Long-term follow up of patients affected by pulmonary carcinoid at the Istituto Nazionale Tumori of Milan: a retrospective analysis.

Neuroendocrine tumors of the lung involve an heterogeneous group of tumors representing a wide range of histological variants, from well-differentiated typical carcinoid (TC) tumors to poorly differentiated small cell carcinomas. The epidemiology, clinical outcome, and management of these neoplasms differ significantly from other lung malignancies. The main aim of this report consists in describing the single Center experience of the Istituto Nazionale Tumori of Milan on neuroendocrine lung tumors, with an emphasis on bronchopulmonary carcinoid subtypes. From 1986 to 2009, 91 cases of carcinoid tumors were diagnosed; these were divided in two series, according to typical (66 patients) or atypical [25] histotypes. These two groups were compared in relation to various features, including pathologic classification, clinical behavior, treatment modalities and long-term survival. At the moment of diagnosis 11 patients had locally advanced/metastatic disease, while 80 patients showed non metastatic disease. The comparative analysis between typical and atypical series disclosed significant differences in terms of long-term survival; in fact, 5-year and 10-year survival rates were 98 % and 94 % for the first carcinoid series versus 76 % and 18 % for the atypical series, respectively (p<0.001). The median overall survival (OS) was 76 months (range 3-182) for atypical carcinoids and has not yet been reached for TCs patients.

Is the new WHO classification of neuroendocrine tumours useful for selecting an appropriate treatment?

BACKGROUND: Neuroendocrine tumours (NETs) are a rare and heterogeneous group of neoplasms. The most recent WHO classification provides clinical tools and indications to make the diagnosis and to suggest the correct treatment in different subgroups of patients. The aim of this trial was to apply the new classification criteria in clinical practice and, accordingly, to choose the most appropriate treatment. PATIENTS AND METHODS: Thirty-one evaluable patients, not previously treated, classified as advanced well differentiated NETs according to the new classification, were given long-acting release octreotide 30 mg every 28 days until evidence of disease progression. The treatment activity was evaluated according to objective, biochemical and symptomatic responses. Safety and tolerability were also assessed. RESULTS: Two partial objective tumour responses were obtained (6%), stabilization occurred in 16 patients (52%) and 95% of patients had a disease stabilisation lasting > or =6 months. However, eight patients showed rapid disease progression within 6 months of therapy and six patients after 6 months. Biochemical responses, evaluated by changes in serum chromogranine A levels were reported in 20/24 patients (83%). Symptomatic responses were observed in 6/14 patients (43%): a complete syndrome remission in one patient, partial syndrome remission in five patients, no change in four patients and progressive disease in four patients. The median overall survival was not reached, and the median time to disease progression was 18 months (range 1-49 months). The treatment was well tolerated, no severe adverse events were observed and no patient withdrew from the study because of adverse events. CONCLUSIONS: The WHO classification enables identification of low-grade NET patients who may be suitable for hormonal treatment. Octreotide LAR was seen to be effective in controlling the disease and was well tolerated. However, eight patients failed to respond to the treatment, despite histological evidence of a well differentiated tumour according to the new classification. This suggests that further histological examination should be carried out, especially in patients with visceral metastases and a short disease-free interval.

Are behaviour and motor performances of rheumatoid arthritis patients influenced by subclinical cognitive impairments? A clinical and neuroimaging study.

OBJECTIVE: To determine whether some behavioural manifestations and poor motor performances in patients affected by rheumatoid arthritis (RA) are due to subclinical cognitive defects. METHODS: We performed a psychometric assessment of 30 patients affected by RA exploring several cognitive domains such as memory, visual-spatial integration, motor planning, mental flexibility, relating performances with morphological and functional neuroimaging (MRI and SPECT). We also related the cognitive data with the Ritchie and Lee indexes and other clinical parameters. RESULTS: We found an impairment in visual-spatial tasks in 71% of patients with a high correlation to activity and disease severity as expressed by the Ritchie and Lee indexes (p < 0.005; p < 0.01). Furthermore, we detected in 38% of patients some difficulties in mental flexibility related to the Lee Index (p < 0.05). These poor performances are related to hypoperfusion of the frontal and parietal lobes as detected by brain SPECT; this finding is more evident in patients with brain white matter alterations on MRI. CONCLUSIONS: Our data allow us to hypothesize that manual dexterity could be due to a disconnection between subcortical white matter and parietal-frontal lobes because of microangiopathy; furthermore, a chronic reduction in sensorial stimuli by impaired joints could lead to produce an alteration in motor planning cognitive processes.

