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The molecular mechanism underlying the development of colorectal cancer (CRC) is not yet fully-understood, but there is evidence that inflammation plays a key role. Several circulating tumor and inflammatory markers can be useful for studying patients with CRC. It has been suggested that high serum levels of C-reactive protein (CRP) are associated with elevated risk of various malignancies and that CRP may affect survival of patients with CRC. We analyzed the relationship existing between the stage of the disease and baseline CRP serum levels in a group of 91 patients undergoing surgery for stage III (N=72, 79.1%) and IVa (N=19, 20.9%) CRC. There were 51 (56%) men and 40 (44%) women, with a median age of 66 years. Prior to surgery, all patients underwent quantitative serum CRP measurement. The overall 5-year survival was 37.1 ± 13.0 months. Patients with stage III disease and the sub-group with CRP3 mg/l (N=43, 47.3%) had a longer survival (p0.01) than patients with stage IVa and the sub-group with CRP ≥ 3 mg/l (N=48, 52.7%). No relationship between the age of the patients and CRP levels was found (R=-0.005, p=0.96), whilst there was a significant inverse relationship between survival and CRP level (R=-0.37, y=37.5343-0.5868x, p=0.0003). Using multivariate Cox model analysis (forward stepwise method), adjusted for age, CRP and CRC stage were independent parameters related to survival, with a relative risk of 3.5 (95% confidence interval=1.5-8.2) and 8.1 (95% confidence interval=3.0-21.3), respectively. In conclusion, CRP is a sensitive and easily detectable serum marker that can be useful in patients with CRC, allowing their better clinical stratification.

Endothelial dysfunction is crucial in Behçet's disease (BD) pathogenesis, and measures of endothelial damage are potential markers of BD activity. Heparan sulfate (HS) is the most abundant proteoglycan in the endothelial cells, and anti-HS antibodies have been reported in subjects with vascular damage, due to vasculitis/vasculopathy. The aim of our study was to measure serum anti-HS antibodies in patients with BD and to determine whether their presence correlates with disease activity or clinical manifestations.Thirty-two patients with BD (21 men, 11 women) (median age 36.81+/-12.0 years) were considered. Of these, 13 had clinically active disease at the time of study. The mean disease duration was 7.31+/- 8.2 years (median 6 years). Anti-HS antibodies were measured by ELISA. As controls, sera from 40 sex- and age-matched healthy subjects, and 78 age-matched patients with systemic lupus erythematosus (SLE) were studied.Anti-HS IgM antibody titres were significantly higher in BD patients compared to healthy subjects (p=0.016) and SLE controls (p=0.0008). No differences in anti-HS IgG antibody titres were observed among the 3 groups. Using categorical data, increased titres of IgM anti-HS antibodies were significantly more frequent in patients with BD vs patients with SLE (p=0.02). The presence of the antibodies, of either isotype, did not correlate with disease duration, disease activity or clinical manifestations.BD patients have increased IgM anti-HS antibody titres compared to healthy and SLE controls. These antibodies did not correlate with disease activity or discrete clinical features, but might be relevant for pathogenic mechanisms of the disease.

Treatment options for glioblastoma (GBM) at recurrence have limited efficacy. Re-surgery has been used for confirmation of recurrent disease and to provide relief of symptoms but the real impact on survival is unknown. PATIENTS AND METHODS: A retrospective analysis was performed for GBM patients followed between 01/2005 and 06/2010 at our Institution. RESULTS: Two hundred and thirty-two patients with recurrent GBM were evaluated. One hundred and two patients (44%) were treated with re-surgery followed by chemotherapy and 130 patients (56%) with chemotherapy alone. In multivariate analysis, no significant effect of re-surgery was found, with age (p=0.001), MGMT methylation (p=0.002) and PFS at 6 months (p=0.0001) being significant prognostic factors. CONCLUSION: Second surgery might have a limited impact in the clinical course of recurrent GBM patients.

