Papillary glioneuronal tumor: case report and review of literature.

Papillary glioneuronal tumor (PGNT) is a recently described central nervous system neoplasm that mostly occurs in the supratentorial system, adjacent to the lateral ventricles. In 2007, WHO classified PGNT as grade I neuronal-glial tumor because of the characteristic papillary architecture and bipartite (astrocytic and neuronal/neurocytic) cell population. As a newly established entity of mixed glioneuronal tumor family, PGNT attracted extensive attention recently. In our report we discuss the clinical, neuroradiological and surgical features. The final result is compared with literature data.

Patient-specific instrumentation for total knee arthroplasty: a literature review.

During the past decade, total knee arthroplasty (TKA) has been markedly increased. Recently, patient-specific custom cutting guides have been commercially introduced in order to achieve an accurate component alignment during TKA. In fact, these cutting blocks are specific to a patient's knee anatomy and should help the surgeons to perform bone cuts, reducing the complexity of conventional alignment and sizing tools. Nevertheless, there are critical arguments against patient-specific cutting guides for routine use, such as poor evidence and higher costs. Additionally, there are still no mild and long-term results available that describe the clinical outcomes following patient-specific instrumentation of TKR, cost-effectiveness and lower revision rates. Aim of the current manuscript was to describe the recent improvements of the surgical technique and instrumentation of TKA, reviewing the recent literature concerning the PSI technology.

Internal haemorrhagic pachymeningiosis: specific disease or complication of chronic subdural hematoma? Report of five cases surgically treated and literature review.

BACKGROUND: Internal haemorrhagic pachymeningiosis (IHP) is a rare disease characterized by a fibrous thickening and inflammatory infiltration in dural space mimicking chronic subdural hematoma. The pathogenesis of IHP is not entirely clear yet and treatment is still controversial. OBJECTIVE: We want to emphasize the importance of differentiating pachymeningiosis from chronic subdural hematoma as distinct pathological entities. PATIENTS AND METHODS: The records of five selected cases of IHP histologically confirmed were reviewed, focusing onset, neuroimaging, surgery and outcomes. CONCLUSIONS: IHP is most likely underestimated. Only through multidisciplinary approach it is possible to plane the proper therapeutic strategy. The diagnosis of IHP is confirmed by definitive histology but in some cases is possible with intraoperative frozen section.

From surgery to neurosurgery: our experience on the efficacy of fleece-bound sealing (TachoSil®) for dural repair.

AIM: To report on our routine use of TachoSil® for dural repair in neurosurgical practice. METHOD: TachoSil® has been applied in different fields of surgery thus far. When using TachoSil®, fibrinogen and thrombin is provided locally at the site of the dural defects. Upon contact with fluid, the clotting factors of TachoSil® dissolve and form a fibrin network, which glues the collagen sponge to the wound surface. RESULTS: In our experience, TachoSil® was found to be effective as support for the suture of the dura in patients undergoing spinal and cranial neurosurgical operations. Two illustrative examples are shown. CONCLUSIONS: Our procedure showed that closing the dural defect with TachoSil® is a technically simple, reliable and safe method for patients. Indeed, no post-operative cerebrospinal fluid leakage was observed. Nonetheless, further studies with larger sample size are warranted to confirm the efficacy of TachoSil® patches for dural repair.

Operative case of Langerhans'cell histiocytosis of the skull with dural invasion. An immunohystochemical study of ki-67 expression of eosinophilic granuloma: case report and review of the literature.

