Upregulated CBX8 Promotes Cancer Metastasis via the WNK2/MMP2 Pathway.

Metastasis is associated with poor prognosis in cancer and is a multistep process that includes invasion and migration. Several epigenetic factors are involved in this process, including chromobox protein homolog 8 (CBX8). Here, we show that CBX8 is overexpressed in many cancers compared with normal tissues. Functional analyses indicated that CBX8 promoted invasion and migration in glioblastoma, breast cancer, and lung cancer in vitro and in vivo. WNK2 was identified as a target gene of CBX8, which interacted with the WNK2 promoter to suppress WNK2 expression and activity. WNK2 acted as an antioncogene, and decreased WNK2 levels resulted in high activity of matrix metalloprotease (MMP)-2 and RAC1, which play a central role in invasion and migration, respectively. There was a positive relationship between MMP2 and RAC1 activity in CBX8-modulated cell lines. In addition, WNK2 negatively regulated MMP2 and RAC1 activity. Collectively, the results indicated that CBX8 promoted invasion and migration by targeting WNK2, which resulted in increased RAC1 and MMP2 expression and activity. Therefore, CBX8 may be a novel therapeutic target to treat metastatic cancers.

Chronic Leptomeningitis and Spinal Intradural Mass Secondary to Alternaria Infection in a Patient with Ventriculoperitoneal Shunt.

Fungal infection following placement of ventriculostomy or ventriculoperitoneal (VP) shunt is uncommon. We report the first case of Alternaria related central nervous system (CNS) shunt infection in a patient with CNS ependymoma manifesting as leptomeningitis and a spinal intradural mass. This case illustrates the diagnostic and management challenges.

Posterior-only approach for lumbar vertebral column resection and expandable cage reconstruction for spinal metastases.

OBJECT: The increasing incidence of spinal metastasis, a result of improved systemic therapies for cancer, has spurred a search for an alternative method for the surgical treatment of lumbar metastases. The authors report a single-stage posterior-only approach for resecting any pathological lumbar vertebral segment and reconstructing with a medium to large expandable cage while preserving all neurological structures. METHODS: The authors conducted a retrospective consecutive case review of 11 patients (5 women, 6 men) with spinal metastases treated at 1 institution with single-stage posterior-only vertebral column resection and reconstruction with an expandable cage and pedicle screw fixation. For all patients, the indications for operative intervention were spinal cord compression, cauda equina compression, and/or spinal instability. Neurological status was classified according to the American Spinal Injury Association impairment scale, and functional outcomes were analyzed by using a visual analog scale for pain. RESULTS: For all patients, a circumferential vertebral column resection was achieved, and full decompression was performed with a posterior-only approach. Each cage was augmented by posterior pedicle screw fixation extending 2 levels above and below the resected level. No patient required a separate anterior procedure. Average estimated blood loss and duration of each surgery were 1618 ml (range 900-4000 ml) and 6.6 hours (range 4.5-9 hours), respectively. The mean follow-up time was 14 months (range 10-24 months). The median survival time after surgery was 17.7 months. Delayed hardware failure occurred for 1 patient. Preoperatively, 2 patients had intractable pain with intact lower-extremity strength and 8 patients had severe intractable pain, lower-extremity paresis, and were unable to walk; 4 of whom regained the ability to walk after surgery. Two patients who were paraplegic before decompression recovered substantial function but remained wheelchair bound, and 2 patients remained paraparetic after the surgery. No patients had lasting intraoperative neuromonitoring changes, and none died. Complications included 2 reoperations, 1 delayed hardware failure (cage subsidence that did not require revision), and 3 incidental durotomies (none of which required reoperation). No postoperative pneumonia, ileus, or deep venous thrombosis developed in any patient. CONCLUSIONS: A posterior-only approach for vertebral segment resection with preservation of spinal nerve roots is a viable technique that can be used throughout the entire lumbar spine. Extensive mobilization of the nerve roots is of utmost importance and allows for insertion and expansion of medium-sized, in situ expandable cages in the midline. This approach, although technically challenging, might reduce the morbidity associated with an anterior approach.

Mini-open transpedicular lumbar vertebrectomy reconstructed with double cages and short segment fixation.

BACKGROUND: The purpose of this study was to assess the feasibility of using dual expandable cages plus short segment posterior fixation for reconstruction of vertebral bodies following a mini-open transpedicular approach. METHODS: A single posterior incision was used to perform a laminectomy of L2, a partial laminectomy of L1 and bilateral transpedicular approaches for a piecemeal vertebrectomy in a patient with spinal compression secondary to metastatic cancer. Subsequently, bilateral cages were placed through the transpedicular corridors and percutaneous pedicle screws were inserted a single level above and below the level of the vertebral column resection. RESULTS: The bilateral transpedicular approach facilitated the use of a mini-open incision (6.0 cm) compared with the extensive dissection normally employed for a lateral extracavitary type approach in the lumbar region. The bilateral transpedicular approach at L2 allowed for a vertebrectomy and complete decompression of neurological elements. The use of expandable cages allowed the nerve roots to be preserved. Placement of the cages in the lateral position was straightforward despite minimal exposure. The reconstruction with double expandable cages appeared robust. CONCLUSIONS: In select patients requiring circumferential decompression of the lumbar spine, dual cage reconstruction decreases the technical difficulty of the operation and facilitates a mini-open approach. The durability of this construct will need biomechanical assessment and long-term clinical follow-up.