The acromegalic spine: fractures, deformities and spinopelvic balance.

INTRODUCTION: Axial skeleton arthropathy and osteoporotic vertebral fractures are common findings in acromegalic patients and can result in severe spinal deformity. OBJECTIVE: To investigate the presence of spinal fractures and deformities, sagittal imbalances, and spinopelvic compensatory mechanisms in acromegalics. PATIENTS AND METHODS: 58 patients with acromegaly from a referral neuroendocrinology center were prospectively evaluated by panoramic spine radiographs to detect the presence of fractures and scoliosis, to measure thoracic kyphosis, lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT) and sagittal vertical axis (SVA). Sagittal imbalance criteria were considered: thoracic kyphosis > 50°, PI-LL > 10°, PT > 20° and SVA > 5 cm. Their medical records were analyzed for clinical and laboratorial data. RESULTS: The prevalence of fractures was 13.8%, predominantly in the thoracic spine, with mild and anterior wedge compressions. Scoliosis was present in 34.5% of the cases, all with degenerative lumbar curve apex. Thoracic kyphosis > 50º occurred in 36.8% of patients, PI-LL > 10° in 48.3%, PT > 20° in 41.4% and SVA > 5 cm in 12.1%. CONCLUSION: Increased number of vertebral fractures and high prevalence of spinal deformities related to sagittal imbalance were detected, indicating the importance of monitoring bone comorbidities in acromegaly, with radiological evaluation of the spine as part of the follow up.

Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPA) are classified as benign tumors of slow growth, but 40% of them present local invasion, a characteristic of behavior still unpredictable with the use of current tumor markers. This work aims to evaluate the tissue markers E-cadherin and NCAM, which act on cell adhesion, in tumor tissue samples of NFPA and its relationship with the degree of local invasiveness. Gene expression of E-cadherin (CDH1) and NCAM (NCAM1) was assessed by real-time PCR and tissue expression by immunohistochemistry. Fifty-three patients with macroadenomas were submitted to transsphenoidal surgery, presented grade II invasive adenomas in 16 cases (30.2%), grade III in 7 (13.2%) and grade IV in 30 (56.6%). In the immunohistochemistry, one case was negative for E-cadherin, 7 showed weak immunostaining, 17 moderate and 28 strong, whereas for NCAM, 5 showed negative, 28 weakly, 14 moderate and 6 strong. Regarding gene expression, 43.3% showed expression for CDH1 (mean of 2.12) and 50% for NCAM1 (mean of 1.86). There was no significant correlation between the immunohistochemical expression of the markers, as well as the gene expression, the degree of invasiveness and clinical data. The results suggest that E-cadherin and NCAM markers are not directly related to the invasiveness in NFPA.

PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are prevalent pituitary neoplasms. Because they do not present with hormonal hypersecretion, there is no marker that indicates regrowth or recurrence, as in other adenomas. OBJECTIVES: Evaluate the immunohistochemical expression of PTTG, CD105 and Ki-67 and their relationships with age, gender, invasiveness, hormonal expression and regrowth or recurrence in the follow-up of NFPA operated and not submitted to radiotherapy. METHODS: Included 56 patients submitted to transsphenoidal surgery. Clinical data were obtained from medical records. The invasion degree was obtained by Hardy's classification. RESULTS: Mean age 55 ±â€¯13.6 years, 62.5% men and 68% invasive. Lesion persistence was present in 62.2% and regrowth in 35.7%. The recurrence-free survival rate was 94.5%, 75.4% and 69.1% (1, 2 and 3 years). No patient presented recurrence. The PTTG was positive in 55.3%, with statistically significant relationship with invasiveness, age and female gender, without relation to regrowth. The microvascular density showed statistically significant relationship with male gender, negative correlation with PTTG (r = -0.434, p = 0.001), and no relation with invasiveness and regrowth. The Ki-67 showed statistically significant relationship with age, tendency towards regrowth (p = 0.054) and, with no relation to invasiveness. CONCLUSIONS: It is suggested that PTTG can be used as a prognostic marker in NFPA.

Aromatase P450 expression in human pituitary adenomas.

