Association between the nuclear to cytoplasmic ratio of p27 and the efficacy of adjuvant polychemotherapy in early breast cancer.

BACKGROUND: The purpose of this study was to evaluate the prognostic and predictive value of p27 expression in patients with early breast cancer. PATIENTS AND METHODS: Quantitative immunofluorescence assays for p27 were done on a tissue microarray that included 823 samples from patients randomized between anthracycline-based chemotherapy and no chemotherapy. Quantification of p27 was done using the AQUA® system (HistoRx, Inc., Branford, CT). Both p27 nuclear expression and the nuclear to cytoplasmic ratio were assessed. RESULTS: Nuclear p27 expression was not predictive for the efficacy of anthracycline-based chemotherapy [adjusted P=0.18 for disease-free survival (DFS)] nor prognostic [95% confidence interval (CI) 0.99-1.01, P=0.49]. However, p27 nuclear/cytoplasmic ratio was predictive for the efficacy of adjuvant chemotherapy (adjusted P=0.016 DFS). The adjusted hazard ratio (HR) for relapse associated with adjuvant chemotherapy was 0.56 (95% CI 0.37-0.84, P=0.005) and 1.06 (95% CI 0.76-1.47, P=0.74) for patients with high and low nuclear/cytoplasmic ratio, respectively. p27 N/C ratio was prognostic in patients treated with chemotherapy (HR for relapse or death for a 1 unit increase in p27 N/C ratio was 0.30, 95% CI 0.12-0.77) but not in the untreated arm (HR for relapse or death was 1.27, 95% CI 0.58-2.8). CONCLUSIONS: This study did not confirm the role of p27 nuclear expression as a prognostic parameter. However, the p27 nuclear/cytoplasmic ratio was predictive in patients treated with anthracycline-based chemotherapy.

Persisting Embryonal Infundibular Recess in Morning Glory Syndrome: Clinical Report of a Novel Association.

Morning glory syndrome is characterized by a congenital optic disc defect that resembles the eponymous flower. We present the MR imaging findings of 2 pediatric patients with morning glory disc anomaly and persisting embryonal infundibular recess, another rare malformative finding, a previously unreported association. Neuroradiologists should be aware of the possible presence of a persisting embryonal infundibular recess in patients with morning glory syndrome, to aid in the differential diagnosis including other pituitary malformations such as pituitary stalk duplication.

Expression patterns and predictive value of phosphorylated AKT in early-stage breast cancer.

BACKGROUND: AKT phosphorylation is a critical step in the activation of growth factor receptors and can mediate tumor resistance to anthracyclines. We evaluated the expression patterns and predictive value of phosphorylated AKT (pAKT) in breast cancer tissues. PATIENTS AND METHODS: pAKT expression was assessed by immunohistochemistry in 823 tumors from patients with early breast cancer enrolled in two randomized trials. The distribution of pAKT expression was correlated with HER2 and epidermal growth factor receptor (EGFR) expression. The predictive value of pAKT for the efficacy of adjuvant chemotherapy was determined by test for interaction. RESULTS: pAKT, EGFR, and HER2 were expressed in 119 of 781 (15%), 118 of 758 (16%), and 99 of 775 (13%) assessable tumors. Staining was positive for pAKT in 28 of 99 (28%) and 90 of 676 (13%) HER2+ and HER2- tumors (P < 0.001). pAKT was expressed in 15 of 94 (16%) and 75 of 563 (13%) HER2-/EGFR+ and HER2-/EGFR- tumors, respectively (P = 0.49). A positive staining for pAKT did not correlate with prognosis (P = 0.94), and did not predict the resistance to anthracyclines (test for interaction, P = 0.70). CONCLUSIONS: AKT phosphorylation is associated with HER2 expression but not EGFR expression in patients with early breast cancer. pAKT is not predictive for the efficacy of anthracycline-based adjuvant chemotherapy.

Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer.

BACKGROUND: Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer. PATIENTS AND METHODS: The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors. RESULTS: Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45-2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2-0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors. CONCLUSION: These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.

A rare symptomatic presentation of ecchordosis physaliphora: neuroradiological and surgical management.

