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We aimed to detail language profiles, brain metabolic patterns and proportion of Alzheimer's disease biomarkers in a cohort of patients with mixed primary progressive aphasia (mPPA). We considered 58 patients with PPA: 10 with non-fluent/agrammatic variant (nfvPPA), 16 with semantic variant (svPPA), 21 with logopenic variant (lvPPA) and 9 with mPPA. Patients with mPPA were further classified as 4 nf/lvPPA (with prevailing features for nfvPPA and lvPPA) and 5 s/lvPPA (with prevailing features for svPPA and lvPPA). Nf/lvPPA patients were characterized by higher proportion of Naming impairment compared to nfvPPA and more frequent Grammatical Errors and Phonologic Errors than lvPPA. S/lvPPA had higher proportion of impairment in Sentences Repetition compared to svPPA and in Single-word Comprehension compared to lvPPA. 100% of nf/lvPPA and 40% of s/lvPPA had Aβ positive biomarkers. Brain hypometabolic pattern in Nf/lvPPA was consistent with lvPPA, while s/lvPPA had a brain metabolism resembling svPPA. We concluded that nf/lvPPA patients might be considered as PPA variant due to Alzheimer's disease and s/lvPPA group mainly included patients with svPPA.

ObjectiveTo study the possible implication of the two biomarkers, intermediate alleles (IAs) of the Huntingtin (HTT) gene and neurofilament light chain (NfL) levels in plasma, in amyotrophic lateral sclerosis (ALS) patients.MethodsWe analyzed IAs in a cohort of 106 Italian ALS patients and measured the plasma NfL levels in 20% of the patients of the cohort. We correlated the two biomarkers with clinical phenotypes.ResultsIntermediate alleles were present in 7.5% of the patients of our cohort, a frequency higher than that reported in general population. Plasma NfL levels increased with age at onset (p < 0.05). Patients with bulbar onset (BO) had higher plasma NfL concentration (CI −0.61 to −0.06, p = 0.02) and a later age at onset of the disease (CI −24.78 to −4.93, p = 0.006) with respect to the spinal onset (SO) form. Additionally, two of the patients, with IAs and plasma NfL concentration lower with respect to normal alleles’ carriers, presented an age at onset higher than the mean of the entire cohort.ConclusionAccording to our findings, plasma NfL and IAs of HTT gene may represent potential biomarkers in ALS, providing evidence of a possible implication in clinical phenotype.

Brain-derived natriuretic factor (BDNF) Val66Met polymorphism has been frequently reported to be associated with Alzheimer's disease (AD) with contrasting results. Numerous studies showed that Met allele increased the risk of AD only in women, while other studies have found worse cognitive performance in Val/Val carriers. We aimed to inquire the effects of Val66Met polymorphism on the progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and from MCI to AD and to ascertain if this effect is modulated by demographic and cognitive variables. For this purpose, we followed up 74 subjects (48 SCD, 26 MCI) for a mean time of 9 years. All participants underwent extensive neuropsychological assessment, cognitive reserve estimation, BDNF and apolipoprotein E (ApoE) genotype analysis at baseline. Personality traits and leisure activities were assessed in a subgroup. Each patient underwent clinical-neuropsychological follow-up, during which 18 out of 48 SCD subjects progressed to MCI and 14 out of 26 MCI subjects progressed to AD. We found that Val66Met increased the risk of progression from SCD to MCI and from MCI to AD only in women. Nevertheless, Val/Val carriers who progressed from SCD to MCI had a shorter conversion time compared to Met carriers. We concluded that Val66Met polymorphism might play different roles depending on sex and stage of the disease.

Background Subjective Cognitive Decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests, showing to increase risk of Alzheimer’s Disease (AD). Cognitive reserve seems to influence the progression from SCD to Mild Cognitive Impairment (MCI) and to AD. The aim of our study was to investigate gender differences in cognitive reserve evaluating how sex might modulate the role of cognitive reserve on SCD. Methods We included 381 SCD patients who underwent clinical evaluation, neuropsychological assessment, evaluation of premorbid intelligence by the Test di Intelligenza Breve (TIB), cognitive complaints by the Memory Assessment Clinics Questionnaire (MAC-Q), and apolipoprotein E (APOE) genotyping. Results The proportion between women and men was significantly different (68.7% [95% CI 63.9–73.4 vs 31.4%, 95% CI 26.6–36.0]). Women were younger than men at onset of SCD and at the baseline visit (p = 0.021), had lower years of education (p = 0.007), lower TIB scores (p p = 0.012). TIB was directly associated with age at onset of SCD in both women and men, while years of education was inversely associated with age at onset only in women. Multivariate analysis showed that sex influences TIB independently from years of education. TIB was directly associated with MAC-Q in men. Conclusions Sex interacts with premorbid intelligence and education level in influencing the age at onset and the severity of SCD. As the effect of education was different between men and women, we speculated that education might act as a minor contributor of cognitive reserve in women.

BACKGROUND Alzheimer's disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. OBJECTIVE We aim to interpret discordances between amyloid positron emission tomography (Amy-PET) and cerebrospinal fluid (CSF) (Aβ42 and Aβ42/40), using Amy-PET semiquantitative analysis, [18F]fluorodeoxyglucose (FDG)-PET pattern, and CSF assays. METHOD Thirty-six subjects with dementia or mild cognitive impairment, assessed by neuropsychological tests, structural and functional imaging, and CSF assays (Aβ42, Aβ42/40, p-tau, t-tau), were retrospectively examined. Amy-PET and FDG-PET scans were analyzed by visual assessment and voxel-based analysis. SUVR were calculated on Amy-PET scans. RESULTS Groups were defined basing on the agreement among CSF Aβ42 (A), CSF Aβ42/40 Ratio (R), and Amy-PET (P) dichotomic results ( ±). In discordant groups, CSF assays, Amy-PET semiquantification, and FDG-PET patterns supported the diagnosis suggested by any two agreeing amyloid biomarkers. In groups with discordant CSF Aβ42, the ratio always agrees with Amy-PET results, solving both false-negative and false-positive Aβ42 results, with Aβ42 levels close to the cut-off in A + R-P- subjects. The A + R + P- group presented high amyloid deposition in relevant areas, such as precuneus, posterior cingulate cortex (PCC) and dorsolateral frontal inferior cortex at semiquantitative analysis. CONCLUSION The amyloid discordant cases could be overcome by combining CSF Aβ42, CSF ratio, and Amy-PET results. The concordance of any 2 out of the 3 biomarkers seems to reveal the remaining one as a false result. A cut-off point review could avoid CSF Aβ42 false-negative results. The regional semiquantitative Amy-PET analysis in AD areas, such as precuneus and PCC, could increase the accuracy in AD diagnosis.