Estrogen has been shown to play an important role in pituitary tumor pathogenesis. In humans, this biosynthesis is mediated by aromatase, an enzyme that converts androgens to estrogens. Just a few studies about aromatase expression in human pituitary gland, both in normal and pathological ones, are found in the literature. This study aimed to assess aromatase enzyme expression in human pituitary adenomas and associate it with gender, tumor size and tumor subtype. We conducted a cross-sectional study, reviewed clinical data and surgical specimens of consecutive 65 patients (35 women and 30 men) with anatomopathologic diagnosis of pituitary adenoma who underwent adenomectomy at a neurosurgical referral center in southern Brazil. Immunohistochemistry was performed to assess aromatase expression and define tumor subtype, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to estimate aromatase gene expression. Mean patient age was 45.6 (±13.3) years (range, 18 to 73 years), 86.2% of our samples were macroadenomas while 13.8% were classified as microadenomas. Based on clinical and immunohistochemical data, 23 (35.4%) patients had non-functioning adenomas, 19 (29.2%) had somatotroph adenomas (acromegaly), 12 (18.5%) had lactotroph adenomas (hyperprolactinemic syndrome), and 11 (16.9%) had corticotroph adenomas (Cushing's disease). Immunohistochemical analysis was performed in 59 cases, and 58 (98.3%) showed no aromatase expression. Quantification by qRT-PCR was performed in 43 samples, and 36 (83.7%) revealed no gene expression. Among tumor specimens examined by both techniques (37 cases), 30 showed no gene or protein expression (concordance index, 0.81). It is possible to mention that aromatase expression was lost in most pituitary adenomas, regardless of gender, tumor subtype, or tumor size.

Prolactin gene expression in primary central nervous system tumors.

BACKGROUND: Prolactin (PRL) is a hormone synthesized in both the pituitary gland and extrapituitary sites. It has been associated with the occurrence of neoplasms and, more recently, with central nervous system (CNS) neoplasms. The aim of this study was to evaluate prolactin expression in primary central nervous system tumors through quantitative real-time PCR and immunohistochemistry (IH). RESULTS: Patient mean age was 49.1 years (SD 15.43), and females accounted for 70% of the sample. The most frequent subtype of histological tumor was meningioma (61.5%), followed by glioblastoma (22.9%). Twenty cases (28.6%) showed prolactin expression by immunohistochemistry, most of them females (18 cases, 90%). Quantitative real-time PCR did not show any prolactin expression. CONCLUSIONS: Despite the presence of prolactin expression by IH, the lack of its expression by quantitative real-time PCR indicates that its presence in primary tumors in CNS is not a reflex of local production.

Expression of cell growth negative regulators MEG3 and GADD45γ is lost in most sporadic human pituitary adenomas.

We aimed at the evaluation of MEG3 and GADD45γ expression in sporadic functioning and clinically non-functioning human pituitary adenomas, morphologically characterized by immunohistochemistry analysis and their association with clinical features. Thirty eight patients who had undergone hypophysectomy at São José Hospital of Irmandade Santa Casa de Misericórdia in Porto Alegre, Brazil, were included in this study. We evaluated tumor-type specific MEG3 and GADD45γ expression by qRT-PCR in the pituitary adenomas, and its association with clinical features, as age, gender and tumor size, obtained from medical records. The patients consisted of 21 males and 17 females and the mean age was 47 ± 14 (mean ± SD), ranging from 18 to 73 years-old. Of these 14 were clinically non-functioning, 10 GH-secreting, 9 PRL-secreting, and 5 ACTH-secreting pituitary adenomas. All samples were macroadenomas, except four ACTH-secreting tumors, which were microadenomas. In summary, MEG3 and GADD45γ expression was significantly lost in most clinically non-functioning adenomas (78 and 92%, respectively). Other assessed pituitary tumor phenotypes expressed both genes at significantly different levels, and, in some cases, with overexpression. There was no significant association between gene expression and the analyzed clinical features. Our results confirm the previous report, which indicated that MEG3 and GADD45γ expression is lost in the majority of human pituitary tumors, mainly in clinically-nonfunctioning adenomas. Functioning tumors had differences of relative expression levels. The two groups of tumors are probably genetically different and may have a different natural history.

