Outcome prediction and risk assessment by quantitative pyrosequencing methylation analysis of the SFN gene in advanced stage,high‐risk,neuroblastic tumor patients

The aim of our study was to identify threshold levels of DNA methylation predictive of the outcome to better define the risk group of stage 4 neuroblastic tumor patients. Quantitative pyrosequencing analysis was applied to a training set of 50 stage 4, high risk patients and to a validation cohort of 72 consecutive patients. Stage 4 patients at lower risk and ganglioneuroma patients were included as control groups. Predictive thresholds of methylation were identified by ROC curve analysis. The prognostic end points of the study were the overall and progression‐free survival at 60 months. Data were analyzed with the Cox proportional hazard model. In a multivariate model the methylation threshold identified for the SFN gene (14.3.3σ) distinguished the patients presenting favorable outcome from those with progressing disease, independently from all known predictors (Training set: Overall Survival HR 8.53, p = 0.001; Validation set: HR 4.07, p = 0.008). The level of methylation in the tumors of high‐risk patients surviving more than 60 months was comparable to that of tumors derived from lower risk patients and to that of benign ganglioneuroma. Methylation above the threshold level was associated with reduced SFN expression in comparison with samples below the threshold. Quantitative methylation is a promising tool to predict survival in neuroblastic tumor patients. Our results lead to the hypothesis that a subset of patients considered at high risk—but displaying low levels of methylation—could be assigned at a lower risk group.     

Natural history of epithelial ovarian cancer and its relation to surgical and medical treatment

Epithelial ovarian cancer (EOC) represents approximately 90% of primary malignant ovarian tumors, the sixth most common cancer in women and the second most common gynecologic cancer. Approximately 80%-85% of all ovarian carcinomas in Western society are serous and up to 95% of patients are in advanced stages (FIGO stage III-IV) at diagnosis. Treatment of ovarian cancer is mainly based on three key approaches: surgical removal of neoplasia; chemotherapy to kill cancer cells; direct chemotherapy on peritoneal surfaces. The application of hyperthermic chemotherapy to the peritoneal cavity (HIPEC) after radical surgery may also be an attractive option. We analyzed the natural history of EOC in the literature and identified various time-points where sensitivity to chemotherapy, freedom from disease and overall survival are different. We propose eight time-points in EOC history with homogeneous oncological findings. The effectiveness of HIPEC in EOC treatment should be evaluated based on these eight time-points and we believe that retrospective and prospective studies of HIPEC should be evaluated according to these time-points.     

Distinct patterns of grey matter abnormality in high-functioning autism and Asperger's syndrome

Background: Autism exists across a wide spectrum and there is considerable debate as to whether children with Asperger’s syndrome, who have normal language milestones, should be considered to comprise a subgroup distinct other from high‐functioning children with autism (HFA), who have a history of delayed language development. Magnetic resonance imaging (MRI) studies of autism are in disagreement. One possible reason is that the diagnosis of autism takes precedence over Asperger’s syndrome and a distinction in language acquisition is rarely made. We therefore planned to examine a whole brain hypothesis that the patterns of grey matter differences in Asperger’s syndrome and HFA can be distinguished. Methods: We used voxel‐based computational morphometry to map grey matter volume differences in 33 children with either Asperger’s syndrome or high‐functioning autism compared to 55 typical developing control children balanced for age, IQ, gender, maternal language and ethnicity. Results: Children with HFA had significantly smaller grey matter volumes in subcortical, posterior cingulate and precuneus regions than the Asperger’s group. Compared to controls, children with HFA had smaller grey matter volumes in predominantly fronto‐pallidal regions, while children with Asperger’s had less grey matter in mainly bilateral caudate and left thalamus. In addition we found a significant negative correlation between the size of a grey matter cluster around BA44 language area and the age of acquisition of phrase speech in the children with HFA. When the groups were combined we confirmed a mixed picture of smaller grey matter volumes in frontal, basal ganglia, temporal and parietal regions. Conclusions: Our study suggests that the underlying neurobiology in HFA and Asperger’s syndrome is at least partly discrete. Future studies should therefore consider the history of language acquisition as a valuable tool to refine investigation of aetiological factors and management options in pervasive developmental disorders.     

