Inflammatory Profiling of Patients Undergoing Lumbar Interbody Fusion by Different Approaches: In Search for Markers of Mini-invasiveness

Abstract

IntroductionMinimally-invasive surgeries have become routinely adopted due to reduced tissue trauma and damage. In spine surgery, and particularly lumbar interbody fusion (LIF) procedures, several minimal invasive approaches are available.1–3 Although these approaches are thought to be less traumatic, and thus less pro-inflammatory, currently there are no scientific evidences about it.4 Creatin kinase (CK), C-reactive protein (CRP), interleukin (IL)-6 and IL-10, have been proposed as molecular discriminants between mini-invasive and conventional procedures.5 The aim of this work was to investigate how different approaches in LIF differed in inflammatory profiles over the immediate peri-surgical period. Material and MethodsSeventy consecutive patients affected by degenerative discopathy were prospectively enrolled. To better characterize the approach-dependent effects, very strict inclusion (single-level discopathy L3-to-S1, healthy status) and exclusion criteria (chronic pathologies, or recent illnesses) were applied. Seventeen patients underwent to anterior LIF (ALIF), 20 to transforaminal posterior LIF (TLIF), and 26 to far-lateral LIF (XLIF). Patients were sampled, by standard venipuncture, 24h pre-surgery (T0), and 24h (T1) and 72h (T2) post-surgery. Blood was collected into serum and plasma (Becton Dickinson & Co., Franklin Lakes, NJ, USA) tubes. Serum and plasma, obtained by centrifugation (1200 g, 10 minute, 4°C), were stored at -80°C until assayed for a panel of 37 molecules involved in inflammation (including cytokines, soluble cytokine receptors and metalloproteinases) were tested by a fluorescent bead-based multiplex system (Bio-Plex®, Bio-Rad Laboratories, Inc., Hercules, CA, USA). One-way ANOVA was used to study within-group time-dependent changes (repeated measures) and between-groups changes, at each time points (Prism v6, GraphPad Software, La Jolla, CA, USA). Significance was set at p < 0.05. ResultsAt baseline no differences were found in any of the subgroup, indicating homogeneity in pre-surgical conditions. In general, the inflammatory responses to ALIF and TLIF were comparable being characterized by an increase from T0 to T1 and a decrease from T1 to T2. Instead, in XLIF we found a stabilization, or even an increase, from T1 to T2. Interestingly, in all the procedure IL-10, IL-26, osteocalcin, osteopontin, pentraxin, and sTNFR-1 showed a linear increase, although delayed in XLIF. By comparing the amplitude of changes between the time-points, both ALIF and TLIF induced significantly much more sCD163, MMP-2, MMP-3, compared with XLIF. XLIF, instead, was more effective in inducing sCD30, IFN-α2, IFN-γ, IL-2, sIL-6R, sIL-6Rβ, IL-8, IL-10, IL-12p40, MMP-1, osteopontin, sTNFR-1, and sTNFR-2. ConclusionOur preliminary results indicate that: i) ALIF and TLIF are comparable in terms of inflammatory profile; ii) the amplitude of changes induced by surgery is greater in XLIF for the majority of the tested molecules; iii) XLIF is more effective in inducing anti-inflammatory mediators. Additional work is evaluating the relationship between the changes observed in these parameters and those recorded in analytes routinely measured in these settings (martial status, muscular enzymes). To have a panel of markers predicting the response of the patients to different surgical approaches could give the surgeon a valuable additional tool in deciding the optimal approach.ReferencesFoley KT, Holly LT, Schwender JD. Minimally invasive lumbar fusion. Spine 2003; 28(15, Suppl)S26–S35Berjano P, Damilano M, Lamartina C. Sagittal alignment correction and reconstruction of lumbar post-traumatic kyphosis via MIS lateral approach. Eur Spine J 2012;21(12):2718–2720Berjano P, Balsano M, Buric J, Petruzzi M, Lamartina C. Direct lateral access lumbar and thoracolumbar fusion: preliminary results. Eur Spine J 2012;21(1, Suppl 1):S37–S42Lombardi G, Grasso D, Berjano P, Banfi G, Lamartina C. Is minimally invasive spine surgery also pro-inflammatory? Muscular markers, inflammatory parameters and cytokines to quantify the operative invasiveness assessment in spine fusion. Eur J Inflam 2014;2:237–249Kim KT, Lee SH, Suk KS, Bae SC. The quantitative analysis of tissue injury markers after mini-open lumbar fusion. Spine 2006;31(6):712–716