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1.
J Clin Med ; 13(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38592365

RESUMO

The transfacet minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a novel approach available for the management of lumbar spondylolisthesis. It avoids the need to manipulate either of the exiting or traversing nerve roots, both protected by the bony boundaries of the approach. With the advancement in operative technologies such as navigation, mapping, segmentation, and augmented reality (AR), surgeons are prompted to utilize these technologies to enhance their surgical outcomes. A 36-year-old male patient was complaining of chronic progressive lower back pain. He was found to have grade 2 L4/5 spondylolisthesis. We studied the feasibility of a trans-Kambin or a transfacet MIS-TLIF, and decided to proceed with the latter given the wider corridor it provides. Preoperative trajectory planning and level segmentation in addition to intraoperative navigation and image merging were all utilized to provide an AR model to guide us through the surgery. The use of AR can build on the safety and learning of novel surgical approaches to spine pathologies. However, larger high-quality studies are needed to further objectively analyze its impact on surgical outcomes and to expand on its application.

2.
J Neurooncol ; 167(1): 219-227, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340295

RESUMO

PURPOSE: During stereotactic radiosurgery (SRS) planning for brain metastases (BM), brain MRIs are reviewed to select appropriate targets based on radiographic characteristics. Some BM are difficult to detect and/or definitively identify and may go untreated initially, only to become apparent on future imaging. We hypothesized that in patients receiving multiple courses of SRS, reviewing the initial planning MRI would reveal early evidence of lesions that developed into metastases requiring SRS. METHODS: Patients undergoing two or more courses of SRS to BM within 6 months between 2016 and 2018 were included in this single-institution, retrospective study. Brain MRIs from the initial course were reviewed for lesions at the same location as subsequently treated metastases; if present, this lesion was classified as a "retrospectively identified metastasis" or RIM. RIMs were subcategorized as meeting or not meeting diagnostic imaging criteria for BM (+ DC or -DC, respectively). RESULTS: Among 683 patients undergoing 923 SRS courses, 98 patients met inclusion criteria. There were 115 repeat courses of SRS, with 345 treated metastases in the subsequent course, 128 of which were associated with RIMs found in a prior MRI. 58% of RIMs were + DC. 17 (15%) of subsequent courses consisted solely of metastases associated with + DC RIMs. CONCLUSION: Radiographic evidence of brain metastases requiring future treatment was occasionally present on brain MRIs from prior SRS treatments. Most RIMs were + DC, and some subsequent SRS courses treated only + DC RIMs. These findings suggest enhanced BM detection might enable earlier treatment and reduce the need for additional SRS.


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Humanos , Radiocirurgia/métodos , Estudos Retrospectivos , Incidência , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética
3.
ArXiv ; 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37608932

RESUMO

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.

4.
ArXiv ; 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37608937

RESUMO

Meningiomas are the most common primary intracranial tumor in adults and can be associated with significant morbidity and mortality. Radiologists, neurosurgeons, neuro-oncologists, and radiation oncologists rely on multiparametric MRI (mpMRI) for diagnosis, treatment planning, and longitudinal treatment monitoring; yet automated, objective, and quantitative tools for non-invasive assessment of meningiomas on mpMRI are lacking. The BraTS meningioma 2023 challenge will provide a community standard and benchmark for state-of-the-art automated intracranial meningioma segmentation models based on the largest expert annotated multilabel meningioma mpMRI dataset to date. Challenge competitors will develop automated segmentation models to predict three distinct meningioma sub-regions on MRI including enhancing tumor, non-enhancing tumor core, and surrounding nonenhancing T2/FLAIR hyperintensity. Models will be evaluated on separate validation and held-out test datasets using standardized metrics utilized across the BraTS 2023 series of challenges including the Dice similarity coefficient and Hausdorff distance. The models developed during the course of this challenge will aid in incorporation of automated meningioma MRI segmentation into clinical practice, which will ultimately improve care of patients with meningioma.