Double-contrast MRI (DC-MRI) in the study of the cirrhotic liver: utility of administering Gd-DTPA as a complement to examinations in which SPIO liver uptake and distribution alterations (SPIO-LUDA) are present and in the identification and characterisation of focal lesions

PURPOSE: The aim of this study was to compare the performance of double-contrast magnetic resonance imaging (DC-MRI) with the sequential use of superparamagnetic iron oxide (SPIO) and gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) contrast agents compared with unenhanced MRI and SPIO-enhanced MRI (SPIO-MRI) in the study of the cirrhotic liver. Special attention was paid to cases in which alterations of liver uptake and distribution of the SPIO contrast medium [SPIO-liver uptake and distribution alterations (SPIO-LUDA)] could lead to diagnostic errors at SPIO-MRI. MATERIALS AND METHODS: We used DC-MRI to study 67 patients suffering from hepatic cirrhosis and on a waiting list for liver transplant. The study was performed with a 1.5-Tesla device and characterised by three phases: the first phase without contrast material (unenhanced MRI), the second after the administration of ferumoxides (SPIO-MRI), and the third, a double-contrast study following the injection of a bolus of paramagnetic contrast material (DC-MRI). The sensitivity of unenhanced MRI, SPIO-MRI and DC-MRI in identifying and characterising hepatic focal lesions was assessed, together with the diagnostic increment of one technique with respect to the others. The gold standard was histological confirmation in 38 cases and clinical-radiological follow-up in all cases. Liver function, kidney function, blood tests and urinalysis were performed in all patients 24-48 h before and after the MRI examination. RESULTS: In 14/67 cases (20.8%), SPIO-LUDA were present, which posed a limitation to the SPIO-MRI examination. Focal lesions were absent in 44 patients, and the action of the ferumoxides was reduced by the presence of SPIO-LUDA in nine cases. There were five cases of confluent fibrosis, two of decompensated cirrhosis, one of vascular thrombosis, and one of scarring in a patient who had undergone hepatic resection for hepatocellular carcinoma (HCC). In all these cases, completion of the MR examination with the DC technique clarified the MR picture, confirming the absence of focal lesions. Twenty-three patients had a total of 68 lesions, which consisted of 37 dysplastic nodules (DN), 19 HCC nodules, two relapses of HCC following chemoembolisation, two HCC associated with portal thrombosis, one cancer-cirrhosis, two angiomas and five small cysts. SPIO-LUDA were present in five patients, thus limiting the identification, characterisation or assessment of the real size of the lesions. SPIO-LUDA were the result of vascular thrombosis in one case and fibrosis in four cases. In all of these cases, DC-MRI proved useful for diagnosis. The sensitivity of unenhanced MRI, SPIO-MRI and DC-MRI for lesion detection was 57.3%, 67.6% and 75%, respectively. The results obtained in the characterisation of the lesions were 20.5%, 63.2% and 73.5% for unenhanced MRI, SPIO-MRI and DC-MRI, respectively. The diagnostic increment of SPIO-MRI over unenhanced MRI for lesion identification and characterisation was 9% and 42.7%, respectively, whereas the diagnostic increment of DC-MRI over SPIO-MRI was 7.4% and 10.3%, respectively. CONCLUSIONS: In our study, the combined use of two contrast agents, negative and positive, provided greater diagnostic confidence and caused no side effects in the patients.     

Advanced virtual magnetic resonance imaging (MRI) techniques in neurovascular conflict: bidimensional image fusion and virtual cisternography

Purpose

The aim of this study was to evaluate the advantages and limits of virtual magnetic resonance techniques in planning surgery for microvascular decompression in patients with neurovascular conflict.