We report a case of ecchordosis physaliphora, an uncommon benign lesion originating from embryonic notochordal remnants, intradurally located in the prepontine cistern, that unusually presented associated with symptoms. MRI detected and precisely located the small mass. At surgery, a cystic gelatinous nodule was found ventral to the pons, contiguous with the dorsal wall of the clivus via a small pedicle. Histological examination diagnosed the lesion as an ecchordosis physaliphora. Here we focus on the analysis of the neuroradiological aspects that play a crucial role from both a diagnostic and a therapeutic standpoint.

[Systemic treatment of brain metastases from breast cancer]. / Métastases cérébrales de cancer du sein: traitements systémiques.

An increase in the incidence of breast cancer patients with brain metastases has been observed over the last years, mainly because the recent development of new drugs including therapies targeting HER2 (human epidermal growth factor receptor 2) resulted in an increased survival of these patients. With HER2+ patients living longer and the well-known neurotropism of HER2+ tumour cells, the resulting high incidence of brain metastases is not really surprising. Moreover, brain metastases more often occur within a context of existing extracranial metastases. These need to be treated at the same time in order to favourably impact patients' survival. Consequently, the management of breast cancer patients with brain metastases clearly relies on a multidisciplinary approach, including systemic treatment. A working group including neuro-oncologists, neurosurgeons, radiation oncologists and oncologists was created in order to provide French national guidelines for the management of brain metastases within the "Association des neuro-oncologues d'expression française" (ANOCEF). The recommendations regarding the systemic treatment in breast cancer patients are reported here including key features of their management.

Mastication induces long-term increases in blood perfusion of the trigeminal principal nucleus.

Understanding mechanisms for vessel tone regulation within the trigeminal nuclei is of great interest because some headache syndromes are due to dysregulation of such mechanisms. Previous experiments on animal models suggest that mastication may alter neuron metabolism and blood supply in these nuclei. To investigate this hypothesis in humans, arterial spin-labeling magnetic resonance imaging (MRI) was used to measure blood perfusion within the principal trigeminal nucleus (Vp) and in the dorsolateral-midbrain (DM, including the mesencephalic trigeminal nucleus) in healthy volunteers, before and immediately after a mastication exercise consisting of chewing a gum on one side of the mouth for 1 h at 1 bite/s. The side preference for masticating was evaluated with a chewing test and the volume of the masseter muscle was measured on T1-weighted MRI scans. The results demonstrated that the mastication exercise caused a perfusion increase within the Vp, but not in the DM. This change was correlated to the preference score for the side where the exercise took place. Moreover, the basal Vp perfusion was correlated to the masseter volume. These results indicate that the local vascular tone of the trigeminal nuclei can be constitutively altered by the chewing practice and by strong or sustained chewing.

'Simple schizophrenia': a controlled MRI and clinical/neuropsychological study.

The present study explored the frequency of neuromorphological, neurological and neuropsychological abnormalities in 13 patients with an ICD-8/9 diagnosis of simple schizophrenia, also fulfilling DSM-IV criteria for 'simple deteriorative disorder', and in 13 matched patients with an ICD-8/9 diagnosis of a subtype of schizophrenia other than simple schizophrenia, fulfilling DSM-IV criteria for schizophrenia. The frequency of neuromorphological abnormalities in the two patient groups was also compared with that observed in 13 neurological control subjects. Both patients with simple schizophrenia and those with other schizophrenia subtypes showed a higher frequency of brain developmental abnormalities and greater ventricular and subarachnoid space volumes than controls. There was no significant difference between the two groups of patients with respect to neuromorphological variables. Two patients with simple schizophrenia (vs. none of those with other schizophrenia subtypes) had gross brain abnormalities; they were the most deteriorated subjects in the whole sample. Patients with simple schizophrenia, as compared to those with other schizophrenia subtypes, presented a higher frequency of soft neurological signs and a greater impairment of social relationships.

Aqueductal stenosis as isolated localization involving the central nervous system in children affected by von Recklinghausen disease.

The Authors report three cases of non tumoral aqueductal stenosis associated with von Recklinghausen disease in children. Moreover, 16 similar cases collected from the literature are illustrated. The clinical features are evaluated in light of literature's data. Among all 19 cases, the median age was 19 years (range 6-46 years) and 9 patients were under the age of 13 years. In this latter group, the most represented clinical symptoms were headache and gait disturbances. As regards the neuroradiological procedures, CT scan represented the best tool in the evaluation of the ventricular size. Our own three cases underwent to ventriculo-atrial shunt procedures, followed by clinical recovery (follow-up: 3 months-5 years). In conclusion it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, aqueductal stenosis seems to belong to the natural history of this disease.