Background: The aims of this study were to compare the diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of different cerebrospinal fluid (CSF) amyloid biomarkers and amyloid-Positron Emission Tomography (PET) in patients with a clinical diagnosis of Alzheimer&rsquo, s disease (AD) and Frontotemporal Dementia (FTD), to compare concordance between biomarkers, and to provide an indication of their use and interpretation. Methods: We included 148 patients (95 AD and 53 FTD), who underwent clinical evaluation, neuropsychological assessment, and at least one amyloid biomarker (CSF analysis or amyloid-PET). Thirty-six patients underwent both analyses. One-hundred-thirteen patients underwent Apolipoprotein E (ApoE) genotyping. Results: Amyloid-PET presented higher diagnostic accuracy, sensitivity, and NPV than CSF A&beta, 1&ndash, 42 but not A&beta, 42/40 ratio. Concordance between CSF biomarkers and amyloid-PET was higher in FTD patients compared to AD cases. None of the AD patients presented both negative A&beta, biomarkers. Conclusions: CSF A&beta, 42/40 ratio significantly increased the diagnostic accuracy of CSF biomarkers. On the basis of our current and previous data, we suggest a flowchart to guide the use of biomarkers according to clinical suspicion: due to the high PPV of both amyloid-PET and CSF analysis including A&beta, 42/40, in cases of concordance between at least one biomarker and clinical diagnosis, performance of the other analysis could be avoided. A combination of both biomarkers should be performed to better characterize unclear cases. If the two amyloid biomarkers are both negative, an underlying AD pathology can most probably be excluded.

Background and purpose CLOCK and PER2 genes have been implicated in sleep-wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. Methods Sixty-eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow-up every 2 years for a mean time of 10 years were included. Subjects who developed AD (SCD-c and MCI-c) and non-converters (SCD-nc, MCI-nc) were considered. Results CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P = 0.049), fewer years of education (P = 0.007) and a lower frequency of family history of AD (P = 0.04) than G non-carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow-up, two SCD and 15 MCI subjects progressed to AD: both of the SCD-c subjects presented the PER2 G allele, while none of the SCD PER2 G non-carriers converted to AD (P = 0.003). Conclusion PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD.

Background: Some genes could interact with cardiovascular risk factors in the development of Alzheimer&rsquo, s disease. We aimed to evaluate the interaction between ApoE &epsilon, 4 status, Clock T3111C and Per2 C111G polymorphisms with cardiovascular profile in Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI). Methods: We included 68 patients who underwent clinical evaluation, neuropsychological assessment, ApoE, Clock and Per2 genotyping at baseline, and neuropsychological follow-up every 12&ndash, 24 months for a mean of 13 years. We considered subjects who developed AD and non-converters. Results: Clock T3111C was detected in 47% of cases, Per2 C111G in 19% of cases. ApoE &epsilon, 4 carriers presented higher risk of heart disease, Clock C-carriers were more frequently smokers than non C-carriers. During the follow-up, 17 patients progressed to AD. Age at baseline, ApoE &epsilon, 4 and dyslipidemia increased the risk of conversion to AD. ApoE &epsilon, 4 carriers with history of dyslipidemia showed higher risk to convert to AD compared to ApoE &epsilon, 4&minus, groups and ApoE &epsilon, 4+ without dyslipidemia patients. Clock C-carriers with history of blood hypertension had a higher risk of conversion to AD. Conclusions: ApoE and Clock T3111C seem to interact with cardiovascular risk factors in SCD and MCI patients influencing the progression to AD.

The aim of this study was to evaluate the effect of cognitive reserve (CR), in progression from subjective cognitive decline (SCD) to mild cognitive impairment (MCI) and Alzheimer's disease (AD). For this purpose, we followed up 263 patients (154 SCD; 109 MCI) for a mean time of 7 years. CR was assessed by the Test di Intelligenza Breve (TIB), functionally equivalent to the National Adult Reading Test. High CR resulted as a protective factor for progression from SCD to MCI. Age at conversion to MCI was delayed 9 years on average in SCD with high CR with respect to SCD with low CR. On the contrary, high CR resulted as a risk factor for progression from MCI to AD dementia only in APOE ε4 carriers. Conversion time from MCI to AD dementia was 3 years shorter in ε4 carriers with high CR than subjects with low CR and ε4 non-carriers with high CR. Consistent with the CR hypothesis, our results showed that higher levels of CR protect against the earliest clinical manifestations of AD. In line with the previous researches, we found an interaction between CR and APOE in progression from MCI to AD dementia.

Background/Objectives Management of patients with pregnancy-associated cyst pancreatic cystic tumors (PA-PCT) is complicated by lack of large series. Methods A systematic literature review was conducted to extrapolate data on management of PA-PCT, and make a questionnaire on pending issues to be administered to the members of the Pancreas Club Inc. Results The literature review demonstrated a total of 35 PA-PCT in 34 women, described exclusively in the form of case reports, and permitted the identification of eleven key questions to be addressed in the survey. The combined analysis of literature review and survery responses provided several information. First, PA-PCT are predominantly located in the body-tail of the pancreas, cause non-specific symptoms, are of large size (mean size: 11.2 ± 4.5 cm), and are nearly always malignant or premalignant, making timing of surgery, and not indication for surgery, the main issue in the management of these tumors. Second, there is a risk of PA-PCT rupture during pregnancy. Ruptured PA-PCT had a mean size 13.5 ± 4.9 cm, but no prognostic factor could be identified. Survey opinions suggested that this occurrence is quite rare, even for large tumors. Third, most pregnancies were conducted to term (mean gestational age: 40.5 ± 0.7 weeks), with a vaginal delivery. Fourth, all procedures were carried out through an open approach and the spleen was rarely preserved. Survey indicated instead that laparoscopy could play a role, and that the spleen should be preserved when feasible. Conclusions PA-PCT require individualized treatment. The definition of a management algorithm requires the implementation of an International Registry.

Purpose To evaluate the efficacy and safety of radiofrequency (RF) ablation in the treatment of benign thyroid nodules (BTNs) by applying a modification of the moving-shot technique. Materials and Methods Fifty-one BTNs in 46 patients for whom surgery was contraindicated or who refused surgery were treated with RF ablation: 31 had lesion volumes 3 (group A) and 20 had volumes ≥ 20 cm 3 (group B). The solid component percentage of each lesion was assessed, and any present fluid component was aspirated. Symptomatic scores and cosmetic scores (CSs) were assessed. All RF ablations were performed under ultrasound (US) guidance with an 18-gauge electrode. Treatment response was evaluated by contrast-enhanced US at 6-month intervals for 18 months in group A. In group B, after the 6- and 12-month follow-up assessments, a second treatment was performed in selected cases, and the 6-month contrast-enhanced US follow-up was started again. Volume reduction rate (VRR) was evaluated at each follow-up examination. Results No permanent paralysis of the laryngeal nerve was observed; 2 patients experienced transient hoarseness. In all nodules treated with a single RF ablation session, the VRRs at 6, 12, and 18 months were 69.4%, 78.7%, and 84% in group A, respectively, and 66.6%, 79.4%, and 81.5% in group B, respectively. The VRRs of group B nodules treated with a second RF ablation procedure (n = 6) were 86.4% and 88.2% at 6 and 12 mo after the second treatment, respectively. All patients reported symptom relief and CS improvement. Conclusions RF ablation is a reliable alternative to surgery in patients affected by BTNs and can be safely repeated in selected cases.

BACKGROUND AND PURPOSE Subjective cognitive decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase the risk of Alzheimer's disease (AD). SCD could also be related to other conditions such as normal aging, psychiatric, neurological or medical disorders. The SCD Initiative proposed a set of features (SCD-plus) that increase the likelihood of preclinical AD in individuals with SCD. Our aim was to assess the effect of these features on the risk of conversion from SCD to AD. METHODS In total 150 SCD subjects who underwent extensive neuropsychological investigation, assessment of cognitive complaints and apolipoprotein E (ApoE) genotyping at baseline and clinical-neuropsychological follow-up for a mean time of 11 years were included. RESULTS During the follow-up, 20 subjects developed AD. Considering SCD-plus features, age at onset ≥60 years and ApoE e4 significantly increased the risk of conversion from SCD to AD. When our sample was stratified into three groups (no risk factor, one risk factor, two risk factors), the proportion of conversion was statistically significantly different between the three groups. CONCLUSIONS Our model allows the risk of AD to be stratified in patients experiencing SCD according to age at onset and ApoE genotype.

