Non-invasive real-time biopsy of intracranial lesions using short time expanded circulating tumor cells on glass slide: report of two cases.

BACKGROUND: Circulating Tumor Cells (CTCs) are promising biomarkers for monitoring solid cancer and were used to monitor brain tumors. Here we report two cases in which, for the first time, CTCs were used in cytological diagnostic evaluation to discriminate a space-occupying lesion of the brain. CASE PRESENTATION: Two cases of focal intracranial lesions, unclassified for diagnosis, untreated and apparently symptomatic, were examined after high-contrast resolution Magnetic Resonance Imaging and/or Computed Tomography scans. CTCs were seeded on chamber slides and short-time expanded under the optimized conditions as we previously reported. The first case was a focal lesion localized in the parietal-occipital area in a 67-year-old woman. The second case was a 31-year-old man with an expansive intracerebral lesion localized in the left peri-trigonal area. Both patients underwent excisional biopsy. Histopathological evaluation of the biopsy confirmed the previous cytological diagnoses, and the analysis of the clinical outcomes retrospectively validated both diagnoses. CONCLUSIONS: The cases here reported illustrate the potential for using expanded CTCs as non-invasive, real-time biopsy. Moreover, non-invasive real-time biopsy can represent an alternative diagnostic tool to be used when a functional area of the brain is at risk of injury from excisional biopsy procedures.

Analysis of UbcH10 expression represents a useful tool for the diagnosis and therapy of astrocytic tumors.

Previous studies suggest the expression of UbcH10 gene, that codes for a protein belonging to the ubiquitin-conjugating enzyme family, as a valid indicator of the proliferative and aggressive status of tumors of different origin. Therefore, to look for possible tools to be used as diagnostic markers in astrocytic neoplasias, we investigated UbcH10 expression in normal brain, gliosis and low-grade and high-grade astrocytic tumors by immunohistochemistry. UbcH10 expression was observed in low-grade astrocytoma and in glioblastoma. Our data indicate a clear correlation between UbcH10 expression and the histological grade of the astrocytic tumors. Moreover, the analysis of UbcH10 expression allows the differentiation between gliotic and malignant tissues. Finally, since proteasome inhibitors have recently been considered as possible drugs in the chemotherapy of various tumors, our results would suggest new perspectives for the treatment of brain malignancies based on the suppression of the UbcH10 function.

Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour.

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual's diagnosis and/or help clarify risk in healthy populations.

Indications and limits of intraoperative cortico-subcortical mapping in brain tumor surgery: an analysis of 101 consecutive cases.

AIM: Here we report our recent experience in supratentorial cortico-subcortical stimulation mapping during surgery for cerebral lesions closely related to sensorimotor and language areas. METHODS: We retrospectively analyzed clinical data of 101 consecutive patients operated on with the aid of electrical stimulation mapping (ESM). Patients harbored a mass lesion situated in or near language (Group A, 30 patients) and sensorimotor (Group B, 71 patients) areas. RESULTS: A macroscopically complete removal of the tumor was carried out in 22 cases out of 28 of group A and in 57 out of 73 of group B. In the first group there was one postoperative death due to a pulmonary embolism. At a mean follow-up of 24.3 months, 15 patients are still alive, 12 out of them are recurrence free and hold a useful language function, while the other 12 patients had a mean survival time of 19.3 months, with a mean high quality survival period (KPS?70) of 17.8 months. In the second group there was no postoperative death. At a mean follow-up of 24.8 months, 55 patients are alive and 47 maintain a useful motor function. Eighteen patients died for tumor progression, with a mean survival time of 18.7 months. Their median high-quality survival period (KPS ? 70), with preservation of a useful motor function, was 16.5 months. CONCLUSION: When properly indicated and correctly carried out, ESM for language and motor functions allows to enhance resection of lesions in eloquent areas with a surgical permanent morbidity comparable to that for lesion in non eloquent areas.

Antithrombotic effect of indobufen in an experimental model of arterio-arterial microanastomosis in the rat.