5.
Int J Spine Surg ; 17(6): 760-770, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-37553259

RESUMO

BACKGROUND: There has been heightened interest in performing percutaneous lumbar interbody fusions (percLIFs) through Kambin's triangle, an anatomic corridor allowing entrance into the disc space. However, due to its novelty, there are limited data regarding the long-term benefits of this procedure. Our objective was to determine the long-term efficacy and durability of the percutaneous insertion of an expandable titanium cage through Kambin's triangle without facetectomy. METHODS: A retrospective review of patients undergoing percLIF via Kambin's triangle using an expandable titanium cage was performed. Demographics, visual analog scale (VAS) scores, Oswestry Disability Index (ODI), radiographic measurements, perioperative variables, and complications were recorded. VAS, ODI, and radiographic measurements were compared with baseline using the generalized estimating equations assuming normally distributed data. Fusion was assessed with computed tomography (CT) at 1 and 2 years after the procedure. RESULTS: A total of 49 patients were included. Spondylolisthesis, lumbar lordosis (LL), sacral slope, pelvic tilt, and anterior/posterior disc space height were all significantly improved postoperatively at each time point of 3, 6, 12, and 24 months (P < 0.001). Pelvic incidence-LL mismatch decreased significantly at each follow-up (P < 0.001) with a mean reduction of 4° by 24 months. VAS back scores reduced by >2 points at the 6, 12, and 24 month follow-ups. ODI scores reduced by >15 points at the 12- and 24-month follow-ups. Of the patients who had 1- and 2-year CT images, fusion rates at those time points were 94.4% (17/18) and 87.5% (7/8), respectively. The mean annual rate of surgically significant adjacent segment disease was 2.74% through an average follow-up of 2.74 years. CONCLUSION: These results highlight that percLIF, a procedure done without an endoscope or facetectomy, can be performed using an expandable titanium cage through Kambin's triangle with excellent radiographic and clinical results. CLINICAL RELEVANCE: percLIF via Kambin's triangle is a safe and succesful procedure with long-term improvements in both clinical and radiographic outcomes.

7.
ArXiv ; 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37396608

RESUMO

Gliomas are the most common type of primary brain tumors. Although gliomas are relatively rare, they are among the deadliest types of cancer, with a survival rate of less than 2 years after diagnosis. Gliomas are challenging to diagnose, hard to treat and inherently resistant to conventional therapy. Years of extensive research to improve diagnosis and treatment of gliomas have decreased mortality rates across the Global North, while chances of survival among individuals in low- and middle-income countries (LMICs) remain unchanged and are significantly worse in Sub-Saharan Africa (SSA) populations. Long-term survival with glioma is associated with the identification of appropriate pathological features on brain MRI and confirmation by histopathology. Since 2012, the Brain Tumor Segmentation (BraTS) Challenge have evaluated state-of-the-art machine learning methods to detect, characterize, and classify gliomas. However, it is unclear if the state-of-the-art methods can be widely implemented in SSA given the extensive use of lower-quality MRI technology, which produces poor image contrast and resolution and more importantly, the propensity for late presentation of disease at advanced stages as well as the unique characteristics of gliomas in SSA (i.e., suspected higher rates of gliomatosis cerebri). Thus, the BraTS-Africa Challenge provides a unique opportunity to include brain MRI glioma cases from SSA in global efforts through the BraTS Challenge to develop and evaluate computer-aided-diagnostic (CAD) methods for the detection and characterization of glioma in resource-limited settings, where the potential for CAD tools to transform healthcare are more likely.