KIBRA is a signal transducer protein, mainly expressed in the kidney and brain. A single-nucleotide polymorphism (SNP rs17070145, T → C exchange) has been linked to different cognitive function. In 2008, we studied 70 subjects who complained of subjective cognitive decline (SCD) and found that CT/TT carriers performed worse than CC carriers on a long-term memory test. We followed up the 70 SCD subjects and also 31 subjects affected by mild cognitive impairment (MCI) for a mean follow-up time of 7 years, during which 16 SCD subjects progressed to MCI and 14 MCI subjects progressed to Alzheimer’s disease (AD). Carrying the T allele was associated with MCI and with a two times-higher risk of developing MCI than CC carriers. In the SCD sample, CT/TT carriers showed a greater worsening on Rivermead Behavioral Memory Test (RBMT) compared to CC carriers. In the MCI sample, CT/TT carriers performed worse than CC carriers on RBMT. There is a lack of consensus on the effect of KIBRA gene variants on cognitive performances in episodic memory and on the risk of AD. Our results confirm a role of T allele on progression of cognitive decline.

The Huntingtin gene (HTT) is within a class of genes containing a key region of CAG repeats. When expanded beyond 39 repeats, Huntington disease (HD) develops. Individuals with less than 35 repeats are not associated with HD. Increasing evidence has suggested that CAG repeats play a role in modulating brain development and brain function. However, very few studies have investigated the effect of CAG repeats in the non-pathological range on cognitive performances in non-demented individuals. In this study, we aimed to test how CAG repeats’ length influences neuropsychological scores in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We included 75 patients (46 SCD and 29 MCI). All patients underwent an extensive neuropsychological battery and analysis of HTT alleles to quantify the number of CAG repeats. Results: CAG repeat number was positively correlated with scores of tests assessing for executive function, visual–spatial ability, and memory in SCD patients, while in MCI patients, it was inversely correlated with scores of visual–spatial ability and premorbid intelligence. When we performed a multiple regression analysis, we found that these relationships still remained, also when adjusting for possible confounding factors. Interestingly, logarithmic models better described the associations between CAG repeats and neuropsychological scores. CAG repeats in the HTT gene within the non-pathological range influenced neuropsychological performances depending on global cognitive status. The logarithmic model suggested that the positive effect of CAG repeats in SCD patients decreases as the number of repeats grows.

Background: Periodic circadian protein homolog 2 (PER2) has a role in the intracellular signaling pathways of long-term potentiation and has implications for synaptic plasticity. We aimed to assess the association of PER2 C111G polymorphism with cognitive functions in subjective cognitive decline (SCD). Methods: Forty-five SCD patients were included in this study. All participants underwent extensive neuropsychological investigation, analysis of apolipoprotein E (APOE) and PER2 genotypes, and neuropsychological follow-up every 12 or 24 months for a mean time of 9.87 ± 4.38 years. Results: Nine out of 45 patients (20%) were heterozygous carriers of the PER2 C111G polymorphism (G carriers), while 36 patients (80%) were not carriers of the G allele (G non-carriers). At baseline, G carriers had a higher language composite score compared to G non-carriers. During follow-up, 15 (34.88%) patients progressed to mild cognitive impairment (MCI). In this group, we found a significant interaction between PER2 G allele and follow-up time, as carriers of G allele showed greater worsening of executive function, visual-spatial ability, and language composite scores compared to G non-carriers. Conclusions: PER2 C111G polymorphism is associated with better language performance in SCD patients. Nevertheless, as patients progress to MCI, G allele carriers showed a greater worsening in cognitive performance compared to G non-carriers. The effect of PER2 C111G polymorphism depends on the global cognitive status of patients.

Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15–20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects.

Objective To compare the efficacy of Radioiodine (RI) and Radiofrequency ablation (RFA) in the treatment of autonomously functioning thyroid nodules (AFTNs). End-points: nodule volume reduction (NVR) and thyroid function normalization. Design, patients and measurements Twenty-two patients (2:20 M:F; 51.9 ± 13.9 years) affected by 25 AFTNs, treated by RFA were retrospectively compared with 25 patients (8:17 M:F; 57.2 ± 12.8 years) affected by a single AFTN treated by RI. Both group showed analogous characteristics as to age, gender, toxic/pretoxic phase and pretreatment nodule volume (calculated by the ellipsoid formula). Thyroid hormone levels and autoimmune thyroid profile were assessed before treatment. A fixed RI activity of 555 MBq (15 mCi) was administered. RFA was performed with an 18G, single-tipped electrode, by the "modified moving shot technique." Thyroid hormones were assessed and the nodule post-treatment volume calculated 12 months after treatment. Results No statistical difference was found between the post-treatment NVR by comparing RI and RFA (P = 0.69). The volume reduction rates were 68.4 ± 28.9% and 76.4 ± 16.9% after RI and RFA, respectively. As to the thyroid function, 5/25 patients developed clinical hypothyroidism after RI. After RFA, all the 22 patients silenced their AFTN and normalized the thyroid hormones. Subclinical hypothyroidism was recorded in two patients after both RI and RFA. Thus, the functional therapeutic success, defined as the restoration of euthyroidism, was achieved in 18/25 (72%) patients treated by RI and in 20/22 (90.9%) treated by RFA. Conclusions No statistical difference in NVR was found between RI and RFA. All patients responded to RI but 5/25 were "over-treated" developing hypothyroidism. RFA was effective in all patients with no case of post-treatment clinical hypothyroidism. No radiation exposure and lower risk of post-treatment hypothyroidism might make RFA the favourite option especially for young patients.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is frequently present in patients with severe obesity but its prevalence especially in women is not well defined. OSAHS and non alcoholic fatty liver disease (NAFLD) are common conditions, frequently associated in patients with central obesity and metabolic syndrome and are both the result of the accumulation of ectopic fat mass. Identifying predictors of risk of OSAHS may be useful to select the subjects requiring instrumental sleep evaluation. In this cross-sectional study we have investigated the potential role of hepatic left lobe volume in predicting the presence of OSAHS. OSAHS was quantified by the apnea/hypopnea index (AHI) and oxygen desaturation index (ODI) in a cardiorespiratory inpatient sleep study of 97 obese women (age: 47±11 yr, body mass index-BMI: 50±8 kg/m2). OSAHS was diagnosed when AHI was ≥ 5. Hepatic left lobe volume (HLLV), subcutaneous and intra-abdominal fat were measured by ultrasound. After adjustment for age and BMI, both HLLV and neck circumference (NC) were independent predictors of AHI. OSAHS was found in 72% of patients; HLLV ≥370 cm3 was a predictor of OSAHS with a sensitivity of 66%, a specificity of 70%, a positive and negative predictive values of 85% and 44%, respectively (AUC=0.67, p

