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1.
Neurooncol Pract ; 11(1): 92-100, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38222047

RESUMO

Background: Electrocorticography (ECoG) language mapping is often performed extraoperatively, frequently involves offline processing, and relationships with direct cortical stimulation (DCS) remain variable. We sought to determine the feasibility and preliminary utility of an intraoperative language mapping approach guided by real-time visualization of electrocorticograms. Methods: A patient with astrocytoma underwent awake craniotomy with intraoperative language mapping, utilizing a dual iPad stimulus presentation system coupled to a real-time neural signal processing platform capable of both ECoG recording and delivery of DCS. Gamma band modulations in response to 4 language tasks at each electrode were visualized in real-time. Next, DCS was conducted for each neighboring electrode pair during language tasks. Results: All language tasks resulted in strongest heat map activation at an electrode pair in the anterior to mid superior temporal gyrus. Consistent speech arrest during DCS was observed for Object and Action naming tasks at these same electrodes, indicating good correspondence with ECoG heat map recordings. This region corresponded well with posterior language representation via preoperative functional MRI. Conclusions: Intraoperative real-time visualization of language task-based ECoG gamma band modulation is feasible and may help identify targets for DCS. If validated, this may improve the efficiency and accuracy of intraoperative language mapping.

2.
Neurospine ; 20(1): 317-326, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37016879

RESUMO

PURPOSE: Carbon-fiber reinforced polyetheretherketone (CFRP)-based spinal implants are an alternative to titanium, offering less image artifact as their metallic counterparts while maintaining similar biomechanical and biocompatibility properties. Its use in the management of spinal tumors has been reported, however the perceived advantages related to improved imaging quality, radiation treatment planning, and detection of tumor recurrence have not been fully assessed. METHODS: We performed a retrospective review of medical records amongst oncologic patients treated at MD Anderson Cancer Center with CFRP implants. Histology, tumor location, construct features, time of follow-up, adjuvant radiation, recurrences, overall survival, and hardware-related complications were recorded. RESULTS: Sixty-nine consecutive patients were assessed (22 primary tumors, 47 metastases) and the median time for follow-up was 5.4 months. Amongst the cohort, a total of 491 CFRP pedicle screws were implanted. Hardware complications were observed in 5 cases (7.04%). Adjuvant radiation was completed in 8 patients with primary tumors and 29 patients with spinal metastases. A total of 28 patients (40.5%) from the combined primary and metastatic cohorts experienced systemic disease progression, with 12 patients (17.3%) demonstrating local recurrences. Amongst primary and metastatic tumors, overall survival (p = 0.363) and rate of local recurrence (p = 0.112) were similar. CONCLUSION: This largest series of CFRP implants demonstrates safe and effective spinal stabilization for patients with both primary and metastatic tumors. Enhanced postoperative imaging led to minimal imaging artifacts which facilitated postoperative radiation planning and the ability to detect local recurrence.

3.
J Neurosurg ; 139(1): 65-72, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-36433877

RESUMO

OBJECTIVE: Robust preoperative imaging can improve the extent of resection in patients with brain tumors while minimizing postoperative neurological morbidity. Both structural and functional imaging techniques can provide helpful preoperative information. A recent study found that transcranial magnetic stimulation (TMS) tractography has significant predictive value for permanent deficits. The present study directly compares the predictive value of TMS tractography and task-based functional MRI (fMRI) tractography in the same cohort of glioma patients. METHODS: Clinical outcome data were collected from charts of patients with motor eloquent glioma and preoperative fMRI and TMS studies. The primary outcome was a new or worsened motor deficit present at the 3-month postoperative follow-up, which was termed a "permanent deficit." Postoperative MR images were overlaid onto preoperative plans to determine which imaging features were resected. Multiple fractional anisotropic thresholds (FATs) were screened for both TMS and fMRI tractography. The predictive value of the various thresholds was modeled using receiver operating characteristic curve analysis. RESULTS: Forty patients were included in this study. Six patients (15%) sustained permanent postoperative motor deficits. A significantly greater predictive value was found for TMS tractography than for fMRI tractography regardless of the FAT. Despite 35% of patients showing clinically relevant neuroplasticity captured by TMS, only 2.5% of patients showed a blood oxygen level-dependent signal displaced from the precentral gyrus. Comparing the best-performing FAT for both modalities, TMS seeded tractography showed superior predictive value across all metrics: sensitivity, specificity, positive predictive value, and negative predictive value. CONCLUSIONS: The results from this study indicate that the prediction of permanent deficits with TMS tractography is superior to that with fMRI tractography, possibly because TMS tractography captures clinically relevant neuroplasticity. However, future large-scale prospective studies are needed to fully illuminate the proper role of each modality in comprehensive presurgical workups for patients with motor-eloquent tumors.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Imagem de Tensor de Difusão/métodos , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Imageamento por Ressonância Magnética , Doença Iatrogênica
5.
J Neurosurg Case Lessons ; 3(20)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-36303481

