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Secondo Lastoria

Publications and source records attributed to Secondo Lastoria.

13 recordsLinked to original sources

Primary gastrointestinal stromal tumor of the liver with lung metastases successfully treated with STI-571 (imatinib mesylate).

We report a case of a primary malignant GIST of the liver metastatic to the lung in a 37 years-old man. The liver tumor showed histological feature of a GIST and expressed vimentin, and diffusely exhibited CD117. One year after the resection of the liver mass, the patient developed multiple small lung metastases which completely disappeared with STI-571 (imatinib mesylate--Gleevec) therapy. C.T. or PET did not show any mass in the abdomen. These findings suggest that the liver mass was a primary rather than a metastatic tumour. They also support the hypothesis that GIST could originate from undifferentiated mesenchymal cells capable to differentiate toward a pacemaker cell phenotype, which are present in sites other than the G.I. tract.

Adult↗

Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington's disease.

UNLABELLED: We studied the anatomic and functional changes in various brain areas during the course of Huntington's disease (HD) in a large cohort of mutation-positive individuals (n = 71) encompassing the complete range of disability (presymptomatic through stage V), and in healthy controls, for the purpose of defining both degenerative and dysfunctional brain changes in the same subjects. METHODS: We used an MRI and unsupervised multiparametric segmentation procedure based on a relaxometric approach to measure in vivo brain volumes in 71 subjects with presymptomatic to advanced HD. The same population was evaluated by 18F-FDG PET to assess variations in brain glucose metabolism. To predict age at onset in unaffected mutation carriers, we considered the estimated number of years from each subject's age to manifested HD symptoms, for a given expanded triplet number. RESULTS: Age-adjusted analyses confirmed that the 71 subjects as a group, as well as the subgroup of 24 unaffected presymptomatic subjects at risk for HD, had significantly smaller gray-matter and white-matter volumes and larger cerebrospinal fluid volumes than did controls (P < 0.0001). In the 24 presymptomatic subjects, we observed a significant inverse linear correlation between white-matter volume reduction and the estimated time to symptom onset (r2= 0.39; P = 0.0011). Both clinically unaffected subjects at risk for HD and symptomatic patients had significantly decreased glucose uptake in the cortex (frontal and temporal lobes) and striatum (caudate and putamen). HD subjects who were followed up longitudinally showed progressive white-matter reduction in the preclinical subjects (n = 10) and decreased glucose uptake in the cortex and striatum in affected (n = 21) and preclinical (n = 10) subjects. CONCLUSION: White-matter volume loss may precede gray-matter atrophy and may be associated with neuronal dysfunction in early disease.

Adult↗

18F-FDG PET is an early predictor of pathologic tumor response to preoperative radiochemotherapy in locally advanced rectal cancer.

UNLABELLED: 18F-FDG PET is a useful tool for assessing the effects of chemo- or radiotherapy. The aim of this study was to correlate the change in tumor 18F-FDG standardized uptake value (SUV) during and after preoperative radiochemotherapy, with the pathologic response achieved in locally advanced rectal cancer (LARC) patients. METHODS: Thirty-three patients with LARC underwent total mesorectal excision after preoperative treatment, including 3 cycles of oxaliplatin, raltitrexed, 5-fluorouracil, and folinic acid during pelvic radiotherapy (45 Gy). Staging procedures included endoscopic ultrasound, MRI, and CT. 18F-FDG PET scans were performed at baseline and 12 d after starting radiochemotherapy (intermediate) in all patients. Seventeen patients also had a presurgical scan. For each scan, mean and maximum SUVs were measured. The percentages of SUV decrease from baseline to intermediate (early change) and to presurgical scan (overall change) were assessed and correlated with pathologic response classified as tumor regression grade (TRG). RESULTS: Eighteen tumors (55%) showed complete (TRG1) or subtotal regression (TRG2) and were classified as responders, whereas 15 cases (45%; TRG3 or TRG4) were considered nonresponders. The early median decrease of tumor SUV significantly differed between responders (-62%; range, -44% to -100%) and nonresponders (-22%; range, -2% to -48%). A significant correlation was also found between TRGs and early SUV changes (P < 0.0001). Responders were identified correctly by an early decrease of the mean SUV of > or =52%. CONCLUSION: This study shows that early 18F-FDG PET can predict pathologic response to preoperative treatment. These findings support the usefulness of (18)F-FDG PET during the management with radiochemotherapy of LARC patients.