8.
World Neurosurg ; 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37355168

RESUMO

OBJECTIVE: While Kambin's Triangle has become an ever more important anatomic window given its proximity to the exiting nerve root, there have been limited studies examining the effect of disease on the corridor. Our goal was to better understand how pathology can affect Kambin's Triangle, thereby altering the laterality of approach for percutaneous lumbar interbody fusion (percLIF). METHODS: The authors performed a single-center retrospective review of patients evaluated for percLIF. The areas of Kambin's Triangle were measured without and with nerve segmentation. For the latter, the lumbosacral nerve roots on 3-dimensional T2 magnetic resonance imaging were manually segmented. Next, the borders of Kambin's Triangle were delineated, ensuring no overlap between the area and nerve above. RESULTS: Fifteen patients (67.5 ± 9.7 years, 46.7% female) were retrospectively reviewed. We measured 150 Kambin's Triangles. The mean areas from L1-S1 were 50.0 ± 12.3 mm2, 73.8 ± 12.5 mm2, 83.8 ± 12.2 mm2, 88.5 ± 19.0 mm2, and 116 ± 29.3 mm2, respectively. When pathology was present, the areas significantly decreased at L4-L5 (P = 0.046) and L5-S1 (P = 0.049). Higher spondylolisthesis and smaller posterior disk heights were linked with decreased areas via linear regression analysis (P < 0.05). When nerve segmentation was used, the areas were significantly smaller from L1-L5 (P < 0.05). Among 11 patients who underwent surgery, none suffered from postoperative neuropathies. CONCLUSIONS: These results illustrate the feasibility of preoperatively segmenting lumbosacral nerves and measuring Kambin's Triangle to help guide surgical planning and determine the ideal laterality of approach for percLIF.

9.
Oper Neurosurg (Hagerstown) ; 24(3): 331-340, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36701664

RESUMO

BACKGROUND: For percutaneous lumbar fusion (percLIF), magnetic resonance imaging and computed tomography are critical to defining surgical corridors. Currently, these scans are performed separately, and surgeons then use fluoroscopy or neuromonitoring to guide instruments through Kambin's triangle. However, anatomic variations and intraoperative positional changes are possible, meaning that safely accessing Kambin's triangle remains a challenge because nerveroot visualization without endoscopes has not been thoroughly described. OBJECTIVE: To overcome the known challenges of percLIF and reduce the likelihood of iatrogenic injuries by showing real-time locations of neural and bony anatomy. METHODS: The authors demonstrate an intraoperative navigational platform that applies nerve root segmentation and image fusion to assist with percLIF. Five patients from a single institution were included. RESULTS: Of the 5 patients, the mean age was 71 ± 8 years and 3 patients (60%) were female. One patient had general anesthesia while the remaining 4 patients underwent awake surgery with spinal anesthesia. The mean area for the L4-L5 Kambin's triangle was 76.1 ± 14.5 mm 2 . A case example is shown where the side of approach was based on the fact that Kambin's triangle was larger on one side compared with the other. The mean operative time was 170 ± 17 minutes, the mean blood loss was 32 ± 16 mL, and the mean hospital length of stay was 19.6 ± 8.3 hours. No patients developed postoperative complications. CONCLUSION: This case series demonstrates the successful and safe application of nerve segmentation using magnetic resonance imaging/computed tomography fusion to perform percLIF and provide positive patient outcomes.


Assuntos
Neoplasias Encefálicas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vigília , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
10.
Sci Rep ; 13(1): 189, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604467

RESUMO

Non-contrast head CT (NCCT) is extremely insensitive for early (< 3-6 h) acute infarct identification. We developed a deep learning model that detects and delineates suspected early acute infarcts on NCCT, using diffusion MRI as ground truth (3566 NCCT/MRI training patient pairs). The model substantially outperformed 3 expert neuroradiologists on a test set of 150 CT scans of patients who were potential candidates for thrombectomy (60 stroke-negative, 90 stroke-positive middle cerebral artery territory only infarcts), with sensitivity 96% (specificity 72%) for the model versus 61-66% (specificity 90-92%) for the experts; model infarct volume estimates also strongly correlated with those of diffusion MRI (r2 > 0.98). When this 150 CT test set was expanded to include a total of 364 CT scans with a more heterogeneous distribution of infarct locations (94 stroke-negative, 270 stroke-positive mixed territory infarcts), model sensitivity was 97%, specificity 99%, for detection of infarcts larger than the 70 mL volume threshold used for patient selection in several major randomized controlled trials of thrombectomy treatment.


