Maciej Radek

Overexpression of prothymosin alpha is related to pituitary adenoma recurrence but not to adenoma invasiveness and proliferation

INTRODUCTION Prothymosin alpha (ProTα) is a peptide initially considered as a thymic hormone, but further studies have shown its wide distribution in different tissues and organs. It has a prevalent nuclear localisation and is thought to be involved in the control of proliferation and apoptosis. In earlier studies, the overexpression of ProTα was found in several human tumours, including pituitary adenomas. The present study deals with the relations of ProTα to the pituitary adenoma hormonal phenotype, proliferation, recurrence and invasiveness. MATERIAL AND METHODS Sixty two pituitary adenomas were included in the study. The invasiveness of the tumours was estimated before surgery by means of magnetic resonance imaging. The paraffin sections of the tumours were immunostained with an antibody against the C-terminal fragment (101-109) of ProTα and with anti-Ki-67 antibody. The hormonal phenotype of the investigated pituitary adenomas had been established previously by means of immunostaining with antibodies to pituitary hormones (GH, PRL, FSH, LH, TSH, ACTH and α-subunit). RESULTS Strong immunostaining with anti-ProTα antibody occurred in the subpopulation of cell nuclei and the walls of intratumoural blood vessels. ProTα index is higher in clinically non-functioning pituitary adenomas (CNFPA) compared to any type of functioning adenomas. There was no difference in the percentage of ProTα- positive cell nuclei in non-invasive vs. invasive adenomas, but it was significantly more frequent in recurrent than in primary tumours. Moreover, the decrease of ProTα index was found in somatotroph tumours treated with somatostatin analogues vs. untreated ones. The percentage of ProTα nuclei did not correlate with Ki-67 index. CONCLUSIONS The overexpression of nuclear ProTα in pituitary adenomas is related to tumour recurrence, but not to proliferation or invasiveness.

Immediate stiffness of the C5-C6 segment after discectomy with the Cloward technique: An in vitro biomechanical study on a human cadaveric model

OBJECTIVE To determine whether the Cloward technique of cervical discectomy and fusion increases immediate postoperative stiffness of single cervical motion segment after application of interbody dowel bone graft. METHODS We measured and compared the stiffness of single-motion segments in cadaveric cervical spines before and immediately after interbody fusion with the Cloward technique. Changes in range of motion and stiffness of the C5–C6 segment were measured in a bending flexibility test (flexion, extension, lateral bending and axial rotation) before and after a Cloward procedure in 11 fresh-frozen human cadaveric specimens from the 4th through the 7th vertebrae. RESULTS The Cloward procedure produced a statistically significant increase in stiffness of the operated segment in flexion and lateral bending when compared with the intact spine. The less stiff the segment before the operation, the greater the increase in its postoperative flexural stiffness (statistically significant). The Cloward procedure produced nonuniform changes in rotational and extensional stiffness that increased in some specimens and decreased in others. CONCLUSION Our data demonstrate that Cloward interbody fusion increases immediate postoperative stiffness of an operated segment only in flexion and lateral bending in cadaveric specimens in an in vitro environment. Thus, Cloward fusion seems a relatively ineffective method for increasing the stiffness of a construct. This may add to discussion on the use of spinal instrumentation and postoperative management of patients after cervical discectomy, which varies from bracing in hard collars through immobilization in soft collars to no external orthosis.

Assessing the correlation between the degree of disc degeneration on the Pfirrmann scale and the metabolites identified in HR-MAS NMR spectroscopy

OBJECTIVE The objective of this study is to assess the correlation between the degree of degeneration of lumbar discs according to the Pfirrmann classification system and the concentrations of metabolites determined by means of 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR MAS NMR) spectroscopy. MATERIALS AND METHODS Twenty-six human intervertebral lumbar discs that were operated on due to degenerative disease were analyzed. Routine preoperative 1.5T, T2-weighed magnetic resonance (MR) images were used to classify the cases according to the Pfirrmann classification system. In all the cases, during microdiscectomy, the fragments of the annulus fibrosus and nucleus pulposus were harvested and their metabolic profile was examined by means of 1H HR MAS. The grades of disc degeneration on the Pfirrmann scale were correlated with the metabolite concentrations. RESULTS Spectral analyses of the intervertebral discs with Pfirrmann grades IV and V demonstrated significantly higher concentrations of creatine, glycine, hydroxyproline, alanine, leucine, valine, acetate, isoleucine, α,β-glucose, and myo-inositol, and a lower intensity of the N-acetyl peak of chondroitin sulfate, compared to the spectra with Pfirrmann grade III. CONCLUSION Our results demonstrate correlations between metabolite concentrations and the degree of lumbar disc degeneration assessed using the Pfirrmann grading system and provide another step toward the potential use of in vivo MR spectroscopy for investigation of biomarkers in lumbar disc degeneration.

