Clinico-pathological features, treatments and survival of malignant insulinomas: a multicenter study.

INTRODUCTION: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. AIM OF THE STUDY: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. MATERIALS AND METHODS: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. RESULTS: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. CONCLUSIONS: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.

Valor de la PET/TC con 68Ga-DOTATOC en la detección de recidiva de un tumor fibroso solitario de la pleura / The role of 68Ga-DOTATOC PET/CT in the detection of relapsed malignant solitary fibrous tumor of the pleura

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Real-life management and outcome of thyroid carcinoma-related bone metastases: results from a nationwide multicenter experience.

PURPOSE AND PATIENTS: The M.O.S.CA.TI. (Metastases of the Skeleton from CArcinoma of the ThyroId) is a multicenter, retrospective study investigating the real-life outcome and management of bone metastases (BM) in 143 patients (63 M, 80 F; median age 64 years, range 11-87) with differentiated thyroid carcinoma (DTC). RESULTS: Radio-active iodine (RAI) treatment was performed in 131 patients (91.6%), surgical approach and/or external radiotherapy in 68 patients (47.6%), and anti-resorptive bone-active drugs in 32 patients (22.4%; in 31 zoledronate and in one denosumab). At the start of treatment, 24 patients (75.0%) receiving anti-resorptive bone-active drugs had at least one clinical skeletal-related event (SRE) (p < 0.001). One or more clinical SREs (pathological fractures and/or malignant hypercalcemia and/or spinal cord compression) developed in 53 patients (37.1%). Development of SREs was significantly associated with metachronous BM (hazard ratio (HR) 2.04; p = 0.04), localization of BM to cervical spine (HR 3.89; p = 0.01), and lack of avid RAI uptake (HR 2.66; p = 0.02). Thirty-nine patients (27.3%) died in correlation with development of SREs (HR 6.97; p = 0.006) and localization of BM to the hip (HR 3.86; p = 0.02). Moreover, overall mortality was significantly decreased by RAI therapy (HR 0.10; p = 0.02), whereas no significant effects were induced by bone-active drugs (p = 0.36), external radiotherapy (p = 0.54), and surgery (p = 0.43) of BM. CONCLUSIONS: SREs are very frequent in BM from DTC and they impact patient survival. In the real life, the use of bone-active drugs is currently limited to zoledronate in patients with pre-existing SREs. In this clinical setting, RAI therapy, but not zoledronate, decreased mortality.

A rare case of schwannomatosis incidentally detected by 18F-FDG PET/CT during metabolic evaluation of a chest wall tumor / Un caso poco frecuente de schwannomatosis detectado incidentalmente mediante PET/TC con 18F-FDG durante la evaluación metabólica de un tumor de la pared torácica

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Quantitative comparison between the commercial software STRATOS(®) by Philips and a homemade software for voxel-dosimetry in radiopeptide therapy.

BACKGROUND: Targeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning systems are entering the market. However, some in-house systems are currently developed for a more flexible and customized dosimetry calculation at voxel-level. For this purpose, we developed a novel software, VoxelMed, and performed a comparison with the software STRATOS. METHODS: The validation of both of them was undertaken using radioactive phantoms with different volume inserts. A cohort of 10 patients was also studied after a therapeutic administration of (177)Lu-labelled radiopeptides. The activity, number of disintegrations, absorbed dose and dose-volume histogram (DVH) were calculated for the phantoms and the kidneys in patients, which were the main critical organs at risk in this study. RESULTS: In phantoms the absorbed doses computed with VoxelMed and STRATOS agree within 5%. In patients at the voxel-level the absorbed dose to kidneys (VoxelMed: mean 0.66 Gy/GBq) showed a limited difference of 5%, but with a remarkable range (-40%, +60%) between the two software packages. Voxel-dosimetry allows to estimate the dose non-homogeneities in volumes, which may be evaluated through DVHs. CONCLUSION: This study demonstrates that a fully 3D voxel-dosimetry with multiple SPECT images is feasible by using home-made or commercial software package and absorbed dose results obtained are similar. The main difference between the studied tools was observed in the activity integration method (effective vs physical half-time to time activity curve tail). We believe that an effective half-time integration method produces a more accurate approximation of clinical uptake and resultant dosimetry.

