Search

Background: Several genetic alterations have been demonstrated to contribute to the development and progression of melanoma. In this study, we further investigated the impact of key-regulator genes in susceptibility and pathogenesis of such a disease., Methods: A large series (N = 846) of sporadic and familial cases originating from South Italy was screened for germline mutations in p16(CDKN2A), BRCA2, and MC1R genes by DHPLC analysis and automated DNA sequencing. Paired primary melanomas and lymph node metastases from same patients (N = 35) as well as melanoma cell lines (N = 18) were analyzed for somatic mutations in NRAS, BRAF, and p16(CDKN2A) genes., Results: For melanoma susceptibility, investigations at germline level indicated that p16(CDKN2A) was exclusively mutated in 16/545 (2.9%) non-Sardinian patients, whereas BRCA2 germline mutations were observed in 4/91 (4.4%) patients from North Sardinia only. Two MC1R germline variants, Arg151Cys and Asp294His, were significantly associated with melanoma in Sardinia. Regarding genetic events involved in melanoma pathogenesis at somatic level, mutually-exclusive mutations of NRAS and BRAF genes were observed at quite same rate (about two thirds) in cultured and in vivo melanomas (either primary or metastatic lesions). Conversely, p16(CDKN2A) gene alterations were observed at increased rates moving from primary to metastatic melanomas and melanoma cell lines. Activation of the ERK gene product was demonstrated to be consistently induced by a combination of molecular alterations (NRAS/BRAF mutations and p16(CDKN2A) silencing)., Conclusion: Our findings further clarified that: a) mutation prevalence in melanoma susceptibility genes may vary within each specific geographical area; b) multiple molecular events are accumulating during melanomagenesis.

The accurate diagnosis of a sentinel node in melanoma includes a sequence of procedures from different medical specialities (nuclear medicine, surgery, oncology, and pathology). The items covered are presented in 11 sections and a reference list: (1) definition of a sentinel node, (2) clinical indications, (3) radiopharmaceuticals and activity injected, (4) dosimetry, (5) injection technique, (6) image acquisition and interpretation, (7) report and display, (8) use of dye, (9) gamma probe detection, (10) surgical techniques in sentinel node biopsy, and (11) pathological evaluation of melanoma-draining sentinel lymph nodes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for good-quality evaluation of possible spread to the lymphatic system in intermediate-to-high risk melanoma without clinical signs of dissemination.

The development of receptor targeting radiolabeled ligands has gained much interest in recent years for diagnostic and therapeutic applications in nuclear medicine. Cholecystokinin (CCK) receptors have been shown to be overexpressed in a subset of neuroendocrine and other tumors. We are evaluating binding and biodistribution properties of a CCK8 peptide derivative labeled with (99m)Tc(I)-tricarbonyl. The CCK8 peptide was modified at its N-terminus by adding to its N-terminus two lysine-histidine modules (KH), where histidine is coupled to the side chain of the lysine ((KH)(2)-CCK8). (99m)Tc(I)-tricarbonyl was generated with the IsoLinktrade mark kit. A431 cells stably transfected with a cDNA encoding for the human CCK2 receptor were utilized to determine binding affinity, internalization, and retention of the labeled peptide, in comparison with wild-type A431 cells. A nude mouse tumor model was obtained by generating A431-CCK2R and A431-control tumors in opposite flanks of the animals. High specific activity labeling with (99m)Tc was achieved. In A431-CCK2R cells, specific saturable binding was observed as well as evident internalization of the radiolabeled peptide after binding. Biodistribution experiments showed rapid, specific localization of (KH)(2)-CCK8 on A431-CCK2R xenografts compared with control tumors, although absolute uptake values were not markedly higher compared with background activity. Clearance of unbound radioactivity was both urinary and hepatobiliary. In imaging experiments, while targeting to CCK2R positive tumors could be appreciated, there was poor contrast between target and nontarget areas. (KH)(2)-CCK8 shows adequate in vitro and in vivo properties for CCK2R targeting although improvement of biodistribution warrant further development., ((c) 2008 Wiley Periodicals, Inc.)

Background: Only 2% to 4% of patients with melanoma will be diagnosed with gastrointestinal metastasis during the course of their disease. The most common sites of gastrointestinal metastases from melanoma include the small bowel (35%-67%), colon (9%-15%) and stomach (5%-7%), with a median survival of 6-10 months after surgery, and 18% survival at five years. Metastatic melanoma to the gallbladder is extremely rare and it is associated with a very poor prognosis., Case Presentation: We report a case of a 54-year old man presented to observation with diagnosis of 6.1 mm thick, Clark's level IV, ulcerated melanoma of the trunk, developing in the course of the disease metastatic involvement of the gallbladder as first site of recurrence, treated by laparoscopic cholecystectomy. To date only few cases of patients with metastatic melanoma of the gallbladder treated by this surgical procedure have been reported in literature., Conclusion: Gallbladder metastasis represents a rare event as a first site of recurrence. It must be considered a possible expression of systemic disease also despite radiological absence of other metastatic lesions. Laparoscopic approach has a possible therapeutic role, but open surgery has also a concomitant diagnostic purpose because gives the possibility of manual exploration of abdominal cavity, useful particularly to reveal bowel metastatic lesions, not easily identifiable by preoperative imaging examinations.

Background: Traditionally metastatic melanoma of the distal leg and the foot metastasize to the lymph nodes of the groin. Sometimes the first site of nodal disease can be the popliteal fossa. This is an infrequent event, with rare reports in literature and when it occurs, radical popliteal node dissection must be performed., Case Presentation: We report a case of a 36-year old man presented with diagnosis of 2 mm thick, Clark's level II-III, non ulcerated melanoma of the left heel, which developed during the course of the disease popliteal node metastases, after a superficial and deep groin dissection for inguinal node involvement. Five months after popliteal lymph node dissection he developed systemic disease, therefore he received nine cycles of dacarbazine plus fotemustine. To date (56 months after prior surgery and 11 months after chemotherapy) he is alive with no evidence of disease., Conclusion: In case of groin metastases from melanoma of distal lower extremities, clinical and ultrasound examination of ipsilateral popliteal fossa is essential. When metastatic disease is found, radical popliteal dissection is the standard of care. Therefore knowledge of anatomy and surgical technique about popliteal lymphadenectomy are required to make preservation of structures that if injured, can produce a permanent, considerable disability.

Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR)=6.31; p=0.0009), multiple primary melanomas (RR=3.43; p=0.0014), and early onset age (RR=4.56; p=0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.

Background: Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM)., Methods: One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up., Results: Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (> or =2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage., Conclusion: Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.

Purpose: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases., Experimental Design: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities., Results: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 mumol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12., Conclusions: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.

The aim of the present study was to assess the prognostic value of soluble interleukin-2 receptor (sIL-2R) serum levels in stage I-III melanoma patients. The levels of sIL-2R were determined using an enzyme immunometric test kit in 329 patients affected by malignant melanoma (MM) from 1995 to 2004. Correlations between sIL-2R values, baseline patients and tumour features were studied by contingency tables and the chi-square test. The Kaplan-Meier product limit method was applied to plot disease-free survival (DFS) curves. Univariate analysis was performed with the Log-rank test. Cox proportional-hazards regression was used to analyse the effect of several risk factors on DFS. In total, 2330 blood samples were collected during follow-up of 329 MM patients. Forty-five (13.7%) patients had Breslow tumour thickness1.00 and 2.00 and 4.00 mm. Ulceration was present in 64 cases (19.4%). Thirty-nine sentinel lymph nodes (SLNs) (11.8%) were infiltrated by MM. Soluble IL-2R values ranged from 130 to 1420 U/ml; median value was 500 U/ml. One hundred twenty-one (36.8%) patients presented with sIL-2R>600 U/ml at first measure (FM), 194 patients (58.9%) with values increasing up to or more than 600 U/ml [increasing values (IV) pattern]. A correlation was found between Breslow's tumour values and the IV sIL-2R pattern group (P=0.0304 with chi2 test). Gender, presence of ulceration, Breslow tumour thickness, FM and IV sIL-2R pattern groups had a significant prognostic value for DFS. At multivariate analysis, presence of ulceration, gender, FM and IV sIL-2R pattern groups emerged as independent prognostic factors for DFS. The 5-year DFS rate was 88% for patients with FM<600 U/ml and 76.9% for patients with FM>600 U/ml. In IV pattern, the 5-year DFS rate was 69.5% compared to 87% for patients with no sIL-2R values>600 U/ml during follow-up. sIL-2R values are associated with progression of MM. Further studies are needed to address the role of the IL-2/IL-2R/sIL-2R axis in melanoma biology.

Merkel cell carcinoma (MCC) is a rare, malignant skin cancer, exhibiting neuroendocrine differentiation, with a significant incidence of locoregional lymph nodal involvement (40%-73%). The accepted staging system classifies MCC as: stage I, localized skin disease; stage II, regional lymph node disease; stage III, metastatic disease. The clinical differentiation of stage I and II patients is difficult and understaging is frequent. Surgery, as first approach, represents the leading treatment for this neoplasm and, depending on stage consists in: local wide excision for stage I patients and local excision and lymphadenectomy for stage II. In our experience, lymphadenectomy, included in the initial treatment of all stage II patients, seemed to influence positively the prognosis. In comparing stage related recurrence and survival rates the results we obtained were better in stage II patients, where lymphadenectomy was included in the initial treatment than in stage I subjects, who received local excision alone as first treatment and lymphadenectomy as secondary treatment for nodal recurrence (overall recurrence rate 86% vs 20%, survival rate 71% vs 80% in stage I vs stage II patients). The performance of lymphadenectomy for stage I MCC could be reconsidered both for a more reliable staging of the disease and for a positive impact on recurrence and survival rates.

Cutaneous squamous cell carcinoma (SCC) is, in its most frequent presentation, a moderately aggressive neoplastic disease. It can, however, present in a moltitude of clinico-pathological variants, some of which are characterized by a more malignant attitude. It is important to determine which tumors, among the various histophenotypes, are high risk in order to establish the appropriate treatment and follow-up. Histologic subtype has been considered as a possible variable in determining the prognosis of cutaneous SCC. We report our experience with 3 cases of peculiar variants of cutaneous SCC.

Solitary metastases to the small bones and/or to the soft tissue of the hands and feet (acrometastases) are rare. We report a case of renal cell carcinoma (RCC) with big toe metastasis revealed before the primary tumor became apparent. The best treatment for a single metastasis is always surgical excision, regardless of the lesion being synchronous or metachronous. The biological behavior of metastatic RCC is unpredictable and only early diagnosis and treatment may favorably affect patient survival. Thus, metastatic RCC should be included in the differential diagnosis of all enlarging cutaneous nodules, wherever they develop.

Unlabelled: Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging and therapy. Receptors of the cholecystokinin family have been shown to be overexpressed in different types of neuroendocrine tumors. The purposes of this study were to evaluate the cholecystokinin octapeptide amide (CCK8) peptide tagged with a diethylenetriaminepentaacetic acid derivative (DTPAGlu) and to test whether a (111)In-labeled conjugate ((111)In-DTPAGlu-G-CCK8, a derivative containing the chelating agent DTPAGlu bound through a glycine linker at the N-terminal end of the bioactive peptide CCK8) is suitable for cholecystokinin-B receptor (CCKBR) imaging., Methods: CCK8 was synthesized by solid-phase techniques and covalently coupled to DTPAGlu through a glycine linker at its amino terminus. The compound was labeled with (111)In. The radiochemical purity and stability of the compound were assessed by chromatographic methods. NIH-3T3 and A431 cells overexpressing CCKBR were used to characterize the in vitro properties of the compound. Nude mice bearing control and CCKBR-overexpressing A431 xenografts were used as an in vivo model., Results: DTPAGlu-G-CCK8 showed rapid and efficient labeling with (111)In. The radiolabeled conjugate showed specific binding to both cell lines overexpressing CCKBR. Binding was saturable, with a dissociation constant of approximately 20 nmol/L in both cell systems. Both cell lines showed internalization of the ligand after interaction with the receptor. Biodistribution studies showed rapid localization of (111)In-DTPAGlu-G-CCK8 on CCKBR-overexpressing A431 xenografts that was severalfold higher than that on control tumors at all time points tested. Unbound activity showed rapid clearance of over 80% through the kidneys by 30 min after injection. The labeled peptide conjugate was very stable in serum but showed a rapid breakdown after injection. Incubation with kidney homogenates suggested that most breakdown occurred in the kidneys, favoring the clearance of unbound activity., Conclusion: Our findings indicate that the in vitro and in vivo characteristics of (111)In-DTPAGlu-G-CCK8 are favorable for CCKBR imaging, as the peptide shows high-affinity binding to the receptor, is internalized in CCKBR-expressing cells, and shows avid uptake in CCKBR-overexpressing xenografts, with rapid clearance of unbound radioactivity through the kidneys. Furthermore, the ease of synthesis, high labeling efficiency, and chemical stability of DTPAGlu make this chelating moiety an ideal candidate for widespread use in peptide radiolabeling for nuclear medicine applications.