The aim of the present study was to analyze whether any correlation exists between breast complaints and the risk of having or developing breast cancer (BC) in a population of self-selected women.A series of 2,561 patients was reviewed. Three age-groups were sorted out: Group A (40 years old or younger, 45.9%), Group B (41-55 years, 27.8%), and Group C (55 years, 26.3%). Breast pain was most common (61.0%) in Group A, and breast lump in Group C (87.8%).BC was found in 271 (10.6%) patients. Breast pain was more frequent in patients without cancer with respect to patients with BC, both in Group B (45.8% vs. 27.9%; p = 0.039) and in Group C (9.2% vs. 1.7%; p = 0.003), but no correlation (p = NS) between BC and breast lump or nipple discharge was found in any Group. Over a median follow-up of 74 months (range 23-146 months). BC arose in 10 (0.44%) patients.The majority of the women with breast complaints did not have BC, and their risk of cancer onset was not dissimilar to that reported for the general population.

The intima-media thickness (IMT) measurement of the common carotid artery is recognized as a reliable marker of systemic atherosclerosis and may be useful in predicting the likelihood of cardiovascular events, since it is related to the extent and severity of coronary artery disease. The aims of this study were to analyze whether correlations exist between the IMT of the common carotid artery and the main clinical and biochemical parameters in patients with primary hyperparathyroidism (PHPT), and to evaluate the possible improvement of the IMT values following parathyroidectomy at long-term follow-up.Twenty-seven patients (5 men, 22 women; median age 59 years, range 36-82 years) with biochemically confirmed PHPT (Group A, cases), and 27 gender- and age-matched healthy volunteers (Group B, controls) were prospectively enrolled in the study. All patients underwent ultrasound examination and the IMT of each carotid artery were recorded, averaging all values. The measurements were repeated 18-22 months (median 20) later in all patients.A significant (p0.05) correlation between age and both systolic BP and IMT, and between IMT and fasting glycaemia was found in each Group. There was an inverse relationship between IMT and serum parathyroid hormone (R = -0.56, p0.01), but no correlation (p=NS) was found between IMT and serum calcium (R = -0.14) or serum phosphate (R = 0.07). At follow-up a slight (10.4%) improvement in the mean IMT was observed among Group A patients (0.86 +/- 0.18 vs. 0.77 +/- 0.24; p = 0.12), but the difference was not significant.At long term follow-up, the IMT values did not improve significantly and no correlation was found between serum calcium and IMT. These results suggest that hypercalcemia does not represent a reliable risk of carotid atherosclerosis in patients with PHPT.

Malignant pleural effusion (MPE) is common in most patients with advanced cancer, especially in those with lung cancer, metastatic breast carcinoma and lymphoma. This complication usually leads patients to suffer from significant dyspnea, which may impair their mobility and reduce their quality of life. In patients with MPE, several interventions have been shown to be useful for palliation of the symptoms, including talc pleurodesis. The aim of this study was to evaluate prognostic factors for survival of patients with symptomatic MPE who underwent palliative video-assisted thoracoscopic (VATS) talc pleurodesis. Thirty-five patients with MPE underwent VATS, evacuation of the pleural fluid and talc pleurodesis with large-particle talc. There were 22 (62.9%) males and 13 (37.1%) females, with an overall median age of 69 years (range 42-81 years). The main causes of MPE were non-small cell lung carcinoma, breast or ovarian cancer and malignant pleural mesothelioma. The age did not differ (p=0.88) between men (68.6±11.6 years) and women (68.0±8.7 years). The mean quantity of pleural effusion was 2005.7±1078.9 ml, while the overall survival was 11.2±8.9 months. We did not find any relationship between survival and gender (log-rank test, p=0.53) or underlying malignancy associated with MPE (p=0.89, 0.48 and 0.36 for secondary cancer, lung cancer and mesothelioma, respectively). Similarly, no correlation was found between survival and age of the patients (Cox's regression, p=0.44) or quantity of pleural effusion (p=0.88). Our results show that the prognosis of patients after talc pleurodesis is independent of age, gender, type of malignancy and amount of pleural effusion, thus, suggesting the utility of treating all patients with symptomatic MPE early.

