TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway.

Ten eleven translocation (TET) enzymes catalyse the oxidative reactions of 5-methylcytosine (5mC) to promote the demethylation process. The reaction intermediate 5-hydroxymethylcytosine (5hmC) has been shown to be abundant in embryonic stem cells and tissues but strongly depleted in human cancers. Genetic mutations of TET2 gene were associated with leukaemia, whereas TET1 downregulation has been shown to promote malignancy in breast cancer. Here we report that TET1 is downregulated in colon tumours from the initial stage. TET1 silencing in primary epithelial colon cells increase their cellular proliferation while its re-expression in colon cancer cells inhibits their proliferation and the growth of tumour xenografts even at later stages. We found that TET1 binds to the promoter of the DKK gene inhibitors of the WNT signalling to maintain them hypomethylated. Downregulation of TET1 during colon cancer initiation leads to repression, by DNA methylation, the promoters of the inhibitors of the WNT pathway resulting in a constitutive activation of the WNT pathway. Thus the DNA hydroxymethylation mediated by TET1 controlling the WNT signalling is a key player of tumour growth. These results provide new insights for understanding how tumours escape cellular controls.

Outcome of lumbar intervertebral foraminal stenosis surgery and depression.

A total of 58 patients consecutively underwent surgical treatment for lumbar intervertebral foraminal stenosis. We performed a microsurgical combined transarticular lateral and medial procedure with partial facetectomy in all patients to decompress the affected nerve root. All patients underwent assessment of depressive symptoms by means of the Zung Self Depression Scale (SDS). Subjective pain was self-evaluated by the Visual Analogue Scale (VAS). Both the tools were administered preoperatively, at 3 and 12 months' follow-up 0. The difference between the three SDS scores was significant (Friedman ANOVA, χ(2) = 53.171, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative SDS scores as compared with three months follow-up (Z = -6.393, p < 0.0001) and the last, in turn, as compared with twelve months follow- up (Z = -3.720, p = 0.0002). The comparison between preoperative and 12 months' follow-up also reached significance (Z = -3.285, p = 0.001). About VAS, the difference between the three VAS scores was significant (Friedman ANOVA, χ(2) = 69.932, p < 0.00001). The Wilcoxon rank test showed significant difference between preoperative VAS scores as compared with 3 months' follow-up (Z = -6.567, p < 0.0001) and the last, in turn, as compared with 12 months' follow-up (Z = -3.153, p < 0.002). The comparison between preoperative and 12 months' follow-up was also significance (Z = -5.520, p < 0.0001). Our results would alert clinicians to accurately consider the real need to treat and to include a careful psychiatric and psychological evaluation of these patients in the diagnosis and follow-up 0.

The effect of inappropriate therapy on bacteremia by ESBL-producing bacteria.

OBJECTIVE: To describe the impact of empiric appropriate treatment and the risk factors associated with mortality in patients with bacteremia by E. coli, K. pneumoniae and P. mirabilis producing ESBL. METHODS: Data were reviewed in an 8-year retrospective study, and 128 bacteremias were found: 80 caused by E. coli (62.5%), 28 by K. pneumoniae (21.9%) and 20 by P. mirabilis (18.6%). RESULTS: The initial antibiotic treatment, administered within 72 h after the first positive blood culture, was appropriate with carbapenems or other antimicrobial agents with documented in vitro sensitivity in 53.8 and 16% of patients, respectively. The overall mortality 21 days after diagnosis was 17.2%, and it was 14.9 and 35.2% for patients adequately and inadequately treated, respectively. At univariate analysis the p value for mortality with and without appropriate treatment was 0.05, and significant differences were found only for previous positive blood cultures (p = 0.004) and presence of septic shock at diagnosis (p = 0.006). CONCLUSION: In this case series there was a high rate of initial appropriate empiric treatment, and only a marginal impact on mortality was found with regard to appropriate and inappropriate treatment. This report shows that the knowledge of ESBL-producing characteristics varies widely among the different case series for reasons that still have to be clarified.

Anatomical variant of origin of ophthalmic artery: case report.