Management of patients with cutaneous melanoma in the absence of lymph node metastases is still controversial. The experience at the National Cancer Institute in Naples was analyzed to evaluate 3-year disease-free survival and overall survival for all patients who underwent sentinel lymph node biopsy (SLB) with Breslow thickness greater than 4 mm. Data from 359 sentinel biopsies performed in the past 5 years were reviewed to determine the effect of the treatment on disease-free survival and overall survival after stratifying patients for node status, tumor ulceration, and Breslow thickness. Statistical analysis showed a better 3-year survival for sentinel node-negative patients than for sentinel node-positive cases (88.4% and 72.9%, respectively; P <.05). Tumor ulceration retained its prognostic significance despite lymph node status, indicating a higher risk for development of distant metastases. Survival curves associated with thicker melanomas did not show significant differences between negative- and positive-SLB patients. SLB provides accurate staging of nodal status in melanoma patients who have no clinical evidence of metastases. Longer follow-up and final results from ongoing trials are necessary to definitively clarify the role of this procedure.

The most powerful prognostic factor in patients with oral cancer is the presence of lymph node metastases. The management of the neck at diagnosis in the absence of adenopathy is still controversial, but sentinel lymph node biopsy (SLB) may help resolve this issue. At the National Cancer Institute in Naples, we performed SLB in 41 patients with T1 to T2 oral cancer. All patients underwent lymphoscintigraphy. Intraoperative blue dye and gamma probe examination identified a sentinel node (SN) in 39 patients. Four patients (10%) had double drainage, and 7 (18%) had drainage beyond the expected anatomical site. Complete concordance between the pathology of the SN and nodes obtained from radical dissection confirmed SLB as a reliable staging procedure. Since January 2001, seven patients with T1 to T2 oral cancers have been staged with SLB only; modified radical neck dissection was carried out only in cases with a positive SN. The rate of SN identification was 100%, and all five cases with negative SNs were free of disease after a median follow-up of 10 months. Lymphoscintigraphy plus SLB seems to be a good staging system for guiding neck management in patients with oral cancer. A larger number of patients and a longer follow-up in a randomized trial will confirm the potential staging value of this procedure and determine which patients might benefit from a conservative approach that avoids radical neck dissection.

Previously reported results suggest that the analogue of the somatostatin des-AA1,2,5[D-Trp8,IAmp9]-somatostatin (CH-275) peptide bearing chelating agents able to coordinate radioactive metals could be used for scintigraphic imaging of tumor lesions overexpressing sstr1. An efficient synthetic procedure for the preparation of the somatostatin analogue CH-275 and its conjugate DTPAGlu-Gly-CH-275, bearing the chelating agent DTPAGlu (DTPAGlu=N,N-bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic acid) on the N-terminus, by solid-phase peptide synthesis and 9-fluorenylmethoxycarbonyl (Fmoc) chemistry, is here reported. Rapid and efficient labeling of DTPAGlu-Gly-CH-275 was achieved by addition of 111In(III) to the compound. Typical yields were greater than 97% as determined by reversed phase high performance liquid chromatography (HPLC) at specific activities in the range 4-9 GBq/micromol (100-250 Ci/mmol). A preliminary biological assay of the binding ability of 111In-DTPAGlu-Gly-CH-275 indicates, however, that the labeled compound does not display any specific interaction with somatostatin sstr1 receptors in the tested cell lines. To confirm this unexpected negative result, competition binding experiments were carried out, in which fixed tracer amounts of the 125I-labeled somatostatin-14 were incubated with the receptor-expressing cells in the presence of DTPAGlu-Gly-CH-275 or CH-275 at concentrations ranging from 10(-10) to 10(-3) M. While CH-275 shows a IC50 of 80 nM similar to that already found in displacement experiments on CHO-K1 sstr1-transfected cells, DTPAGlu-Gly-CH-275 displays instead very low or negligible affinity towards this receptor. The NMR solution characterization indicates that the presence of DTPAGlu does not influence the conformational and chemical features of the peptide moiety, thus suggesting that the loss in binding activity should be due to steric hindrance of either the chelating agent DTPAGlu or its indium complex.

Palmoplantar keratoderma (PPK) refers to a genetically heterogeneous group of skin diseases, which may be inherited in autosomal dominant or recessive fashion. We observed a case of a 74-year-old man with Mal de Meleda, who developed malignant melanoma inside the hyperkeratotic palmar skin of the right hand. Many authors have reported a higher incidence of cancer in cases affected by palmoplantar hyperkeratosis both for hereditary association and particularly for mechanical damage of the affected areas. The association with melanoma has already been described, but not in a true Mal de Meleda type syndrome as in the case reported in this paper.

Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.