RESUMO

BACKGROUND: In patients with perieloquent tumors, neurosurgeons must use a variety of techniques to maximize survival while minimizing postoperative neurological morbidity. Recent publications have shown that conventional anatomical features may not always predict postoperative deficits. Additionally, scientific conceptualizations of complex brain function have shifted toward more dynamic, neuroplastic theories instead of traditional static, localizationist models. Functional imaging techniques have emerged as potential tools to incorporate these advances into modern neurosurgical care. In this case report, we describe our observations using preoperative transcranial magnetic stimulation data combined with tractography to guide a nontraditional surgical approach in a patient with a motor eloquent glioblastoma. OBSERVATIONS: The authors detail the use of preoperative functional and structural imaging to perform a gross total resection despite tumor infiltration of conventionally eloquent anatomical structures. The authors resected the precentral gyrus, specifically the paracentral lobule, localized using intraoperative mapping techniques. The patient demonstrated mild transient postoperative weakness and made a full neurological recovery by discharge 1 week later. LESSONS: Preoperative functional and structural imaging has potential to not only optimize patient selection and surgical planning, but also facilitate important intraoperative decisions. Innovative preoperative imaging techniques should be optimized and used to identify safely resectable structures.

6.
Neurooncol Adv ; 4(1): vdac126, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36128584

RESUMO

Background: For patients with brain tumors, maximizing the extent of resection while minimizing postoperative neurological morbidity requires accurate preoperative identification of eloquent structures. Recent studies have provided evidence that anatomy may not always predict eloquence. In this study, we directly compare transcranial magnetic stimulation (TMS) data combined with tractography to traditional anatomic grading criteria for predicting permanent deficits in patients with motor eloquent gliomas. Methods: We selected a cohort of 42 glioma patients with perirolandic tumors who underwent preoperative TMS mapping with subsequent resection and intraoperative mapping. We collected clinical outcome data from their chart with the primary outcome being new or worsened motor deficit present at 3 month follow up, termed "permanent deficit". We overlayed the postoperative resection cavity onto the preoperative MRI containing preoperative imaging features. Results: Almost half of the patients showed TMS positive points significantly displaced from the precentral gyrus, indicating tumor induced neuroplasticity. In multivariate regression, resection of TMS points was significantly predictive of permanent deficits while the resection of the precentral gyrus was not. TMS tractography showed significantly greater predictive value for permanent deficits compared to anatomic tractography, regardless of the fractional anisotropic (FA) threshold. For the best performing FA threshold of each modality, TMS tractography provided both higher positive and negative predictive value for identifying true nonresectable, eloquent cortical and subcortical structures. Conclusion: TMS has emerged as a preoperative mapping modality capable of capturing tumor induced plastic reorganization, challenging traditional presurgical imaging modalities.

7.
Surg Neurol Int ; 13: 311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928321

RESUMO

Background: Repeat craniotomy in patients with primary and metastatic brain tumors carries significant morbidity and can delay adjuvant treatments. Repeat laser interstitial thermal therapy (LITT) for recurrent disease has been described and could benefit patients with limited cytoreductive options. We aim to describe the indications, safety, and efficacy of repeat LITT for recurrent primary and metastatic intracranial tumors. Methods: Patients undergoing repeat ablations for the same lesion were included in the study. We retrospectively analyzed 13 patients treated with 29 total LITT ablations. Results: Eleven patients were treated for glioblastoma (GBM), while two had brain metastases. Eleven patients had LITT performed only 2 times, while three patients underwent three total iterations of LITT for disease recurrence. Median length of stay after the 1st ablation was 2 days, while the median length of stay after the 2nd ablation was 1 day. The median time to resuming adjuvant treatments after the 1st LITT was 11 days. The median time to resuming adjuvant treatments after the 2nd LITT was 28 days. Four patients after the 1st and 2nd LITT sustained deficits persisting through 30-day follow-up. The median progression-free survival among the GBM patients from the first ablation was 6.0 months, 3.2 months from the 2nd ablation, and 2.1 months from the 3rd ablation. Conclusion: Recurrent tumors, especially GBM, can be safely treated using repeat LITT when surgery cannot be effectively performed. Our results indicate that patients tolerate the procedure well and have a meaningful survival given the salvage nature of the procedure.

