[The role of matrixmetalloproteinases in the tumor growth and metastasis].

Many authors have described the role ofmatrixmetalloproteinases (MMP) in tumor invasion. MMPs are a family of zinc-dependent endopeptidases, which through degradation of the extracellular matrix (ECM) and the basal membrane induce tumor spread and metastasis. There are more than 20 enzymes classified into 6 groups: Collagenases (MMP-1,-8,-13 and -18), Gelatinases (MMP-2 and MMP-9, Stromelysins (MMP-3,-7,-10,-11,-26,-27), Elastases (MMP-12), Membrane type specific MMPs (MMP-14,-15,-16,-17,-24 H -25) and other MMPs (MMP-19,-20,-28,-21,-22,-23). Many authors have demonstrated a positive correlation between the pattern of MMP expression and the tumor invasive and metastatic potential including: rectal and gastric cancer, lung carcinoma, breast, ovarian, prostate, thyroid cancer and brain tumors. The increased expression of tissue inhibitors of MMPS (TIMPs) is a response against the tumor progression leading to suppression of the MMP-activity and preservation of the ECM integrity. Due to the dual role of TIMPs, which together with MT1-MMP activate pro-MMPs it is possible that the correlation between activator/inhibitor is the one defining the tumor growth and metastasis.

[Late metastases from breast cancer--report of two cases].

INTRODUCTION: Breast cancer is amongst the commonest reasons for brain metastases involving 15-20% of the patients. Metastases discovered 10 or more years after the initial diagnosis of breast cancer are defined as late metastases and present a rare event. We present two cases of late brain metastases of breast cancer discovered 15 and 17 years after initial diagnosis. MATERIALS AND METHODS: In a 46-year old female patient a 5 x 6 cm lesion in the breast was observed and was histologically diagnosed to be a breast invasive ductal carcinoma. Mastectomy was performed (TNM grade - T2N1bM0) with postoperative radiotherapy (40 Gy for 20 days) combined with chemotherapy. All control investigations were normal for the next 17 years. During the last examination CA-15-3 levels were raised. CT scan revealed a lesion involving the frontal, temporal and parietal bones and the adjacent soft tissues as well as dura mater and the subdural space. Gross total resection was performed. In a 38-year old female patient a 3 cm lesion in the breast was observed and was histologically diagnosed to be a low differentiated invasive ductal breast carcinoma. Radical mastectomy was performed TNM grade (T2N1M0) with radio- and chemotherapy. For 13 years all control markers were negative. Last examination demonstrated increase of CA-15-3 levels. Due to complain of headache and nausea CT scan was performed showing a tumor lesion in the right frontal lobe. Gross total resection was performed. CONCLUSION: In the presented cases we describe late brain metastasis from breast cancer 15 and 17 years after initial diagnosis. This observation is important because, regular followup for patients with breast cancer is 6-10 years. Obviously this approach in clinical practice could lead to mistakes and misdiagnosis of these rare lesions. Based on our experience we suggest that the follow-up, in patients treated for breast cancer, even with apparently total regression of the disease, should be extended beyond the routine period of 10 years and tumour markers should be investigated regularly. Metastasis in CNS should be taken into consideration in patients treated for breast cancer no matter the time from the initial diagnosis when clinical symptoms appear.

[Sciatic xeuropathy secondary to compression by a heterotopic ossification due to myositis ossificans traumatica. (Case report and review of the literature)].

We describe a case of sciatic nerve entrapment neuropathy due to a posttraumatic heterotopic ossification (myositis ossificans traumatica). A 52 y.o. man was examined complaining from right lower limb pain and weakness progressing for one year after a blunt trauma and a hematoma of the hip. Clinical examination demonstrated sciatic nerve palsy with pain and paresthesia felt distal to the lesion. Electrodiagnostic studies show severe denervation changes in the tibialis anterior, extensor digitorum brevis and gastrocnemius muscles. Both radiography and CT scan revealed new bone formation in the soft tissue in the upper third of the hip. Surgical exploration discovered an osseous tunnel in the fascial plane between the semitendinous and biceps femoris muscles, encasing the sciatic nerve in a length of 12 cm. The lesion was hard and intimately associated with the epineuria. Histopathological examination of the lesion demonstrated mature, lamellar bone structure. Under optical magnification the ectopic bone was totally removed and decompression of the sciatic nerve was achieved. Nevertheless neurological recovery was absent at one year follow-up after surgery.

[Application of intervertebral carbon implants for the treatment of cervical disk herniation].