A false positive finding on the PET of somatostatin receptor due to a chondromyxoid fibroma / Un resultado falso positivo de PET de receptores de somatostatina debido a un fibroma condromixoide

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Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of giant malignant solitary fibrous tumor of the pleura / Dificultades diagnósticas en la evaluación preoperatoria con 18F-FDG PET/TC en un caso de tumor fibroso solitario maligno gigante de la pleura

Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with an indolent behavior. Nevertheless, some malignant forms have been rarely reported. These, often have an aggressive biological behavior with pathological findings of invasiveness. The preoperative diagnosis and evaluation of the grade of malignancy are extremely challenging. Herein we report a case of a 64-year-old man who presented with a left giant intra-thoracic mass imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and FNAB findings showed suspicion of a benign form of SFTP. Surgical radical resection of the giant mass was performed. The definitive histological diagnosis showed a malignant SFTP. Based on this report, we take the opportunity to briefly discuss the insidious pitfalls concerning the radiological and 18F-FDG/PET-CT features as well as cyto/histological findings in the pre-operative diagnostic work-up examination of this rare entity (AU)

El tumor fibroso solitario de la pleura (TFSP) es una entidad poco frecuente, en general con un comportamiento indolente. Sin embargo, algunas formas malignas rara vez han sido publicadas, presentando a menudo un comportamiento biológico agresivo con hallazgos patológicos de invasión. El diagnóstico preoperatorio y la evaluación del grado de malignidad es extremadamente difícil. Presentamos el caso de un paciente de 64 años de edad con una masa intratorácica gigante. Se realizó TC, 18F-FDG/PET-TC y biopsia por aspiración con aguja fina. Los hallazgos de imagen y de la biopsia hacían sospechar de una forma benigna de TFSP. Se realizó la resección quirúrgica radical de la masa gigante. El diagnóstico histológico definitivo mostró el TFSP maligno. Aprovechamos la oportunidad de este caso para revisar los aspectos relativos a los estudios radiológicos, características de la 18F-FDG/PET-TC y los hallazgos cito-histológicos en la evaluación preoperatoria de esta rara entidad (AU)

Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of giant malignant solitary fibrous tumor of the pleura.

Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with an indolent behavior. Nevertheless, some malignant forms have been rarely reported. These, often have an aggressive biological behavior with pathological findings of invasiveness. The preoperative diagnosis and evaluation of the grade of malignancy are extremely challenging. Herein we report a case of a 64-year-old man who presented with a left giant intra-thoracic mass imaged with fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and FNAB findings showed suspicion of a benign form of SFTP. Surgical radical resection of the giant mass was performed. The definitive histological diagnosis showed a malignant SFTP. Based on this report, we take the opportunity to briefly discuss the insidious pitfalls concerning the radiological and (18)F-FDG/PET-CT features as well as cyto/histological findings in the pre-operative diagnostic work-up examination of this rare entity.

Radiolabeled somatostatin analogues therapy in advanced neuroendocrine tumors: a single centre experience.

The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33-83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using (68)Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq ((90)Y-DOTATOC/DOTATATE) or 6.0 GBq ((177)Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%). Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs.

Post-treatment residual tissue in idiopathic retroperitoneal fibrosis: active residual disease or silent "scar" ? A study using 18F-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: Medical treatment is often effective in idiopathic retroperitoneal fibrosis (IRF) but frequently leads to residual retroperitoneal masses that may represent active disease or simply consist of inactive fibrotic tissue. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality that reliably assesses disease activity in a number of inflammatory diseases including IRF. We used 18F-FDG PET to evaluate the metabolic activity of residual masses in a series of IRF patients. METHODS: We studied 7 consecutive IRF patients, all of whom presented constitutional symptoms and/or pain, and had high acute-phase reactant levels; 6 had ureteral involvement. IRF was diagnosed by means of computed tomography (CT), which revealed a peri-aortoiliac mass in all cases. Three patients underwent surgical ureterolysis and 2 received ureteral stents. Subsequently, 5 patients received prednisone, one sequential treatment with prednisone and tamoxifen, and one prednisolone plus methotrexate. All of the patients underwent 18F-FDG PET at varying times after the end of treatment. RESULTS: The presenting signs/symptoms improved in all patients and the levels of acute-phase reactants significantly decreased or normalised. Ureteral obstructive disease resolved in all cases. Post-treatment CT revealed a considerable reduction in the amount of IRF but all of the patients had a residual retroperitoneal mass. PET revealed slight aorto-iliac 18F-FDG uptake in only one patient; all of the others were negative. No patient relapsed during the follow-up. CONCLUSIONS: Post-treatment residual masses are frequent in IRF patients but, in most cases, probably represent metabolically inactive tissue.