Surgical removal is recommended for recurrent thyroid carcinomas (RTCs) unable to uptake radioiodine and/or not responsive to chemotherapy. However, repeated neck dissection is difficult for surgeons. Thus, radiofrequency ablation (RFA) was proposed for RTCs. The aim of this prospective study is to assess RTC treatment response after RFA, according to well-established criteria. Sixteen lesions in 13 patients were treated by RFA. All patients refused/were excluded from repeated surgery or other conventional therapy. CT and US examinations were performed before RFA to evaluate lesion volume and vascularization. All RFA procedures were performed under US-guidance by an 18-gauge, electrode. Treatment response was evaluated by CT, according to RECIST 1.1 and to mRECIST guidelines; CT examinations were performed during follow-up (6–18 months); the volume of residual vital tumour tissue and the percentage of necrotic tissue were estimated by contrast enhanced CT. RFA was well tolerated by all patients; in two cases laryngeal nerve paralysis was observed. Mean pre-treatment volume was 4.18 ± 3.53 ml. Vital tumour tissue and percentage of necrosis at 6, 12 and 18 months were 0.18 ± 0.25, 0.11 ± 0.13, 0.29 ± 0.40 ml and 91.9 ± 11.1, 90.4 ± 13.3, 80.8 ± 23.1%. According to RECIST 1.1, target lesion response was classified as complete response (CR) in one case, partial response (PR) in 11/16, stable disease in 4/16 cases. According to mRECIST, 11/16 cases were classified as CR and the remaining 5 as PR. RFA is a safe procedure to treat the viable tumour tissue and to reduce the RTC volume; as to the criteria to assess treatment response, mRECIST appears to be more accurate.

BACKGROUND Correctly diagnosing Alzheimer's disease (AD) in prodromal phases would allow the adoption of experimental therapeutic strategies that could selectively interrupt the pathogenetic process before neuronal damage becomes irreversible. Therefore, great efforts have been aimed at finding early reliable disease markers. OBJECTIVE The aim of this study was to identify a simple, cost effective, and reliable diagnostic algorithm to predict conversion from mild cognitive impairment (MCI) to AD. METHODS 96 consecutive MCI patients admitted to the Neurology department of San Raffaele Hospital in Milan between January 2009 and January 2015 were included. All patients underwent neuropsychological assessment and lumbar puncture with CSF analysis of amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) levels. Each patient underwent clinical and neuropsychological follow-up, in order to identify a possible progression from MCI to AD. The mean follow up time was 36.73 months. RESULTS 37 out of 96 MCI converted to AD during follow up. CSF analysis and neuropsychological assessment reliably detected MCI patients who developed AD. In a subsample of 43 subjects, a Composite Cognitive Score (CCS) was calculated including episodic memory, executive function, and verbal fluency tests. Combining together CSF biomarkers and CCS increased the accuracy of the single predictors, correctly classifying 86% of patients with a specificity of 96% and a Positive Predictive Value of 93%. DISCUSSION Even if preliminary, our data seem to suggest that CSF analysis and neuropsychological assessment could detect MCI patients who will convert to AD with high confidence. Their relative low cost and availability could make them worldwide essential tools in future clinical trials.

Previous studies suggest that genetic variants in CHRNA7, which encodes for the major subunit of the acetylcholine receptor (α7-nAChR), are associated with the clinical response to cholinesterase inhibitors (ChEI) in Alzheimer's disease (AD) patients. We sought to replicate the association of two SNPs in the CHRNA7 gene, rs6494223 and rs8024987, with response to ChEI treatment in an Italian cohort of 169 AD patients, further extending the study to gene-level analysis. None of the tested variants was associated with clinical response. However, rs6494223 showed a consistent effect direction (OR = 1.4; p = 0.17), which after meta-analysis with previous study yielded a significant result (OR = 1.57, p = 0.02, I2 = 0%).

Background The purpose of this study was to evaluate the operative risk and the prognostic implications of pancreatectomy plus resection and reconstruction of peripancreatic vessels (PPV) in patients with pancreatic adenocarcinoma. Methods One hundred ten patients who underwent pancreatectomy with PPV resection and reconstruction (Study Group; SG) were retrospectively compared with 62 patients without distant metastasis who were palliated, (Control Group 1; CG-1), as well as 197 patients who underwent “conventional”pancreatectomy (Control Group 2; CG-2). Results Postoperative morbidity and mortality were similar in SG (33% and 3%), in CG-1 (26% and 3%), and in CG-2 (40% and 6%) patients. Median survival time (MST) of SG patients (15 months) was longer than that of CG-1 patients (6 months; P < .0001) and similar to that of CG-2 patients (18 months). Patients undergoing isolated venous resection (n = 84) had the best outcome (MST: 15 months) ( P < .0001 vs CG-1 patients), while patients undergoing resection of multiple PPV (n = 14) had the worst outcome (MST: 8 months). PPV infiltration, histologically proven in 64 patients (65%), was associated with decreased MST only if the tunica intima was infiltrated (26%) (11 months; P < .001). Multivariate analysis showed that no adjuvant therapy, intimal invasion, and poorly differentiated histology were associated with a higher hazard of death by 2.2, 2.2, and 2.5-fold, respectively. Conclusion In properly selected patients, pancreatectomy plus resection and reconstruction of PPV was performed as safely as palliation or “conventional” pancreatectomy and was associated with better survival when compared to palliation.

Lenvatinib is a small oral molecule able to inhibit three of the extracellular and intracellular molecules involved in the modulation of angiogenesis and lymphangiogenesis: vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–4, and platelet-derived growth factor receptor alpha. Since it is also able to inhibit the REarranged during Transfection oncogene and the protooncogene c-KIT, this drug can also be used to control tumor cell proliferation. The maximum tolerated dose, as demonstrated in Phase I studies, is 25 mg daily. The drug is rapidly absorbed with maximum concentrations achieved within 3 and 5 hours after administration in fasting and nonfasting treated patients, respectively. The most common adverse events, reported in Phase I study and confirmed in the subsequent Phase II and III studies, are hypertension, proteinuria, and gastrointestinal symptoms such as nausea, diarrhea, and stomatitis. In Phase I studies, efficacy of lenvatinib in solid tumors was demonstrated, and these encouraging results have led to the development of a Phase II study using lenvatinib in advance radioiodine-refractory differentiated thyroid cancer (DTCs) patients. Since an overall response rate of 50% was reported, this study also confirmed the efficacy of lenvatinib in DTCs patients with an acceptable toxicity profile. Recently, a Phase III study in patients with DTCs (SELECT study) demonstrated the lenvatinib efficacy in prolonging progression-free survival with respect to the placebo (18.3 vs 3.6 months; P65 years). The study confirmed that the most common side effects of this drug are hypertension, diarrhea, decreased appetite, weight loss, nausea, and proteinuria. In this review, we report the results of the main studies on lenvatinib efficacy in patients with advanced and progressive thyroid cancer, mainly in DTCs but also in medullary and anaplastic thyroid cancer. We also compared the efficacy of lenvatinib with that of other tyrosine kinase inhibitors, mainly sorafenib, already tested in the same type of patient population.

To assess vascular infiltration is crucial in surgical planning of pancreatic cancer. Our aim was to assess the capability of multidetector CT in detecting vascular infiltration. We evaluated 37 patients with pancreatic tumors. The relation between tumor and vessels was classified: grade 0: no contact between lesion and vessel; grade I: focal contiguity without modification of the vessel caliber; grade II: lesion surrounding the vessel, without reduction of its lumen; grade III: cancer surrounding the vessel with reduction or obstruction of its lumen. CT grades were compared to intraoperative findings and histopathology. We evaluated 52 critical vessels with the following CT grades: grade 0 (4 cases), grade I (13 cases), grade II (17 cases), grade III (18 cases). Vascular resection was performed in 26 patients, with a total of 31 resected vessels (3 of grade 0, 5 of grade I, 8 of grade II, 15 of grade III). Histopathology excluded vascular infiltration in 4/4 cases with grade 0 and in 10/13 cases with grade I and confirmed it in 14/17 cases with grade II and 14/18 cases with grade III. Multidetector CT is accurate in detecting vascular involvement and provides pre-operative information to effectively plan resection.