INTRODUCTION: We are presenting our preliminary experience with the cervical intervertebral carbon cages (CICC) as a treatment option for interbody fusion in cases with cervical disk herniation. MATERIAL AND METHODS: For the period 08.2003-08.2004, 33 CICC were been implanted in 20 patients. Mean age--45 years, M:F = 12:8. In 10 cases (50%) we implanted 1 CICC, in 8 (40%)--2, in 1 (5%)--3, and in 1 (5%) case we implanted 4 CICC. In 40% the affected level was C5-6, in 30%--C6-7, in 15%--C3-4 and in 15%--C4-5. Large CICC (L) were used in 11 cases and small (S)--in 22. The most frequently used height of the CICC was 5 mm. RESULTS: In all the cases of our series CICC ensured the preservation of normal anatomical relationships in the treated segment and avoidance of the donor-site morbidities. No additional surgical time was needed for the procedure. No complications related to the CICC implantation were observed. A favorable clinical outcome has been observed in all cases. CONCLUSION: Our preliminary experience confirmed that the CICC present a safe and reliable alternative to the allo- and autogenous bone grafts.

[Primary ectopic intraosseous meningioma associated with multiple meningioma in a patient with central neurofibromatosis].

We present a case of multiple meningiomas (MM) as initial manifestation of central neurofibromatosis (NF2). A 19 y. o. woman was admitted with increasing signs of spinal cord compression at Th5-7 level. At CT assisted myelography, an entirely extradurally situated meningioma was detected and totally removed. Two years later increasing right-sided exophthalmos, without visual impairment was observed. The CT scan revealed thickening and abnormal shape of the sphenoid and the bony structures of the orbit. The retrobulbar space was narrowed and the optic nerve was shifted. At operation, ala parva of the sphenoid bone, the roof and the lateral orbital wall appeared thickened, laminated, fragile and exceedingly vascularized. The subdural space was found intact. The histopathological study revealed primary intraosseous meningioma of the sphenoid. There was no family history for neurofibromatosis (NF). The clinical findings at this time could not fulfil the criteria for NF2 and the case was considered as "true" multiple meningiomas occurring in different compartments of the neuraxis. The cytogenetical examination demonstrated a deletion of the long arm of the chromosome 22: 46 XX, del 22 (q 11.2). She was followed up and five years after the initial symptoms asymptotic bilateral vestibular schwannomas were found at CT and MRI. These findings finally led to the diagnosis NF2. There are no specific features distinguishing true MM from those associated with NF2, but we recall the importance of such manifestations for this diagnosis. We have not found any comparable case with these features in the medical literature.

[Multiple meningiomas. Part II. Sporadic multiple meningiomas (report of 19 cases and review of the literature)].

The objective of the investigation was to document the clinical presentations of a group of 19 patients with sporadic multiple meningiomas without evidence of NF2. The male/female ratio was 4/15. The mean age at the time of presentation was 54.95 years. The diagnosis of the clinically significant tumours was demonstrated in each patient with MRI and CT of the head and spine. Histopathological findings in all tumour specimens demonstrated benign (WHO grade I meningiomas). Meningiomas were localized in a higher incidence in the supratentorial space. The management of multiple meningiomas is discussed and the contemporary literature on this topic is briefly reviewed.

[Neurofibromatosis type 2--initial symptoms and diagnostic problems]. / Nevrofibromatoza tip 2--nachalni simptomi i diagnostichni problemi.

The presenting symptoms in a group of 16 NF2 patients treated in neurosurgical tertiary referral centers are reviewed. Eight of the cases are distinct severe forms (Wishart type) and one demonstrated a mild disease course (Gardner type). Fourteen cases represent new mutations. The mean age of onset was 17.88 years. Twenty-five percent of the cases initially fulfill the established diagnostic criteria. More than a half of the patients presented initial symptoms related to tumors other than vestibular schwannomas. The mean interval between the age of onset and the age at diagnosis was 7.19 years. The reasons of the delay are discussed.

High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

[Neurofibromatoses. Types, classification and diagnostic criteria]. / Nevrofibromatozi. Vidove, klasifikatsiia i diagnostichni kriterii.

According to the worldwide-accepted classification of the neurofibromatoses only neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) are well defined. Other described forms of neurofibromatosis are rare. The aim of this paper is to review the contemporary classification and diagnostic criteria of the different types of neurofibromatoses.

[Multiple meningiomas. Part I. Types. Classification. Differential Diagnosis]. / Mnozhestveni meningiomi. Chast I. Vidove. Klasifikatsiia. Diferentsialna diagnoza.

Meningiomas usually are solitary tumors but they can be multiple in various conditions. True multiple meningiomas in the sense of Cushing are rare. The development of more than one meningioma in the same individual may be due to central neurofibromatosis or following external cranial irradiation. Multiple meningiomas can occur after dissemination of the tumor cells following surgery. The purpose of this review is to define and discuss the different types and the criteria of differential diagnosis for MM.

[Lipoma of the temporal lobe]. / Lipom na temporalniia mozuchen dial.

This is a case report on a 16-year-old girl presenting lipoma located in the temporal cerebral lobe, in conjunction with an ever increasing frequency of epileptic seizures, unresponsive to the anticonvulsive treatment carried out. A comprehensive analysis is done of the data concerning clinical course, diagnostic examinations' specificity and microsurgical removal of the lipoma with ensuing optimal postoperative results--total abatement of epileptic seizures against the background of reduced anticonvulsive therapy throughout the 3.5 years observation period. The literature survey shows that intracranial lipomas with the location described represent as casuistic rarity.