We report on one case of variant origin of right ophthalmic artery (OA) from C4 choroidal segment of the right supraclinoid internal carotid artery. A 41-year-old woman affected by bitemporal hemianopsia performed Magnetic Resonance Imaging with gadolinium showing tuberculum sellae meningioma. During angiography we observed this variant of origin of OA. At surgical dissection, we observed this variant in carotid cistern.

Ultrastructural profile of microcystic meningioma.

OBJECTIVE: Microcystic meningioma was originally classified as a subtype of meningioma by the World Health Organization classification of brain tumours in 1993, and accounts for 1.6% of intracranial meningiomas. This subtype is a variety of meningioma in which micro- and macro-cysts are diffuse. The morphologic characteristics are well defined, while the histogenetic mechanism that give rise to these patterns remain unclear. MATERIALS AND METHODS: The authors present an electron microscopic study of an unusual case of fronto-temporal microcystic meningioma, manifesting as history of headache, right paresis and dysphasia in a 73-year-old female. Computer tomography revealed a large hypodense mass in the left fronto-temporal region, with slight contrast enhancement. RESULTS: Ultrastructural observation showed complex alterations among small vessels and intratumoral capillaries in a background of severe modification in vessel permeability. CONCLUSIONS: This electronic microscopy study documented that growth of the cyst was due not only to accumulation of in extracellular fluid, but also to cytolysis consequent to ingravescent hydropic degeneration.

Giant intracranial chordoma: neuroradiological and radiotherapeutic aspects.

We describe a rare case of giant intracranial chordoma, emphasizing the patient's long survival and his excellent response to radiotherapy that led to a progressive regression of neurological symptomatology up to disappearance, in the absence of cerebral white matter damages.

Prognostic role of depression after lumbar disc surgery.

A total of 73 patients underwent microdiscectomy for lumbar disc herniation between September 2001 and May 2002 at the Department of Neurosurgery of the Second University of Naples. Preoperatively and 3 and 6 months after surgery, patients were assessed on the Zung Self-rating Depression Scale (SDS) and on a visual analogue scale (VAS) for the subjective perception of pain. At 3 and 12 months, we found that patients with lower SDS scores (n=41) had a better outcome regarding pain than patients with relevant depressive symptoms (n=32). In agreement with the literature, our results confirm the negative role of depression in outcome after lumbar disc surgery. We emphasize the consideration of psychological factors in the management of lumbar disc herniation.

Management of benign craniovertebral junction tumors.

BACKGROUND: We report our surgical experience in the treatment of fifteen consecutive patients with benign craniovertebral junction tumors, observed from 1993 to 2000 at our department. METHOD: We treated 7 meningiomas, 3 epidermoids, 3 C1 neurinomas and 2 neurinomas of the lower cranial nerves. Clinical results were evaluated by Karnofsky Performance Scale and all patients underwent preoperative neuroradiological evaluation with CT, MRI and MRA; angiography was not routinely performed and was considered for each individual case. FINDINGS: 11 partial transcondilar and 4 retrocondilar approaches were performed. Total removal was achieved in 11 cases (73,3%) and subtotal removal in 4 patients (26,7%). None of the patients required occipitocervical fusion. Patients were followed for an average period of 24+/-31 months. Clinical and radiological follow-up showed no recurrence in cases with total removal. In all patients a statistically significant postoperative increase of KPS scores was recorded. The treatment of epidermoid tumors presented particular issues: debulking the lesion, we obtained a surgical window, avoiding a large removal of bone. In Nakasu grade 1 or 2 meningiomas, we carried out total removal by piecemeal resection and without complete condylectomy and bone fixation. INTERPRETATION: The choice of these approaches and the extent of bone resection should be defined according to the tumor's location and size. Moreover we emphasize that preoperative neuroradiological evaluations on presumptive tumor type could be helpful to the surgeon in order to tailor the technique to different lesions, providing the required exposure, without unnecessary surgical steps.

Lumbosacral dural ectasia in type 1 neurofibromatosis. Report of two cases.

