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.

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.

Bruns Syndrome Caused by Intraventricular Neurocysticercosis: Literature Review

Bruns syndrome is one of the clinical presentations of intraventricular neurocysticercosis, and it is characterized by episodes of headache, vertigo and vomiting. The intraventricular form of neurocysticercosis occurs in 7% to 20% of the cases, and it is more serious than the intraparenchymal form. The management is primarily surgical, associated with pharmacological therapy with anthelmintic drugs and corticosteroids. We report the case of a patient who presented Bruns syndrome due to neurocysticercosis.

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.

Physiopathological Aspects of Sellar Epidermoid Cyst Determining Endocrine Disturbances: A Case Report

Epidermoid cysts (ECs) of the central nervous system (CNS) constitute benign circumscribed lesions that aremore common in lateral than in midline sites. Epidermoid cysts of the CNS arise more frequently in the cerebellopontine angle, around the pons, near the sella, within the temporal lobe, in the diploe, and in the spinal canal. Most common tumoral lesion of sellar region is pituitary adenoma, and sellar cystic epithelial masses may be difficult to differentiate based only on clinical and imaging findings. Epidermoid cysts are covered by keratinized squamous epithelium and are usually filled with keratin lamellae. The process is, for the most part, maldevelopmental in origin, presumably arising from trapped surface ectodermal elements in association with the developing CNS during the closure of the neural groove or formation of the secondary cerebral vesicles. In the present study, the authors describe a case of sellar epidermoid cyst producing endocrine alterations and visual disturbance in a 35 years woman, and review the physiopathological and diagnostic criteria of this lesion.

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.

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%.

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.

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.

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.

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.

A simple scoring system for predicting early major complications in spine surgery: the cumulative effect of age and size of surgery.

OBJECTIVE: To analyze the cumulative effect of risk factors associated with early major complications in postoperative spine surgery. METHODS: Retrospective analysis of 583 surgically-treated patients. Early "major" complications were defined as those that may lead to permanent detrimental effects or require further significant intervention. A balanced risk score was built using multiple logistic regression. RESULTS: Ninety-two early major complications occurred in 76 patients (13%). Age > 60 years and surgery of three or more levels proved to be significant independent risk factors in the multivariate analysis. The balanced scoring system was defined as: 0 points (no risk factor), 2 points (1 factor) or 4 points (2 factors). The incidence of early major complications in each category was 7% (0 points), 15% (2 points) and 29% (4 points) respectively. CONCLUSIONS: This balanced scoring system, based on two risk factors, represents an important tool for both surgical indication and for patient counseling before surgery.

A simple scoring system for predicting early major complications in spine surgery: the cumulative effect of age and size of surgery / Escore simples para predizer complicações precoces graves em cirurgia de coluna: o efeito cumulativo da idade e tamanho da cirurgia

ABSTRACT Objective To analyze the cumulative effect of risk factors associated with early major complications in postoperative spine surgery. Methods Retrospective analysis of 583 surgically-treated patients. Early “major” complications were defined as those that may lead to permanent detrimental effects or require further significant intervention. A balanced risk score was built using multiple logistic regression. Results Ninety-two early major complications occurred in 76 patients (13%). Age > 60 years and surgery of three or more levels proved to be significant independent risk factors in the multivariate analysis. The balanced scoring system was defined as: 0 points (no risk factor), 2 points (1 factor) or 4 points (2 factors). The incidence of early major complications in each category was 7% (0 points), 15% (2 points) and 29% (4 points) respectively. Conclusions This balanced scoring system, based on two risk factors, represents an important tool for both surgical indication and for patient counseling before surgery.

RESUMO Objetivo Analisar os efeitos cumulativos dos fatores de risco associados com complicações precoces graves relacionadas à cirurgia da coluna. Métodos Análise retrospectiva de 583 pacientes tratados cirurgicamente. Complicações graves foram definidas como as que pudessem levar a danos permanentes ou que necessitassem de reinterveção. Um escore foi construído usando modelo de regressão logística. Resultados Noventa e duas complicações precoces graves ocorreram em 76 pacientes (13%). Idade > 60 anos e cirurgia > 3 níveis foram identificadas como fatores de risco independentes na análise multivariada. O escore foi definido como: 0 pontos (nenhum fator de risco), 2 pontos (1 fator) ou 4 pontos (2 fatores). A incidência de complicação grave precoce em cada categoria foi 7% (0 pontos), 15% (2 pontos) e 29% (4 pontos). Conclusões Esse escore balanceado baseado em 2 fatores de risco representa uma ferramenta útil na indicação cirúrgica e para o aconselhamento dos pacientes antes da cirurgia.

Autologous cranial bone graft use for trepanation reconstruction.

BACKGROUND: Esthetic deformities in the human skull are a subject of concern among neurosurgical patients and neurosurgeons; they can be disfiguring and harm the patient's social relationships. To access inner structures, neurosurgical operations require skull trepanation, a process that frequently involves loss of bone tissue and leads to esthetic problems. Satisfactory reconstruction is a challenge, and neurosurgeons search for an implant which ideally is organic and low cost and does not cause an immunological or allergic reaction. Therefore, autologous bone tissue remains the gold standard for reconstruction. OBJECTIVES: To develop a technique that allows neurosurgeons to rebuild the trepanation hole with a better esthetic outcome. METHOD: Craniotomy orifices in 108 patients were closed with a graft obtained from the cranial bone inner layer. In order to remove the graft a specially made trephine was used. RESULTS: No grafts dislocated during follow-up. Cosmetic outcomes and results seen on image examinations were favorable for this new technique when compared with others previously described in medical literature. CONCLUSION: The authors present a new and feasible trepanation reconstruction technique that allows a better esthetic outcome without increasing the surgical risk for the patient, or making the surgical procedure longer or more expensive.

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.

Expression of somatostatin receptors (SSTR1-SSTR5) in meningiomas and its clinicopathological significance.

Meningiomas are benign brain tumors that are usually to recur. Studies have shown in vitro and in vivo that meningiomas, regardless of histology and classification, express somatostatin receptors (SSTRs). We investigated the immunohistochemical expression of five SSTR subtypes (SSTR1-SSTR5) in tumor tissue sections from 60 patients with diagnosis of meningioma who underwent surgical resection and relating it to patient age and sex, tumor histology, location, regrowth/recurrence and follow-up. Mean (SD) patients age was 53.18 (12.6) years and 44 were women (73.3%). According to the WHO histological grading criteria, 47 (78.3%) meningiomas were grade I, 11 (18.3%) were grade II, and 2 (3.3%) were grade III. All five SSTRs were expressed in our sample, at frequencies ranging from 61.6 to 100%, with a predominance of SSTR2. SSTR5 was more frequently expressed in tumors benign than in tumors malignant (P<0.013). Recurrence-free survival rate at 2 years was 75.2%. There were no significant differences in SSTR expression regarding age, sex, tumor location and regrowth/recurrence. SSTR expression was detected at a significant frequency in this series. SSTR5 showed higher expression in tumors benign supporting the use of these SSTRs in diagnostic of meningiomas and their influence in process of tumorigenesis in meningiomas recurrence.

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.

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.

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.