Quantitative computed tomography and cranial burr holes: a model to evaluate the quality of cranial reconstruction in humans.

Current methods to evaluate the biologic development of bone grafts in human beings do not quantify results accurately. Cranial burr holes are standardized critical bone defects, and the differences between bone powder and bone grafts have been determined in numerous experimental studies. This study evaluated quantitative computed tomography (QCT) as a method to objectively measure cranial bone density after cranial reconstruction with autografts. In each of 8 patients, 2 of 4 surgical burr holes were reconstructed with autogenous wet bone powder collected during skull trephination, and the other 2 holes, with a circular cortical bone fragment removed from the inner table of the cranial bone flap. After 12 months, the reconstructed areas and a sample of normal bone were studied using three-dimensional QCT; bone density was measured in Hounsfield units (HU). Mean (SD) bone density was 1535.89 (141) HU for normal bone (P < 0.0001), 964 (176) HU for bone fragments, and 453 (241) HU for bone powder (P < 0.001). As expected, the density of the bone fragment graft was consistently greater than that of bone powder. Results confirm the accuracy and reproducibility of QCT, already demonstrated for bone in other locations, and suggest that it is an adequate tool to evaluate cranial reconstructions. The combination of QCT and cranial burr holes is an excellent model to accurately measure the quality of new bone in cranial reconstructions and also seems to be an appropriate choice of experimental model to clinically test any cranial bone or bone substitute reconstruction.

Immunohistochemical expression of aromatase and estrogen, androgen and progesterone receptors in normal and neoplastic human meningeal cells.

Evidence suggests that sex hormones may play a role in the tumorigenesis of meningiomas, and studies have demonstrated the expression of hormone receptors in these tumors. Aromatase expression has been detected in several normal tissues, including neurons in the CNS, and tumor tissues. We aim to assess the expression of aromatase (ARO) and of progesterone receptor (PR), estrogen receptor (ER) and androgen receptor (AR) in both normal and neoplastic meningeal cells. A cross-sectional study was conducted with 126 patients diagnosed with meningioma (97 women and 29 men; mean age, 53.6 years) submitted to neurosurgery at Hospital São José, Complexo Hospitalar Santa Casa de Porto Alegre, southern Brazil. Control sections of normal meningeal cells, 19 patients, were obtained by evaluating the arachnoid tissue present in the arachnoid cyst resected material. Immunohistochemistry was applied to assess ARO, PR, ER and AR. Aromatase expression was detected in 100% of the control patients and in 0% of the patients with meningioma. ER was present in 24.6% of the meningiomas and in 0% of the controls, AR in 18.3% of the meningiomas and in 0% of the controls, and PR in 60.3% of the meningiomas and in 47.4% of the controls. A positive association was observed between the presence of AR and ER (OR 3.7; P = 0.01) in meningiomas. There were no significant differences in the presence of hormone receptors between meningioma histological subtypes. PR expression in women with meningioma was significantly higher than that found in men (OR 2.3; P = 0.08). Behavior pattern differences observed between aromatase expression, present in normal tissues and absent in meningiomas, and estrogen and androgen hormone receptors, absent in normal tissues and present in meningiomas, suggest that there is heterogeneity in modulation by sex steroids in the development of these tumors.

DNA repair and cell synthesis proteins: immunohistochemical expression and correlation with recurrence-regrowth in meningiomas.

Meningiomas are considered the second most common neoplasm of the central nervous system in adults. Most of them are benign with slow growth, frequent in women and with a high recurrence rate. In tumors, DNA error repair processes lose efficacy, providing mutagenesis and genomic instability. This work evaluated the expression of proteins involved in cell synthesis (cyclin D1) and DNA errors repair (MUTYH, XPF, XPG) in meningiomas, relating them to clinical, tumor and survival variables. The study included 85 patients, with a mean age of 52 ± 13.3 years and most of them women (2:1 ratio). Sixty-seven cases were grade I (79%). Grade II tumors were independent predictors of recurrence-regrowth (HR: 2.8; p = 0.038). The high expression of cyclin D1 was associated with grade II (p = 0.001) and low MUTYH expression with grade I (p = 0.04). Strong expression of XPF and XPG was associated with grade II (p = 0.002; p < 0.001) and with recurrence-regrowth (p = 0.04; p = 0.003). Strong XPF expression was significantly related to large tumors (p = 0.03). An association of cyclin D1, MUTYH and XPF were found. Survival was not associated with the expression of any of the proteins studied. To know the role of DNA repair proteins and cell synthesis is important for understanding the processes of origin and tumor development. Grade II meningiomas and strong expression of XPF and XPG were predictors of recurrence or regrowth and may assist in clinical management, considering the high recurrence of meningiomas and the absence of consensus regarding treatment.