Dural ectasia denotes circumferential expansion or dilatation of the dural sac, and has been frequently reported in association with type 1 neurofibromatosis (NF1). The pathogenesis has not been defined, but its correlation with NF1 infers a congenital malformative hypothesis. The neural elements in the dilated sleeve typically are not enlarged or abnormal, nevertheless the enlarged area contain an increased amount of cerebrospinal fluid. The dura in the area of ectasia is extremely thin and fragile, and erodes the surrounding bony structures destabilising the spine and permitting spectacular spinal deformities. We present two cases with lumbosacral dural ectasia, enlargement of the intervertebral foramina and posterior scalloping of vertebral bodies. Neurological examination showed sciatic nerve irritation. As the etiology of this malformation remains uncertain and dysplastic changes of the spine may be intrinsic or secondary controversies remain about optimum treatment. We conclude that patients affected by NF-1 require an accurate neuroradiological study of the whole spine in order to detect possible dural and spinal anomalies. Surgical treatment is indicated only in patients with progressive neurological deterioration. The thin dural sac predisposes to a high morbidity if surgery is undertaken.

Traumatic subependymal hematoma during endoscopic third ventriculostomy in a patient with a third ventricle tumor: case report.

Endoscopic third ventriculostomy has become a routine intervention for the treatment of non-communicating hydrocephalus. This technique is largely considered safe and a very low incidence of complications is reported. However, hemorrhage in the course of neuroendoscopy is still a problem difficult to manage. The authors present a case in which endoscopic third ventriculostomy and tumor biopsy were performed in a young patient with a huge tumor growing in the posterior part of the third ventricle. The surgical approach to realize the stoma was difficult because the tumor size reduced the third ventricle diameter. Surgical manipulation produced a traumatic subependymal hematoma. This hematoma drained spontaneously after few minutes into the ventricle and the blood was washed away. The postoperative neurological course was uneventful and the ventriculostomy showed to work well by reducing the size of the lateral ventricles and the intracranial pressure in three days. This complication during endoscopic third ventriculostomy has never been reported before. We emphasize the difficulty of endoscopic procedures in patients with huge tumors in the third ventricle. Where reduction in size of the third ventricle and of the foramen of Monro ist present we suggest a careful approach to the third ventricle.

Spontaneous resolution of chronic subdural hematoma.

BACKGROUND: Spontaneous resolution of chronic subdural hematoma has rarely been reported in the literature, and its mechanism has not been fully investigated. Response to surgery has been very satisfactory; in fact, this is generally considered the treatment of choice. METHODS: From a series of 24 cases of chronic subdural hematomas, we observed five patients between 1996 to 1998. These patients showed headache and decrease of cognitive level, 4-5 weeks after minor head injury. Neurologic evaluation revealed only worsening of mental function according to Mini Mental State Examination (MMSE). Computed tomography (CT) scans showed brain atrophy and chronic subdural hematoma without increased intracranial pressure. These patients were treated by clinical observation and serial cerebral CT scans. RESULTS: After 7 to 10 days, all patients showed improvement of clinical signs. After 30 to 45 days, radiological disappearance or marked reduction in size of the hematoma and complete clinical recovery were obtained. No neurological deficits and no recurrences have been observed during follow-up (3 months to 2 years). CONCLUSIONS: We believe that age greater than 70 years, decreased cognitive level (MMSE = 21), brain atrophy, and absence of increase of intracranial pressure are clinical and radiological signs that allow one to choose conservative treatment.

Tissue expansion in neurosurgical reconstructive technique: case report.

BACKGROUND: Various reconstructive techniques using hair-bearing scalp to manage unsightly scalp defects have been described. In 1983, Fonseca and in 1984, Horowitz emphasized the use of galeal-pericranial flaps in scalp wounds with exposed bone. In 1986, Matthews and Missoten described early tissue expansion to close a traumatic defect of the scalp, and in 1990 Kiyono placed tissue expander in a pocket adjacent to the defect that was covered with Marlex Mesh. METHODS: The authors present a case of 23-year-old man with a scalp laceration over a depressed fracture of the skull and a dural tear, after a traffic accident. The repair procedures at another hospital failed, resulting in an area of scalp necrosis with a cerebrospinal fluid (CSF) leak. At our observation, the reconstructive technique using hair-bearing scalp with tissue expander was performed to manage unsightly scalp necrosis. Moreover the neurosurgical treatment was necessary to avoid the complications of the CSF leak. CONCLUSIONS: A 9-year review showed more than 40 patients treated by this technique that allows a pericranial flap of every size. When scalp defects are too large, the tissue expander allows good aesthetic results.