Lack of technetium-99m methoxyisobutylisonitrile ((99m)Tc-MIBI) uptake is consistently reported to predict poor response to subsequent chemotherapy in a variety of human malignant tumours. Since (99m)Tc-MIBI accumulates within mitochondria, which also play a central role in apoptosis through the integration of death signals by Bcl-2 family members, we tested whether early (99m)Tc-MIBI uptake is affected by alterations of the apoptotic pathway. Forty-two breast cancer patients were intravenously injected with 740 MBq of (99m)Tc-MIBI and planar images were obtained 10 min post injection with the patients in the prone lateral position. Ten carcinomas failed to accumulate (99m)Tc-MIBI and could not be visualised on scintigraphic images despite being larger than 1.8 cm (MIBI negative). Thirty-two of the 42 breast carcinomas showed focal uptake of (99m)Tc-MIBI (MIBI positive), and 10 min tumour-to-background ratios (T/B) varied between 1.14 and 6.93. The apoptotic index, the rate of proliferation, and the expression of the anti-apoptotic Bcl-2 protein and pro-apoptotic Bax protein were assessed in surgically excised tumours. All MIBI-negative carcinomas showed a dramatic and statistically significant reduction in the apoptotic index as compared with MIBI-positive lesions (mean+/-SD, 0.14+/-0.15 vs 1.28+/-0.83, P<0.0001) independently of rate of proliferation, tumour size and P-glycoprotein expression. Significantly higher levels of Bcl-2 were also found in MIBI-negative as compared with MIBI-positive carcinomas. In MIBI-positive lesions, an inverse significant correlation was found between T/B ratios and Bcl-2 levels ( r=-0.50, P<0.01). Our findings indicate that early uptake of (99m)Tc-MIBI in breast carcinomas is affected by alterations of apoptotic pathway. High levels of Bcl-2, despite the stabilisation of mitochondrial membrane potentials, prevent accumulation of (99m)Tc-MIBI in tumour cells. In conclusion, absent or reduced early (99m)Tc-MIBI uptake in large tumours may indicate a Bcl-2-mediated resistance to chemo- and radiotherapy.

Purpose: Factors that are predictive of prognosis in patients who are diagnosed with malignant melanoma (MM) are widely awaited. Detection of circulating melanoma cells (CMCs) by reverse transcriptase-polymerase chain reaction (RT-PCR) has recently been postulated as a possible negative prognostic factor. Two main questions were addressed: first, whether the presence of CMCs, defined as the patient being positive for any of the three markers, had a prognostic role; and second, what the predictive value of each individual marker was., Patients and Methods: A consecutive series of 200 melanoma patients observed between January 1997 and December 1997, with stage of disease ranging from I to IV, was analyzed by semiquantitative RT-PCR. Tyrosinase, p97, and MelanA/MART1 were used as markers to CMCs on baseline peripheral blood samples. Progression-free survival (PFS) was used as a unique end point and was described by the product limit method. Multivariable analysis was applied to verify whether the auspicated prognostic value of these markers was independent of the stage of disease, and a subgroup analysis was performed that excluded patients with stage IV disease., Results: Overall, 32% (64 of 200) of patients progressed, and a median PFS of 52 months in the whole series was observed. The presence of CMCs and the markers individually or combined was predictive of prognosis in the univariate analysis but did not provide additional prognostic information to the stage of disease in multivariable models. In the subgroup analysis of stage (ie, I-III subgroup), similar results were observed., Conclusion: Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.

Characteristic patterns of regional cerebral blood flow (rCBF) reduction, as detected by technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission tomography (SPET), may help clinicians in differentiating patients with frontotemporal dementia (FTD) from those with Alzheimer's disease (AD). However, in some cases these patients may share common rCBF abnormalities and the visual analysis and/or the region of interest (ROI) approach may not sensitively detect more localised focal changes that could be more specific for each pathology. Recently, automated voxel-by-voxel statistical analysis of perfusion brain maps has been applied to SPET images. This method has the advantage of including the rCBF information for the whole brain for statistical analysis without any a priori hypothesis regarding the regions possibly involved. This could result in a better characterisation of rCBF differences in brain regions while also reducing the operator's subjectivity and the time required for data analysis. The purpose of this study was to apply such a technique to highlight the specific brain areas showing a relative functional involvement in FTD and AD. Thus, we compared the relative rCBF patterns obtained in eight FTD patients with those obtained in 21 AD patients using (99m)Tc-HMPAO SPET and statistical parametric mapping (SPM). When FTD patients were compared with AD patients, relatively lower rCBF was observed in right medial frontal cortex (BA 8, 9, 10), right anterior cingulate cortex (BA 32), right temporal cortex (BA 21/22), right orbitofrontal cortex (BA 11) and ventrolateral prefrontal cortex (BA 47); in BA 47 the reduction was evident bilaterally but was more marked on the right side. On the other hand, when AD patients were compared with FTD patients, a significant relative rCBF decrease was found in the bilateral superior parietal cortex (BA 7); this decrease was more extensive on the left side, where it also included the inferior parietal (BA 40), superior occipital (BA 19) and temporo-occipital regions (BA 39, 19). The results of this study confirm the preferential involvement of the frontotemporal regions in FTD patients and of the temporoparietal regions in AD patients. Furthermore, they highlight the networks that are more specifically impaired in these disorders and that could be implicated in the emotional-behavioural and cognitive disturbances that characterise FTD and AD respectively.

Our previous studies showed that the efflux rate of technetium-99m methoxyisobutylisonitrile (MIBI) is directly correlated to P-glycoprotein (Pgp) levels in breast carcinoma. The aim of this study was to test whether the Pgp-dependent efflux of 99mTc-MIBI is related to the apoptotic pathway activation in breast carcinoma. Thirty-three untreated non-consecutive patients were intravenously injected with 740 MBq 99mTc-MIBI and serial images were obtained up to 4 h. The rate of efflux was determined by mono-exponential fitting of decay-corrected time-activity curves. Tumour specimens were then obtained at surgery and processed for the determination of the apoptotic index by in situ end-labelling of DNA fragments (Tunel). The rate of tumour cell proliferation was also determined using Ki67 monoclonal antibody. All breast carcinomas showed focal uptake of 99mTc-MIBI and the time to half clearance varied between 85 and 574 min. The apoptotic index ranged between 0.3% and 4.2%, whereas the rate of proliferation varied between 13% and 40%. We found a positive and significant correlation between the apoptotic index and the rate of proliferation (r=0.79, P<0.0001). The efflux rate of 99mTc-MIBI was directly and significantly correlated with the apoptotic index (r=0.74, P<0.0001) and with the rate of proliferation (r=0.58, P<0.001). After partial correlation analysis, only the apoptotic index showed a significant correlation with the efflux rate of 99mTc-MIBI (r=0.57, P<0.001). Our findings indicate that enhanced transport activity of Pgp is associated with increased activation of the apoptotic pathway, suggesting that inhibition of Pgp function with specific modulators may be effective in these patients. Furthermore, since mitochondria are central executioners of apoptosis and intracellular sites of 99mTc-MIBI sequestration, a model for the dynamic coupling of Pgp-dependent 99mTc-MIBI efflux and apoptotic pathway activation may be derived.