Evaluation of the potential of the Ki67 index to predict tumor evolution in patients with pituitary adenoma.

The aggressive course of a number of pituitary adenomas requires the investigation of potential predictors. This study aimed to investigate the proliferation marker Ki67 as a predictor of postoperative outcome in patients with pituitary adenoma regarding recurrence and regrowth of the tumor, using a Ki67 cut-off value of 3%. This retrospective study included 52 patients with pituitary adenoma who had undergone adenomectomy and had a pituitary image taken at least 1 year after surgery. Patients were divided according to Ki67 expression into high (≥3%) vs. low (<3%) levels of Ki67. The two groups were similar regarding the preoperative tumor invasion grade. The Ki67 index ranged from 0 to 30%; in 23 cases, Ki67 was ≥3%. The two groups were similar regarding tumor recurrence and regrowth: 4 cases (28%) of recurrence in the Ki67<3% group vs. none in the Ki67≥3% group (P=0.26); and 2 cases (13%) of regrowth in the Ki67<3% group vs. 7 cases (43%) in the Ki67≥3% group (P=0.11). A subgroup analysis was performed for nonfunctioning adenomas. Recurrence rates remained similar between groups (Ki67<3% group: 1 case [20%]; Ki67≥3% group: none; P>0.99), whereas regrowth rates were higher in the Ki67≥3% group (6 cases [67%] vs. 2 cases [17%] in the Ki67<3% group; P=0.03). The patient with the highest Ki67 index (30%) developed pituitary carcinoma. The results allow us to suggest the adoption of a stricter control of image monitoring in nonfunctioning adenomas with incomplete resection associated with a Ki67 index ≥3%.

Cervicothoracic Lordosis Can Influence Outcome After Posterior Cervical Spine Surgery.

BACKGROUND: Previous studies on the correlation between cervical sagittal balance with improvement in quality of life showed significant results only for parameters of the anterior translation of the cervical spine (such as C2-C7 SVA). OBJECTIVE: We test whether a new parameter, cervicothoracic lordosis, can predict clinical success in this type of surgery. METHODS: The focused group involved patients who underwent surgical treatment of cervical degenerative disk disease by the posterior approach, due to myelopathy, radiculopathy or a combination of both. Neurologic deficit was measured before and after surgery with the Nurick Scale, postoperative quality of life, physical and mental components of SF-36 and NDI. Cervicothoracic lordosis and various sagittal balance parameters were also measured. Cervicothoracic lordosis was defined as the angle between: a) the line between the centroid of C2 and the centroid of C7; b) the line between the centroid of C7 and the centroid of T6. Correlations between postoperative quality of life and sagittal parameters were calculated. RESULTS: Twenty-nine patients between 27 and 78 years old were evaluated. Surgery types were simple decompression (laminectomy or laminoforaminotomy) (3 patients), laminoplasty (4 patients) and laminectomy with fusion in 22 patients. Significant correlations were found for C2-C7 SVA and cervicothoracic lordosis. C2-C7 SVA correlated negatively with MCS (r=-0.445, p=0.026) and PCS (r=-0.405, p=0.045). Cervicothoracic lordosis correlated positively with MCS (r=0.554, p= 0.004) and PCS (r=0.462, p=0.020) and negatively with NDI (r=-0.416, p=0.031). CONCLUSION: The parameter cervicothoracic lordosis correlates with improvement of quality life after surgery for cervical degenerative disk disease by the posterior approach.

