Experience of 300 cases of prenatal fetoscopic open spina bifida repair: report of the International Fetoscopic Neural Tube Defect Repair Consortium.

BACKGROUND: The multicenter randomized controlled trial Management of Myelomeningocele Study demonstrated that prenatal repair of open spina bifida by hysterotomy, compared with postnatal repair, decreases the need for ventriculoperitoneal shunting and increases the chances of independent ambulation. However, the hysterotomy approach is associated with risks that are inherent to the uterine incision. Fetal surgeons from around the world embarked on fetoscopic open spina bifida repair aiming to reduce maternal and fetal/neonatal risks while preserving the neurologic benefits of in utero surgery to the child. OBJECTIVE: This study aimed to report the main obstetrical, perinatal, and neurosurgical outcomes in the first 12 months of life of children undergoing prenatal fetoscopic repair of open spina bifida included in an international registry and to compare these with the results reported in the Management of Myelomeningocele Study and in a subsequent large cohort of patients who received an open fetal surgery repair. STUDY DESIGN: All known centers performing fetoscopic spina bifida repair were contacted and invited to participate in a Fetoscopic Myelomeningocele Repair Consortium and enroll their patients in a registry. Patient data entered into this fetoscopic registry were analyzed for this report. Fisher exact test was performed for comparison of categorical variables in the registry with both the Management of Myelomeningocele Study and a post-Management of Myelomeningocele Study cohort. Binary logistic regression analyses were used to assess the registry data for predictors of preterm birth at <30 weeks' gestation, preterm premature rupture of membranes, and need for postnatal cerebrospinal fluid diversion in the fetoscopic registry. RESULTS: There were 300 patients in the fetoscopic registry, 78 in the Management of Myelomeningocele Study, and 100 in the post-Management of Myelomeningocele Study cohort. The 3 data sets showed similar anatomic levels of the spinal lesion, mean gestational age at delivery, distribution of motor function compared with upper anatomic level of the lesion in the neonates, and perinatal death. In the Management of Myelomeningocele Study (26.16±1.6 weeks) and post-Management of Myelomeningocele Study cohort (23.3 [20.2-25.6] weeks), compared with the fetoscopic registry group (23.6±1.4 weeks), the gestational age at surgery was lower (comparing fetoscopic repair group with the Management of Myelomeningocele Study; P<.01). After open fetal surgery, all patients were delivered by cesarean delivery, whereas in the fetoscopic registry approximately one-third were delivered vaginally (P<.01). At cesarean delivery, areas of dehiscence or thinning in the scar were observed in 34% of cases in the Management of Myelomeningocele Study, in 49% in the post-Management of Myelomeningocele Study cohort, and in 0% in the fetoscopic registry (P<.01 for both comparisons). At 12 months of age, there was no significant difference in the number of patients requiring treatment for hydrocephalus between those in the fetoscopic registry and the Management of Myelomeningocele Study. CONCLUSION: Prenatal and postnatal outcomes up to 12 months of age after prenatal fetoscopic and open fetal surgery repair of open spina bifida are similar. Fetoscopic repair allows for having a vaginal delivery and eliminates the risk of uterine scar dehiscence, therefore protecting subsequent pregnancies of unnecessary maternal and fetal risks.

Second opinion for degenerative spinal conditions: an option or a necessity? A prospective observational study.

BACKGROUND: Second opinions may improve quality of patient care. The primary objective of this study was to determine the concordance between first and second diagnoses and opinions regarding need for spinal surgery among patients with back or neck pain that have been recommended spinal surgery. METHODS: We performed a prospective observational study of patients who had been recommended for spinal surgery and received a second opinion between May 2011 and May 2012 at the Hospital Israelita Albert Einstein on the advice of their health insurance company. A physiatrist and orthopaedic surgeon independently performed the second assessment. If both agreed surgery was indicated, or consensus could not be reached, participants attended a spine review panel for a final recommendation. Descriptive analyses compared diagnoses and management plans of the first and second opinions. RESULTS: Of 544 referred patients, 16 (2.9%) did not meet inclusion criteria, 43 (7.9%) refused participation and 485 were included. Diagnoses differed from the first opinion for 290 (59.8%). Diagnoses of cervical and lumbar radiculopathy were concordant in 36/99 (36.4%) and 116/234 (49.6%) respectively. The second opinion was for conservative treatment for 168 (34.6%) participants, 27 (5.6%) were not considered to have a spine condition, and 290 (59.8%) were referred to the review board. 60 participants did not attend the board review and therefore did not receive a final recommendation. Board review was conservative treatment for an additional 67 participants, 20 were not considered to have a spine condition and 143 participants were recommended surgery. Overall, 33.6% received a final opinion of surgery (143/425) although only 66 (15.5%) received the same surgical recommendation, 235 (55.3%) were advised to have conservative treatment, and 47 (11.1%) were not considered to have a spinal diagnosis. CONCLUSIONS: We found a large discordance between first and second opinions regarding diagnosis and need for spinal surgery. This suggests that obtaining a second opinion could reduce potentially unnecessary surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07143259 . Registered 21 November 2011.

