Multiprofessional Management of Giant Cell Tumors in the Cervical Spine: A Systematic Review.

BACKGROUND: Giant cell tumors of the bone (GCTB) are rare bone tumors, especially in the cervical spine. Generally considered benign, local aggressiveness and metastatic growth have been described. Surgical concepts for GCTB are challenged by complex neurovascular anatomy. Specific clinical management guidelines are nonexistent. This systematic review aims to compile existing evidence on the treatment of GCTB of the cervical spine. METHODS: Four electronic databases were searched: Medline, Embase, Web of Science, and Cochrane Library. All clinical studies reporting the treatment of GCTB in the human cervical spine in English language were found eligible for review. RESULTS: Seven studies were included in the synthesis including a total number of 54 patients. Of those patients, 46 (85%) were treated for naive nonrecurrent GCTB. Only 1 study is considered a cohort study; all other studies were case reports. Generally, intralesional procedures were performed in 13 (24%) cases. Subtotal resections were reported for 11 (20%) patients. Twenty-eight (52%) patients were surgically treated with piecemeal resection, en-bloc resection, or spondylectomy. Thirty-six (67%) patients underwent adjuvant radiotherapy. A combination of radiotherapy and chemotherapy was reported in 2 (4%) cases. Bisphosphonates were prescribed for 9 (17%) patients. Inconsistent reporting of outcome data did not allow for comparative analyses. CONCLUSIONS: Best available evidence suggests that the most aggressive surgical approach should be the main goal of any GCTB surgery. No specific adjuvant or neoadjuvant treatment can be recommended as superior due to a lack of comparative data. Therapeutic approaches need to be planned thoroughly on an individual basis.

In-Vitro Use of 5-ALA for Photodynamic Therapy in Pediatric Brain Tumors.

BACKGROUND: Light irradiation (635 nm) of cells containing protoporphyrin IX (PPIX) after 5- aminolevulinic acid (5-ALA) pretreatment causes cell death via different pathways including apoptosis and necrosis, as previously demonstrated for malignant glioma cells. OBJECTIVE: To elucidate whether various malignant pediatric brain tumors, which have been shown to accumulate PPIX, would also be susceptible to photodynamic therapy (PDT). METHODS: Medulloblastoma (DAOY, UW228), pNET (PFSK-1), and rhabdoid tumor (BT16) cell lines were incubated with 5-ALA in variable concentrations for 4 h. Consequently, cells were irradiated by 635 nm diode laser light. After 12 h, cell viability was measured by WST-1 testing and these results were compared to control cells incubated with 5-ALA without irradiation or irradiation only without prior incubation with 5-ALA. RESULTS: We demonstrated significant cell death in malignant pediatric tumor cells after incubation with 5-ALA and laser irradiation in comparison to control groups. In all cell lines, we noticed significant cell death above a 5-ALA concentration of 50 µg/ml (P < .05). Neither 5-ALA incubation alone nor irradiation alone caused cell death. DAOY and PFSK cell lines were more susceptible than UW228 and BT16 cells. CONCLUSION: We conclude that PDT causes cell death with higher PPIX concentrations after exposure to 5-ALA in vitro in accordance to similar studies with glioma cells. This indicates that PDT might be feasible for eliminating brain tumor cells in malignant pediatric brain tumors. Additionally, we noticed a dependency between fluorescence intensity and death rates.

Surgical treatment of lumbosacral pseudarthrosis and spondyloptosis in a patient with neurofibromatosis type 1 and a large lumbar anterior meningocele. Case report and review of the literature.

BACKGROUND: Lumbar anterior meningocele (MC) is rare in patients with neurofibromatosis type 1 (NF1). Although spinal fusion with maximum possible resection of the cele might be indicated in these special cases, reports describing operative procedures are lacking. CLINICAL PRESENTATION: We present a young woman with NF1 and lower back pain due to lumbar anterior MC, extensive osteolysis, and deformation of the lumbar spine. After Harrington spondylodesis from T12 to S1 in 1989, she developed lumbosacral pseudarthrosis and transcutaneous migration of the spondylodesis. Thus the left pole of the spondylodesis was shortened below the level of L5 in 2005. Years later, the patient presented with lower back pain and wound infection. Imaging revealed the MC and avulsion of the right S1 screw with lumbosacral pseudarthrosis and spondyloptosis, and transcutaneous migration of the right spondylodesis pole. Three-stage surgery was indicated with explantation of the Harrington system in the first step and posterior fusion from T10 to S2 in the second step. Finally, vertebral resection, gathering of the cele, and implantation of a customized titanium cage was achieved through an anterior transabdominal approach. Postoperatively, the patient reported sufficient reduction of lower back pain. CONCLUSIONS: Lumbar anterior MC is rare in patients with NF1 and may cause spinal instability. When surgery is indicated, long-range spinal fusion and reduction of the cele should be considered. Surgery may be challenging requiring a staged operative procedure and an interdisciplinary collaboration.

Glioma tissue obtained by modern ultrasonic aspiration with a simple sterile suction trap for primary cell culture and pathological evaluation.

OBJECTIVES: Ultrasonic aspiration is widely used in the resection of brain tumors. Nevertheless, tumor tissue fragments obtained by ultrasonic aspiration are usually discarded. In this study, we demonstrate that these fragments are possible sources of material for histopathological study and tissue culture and compare their microscopic features and viability in tissue culture of cavitron ultrasonic surgical aspirator tissue fragments. METHODS: Brain tumor tissue collected by ultrasonic aspiration (CUSA EXcel®; Integra Radionics Inc.) in a simple sterile suction trap during resection was processed for primary cell culture. Cell viability and immunohistological markers were measured by the WST-1 test, microscopy and immunofluorescent evaluation. RESULTS: Six gliomas are presented to demonstrate that these tissue fragments show good preservation of histological detail and tissue viability in culture. CONCLUSION: Utilization of this material may facilitate pathological interpretation by providing a more representative sample of tumor histology as well as an adequate and sterile biosource of material for tissue culture studies.