Hyperprolactinemia and immunohistochemical expression of intracellular prolactin and prolactin receptor in primary central nervous system tumors and their relationship with cellular replication.

The role of prolactin (PRL) in the CNS remains uncertain. We evaluated the presence of hyperprolactinemia, intracellular prolactin (ICP), and prolactin receptor (PRL-R) in primary CNS tumors, and their relationship with cellular replication with a prospective cross-sectional study of 82 consecutive patients with primary CNS tumors admitted for neurosurgical resection between October 2003 and September 2005. Patients submitted to a questionnaire, and venous blood samples were obtained for measurement of serum PRL and TSH. Immunohistochemical analyses were performed to evaluate the presence of ICP, PRL-R, and Ki-67. Serum PRL levels ranged from 2 to 70 ng/ml, and hyperprolactinemia was detected in 25 cases (30.5%). ICP was detected in 18 patients (21.9%), in whom PRL ranged from 2 to 32 ng/ml. A positive correlation was found between PRL levels and the presence of ICP (Student's t test, P = 0.022). The PRL-R was observed immunohistochemically in 32 cases (39%). The frequencies of hyperprolactinemia, ICP, and PRL-R were similar across the several histological types of CNS tumors. Ki-67 index was similar in all groups. Hyperprolactinemia and intracellular presence of PRL and PRL-R were common findings in this population, suggesting a role for PRL in CNS tumor genesis.

Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease.

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.

Recurrence of Anaplastic Large Cell Lymphoma in the Frontal Lobe After Eleven Years of the Initial Diagnosis: Histopathological Findings and Prognosis / Recorrência de linfoma anaplásico de grandes células no lobo frontal onze anos após o diagnóstico inicial: Achados histopatológicos e prognóstico

Anaplastic large cell lymphoma (ALCL) is a rare, high-grade, T-cell neoplasm classified into cutaneous primary, systemic primary ALK-positive (ALKþ), systemic primary ALK-negative, or breast-implant associated. Secondary involvement of the central nervous system (CNS) by systemic primary ALKþ ALCL is a rare occurrence. We present a case of CNS involvement by ALKþ ALCL eleven years after diagnosis of the primary tumor in the thoracic vertebra. The anatomopathological examination confirmed the diagnosis of ALKþ ALCL. A brief review of the treatment and the clinical and pathological aspects is presented.

O linfoma anaplásico de grandes células (LAGC) corresponde a uma neoplasia de alto grau rara, com imunofenótipo T, que podendo ser dividido em primário cutâneo, primário sistêmico ALK positivo (ALKþ), primário sistêmico ALK negativo, e associado a próteses mamárias. Acometimento secundário do sistema nervoso central (SNC) por LAGC primário sistêmico ALKþ é uma rara entidade. Os autores apresentam um caso de acometimento do SNC por LAGC ALKþ onze anos após o diagnóstico do tumor primário em vértebra torácica. O exame anatomopatológico confirmou o diagnóstico de LAGC ALKþ. Fez-se também uma breve revisão de aspectos clínicos e patológicos e tratamento.

Enterogenous Cyst and Glioblastoma: A Brief Histopathological Review of Two Uncommon Cystic Lesions of the Central Nervous System / Cisto entérico e glioblastoma: Uma breve revisão histopatológica de duas lesões císticas incomuns do sistema nervoso central

Intracranial cystic lesions are common findings in cerebral imaging and might represent a broad spectrum of conditions. These entities can be divided into nonneoplastic lesions, comprising Rathke cleft cyst, arachnoid cyst, and colloid cyst, as well as neoplastic lesions, including benign and malignant components of neoplasms such as pilocytic astrocytoma, hemangioblastoma, and ganglioglioma. Surgical resection and histological evaluation are currently the most effective methods to classify cysts of the central nervous system. The authors report two uncommon cases presenting as cystic lesions of the encephalic parenchyma­a enterogenous cyst and a glioblastoma­and discuss typical histological findings and differential diagnosis.