Adenocarcinoma↗

Juvenile Huntington's disease: does a dosage-effect pathogenic mechanism differ from the classical adult disease?

Huntington's disease (HD) is caused by a CAG repeat mutation translating as a polyglutamine (poly(Q)) expansion in the huntingtin protein, whose main pathogenic mechanism is a gain of toxic function. In the case of large expansions beyond 60 repeats onset may result in juvenile HD (JHD, onset before 20 years of age). However, the triplet number does not represent the only onset modifier even in case of large expansions, mechanisms other than the size of the mutation contribute to the phenotype. In this review we discuss the possibility that some of the pathogenic mechanisms contributing to age at onset and progression may differ in the early onset HD compared with the classical adult pathology.

Adolescent↗

Huge parathyroid carcinoma: clinical considerations and literature review.

BACKGROUND: Parathyroid carcinoma is a rare malignancy, with an incidence of 0.5 to 4% of all cases of primary hyperparathyroidism. Surgery is the only curative treatment. CASE PRESENTATION: We report the case of a 66-year-old man referred for a large suspicious substernal goitre associated with severe hypercalcemia due to hyperparathyroidism. After normalization of serum calcium levels, patient underwent surgery. The voluminous cervicomediastinal firm mass could not be removed through the cervical incision; therefore a cervicothoracic approach was employed. Histopathology revealed a giant parathyroid cancer of 450 grams. A review of the literature was also undertaken to summarize the current treatment approaches for this rare malignancy. CONCLUSION: Parathyroid cancer is usually not recognized either preoperatively or intra-operatively. En bloc resection of the tumour with the adjacent tissue is the treatment of choice and it is very important to avoid the rupture of the capsule during operation. Neither tumour size, nor the lymph node status appears to play a role in prognosis. The management of parathyroid carcinoma is a challenge even for experienced surgeons.

Journal Article↗

Initial staging of lymphoma with octreotide and other receptor imaging agents.

Somatostatin receptor scintigraphy is useful in diagnosing tumors with increased expression of somatostatin receptors. The correct use of this technique reveals the localization of neuroendocrine primary tumors and unknown metastases in approximately 90% of patients. However, somatostatin receptor scintigraphy also can image many other human tumors expressing somatostatin receptors, including malignant lymphomas and thymomas. The sensitivity of somatostatin receptor scintigraphy to image somatostatin receptor-positive tumors is very high, but due to the variable expression of specific receptor subtypes, the specificity can be relatively low. This drawback is crucial in evaluating lymphoproliferative diseases, or, in general, when immune cells are involved. The sensitivity of somatostatin receptor scintigraphy for Hodgkin's lymphoma is 95%-100%, whereas for non-Hodgkin's lymphoma it is around 80%. It has been shown that the uptake of [(111)In-DTPA(0)]octreotide in lymphomas is lower compared to the uptake in neuroendocrine tumors. This is mainly attributed to the low number of receptors on immune cells compared to neuroendocrine cells; however, ligand-induced internalization and differential receptor regulation may also participate in determining this phenomenon. Therefore, caution should be taken when interpreting data from some studies. Several new ligands are currently under study to improve these limits and the expression of other neuropeptide receptors is being investigated to provide a molecular basis for in vivo multireceptor targeting of tumors. With the use of currently available somatostatin analogs, somatostatin receptor scintigraphy does not seem to have a significant impact in patients with lymphomas for diagnostic purposes. There are a few exceptions, however. Among these, the staging and restaging of extragastric lymphoma MALT-type may present some advantages. Conversely, somatostatin receptor scintigraphy in the imaging of thymic malignancies could enhance both our diagnostic and therapeutic capabilities. Somatostatin receptor scintigraphy is diagnostically relevant in differentiating malignant from benign lesions, especially in those patients with associated paraneoplastic syndromes, and is the main criterion to select patients suitable for therapy with somatostatin analogs. Recent findings emerging from in vitro studies on somatostatin receptor physiology in immune cells will certainly reopen and expand the potential applications of somatostatin analogs for in vivo diagnostic and therapeutic options.