8.
Neurospine ; 19(2): 434-440, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35577332

RESUMO

OBJECTIVE: Spinal reconstruction after resection of invasive craniocervical junction malignancies is fraught with technical and management considerations as well as a paucity of data in the existing literature. In this study, we describe our experience with craniocervical junction malignancies, especially the influence of radiation on the need for revision spinal instrumentation. METHODS: We performed a retrospective chart review of all patients who underwent occipitocervical fixation between 2011 and 2019 at The University of Texas MD Anderson Cancer Center. RESULTS: Twenty-five patients had primary malignancies and 12 (30%) had metastatic tumors. Thirteen (33%) underwent a staged resection in multiple operations during their hospital stay. Tumor resection was performed in 19 patients (48%), while only stabilization was performed in 21 patients (52%). Nine patients (23%) underwent expanded endoscopic transclival approaches for tumor resection, 10 patients (25%) an extreme lateral approach, and 2 patients (5%) an anterior open approach. Eleven patients underwent early postoperative radiation therapy (within 3 months) and 8 underwent delayed radiation therapy (between 3 months and 1 year in 7 patients). The revision rate was 8%, with a median time to revision surgery of 42 months. The administration and timing of adjuvant radiation therapy relative to surgery had no significant effect on the need for instrumentation revision on log-rank and Cox regression analyses (p < 0.05). CONCLUSION: Revision surgery was needed infrequently in our patients. Postoperative radiation therapy was not associated with hardware failure, indicating that the timing of radiation therapy should be dictated by the diagnosis and can be initiated postoperatively without delay.

9.
World Neurosurg ; 162: e561-e567, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35331948

RESUMO

BACKGROUND: Adult spinal deformity (ASD) surgery is becoming increasingly prevalent. Soft tissue defects arising from revision closure and impaired healing can predispose to wound complications including dehiscence and infection. Soft tissue coverage with local muscle flaps has been shown to minimize wound complications in high-risk patients. In this study we evaluate the role of complex wound closure in preventing wound complications in high-risk spinal deformity patients. METHODS: The authors retrospectively reviewed charts of patients who underwent ASD surgery. Patients were stratified into muscle flap advancement (by neurosurgery or plastic surgery) closure versus primary approximation by neurosurgery. Relevant patient and operative factors were collected and summarized using descriptive statistics. Outcomes of interest included wound complication and revision surgery. RESULTS: Ninety-four cases met inclusion criteria including 56 wounds closed by neurosurgery and 38 wounds closed by plastic surgery (PRS). Of the neurosurgery wounds, 31 and 25 were closed by primary approximation and muscular flap advancement, respectively. Patients operated on by PRS were higher risk than all patients operated on only by neurosurgery (P = 0.0037) but were not significantly higher risk than the neurosurgery performed flap cohort (P = 0.4914). In subgroup analysis, despite similar levels of risk, the PRS population experienced lower rates of any wound complication (P = 0.028) and specifically dehiscence (P = 0.029) compared with the neurosurgery performed flap closure cohort. CONCLUSIONS: Prophylactic involvement of plastic surgery in ASD surgery wound closure may improve wound outcomes in higher risk patients. A multidisciplinary approach with plastic and spine surgeons may lessen the risk of wound complications in high-risk spine surgeries.