Spinal ossifying arachnoiditis. Case report.

A case of low dorsal spinal cord compression, due to ossifying arachnoiditis, is reported. Its relationship with a venous malformation overlying the dorsal surface of the spinal cord is mentioned. The literature is reviewed and possible etiopathogenetic factors favouring this rare condition are discussed in the light of few similar reports. The value of surgical treatment is stressed.

Role of antepartum computerized fetal heart rate analysis in the prediction of fetal distress during labor.

OBJECTIVE: To ascertain the diagnostic ability of a computerized fetal heart rate (FHR) analysis system in the identification of patients at risk of fetal distress in labor. STUDY DESIGN: Five-hundred and seventy-seven healthy term pregnancies were enrolled in a prospective, cross-sectional study and subdivided into two groups, with (n = 90) or without (n = 487) fetal distress in labor. Computerized FHR recordings were performed periodically and regression analysis was performed in a univariate and multivariate way to assess the ability of the last FHR recordings in the prediction of subsequent fetal distress. RESULTS: The two groups showed a significant difference in almost all of the FHR parameters studied. The multivariate analysis showed that only the FHR baseline and the percentage of small acceleration were independently and significantly related to the labor outcome. The combination of these two parameters reaches a sensitivity of 45%, specificity of 91%, positive predictive value of 48% and negative predictive value of 90%, with an overall accuracy of 84%. CONCLUSIONS: The increase in FHR baseline and in small FHR accelerations can be major factors in the prediction of subsequent fetal distress in healthy term fetuses.

[Umbilical flowmetry: effect of measurement sites on the results]. / Flussimetria ombelicale: influenza del sito di misurazione sui risultati ottenuti.

Pulsed Doppler duplex sonography was performed longitudinally on 11 uncomplicated singleton pregnancies from 20 to 41 week's gestation (87 measurements). Blood flow velocities were recorded at 3 locations: abdominal insertion site (O), in the free floating part (C), placental insertion site (PL). The objective of the study was to determine whether the C site S/D ratio, the quickest and easiest to perform, relates to the other sites. The S/D ratio measurements fell from the near abdomen (O) to the free floating part (C) to the placental insertion site (PL) between 25-35 week's gestation. Statistical analysis, including analysis of variance for repeated measures and student t test, showed no significant difference in S/D ratio among the locations before 25 and after 35 week's gestation. The S/D ratio at the O site was significantly higher than at the PL site between 25-35 week's gestation; the C site was not significantly different from the PL site.

Cerebral cavernous angioma. Diagnostic considerations.

Eighteen cases of cerebral cavernous angiomas are reported, and their histopathological, clinical and radiological features are reviewed. MR complements TC in characterizing cavernomas and in distinguishing them from similar-appearing lesions. However, when such lesions are seen with atypical features, discrimination from hemorrhagic tumors remains problematic. More malignant lesions present, on MRI, a much larger area of abnormality and make themselves obvious in a shorter period. Gadolinium administration may allow a more specific interpretation of small lesions.

Herniated disk in adolescents.

Twenty-one patients (9 female and 12 male) aged from 13 to 22 years were observed for lumbago and lumbo-sciatica caused by a discopathy which was subsequently confirmed by radiology and surgery. None of these patients had a history of trauma. It must be underlined that the painful symptoms exhibited and the young age of the patients suggest such pathologies as infections, tumours or malformations, but the possibility of discopathy must always be considered. It is also interesting to note the differences observed in symptomatology between adults and adolescents and to consider the various pathogenetic factors which might cause discopathy in adolescents while it was until now believed to be reserved to adults.

Paget's Disease. A Case Report.

