellum. From the counts obtained on the ROIs the rCBF values were calculated in percentage units with Lassen's algorithm. We found no significant differences between the rCBF values of the two groups. In 5 hypertensive patients, however, focal areas of hypoperfusion were evidenced. These patients did not differ from the other hypertensives by pressure levels or other risk factors. Neurological, tomographic and flowmeter examinations of the supraaortic arteries proved to be normal. It is possible that SPECT with 99mTc-HM-PAO identifies a subgroup of hypertensives at risk of future cerebrovascular pathology despite the setting up of an effective antihypertensive therapy.

Atypical thyroid dermopathy: clinical and immunological features of two cases.

Two cases of pretibial and atypical dermopathy in Graves' disease, showing many similarities in clinical pictures and natural histories, are reported. In both patients we observed abnormalities of some immunological parameters, namely reduction of Fc-positive T lymphocytes and positive TBI indexes. These abnormalities were concomitant to the appearance of dermopathy and apparently unrelated to other clinical manifestations of Graves' disease.

[New medico-nuclear applications in the postoperative study of kidney transplant]. / Moderne applicazioni medico-nucleari nello studio postoperatorio del trapianto renale.

Isotope nephrography is nowadays widely applied to the study of renal transplants. Major advantages of this technique have been obtained for the prognostic evaluation of transplant rejection and in the differential diagnosis of oliguria and anuria. The authors report on 14 cases of renal transplant recipients examined with renal scintigraphy 3-4 days after surgery. In agreement with literature data, the authors wish to stress the importance of the correct use of different tracers (DTPA, MAG3) for renal scintigraphy and nephrography. Problems and complications in renal transplants are studied with the simultaneous use of these tracers. The evaluation of renal blood flow and vascular complications requires radiopharmaceutical DTPA, which is excreted only by glomerular filtration. In contrast to 99mTc-DTPA, 99mTc-MAG3 is now the tracer of choice in the evaluation of tubular function. Some problems are still to be solved regarding patients management, such as the necessary chronologic relationship between surgical phases and nephrographic/scintigraphic examinations and early and late follow-up of renal transplant recipients.

Radioiodinated meta-iodobenzylguanidine in the diagnosis of childhood neuroblastoma.

In a group of 97 patients aged from 6 months to 12 years, all with suspected or proven neural crest tumours, metaiodobenzylguanidine (MIBG) scintigraphy was performed at the time of diagnosis and, in some instances, after induction chemotherapy. All the patients underwent a tumour biopsy with cytological and histological analysis, in addition to imaging examinations such as X-rays, ultrasound, computed tomography and magnetic resonance, within a short period before or after scintigraphy. In 82 of 97 cases MIBG was effective in detecting the primary tumour, hence the technique's sensitivity was 84%. A significant different of sensitivity between [131I]MIBG and [123I]MIBG was not demonstrated. As regards metastatic locations, MIBG scans revealed one or more bone metastases in 12 cases, bone marrow involvement (assumed to be present when diffuse and symmetric uptake in the spine, pelvis and possibly other skeletal sites were visualized) in 9 cases, and focal liver metastases or hepatomegaly in 4 cases. Probably owing to the restrictive diagnostic criterion adopted or to the early phase of the bone marrow involvement, the last was found by biopsy but missed by MIBG in 25 cases. The overall sensitivity in detecting metastases was low (48%), but it was much higher if only bone metastases were considered (81%). Twenty-nine patients who had positive scans at diagnosis were checked following 1-2 courses of induction chemotherapy (IC). MIBG scans remained positive in 22 primary tumours, while 7 primary masses were no longer detected. Out of 12 cases showing metastases at diagnosis, two cases with liver lesions became normal and in one case some, but not all, of the bone lesions were not detectable; 4 cases remained abnormal, while in 5 cases bone marrow involvement was not confirmed. Three cases were confirmed to be true negatives; in 4 other cases bone marrow involved not showing at diagnosis was revealed and confirmed by biopsy; 3 cases in which bone marrow involvement was not revealed by MIBG at diagnosis, had normal MIBG and biopsy results after IC; finally, 2 false negative bone marrow cases and 5 true negative cases at diagnosis remained unchanged, but were not checked by biopsy. Performing total body MIBG scintigraphy in childhood neuroblastoma at diagnosis is useful: 1) to predict the nature of the masses detected by other imaging techniques, when biopsy has not yet been performed; 2) for more accurate tumour staging, in addition to standard imaging investigations, MDP scintigraphy and bone marrow aspiration biopsy, thanks to its ability to detect metastatic lesions; 3) to anticipate the decrease in sensitivity of the technique in detecting both the primary mass and the metastases following induction chemotherapy.

Place of meta-[131I]iodobenzylguanidine in the treatment of neuroblastoma: the Genoa experience.

The aim of this paper is to focus on our previous experience with the treatment of Group 3 and 4 neuroblastoma patients and on the therapeutic use of [131I]MIBG, to better define the role of this radioactive drug in the treatment of neuroblastoma (NB). Analysis of the studies on Group 3 patients treated with chemotherapy and surgery showed that the progression-free survival (PFS) increased from 45% for patients treated before 1985 to 63% for patients treated in the period of 1985-1989 and to 78% for patients treated after 1989. [131I]MIBG administered in 17 Group 3 patients who did not achieve a radical excision of the primary resulted in 7 partial response (PR) and 5 minor response (MR), with 10 cases of long term survival. Results in Group 4 patients confirmed the good prognosis in the subset of children aged 6-12 months at diagnosis (PFS 86% at 5 years). In patients aged > 12 months at diagnosis intensive induction chemotherapy induced a higher response rate of 69% and PFS was 26% at 5 years. [131I]MIBG administered in advanced stage 4 patients induced a response in 50% of the cases (2 complete response [CR], 13 PR and 2 MR out of 34 children) and 8 children treated for residual primary (4 cases) or residual bone metastases (4 cases) are long term survivors. We conclude that [131I]MIBG is the treatment of choice in Group 3 patient with a residual primary tumor and could contribute to consolidate the response obtained in Group 4 patients.