Efficacy of a chemotherapy combination for the treatment of metastatic neuroendocrine tumours.

OBJECTIVES: Neuroendocrine tumours (NETs) are heterogeneous neoplasms for which there is no standard treatment. We have previously proposed an effective polychemotherapy (5-fluorouracil, dacarbazine and epirubicin), which only produced objective responses of brief duration. The present study aimed to assess in a multidisciplinary manner the efficacy of the same regimen at intensified doses in patients with advanced NETs. PATIENTS AND METHODS: Eighty-two consecutive patients entered the study, of whom 21 had inoperable, locally advanced disease and 61 had metastatic disease. Seventy-two patients were evaluated for objective, biochemical and subjective responses. Response rate, time to progression (TTP) and overall survival (OS) were evaluated based on histotype. RESULTS: An objective response was observed in 20 patients (intention-to-treat and standard analysis 24.4% and 27.8%, respectively). Complete biochemical and subjective responses were obtained in 25.1% and 38.9% of the cases. The median duration of treatment was 4 months and the objective responses had a median duration of 38 months. After a 60-month follow-up the median TTP and OS were 21 and 38 months, respectively. CONCLUSIONS: Our polychemotherapy regimen is effective, with long duration, and is well tolerated both for gastroenteropancreatic and lung NETs, as well as for tumours with a more aggressive clinical behaviour. The new WHO endocrine tumour histotyping, examining also the tumour biology, may give additional information for selecting patients to chemotherapy.

Short-term effects of anastrozole treatment on insulin-like growth factor system in postmenopausal advanced breast cancer patients.

Insulin-like growth factors (IGFs) play a fundamental role in cancer development by acting in both an endocrinal and paracrinal manner, and hormone breast cancer treatments affect the IGF system by modifying circulating growth factor levels. We evaluated total IGF-1, IGF-2, IGF binding protein (IGFBP)-1 and IGFBP-3 in the blood of 34 postmenopausal advanced breast cancer patients (median age 63 years, range 41-85) treated with anastrozole, a non-steroidal structure aromatase inhibitor (NSS-AI). The plasma samples were obtained at baseline, and after 2, 4, 8 and 12 weeks of treatment. The IGFs were quantitated by means of sensitive radioimmunoassays (RIAs). IGF-1 significantly increased during anastrozole treatment (baseline versus 12 weeks, P=0.031), IGF-2 showed a trend towards an increase, and IGFBP-1 constantly but not significantly decreased; IGFBP-3 did not seem to be affected at all. The anastrozole-induced changes in IGFs and IGFBP-1 appeared to be different in the patients receiving a clinical benefit from those observed in non-responders. We have previously shown that letrozole (a different type of NSS-AI) modifies blood IGF-1 levels, and the results of this study of the biological effects of anastrozole on the components of the IGF system confirm our previous observations.

Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.

OBJECTIVE: To evaluate the efficacy and safety of prostaglandin (PG) E1alpha-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator (t-PA). METHODS: We studied 36 women with SSc, 24 of them given three 60 microg intravenous PGE1alpha-cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions were evaluated. Twenty age matched healthy women were the controls. TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGEE1alpha-cyclodextrin and correlated with clinical features. RESULTS: RP symptoms improved in 87% of the patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%. PGE1alpha-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p < 0.05), 41% (p < 0.005), and 53% (p < 0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with digital lesions, these healed completely. Ten patients had mild side effects during treatment (headache, increased intestinal motility, flushing). TNF-alpha, sIL-2R, cICAM-1, vWF, and t-PA plasma concentrations were significantly higher in patients with SSc than controls (p < 0.05, p < 0.001). TNF-alpha, sIL-2R, and cICAM-1 were higher in diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and t-PA were significantly reduced after the 1st infusion of PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005). CONCLUSION: PGE1alpha-cyclodextrin reduces RP symptoms and plasma levels of the markers of endothelial injury in SSc, suggesting that an improvement of endothelial dysfunction contributes to its prolonged therapeutic effect.

Advances in diagnosis and therapy of neuroendocrine tumors.

Neuroendocrine tumors represent a group of neoplasias characterized by significant histopathologic and biological heterogeneity. Diagnosis of neuroendocrine tumors relies upon histological examination augmented by newer techniques such as position emission tomography, meta-iodobenzylguanidine scintigraphy or octreoscan. Surgery represents the definite and curative therapeutic approach in early phase tumors. In metastatic or advanced disease, medical treatment is the best choice. Somatostatin analogs allow adequate control of the carcinoid syndrome, without a significant effect on tumor cell growth. Interferon-alpha may represent an alternative, alone or in association with somatostatin analogs. Chemotherapy is the best choice in the treatment of neuroendocrine tumors characterized by a poor differentiation grade and a high proliferation rate.