Lesões císticas intracranianas são achados comuns em imagens cerebrais e podem representar um amplo espectro de condições. Essas entidades podem ser divididas em lesões não neoplásicas, compreendendo cisto da bolsa de Rathke, cisto aracnoide e cisto colóide, e lesões neoplásicas, incluindo componentes benignos e malignos de neoplasias, como astrocitoma pilocítico, hemangioblastoma e ganglioglioma. A ressecção cirúrgica e a avaliação histológica são atualmente os métodos mais eficazes para classificar os cistos do sistema nervoso central. Os autores relatam dois casos incomuns que se apresentam como lesões císticas do parênquima encefálico, um cisto entérico e um glioblastoma, e discutem achados histológicos típicos e diagnósticos diferenciais.

Pre-clinical evaluation of voltage-gated calcium channel blockers derived from the spider P. nigriventer in glioma progression.

This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1ß from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells. PhTx3-3, Phα1ß and MVIIA displayed significant inhibitory effects on the proliferation and viability of all tested glioma cell lines, and evoked cell death mainly with apoptosis characteristics, as indicated by Annexin V/propidium iodide (PI) positivity. The antiproliferative effects of toxins were confirmed by flow cytometry using Ki67 staining. None of the tested toxins altered the proliferation rates of the N9 non-tumor glial cell line. Noteworthy, the administration of the preferential N-type VGCC inhibitors, Phα1ß (50 pmol/site; i.c.v.), its recombinant form CTK 01512-2 (50 pmol/site; i.c.v. and i.t.), or MVIIA (10 pmol/site; i.c.v.) caused significant reductions of tumor areas in vivo. N-type VGCC inhibition by Phα1ß, CTK 01512-2, and MVIIA led to a marked increase of GFAP-activated astrocytes, and Iba-1-positive microglia, in the peritumoral region, which might explain, at least in part, the inhibitory effects of the toxins in tumor development. This study provides novel evidence on the potential effects of P. nigriventer-derived P/Q-, and mainly, N-type VGCC inhibitors, in glioma progression.

Impact of surgery on ambulatory status in patients with symptomatic neoplastic spinal cord compression in southern brazil / Impacto da cirurgia sobre a capacidade de ambulatória em pacientes com compressão neoplásica sintomática da medula espinalno sul do brasil / Impacto de la cirugía en la capacidad de ambulación en pacientes con compresión medular neoplásica sintomática en el sur de brasil

ABSTRACT Background: Spinal cord compression is a common complication of spine metastasis and multiple myeloma. About 30% of patients with cancer develop symptomatic spinal metastases during their illness. Prompt diagnosis and surgical treatment of these lesions, although palliative, are likely to reduce the morbidity and improve quality of life by improving ambulatory function. Study Design: Retrospective review of medical records. Objective: To evaluate postoperative functional recovery and the epidemiological profile of neoplastic spinal cord compression in two neurosurgical centers in southern Brazil. Methods: We retrospectively analyzed the data of all patients who underwent palliative surgery for symptomatic neoplastic spine lesion from metastatic cancer, in two neurosurgical centers, between January 2003 and July 2021. The variables age, sex, neurological status, histological type, affected segment, complications and length of hospitalization were analyzed. Results: A total of 82 patients were included. The lesions occurred in the thoracic spine in 60 cases. At admission, 95% of the patients had neurological deficits, most of which were Frankel C (37%). At histopathological analysis, breast cancer was the most common primary site. After surgery, the neurological status of 46 patients (56%) was reclassified according to the Frankel scale. Of these, 22 (47%) regained ambulatory capacity. Conclusion: Surgical treatment of metastatic spinal cord compression improved neurological status and ambulatory ability in our sample. Level of evidence II; Retrospective study.