Typical and atypical antipsychotics, the mainstay of schizophrenia pharmacotherapy, have been demonstrated to affect differently neuronal gene expression in several preclinical paradigms. Here we report the differential gene expression of the glutamatergic post-synaptic density proteins Homer and PSD-95 in rat forebrain following acute haloperidol or olanzapine treatment. Moreover, considering the extensive interactions between dopaminergic and opioidergic systems we also measured striatal preproenkephalin mRNA. Male Sprague-Dawley rats were treated with haloperidol 1 mg/kg or olanzapine 0.5 mg/kg or vehicle, i.p. and sacrificed 3 h after the injection. Homer gene expression was significantly increased in caudate putamen and nucleus accumbens of rats treated with haloperidol and in the core of accumbens of rats treated with olanzapine. No changes were detected for Homer in prefrontal and parietal cortex in any of the experimental groups. PSD-95 gene expression was not modulated in our paradigm by administration of either typical or atypical antipsychotics. These results (1) suggest a differential modulation of Homer by typical and atypical antipsychotics; (2) confirm that Homer can be induced as an early gene with putative direct effect on neuronal plasticity and (3) demonstrate different response to antipsychotics by different classes of postsynaptic density proteins at glutamatergic synapses.

The purpose of this study was to assess the value of sentinel node (SN) biopsy in oral cancer by means of a lymphoscintigraphic technique and intraoperative detection by blue-dye combined with gamma-ray probe to facilitate identification of the SN. Forty-one T1-T2N0 patients underwent lymphoscintigraphy, SN biopsy, and modified radical neck dissection. An SN was identified in 39 of 41 patients by the combined use of intraoperative blue dye and the probe and was removed. Complete neck dissections were performed and the histological evaluation compared. Thirty-eight SNs in 35 patients were negative at final pathology and correctly predicted the pathological status of the specimens from the full-neck dissections. Five SNs in four patients had micrometastases and were the only metastatic nodes identified. The results of this study on a homogenous series of patients show that SN biopsy is a valuable staging technique in T1 and T2 oral cancer with uninvolved neck, provided that no previous surgery or radiotherapy has altered lymphatic drainage in the oral cavity or in the neck. In a large number of patients, SN biopsy can avoid unnecessary neck dissection and its relevant morphofunctional sequelae.

Drainage in thyroid surgery is still an area of controversy. We analysed the results of a prospective randomised trial conducted in our institution in order to assess the utility of drainage after thyroid surgery. Sixty patients were entered into the study, thirty of whom were drained after surgery and thirty who received no drainage. The two groups were well matched with regard to most characteristics. There was no difference between the two groups in terms of early or late postoperative complications. We therefore conclude that, in our experience, drainage after uncomplicated thyroid surgery is of no benefit.

Purpose: Detection of occult metastasis before the development of clinical disease could allow more accurate staging, appropriate follow-up procedures, and adjuvant therapies in patients with malignant melanoma (MM). The sentinel lymph node (SLN) has been proposed as a reliable predictor of metastatic disease in the lymphatic basin draining the primary melanoma. In this study, we screened both paraffin-embedded SLNs and peripheral-blood (PB) samples from MM patients at various stage of disease using a multimarker reverse transcriptase polymerase chain reaction (RT-PCR) assay. The prognostic significance of the presence of PCR-positive markers was also evaluated., Patients and Methods: Total RNA was obtained from paraffin-embedded SLN sections and PB samples of 75 MM patients. RT-PCR was performed using tyrosinase and MelanA/MART1 as melanoma-associated markers. Radiolabeled PCR products were analyzed on denaturing polyacrylamide gels., Results: Good sensitivity of the RT-PCR assay on archival tissues was demonstrated after comparison of RT-PCR results on frozen and paraffin-embedded SLNs from 16 MM patients. Significant correlation between the disease stage and marker expression in both PB and SLN samples was observed; the highest value was for patients who were positive for both markers in SLN (P =.006). Progression of disease was significantly associated with the total number of PCR-positive markers in both PB (P =.034) and SLN (P =.001) samples., Conclusion: Although sensitivity is lowered by the use of paraffin-embedded specimens, our data indicate that RT-PCR analysis of serial sections from archival SLNs may be helpful in improving detection of occult micrometastases, thus improving staging of patients with melanoma.

Many studies in the literature have confirmed the role of combined therapy in the treatment of rectal neoplasms. Aim of the Authors' study was to evaluate the efficacy of preoperative neoadjuvant radiochemotherapy in these patients. The study group consisted of 15 patients, affected by rectal adenocarcinoma T < 4 M0 with age < 75 years, observed from January to August 1998, who underwent to RT of pelvis with three fields--total dose 32 Gy- in ten days associated with 5 FU(500 mg/m2) during the first five. After restaging the patients were operated on. Anterior resections (AR) were followed by mechanical colorectal anastomosis in 10 patients, coloendoanal anastomosis in 4, while in 1 case an abdominoperineal resection (APR) was performed. The protocol was well tolerated in every patient and perioperative complications were similar to those in the control group. A considerable reduction of the mass was obtained in a great percentage of patients studied, confirmed by pathologic examination like "down staging" of cancer. In no case a complete response to the therapy was observed (pT0N0). Survival in the patients operated on for rectal adenocarcinoma in about 50% and local relapse is the most important site of recurrent disease. The aim of neoadjuvant protocol is the control of lymphatic spread and reduction rectal neoplasm allowing coloanal anastomosis in the treatment of the 1/3 inferior rectal cancer. Literature data confirm a significant decrease of local relapse, probably with a better survival. The Authors study confirms that combined preoperative therapy is well tolerated in most of the cases and it represents the protocol of choice in the patient affected by rectal cancer.