Assuntos
Procedimentos de Cirurgia Plástica , Infecção da Ferida Cirúrgica , Adulto , Humanos , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Retalhos Cirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle
10.
Front Neurosci ; 16: 833073, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299624

RESUMO

Many studies have established a link between extent of resection and survival in patients with gliomas. Surgeons must optimize the oncofunctional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Preoperative functional imaging modalities are important tools for optimizing the oncofunctional balance. Transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) are non-invasive imaging modalities that can be used for preoperative functional language mapping. Scarce data exist evaluating the accuracy of these preoperative modalities for language mapping compared with gold standard intraoperative data in the same cohort. This study compares the accuracy of fMRI and TMS for language mapping compared with intraoperative direct cortical stimulation (DCS). We also identified significant predictors of preoperative functional imaging accuracy, as well as significant predictors of functional outcomes. Evidence from this study could inform clinical judgment as well as provide neuroscientific insight. We used geometric distances to determine copositivity between preoperative data and intraoperative data. Twenty-eight patients were included who underwent both preoperative fMRI and TMS procedures, as well as an awake craniotomy and intraoperative language mapping. We found that TMS shows significantly superior correlation to intraoperative DCS compared with fMRI. TMS also showed significantly higher sensitivity and negative predictive value than specificity and positive predictive value. Poor cognitive baseline was associated with decreased TMS accuracy as well as increased risk for worsened aphasia postoperatively. TMS has emerged as a promising preoperative language mapping tool. Future work should be done to identify the proper role of each imaging modality in a comprehensive, multimodal approach to optimize the oncofunctional balance.

11.
Cancers (Basel) ; 14(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35053503

RESUMO

Surgeons must optimize the onco-functional balance by maximizing the extent of resection and minimizing postoperative neurological morbidity. Optimal patient selection and surgical planning requires preoperative identification of nonresectable structures. Transcranial magnetic stimulation is a method of noninvasively mapping the cortical representations of the speech and motor systems. Despite recent promising data, its clinical relevance and appropriate role in a comprehensive mapping approach remains unknown. In this study, we aim to provide direct evidence regarding the clinical utility of transcranial magnetic stimulation by interrogating the eloquence of TMS points. Forty-two glioma patients were included in this retrospective study. We collected motor function outcomes 3 months postoperatively. We overlayed the postoperative MRI onto the preoperative MRI to visualize preoperative TMS points in the context of the surgical cavity. We then generated diffusion tensor imaging tractography to identify meaningful subsets of TMS points. We correlated the resection of preoperative imaging features with clinical outcomes. The resection of TMS-positive points was significantly predictive of permanent deficits (p = 0.05). However, four out of eight patients had TMS-positive points resected without a permanent deficit. DTI tractography at a 75% FA threshold identified which TMS points are essential and which are amenable to surgical resection. TMS combined with DTI tractography shows a significant prediction of postoperative neurological deficits with both a high positive predictive value and negative predictive value.

12.
Lasers Med Sci ; 37(3): 1811-1820, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34687390

RESUMO

Gliomas are the most frequent primary brain tumor in adults. Patients with glioblastoma (GBM) tumors deemed inoperable with open surgical techniques and treated only with chemo/radiation have a median overall survival of less than 9 months. Laser interstitial thermal therapy (LITT) has emerged as a cytoreductive alternative to surgery for these patients. The present study describes the outcomes of twenty patients with newly diagnosed, IDH wild-type glioblastoma treated with LITT. We retrospectively reviewed patients with newly diagnosed, unresectable GBM who underwent LITT at our institution. Progression-free survival (PFS) was the primary endpoint measured in our study, defined as time from LITT to disease progression. Results Twenty patients were identified with newly diagnosed, inoperable GBM lesions who underwent LITT. The overall median PFS was 4 months (95% CI = 2 - N/A, upper limit not reached). The median progression-free survival (PFS) for patients with less than 1 cm 3 residual tumor (gross total ablation, GTA) was 7 months (95% CI = 6 - N/A, upper limit not reached), compared to 2 months (95% CI = 1 - upper limit not reached) for patients with a lower GTA (p = .0019). The median overall survival was 11 months (95% CI = 6 - upper limit not reached). Preoperative Karnofsky performance score (KPS) less than or equal to 80 and deep-seated tumor location were significantly associated with decreased PFS (HR, .18, p = .03; HR, .08, p = .03, respectively). At the end of 1 month, only 4 patients (20%) experienced persistent motor deficits. LITT is a safe and effective treatment for patients with unresectable, untreated GBM with rates of survival and local recurrence comparable to patients with surgically accessible lesions treated with conventional resection. Careful patient selection is needed to determine if GTA is attainable.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Terapia a Laser , Adulto , Neoplasias Encefálicas/terapia , Glioblastoma/radioterapia , Humanos , Terapia a Laser/métodos , Lasers , Estudos Retrospectivos , Resultado do Tratamento
13.
Neurosurg Focus ; 50(5): E9, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33932939