Preoperative suspicion of malignancy in pancreatic neuroendocrine tumours (pNETs) is mostly based on tumour size. We retrospectively reviewed the contrast enhancement pattern (CEP) of a series of pNETs on multiphasic multidetector computed tomography (MDCT), to identify further imaging features predictive of lesion aggressiveness. Sixty pNETs, diagnosed in 52 patients, were classified based on CEP as: type A showing early contrast enhancement and rapid wash-out; type B presenting even (B1) or only (B2) late enhancement. All tumours were resected allowing pathologic correlations. Nineteen pNETs showed type A CEP (5–20 mm), 29 type B1 CEP (5–80 mm) and 12 type B2 (15–100 mm). All tumours were classified as well differentiated tumours, 19 were benign (WDt-b), 15 with uncertain behaviour (WDt-u) and 26 carcinomas (WDC). None of A lesions were malignant (12 WDt-b; 7 WDt-u), all B2 lesions were WDC, 7 B1 lesions were WDt-b, 8 WDt-u and 14 WDC; 4/34 (12 %) lesions ≤2cm were WDC. CEP showed correlation with all histological prognostic indicators. Correlating with the lesion grading and other histological prognostic predictors, CEP may preoperatively suggest the behaviour of pNETs, assisting decisions about treatment. Moreover CEP allows recognition of malignant small tumours, incorrectly classified on the basis of their dimension. • Neuroendocrine pancreatic tumours (pNETs) show different post-contrast behaviour on CT. • P NETs can be classified on the basis of contrast enhancement into three categories. • CT classification of pNETs shows strong correlation with histological prognostic factors. • CT pattern may suggest the optimal management of pNETs.

Once the clinical diagnosis of primary hyperparathyroidism (PHPT) and indications for surgery have been established, accurate preoperative localization of the hyperfunctioning parathyroid(s) is key to the success of minimally invasive surgery. Imaging currently plays a major role in localizing parathyroid adenomas either in their normal location and/or in ectopic sites, the latter condition occurring in approximately 15–20% of PHPT cases.

Introduction: Until recently, no therapeutic options were available for the treatment of advanced medullary thyroid cancer (MTC). Cabozantinib (XL184) is a novel tyrosine kinase inhibitor (TKI) that inhibits several tyrosine kinase receptors, in particular those coded by MET, VEGFR-2 and RET oncogenes that are considered to be involved in the pathogenesis of MTC.Areas covered: This article provides an overview of the phase I and III trials that demonstrated the efficacy of cabozantinib in two cohorts of advanced MTC patients who were naive or previously treated with other TKIs. The benefits in terms of progression-free survival (PFS), overall survival (OS) and the demographic clinical and mutational status of the two cohorts of MTC patients are reported and discussed.Expert opinion: The possibility to have a therapeutic option for the treatment of patients with advanced and progressive MTC and, in particular, the evidence that the drug can be active also in those patients who already experienced disease p...

Purpose: To assess the usefulness of US contrast media in the evaluation of patients with primary hyperparathyroidism, with a nodule showing US features of a primary parathyroid lesion but lacking the color Doppler US appearance of a parathyroid mass. Material and Methods: Thirteen patients (7 female, 6 male; age range 51-79 years) were examined with US before and after administration of a stabilized galactose-based microbubble contrast agent. Ten patients underwent surgery and the final histological examination demonstrated parathyroid adenoma in 9 cases and a mesenchymal benign nodule in 1 case. Three nodules were proved to be of thyroid origin at fine-needle aspiration biopsy. Results and Conclusion: The use of a US contrast agent resulted in a diagnostic gain compared to unenhanced studies in 12/13 cases. Color Doppler findings characteristic of parathyroid lesions were observed in 7/13 cases, of thyroid nodules in 4/13 cases, and nonspecific patterns in 2/13 cases. Contrast-enhanced color Doppler US can be proposed in selected patients in whom unenhanced color Doppler provides uncertain findings. Its ideal application should be the evaluation of cervical lesions without detectable intranodular flow at unenhanced Doppler studies. In these cases, the contrast agent helps in visualizing typical color Doppler signals of the parathyroid lesions (“vascular pole” and “mixed pattern”).

Background: Preoperative localization of parathyroid lesions and intraoperative quick parathyroid hormone (PTH) assay have been proposed to minimize the extent of operation in primary hyperparathyroidism. To this purpose, endoscopic procedures have been introduced recently. Methods: During a period of 13 months, 39 of 65 consecutive patients with primary hyperparathyroidism were selected for endoscopic parathyroidectomy on the basis of the following criteria: preoperative echographic diagnosis of a single adenoma, absence of nodular goiter, and no prior neck operations. Unilateral neck exploration and excision of the adenoma was performed through a gasless procedure combined with intraoperative PTH measurements. Mean follow-up after the operation was 7 months (range 1 to 13 months). Results: Thirty-nine parathyroid adenomas were removed; the mean diameter was 21 mm (range 5 to 30 mm). The mean operative time was 65 minutes (range 30 to 180 minutes). In all cases PTH concentration decreased significantly. Patients who underwent endoscopic parathyroidectomy had less postoperative pain compared with patients who underwent conventional hemithyroidectomy. At follow-up, serum calcium and PTH levels were normal in all cases. Conclusions: Endoscopic parathyroidectomy proved to be a feasible surgical procedure that can be performed in an acceptable operative time with an excellent cosmetic result. The gasless approach avoided any emphysema. (Surgery 1998;124:1077-80.)

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.

Amiodarone-induced thyrotoxicosis (AIT) occurs both in abnormal thyroid glands (nodular goiter, latent Graves' disease) (type I AIT) or in apparently normal thyroid glands (type II AIT). Differentiation of the two forms is crucial, because type I AIT responds well to methimazole and potassium perchlorate combined treatment, whereas type II AIT is effectively managed by glucocorticoids. Differential diagnosis is often difficult, although thyroid radioactive iodine uptake is usually low-to-normal in type I and low-suppressed in type II, and serum interleukin-6 levels are normal/slightly elevated in type I, markedly elevated in type II. Color flow Doppler sonography (CFDS) is a technique that shows intrathyroidal blood flow and provides real-time information on thyroid morphology and hyperfunction. To investigate the usefulness of CFDS in differentiating the two types of AIT, 27 consecutive AIT patients, 11 type I and 16 type II, were evaluated by CFDS before starting antithyroid treatment. Gender, age, severity of thyrotoxicosis, and cumulative amiodarone dose were similar in the two groups. All type II AIT patients had a CFDS pattern 0 (ie, absent vascularity), in agreement with the pathogenesis of the disease, due to thyroid damage. Likewise, nine patients with subacute thyroiditis, another destructive process of the thyroid gland, also had a CFDS pattern 0. Eleven patients with type I AIT had a CFDS pattern ranging from pattern I (presence of parenchymal blood flow with patchy uneven distribution) (7 patients, 64%) to pattern II (ie, mild increase of color flow Doppler signal with patchy distribution) (1 patient, 9%) and pattern III (markedly increased color flow Doppler signal with diffuse homogeneous distribution)(3 patients, 27%), similar to that found in patients with untreated Graves' disease patients, thus indicating a hyper-functioning gland. Control subjects and euthyroid patients under long-term amiodarone treatment had absent thyroid hypervascularity and a CFDS pattern 0. These findings demonstrate that CFDS distinguishes type I and II AIT. Because of its rapidity and noninvasive features, CFDS represents a valuable tool for a quick differentiation between the two types of AIT. This can avoid any delay in initiating the appropriate treatment for a rapid control of thyrotoxicosis in patients whose tachyarrhythmias or other cardiac disorders make thyroid hormone excess extremely deleterious.