Using an end-to-side microanastomosis of the left common carotid into the right common carotid of rats, implementing a potentially thrombogenic situation, we have investigated the possible antithrombotic effect of indobufen, a new antiplatelet drug. In eight of 15 untreated rats the anastomosis was totally obstructed by a single thrombus growing from the anastomotic wall. Indobufen treatment prevented thrombus formation completely in 14 of 15 rats (p less than 0.02). In treated animals indobufen also produced a statistically significant reduction of ADP-induced platelet aggregation relative to basal values. Platelet count were not influenced by drug treatment. Our experimental results suggest the potential usefulness of indobufen as an antithrombotic agent.

Telangiectatic osteosarcoma of the skull. A post-Paget case.

We report a case of post-Paget telangiectatic osteosarcoma of the skull in a 75-year-old woman. Such a neoplasia is a rare variant of osteosarcoma, a tumor rare in the cranic bones. The patient was submitted for a careful analysis by the following procedures: technetium scintigram, X-rays, CT scan, and MRI. After the surgical procedure, pathological examination confirmed the diagnosis. Both radiological and pathological pattern of this tumor are discussed in relation to the differential diagnosis. Our report shows that benign lesions may represent a possible cause of diagnostic errors. They must be excluded by histological analysis.

Calf pseudohypertrophy in a patient with double neurogenic pathology.

A pseudohypertrophy of the calf can be rarely associated with neurogenic pathologies as S-1 radiculopathy, poliomyelitis, spinal muscular atrophy, traumatic lesions of peripheral nerves, intraspinal neurinoma. The causes of this particular phenomenon are unknown. The authors present the case of a 52-year-old man with an enlargement of the left calf suffering from a mild form of spinal paralytic poliomyelitis in the early childhood and episodes of severe left sciatica in the last four years. Electromyography demonstrated a pattern of denervation in both legs and an H-reflex absent when the left tibial nerve was stimulated. An open muscle biopsy of the left calf was performed. Light microscopic and ultrastructural examination of the muscle confirmed the presence of a pattern of "neurogenic type" pseudohypertrophy. Our results could be interesting for the understanding of the mechanism of neurogenic pseudohypertrophy. This case suggests that timing of stimulus or "dose" of denervation may be important factors in such a phenomenon.

Use of chronic sacral nerve stimulation in neurological voiding disorders.

AIM: Neurogenic low urinary tract dysfunctions unresponsive to medical and conservative therapy are difficult to manage. Nowadays they can be treated with Sacral Nerve Stimulation (SNS), even if clinical experiences reported in literature are still limited. METHODS: We performed SNS in 6 patients with neurogenic bladder: 3 patients had incontinence-urgency (1 myelitis, 1 multiple sclerosis, 1 autonomic polineuropathy) and 3 patients had urinary retention (1 incomplete spinal cord lesion, 1 operation for discal hernia T5-T6, 1 hysterectomy). RESULTS: Among cases with incontinence-urgency we achieved complete control of the bladder in 2 patients while in 1 patient the number of urinary losses was reduced of the 80%. In 2 patients with urinary retention we obtained complete recovery of the bladder function, while in 1 patient the number of cateterisms/die reduced of 50%, the urinary volume for micturion increased and residual urinary volume decreased. Results were unchanged during the follow-up (maximum 26 months), except for 1 patient in which a partial loss of effectiveness occurred. CONCLUSIONS: Chronic electric stimulation of S3 sacral roots via an implanted neuroprotesis is therefore an effectiveness, save and promising therapeutic option in treatment of neurogenic bladder dysfunctions.

Symptomatic tension pneumocephalus after evacuation of chronic subdural haematoma: report of seven cases.

We present seven cases of tension pneumocephalus developing after burr hole evacuation of chronic subdural haematoma. After a careful review of the literature we discuss the physiopathology, the diagnosis and the treatment of this complication of chronic subdural haematoma surgery.

Effects of Ginko Biloba and caspase inhibitors on brain ischemia in the Mongolian Gerbil.