Percutaneous balloon kyphoplasty in the treatment of painful vertebral compression fractures: Effect on local kyphosis and one-year outcomes in pain and disability

BACKGROUND AND PURPOSE The aim of the study was to determine the effectiveness of percutaneous balloon kyphoplasty for treatment of compressive vertebral fractures. MATERIALS AND METHODS A retrospective analysis was conducted on 24 patients with 58 symptomatic vertebral fractures treated by balloon kyphoplasty. Visual Analogue Pain Scale (VAS) and Oswestry Disability Index (ODI) were used to assess fracture-related pain and patients disability: preoperatively and within 12-months follow-up. Following the procedures to evaluate the change of vertebral deformity, the angle of local kyphosis was measured. RESULTS Preoperative VAS score was 6.54, at discharge it significantly regressed in 95.8% of patients. The overall VAS score at discharge was 1.25 and within 12 months decreased to 0.26. Preoperative ODI score was 50%, at follows-up in all patients it decreased, ranging from 21% to 10%. Reduction of local kyphosis was achieved in 30 (51.7%) vertebrae by average 4.3°. In 9 (37.5%) patients kyphosis of all augmented vertebrae was reduced, in 7 (29.2%) patients procedures reduced kyphosis in part of augmented vertebrae and in 8 patients (33.3%) kyphosis remained unchanged. Asymptomatic complications included cement leak in 10 (17%) vertebrae and intraoperative rupture of 4 (4%) balloons. CONCLUSIONS Rapid significant pain relief after kyphoplasty followed by long-term pain release and disability reduction obtained in all patients was most probably the result of vertebral augmentation. The correction of local kyphosis had no influence on the outcome.

The antero-lateral approach with corpectomy in the management of the ventral meningioma of the spinal canal

The authors present the anterior approach to cervical spine, which enabled complete resection of tumor located in the anterior part of the spinal canal. Considering there are not many reports in the literature, the authors present a case of a meningioma at the level C5-C6 resected with good result through anterolateral approach.

Expression of follicle stimulating hormone receptors in pituitary adenomas — a marker of tumour aggressiveness?

INTRODUCTION In our earlier study, we found that pituitary adenomas, like other human tumours, express ectopically follicle stimulating hormone receptors (FSHR) in intratumoural blood vessels endothelia and/or tumoural cells. The aim of the present paper was to provide more detailed data on FSHR expression in different subtypes of pituitary adenomas and to evaluate its possible role as a prognostic and/ or predictive biomarker in these tumours. MATERIAL AND METHODS Forty two pituitary adenomas, surgically removed, were immunostained with antibodies against the pituitary hormones, antigen Ki-67 and 1-190 fragment of FSHR. RESULTS The positive FSHR immunostaining was found in blood vessels endothelia of 88% of adenomas and in tumoural cells of 40% adenomas. In tumoural cells, the incidence of at least moderate FSHR immunostaining is significantly higher in invasive tumours (68%) compared to non-invasive (12%) ones, and higher (albeit not statistically significantly) in invasive-proliferating adenomas (Ki-67 > 3%, grade 2b) compared to invasive but non-proliferating (Ki-67 < 3%, grade 2a) ones. CONCLUSIONS The present study confirms that pituitary adenomas ectopically express FSHR in intratumoural blood vessels endothelia and tumoural cells. Moreover, the expression in tumoural cells is prevalent in invasive and proliferating adenomas vs. non-invasive and non-proliferating tumours.

Neurofibromatosis type 2 (NF 2) or schwannomatosis? – Case report study and diagnostic criteria

INTRODUCTION Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25,000 and 1:40,000. The genes associated with the development of the aforementioned disorders are located on chromosome 22 and lay in proxmity. Schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. CASE REPORT Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1-C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. CONCLUSIONS The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely.

An evaluation of the effects of somatostatin analogue therapy in non-functioning pituitary adenomas in comparison to acromegaly

INTRODUCTION Non-functioning pituitary adenomas (NFPA) are often diagnosed late as invasive macroadenomas. The surgical resection is usually incomplete and about 50% of patients require additional surgery. Recent data suggest that somatostatin analogues (SSA), so important in the pharmacotherapy of acromegaly, can also be effective in the management of NFPA. MATERIAL AND METHODS We analysed data of patients who had been treated up to 10 years previously with SSA: 40 with acromegaly (23 - primary, 17 - recurrent tumours) and 22 with NFPA (4 - primary, 18 - recurrent tumours). Hormonal profile, dynamics of tumour size change, ophthalmic syndromes, somatostatin receptor (SSTR) scintigraphy, and immunohistochemistry of SSTR subtypes of operated tumours as well as side effects were investigated. RESULTS Biochemical cure of acromegaly was achieved in 57.5% of patients, while reduction of tumour size was observed in 37% of patients and it was more frequent in not-operated cases. Regarding NFPA, stabilisation of tumour size was noticed in 68% of patients. Tumour shrinkage was reported in 9% of cases, but in 23% of the study group the adenoma size increased with indication for reoperation. CONCLUSIONS The efficacy of SSA in NFPA is much lower in comparison to their well-established effects in the treatment of acromegaly. Stabilisation of tumour size, which is observed in the majority of NFPA, is significantly more frequent in comparison to the natural history of untreated NFPA and our previous studies as well. Analysis of SSTR subtypes is an argument in favour of introduction of novel broad-spectrum SSA that may be more effective in the treatment of NFPA. Referring to acromegaly, adenoma size decrease was reported more frequently in primary therapy. Considering recurrent tumours better outcomes were achieved in patients who were pre-treated with SSA before planned surgery. (Endokrynol Pol 2016; 67 (3): 292-298).