Larger axillary metastases in obese women and smokers with breast cancer--an influence by host factors on early tumor behavior.

To better define the influence by host factors on very early breast cancer behavior, we retrospectively analyzed nodal status, diameter of the largest axillary metastasis (M), diameter of the primary tumor (P), the M/P ratio, tumor estrogen receptor status, age, obesity, and smoking habits in 176 women with node-positive breast cancer. Both M/P ratios and M were larger in the 72 obese women and in the 40 nonobese smokers than in the 64 nonobese nonsmokers after control for other factors. Step-wise regression analysis demonstrated independent associations between M/P ratios and obesity (p = 0.0002), larger primary tumors (p < 0.0001), more positive nodes (p < 0.0001), and smoking (p = 0.0268), as well as between M and obesity (p = 0.0201), larger primary tumors (p = 0.0093), and more positive nodes (p = 0.0001). Among the 104 nonobese women, smoking was associated both with larger M (p = 0.0257) and larger M/P (p = 0.0055). Our observations suggest more rapid growth by metastases in obese women and smokers with breast cancer, as well as earlier metastasis from their primary tumors.

[Efficacy of flecainide in the treatment of ventricular tachycardia in the elderly. Dynamic electrocardiographic study]. / Efficacia della flecainide nel trattamento della tachicardia ventricolare dell'anziano. Studio elettrocardiografico dinamico.

The antiarrhythmic activity of flecainide has been tested in seven old patients (mean age 71 years) suffering from recurrent episodes of ventricular tachycardia. A basal 24-hour dynamic electrocardiogram was recorded for each patient and was repeated on day 5 of oral flecainide treatment (200 mg). A significant reduction (p less than 0.0001) of premature ventricular beats, of bigeminism (p = 0.0025) and of the episodes of ventricular tachycardia (p = 0.017) was obtained with plasma flecainide levels between 322 and 614 ng/ml. In addition, sinus rhythm was restored in two patients with stable atrial fibrillation and in the others ectopic atrial beats were markedly reduced. Among the ECG parameters examined, only QRS was significantly increased (p = 0.034). No significant change of blood pressure and laboratory parameters was observed. Untoward side effects were not observed.

[Personal experiences concerning the usefulness of the exercise test in the diagnosis of ischemic heart disease in aged patients with atypical symptomatology]. / Esperienze personali sull'utilità della prova da sforzo nella diagnosi di cardiopatia ischemica in pazienti anziani con sintomatologia atipica.

Present-day therapeutic possibilities, both medical and surgical, make it mandatory for the practitioner to identify elderly patients with ischemic heart disease which in these patients often presents with atypical symptoms. Twenty elderly patients with not clear-cut symptoms of coronary disorder were submitted to an exercise test on a walking belt. In 14 (70%) the test was positive and in 8 of these 14 cases previous dynamic electrocardiography had not yielded signs of ischemia. The authors consider correctly performed exercise testing the best means for identifying the often not diagnosed coronary impairment of elderly subjects.

[Effects of acute loading of alcohol on platelet aggregation in normal subjects]. / Effetto del carico acuto di alcool sull'aggregazione piastrinica in soggetti normali.

Ten healthy subjects were submitted to alcohol loading (0.8 g/kg body weight; average alcohol blood level 0.97 g 0/00). The number of platelets, hematocrit and ADP-induced platelet aggregation curves did not show any variation from baseline. Significant changes (p less than 0.05) were observed as regards latent period (increased) and maximum amplitude (reduced) for collagen-induced platelet aggregation. In agreement with others, the authors conclude that alcohol definitely inhibits platelet aggregation.