Assuntos
Aprendizado Profundo , Acidente Vascular Cerebral , Humanos , Tomografia Computadorizada por Raios X , Acidente Vascular Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Infarto da Artéria Cerebral Média
11.
Neurosurg Focus ; 54(1): E6, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36587400

RESUMO

OBJECTIVE: The authors sought to analyze the current literature to determine dimensional trends across the lumbar levels of Kambin's triangle, clarify the role of imaging techniques for preoperative planning, and understand the effect of inclusion of the superior articular process (SAP). This compiled knowledge of the triangle is needed to perform successful procedures, reduce nerve root injuries, and help guide surgeons in training. METHODS: The authors performed a search of multiple databases using combinations of keywords: Kambin's triangle, size, measurement, safe triangle, and bony triangle. Articles were included if their main findings included measurement of Kambin's triangle. The PubMed, Scopus, Ovid, Cochrane, Embase, and Medline databases were systematically searched for English-language articles with no time frame restrictions through July 2022. RESULTS: Eight studies comprising 132 patients or cadavers were included in the study. The mean ± SD age was 66.69 ± 9.6 years, and 53% of patients were male. Overall, the size of Kambin's triangle increased in area moving down vertebral levels, with L5-S1 being the largest (133.59 ± 4.36 mm2). This trend followed a linear regression model when SAP was kept (p = 0.008) and removed (p = 0.003). There was also a considerable increase in the size of Kambin's triangle if the SAP was removed. CONCLUSIONS: Here, the authors have provided the first reported systematic review of the literature of Kambin's triangle, its measurements at each lumbar level, and key areas of debate related to the definition of the working safe zone. These findings indicate that CT is heavily utilized for imaging of the safe zone, the area of Kambin's triangle tends to increase caudally, and variation exists between patients. Future studies should focus on using advanced imaging techniques for preoperative planning and establishing guidelines for surgeons.


Assuntos
Radiculopatia , Cirurgiões , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Cadáver
12.
Int J Radiat Oncol Biol Phys ; 115(3): 779-793, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36289038

RESUMO

PURPOSE: We sought to develop a computer-aided detection (CAD) system that optimally augments human performance, excelling especially at identifying small inconspicuous brain metastases (BMs), by training a convolutional neural network on a unique magnetic resonance imaging (MRI) data set containing subtle BMs that were not detected prospectively during routine clinical care. METHODS AND MATERIALS: Patients receiving stereotactic radiosurgery (SRS) for BMs at our institution from 2016 to 2018 without prior brain-directed therapy or small cell histology were eligible. For patients who underwent 2 consecutive courses of SRS, treatment planning MRIs from their initial course were reviewed for radiographic evidence of an emerging metastasis at the same location as metastases treated in their second SRS course. If present, these previously unidentified lesions were contoured and categorized as retrospectively identified metastases (RIMs). RIMs were further subcategorized according to whether they did (+DC) or did not (-DC) meet diagnostic imaging-based criteria to definitively classify them as metastases based upon their appearance in the initial MRI alone. Prospectively identified metastases (PIMs) from these patients, and from patients who only underwent a single course of SRS, were also included. An open-source convolutional neural network architecture was adapted and trained to detect both RIMs and PIMs on thin-slice, contrast-enhanced, spoiled gradient echo MRIs. Patients were randomized into 5 groups: 4 for training/cross-validation and 1 for testing. RESULTS: One hundred thirty-five patients with 563 metastases, including 72 RIMS, met criteria. For the test group, CAD sensitivity was 94% for PIMs, 80% for +DC RIMs, and 79% for PIMs and +DC RIMs with diameter <3 mm, with a median of 2 false positives per patient and a Dice coefficient of 0.79. CONCLUSIONS: Our CAD model, trained on a novel data set and using a single common MR sequence, demonstrated high sensitivity and specificity overall, outperforming published CAD results for small metastases and RIMs - the lesion types most in need of human performance augmentation.


Assuntos
Neoplasias Encefálicas , Aprendizado Profundo , Radiocirurgia , Humanos , Estudos Retrospectivos , Radiocirurgia/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/secundário
13.
Oper Neurosurg (Hagerstown) ; 21(6): 400-408, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34624892