RESUMO

OBJECTIVE: Survival of cancer patients continues to improve with systemic treatment advancements, leading to an increase in cancer-related complications such as pathological spinal fractures. In this study, the authors aimed to evaluate the outcome of percutaneous stabilization with cement augmentation of the pedicle screws in the management of patients with metastatic cancer to the spine. METHODS: The authors reviewed a retrospective case series of 74 patients with symptomatic pathological spine fractures treated with cement-augmented pedicle screws implanted with a percutaneous technique. The mean imaging follow-up was 11.3 months. Data on demographics, clinical outcomes, and complications were collected. Cement extravasation, spinal hardware integrity, and fusion rates were assessed on CT scans. RESULTS: Among 50 patients with follow-up imaging, 23 patients (46%) showed facet joint fusion. The length of segmental stabilization was not a significant predictor of the occurrence of fusion. Pre- or postoperative radiation therapy, postoperative chemotherapy, and the location of spinal lesions did not have a statistically significant effect on the occurrence of fusion. Patients older than 60 years of age were more likely to have fusion across facet joints compared with younger patients. There was a significant difference in the mean visual analog scale pain score, with 6.28 preoperatively and 3.41 postoperatively, regardless of fusion status (p < 0.001). Cement extravasation was seen in 51% of the cohort, but in all instances, patients remained asymptomatic. Most importantly, the incidence of hardware failure was low (4%). CONCLUSIONS: Percutaneous fixation with cement-augmented pedicle screws in patients with pathological spine fractures provides an improvement in mechanical back pain, with a low incidence of failure, and in some patients, spontaneous facet fusion was observed. Further research is necessary with regard to both short-term benefits and long-term outcomes.


Assuntos
Parafusos Pediculares , Fraturas da Coluna Vertebral , Fusão Vertebral , Articulação Zigapofisária , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
14.
Oper Neurosurg (Hagerstown) ; 21(3): E193-E198, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34038952

RESUMO

BACKGROUND: With the advent of intraoperative computed tomography (CT) for image guidance, numerous examples of accurate navigation being applied to cranial and spinal pathology have come to light. For spinal disorders, the utilization of image guidance for the placement of percutaneous spinal instrumentation, complex osteotomies, and minimally invasive approaches are frequently utilized in trauma, degenerative, and oncological pathologies. The use of intraoperative CT for navigation, however, requires a low target registration error that must be verified throughout the procedure to confirm the accuracy of image guidance. OBJECTIVE: To present the use of skin staples as a sterile, economical fiducial marker for minimally invasive spinal procedures requiring intraoperative CT navigation. METHODS: Staples are applied to the skin prior to obtaining the registration CT scan and maintained throughout the remainder of the surgery to facilitate confirmation of image guidance accuracy. RESULTS: This low-cost, simple, sterile approach provides surface landmarks that allow reliable verification of navigation accuracy during percutaneous spinal procedures using intraoperative CT scan image guidance. CONCLUSION: The utilization of staples as a fiducial marker represents an economical and easily adaptable technique for ensuring accuracy of image guidance with intraoperative CT navigation.


Assuntos
Doenças da Coluna Vertebral , Cirurgia Assistida por Computador , Marcadores Fiduciais , Humanos , Procedimentos Neurocirúrgicos , Doenças da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios X
15.
World Neurosurg ; 149: e244-e252, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33610872

RESUMO

BACKGROUND: Surgical resection has been shown to prolong survival in patients with glioblastoma multiforme (GBM), although this benefit has not been demonstrated for reoperation following tumor recurrence. Laser interstitial thermal therapy (LITT) is a minimally invasive ablation technique that has been shown to effectively reduce tumor burden in some patients with intracranial malignancy. The aim of this study was to describe the safety and efficacy of LITT for recurrent and newly diagnosed GBM at a large tertiary referral center. METHODS: Patients with GBM receiving LITT were retrospectively analyzed. Overall survival from the time of LITT was the primary end point measured. RESULTS: There were 69 patients identified for inclusion in this study. The median age of the cohort was 56 years (range, 15-77 years). Median tumor volume was 10.4 cm3 (range, 1.0-64.0 cm3). A Kaplan-Meier estimate of median overall survival for the series from the time of LITT was 12 months (95% confidence interval 8-16 months). Median progression-free survival for the cohort from LITT was 4 months (95% confidence interval 3-7 months). Adjuvant chemotherapy significantly prolonged progression-free survival and overall survival (P < 0.01 for both) in the cohort. Gross total ablation was not significantly associated with progression-free survival (P = 0.09). CONCLUSIONS: LITT can safely reduce intracranial tumor burden in patients with GBM who have exhausted other adjuvant therapies or are poor candidates for conventional resection techniques.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Hipertermia Induzida/métodos , Terapia a Laser/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
16.
Surg Neurol Int ; 11: 95, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33030461