RESUMO: Introdução: A compressão medular é uma complicação comum de metástases da coluna vertebral e de mieloma múltiplo. Cerca de 30% dos pacientes com câncer desenvolvem metástases sintomáticas na coluna no decorrer da doença. O diagnóstico imediato e o tratamento cirúrgico dessas lesões, embora paliativos, em geral reduzema morbidade e melhoram a qualidade de vidaao ampliar a capacidade de deambular. Desenho do estudo: Revisão retrospectiva de prontuários médicos. Objetivo: Avaliar a recuperação funcional pós-operatória e o perfil epidemiológico da compressão medular neoplásica em dois centros de neurocirurgia do sul do Brasil. Métodos: Analisamos retrospectivamente os dados de todos os pacientes submetidos à cirurgia paliativa de lesão neoplásica sintomática da coluna decorrente decâncer metastático, em dois centros neurocirúrgicos entre janeiro de 2003 e julho de 2021. Foram analisadas as variáveis idade, sexo, estado neurológico, tipo histológico, segmento acometido, complicações e tempo de internação. Resultados: Foram incluídos 82 pacientes no estudo. As lesões ocorreram na coluna torácica em 60 casos. À internação, 95% dos pacientes apresentavam déficits neurológicos, sendoa maioria classificada como Frankel C (37%). Na análise histopatológica, o câncer de mama foi o sítio primário mais comum. Depois da cirurgia, 46 pacientes (56%) tiveram o estado neurológico reclassificado pela escala de Frankel. Entre eles, 22 (47%) recuperaram a capacidade de deambular. Conclusões: O tratamento cirúrgico da compressão medular metastática melhorou o estado neurológico e a capacidade de deambulação em nossa amostra. Nível de evidência II; Estudo retrospectivo.

RESUMEN: Introducción: La compresión de la médula espinal es una complicación común de la metástasis de la columna vertebral y el mieloma múltiple. Aproximadamente el 30% de los pacientes con cáncer desarrollan metástasis espinales sintomáticas en el curso de la enfermedad. El diagnóstico precoz y el tratamiento quirúrgico de estas lesiones, aunque son paliativos, suelen reducir la morbilidad y mejor en lacalidad de vida al aumentar la de ambulación. Diseño del estudio: Revisión retrospectiva de registros médicos. Objetivo: Evaluarla recuperación funcional postoperatoria y el perfil epidemiológico de la compresión medular neoplásica en dos centros neuroquirúrgicos del sur de Brasil. Métodos: Analizamos retrospectivamente los datos de todos los pacientes sometidos a cirugía paliativa por lesión vertebral neoplásica sintomática por cáncer metastásico, en dos centros neuroquirúrgicos entre enero de 2003 y julio de 2021. Se analizaron las variables edad, sexo, estado neurológico, tipo histológico, segmento afectado, complicaciones y duración de la hospitalización. Resultados: Se incluyeron 82 pacientes en el estudio. Las lesiones se produjeron en la columna torácica en 60 casos. Al ingreso, el 95% de los pacientes presentaban déficits neurológicos y la mayoría de ellos eran clasificados como Frankel C (37%). En el análisis histopatológico, elcáncer de mama fue el sitio primario más común. Después de la cirugía, se reclasificó el estado neurológico de 46 pacientes (56%) por la escala de Frankel. Entre ellos, 22 (47%) recuperaron la capacidadde deambulación. Conclusiones: El tratamiento quirúrgico de la compresión medular metastásica mejoró el estado neurológico y la capacidad de deambulación en nuestra muestra. Nivel de evidencia II; Estudio retrospectivo.

Decreased TAp63 and ΔNp63 mRNA Levels in Most Human Pituitary Adenomas Are Correlated with Notch3/Jagged1 Relative Expression.

Despite recent advances in molecular genetics, the pituitary adenoma initiation, development, progress, and the molecular basis of their unique features are still poorly understood. In this sense, it is proposed that stem cell could be involved in pituitary adenoma tumorigenesis. It is suggested that TP63 has important functions in stem cells, and it may have interplay of TP63 and Notch and its ligand Jagged in this process. This study aimed to evaluate the distinct expression of TP63 isoforms (TAp63 and ΔNp63), as well as its correlation with Notch3 receptor and its ligand Jagged1 in human pituitary adenomas at the messenger RNA (mRNA) level. We included 77 pituitary adenoma tumor samples from patients who underwent surgical resection. The expression levels of TP63 isoforms (TAp63 and ΔNp63) and Notch3 and its ligand Jagged1 were evaluated by qRT-PCR using isoform-specific primers. We also evaluated proliferation index immunohistochemically using KI-67 antibody. The expression levels were associated with clinical outcomes, as age, gender, tumor size, and tumor subtype. In summary, we found that mRNA expression of both TP63 isoforms decreased in pituitary adenomas compared with normal pituitary control. On the other hand, there was an increase of relative Notch3 and Jagged1 mRNA expression in the majority of examined samples. The mRNA expression of three genes evaluated was correlated and statistically significantly. There was no significant association between gene expression and the analyzed clinical data. The current study has provided the first time evidence that Tap63 and ΔNp63 isoforms are underexpressed in most pituitary adenomas. These results are correlated with Notch3 and its ligand Jagged1 overexpression, corroborating previous studies pointing its antagonistic interactions.