The assessment of testosterone and radioisotopic index of bone metabolism and bone mineral density in men with testosterone deficiency after one year of testosterone therapy

BACKGROUND Testosterone deficiency in men is characterized by typical symptoms of hypogonadism and negative influence on the preservation of bone mass. In this study, we analysed the relationship between testosterone concentration and bone metabolism. Moreover, we assessed the impact of one-year compensation of testosterone deficiency in elderly men on bone metabolism and bone mineral density. Radioisotopic methods of bone metabolism assessment provide new research opportunities. MATERIALS AND METHODS Men with total testosterone concentration (TT) ≤ 3 ng/ml were included into this study. Patients with disorders or injuries of bone system, elevated prostate-specific antigen (PSA), enlarged prostate, disorders of thyroid and liver, diabetes mellitus or a history of chemotherapy as well as those treated for a long time with antibiotics were excluded from this study. The results of 50 men aged 57.52 ± 6.71 years obtained before the treatment (I test) and after one year of oral testosterone supplementation (test II) were analysed in this study. The following examinations and analyses were performed: interview and physical examination, orthopaedic, neurological and urological consultations, blood biochemistry, determination of hormones levels, assessment of Testosterone Deficiency Syndrome (TDS), densitometric and radioisotope assessment of bone metabolism. Moreover, radioisotopic index of bone metabolism was calculated. Testosterone therapy with oral preparation Undestor Testo Caps (Organon) containing 40 mg of testosterone lasted for 12 months. Statistical analysis was performed using Statistica 12 and Excel 2010 programs. Correlations between results before and after treatment were analysed. RESULTS After 12 months of treatment, testosterone concentration increased by mean 78% and the level of luteinizing hormone (LH) decreased by 62%. TDS index increased from 0.53 ± 0.21 (in test I) to 1.91 ± 0.60 (in test II). After the therapy this index was significantly higher in all men (p < 0.0001). Moreover, BMD was also improved following therapy, however, the difference between test I and II was statistically insignificant. The greatest change was found in case of IBM (Index of Bone Metabolism). We observed a positive correlation between IBM and BMD before treatment (r = 0.7991), however, its strength decreased after one-year therapy (r = 0.6757). CONCLUSIONS In our opinion, IBM is more sensitive than other methods of the assessment of changes occurring in bone system under the influence of testosterone therapy. The observed changes in IBM were proportional to changes in testosterone concentration. Testosterone level, TDS and radioisotopic assessment of bone metabolism may be used as prognostic and therapeutic factors of osteoporosis and bone fractures in elderly men.

Radioisotopic assessment of bone metabolism of the operated vertebra after inter-process stabilizer implantation in the lumbar segment of the spine

Introduction Lack of efficacy of pharmacotherapy and physiotherapy in spinal pain syndrome is an indication for intervertebral stabilizer implantation between the processes in the lumbar segment of the spine. Material and methods The group consisted of 32 patients qualified after radioisotopic single-photon emission computed tomography/computed tomography (SPECT/CT) examinations with assessment of bone metabolism and mineral density. For comparative purposes, the L2 vertebra was defined as normal. Parameters defined in the area of operated vertebrae were comparable to L2. Imaging examinations and a pain intensity test were performed before and 12 months after the procedure. Results In SPECT, osteotropic isotope (OI) activity in spinous bodies and processes was close to L2 values. Density assessed in CT of analysed vertebrae was close to L2. In the control examination, activity of OI in spinous bodies and processes was higher in the procedure area. Under the stabilizer, there was a strong positive correlation with the L2 parameters. The differences were statistically significant (p = 0.0002). The increase of OI activity in the elements above the stabilizer was variable. In the control examination, there was higher density of spinous processes and bodies above and under the stabilizer. The difference, compared to the L2 density, was statistically significant. Conclusions The radioisotopic method with SPECT/CT allows for the precise assessment of bone metabolism in the spine. After the procedure, a negative correlation was observed between bone metabolism changes and pain intensity test results.