RESUMO

BACKGROUND: Minimally invasive spine surgery (MISS) has the potential to further advance with the use of robot-assisted (RA) techniques. While RA pedicle screw placement has been extensively investigated, there is a lack of literature on the use of the robot for other tasks, such as accessing Kambin's triangle in percutaneous lumbar interbody fusion (percLIF). OBJECTIVE: To characterize the surgical feasibility and preliminary outcomes of an initial case series of 10 patients receiving percLIF with RA cage placement via Kambin's triangle. METHODS: We performed a single-center, retrospective review of patients undergoing RA percLIF using robot-guided trajectory to access Kambin's triangle for cage placement. Patients undergoing RA percLIF were eligible for enrollment. Baseline health and demographic information in addition to peri- and postoperative data was collected. The dimensions of each patient's Kambin's triangle were measured. RESULTS: Ten patients and 11 levels with spondylolisthesis were retrospectively reviewed. All patients successfully underwent the planned procedure without perioperative complications. Four patients underwent their procedure with awake anesthesia. The average dimension of Kambin's triangle was 66.3 m2. With the exception of 1 patient who stayed in the hospital for 7 d, the average length of stay was 1.2 d, with 2 patients discharged the day of surgery. No patients suffered postoperative motor or sensory deficits. Spinopelvic parameters and anterior and posterior disc heights were improved with surgery. CONCLUSION: As MISS continues to evolve, further exploration of robot-guided surgical practice, such as our technique, will lead to creative solutions to challenging anatomical variation and overall improved patient care.


Assuntos
Parafusos Pediculares , Procedimentos Cirúrgicos Robóticos , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/métodos
14.
Neuroimaging Clin N Am ; 28(3): 525-536, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30007760

RESUMO

Computed tomography is often the first-line diagnostic imaging modality in the evaluation of patients with neurologic emergencies. A patient-centered approach to radiation dose management in emergent neuroimaging thus revolves around the appropriate use of computed tomography, including clinical decision support for ordering providers, thoughtful protocol design, the use of available technological advances in computed tomography, and radiation exposure monitoring at a population level. A multifaceted approach can help to minimize radiation exposure to individual patients while preserving diagnostic quality imaging.


Assuntos
Encefalopatias/diagnóstico por imagem , Traumatismo Cerebrovascular/diagnóstico por imagem , Traumatismos Craniocerebrais/diagnóstico por imagem , Neuroimagem , Doses de Radiação , Serviço Hospitalar de Emergência , Humanos , Tomografia Computadorizada por Raios X
15.
Abdom Radiol (NY) ; 42(8): 2168-2174, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28349225

RESUMO

PURPOSE: To assess the impact of hepatobiliary phase images obtained during intravenous gadoxetate disodium-enhanced liver MRI in the planning of image-guided liver tumor ablations. METHODS: This institutional review board-approved retrospective study included 34 patients (21 men, 13 women, ages 25-80) who underwent 36 liver MRI examinations with gadoxetate disodium within 12 weeks prior to image-guided thermal ablation of 62 liver tumors during 36 procedures. Visibility of bile ducts, subdivided by branch order, on hepatobiliary phase images was compared to standard MRI sequence images by an attending abdominal radiologist and fellow. Interventional decision making (whether or not to ablate and technical plan) using hepatobiliary phase images was compared with standard MRI sequences by the ablationists. The technical success and adverse events of ablation procedures were noted. RESULTS: Bile duct visibility was significantly increased by at least one branch order in 18/36 (50%) examinations (p < 0.0001). Interventional decisions were significantly impacted in 15 (41.7%) of 36 ablation procedures (p < 0.0001), including changes to the technical plan in six (16.7%) of these procedures (p = 0.005). Technical success was achieved for 60/62 (97%) of tumors. Mild (grade 1) adverse events occurred in 4/36 (11%) procedures; no biliary complications occurred. CONCLUSIONS: Use of hepatobiliary phase images obtained during gadoxetate disodium-enhanced liver MRI impacted both when and how to perform image-guided liver tumor ablations in our practice.