Primary Role for Kinin B1 and B2 Receptors in Glioma Proliferation.

This study investigated the role of kinins and their receptors in malignant brain tumors. As a first approach, GL-261 glioma cells were injected (2 × 105 cells in 2 µl/2 min) into the right striatum of adult C57/BL6 wild-type, kinin B1 and B2 receptor knockout (KOB1R and KOB2R) and B1 and B2 receptor double knockout mice (KOB1B2R). The animals received the selective B1R (SSR240612) and/or B2R (HOE-140) antagonists by intracerebroventricular (i.c.v.) route at 5, 10, and 15 days. The tumor size quantification, mitotic index, western blot analysis, quantitative autoradiography, immunofluorescence, and confocal microscopy were carried out in brain tumor samples, 20 days after tumor induction. Our results revealed an uncontrolled tumor growing in KOB1R or SSR240612-treated mice, which was blunted by B2R blockade with HOE-140, suggesting a crosstalk between B1R and B2R in tumor growing. Combined treatment with B1R and B2R antagonists normalized the upregulation of tumor B1R and decreased the tumor size and the mitotic index, as was seen in double KOB1B2R. The B1R was detected on astrocytes in the tumor, indicating a close relationship between this receptor and astroglial cells. Noteworthy, an immunohistochemistry analysis of tumor samples from 16 patients with glioma diagnosis revealed a marked B1R immunopositivity in low-grade gliomas or in older glioblastoma individuals. Furthermore, the clinical data revealed a significantly higher immunopositivity for B1R, when compared to a lower B2R immunolabeling. Taken together, our results show that blocking simultaneously both kinin receptors or alternatively stimulating B1R may be of therapeutic value in the treatment of brain glioblastoma growth and malignancy.

Early surgical treatment of nonsyndromic craniosynostosis.

BACKGROUND: Craniosynostosis, a premature fusion of cranial sutures, can happen as an isolated defect (nonsyndromic) or as part of a syndrome. It may lead to raised intracranial pressure and deformity of both the cranial and facial skeletons. Early surgery is usually the best treatment choice. The aim of this study was to review the experience of a multidisciplinary staff with the surgical treatment of nonsyndromic craniosynostosis. METHODS: All the nonsyndromic craniosynostosis cases treated surgically from 1991 to 2005 at 2 neurosurgical centers were reviewed. The variables analyzed were sex, age, weight, type of deformity, estimated volemia, surgical technique, surgical time, blood loss, PO hospitalization time, and complications. All data were stored in a database and analyzed with Microsoft Access (Microsoft Corp, Seattle, WA) and SPSS V11.0 (SPSS, Inc, Chicago, IL). RESULTS: The sample consisted of 120 patients (70 males, 50 females). Six patients were excluded because of their atypical timing of treatment (average age, 72 months). The final average age was 7.08 months (variation, 1-18), and the average weight was 7.8 kg. The types of deformities found were scaphocephaly (n = 54, 45%), plagiocephaly (n = 27, 22%), trigonocephaly (n = 19, 16%), brachycephaly (n = 16, 13%), and oxycephaly (n = 4, 3%). The mean surgical time was 186 minutes and the mean PO hospitalization time was 6.8 days. The mortality on this series was 2.6% (3 patients). In the last operated cases, a significant improvement in morbid-mortality was observed. CONCLUSION: A multidisciplinary approach, including neurosurgeons, neurologists, and pediatricians, and appropriate training of the clinical surgical staff can minimize the risks and decrease the complications in the treatment of craniosynostosis, leading to a satisfactory outcome.