Eosinophilic granuloma (EG), Letterer-Siwe disease and Hand-Schuller-Christian disease are collectively called Langherans-cell histiocytosis (LCH). While the latter two are systemic diseases, the former is a localized form of histiocytosis. Solitary EG of the skull are rare lesions characterized by a natural history not well defined yet. In this context, we report a case of a 23-year-old male suffering for a recurrent and progressive right parietal headache. On computed tomography (CT) it was observed an ostelytic lesion which on magnetic resonance imaging (MRI) appeared as an hyperintense soft mass on both T1 and T2 weighted images. The lesion showed a marked and heterogeneous enhancement after gadolinium administration. The surgical excision was complete and the severe headache disappeared. Immunohistochemical analysis of the specimen indicated an eosinophilic granuloma characterized by Ki-67 nuclear antigen expression with a labeling index of 20%. In the pertinent literature we have found two aggressive cases of EG showing the Ki-67 expression with a respectively 6.2% (occipital bone granuloma) and 10% (parietal bone granuloma) labeling index. That high proliferative activity suggests a local Langherans' cell proliferation along with an exuberant inflammatory response and also explains the aggressive clinical course and the rapid expansion of the lesion observed in some rare cases of solitary EG. This is the third case-report of calvarial EG characterized by Ki-67 nuclear antigen expression.

Schwannoma of median nerve at the elbow. Case report and short review of the literature.

The Authors present a case of rare elbow localization of schwannoma of the median nerve, in 42 year old woman. The surgical treatment and the short follow-up are presented.

Therapeutic strategy of late cerebral radionecrosis. A retrospective study of 21 cases.

AIM: Late cerebral radiation necrosis (LCR) is a serious complication of radiation treatment for brain tumors. This study investigates the diagnosis and management of patients with late clinical and neuroradiological cerebral radionecrosis after primary removal of brain neoplasm. The authors discuss the clinical features and long-term outcome of 21 patients with late cerebral radionecrosis and emphasize the importance of surgical and medical therapy. METHODS: Twenty-one patients with brain tumor treated by surgical resection or brain biopsy alone after radiotherapy during follow-up developed radionecrosis. The magnetic resonance imaging (MRI), surgical and clinical findings of these patients with radionecrosis are reviewed. RESULTS: MRI showed radionecrosis in 21 patients, 9 of which had undergone craniotomy for lesion removal. CONCLUSION: Late radionecrosis is infrequent following radiation therapy and may simulate tumor recurrence on MRI scans. From the authors' experience it is evident that, once begun, radiation treatment of neoplastic lesions can lead to complications such as late cerebral radionecrosis which often require surgical treatment. As correct diagnosis is necessary for appropriate treatment, a fair balance needs to be struck when considering ionizing radiation, medical therapy, surgery and diagnostic imaging.

Total occlusion of a conus medullaris pial arteriovenous malformation obtained with one session of superselective embolization.

The authors report about a case of the endovascular treatment of a pial arteriovenous malformation (AVM). The lesion was located on the conus medullaris. This injury is a rare spinal AVM. The diagnostic management and surgical treatment was chosen with a collaboration between neurosurgeons and neuroradiologists. The diagnostic management was based on clinical validation and magnetic resonance with angiographic technique as a gold standard. With regard to the surgical treatment of spinal AVM, endovascular and radiotherapy is a decision which should be taken multidisciplinarily. The treatment is crucial in resolving this lesion. The authors describe the case of a 38-year-old girl with clinical findings of progressive radiculomedullary ischemic process caused by the presence of spinal AVM. The angiographic images showed a pial AVM of the conus medullaris fed by an anterior radiculomedullary artery (Adamckiewiz artery) originated from a left T11 dorsospinal artery and by a posterior radiculopial artery originated from the left L1 artery. The draining veins were posterior pial veins, and accessory anterior subpial veins. Even if the first treatment of a pial arteriovenous malformation (AVM) of conus medullaris can be the surgical treatment for posterior localization, a neurointerventional angiographic and modern materials make it possible to reach pial AVMS of conus medullaris avoiding surgery. The authors describe a successful treatment of conus medullaris arteriovenous malformation with a one session of superselective embolization.

Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors.

