Research news and notes
Article Outline
- 1. Antiangiogenic treatment for glioblastoma multiform
- 2. A biologic approach to the surgical treatment of degenerative disc disease
- 3. Anesthetics cause pain?
- References
- Copyright
1. Antiangiogenic treatment for glioblastoma multiform
The treatment of glioblastoma (GBM) remains limited and frustrating. This situation may change soon because new research and discoveries seem poised to significantly increase the options available to treat this horrible disease.
A recent study from Duke University (Durham, NC) [7] used a combination of the antiangiogenic antibody bevazicumab in combination with the cytotoxic drug irinotecan. The study was not designed to compare this regimen with any other treatment. The entire group of 35 patients was divided into a cohort of 23 who received 10 mg/kg of bevazicumab and irinotecan every 2 weeks. The other 12 patients served as preliminary evaluations of a different regimen: bevazicumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. The 6-month, progression-free survival among all 35 patients was 46%; the 6-month overall survival was 77%. These results appear very promising, given the usually disappointing response of GBM to chemotherapy. It is too early to celebrate because this is not a cure, and proof that survival is really better will have to await Phase 3 studies. Increasing knowledge of the many factors that contribute to growth and invasiveness of GBM will lead to new treatment paradigms.
2. A biologic approach to the surgical treatment of degenerative disc disease
Degenerative disc disease is very common in neurosurgical practice. Many cases of back pain are blamed on disc degeneration. However, our treatment of this common ailment may appear barbaric to the next generation of surgeons: we offer discectomy, interbody fusion, and artificial discs. Even if done through a small incision, the procedures are destructive in nature and illustrate our lack of knowledge and dearth of more appropriate technologies.
Two major problems have limited the efficacy of surgical treatment of degenerative disc disease: (1) inflammation develops in the laminectomy area, often causing symptoms that includes chronic pain and radiculopathy, and (2) surgery does not restore the biomechanical properties of the disc. Moreover, surgery may increase inflammation and degeneration within the disc. In a rat model, Ulrich et al [6] demonstrated that repeated disc injury during the healing phase leads to persistent inflammation and increases disc degeneration. This study illustrates how our current method of discectomy involves new injury and most likely promotes further inflammation.
Some solutions for both problems may be in sight. In a study of postlaminectomy healing in a rat model, Schimizzi et al [5] demonstrated a decrease in the concentration of inflammatory cells and cytokines when a high molecular weight hyaluronan gel was applied to the laminectomy site. Controls received only laminectomy and disc injury. The authors speculated that the gel may act by simple dilution, or may provide a viscous environment that delays the diffusion of inflammatory cytokines. I speculate that the gel occupies the space that would otherwise be filled with blood and inflammatory exudates. A different gel, carboxymethylcellulose/polyethylene oxide, has been available in Europe for use after laminectomy or discectomy and shows promise in preliminary uncontrolled case series [1]. Research into actual restoration of the nucleus pulposus is advancing quite rapidly. A group of researchers from the Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (Bethesda, MD), combined stem cell biology with construction of a scaffold that resembles the native disc structure [4]. They constructed a ring of nanofibrous material enveloping a center made of hyaluronic acid hydrogel. The construct was seeded with mesenchymal stem cells that were induced to undergo chondrogenesis. The cells differentiated and developed chondrocytic morphology. The study demonstrated the potential for the engineering of a new disc—a biological replacement organ, rather than prosthesis.
3. Anesthetics cause pain?
General anesthetics control pain, right? Well, not exactly. Common general inhalational anesthetics isoflurane, sevoflurane, enflurane, and desflurane were found to directly activate transient receptor potential A1 channel, typically activated by prostaglandins [2], [3]. The same anesthetics also sensitize the capsaicin receptor (transient receptor potential V1), a key ion channel expressed in nociceptive neurons. They appear to reduce the threshold for nociceptive neuron activation by heat as well as by bradykinin, a key mediator of inflammation [2]. Bradykinin is formed during tissue injury. It is unclear how long the effect of the general inhalational anesthetics lasts. It is possible that the administration of general inhalational anesthesia increases postoperative pain and inflammation? Will there be practical implications?
References
- . Use of carboxymethylcellulose/polyethylene oxide gel in microdiscectomy with interlaminectomy: a case series comparison with long-term follow-up. Spine. 2008;33(16):1762–1765
- . General anesthetics sensitize the capsaicin receptor TRPV1. Mol Pharmacol. 2008;[Electronic publication ahead of print]
- . Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2008;105(33):12045–12050
- . Intervertebral disc tissue engineering usingnanofibrousscaffoldamalgam. Tissue Eng Part A. 2008;14(9):1527–1537
- . High-molecular-weight hyaluronan inhibits macrophage proliferation and cytokine release in the early wound of a preclinical postlaminectomy rat model. Spine J. 2006;6(5):550–556
- . ISSLS prize winner: repeated disc injury causes persistent inflammation. Spine. 2007;32(25):2812–2819
- . Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007;25(30):4722–4729
PII: S0090-3019(08)00874-4
doi:10.1016/j.surneu.2008.09.024
© 2008 Published by Elsevier Inc.