Laparoscopic cholecystectomy is currently the gold standard in the treatment of symptomatic gallstones but has been shown to have a higher incidence of biliary tree lesions (0.3-1%) compared with reported traditional open approaches. Loss of three-dimensional view and of depth perception is the main limit of the laparoscopic approach, especially if particular risk factors are associated (e.g., postinflammatory fibrosis, anatomic variations). Moreover, inadequate training may justify the increase of biliary tract lesions. The authors describe a unique case of left hepatic duct clipped without section of the duct itself during an otherwise "easy" operation. At the reintervention, because of the favorable local condition, a reconstruction was possible after a small duct resection with a ductal-hepatic anastomosis over a T-tube. This was removed after 8 months because of the good patency of the biliary tree and the absence of cholestasys. A long-term follow-up is mandatory for a complete functional evaluation.

The authors report a case of follicular thyroid cancer in "hot nodule" with micronodular synchronous lung metastases. The treatment consisted in TT associated with radioiodine therapy at the dose of 170 mCi with remission of cancer after six months of follow-up. Follicular variant is a prognostic unfavorable factor such as synchronous or metachronous pulmonary metastases. In those patients prognostic unfavorable variants are also age over 40 years, a poor radiofixation capacity, and a lesion of diameter up 1 cm. A strictly instrumental follow-up is mandatory to obtain diagnosis in a subclinical stage. In such cases the radiometabolic therapy agree to a remission of cancer with high survival after many years. TT yet represents a "minimal" surgical treatment for an accurate radioisotopic diagnosis.

Background: Surgical treatment in the patient effected by secondary hyperparathyroidism consists in subtotal parathyroidectomy or total parathyroidectomy plus autotransplantation of parathyroid tissue., Methods: The results obtained with surgical treatment of 6 patients observed in the years 1995-1996 are analyzed. Two glands were hyperplastic in four patients, 3 in the others. Every patient was submitted to a subtotal parathyroidectomy., Results: Postoperative course was marked by transient hypoparathyroidism in one case. After 18 months of follow-up, no recurrences were observed., Conclusions: It is pointed out that in case of secondary hyperparathyroidism subtotal parathyroidectomy represents the surgical treatment of choice, according with literature data. Otherwise total parathyroidectomy plus autotransplantation, characterized by a more complex surgical technique, lead to the same results.

Unlabelled: The goal of this study was to investigate whether 18F-labeled transferrin (Tf), which has a molecular weight (Mr) of approximately 79,000, binds to Tf receptor sites in tumors in a specific manner within the time frame commensurate with the half-life of 18F (109.7 min). We have previously shown that [18F]holo-Tf ([18F]Tf) maintains all properties of native Tf in vitro and that it can specifically target liver Tf receptor sites in vivo., Methods: The distribution of [18F]Tf, using [18F]albumin (Alb) or [14C]Alb as a control, was studied over a 6-h period in nude mice bearing LS174T and A431 xenografts of a high- and low-permeability tumor, respectively., Results: Measurements of Tf receptor concentration in the tumor extracts suggest similar binding capacities. In vivo, liver uptake values were higher for [18F]Tf than for both [18F]Alb and [14C]Alb throughout the study, indicating specific binding. In contrast, tumor Tf uptake values remained below those of the Alb tracers, and tumor-to-blood ratios of [18F]Tf in each xenograft increased in parallel with those of the Alb tracers. The permeabilities of [14C]Alb and [18F]Tf in LS174T were calculated to be 1.29+/-0.49 and 1.03+/-0.38 microL/min/g (mean +/- SD), respectively, whereas the permeabilities of the two tracers in A431 were 0.79+/-0.24 and 0.44+/-0.04 microL/min/g. Pharmacokinetic modeling of the data using these permeabilities and the high plasma and extracellular concentrations of endogenous Tf showed that the observed uptake values in the two xenografts are consistent with a non-receptor-mediated distribution. In the liver, the absence of permeability barriers yields specific [18F]Tf binding to receptors compared with the [14C]Alb control, within 5 min after injection., Conclusion: Receptor-mediated accumulation of [18F]Tf in tumor xenografts is impaired by rate-determining permeability and competition from endogenous Tf and is not achieved in a time frame of 6 h.

The Authors analyze 152 consecutive patients who underwent thyroidectomy for differentiated thyroid cancer, observed from 1978 to 1996, evaluating specifically prognostic factors. In accord with literature, total thyroidectomy represents the "gold standard" surgical treatment that allows diagnostic-therapeutic use of 131I and results. The Authors in case of N+ as routine perform a node picking with MRND (modified radical neck dissection) reserved to high risk patients. Age represents only independent prognostic factor that in association with M+ and follicular histotype classifies high risk patients in whom a more aggressive therapeutic approach is necessary.

Follicular carcinoma, in association with other prognostic factors, identifies a class of "high-risk" patients in which a more aggressive treatment is indicated. In fact, in patients operated on for follicular carcinoma bone metastases, also many years after primary surgery, are reported. A case of skull metastases in a young women occurred 3 years after a near total lobectomy for follicular thyroid carcinoma is described. After six years the patient underwent total thyroidectomy, resection of skull metastases, radiometabolic therapy with I131 180 m Ci; now she is disease free at three years of follow-up. The biology of metastases in thyroid follicular carcinoma, risk factors and diagnostic and therapeutic controversies are analyzed. Good prognostic factors are considered age < 45 years, good degree of differentiation of primary tumor, small size of bone metastases and early appearance after primary diagnosis. The conclusions is drawn that bone metastases are the worst prognostic factors. In case of single lesion, surgical treatment allows good results.