Ovarian ablation for premenopausal early-stage breast cancer: an update.

Ovarian ablation is the oldest form of systemic treatment of breast cancer and consists of removal of the main source of estrogen biosynthesis in premenopausal women: Over the last century several different means of stopping ovarian function have been studied: surgical oophorectomy, ovarian irradiation, and more recently, chemical castration by gonadotropin-releasing hormone analog therapy. In unselected patients the response rate to ovarian ablation is of about 35% but the likelihood of response is considerably higher for patients with hormonal receptor-positive tumors, the therapy being most effective in women who are actively menstruating. In spite of this evidence, the role of ovarian ablation in the management of early-stage breast cancer still remains controversial. Here we review current evidence supporting the value of this ablative procedure as an adjuvant and update ongoing clinical research to refine our knowledge about its use.

Sonography in neonatal congenital adrenal hyperplasia.

Adrenal gland size was evaluated in six infants with congenital adrenal hyperplasia. All of the infants had a severe deficiency of the 21-hydroxylase enzyme resulting in the salt-losing form of congenital adrenal hyperplasia. The adrenal measurements were compared with those of 40 consecutive age-matched, asymptomatic infants. Mean adrenal length was 14.4 mm and width was 1.9 mm in asymptomatic infants, whereas in infants with congenital adrenal hyperplasia mean adrenal length was 23.7 mm and width was 5.3 mm. Although infants with congenital adrenal hyperplasia may have normal-sized adrenal glands, mean length measurements of 20 mm or greater and mean width measurements of 4 mm or greater suggest the diagnosis.

Intracranial abnormalities in infants treated with extracorporeal membrane oxygenation: imaging with US and CT.

Findings at neuroimaging in 100 consecutive infants treated with extracorporeal membrane oxygenation (ECMO) are presented. Imaging in these infants consisted of pretreatment cranial ultrasonography (US), daily US studies while on ECMO, and follow-up cranial computed tomography (CT) after treatment. There were findings of abnormalities in 43 patients. Thirty had intracranial bleeding, often of unusual extent and distribution. Thirteen additional infants had nonhemorrhagic abnormalities alone. Bleeding considered to be major was seen in 12% of infants. Large parenchymal hemorrhages and infarcts, cerebellar hemorrhages, and diffuse edema were the most significant abnormalities, with a 50% mortality (eight of 16 patients). No lateralization was noted with respect to distribution of bleeding sites or areas of nonhemorrhagic abnormalities. US was a sensitive but imperfect screening tool for intracranial abnormalities. Abnormalities missed with US included peripheral and small parenchymal lesions, subarachnoid hemorrhage, cerebral atrophy, and sagittal sinus thrombosis.

Intracranial flow patterns in infants undergoing extracorporeal membrane oxygenation: preliminary observations with Doppler US.

Transcutaneous Doppler ultrasound was used to monitor changes in intracranial hemodynamics in 13 infants undergoing extracorporeal membrane oxygenation (ECMO). Recordings for the pericallosal portion of an anterior cerebral artery were obtained before ECMO and daily during ECMO bypass, with use of a range-gated, pulsed Doppler imaging system. Obvious changes occurred with the onset of ECMO: the systolic phase broadened, and diastolic flow velocities markedly increased. The mean pulsatility value, as measured with the Pourcelot pulsatility index, decreased significantly at the start of ECMO and over time during ECMO bypass. Marked increases in the area under the velocity curve (AUTC) were also observed with the institution of ECMO bypass (mean percentage change in AUTC from baseline, 133%). Factors that appeared to affect AUTC included PCO2, mean blood pressure, and ECMO bypass rate. AUTC tended to decrease during the course of ECMO. Although the clinical significance of these findings remains unclear, the data indicate that ECMO bypass is associated with marked changes in intracranial hemodynamics.

Bladder pseudomass following cystography-related bladder trauma.

Transient sonographic abnormalities of the urinary bladder in children can be identified immediately after performance of voiding cystourethrography. Both cystic and solid masses may be mimicked by transient hematuria induced by minor, cystography-related trauma. After the bladder has been emptied and refilled, reexamination shows prompt resolution of these pseudo-masses.