The aim of this study was to investigate the usefulness of unenhanced and enhanced MR imaging in evaluating the response of hepatocellular carcinoma to percutaneous injection of ethanol.Thirty-one patients with 40 hepatocellular carcinomas less than 5 cm in diameter were examined with MR imaging before and after percutaneous injection of ethanol. Unenhanced T1- and T2-weighted and contrast-enhanced T1-weighted spin-echo images were obtained. CT and percutaneous biopsy were performed 1 month after the final injection of ethanol and repeated at 6-month intervals to establish the outcome of treatment: complete tumor necrosis was shown in 36 lesions and incomplete tumor necrosis was seen in four lesions.Of the 36 proved necrotic lesions, 31 showed homogeneously low signal intensity on T2-weighted MR images obtained after treatment, owing to coagulative necrosis of the tumor. In the remaining five necrotic lesions, hypointense and hyperintense areas coexisted; the hyperintense areas were caused by liquefactive necrotic material in two cases and by chronic inflammatory tissue along the boundary of the necrotic area in three cases. None of the 36 necrotic lesions showed contrast enhancement on T1-weighted images obtained after IV injection of gadopentetate dimeglumine. In the four lesions with incomplete necrosis, the viable portion of the tumor was identified as a hyperintense area on T2-weighted images and as an enhancing area on contrast-enhanced T1-weighted images. No correlation was found between lesion features on unenhanced T1-weighted images and outcome of therapy.Contrast-enhanced T1-weighted MR images allow a reliable evaluation of the effectiveness of treatment and are more accurate than unenhanced MR studies. Contrast-enhanced MR imaging may be considered a valuable alternative to contrast-enhanced CT in the follow-up of hepatocellular carcinomas treated with percutaneous injection of ethanol.

Nonalcoholic fatty liver disease is a common finding in obese subjects. Increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome.Aim of this longitudinal study was to evaluate the relationships between several anthropometric measures, including the hepatic left lobe volume (HLLV), and various indicators of the metabolic syndrome in a cohort of severely obese women before and after laparoscopic adjustable gastric banding (LAGB).Seventy-five obese women (mean age 45 ± 10 years and body mass index (BMI) 42.5 ± 4.8 kg m(-2)) underwent LAGB and completed an average (± s.d.) post-surgical follow-up of 24 ± 6 months. Determination of HLLV, subcutaneous and intra-abdominal fat (IAF) was based on ultrasound. The principal component statistical analysis applied to pre-operative measurements, highlighted HLLV as a parameter that clustered with serum insulin, IAF, serum glucose and uric acid, along with triglycerides (TGs), alkaline phosphatase and high-density lipoprotein cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight, BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of reduction of serum transaminases and γ-Glutamyltransferase, glucose, insulin and TGs.In severely obese women: (i) HLLV is a sensitive indicator of ectopic fat deposition, clustering with parameters defining the metabolic syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of liver volume as estimated by HLLV; (iii) among various anthropometric parameters measured, reduction of HLLV that follows LAGB represents the best single predictor of improvement of various cardiometabolic risk factors.

(131)I therapy is effective in reducing the volume of large nodular goiters (thyroid volume [TV]), mainly after stimulation with recombinant human thyrotropin (rhTSH). The amount of (131)I to be administered inversely depends on thyroid radioactive iodine uptake (RAIU). In patients with low RAIU, we evaluated the efficacy of (131)I treatment at lower doses with respect to those calculated on the basal RAIU, after rhTSH stimulation.Eighteen consecutive patients (17 women and 1 man, 49-83 years) with large nodular goiter were included in the study. At enrollment, 24th h RAIU, TSH, free thyroxine, free triiodothyronine, thyroglobulin antibodies, thyroid peroxidase antibodies, TSH receptors antibodies, urinary iodine, and TV were measured. RAIU was40% in 11 patients (lower uptake group [LUG]) and40% in 7 (higher uptake group [HUG]). RAIU difference in the two groups was significant (p0.0001). LUG patients were treated with rhTSH (0.03 mg i.m.) and RAIU was measured again after 24 hours. The administered amount of (131)I was aimed to give the thyroid a dose of 100 Gy, by the formula: (131)I activity = 370 MBq × TV (mL)/RAIU(%), taking into account RAIU value after rhTSH for LUG patients. Patients were re-evaluated 3 and 12 months after therapy.At enrollment, LUG and HUG patients did not differ for TV, free thyroxine, free triiodothyronine, TSH, and urinary iodine. LUG patients were older than HUG patients (p = 0.027). In LUG, the uptake increased after rhTSH (42.8% [36%-47.5%] vs. 30% [23.4%-31.6%], p = 0.0044). The (131)I activity was 1073 MBq (740-1103 MBq) in LUG and 851 MBq (677-918 MBq) in HUG (p = 0.22, NS), vs. 1300 MBq (1077-2150 MBq) in LUG, based on RAIU before rhTSH. At 3 and 12 months after radioiodine, TV was reduced to 74% [59%-84%] and 53% [42%-72%] in LUG and 75% [70%-77%] and 65% [54%-74%] in HUG, respectively. The reduction was significant with respect to the basal, both at 3 and 12 months, but not different between the two groups.One single dose of 0.03 mg of rhTSH increased the thyroid RAIU by 40% in patients with nodular goiter and low basal uptake. This allowed a mean reduction of 36% (26%-42%) in the administered (131)I activity without loss of effectiveness. In patients with low RAIU, rhTSH pre-treatment may optimize (131)I therapy.

Percutaneous fine needle biopsy (FNB), under sonographic guidance, of local pancreatic lesions was studied by comparing the results of smear cytology (SC) with microhistology (MH) in 34 patients in whom both sampling procedures were carried out. MH suffered from a higher number of inadequate samples (retrieval rate: 94.1% SC, 85.3% MH), but reached a superior sensitivity rate as regard to the diagnosis of pancreatic malignancy (91.7% MH, 80.8% SC). Both samples obtained an absolute specificity rate (100%. A 96.3% sensitivity rate was obtained by combination of the two techniques in the absence of complications. Thus, the combined use of SC and MH in pancreatic fine needle biopsy was proven to be a safe and reliable procedure.

Neoplastic infiltration of the retroportal fat tissue is a critical parameter in tumor staging and in surgical planning because it frequently represents a site of persistence and recurrence of disease. We evaluated 64 patients affected by ductal adenocarcinoma of the pancreatic head/uncinate process, submitted to curative surgery. Suspicion of infiltration (micro or macroinfiltration) of the retroportal margin arose at MDCT in cases of obliteration, irregularity, or abnormal density of the fatty layer localized between the medial surface of the pancreatic head/uncinate process and the mesenteric artery. CT suggested the infiltration of the retroportal tissue in 27 cases (10 microinfiltration, 17 macroinfiltration). At histopathology, the presence of infiltration was confirmed in 21/27 (78%) cases. In all CT cases of microinfiltration, the retroperitoneal resection margin was not infiltrated, while all cases (6) with infiltration of the retroperitoneal margin were macroinfiltrated at CT. The sensitivity of CT was 80%, specificity of 84% with an overall diagnostic accuracy of 82%. MDCT is accurate in the assessment of the neoplastic infiltration of the retroportal fat tissue.