RESUMO

BACKGROUND: Mesenchymal chondrosarcoma is a rare cartilaginous neoplasm that typically involves the axial skeleton. Despite a well-circumscribed appearance, this tumor has a tendency to recur both locally and with distant metastases. CASE DESCRIPTION: A 17-year-old patient presented with numbness and paresthesias in the lower extremities attributed to a T10-T11 intradural extramedullary mesenchymal chondrosarcoma. The patient was treated with aggressive local resection and adjuvant therapy. Here, this case and present literature are appropriately reviewed. CONCLUSION: Although uncommon, intraspinal mesenchymal chondrosarcomas warrant both radical local resection and aggressive adjuvant therapy with chemoradiation to provide the greatest chance of progression-free survival.

17.
Expert Opin Ther Targets ; 24(7): 605-614, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32394767

RESUMO

INTRODUCTION: The increasingly detailed genetic characterization of glioblastoma (GBM) has failed to translate into meaningful breakthroughs in treatment. This is likely to be attributed to molecular heterogeneity of GBM. However, the understanding of the tumor microenvironment in GBM has become more refined and has revealed a wealth of therapeutic targets that may enable the disruption of angiogenesis or immunosuppression. AREAS COVERED: This review discusses the selective targeting of tumor-intrinsic pathways, therapies that target the GBM tumor microenvironment and relevant preclinical studies and their limitations. Relevant literature was derived from a PubMed search encompassing studies from 1989 to 2020. EXPERT OPINION: Despite appropriate target engagement, attempts to directly inhibit oncogenic pathways in GBM have yielded little success. This is likely attributed to the molecular heterogeneity of GBM and the presence of redundant signaling that allow for accumulation of adaptive mutations and development of drug resistance. Subsequently, there has been a shift toward therapies modulating the pro-angiogenic, immunosuppressive tumor microenvironment in GBM. The non-transformed cells in the microenvironment which includes endothelial cells, myeloid cells, and T cells, are presumably genetically stable, less susceptible to heterogeneity, and easier to target. This approach offers the highest potential for a therapeutic breakthrough in GBM.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Terapia de Alvo Molecular , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , Oncogenes/genética , Microambiente Tumoral
18.
J Neurol Surg A Cent Eur Neurosurg ; 81(4): 348-354, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361984

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM) is an aggressive intracranial malignancy that confers a poor prognosis despite maximum surgical resection and chemoradiotherapy. Survival decreases further with deep-seated lesions. Laser interstitial thermal therapy (LITT) is an emerging minimally invasive technique for tumor ablation shown to reduce tumor burden effectively, particularly in deep-seated locations less amenable to gross total resection. We describe our initial technical experience of using the combination of LITT followed by surgical resection in patients with GBMs that exhibit both an easily accessible and deep-seated component. MATERIALS AND METHODS: Patients with GBM who received concurrent LITT and surgical resection at our institution were identified. Patient demographic and clinical information was procured from the University of Texas MD Anderson Cancer Center electronic medical record along with preoperative, postoperative, and 1-month follow-up magnetic resonance imaging (MRI). RESULTS: Four patients (n = 2 male, n = 2 female) with IDH-wild type GBM who received combined LITT and surgical resection were identified and analyzed retrospectively. All patients received chemoradiotherapy before presentation. All but one patient (75%) received resection before presentation. Median age was 54 years (range: 44-56 years). Median length of hospital stay was 6.5 days (range: 2-47 days). Median extent of combined ablation/resection was 90.4%. One of the four patients experienced complications in the perioperative or immediate follow-up periods. Local recurrence was observed in one patient during the follow-up period. CONCLUSION: Malignant gliomas in deep-seated locations or in close proximity to white matter structures are challenging to manage. LITT followed by surgical resection may provide an alternative for tumor debulking that minimizes potential morbidities and extent of residual tumor. Further studies comparing this approach with standard resection techniques are warranted.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Terapia a Laser/métodos , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Terapia Combinada , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
19.
World Neurosurg ; 132: e124-e132, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518744