Animals↗

Sentinel lymph node biopsy does not change melanoma-specific survival among patients with Breslow thickness greater than four millimeters.

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.

Adolescent↗

Therapeutic implications of sentinel lymph node biopsy in the staging of oral cancer.

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.

Coloring Agents↗

Somatostatin analogs and prednisone in advanced refractory thymic tumors.

BACKGROUND: Therapeutic options to cure advanced, recurrent, and metastatic thymic tumors are limited. Evidence of a high uptake of indium-labeled octreotide ((111)In-DTPA-D-Phe(1)-octreotide) in thymic tumors and the curative application of somatostatin analogs and prednisone in one patient with thymoma and pure red cell aplasia led the authors to start a Phase II study. METHODS: Sixteen patients with advanced thymic tumors, unresponsive to conventional chemotherapeutic regimens, were enrolled in the study. The schedule includes administration of somatostatin analog octreotide (1.5 mg/day subcutaneously) associated with prednisone (0.6 mg/kg/day orally for 3 months, 0.2 mg/kg/day orally during follow-up). In 8 cases, octreotide was replaced by the long-acting analog lanreotide (30 mg/every 14 days intramuscolarly). Treatment was prolonged until progression of disease was documented. Overall response rate, survival, progression free survival, and toxicity were evaluated. RESULTS: The overall response rate among 16 evaluable patients was 37%. One patient (6%) had a complete response, 5 (31%) had a partial response, 6 obtained a stabilization of disease, and 4 progressed during the treatment. After a median follow-up of 43 months, the median survival was 15 months, and median time to progression was 14 months. Treatment was generally well tolerated with acceptable toxicity: cholelithiasis (1 patient), Grade 2 cushingoid appearance (3 patients), Grade 1 diarrhea (5 patients), Grade 2 hyperglycemia (3 patients). CONCLUSIONS: Treatment with somatostatin analogs and prednisone has shown efficacy in patients with recurrent and metastatic malignant thymic tumors refractory to standard therapeutic options. The results obtained are very satisfactory given the lack of effective alternative treatments. Such therapy is not burdened by the same toxicity of chemotherapy; thus, it can be administered to heavily pretreated patients. Somatostatin analogs and prednisone are well tolerated, and the long-acting analog lanreotide, which requires fewer injections, improves patients' compliance.

Administration, Oral↗

Functional imaging of Langerhans cell histiocytosis by (111)In-DTPA-D-Phe(1)-octreotide scintigraphy.

BACKGROUND: Langerhans cell histiocytosis is a rare group of diseases of unknown pathogenesis, variable clinical presentation, and behavior. It encompasses highly aggressive, often fatal, and indolent diseases, with a variety of intermediate forms between the two extremes. Localization and monitoring of Langerhans cell histiocytosis deposits are based on the combined use of different imaging modalities, which include magnetic resonance, computed tomography, and nuclear medicine procedures. Somatostatin receptor scintigraphy recently has been used to image immune-mediated diseases with excellent results. METHODS: In this study, the authors have evaluated the potential role of somatostatin receptor scintigraphy by using (111)In-DTPA-D-Phe(1)-octreotide in a series of patients with Langerhans cell histiocytosis. Eight consecutive patients (2 males, 6 females; mean age, 43 years; age range, 29-60 years) with histologically proven Langerhans cell histiocytosis, in various phases of their disease, were imaged 24 hours after intravenous injection of 111-222 MBq of (111)In-DTPA-D-Phe(1)-octreotide, by using total body and spot view images. The objective of the study was to preliminarily evaluate this technique in the evaluation of Langerhans cell histiocytosis. RESULTS: Most Langerhans cell histiocytosis deposits were clearly documented by somatostatin receptor scintigraphy, independently from the anatomic location (i.e., skeleton, mucosae, soft tissue, etc.). The correlation between conventional imaging modalities and somatostatin receptor scintigraphy results was fairly good, though this was not considered a primary objective of the study. CONCLUSIONS: Among the various imaging modalities for Langerhans cell histiocytosis, somatostatin receptor scintigraphy is unique, because it accurately depicts the active sites of disease and thus can help in monitoring the response to treatment, together with conventional imaging modalities. Further studies are necessary to confirm the diagnostic value of this technique and clarify the biologic significance of the expression of somatostatin receptors in Langerhans cell histiocytosis.