The aim of this study was to compare the sensitivity of different pre-operative parameters in patients with breast cancer (BC) recurrence using univariate and multivariate analysis.We retrospectively analyzed a series of 387 women (median age 60 years, range 35-83 years) who underwent curative surgery for pT1-2 BC. The patients were divided into two groups: Group 1: 325 (84.0%) patients with no evidence of disease during a median follow-up of 53 months (range 25-149 months) and Group 2: 62 (16.0%) patients who developed local or distant recurrences.Univariate analysis showed significant (p0.01) differences between the two Groups in age, size and grading of the tumor and hormone receptor rate. MIB1 proliferation rate, serum markers CEA and CA 15-3, and lymph node status were not useful in predicting relapse. Multivariate analysis using a logistic regression model showed that only age, size of the tumor and hormone receptor rate independently correlate with the onset of recurrences.There is no clear correlation between BC recurrence and the majority of the prognostic factors available. Multivariate analysis of several pre-operative parameters may help to correctly select the high risk population.

Objectives A strikingly increased headache prevalence was recently noted in Sri Lankan beta-thalassemia patients, raising several concerns regarding long-term neurological involvement in this condition. Methods We interviewed on headache occurrence and characteristics 102 Italian beta-thalassemia patients and 129 healthy controls. 3T-MRI, MR-angiography, MR-venography, cognitive and psychiatric findings were considered. Results Headache was diagnosed in 39/102 (38.2%) beta-thalassemia patients without significant phenotype-related differences and in 51/129 (39.5%) controls. Patients and controls did not differ significantly regarding episode number (5.9 ± 6.2 vs 5.4 ± 4.4 days/month), subjective severity-score (6.8 ± 1.4 vs 7.1 ± 1.3), age-at-onset (24.3 ± 13.0 vs 19.5 ± 9.6 years) and headache-subtype rate. No main demographic, clinical or laboratory data was associated with headache but female gender. Headache was not associated with white matter lesions (number or maximal diameter), intracranial aneurysms, intracranial artery stenoses or venous sinus thrombosis. Cognitive and psychiatric evaluations were worse in beta-thalassemia, however, headache did not correlate with full-scale Intelligence Quotient (75.4 ± 18.0 vs 76.7 ± 15.3, with and without headache, respectively) or Brief Psychiatric Rating Scale scores (29.1 ± 2.7 vs 28.5 ± 3.4). Conclusions Among Italian beta-thalassemia patients, headache does not seem to be more common or severe than in the general population. In addition, patients with headache do not seem to present increased conventional MRI, MR-angiography and cognitive/psychiatric changes.

Objective: The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods: Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results: The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions: Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB.

Lenalidomide, an immunomodulatory drug used in myeloma therapy, has been claimed to be less neurotoxic than thalidomide, but evidence is still weak. We prospectively assessed lenalidomide safety in myeloma patients to evaluate whether it would induce or modify a previously ensued chemotherapy-induced peripheral neuropathy (CIPN). Thirty consecutive patients (17 men, mean age 63.7 ± 9.4) previously treated with bortezomib and/or thalidomide and starting on lenalidomide (25 mg/day for 21-day cycles) for relapsed or refractory myeloma were assessed at baseline, 6, and 12 months from the beginning of lenalidomide with Total Neuropathy Score clinical version (TNSc), Eastern Cooperative Oncology Group (ECOG) performance status, and numeric rating scale (NRS) for pain. TNSc >2 was considered significant for CIPN. TNSc changes of at least 4 points from baseline value were considered clinically relevant. At baseline 16 of the 30 patients (53.3%) had CIPN (mean TNSc 5.8, range 3–15). After 6 months, 13 patients were unchanged, 1 improved, and 2 worsened. After 12 months the patient who had improved persisted stable, and the two who had worsened returned to TNSc baseline value. The 14 patients without CIPN at baseline did not develop neuropathy. NRS and ECOG performance status persisted unchanged. Our results demonstrate lenalidomide safety and very low neurotoxicity also in patients with pre-existing CIPN treated for 1 year.