Can lumbar hemorrhagic synovial cyst cause acute radicular compression? Case report / O cisto sinovial hemorrágico lombar pode causar compressão radicular aguda? Relato de caso

Lumbar synovial cysts are an uncommon cause of back pain and radiculopathy, usually manifesting with gradual onset of symptoms, secondary to involvement of the spinal canal. Rarely, intracyst hemorrhage occurs, and may acutely present as radicular - or even spinal cord - compression syndrome. Synovial cysts are generally associated with degenerative facets, although the pathogenesis has not been entirely established. We report a case of bleeding complication in a synovial cyst at L2-L3, adjacent to the right interfacet joint, causing acute pain and radiculopathy in a patient on anticoagulation therapy who required surgical resection.

Cistos sinoviais da coluna lombar são uma causa incomum de dor na coluna e radiculopatia, geralmente com evolução gradual dos sintomas, que são secundários ao comprometimento do canal vertebral. Raramente, há hemorragia intracística, que pode se manifestar de forma aguda com síndrome compressiva radicular ou mesmo medular. Habitualmente, os cistos sinoviais associam-se a doença degenerativa facetária, embora a patogênese não esteja completamente estabelecida. Relatamos aqui um caso em que uma complicação hemorrágica em um cisto sinovial no nível L2-L3, adjacente à interfacetária direita, causou dor lombar e radiculopatia em um paciente em terapia anticoagulante, sendo necessária a ressecção cirúrgica.

In vitro Analysis of Neurospheres Derived from Glioblastoma Primary Culture: A Novel Methodology Paradigm.

Glioblastomas are the most lethal primary brain tumor that frequently relapse or progress as focal masses after radiation, suggesting that a fraction of tumor cells are responsible for the tumor regrowth. The identification of a brain tumor cell subpopulation with potent tumorigenic activity supports the cancer stem cell hypothesis in solid tumors. The goal of this study is to determine a methodology for the establishment of primary human glioblastoma cell lines. Our aim is achieved by taking the following approaches: (i) the establishment of primary glioblastoma cell culture; (ii) isolation of neurospheres derived from glioblastoma primary cultures; (iii) selection of CD133 cells from neurospheres, (iv) formation of subspheres in the CD133-positive population, (v) study of the expression level of GFAP, CD133, Nestin, Nanog, CD34, Sox2, CD44, and CD90 markers on tumor subspheres. Hence, we described a successful method for isolation of CD133-positive cell population and establishment of glioblastoma neurospheres from this primary culture, which are more robust than the ones derived straight from the tumor. Pointed out that the neurospheres derived from glioblastoma primary culture showed 29% more cells expressing CD133 then the ones straight tumor-derived, denoting a higher concentration of CD133-positive cells in the neurospheres derived from glioblastoma primary culture. These CD133-positive fractions were able to further generate subspheres. The subspheres derived from glioblastoma primary culture presented a well-defined morphology while the ones derived from the fresh tumor were sparce and less robust. And the negative fraction of CD133 cells was unable to generate subspheres. The tumor subspheres expressed GFAP, CD133, Nestin, Nanog, CD44, and CD90. Also, the present study describes an optimization of neurospheres/subspheres isolation from glioblastoma primary culture by selection of CD133-positive adherent stem cell.

Can lumbar hemorrhagic synovial cyst cause acute radicular compression? Case report.

Lumbar synovial cysts are an uncommon cause of back pain and radiculopathy, usually manifesting with gradual onset of symptoms, secondary to involvement of the spinal canal. Rarely, intracyst hemorrhage occurs, and may acutely present as radicular - or even spinal cord - compression syndrome. Synovial cysts are generally associated with degenerative facets, although the pathogenesis has not been entirely established. We report a case of bleeding complication in a synovial cyst at L2-L3, adjacent to the right interfacet joint, causing acute pain and radiculopathy in a patient on anticoagulation therapy who required surgical resection.

Glioblastoma: approach to treat elderly patients / Glioblastoma: enfoque no tratamento de pacientes idosos

Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection and have maintained a good performance status. Rather than being ruled out, chemotherapy should be considered, and temozolomide is the chosen drug. A comprehensive geriatric assessment is a valuable tool to help guiding treatment decisions in elderly patients with glioblastoma.

O tratamento de idosos com câncer é um desafio para a prática oncológica, especialmente no que se refere à terapêutica multimodal do glioblastoma. Nessa população, a ressecção ampla do tumor oferece a melhor chance de controle local e, naqueles pacientes que mantenham um bom performance status, a radioterapia complementar deve sempre ser levada em consideração. A quimioterapia também tem um papel no tratamento, sendo a temozolomida a droga de eleição. Frente à heterogeneidade desses pacientes, uma avaliação geriátrica ampla é um instrumento valioso no auxílio da decisão terapêutica em idosos com glioblastoma.

Tumor growth analysis by magnetic resonance imaging of the C6 glioblastoma model with prospects for the assessment of magnetohyperthermia therapy.