Unlabelled: Many tumors with neuroendocrine characteristics express high amounts of somatostatin receptors that enable in vivo imaging with [(111)In-DTPA-D-Phe1]-octreotide. In this study, we have analyzed the feasibility in detecting and characterizing thymic masses by somatostatin receptor scintigraphy (SRS)., Methods: Eighteen patients (13 women, 5 men, ages 18-78 yr; mean +/- s.d. = 42.1 +/- 17.6 yr) were enrolled in this study. Eleven patients were studied during diagnosis and seven during routine follow-up. In seven patients, myasthenia gravis was the presenting symptom. SRS was performed within 4 wk after CT and/or MRI. Planar and tomographic images were acquired within 24 hr after the injection of approximately 111 MBq of [(111)In-DTPA-D-Phe1]-octreotide. The scintigraphic results were categorized according to the histologic findings., Results: Histology diagnosed 10 mixed epithelial/lymphoid thymomas (8 with prevalent epithelial component), 2 thymic carcinomas, 1 thymic carcinoid, 1 lymphangioma and 4 thymic hyperplasias. Two thymoma were Stage I, 3 were Stage II, 2 were Stage III and 5 were Stage IV, as was the thymic carcinoid. Indium-111-DTPA-D-Phe1-octreotide concentrated in primary and/or metastatic sites of thymic tumors, thereby enabling successful external gamma imaging of sites greater than 1.5 cm in size. Tumor-to-lung (T/L) ratios were as high as 7.6-fold (range 1.7-7.6). Untreated thymomas showed higher T/L (4.34 +/- 1.57) than treated ones (2.68 +/- 1.18). No uptake was detectable in the four patients with benign thymic hyperplasia and the patient with the lymphangioma., Conclusion: Indium-111-DTPA-D-Phe1-octreotide is avidly concentrated within thymic tumors, but it is not concentrated by thymic hyperplasia, which allows differential diagnosis. Thus, in patients with myasthenia gravis, SRS may have a role in characterizing thymic masses, thereby overcoming the limits of cross-sectional imaging modalities.

Introduction: Magnetic Resonance Imaging (MRI) has been proposed as the diagnostic technique of choice to characterize adrenal tumors. However, the results of the current studies are controversial., Material and Methods: Forty-nine patients with unilateral adrenal masses were submitted to MRI for lesion characterization on the basis of MR signal intensity. Cytology and/or histology demonstrated 14 pheochromocytomas (pheos), 11 adenomas, 3 cysts, 2 myelolipomas, 4 carcinomas, 3 metastases and 1 fibrosarcoma; a clinical diagnosis of adenoma was made in the remaining 11 patients. MR studies were performed using spin-echo (SE) sequences with T1 (TR/TE = 600/17 ms) and T2 (TR/TE = 2000/15-90 ms) weighting. T1-weighted images were also acquired after Gadolinium-DTPA (Gd-DTPA) administration. MR studies were integrated with in- and out-of-phase (TR/TE = 100/4-6 ms) chemical-shift (CS) sequences. MR signal intensity (SI) was analyzed qualitatively and quantitatively; MR results were correlated with tumor type and hormone secretion., Results: The qualitative analysis of T2 images showed high signal intensity in the majority (80%) of adrenal lesions (14 pheos, 12 adenomas, 3 cysts, 2 myelolipomas and 8 malignancies). The quantitative analysis of post-Gd-DTPA T1 images permitted to distinguish adenomas, cysts and myelolipomas from pheos and malignancies. The qualitative analysis of post-Gd-DTPA T2 and T1 images permitted to distinguish pheos and cysts from adenomas and malignancies (p < .05); however, pheos and cysts as well as adenomas and malignancies were not differentiated. MR SI was similar in secreting and nonsecreting adenomas from both a qualitative and a quantitative viewpoints. CS MRI permitted to distinguish adenomas (decreased signal intensity on out-phase relative to in-phase images) from other benign and malignant lesions (no signal change from out-phase to in-phase images)., Conclusions: The qualitative analysis of MR SI on conventional T1 and T2 images does not permit to differentiate adrenal masses. The qualitative evaluation of T1 images after Gd-DTPA administration, the quantitative analysis and CS sequences are technical options improving lesion characterization.

Paraesophageal hernia incidence is around 5-8%. The Authors analyze their experience of 5 patients operated on for paraesophageal hernia after preoperative manometric and pHmetric studies. Despite only in 3 patients a gastro-esophageal reflux was present, in all cases a suture of the diaphragmatic defect together with a modified Lortart-Jacob antireflux operation was performed. The results were considered satisfactory in all cases and there was no relapse after a 2 year follow-up. Following an accurate analysis of the literature the Authors conclude that in paraesophageal hernia a surgical treatment is mandatory. However, diagnostic instrumental preoperative data influence the choice of the appropriate surgical treatment for each patient.

Small papillary cancer of the thyroid (SPC), conventionally defined as a tumor less than 10 mm in diameter, today is considered quite interesting. In fact, autoptic incidence is higher than reported in clinical series. Generally SPC has a good evolution, however, particularly aggressive forms are described. The Authors review Literature data and evaluate pathogenesis and diagnostic problems of SPC. The Authors agree on a multidisciplinary therapeutic protocol in which total thyroidectomy is the elective intervention associated, in selected patients, to metabolic radiotherapy.

We investigated the role of radiolabeled somatostatin analogs (SAs) in adrenal imaging. We evaluated 15 patients (6 men and 9 women, mean age 47 +/- 17 years) with imaging-detected adrenal tumors. Patient population was divided into two groups on the basis of the nature of adrenal lesions. Group 1 consisted of patients with benign adrenal lesions (n = 10). Group 2 consisted of patients with malignant adrenal lesions (n = 5). Pathology examinations were obtained in 13 cases: 7 pheochromocytomas, 2 adenomas, 2 cysts, 1 carcinoma, and 1 fibro-histiocytoma. One patient had a proven diagnosis of non-small-cell lung cancer associated with the presence of a right adrenal mass. The last patient had a clinical diagnosis of Werner syndrome associated with the presence of a large left adrenal mass. All patients underwent scientigraphic studies using radiolabeled SAs, of which indium-111 (In-111) pentetreotide was used in 11 cases and technetium-99m (Tc-99m)-labeled peptides (P-587 or P-829) were used in the remaining four cases. No significant labeled SAs uptake was observed in the majority (8 of 10, 80%) of the benign adrenal lesions (Group 1); however, increased uptake was found in two benign pheochromocytomas. Conversely, significant labeled SAs uptake was observed in the majority (4 of 5, 80%) of the malignant adrenal lesions (Group 2); however, the last lesion (carcinoma) did not show abnormal uptake. Results of this study show that the majority of benign adrenal tumors do not concentrate radiolabeled SAs; conversely, the majority of malignant adrenal lesions show significant SAs uptake, suggesting the presence of somatostatin receptors. This finding may allow the use of somatostatin as a treatment agent in malignant adrenal tumors. Thus, the main role of labeled SAs in adrenal imaging consists of lesion characterization rather than tumor detection and localization.