Background and purpose Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. Patients and methods Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37–75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. Results Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. Discussion Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings.

Objective: To test the effect of the single nucleotide polymorphism −66 T>G (rs28357094) in the osteopontin gene ( SPP1 ) on functional measures over 12 months in Duchenne muscular dystrophy (DMD). Methods: This study was conducted on a cohort of ambulatory patients with DMD from a network of Italian neuromuscular centers, evaluated longitudinally with the North Star Ambulatory Assessment (NSAA) and the 6-Minute Walk Test (6MWT) at study entry and after 12 months. Genotype at rs28357094 was determined after completion of the clinical evaluations. Patients were stratified in 2 groups according to a dominant model (TT homozygotes vs TG heterozygotes and GG homozygotes) and clinical data were retrospectively compared between groups. Results: Eighty patients were selected (age 4.1–19.3 years; mean 8.3 ± 2.7 SD). There were no differences in age or steroid treatment between the 2 subgroups. Paired t test showed a significant difference in both NSAA ( p = 0.013) and 6MWT ( p = 0.03) between baseline and follow-up after 12 months in patients with DMD carrying the G allele. The difference was not significant in the T subgroup. The analysis of covariance using age and baseline values as covariate and SPP1 genotype as fixed effect showed that these parameters are significantly correlated with the 12-month values. Conclusions: These data provide evidence of the role of SPP1 genotype as a disease modifier in DMD and support its relevance in the selection of homogeneous groups of patients for future clinical trials.

BACKGROUND No data on the role of chemotherapy in recurrent ependymal tumors are available in adults. The aim of the current study was to investigate outcomes after salvage chemotherapy in this setting. METHODS A retrospective review was made of the charts of 28 adults (≥ 18 years) with progressive or recurrent ependymal tumors after surgery and radiotherapy, who received chemotherapy between 1993 and 2003 in 3 institutions of the Gruppo Italiano Cooperativo di Neuro-Oncologia network. RESULTS Thirteen patients (46.3%) received cisplatin-based chemotherapy (Group A) and 15 (53.7%) received regimens without cisplatin (Group B). Platinum-based chemotherapy yielded 2 complete responses (CR) (15.4%) and 2 (15.4%) partial responses (PR), whereas 7 patients (53.8%) remained stable (SD). After regimens without cisplatin, there were no CR, 2 PR (13.3%), and 11 SD (73.3%). The overall median time to progression was 9.9 months (95% confidence interval [95% CI], 7.5–21.7 months), 9.9 months (5.2–not reached) for Group A and 10.9 months (95% CI, 7.17–23.9 months) for Group B. The overall median survival (OS) was 40.7 months (95% CI, 16–not reached), 31 months (21–not reached) for Group A and 40.7 months (13.4–not reached) for Group B. CONCLUSIONS Cisplatin-based chemotherapy achieved a higher response rate, but did not prolong disease progression-free survival or OS. More active regimens for the salvage treatment of ependymal tumors have yet to be found. Cancer 2005. © 2005 American Cancer Society.

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.