OBJECTIVE: The objective was to establish a pattern of tumor growth of the C6 model of glioblastoma multiform in Wistar rats via magnetic resonance imaging (MRI) for the subsequent verification of tumor volume reduction due to magnetic hyperthermia therapy. METHODS: Young male Wistar rats weighing between 250 and 300 g were used for the C6 model. After the rats were anesthetized (55 mg/ kg ketamine and 11 mg/kg xylazine), C6 lineage tumorigenic cells suspended in culture medium (10(5) cells in 10 microl) were stereotaxically injected into the right frontal cortex (bregma coordinates: 2.0 mm anteroposterior, 3.0 mm laterolateral, and 2.5 mm depth) of the rats using a Hamilton syringe. For the control group, the rats were injected with culture medium without cells. MRI scans were performed at 14, 21, and 28 d after the injection using a 2.0 T MRI scanner (Bruker BioSpec, Germany). The animals were anesthetized with 55 mg/kg ketamine and 11 mg/kg xylazine before being examined. Coronal multilayers were acquired using a standard spin echo sequence with the following parameters: repetition/echo time = 4.000 ms/67.1 ms, field of view = 3.50, matrix = 192, slice thickness = 0.4 mm, and slice separation = 0 mm. RESULTS: The MRI analysis enabled a clear visualization of the tumor mass, and it was possible to establish the tumor volume parameters on the various days that were examined. The volume at 14 d after induction was 13.7 +/- 2.5 mm3. On days 21 and 28, the tumor volumes were 31.7 +/- 6.5 mm3 and 122.1 +/- 11.8 mm3, respectively. CONCLUSION: These results demonstrated that it is possible to evaluate the C6 model tumor volume in rats, which will allow for the future implementation and verification of magnetic hyperthermia therapy.

Isolation, cultivation and characterization of CD133+ stem cells from human glioblastoma.

OBJECTIVE: To establish the method of isolation and culture of human glioblastoma neurospheres, and the purification of their stem cells, followed by the process of obtaining tumor subspheres, immunophenotypically characterizing this clonogenic set. METHODS: Through the processing of glioblastoma samples (n=3), the following strategy of action was adopted: (i) establish primary culture of glioblastoma; (ii) isolation and culture of tumor neurospheres; (iii) purify cells that initiate tumors (CD133+) by magnetic separation system (MACS); (iv) obtain tumor subspheres; (v) study the expression of the markers nestin, CD133, and GFAP. RESULTS: The study successfully described the process of isolation and culture of glioblastoma subspheres, which consist of a number of clonogenic cells immunophenotypically characterized as neural, which are able to initiate tumor formation. CONCLUSION: These findings may contribute to a better understanding of the process of gliomagenesis.

Ética médica no novo milênio

O artigo trata do surgimento de novos desafios éticos face ao avanço da medicina técnica, como a possibilidade de clonagem de seres humanos, a capacidade de diagnosticar precocemente o surgimento de doenças graves ou até então incuráveis e a realização de transplantes de uma variedade crescente de órgãos.

Isolation, cultivation and characterization of CD133+ stem cells from human glioblastoma / Isolamento, cultivo e caracterização de células-tronco CD133+ de glioblastoma humano

Objetivo: Estabelecer o método de isolamento e cultivo das neuroesferas de glioblastoma humano, bem como purificação de suas células-tronco, seguido do processo de obtenção de subesferas tumorais, caracterizando imunofenotipicamente esse conjunto clonogênico. Métodos: Por meio do processamento de amostras de glioblastomas (n=3), cumpriu-se a seguinte estratégia de ação: (i) estabelecimento da cultura primária de glioblastoma; (ii) isolamento e cultura de neuroesferas tumorais; (iii) purificação das células que iniciam os tumores (CD133+) por sistema de separação magnética (MACS); (iv) obtenção subesferas tumorais; (v) estudo da expressão de marcadores GFAP, CD133 e nestina. Resultados: Este estudo descreveu com sucesso o processo de isolamento e cultivo de subesferas de glioblastoma, as quais são constituídas por um conjunto clonogênico de células caracterizadas imunofenotipicamente como neurais, capazes de iniciar a formação tumoral. Conclusão: Estes achados poderão contribuir para a compreensão do processo de gliomagênese.

Glioblastoma: approach to treat elderly patients.

Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection and have maintained a good performance status. Rather than being ruled out, chemotherapy should be considered, and temozolomide is the chosen drug. A comprehensive geriatric assessment is a valuable tool to help guiding treatment decisions in elderly patients with glioblastoma.

Estenose do canal vertebral cervical e lombar / Cervical and lumbar spinal canal stenosis

A estenose de canal vertebral é uma doença degenerativa da colunavertebral estreitamente relacionada ao envelhecimento humano, poistem como causa a doença degenerativa dos discos intervertebrais eartrose das facetas articulares posteriores da coluna vertebral, comconseqüente estreitamento do canal vertebral. Com o aumento dalongevidade da população, é esperada também maior freqüênciade pacientes com doenças degenerativas da coluna vertebral,necessitando uma abordagem clínica adequada. Dessa formaapresentamos um artigo abordando aspectos clínicos, diagnósticose tratamentos da estenose do canal vertebral.