Materials and methods

Between December 2010 and December 2011, we prospectively observed 32 patients (30 with trigeminal neuralgia and two with hemifacial spasm), with a suspected clinical diagnosis of neurovascular conflict. To assess the contact between nerve and vessel, magnetic resonance imaging (MRI) by three-dimensional (3D) constructive interference in steady state (CISS) and high-resolution MR angiography (MRA) were performed in all cases. Moreover, we performed presurgical simulation of microvascular decompression using MR two-dimensional image fusion and virtual cisternography. The neuroradiological findings were compared with the surgical findings.

Results

In all cases, we demonstrated the anatomical relations between cranial nerves and offending vessels with an optimal correlation between radiological and surgical patterns.

Conclusions

Advanced virtual MRI techniques, such as image fusion and virtual cisternography, are able to depict the complex anatomical relationships between neural and vascular structures within the cisternal spaces of the skull base. These techniques can be considered an optimal presurgical tool to support traditional MRI evaluation of this region.     

Histologic evaluation of autogenous calvarial bone in maxillary onlay bone grafts: a report of 2 cases

Bone augmentation for implant dentistry has become a necessary procedure for a number of edentulous patients. Calvarial bone grafting constitutes an important tool in achieving maxillary augmentation and sinus elevation. Much effort has been directed toward improving graft survival and volumetric maintenance. The purpose of the present study was to evaluate the histologic results of the calvarial onlay graft for maxillary reconstruction before implant placement. Two patients underwent maxillary augmentation using autogenous calvarial onlay grafts. After a 4-month healing period, biopsies of the augmented regions were performed and implants were placed. The implants were loaded after 5 months and then clinically examined after 15 months of function. Biopsies showed that calvarial onlay grafts were well incorporated into the preexisting bone after a 4-month period. Histologic and histomorphometric findings demonstrated a living bone that showed features characteristic of mature and compact osseous tissue. The restored Implants were stable and osseointegrated after a 15-month period of follow-up. The use of calvarial onlay grafts can be a predictable and successful method to achieve maxillary augmentation, allowing appropriate placement of implants and stable prosthetic restorations.     

Sexual Functioning in Women with Mild and Severe Symptoms of Charcot-Marie-Tooth Disease

IntroductionCharcot-Marie-Tooth (CMT) disease is one of the most frequently inherited neurological disorders, and while it is known that individuals suffering from this condition have low quality of life, little is known about their sexual function and satisfaction.AimTo describe the functioning on different domains of sexuality in a relatively large sample of women with CMT, provide comparisons between mildly and severely affected patients and between women with the two different types of CMT (demyelinating vs. axonal), and assess the relationship between sexual function and age of onset.MethodsFifty-seven women (age: 18–60 years) were approached in a CMT rehabilitation clinic by a psychologist and administered the Italian version of the McCoy Female Sexuality Questionnaire (MFSQ). Data from 40 patients who had had sexual intercourse in the previous 4 weeks were analyzed.Main Outcome MeasureThe main outcome measures are the factors MFSQ-SEX and MFSQ-PARTNER, which describe sexual functioning and sexual satisfaction with a partner, respectively.ResultsAlmost 30% of women did not engage in sexual intercourse with a partner. Overall sexual problems were more prominent in younger women and tended to be lower as age increased: this pattern was different from what was reported in previous studies in comparable samples of healthy Italian women. Severity of CMT was associated with better sexual functioning in the areas of desire, arousal, orgasm, and satisfaction, with women with more severe symptoms reporting greater functioning. Women with more severe CMT symptoms reported more pain during intercourse. Age of CMT onset and type of CMT (demyelinating vs. axonal) were not associated with differences in sexual functioning.ConclusionsFindings point to the importance of including assessment of sexual dysfunction in young women with mild CMT symptoms and the importance of providing sex therapy or counseling to these patients. Gargiulo P, Vinci P, Navarro-Cremades F, and Rellini AH. Sexual functioning in women with mild and severe symptoms of Charcot-Marie-Tooth Disease.