Study was performed in Fischer-344 rats to test the effects of the intravenous anesthetic propofol on cerebral content of high-energy metabolites, glucose, and lactate in normoxic and severely hypoxic rats. General and local anesthetics (isoflurane, N(2)O 70%, pancuronium bromide, bupivacaine hydrochloride) were used for surgery (tracheostomy, femoral artery and vein cannulation, skull exposure, ligature of right-sided carotid and EEG needle electrodes only in rats devoted to the hypoxia study). For normoxia study, four groups of 7 rats each were treated for 60 min as it follows: the control group with N(2)O plus propofol vehicle and the other three with propofol 12.5, 25, or 50 mg x kg(-1) x h(-1) respectively. For the hypoxia-study five groups of 7 rats each were planned to have two control (one normoxic) and three propofol-treated groups, drug treatments being the above indicated and of 80 min. During the last 20 min Pa(O(2)) was lowered to 15-20 mmHg. Pa(CO(2)) was maintained between 35-40 mmHg, rectal temperature at 37 degrees C, MABP near to 100 mmHg and pH on the basal values during the whole procedure. Then brains were frozen in vivo, and cortical tissue was excised and analyzed for labile metabolites using fluorometric techniques. Propofol, at all the doses tested, did not alter the concentrations of adenine nucleotides, phosphocreatine, lactate, pyruvate, or glucose in normoxic rats. In rat brain, hypoxia did not produce significant changes in the concentrations of adenine nucleotides. PCr concentration was decreased both in the ligated and unligated side, and lactate levels exceeded 21 and 18 micromol/g in the right and left cortices, respectively. While the lowest dose of propofol was ineffective in preventing PCr decrease and lactate increase, both 25 and 50 mg x kg(-1) x h(-1) significantly reduced those adverse effects of hypoxia.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) has been found to be strongly related to an increased arterial stiffness in patients with essential hypertension, suggesting a pathophysiologic link between major cardiovascular and metabolic abnormalities associated with liver steatosis and the functional and structural alterations of the arterial wall. The aim of our study was to investigate, in a group of essential hypertensive patients without additional cardiovascular risk factors, the relationship between NAFLD and arterial stiffness. METHODS AND RESULTS: Sixty-eight consecutive patients with essential hypertension underwent 24-h ambulatory blood pressure monitoring (ABPM) and were separated according to the presence (n = 40) or absence (n = 28) of NAFLD at liver ultrasonography. The Ambulatory Arterial Stiffness Index (AASI) and Symmetric AASI (Sym-AASI) were derived from ABPM tracings. Patients with diabetes, obesity, hyperlipidaemia or other risk factors for cardiovascular or liver disease were excluded. Hypertensive patients were compared with a normotensive control group.The two hypertensive groups had comparable age, sex distribution and clinic/ABPM blood pressure levels. In hypertensive patients with NAFLD, body mass index, fasting glucose, insulin, homeostasis model of assessment of insulin resistance index and triglyceride levels were higher, whereas plasma adiponectin was lower than in patients without NAFLD. In hypertensive patients, AASI and Sym-AASI were higher (P < 0.001) than in normotensive subjects, but both indices of vascular stiffness were comparable in patients with and without NAFLD. CONCLUSIONS: In essential hypertensive patients without additional cardiovascular risk factors, NAFLD is associated with insulin resistance but not with increased arterial stiffness.

Background Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Methods Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100–75 mg m2) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m2) every 3 weeks for ≤1 year. Results Forty-three patients (29 M, 14 F; median age 51 years, range 34–68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9–33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5–7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. Conclusions The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

Purpose Standard therapy for glioblastoma (GBM) is temozolomide (TMZ) administration, initially concurrent with radiotherapy (RT), and subsequently as maintenance therapy. The radiologic images obtained in this setting can be difficult to interpret since they may show radiation-induced pseudoprogression (psPD) rather than disease progression. Methods Patients with histologically confirmed GBM underwent radiotherapy plus continuous daily temozolomide (75 mg/m2/d), followed by 12 maintenance temozolomide cycles (150 to 200 mg/m2 for 5 days every 28 days) if magnetic resonance imaging (MRI) showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. The first MRI scan was performed 1 month after completing combined chemoradiotherapy. Results In 103 patients (mean age, 52 years [range 20 to 73 years]), total resection, subtotal resection, and biopsy were obtained in 51, 51, and 1 cases, respectively. MGMT promoter was methylated in 36 patients (35%) and unmethylated in 67 patients (65%). Lesion enlargement, evidenced at the first MRI scan in 50 of 103 patients, was subsequently classified as psPD in 32 patients and early disease progression in 18 patients. PsPD was recorded in 21 (91%) of 23 methylated MGMT promoter and 11 (41%) of 27 unmethylated MGMT promoter (P = .0002) patients. MGMT status (P = .001) and psPD detection (P = .045) significantly influenced survival. Conclusion PsPD has a clinical impact on chemotherapy-treated GBM, as it may express the glioma killing effects of treatment and is significantly correlated with MGMT status. Improvement in the early recognition of psPD patterns and knowledge of mechanisms underlying this phenomenon are crucial to eliminating biases in evaluating the results of clinical trials and guaranteeing effective treatment.