Trigeminal neuralgia treated by percutaneous thermocoagulation. Comparative analysis of percutaneous thermocoagulation and other surgical procedures.

The authors analyze the results they obtained by percutaneous radiofrequency technique for trigeminal neuralgia. The clinical material consists of 605 cases observed from 1977 to 1986 at their Institute. There was a female preponderance (62%) and an average age of 65 years. Idiopathic, atypical and symptomatic trigeminal neuralgia has been diagnosed respectively in 568, 21 and 16 cases. From 1977 to 1980 the working temperature was above 65 C, thereafter a lower temperature has been employed to coagulate the Gasserian ganglion. The rate of pain relief was 97% for idiopathic trigeminal neuralgia, 75% for symptomatic and 21% for atypical. The loss of facial sensation accounts for 80% of side effects of this procedure in their series. The recurrence of pain was observed in 16% of cases with a follow-up ranging from 2 to 10 years. It is noteworthy that there is a correlation between the coagulation temperature and the rate of recurrence, the higher the former, the lower the latter. The authors compare their results (rate of pain relief, morbidity, mortality, rate of recurrence) with those of major reports in the literature concerning either percutaneous or other surgical procedures (mircosurgical decompression of the trigeminal nerve, glycerol injection into the trigeminal cistern and percutaneous microcompression).

Microsurgical management of suprasellar and intraventricular meningiomas.

A series of 78 intracranial meningiomas (68 suprasellar, 10 intraventricular) were operated on in our Institute after the advent of the operating microscope. In our review, we discuss the microsurgical technical problems related to the preservation of vascular and brain structures in the removal of intraventricular and parasellar meningiomas. Basic diagnostic criteria to plan correctly the surgical approach will be emphasized. Mortality and morbidity in parasellar meningiomas is, in our opinion, related to the experience of the surgeon in using the operating microscope rather then in using the laser and CUSA. We will also discuss the utility of preoperative embolization of the lesion as well as the indications for intraoperative EC/IC bypass. Finally, morbidity and mortality related to different approaches for intraventricular meningiomas will be discussed.

Simultaneous multiple brain tumors of different histological nature. Report of two cases.

Two cases of patients harbouring simultaneously multiple brain tumors of different histological nature are here reported. Clinical presentation, site of growth and neuroradiological findings are illustrated and discussed in light of the data previously reported by the literature.

Medical and surgical treatment of Acanthamoeba keratitis.

We examined seven patients with Acanthamoeba keratitis. All patients had a history of soft contact lens use. Predisposing factors included use of homemade saline, hydrogen peroxide disinfection, a history of improper lens care, and swimming with contact lenses. Currently recommended medical therapy, including topical propamidine isethionate and dibromopropamidine isethionate, miconazole, Neosporin, corticosteroids, and systemic ketoconazole, was used in all patients. Five patients have undergone penetrating keratoplasty for progressive primary Acanthamoeba keratitis (four patients) or recurrent infection (one patient) after maximal medical therapy. Two patients who began medical therapy less than three weeks after the onset of symptoms have done well. Early diagnosis of Acanthamoeba keratitis appears critical for successful medical therapy. Penetrating keratoplasty continues to have a central role in the management of more advanced cases that are unresponsive, or only transiently responsive, to medical therapy.

Bilateral calcified chronic subdural hematoma. Further pathogenetic and clinical consideration on the so-called "armored brain".

Calcified chronic subdural hematomas after shunting procedures for treatment of hydrocephalus have been rarely described. When the calcified wall is so large to extensively cover the surface of the cerebral hemispheres, this instance has been defined "Armored Brain". The Authors report the case of an eleven-year-old patient affected by triventricular hydrocephalus due to aqueductal stenosis, that was treated by a ventriculoatrial shunt. The post-operative course was uneventful and the patient recovered completely from the preexisting neurological deficits. Nevertheless, a CT scan performed 2 and 1/2 years later, revealed the development of a bilateral calcified chronic subdural hematoma, to such extent to configure a so-called "Armored Brain". Clinical course, pathogenesis and treatment of such kind of pathology are discussed in light of the data reported from the literature.