Assuntos
Técnicas de Ablação , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
J Bone Joint Surg Am ; 98(1): 48-55, 2016 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-26738903

RESUMO

BACKGROUND: Radiation-induced fibrosis (RIF) of musculoskeletal tissue is a common complication of radiation therapy for extremity soft-tissue sarcoma, with no standardized strategy for prevention and treatment. Angiotensin-(1-7) (Ang-[1-7]), a well-tolerated endogenous heptapeptide hormone with antitumor and antifibrotic properties, was tested as a radioprotectant for RIF and stiffening of irradiated muscles. METHODS: Male CD-1 mice were randomized to one of three treatment groups: control, simulated sarcoma radiation therapy to the gastrocnemius and soleus muscles, or radiation therapy along with continuous Ang-(1-7) delivery initiated three days before radiation therapy. The biologically equivalent dose of radiation (∼100.3 Gy) absorbed by normal musculature during the course of radiation therapy for extremity sarcoma was delivered by means of four dose fractions of 7.3 Gy over two weeks. Fibrosis (n = 5 per group) and mechanical properties (n = 4 to 6 per group) of the muscles were measured at six weeks and four months after radiation therapy, and the intramuscular concentration of the profibrotic cytokines transforming growth factor-beta (TGF-ß) and connective tissue growth factor (CTGF) (n = 8 to 10 per group) were measured at six weeks. RESULTS: Interstitial (p < 0.01) and perivascular (p < 0.05) fibrosis increased significantly in the muscles treated with radiation therapy alone versus the nonirradiated controls at both six weeks (interstitial, +89%; perivascular, +112%) and four months (interstitial, +154%; perivascular, +88%). The muscles treated with radiation alone also exhibited increased tension (p < 0.01) versus nonirradiated controls at both six weeks (+779%) and four months (+1761%) when placed under 5% strain, and at four months (+1390%; p < 0.001) under 10% strain. At four months, muscle stiffness had increased in the mice treated with radiation therapy alone (+90%; p = 0.002) compared with nonirradiated controls. TGF-ß production was also greater in this group at six weeks (+37%; p = 0.06) versus control. Ang-(1-7) administration prevented RIF and stiffening, with no differences observed for any other outcome between those receiving radiation therapy with Ang-(1-7) and the nonirradiated controls. Likewise, Ang-(1-7) mitigated the increase in TGF-ß and CTGF concentration from radiation therapy. CONCLUSIONS: Ang-(1-7) attenuated RIF, stiffening, and production of profibrotic cytokines that were elevated in mouse skeletal muscles after simulated radiation therapy for extremity sarcoma. CLINICAL RELEVANCE: Ang-(1-7) may serve as a potential therapy for the prevention of RIF in patients who require radiation therapy as adjuvant treatment for soft-tissue sarcoma.


Assuntos
Angiotensina I/administração & dosagem , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/efeitos da radiação , Fragmentos de Peptídeos/administração & dosagem , Sarcoma Experimental/terapia , Espasmo/prevenção & controle , Análise de Variância , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Fibrose/etiologia , Fibrose/prevenção & controle , Membro Posterior , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos , Neoplasias Musculares/patologia , Neoplasias Musculares/terapia , Músculo Esquelético/patologia , Distribuição Aleatória , Valores de Referência , Sarcoma Experimental/patologia , Sensibilidade e Especificidade , Espasmo/patologia
17.
J Neurooncol ; 123(2): 259-66, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25947286

RESUMO

Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in preclinical models. We report final data from a prospective, multi-institutional study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in patients with newly diagnosed malignant glioma. 65 patients were consented in 4 institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After resection and BCNU wafer placement, TMZ began on day four postoperatively. Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200 mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining 20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %) who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2, experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS) and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year OS rate was 76 %, which is a significant improvement compared with the historical control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1-year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely administered with BCNU wafers following resection of malignant glioma at the 150 mg/m2 dose level. Although there was an OS benefit compared to historical control, there was no indication of benefit for BCNU wafers and early TMZ in addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers followed by RT/TMZ.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Glioma/mortalidade , Glioma/terapia , Adulto , Idoso , Neoplasias Encefálicas/patologia , Carmustina/administração & dosagem , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Feminino , Seguimentos , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Período Pós-Operatório , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Taxa de Sobrevida , Temozolomida
18.
Int J Radiat Oncol Biol Phys ; 88(4): 899-906, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24606851