Humoral immune mechanisms may have a role in the neurological complications of celiac disease (CD). We assessed 71 CID patients for neurologic manifestations and presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were found to have neurological deficits including headache, depression, entrapment syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural antigens was detected in 30/71 (42.2%) patients. There was no clear correlation between anti-neural reactivity and neurologic dysfunction. Follow-up of 62 patients did not reveal change in electrophysiology or antibodies, regardless of diet. However, in 2 patients with neuropathy, symptoms improved or worsened depending on the diet. (C) 2008 Elsevier B.V. All rights reserved.

Purpose To date, no data are available on the relationship between 1p/19q deletions and the response to temozolomide (TMZ) in primary anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) recurrent after surgery and standard radiotherapy. The aim of this study was to evaluate correlations between 1p/19q deletions, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation, and response rate to TMZ in this setting. Patients and Methods From June 2000 to February 2005, 67 patients were enrolled; 39 patients (58%) had AO and 28 patients (42%) had AOA. All patients received 150 to 200 mg/m2 of TMZ every 28 days. Chromosome 1p and 19q deletions were detected by fluorescence in situ hybridization and MGMT promoter methylation was analyzed using methylation specific polymerase chain reaction. Results The overall response rate was 46.3% (17 complete responses and 14 partial responses). The response rate was higher in patients with AO than in those with AOA (61.5% v 25%, P = .003). Combined 1p/19q allelic loss was found in 32 patients (47.8%), while MGMT methylation occurred in 37 (68.5%) of 54 assessable patients. 1p/19q loss was significantly correlated with response rate (P = .04), time-to-progression (P = .003), and overall survival (P = .0001). Despite the significant concordance found between MGMT promoter methylation and 1p/19q deletions (P = .02), MGMT promoter methylation showed only a borderline correlation with overall survival (P = .09). Conclusion TMZ is active in anaplastic oligodendroglial tumors treated at first recurrence. In this setting, 1p/19q allelic loss is an important predictive and prognostic factor. Further studies on MGMT promoter methylation should be performed in randomized trials to test its correlation with survival.

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti -ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

Purpose Glioblastoma multiforme (GBM), the most frequent brain tumor in adults, is not considered chemosensitive. Nevertheless, there is widespread use of first-line chemotherapy, often with temozolomide, as a therapeutic option in patients with progressive disease after surgery and radiotherapy. However, at the time of second recurrence and/or progression, active and noncross-resistant chemotherapy regimens are required. The aim of the present multicenter phase II trial, therefore, was to ascertain the efficacy of second-line carmustine (BCNU) and irinotecan chemotherapy. Patients and Methods Patients with histologically confirmed GBM, recurring or progressing after surgery, standard radiotherapy and a first-line temozolomide-based chemotherapy, were considered eligible. The primary end-point was progression-free survival at 6 months (PFS-6), and secondary end-points included response rate, toxicity, and survival. All patients were on enzyme-inducing antiepileptic prophylaxis. Chemotherapy consisted of BCNU (100 mg/m2 on day 1) plus irinotecan (175 mg/m2/weekly for 4 weeks), every 6 weeks, for a maximum of eight cycles. In the absence of grade 2 toxicity, the irinotecan dose was increased to 200 mg/m2. Results A total of 42 patients (median age, 53.4 years; median Karnofsky performance status, 80; range, 60 to 90) were included in the study. PFS-6 was 30.3% (95% CI, 18.5% to 49.7%). Median time to progression was 17 weeks (95% CI, 11.9 to 23.9). Nine partial responses (21.4%; 95% CI, 9% to 34%) were obtained. Toxicity was manageable. Conclusion The BCNU plus irinotecan regimen seems active and non–cross-resistant in patients with GBM with recurrence after temozolomide-based chemotherapy.