Adult↗

(99m)Technetium pentavalent dimercaptosuccinic acid scintigraphy in the follow-up of clinically nonfunctioning pituitary adenomas after radiotherapy.

BACKGROUND: It is still difficult to differentiate pituitary adenoma remnants from postradiotherapy fibrosis by computed tomography (CT) or magnetic resonance imaging (MRI), especially in patients with clinically nonfunctioning pituitary adenomas (NFA), lacking circulating markers to follow disease progression or cure. OBJECTIVE: We investigated the usefulness of scintigraphy with technetium-99m pentavalent dimercaptosuccinic acid [(99m)Tc(V)DMSA], shown previously to detect most pituitary GH- and PRL-secreting adenomas and NFA, with tumour-to-background ratios (T/B) as high as 25-fold. PATIENTS: Eighteen patients with NFA (study group), 10 patients with GH- and three patients with PRL-secreting adenomas (control group), all of whom had undergone previous surgery. DESIGN: The study was an open longitudinal design. Pituitary CT/MRI and (99m)Tc(V)DMSA scintigraphy was performed before and 1, 3 and 5 years after conventional radiotherapy. Tumour size was measured as maximal diameter of the residual lesion, while uptake of (99m)Tc(V)DMSA was measured as a T/B ratio. RESULTS: At study entry, pituitary (99m)Tc(V)DMSA uptake was found in 13 NFA (72.2%), seven GH-secreting (70%) and all PRL-secreting adenomas; remnant tumour was documented by CT/MRI in all 31 patients. Maximal remnant diameter was significantly higher in patients with positive (13.3 +/- 0.9 mm) than in those with negative scintigraphy (7.0 +/- 0.3 mm, P < 0.001). During the 5-year follow-up postradiotherapy, a significant decrease in (99m)Tc(V)DMSA uptake (9.7 +/- 0.8 vs. 3.2 +/- 0.5, P < 0.0001) occurred in all but three patients. Two NFA patients died of tumour invasion 19 and 36 months after radiotherapy and one acromegalic patient had no change in his hormone levels. In the eight negative patients (five NFA and three GH), scintigraphy remained negative throughout follow-up. A remarkable shrinkage of the remnant tumour was observed in both the patients with negative (from 7.0 +/- 0.3 to 1.9 +/- 0.6 mm, P < 0.001) and in those with positive scintigraphy (from 13.3 +/- 0.9 to 7.3 +/- 0.6 mm, P < 0.001). At the end of the study, CT/MRI showed evident remnant tumour in 13 of 16 NFA (81.2%), nine GH-secreting (90%) and all three prolactinomas (100%), while the scintigraphy was negative (T/B < 1) or faintly positive (T/B 1-2) in eight of 16 NFA (50%), five GH-secreting (50%) and one prolactinoma (33.3%). CONCLUSIONS: Functional imaging of pituitary remnant adenomas (> 10 mm in size) by (99m)Tc(V)DMSA depicts viable pituitary adenoma remnants. This approach may be of clinical value in patients with clinically nonfunctioning adenomas to monitor the effects of radiotherapy.

Adenoma↗

In vitro and in vivo expression of somatostatin receptors in intermediate and malignant soft tissue tumors.

BACKGROUND: Previous studies showed that the subtype 2 of somatostatin receptors (sstr2) is generally expressed by soft tissue sarcomas. MATERIALS AND METHODS: Using reverse transcription-polymerase chain reaction (RT-PCR), the present study evaluated the expression of sstr mRNA in 31 human intermediate and malignant soft tissue tumors. In 8 patients somatostatin receptor scintigraphy was performed to detect soft tissue tumor sites and visualize in vivo sstr expression. RESULTS: Somatostatin receptors were identified in 84% of the tumors analyzed by RT-PCR analysis. sstr1 and sstr2 were the receptors most frequently detected. Somatostatin receptor scintigraphy was able to identify primary and/or metastatic sites in 7 out of 8 patients, with an overall sensitivity per site of 87%. Concordant results were found between in vitro and in vivo techniques. CONCLUSION: The wide expression of sstrs in soft tissue tumors suggest a relevant role for these receptors in diagnosis and may have therapeutic applications.

Adult↗