RESUMO

PURPOSE: Resected brain metastases (BM) require radiation therapy to reduce local recurrence. Whole brain radiation therapy (WBRT) reduces recurrence, but with potential toxicity. Postoperative stereotactic radiosurgery (SRS) is a strategy without prospective data and problematic target delineation. SRS delivered in the preoperative setting (neoadjuvant, or NaSRS) allows clear target definition and reduction of intraoperative dissemination of tumor cells. METHODS AND MATERIALS: Our treatment of resectable BM with NaSRS was begun in 2005. Subsequently, a prospective trial of NaSRS was undertaken. A total of 47 consecutively treated patients (23 database and 24 prospective trial) with a total of 51 lesions were reviewed. No statistical difference was observed between the 2 cohorts, and they were combined for analysis. The median follow-up time was 12 months (range, 1-58 months), and the median age was 57. A median of 1 day elapsed between NaSRS and resection. The median diameter of lesions was 3.04 cm (range, 1.34-5.21 cm), and the median volume was 8.49 cc (range, 0.89-46.7 cc). A dose reduction strategy was used, with a median dose of 14 Gy (range, 11.6-18 Gy) prescribed to 80% isodose. RESULTS: Kaplan-Meier overall survival was 77.8% and 60.0% at 6 and 12 months. Kaplan-Meier local control was 97.8%, 85.6%, and 71.8% at 6, 12, and 24 months, respectively. Five of 8 failures were proved pathologically without radiation necrosis. There were no perioperative adverse events. Ultimately, 14.8% of the patients were treated with WBRT. Local failure was more likely with lesions >10 cc (P=.01), >3.4 cm (P=.014), with a trend in surface lesions (P=.066) and eloquent areas (P=.052). Six of the 8 failures had an obvious dural attachment or proximity to draining veins. CONCLUSIONS: NaSRS can be performed safely and effectively with excellent results without documented radiation necrosis. Local control was excellent even in the setting of large (>3 cm) lesions. The strong majority of patients were able to avoid WBRT. NaSRS merits consideration in a multi-institution trial.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Radiocirurgia/métodos , Adulto , Idoso , Análise de Variância , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/mortalidade , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Radiocirurgia/mortalidade , Dosagem Radioterapêutica , Estudos Retrospectivos , Tempo para o Tratamento , Carga Tumoral
19.
J Hand Surg Am ; 36(2): 222-31, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21276885

RESUMO

PURPOSE: The chemical denervation that results from botulinum neurotoxin A (BoNT-A) causes a temporary, reversible paresis that can result in easier surgical manipulation of the muscle-tendon unit in the context of tendon rupture and repair. The purpose of the study was to determine whether BoNT-A injections can be used to temporarily and reversibly modulate active and passive skeletal muscle properties. METHODS: Male CD1 mice weighing 40-50 g were divided into a 1-week postinjection group (n = 13: n = 5 saline and n = 8 BoNT-A) and a 2-week postinjection group (n = 17: n = 7 saline and n = 10 BoNT-A). The animals had in vivo muscle force testing and in vivo biomechanical evaluation. RESULTS: There was a substantial decline in the maximal single twitch amplitude (p < .05) and tetanic amplitude (p < .05) at one week and at 2 weeks after BoNT-A injection, when compared to saline-injected controls. BoNT-A injection significantly reduced the peak passive properties of the muscle-tendon unit as a function of displacement at one week (p < .05). Specifically, the stiffness of the BoNT-A injected muscle-tendon unit was 0.417 N/mm compared to the control saline injected group, which was 0.634 N/mm, a 35% reduction in stiffness (p < .05). CONCLUSIONS: Presurgical treatment with BoNT-A might improve the surgical manipulation of the muscle-tendon unit, thus improving surgical outcomes. The results implicate neural tone as a substantial contributor to the passive repair tension of the muscle-tendon unit. The modulation of neural tone through temporary, reversible paresis is a novel approach that might improve intraoperative and postoperative passive muscle properties, allowing for progressive rehabilitation while protecting the surgical repair site.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Denervação Muscular/métodos , Animais , Modelos Animais de Doenças , Injeções Intramusculares , Masculino , Camundongos , Camundongos Endogâmicos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/cirurgia , Procedimentos Ortopédicos/métodos , Cuidados Pré-Operatórios/métodos , Probabilidade , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Tendões/cirurgia
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