Non-alcoholic fatty liver disease is a common finding in obese subjects, and increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. The aim of this study was to evaluate whether the extent of liver enlargement is related to the severity of the metabolic syndrome in obese women. The relationship between ultrasound- measured hepatic left lobe volume (HLLV) and various features of the metabolic syndrome was evaluated in 85 obese women. The mean+/-SD value of HLLV in obese women was 431+/-214 ml (range 46-1019 ml) while it was 187+/-31 ml (range 143-258 ml) in lean subjects. In a multiple logistic regression analysis, ultrasound-measured intra-abdominal fat was the only anthropometric measure independently associated with HLLV. A strong positive association was found between HLLV and serum liver enzymes, triglycerides, glucose, insulin, uric acid, C reactive protein, systolic and diastolic blood pressure, while a negative correlation was observed between HLLV and HDL cholesterol. The values of HLLV corresponding to the cut-off values of various risk factors for the diagnosis of the metabolic syndrome were calculated, yielding a mean value of 465 ml. In conclusion, ultrasound measurement of HLLV represents a simple, reliable and low-cost tool for the evaluation of liver involvement in the metabolic syndrome. The strong association between liver enlargement and various cardiovascular risk factors associated with insulin resistance supports the role of liver steatosis as an important link among the many facets of the metabolic syndrome in human obesity.

This study was performed to evaluate the accuracy of multidetector computed tomography (MDCT) in detecting parathyroid lesions in patients with primary hyperparathyroidism.We included 60 patients with primary hyperparathyroidism. Preoperative first-line examinations revealed negative and doubtful ultrasound (US) findings in 34 and 26 cases, respectively, and negative, doubtful and positive scintigraphic findings in 19, 20 and 21 cases, respectively. CT findings were compared with the surgical results.CT examination was positive in 35 cases, negative in 15 cases and doubtful in ten cases. Forty out of 60 patients underwent surgery, and 39 lesions (37 adenomas, two primary hyperplasias) were identified. Surgery was negative in two cases. In eight cases, lesions had ectopic location. Surgery confirmed the CT findings in 23 positive cases. In 8/10 doubtful cases, surgery confirmed the location of the lesion in five cases, identified the ectopic location of lesions in two cases, and was negative in one case. In 9/15 cases with negative CT findings, surgery identified the lesion in eight cases. Sensitivity, specificity and diagnostic accuracy values were 78%, 25% and 73%, respectively.MDCT is an accurate second-line diagnostic technique in the detection of parathyroid lesions, allowing exploration of the entire cervical and mediastinal regions.

The objective of this study is to describe a technique for balanced orbital decompression and to analyze the results.We conducted a retrospective study of 140 patients (276 orbits). Orbital decompression was carried out by removal of the medial orbital wall by ethmoidectomy and complete removal of the lateral wall by bringing out the entire sphenoid wing together with part of the zygomatic bone down to the inferior orbital fissure.One hundred thirty-six patients underwent bilateral decompression, 4 patients underwent monolateral decompression. Proptosis was reduced on average by 5.3 mm; 28 (20%) patients showed onset or worsening of diplopia.Medial and lateral approach allows a balanced orbital decompression. As some patients may present different degrees of proptosis and visual impairment, we stress the importance of carefully weighing the preoperative conditions of the individual patient when choosing the surgical approach.

We investigated the long-term side-effects of orbital radiotherapy (OR) in 204 patients with Graves' ophthalmopathy (GO), irradiated from 1972-1996 [44 by cobalt unit (CU) and 160 by linear accelerator (LA), mostly combined with glucocorticoids], with a 5- to 25-yr follow-up (median, 11 yr). Cataract was observed in 21 patients (10%) 3-21 yr after OR, with a higher (not significant) prevalence in CU-treated patients (18% vs. 8% in LA-treated patients). The prevalence of cataract was higher, although not significantly, in CU-treated patients aged less than 60 yr, but not in LA-treated patients, compared with the general population. Mild, asymptomatic retinopathy was observed in 1 of 7 patients (14%) with diabetes and hypertension, in 1 of 31 patients (3%) with hypertension alone, and in 0 of 11 patients with diabetes alone. No tumors were observed in 157 patients submitted to computed tomography scan of orbital and adjacent regions. In conclusion, OR is a safe treatment, not associated with an increased frequency of cataract, provided a high voltage apparatus is used. Hypertension, especially if associated with diabetes, may represent a relative contraindication, as it may cause retinopathy. Although no secondary tumors were detected, due to the long latency of radiation-induced tumors, OR should be restricted to patients older than 35 yr.

OBJECTIVES: The purpose of this study was to measure the oxidative and antioxidant biochemical parameters in the serum of Italian patients with age-related maculopathy (ARM) and in a similar age control group from the same area, in order to determine the weight of oxidative status as risk factor in the early stage of macular degeneration onwards. DESIGN AND METHODS: Forty-eight ARM patients (19 early and 29 late form) and 46 normal subjects, similar for age, sex and life-style, were studied. A series of serum and/or plasma antioxidants (vitamins C, E, A, total and individual carotenoids, zinc, total plasma antioxidant capacity--TRAP) and oxidative parameters (reactive oxygen metabolites--ROM, oxidized-low-density lipoprotein antibodies-anti-Ox-LDL) were evaluated in both groups, also with regard to age and disease stage. RESULTS: Levels of vitamins C, E, total carotenoids and beta-cryptoxanthine were lower in late ARM than in early ARM (p

Purpose Our aim was to evaluate the accuracy of spiral CT study of small-bowel Crohn disease with use of oral hyperhydration with isoosmotic solution. Method We prospectively analyzed 33 consecutive patients and 10 control subjects with spiral CT after oral administration of 2,000 ml of polyethylene glycol electrolyte-balanced solution. The CT diagnoses were compared with the results of conventional radiologic oral barium examination (33 cases), ileum colonoscopy (8 cases), and surgery (4 cases). Results The final diagnoses were Crohn disease (14 cases), no small-bowel disease (16 cases), cancer of ileocecal valve (1 case), carcinosis of mesenteric root (1 case), and intestinal lymphangiectasia (1 case). In the control group, no abnormalities of the small bowel were found. The sensitivity of spiral CT was 85.7%, specificity 100%, positive predictive value 100%, negative predictive value 90%, and diagnostic accuracy 93.9%. Conclusion Our method allowed adequate distension of the small bowel for spiral CT studies, thus resulting in a safe and effective alternative to small-bowel spiral CT enema, which can be used in patients that refuse the nasojejunal balloon catheter.

The aim of our study was to clarify possible differential color Doppler US features between parathyroid lesions and other cervical masses. A total of 56 parathyroid lesions in 54 patients with primary hyperparathyroidism were preoperatively examined with color Doppler sonography. Color Doppler flow patterns were compared with those of 72 thyroid nodules and 20 cervical lymph nodes. In 38 parathyroid lesions a correlation between color Doppler patterns and size, location, and pathological findings was performed. Color Doppler sonography showed five vascular distribution patterns: pattern I, absence of flow; pattern II, focal peripheral flow (“vascular pole”) with arterial Doppler spectrum; pattern III, peripheral flow; pattern IV, internal flow (“parenchymal pattern”); pattern V, peripheral and intranodular flow. Pattern I was not specific for any cervical lesion considered. Conversely, pattern IV was observed solely in parathyroid lesions, and pattern II was observed in only one nonparathyroid lesion (thyroid nodule). Mixed pattern (pattern V) was observed solely in thyroid nodules. In addition, pattern III was a characteristic finding of thyroid nodules and was observed in only one parathyroid lesion. Color Doppler patterns of the parathyroid masses did not correlate with the size of the lesion or pathological findings, but only with the location of the gland. Our study showed that color Doppler assessment of parathyroid lesions is a useful integration of gray-scale US and may be helpful in distinguishing parathyroid lesions from other cervical masses.