The authors explain their experience about 136 patients affected by differentiated thyroid carcinoma. They compare different surgical procedure (total thyroidectomy vs conservative surgery). Although the surgical significance above the survival is discuss again, the authors, analysing the prognostic factors and the long term results, identify the total thyroidectomy maybe associated to lymphectomy and radioiodine therapy like the best treatment for this pathology.

Laparoscopic cholecystectomy represents elective the treatment of symptomatic lithiasis of gallbladder, due to advantages of shorter hospitalization and lower cost. The evolution of technological instruments permits today an easy and rapid execution of intraoperative cholangiography (IC). Therefore the elective or selective application of IC is debated, because of the effective determination of iatrogenic lesions and the real possibility of diagnosis for unknown lithiasis of biliary tract. Some authors agree that anatomic lesions cannot be prevented by IC, because 50% of its occur during the surgical dissection to prepare structures of Calot's triangle to make cholangiography. On the other hand the early diagnosis of iatrogenic lesions is fundamental for the results. The previous biliary symptomatology (jaundice), the elevation of biochemical parameters of biliary function (bilirubinemia, transaminase and alkaline phosphatase) and the dilatation of biliary ducts represents the indication to IC. The examination is also recommended in case of difficulties of dissection due to inflammatory process, to clarify the anatomy with more safety. Finally, the technique is well defined. The choice of patients is made on the basis of surgeon's opinions but we think that a good selection of patient is the only chance to perform IC with the best results.

Laparoscopic cholecystectomy is became the elective operation in the treatment of symptomatic lithiasis of gallbladder, and it represent the surgical choice in 96% of cases. The authors on the base of their first years experience analyzes the results of literature with particular reference to the complications, like lesion of principal biliary tract and of other organs or vessels, underlining how the right selection of patients can be reduce morbidity. In this direction the subdivision of contraindication, in relative and absolute, already described in literature, represent an obliged chose to respect the mini-invasive principle which laparoscopic technique mean.

Unlabelled: The rationale of this study was the evaluation of response to chemotherapy in children with advanced neuroblastoma using currently available diagnostic modalities., Methods: Iodine-131-metaiodobenzylguanidine (MIBG) imaging and 24-hr urinary vanillylmandelic acid (VMA) measurement were evaluated in 14 patients (7 males, 7 females, age range: 2-68 mo) with advanced neuroblastoma both pre- and postchemotherapy (5.6 +/- 2.8 mo) as well as serum ferritin (FER) and neuron-specific enolase (NSE) levels in 9 and 8 patients, respectively. MIBG images were qualitatively compared in each patient., Results: Prechemotherapy, a total of 39 abnormal foci of MIBG uptake was detected. Postchemotherapy, 15 of these showed unchanged MIBG uptake, 7 had decreased uptake and 17 showed no uptake. In addition, four new abnormal foci of uptake were found. Postchemotherapy, a significant reduction of abnormal MIBG uptake (p < 0.01) was observed using a lesion-by-lesion analysis. When biochemical and MIBG postchemotherapy changes were compared, a significant relationship was found only between MIBG and VMA results (r = 0.84, p < 0.01)., Conclusions: In postchemotherapy follow-up of children with advanced neuroblastoma, laboratory evaluation using VMA, FER and NSE measurements reflect only the global functional status of the disease, and are not helpful in defining the response of individual tumor lesions to treatment. Conversely, qualitative analysis using MIBG imaging may allow lesion-by-lesion evaluation of the heterogeneity of neuroblastoma response to chemotherapy. In this setting, changes in MIBG uptake are mirrored by the changes in catecholamine production, as measured by VMA levels.

Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy, computed tomography (CT) and ultrasonography (US) were used to localize tumour lesions in 28 children with histologically proven neuroblastoma. Overall, a total of 73 lesions were detected on imaging studies. MIBG scintigraphy, CT and US localized 63 (86%), 49 (67%) and 36 (49%) of these lesions, respectively. The findings of the three imaging techniques were concordant in respect of only 31 (42%) of the lesions. The best agreement among MIBG scintigraphy, CT and US was observed for abdominal lesions (the techniques were concordant for 22 of 23 lesions, i.e. 96%). MIBG scintigraphy detected nine out of ten (90%) liver metastases, but agreement with CT and US was observed in only six instances (60%). The imaging findings were concordant in respect of only two (33%) out of six lymph node metastases; the MIBG scan was normal in the other four cases. Imaging agreement was observed for a lesion located in the pelvis. MIBG and CT findings were concordant in four lesions located in the chest, but US was not performed. MIBG scintigraphy depicted the majority (96%) of the skeletal lesions (23/24); CT showed five of these, but, again, US was not performed. The imaging findings were not concordant as regards the remaining five lesions located in different anatomical sites. The results indicated that MIBG imaging is more sensitive that CT and US in localizing the majority of neuroblastoma lesions. Since the metastatic spread of neuroblastoma is unpredictable, we recommend MIBG scintigraphy as the initial imaging modality for staging of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of gastrointestinal tumors by means of labeled monoclonal antibodies is a new, sensitive and suitable technique currently used in several centers. Encouraging results have been documented with several monoclonal antibodies by different authors. This article reviews our experience with radioimmunoscintigraphy in 59 patients with colorectal cancer in follow-up, using 131I and 111In labeled B72.3, and in 16 patients with primary gastrointestinal tumors using 99mTc anti-CEA monoclonal antibody (type F023C5). The sensitivity of both B72.3 and anti-CEA was greater than 70% either for primary tumors and abdominal recurrences or distant metastases except hepatic ones. A significant gradient in antibody uptake was measured on surgical biopsies between tumors and normal tissues allowing a good in vivo contrast for gamma detection. We have defined the impact of some factors affecting in vivo tumor targeting. In fact, pharmacodynamics of MAbs, percentage of injected dose bound to tissues were measured, and in particular antigenic content in tumor nodules was quantified. Furthermore, the results of RIS were compared to those obtained by CT and other imaging modalities.