AIM: Data reported in previous studies and our own previous experience have led us to explore the mechanism of and the degree of protection afforded by Ginko Biloba in a model of cerebral ischemia in the Mongolian Gerbil evaluating histological and neurological effects in this rodent. METHODS: Mongolian Gerbils were divided into experimental groups: Group A consisted of animals subjected only to experimental ischemia; 5 minutes occlusion of the carotid arteries. Group B consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately before the surgical procedure. Group C consisted of animals subjected to experimental ischemia and to a dose of Ginko Biloba, given intraperitoneally immediately after the surgical procedure. Group D consisted of animals subjected to experimental ischemia and to a dose of the caspase inhibitors z-VAD.FMK and z-DEVD.FMK injected intracerebroventricularly through the right hemisphere before the surgical procedure. Group E consisted of animals subjected to experimental ischemia and to a dose of caspase inhibitors injected after the surgical procedure. Group F consisted of Sham-operated animals. Histological controls were done by H and E and the TUNEL method in the frontal cortex and caudate-putamen. RESULTS: The percentage of normal cells was not statistically significant at analysis with H and E, whereas the TUNEL method showed good protection with Ginko Biloba and caspase inhibitors, when the latter is given in the reperfusion phase. These data were in agreement with data obtained at neurological examination. CONCLUSION: We could say that cellular morphology is in itself an untrustworthy tool for judging the effects of ischemia and protective drugs; the TUNEL method may add important information about the different components of cellular death; the reperfusion phase may be critical for apoptotic phenomena; Ginko Biloba might protect neurons of the frontal cortex from both necrotic and apoptotic death in this model of ischemia.

Tuberculosis of the lower cervical spine: a description of two cases.

Tubercular infection is a rare occurrence in the lower cervical spine. The isolated involvement of the posterior arch is particularly rare, and the very few cases in which it is reported at the thoracic or lumbar levels were principally observed in immunodepressive patients. It is the purpose of this study to describe two cases of tuberculosis of the lower cervical spine with neurological deficit: one expansive neoformation at the level of the arch of C7, with saving of the vertebral body and the discs, and a spondylodiscitis at C4-C5, treated conservatively, the healing process of which was followed by MRI.

Percutaneous treatment of lumbar intervertebral disc hernias with discogel.

A new percutaneous technique for the treatment of the backache and sciatica related to the lumbar disc herniation was applied in 34 patients at 40 levels. The technique is easy, safe, efficacious and without complications. In particular it is useful for the diagnosis and treatment of the underestimated "internal disc disruption" syndrome.

Postoperative intracerebral haemorrhages remote from the site of the initial operation.

Two cases of postoperative intracerebral haemorrhages remote from the site of the initial craniotomy for saccular aneurysms are reported and the other cases from the literature are reviewed. Lack of a good postoperative recovery and the appearance of neurological signs not related to the site of the operation may suggest this complication, which is associated with high mortality and disability rate. The possible pathogeness of those postoperative haemorrhages is discussed.

The extracellular matrix in slow-growing tumors of the central nervous system.

This report describes and illustrates the results of the histopathological and histochemical investigation on five slow-growing tumors of the central nervous system: four meningiomas and an ependymoma of the spinal cord. We have studied, by means of polarizing microscopy, sections stained with picro-sirius red F3BA that enhance the birefringence of collagen and reticulum fibres. The heterogeneous behaviour of the distribution of the collagen let us conclude that the fibrillar component of the extracellular matrix have a scarce importance for the speed of growth of these tumours.

Serum neuron-specific enolase in various pathological conditions.

Quantitative determination of neuron-specific enolase in the serum was performed by RIA method in 18 neurological patients and in 22 patients with pulmonary diseases. The data confirmed that the specificity of this marker is not absolute for the detection both of the nature and of the seat of origin of the disease. Further problems are posed in patients which simultaneously suffer from endocrine, nervous and pulmonary abnormality.

[Histopathologic examination of the intervertebral lumbar disk. Evaluation of its usefulness and limitations]. / L'esame istopatologico del disco intervertebrale lombare. Valutazione dell'utilità e dei limiti.

A retrospective clinical-pathological review of 192 lumbar intervertebral discs removed via an interlaminar approach or percutaneous nucleotomy from patients suffering from sciatic pain was carried out in order to assess if routine examination is useful. Only for a case of our series, which showed ill defined features at preoperative neuroradiologic imaging, an intraoperative pathologic examination was necessary. Immunohistochemical study was never required. A routine examination with a hematoxilin-eosin stain was sufficient also to recognize postoperative scar in patients reoperated. In conclusion we think that routine examination of the intervertebral disc is a procedure which is not expensive and useful to assess the nature of the lesion in reoperated patients and in rare cases showing unclear radiologic pattern.