UNLABELLED: Pentraxin 3 (PTX3) is an acute phase protein strongly expressed by advanced atherosclerotic lesions. We investigated (a) PTX3 expression and secretion in subcutaneous adipose tissue (SAT) and omental visceral adipose tissue (VAT) obtained from 21 obese (37.4+/-8.15 yr) and 10 normal weight subjects (43.7+/-11.07 yr) and (b) the relationships of adipose PTX3 with tumour necrosis factor alpha (TNFalpha) and adiponectin expression and with cardiometabolic risk factors. Real-time PCR was used to quantify specific mRNA for PTX3, CD68 (macrophage marker), TNFalpha and adiponectin. Fresh adipose tissue was cultured and PTX3 measured in the medium. Serum insulin, glucose, HDL and LDL cholesterol, triglycerides, C-reactive protein (CRP), fibrinogen, adiponectin, TNFalpha and PTX3 were measured. PTX3 expression was similar in the two fat compartments and tended to be higher in obese than in normal weight subjects in VAT only (p=0.05). CD68 and PTX3 expressions were correlated with each other in SAT but not in VAT. After adjustment for age and sex, VAT-PTX3 expression and release were correlated with VAT-TNFalpha expression (p<0.01 for both) and with LDL/HDL ratio (p<0.01 and p<0.001). VAT-PTX3 expression was also correlated with BMI, triglycerides, CRP, fibrinogen and adiponectin (p<0.05 for all). In the multivariate analysis with VAT-PTX3 RNA levels as dependent variable, LDL/HDL ratio and fibrinogen remained independently associated with VAT-PTX3 expression (p<0.01 for both). These associations were not seen within SAT. CONCLUSIONS: Human adipose tissue expresses and releases PTX3 likely under TNFalpha control. VAT production of PTX3 seems to contribute to the mechanisms underlying the development of atherosclerosis.

Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells.

Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells.

Adult stem cells: the real root into the embryo?

During embryonic development, a pool of cells may become a reserve of undifferentiated cells, the embryo-stolen adult stem cells (ESASC). ESASC may be responsible for adult tissue homeostasis, as well as disease development. Transdifferentiation is a sort of reprogramming of ESASC from one germ layer-derived tissue towards another. Transdifferentiation has been described to take place from mesoderm to ectodermal- or endodermal-derived tissues and viceversa but not from ectodermal- to endodermal-derived tissues. We hypothesise that two different populations of ESASC could exist, the first ecto/mesoblast-committed and the second endo/mesoblast-committed. If confirmed, this hypothesis could lead to new studies on the molecular mechanisms of cell differentiation and to a better understanding of the pathogenesis of a number of diseases.

Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia?

INTRODUCTION: Morphological anomalies of the extracranial internal carotid artery (ICA) cause symptomatic cerebrovascular insufficiency in 4-16% of the cases. The aim of the present study is to evaluate macroscopic and microscopic features of a group of extracranial ICA anomalies, specifically kinking, coiling, and tortuosity, eventually affecting the surgical approach. MATERIALS AND METHODS: From January 2003 to December 2005, 10 out of 169 (6%) revascularized patients (pts) were operated upon because of an ICA anomaly. They were all but two symptomatics. Seven pts were treated by ICA transection and end-to-side reimplantation of the ICA at the level of the carotid bulb; three pts were treated by ICA resection and end-to-end anastomosis. In all the cases a segment of ICA was resected; in three cases one more segment was also obtained from a common carotid artery (CCA) and these specimens were histologically examined. Patients were followed-up through a 3-year period. RESULTS: No pts died and none suffered of neurologic events. Duplex scan and arteriographic postoperative control showed the correct surgical reconstruction. Matching preoperative clinical findings with presence or absence of significant atherosclerotic stenotic lesion, we found out a positive cerebral CT in one pt (20%) in both groups; fluent neurological deficit was preeminent in pts with pure ICA anomalies (40% vs. 0%) (P = 0.2); pts with pure ICA anomalies were significantly younger than 65 years old (80% vs. 0%) (P = 0.03) and males were more involved by pure ICA anomalies (60% vs. 40%) (P = 0.1). The histological examination of ICA specimens showed a reduction of elastic fibers and muscular cells with a compensative increase of connective fibers. CONCLUSIONS: At our knowledge this is the first study focused on ICA anomalies like kinking, coiling, and tortuosity, comparing histologic features of CCA and ICA specimens coming from the same affected carotid axis. Our results, although preliminary, show elastic and muscular tissue substituted by loose connective tissue, configuring a metaplasia of tunica media limited to the ICA. Our hypothesis is that extracranial ICA, being a segment of transition between an elastic vessel (CCA) and a muscular vessel (intracranial ICA), is particularly subject to metaplastic transformation, analogously to other transition zones in human body. Our purpose is now to confirm by ultrastructural and molecular biology techniques, in a wider series, the presence of this metaplasia, since this could condition also the revascularization techniques.