Paget's disease (PD) is a common focal progressive osteometabolic disorder characterised by a disturbance in bone modelling and remodelling, because of an increase in osteoblastic and osteoclastic activity. It is a condition of unknown aetiology affecting approximately 3% of the population over 40 years of age and, approximately 10% of those over the age of 85 years. It is most common in Northern Europe and Australia and is rare in Asia and Africa. We describe the case of a 71-year-old man diagnosed with PD confined to the sacrum. After laboratory test, an imaging study with radiography, scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI) was performed disclosing findings compatible with Paget's disease in middle pathologic phase. The diagnosis was confirmed at biopsy. The structural modification of the sacrum with spongiosa rarefaction, thickening of bone and intact bone cortical, confirmed by CT, are tipical of an intermediate phase of PD. This was also supported by signal MRI changes showing substitution of the red by the fat medulla, visualized by FS sequences. Once the treatment for the bone disease was established, the patient no longer complained of pain. Special attention should be paid to male and elderly patients with pain in the lumbar spine because of the potential risk cancer development (21). The radiologist must be attentive to the possible presentations and complications of PD, even in uncommon sites, trying whenever possible to correlate the radiological features with the patient's clinical symptoms.

Cervical chordoma. A case report and differential diagnosis.

Chordomas are rare and aggressive tumors derived from notochordal remnants, usually arising in the axial skeleton. The most frequently reported anatomic distribution of chordoma is 50% sacral, 35% spheno-occipital and 15% spinal. We describe the case of an elderly lady presenting with progressive dysphagia, headache and neck pain. We found an expansile mass extending from C1 to C3. While running the diagnostic plan we considered a variety of lesions possibly involving the cervical spine. Biopsy revealed the mass was a chordoma.

Giant dilatations of virchow-robin spaces in the midbrain. MRI aspects and review of the literature.

Virchow-Robin spaces are lesions often seen in the brain parenchyma but their etiopathogenesis remains unsettled. Giant Virchow-Robin spaces placed in the midbrain are extremely rare. We describe three patients with a diagnosis of giant Virchow-Robin spaces in the midbrain, and their clinical and radiologic findings. We reviewed the literature in terms of the etiopathology, anatomic and radiologic appearance and differential diagnosis of the giant Virchow-Robin spaces. The diagno-stic role of the high Tesla magnetic resonance devices and new sequences techniques such as three dimensional isotropic acquisition and diffusion tensor imaging were also evaluated in this case series.

Widespread microstructural white matter involvement in amyotrophic lateral sclerosis: a whole-brain DTI study.

BACKGROUND AND PURPOSE: The extensive application of advanced MR imaging techniques to the study of ALS has undoubtedly improved our knowledge of disease pathophysiology, even if the actual spread of the neurodegenerative process throughout the central nervous system is not fully understood. The present study aimed to detect WM patterns of microstructural abnormalities to better investigate the pathologic process in ALS, within but also beyond CSTs, in a whole-brain analysis. MATERIALS AND METHODS: DTI was performed in 19 patients with ALS and 20 matched healthy controls, by using whole-brain TBSS and VOI analyses. RESULTS: We observed a significant decrease of FA in the body of CC of the ALS group (P < .05). At the VOI level, both FA decrease and RD increase in the body of CC significantly correlated with the UMN score (P = .003 and P = .02). Additionally, significant voxelwise positive correlations between FA and the ALSFRS-R were detected in the WM tracts underneath the left premotor cortex (P < .05). CONCLUSIONS: The correlations between reduction of FA and increase of RD in the body of CC with the UMN score indicate that the WM degeneration in the CC is strictly related to the ALS pyramidal impairment, while the correlation between FA and ALSFRS-R in the associative tracts underneath the left premotor cortex might reflect the progressive spread of the disease from the motor toward the extramotor areas.

Spontaneous resolution of eosinophilic granuloma in a patient with a psychotic disorder.

A 16-year-old female who manifested psychotic symptoms underwent CT and MRI for the evaluation of an incidentally discovered asymptomatic palpable mass of the right occipital region of the skull. The correlation between clinical and radiological data and biopsy data led to the diagnosis of eosinophilic granuloma. The radiological finding is discussed and reviewed in relation to clinical aspects and literature data.

Role of Magnetic Resonance Imaging in Duane's Retraction Syndrome: Presence of the Abducens Nerve Depending on Type. A Clinical-Anatomical Study.

This study correlated anatomical findings and clinical evidence in Duane's Retraction Syndrome using brain MRI. The study included 11 patients with different types of Duane's Retraction Syndrome (DRS). Each patient underwent brain MRI. The VI(th) nerve was absent in all patients with DRS-I, present in all patients with DRS-II, while findings varied in patients with DRS-III. Our study confirms the literature on the usefulness of brain MRI in diagnosis of Duane's Retraction Syndrome in children.