This study prospectively evaluated the sensitivity of high-resolution sonography compared with double-tracer 201Tl-99mTc scintigraphy (Tl-Tc) subtractive scintigraphy and double-phase 99mTc-sestamibi (Tc-MIBI) scintigraphy prior to surgery in the assessment of patients with primary hyperparathyroidism in a geographic region where areas of endemic thyroid goiter are present.Sonography and scintigraphy were used as first-step imaging procedures in 73 patients with primary hyperparathyroidism. In 30 (41%) of 73 cases, we found an association with a thyroid abnormality. We compared sonography with double-tracer Tl-Tc scintigraphy in 41 cases, with Tc-MIBI scintigraphy in 22 other cases, and with both scintigraphic studies in 10 other cases.Surgery demonstrated 68 solitary parathyroid lesions (66 adenomas, one hyperplasia, and one carcinoma), two adenomas in two patients, and multiple hyperplastic glands in two patients for a total of seven lesions. In one case no abnormal parathyroid gland was found. Overall sensitivity of sonography, Tl-Tc, and Tc-MIBI scintigraphy was 85%, 62%, and 82%, respectively. In patients with concomitant thyroid disease, the sensitivity of sonography, dual-tracer Tl-Tc, and Tc-MIBI was 77%, 67%, and 80%, respectively.Our study proves that sonography and scintigraphy are equally able to detect parathyroid lesions before surgery in patients with concomitant thyroid diseases. In patients without thyroid abnormalities, detection rates of sonography and Tc-MIBI do not show any statistical difference, and the detection rate of Tl-Tc is significantly inferior to that of sonography. Sonography alone should be used as the first step for localization of abnormal parathyroid glands prior to surgery, and Tc-MIBI scintigraphy should be used as the second step when sonography is negative.

Thyroid hypoechogenicity at ultrasound is a characteristic of autoimmune thyroid diseases, with an overlap of this echographic pattern in patients affected by Graves' disease or Hashimoto's thyroiditis. Aim of the present paper was to study the thyroid blood flow (TBF) by color-flow doppler (CFD) and peak systolic velocity (PSV) at the inferior thyroid artery in 37 Graves' and 45 goitrous Hashimoto's thyroiditis patients. CFD pattern was defined as normal (or type 0): TBF limited to peripheral thyroid arteries (PSV = 17.7 +/- 3 cm/sec, mean +/- SD); type I: TBF mildly increased; type II: TBF clearly increased; type III: TBF markedly increased. The CFD was in direct relationship to the PSV. Out of 18 patients with Graves' disease and untreated active hyperthyroidism CFD pattern was type III in 17 and type II in 1. The PSV was 42.1 +/- 15 cm/sec. In 17 patients euthyroid under methimazole, the CFD pattern was type 0 in 3 (17%) type I in 5 (30%), type II in 5 (30%), type III in 4 (23%). In this group of Graves' patients the PSV was 36 +/- 14 cm/sec. In two patients, hypothyroid after radioiodine treatment, the CFD pattern was type 0 in 1 and type I in 1. In the group of Hashimoto's patients TBF was in no relationship with thyroid status or treatment and was type 0 in 22 (49%), type I in 20 (44%), type II in 3 (7%), while none had type III CFD pattern. Thyroid hypoechogenicity at ultrasound was present in 32/37 (86%) Graves' and 41/45 (91%) Hashimoto's patients. All the four patients with Hashimoto's thyroiditis and normal thyroid ultrasound pattern had also a normal CFD pattern, while 4/5 patients with Graves' disease and normal echographic pattern had an increased TBF. In conclusion, a diffusely increased thyroid blood flow is pathognomonic of untreated Graves' disease and an abnormal CFD pattern identifies the majority of Graves' patients with a normal thyroid ultrasound pattern. Thus, CFD sonography may be useful in distinguishing patients with Graves' disease and Hashimoto's thyroiditis having a similar thyroid echographic pattern at ultrasound.

To compare the efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection (PEI) versus repeated TACE in the treatment of large hepatocellular carcinoma (HCC).Fifty-three patients with cirrhosis and a large HCC (main tumor, 3.1-8.0 cm in diameter with no more than two daughter nodules) were enrolled in a prospective, randomized study. Twenty-six patients underwent a single TACE session followed by PEI (TACE-PEI group), whereas 27 patients underwent two to five TACE sessions (TACE group). Both groups of patients were similar with regard to liver function. Follow-up ranged from 8 to 39 months.Complete therapeutic responses were higher (P.05) and tumor recurrences during follow-up were lower (P.05) in the TACE-PEI group than in the TACE group. Patients in the TACE-PEI group survived longer than those in the TACE group, although the difference was not significant (P.1). The rates of survival without recurrence were better in the TACE-PEI group than in the TACE group (P.05).Use of a single TACE session combined with PEI is more effective than repeated TACE in the treatment of large HCC.

In a retrospective analysis performed on 4167 routine abdominal sonographic (US) examinations (September 1989 to December 1991), 93 US reports strongly suggesting the presence of gastrointestinal (GI) tract disorders were found. Neoplastic GI tract diseases were indicated in 65.6 % of cases and non-neoplastic conditions in 34.4 %. The final diagnoses confirmed all the cases of non-neoplastic disease, while 3 patients sonographically suspected as having a neoplasm proved not to have any GI tract abnormality. In the period January 1992 to December 1992, 62 patients with a suspected GI tract abnormality were enrolled in a prospective double-masked US study after being submitted to conventional radiological studies only in 28 of 62 cases, after conventional studies and CT in 24 of 62 cases, and after CT only in 10 of 62 cases. Sonography furnished additional diagnostic information in 28 of 62 cases when the previous radiological examination did not include CT, but sonography misinterpreted 4 inflammatory disorders as tumours. Our study confirmed the important role of US alone or in association with other imaging modalities in the study of GI tract diseases.

The aim of this study was to evaluate the effectiveness of transcatheter arterial embolization (TAE) followed by percutaneous ethanol injection (PEI) in the treatment of large hepatocellular carcinoma (HCC) lesions.Fifteen patients with HCC were treated by means of TAE followed by 6-16 ethanol injections. In 10 patients, the HCC was solitary (3-8 cm); 3 patients had 1, and 2 patients had 2 daughter nodules (3 cm or smaller) in addition. In 12 of 15 main tumors and in 4 of 7 daughter nodules, a tumor capsule was observed by computed tomography or magnetic resonance imaging.Combined treatment with TAE and PEI resulted in complete necrosis of 12 of 15 main tumors and 7 of 7 daughter nodules on biopsy. Treatment failure (incomplete necrosis) occurred in 3 unencapsulated main tumors. The 1-year survival rate in 10 patients was 100%.The combination of TAE and PEI proved to be an effective treatment for large HCC, including those with 1-2 small daughter nodules. The presence of a tumor capsule significantly correlates (p0.05) with a favorable outcome of treatment.