Kinetics of porphyrin fluorescence accumulation in pediatric brain tumor cells incubated in 5-aminolevulinic acid.

BACKGROUND: Fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) enables more complete resections of tumors in adults. 5-ALA elicits accumulation of fluorescent porphyrins in various cancerous tissues, which can be visualized using a modified neurosurgical microscope with blue light. Although this technique is well established in adults, it has not been investigated systematically in pediatric brain tumors. Specifically, it is unknown how quickly, how long, and to what extent various pediatric tumors accumulate fluorescence. The purpose of this study was to determine utility and time course of 5-ALA-induced fluorescence in typical pediatric brain tumors in vitro. METHODS: Cell cultures of medulloblastoma [DAOY and UW228], cPNET [PFSK] atypical teratoid rhabdoid tumor [BT16] and ependymoma [RES196] were incubated with 5-ALA for either 60 minutes or continuously. Porphyrin fluorescence intensities were determined using a fluorescence-activated cell sorter (FACS) after 1, 3, 6, 9, 12 and 24 hours. C6 and U87 cells served as controls. RESULTS: All pediatric brain tumor cell lines displayed fluorescence compared to their respective controls without 5-ALA (p < 0.05). Sixty minutes of incubation resulted in peaks between 3 and 6 hours, whereas continuous incubation resulted in peaks at 12 hours or beyond. 60 minute incubation peak levels were between 52 and 91 % of maxima achieved with continuous incubation. Accumulation and clearance varied between cell types. CONCLUSIONS: We demonstrate that 5-ALA exposure of cell lines derived from typical pediatric central nervous system (CNS) tumors induces accumulation of fluorescent porphyrins. Differences in uptake and clearance indicate that different application modes may be necessary for fluorescence-guided resection, depending on tumor type.

Evaluation of post-operative complications associated with repeat resection and BCNU wafer implantation in recurrent glioblastoma.

BACKGROUND: Patients with glioblastoma treated with BCNU wafer implantation for recurrence frequently receive frontline chemoradiotherapy with temozolomide as part of the Stupp protocol. A retrospective investigation was conducted of surgical complications in a cohort of these patients treated at a single institution. METHODS: We searched our institutional database for patients treated between January 2006 and October 2012 who had recurrent glioblastoma previously treated with open surgery followed by the Stupp protocol and then underwent repeat resection with or without BCNU wafers for recurrent disease. Rates of select post-operative complications within 3 months of surgery were estimated. RESULTS: We identified 95 patients with glioblastoma who underwent resection followed by the Stupp protocol as frontline treatment. At disease recurrence (first and second recurrence), 63 patients underwent repeat resection with BCNU wafer implantation and 32 without implantation. Generally, BCNU wafer use was associated with minor to moderate increases in rates of select complications versus non-implantation-wound healing abnormalities (14.2 vs. 6.2 %), cerebrospinal fluid leak (7.9 vs. 3.1 %), hydrocephalus requiring ventriculoperitoneal shunt (6.3 vs. 9.3 %), chemical meningitis (3.1 vs. 0 %), cerebral infections (3.1 vs. 0 %), cyst formation (3.1 vs. 3.1 %), cerebral edema (4.7 vs. 0 %), and empyema formations (1.5 vs. 0 %). Performance status was well maintained post-operatively in both groups. Median progression-free survival from the time of first recurrence was 6.0 and 5.0 months, respectively. CONCLUSIONS: The use of the Stupp protocol as frontline therapy in patients with glioblastoma does not preclude the use of BCNU wafers at the time of progression.

Aquaporin-4 in glioma and metastatic tissues harboring 5-aminolevulinic acid-induced porphyrin fluorescence.

INTRODUCTION: Aquaporin channels (AQPs) are a group of integral membrane proteins that regulate the transport of water through cell membranes. Previous studies have shown that up-regulation of AQP1 and AQP4, two of the predominant AQPs in the human brain, in high grade glial tumors contribute to cerebral edema. Others link AQPs to the regulation of human glioma cell migration and invasion. The aim of this study was to determine AQPs expression in tumor tissue harboring 5-aminolevulinic acid (ALA)-induced porphyrin fluorescence with flow cytometry and compare it to the expression in normal brain tissue. METHODS: Tissue samples were obtained from fluorescing brain tumors of 26 patients treated with ALA prior to surgery (20 mg/kg b.w.). Expression levels of aquaporin channels were measured in primary tissue cultures using a FACS CANTO I flow cytometer. A control group consisted of four non-fluorescing tissue samples, the C6 and the U87 cell line. RESULTS: Nineteen gliomas (14 high grade, 5 low grade) and 7 metastases were analyzed. On the 4th post-operative day, expression levels of AQP4 channels, but not of AQP1 channels, were significantly increased in samples from fluorescing tissue compared to non-fluorescing tissue. In addition we could see how ALA induces fluorescence in metastases. CONCLUSION: Flow cytometry appears to be an auspicious method for the analysis of porphyrins and AQPs in primary brain cell tumor cultures. ALA fluorescing tissue showed higher AQP4 expression compared to normal brain tissue. The demonstrated expression in a context with ALA could open a targeted therapeutic spectrum, for example to selectively target AQP4.