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.

Private health care sector investment in Brazil: opportunities and obstacles.

The Brazilian health system is based upon the constitutional right formulated in 1988, according to which health is the peoples' right and duty of the State. So being, it is essentially the government's responsibility, expressed in the so-called Sistema Unico de Saúde--SUS (single health system) Since its creation, however, it admits the existence of a supplementary health system, left to the private sector. In general terms, the public system is considered unsatisfactory in the services it renders. Its resources are distributed heterogeneously, favoring centers of advanced medical practice, to the detriment of basic health care. The supplementary system is considered of better quality, however with great variations and frequent accusations of being essentially profit driven, instead of being driven to the needs of the assisted population. The growing search for health plans is a direct consequence of the image perceived by the population regarding the quality and accessibility of the public services, as well as of the peoples' growing consciousness of their needs, rights and duties as citizens. The need for continuous quality improvement and cost reduction offers numberless opportunities for actions and investments. Initiatives to identify and implement the best medical practices, medical guidelines and actions are essential regarding those illnesses which are most frequent, of higher cost and of greater risk. Health plans and healthcare providers will necessarily have to focus on their common client. Therefore, organizations must be created in order to develop initiatives aimed to the quality of patient care, as well as to the collection and dissemination of data regarding the production and results of the main service providers. Consequently, immense opportunities are being opened for investments in the area of Information Technology, collection, analysis, and data dissemination. This paper analyses the main trends in the Brazilian health sector and from the data and tendencies, draws various conclusions on the opportunities and barriers for private investment.

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.

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.

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.

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.

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.

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.

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.

Radiosurgical boost for primary high-grade gliomas.

The purpose of this study was to retrospectively evaluate the survival of patients with high-grade gliomas treated with external beam radiotherapy with or without radiosurgical boost. From July 1993 to April 1998, 32 patients were selected, 15 of which received radiosurgery. Inclusion criteria were age > 18 years, histological confirmation of high-grade glioma, primary tumor treatment with curative intent, unifocal tumor and supratentorial location. All patients were found to be in classes III-VI, according to the recursive partitioning analysis proposed by the Radiation Therapy Oncology Group. The median interval between radiotherapy and radiosurgery was 5 weeks (range 1-13). Treatment volumes ranged from 2.9 to 70.3 cc (median 15.0 cc). Prescribed radiosurgery doses varied from 8.0 to 12.5 Gy (median 10.0 Gy). Radiosurgery and control groups were well balanced with respect to prognostic factor distributions. Median actuarial survival time in radiosurgery and control groups was 21.4 months and 11.6 months, respectively (p = 0.0254). Among patients with KPS > 80, median survival time was 11.0 months and 53.9 months in the control and radiosurgery groups, respectively (p = 0.0103). Radiosurgery was the single factor correlated with survival on Cox model analysis (p = 0.0362) and was associated with a 2.76 relative reduction in the risk of cancer death (95% confidence interval (CI) 1.07-7.13). Our results suggest that radiosurgery may confer a survival advantage for patients in RPA classes III-VI, especially for those with Karnofsky performance status >80. The definitive role of radiosurgical boost for patients with high-grade gliomas awaits the results of randomized trials.

Headaches and pineal cyst: a (more than) coincidental relationship?

Pineal cysts are common findings in neuroimaging studies. The cysts are more frequent in women in their third decade of life. Pineal cysts can be symptomatic, headache is the most common symptom. The pineal gland has important physiological implications in humans, but little is known about the impact of pineal cysts in human physiology. We report 5 headache patients with pineal cyst, 4 women, 1 man, mean age 37.6, mean cyst diameter 10.1 mm. Two patients had migraine without aura, 1 migraine with aura, 1 chronic migraine, and 1 hemicrania continua. Three patients had strictly unilateral headaches. We hypothesize pineal cysts may be not incidental in headache patients, inducing an abnormal melatonin secretion.

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.

Validando o SIR: um melhor índice prognóstico para pacientes com metástases cerebraistratados com cirurgia estereotática / Validating the SIR: a better prognostic score index for patients with brain metastases treated with stereotactic radiosurgery

Objetivo: Validar o SIR (score index for survival in patients with brain metastasis treated with stereotatic radiosurgery) [índice de escore paraavaliar a sobrevida de pacientes com metástases cerebrais tratadoscom radiocirurgia estereotática], uma classificação elaborada paramelhor prever o prognóstico de pacientes com metástases cerebraistratados com radiocirurgia, reavaliar a sobrevida dos pacientes e revisara literatura médica. Métodos: Foram analisados dados de 100 pacientes com metástases cerebrais tratados com radiocirurgia estereotática um uma única instituição, entre julho de 1993 e fevereiro de 2002. Os fatores prognósticos e índices estudados foram: idade, índice de desempenho de Karnofsky, estado da doença extracraniana, número de lesões cerebrais, volume da maior lesão, tipode tumor primário, tratado ou não tratado com radioterapia cerebral total,SIR e RPA (Recursive Partitioning Analysis – classificação por análiserecursiva fragmentada). As curvas atuariais de sobrevida de Kaplan-Meier foram calculadas e comparadas. Os modelos Cox – completo e de eliminação retrógrada – foram utilizados para identificar os fatores prognósticos e índices, associados à sobrevida. Resultados: Ao analisar as curvas de sobrevida de Kaplan-Meier, o índice de desempenho de Karnofsky, o estado da doença extracraniana, o volume da maior lesão cerebral, a RPA e o SIR mostraram correlação significativa com o prognóstico. Aplicando os modelos de Cox, observou-se significância para índice de desempenho de Karnofsky (p < 0,0001) e volume da maior lesão (p = 0,0182), assim como para o SIR e paraa RPA, quando testados individualmente (p < 0,0001 e p = 0,0002). Contudo, testando SIR e RPA conjuntamente, só o SIR alcançou significância estatística independente (p < 0,0001). Conclusão: Ao reavaliar nossa casuística, a classificação SIR mostrou maior precisão do que a RPA para prever o tempo de sobrevida de pacientes com metástases cerebrais tratados com radiocirurgia.

Objective: The aim of this paper is to validate the score index forsurvival in patients treated with stereotactic radiosurgery, using aclassification prepared to better evaluate the prognosis of patientswith brain metastasis submitted to stereotactic surgery, re-evaluatingsurvival of patients and reviewing the medical literature. Methods:Data from 100 patients with brain metastases treated with stereotacticradiosurgery at a single institution, between July 1993 and February2000, were retrospectively analyzed. The prognostic factors andscores studied were age, Karnofsky performance status, extracranialdisease status, number of brain lesions, volume of the largest lesion,primary tumor type, treated or not with whole brain radiation therapy,SIR, and RPA. Kaplan-Meier actuarial survival curves for subsets werecalculated and compared by log-rank test. Complete and backwardelimination Cox models were utilized to identify the prognostic factorsand scores independently associated with survival. Results: Karnofskyperformance status, extracranial disease status, volume of the largestbrain lesion, RPA, and SIR were significantly correlated with prognosisin Kaplan-Meier survival analysis. Applying Cox models, significancewas observed for KPS and volume of the largest lesion (p < 0.0001and p = 0.0182, respectively), as well as for SIR and RPA when testedindividually (p < 0.0001 and p = 0.0002, respectively). However, whentesting SIR and RPA together, only SIR reached independent statisticalsignificance (p < 0.0001). Conclusion: SIR classification demonstrateda better accuracy in predicting survival time than RPA. SIR was testedin other centers, showing superior accuracy and applicability than theRPA, thus validating this score.