RESUMO

BACKGROUND: Posterior fossa tumors are rare in adults and pose a challenge to treat due to the bony contour of the posterior fossa, complex anatomical structures including deep venous sinuses, and the proximity of the fourth ventricle and brain stem. We describe our experience with laser interstitial thermal therapy (LITT) for the management of brain metastases and radiation necrosis of the posterior fossa. METHODS: We retrospectively analyzed 13 patients with metastases and radiation necrosis of the posterior fossa managed with LITT. RESULTS: Thirteen patients with histopathologically confirmed radiation necrosis (n = 5) and metastases (n = 8) of the posterior fossa underwent LITT. The median preoperative tumor was 4.66 cm3, and median postoperative ablation cavity volume was 6.29 cm3. The median volume of the ablation cavity was decreased to 2.90 cm3 at a 9-month follow-up. The median volume of peritumoral edema was 12.25 cm3, which fell to a median of 5.77 cm3 at 1-month follow-up. The median progression-free survival was 7 months (range, 3-14 months) and the mean overall survival was 40 months (range, 2-49 months) after LITT. There were no intraoperative complications. One patient experienced palsy of the seventh and eighth cranial nerves on follow-up, attributable to LITT. CONCLUSIONS: Lesions of the posterior fossa are challenging to treat given their proximity to the dura and venous sinuses. Our findings demonstrate that LITT ablation may be a safe and feasible option for metastases and radiation necrosis of the posterior fossa. Larger studies are needed to confirm the efficacy of this approach.


Assuntos
Fossa Craniana Posterior/cirurgia , Hipertermia Induzida/métodos , Neoplasias Infratentoriais/terapia , Terapia a Laser/métodos , Adulto , Idoso , Edema Encefálico/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Fossa Craniana Posterior/patologia , Feminino , Seguimentos , Humanos , Neoplasias Infratentoriais/secundário , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/etiologia , Complicações Pós-Operatórias/epidemiologia , Intervalo Livre de Progressão , Radiocirurgia , Estudos Retrospectivos , Análise de Sobrevida
20.
J Clin Neurosci ; 70: 108-112, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31492483

RESUMO

PURPOSE: To describe 30-day outcomes following craniotomy for arteriovenous malformation in children and identify risk factors for readmission, reoperation, and perioperative complication using the National Surgical Quality Improvement Program (NSQIP) Pediatric database. METHODS: Patients aged 0-18 years who underwent surgery for arteriovenous malformations (years 2015-2016) were identified from the NSQIP Pediatric database. Descriptive statistics, uni-variate, and multi-variate regression analysis were performed using preoperative and perioperative data. The outcome of interest was postoperative adverse event including reoperation within 30 days, readmission within 30 days, discharge to rehab, and the complications wound infection/dehiscence, pneumonia, unplanned reintubation, pulmonary embolism (PE), renal insufficiency, urinary tract infection (UTI), stroke, venous thromboembolism (VT), and sepsis. RESULTS: 167 patients were identified who met study criteria. 58% were male, and the majority had an ASA classification of 3 or greater (68%). 96 (57%) patients were found to have a preoperative comorbidity, with the most common comorbidity being seizure disorder (54 patients, 32%). 76 patients (46%) had documented perioperative events or complications. The incidence of wound infection/dehiscence was 4%; and of pneumonia, PE, unplanned reintubation, renal insufficiency, UTI, stroke, VT, sepsis were <1%. There were no deaths. The incidence of unplanned reoperation was 10% and unplanned readmission was 12%. Most (90%) were discharged to home. Operative time (p = .0001, OR = 9.53), emergent surgery status (p = .0001, OR = 8.19) and preoperative comorbidities (p = .007) were found to be significant predictors of poor outcome. CONCLUSION: In the NSQIP-P dataset, the incidence of perioperative complications and suboptimal outcomes among patients undergoing AVM resection were low.


Assuntos
Fístula Arteriovenosa/cirurgia , Craniotomia/efeitos adversos , Malformações Arteriovenosas Intracranianas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Complicações Pós-Operatórias/etiologia , Fatores de Risco
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