Scleroderma fibroblasts constitutively express the long pentraxin PTX3.

OBJECTIVE: PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein) and of an unrelated N-terminal domain. Unlike the classical pentraxins, PTX3 is expressed in response to IL-1beta and TNF-alpha but not to IL-6. The present study was designed to investigate the expression of PTX3 in normal and scleroderma fibroblasts. METHODS: Normal and SSc fibroblasts were cultured in the presence and absence of inflammatory cytokines. PTX3 mRNA expression in fibroblasts was evaluated by Northern analysis. PTX3 protein levels in fibroblast culture medium were estimated by ELISA. RESULTS: Normal fibroblasts were induced to express high levels of P7X3 mRNA by IL-1beta and TNF-alpha but not by other cytokines or growth factors. Scleroderma fibroblasts, unlike normal fibroblasts, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in SSc fibroblasts was not modified by anti-TNF-alpha antibodies or IL-1 receptor antagonist. In contrast, IFN-gamma and TGF-beta inhibited the constitutive but not the stimulated expression of PTX3 in SSc fibroblasts. CONCLUSIONS: PTX3 is a main feature of activated scleroderma fibroblasts.

Interleukin 2 and interleukin 15 differentially predispose natural killer cells to apoptosis mediated by endothelial and tumour cells.

Human natural killer (NK) cells constitutively express the beta- and gamma-chains of the interleukin 2 (IL-2)/IL-15 receptor, and both IL-2 and IL-15 are able to activate NK cell proliferation and cytotoxicity. When IL-2-primed human NK cells are exposed to sensitive targets (i.e. K562) they undergo apoptosis mediated by the beta(2)-integrin CD18. Here, we demonstrate that: (i) endothelial cells, similar to K562 tumour target cells, induce apoptosis of IL-2-primed NK cells; (ii) endothelial- and K562 cell-induced apoptosis is significantly lower in IL-15 than in IL-2-stimulated NK cells; (iii) a critical role in the apoptosis of IL-2-primed NK cells is played by the alpha-chain of the IL-2 receptor. Our data show for the first time that IL-2-activated NK cells can die by apoptosis upon contact with the vascular endothelium, which is a necessary step for their extravasation, with a direct pathophysiological relevance on the strategy of adoptive immunotherapy of cancer. On the other hand, IL-15, although generating a similar level of activation of NK cells, largely prevents their apoptotic fate. Therefore, IL-15 produced early in the immune response, when T cells are not yet activated, generates lymphokine-activated killer cells that are efficient killers relatively protected from apoptosis. Once activated, T cells produce IL-2 that overcomes the effect of IL-15 on NK cells, paving the way for their death by apoptosis.

[Role of inflammation mediators in the pathogenesis of heart failure]. / Ruolo dei mediatori dell'infiammazione nella patogenesi dello scompenso cardiaco.

A number of factors are involved in congestive heart failure pathogenesis. Among these, inflammatory mediators could have a crucial role. Patients with congestive heart failure show increased plasma levels of "proinflammatory cytokines", in particular tumor necrosis factor-alpha and interleukin-6. Clinical and experimental models have demonstrated that these cytokines induce left ventricular dysfunction, pulmonary edema, ventricular remodeling, skeletal muscle abnormalities, myocyte apoptosis and endothelial dysfunction, suggesting the possibility that increased plasma concentration of cytokines could not be just an epiphenomenon, but an effective pathogenetic mechanism of disease progression. Additional inflammatory proteins involved in the acute phase response could play a part in the pathogenesis of heart failure. Pentraxin 3 is a prototypical long pentraxin, structurally related, although with different functions, to C-reactive protein, is produced by immune system cells, fibroblasts and particularly by cardiac endothelial cells and myocytes, as demonstrated in murine and human models. Its synthesis is rapidly induced after exposition to bacterial lipopolysaccharide and proinflammatory cytokines, as interleukin-1beta and tumor necrosis factor-alpha. In heart diseases, pentraxin 3 could be involved in the acute local inflammatory response to myocardial injury (e.g. necrosis) and in heart failure pathogenetic mechanisms, but its exact role is not yet settled. Defining the specific part played by these molecules in the pathogenesis of heart failure could lead to new therapeutic approaches in the treatment of cardiac insufficiency.

PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation.

OBJECTIVE: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. RESULTS: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. CONCLUSION: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.

The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells.

Pentraxins are acute-phase proteins produced in vivo during inflammatory reactions. Classical short pentraxins, C-reactive protein, and serum amyloid P component are generated in the liver in response to interleukin (IL)-6. The long pentraxin PTX3 is produced in tissues under the control of primary proinflammatory signals, such as lipopolysaccharide, IL-1 beta, and tumor necrosis factor-alpha, which also promote maturation of dendritic cells (DCs). Cell death commonly occurs during inflammatory reactions. In this study, it is shown that PTX3 specifically binds to dying cells. The binding was dose dependent and saturable. Recognition was restricted to extranuclear membrane domains and to a chronological window after UV irradiation or after CD95 cross-linking-induced or spontaneous cell death in vitro. PTX3 bound to necrotic cells to a lesser extent. Human DCs failed to internalize dying cells in the presence of PTX3, while they took up normally soluble or inert particulate substrates. These results suggest that PTX3 sequesters cell remnants from antigen-presenting cells, possibly contributing to preventing the onset of autoimmune reactions in inflamed tissues. (Blood. 2000;96:4300-4306)

Age-related changes in skeletal muscle fiber composition in two swine muscles.

This study focuses the aging-related modification of skeletal fiber types in two skeletal muscles of different-age swine (6 and 18 month). Rectus abdominis and vastus medialis were employed. It was performed an immunohistochemical staining for slow fibers and it was made a quantitative evaluation, using an automatic interactive image analysis system. The percentage of slow fibers decreased in adult swine. Moreover, slow fibers in rectus abdominis were less numerous than in vastus medialis. Aging and muscle function are two important factors able to modify fiber types. Morphometric analyses can ascertain this modification for diagnostic or nourishmental purposes.

Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease.

Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 +/- 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 +/- 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation co-localized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD.

Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians.

Several lines of evidence point to a profound remodelling of the cytokine network in healthy elderly subjects, with decreased type-1 cytokine production (IL 2) and a shift to type 0 and 2. We have also observed an increase of proinflammatory cytokines (IL-1, IL-6, TNF-alpha) in vitro, and an increase of circulating stem cell factor in vivo. In this setting, we studied changes of chemokines (MCP-1 and RANTES) with aging, as well as other molecules, namely, sTNF-RI and sTNF-RII, and the soluble form of the CD30 molecule (sCD30), involved in the pro- and antiinflammatory cytokine balance. The subjects enrolled in the study belonged to three different selected healthy groups of young, aged and centenarians. The presence of rheumatoid factor (RF) and antinuclear antibodies (ANA) was simultaneously assessed. The results show that MCP-1 serum levels were higher in the healthy aged and lowest in the young, while RANTES increased exclusively in centenarians. Only centenarians had autoantibodies (ANA and RF). sTNF-RI and sTNF-RII were significantly elevated in healthy old subjects compared to the young, and even higher in selected centenarians compared to the other age groups. sCD30 serum levels were significantly raised in centenarians compared to the young, despite absence of circulating CD30+ cells in the peripheral blood of the whole study population. No relationship among serum values of these different members of the TNF-R family was found, despite a strong correlation for sTNF-RI and sTNF-RII in all groups. We hypothesize that the increased chemokine levels in aged people, and raised sCD30 levels in centenarians, may reflect a general shift towards type 0/2 cytokines in normal aging, which may be responsible, at least in part, for the appearance of circulating autoantibodies without definite clinical consequences at advanced age.