Frank La Marca

Changes in the utilization of spinal fusion in the United States

OBJECTIVE Several reports suggest that spine surgery has experienced rapid growth in the past decade. Limited data exist, however, documenting the increase in spinal fusion. The objective of this work was to quantify and characterize the contemporary practice of spinal fusion in the United States. METHODS Clinical data were obtained from the Nationwide Inpatient Sample for the years from 1993 to 2003. All patients with International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes indicating cervical fusion, thoracolumbar fusion, lumbar or unspecified fusion were identified (n = 471,990). Primary ICD-9-CM diagnosis codes were used to determine the rationale for surgical fusion. Population-based utilization rates overall and for each procedure were calculated from United States census data. Rank order of spinal fusion compared with other inpatient procedures from the Nationwide Inpatient Sample was reported for the years 1997 to 2003. RESULTS Overall utilization increased during the time period for cervical, thoracolumbar, and lumbar fusions by 89, 31, and 134%, respectively. Patients aged 40 to 59 years experienced the rapid rise in utilization for cervical fusions (60-110 per 100,000) and lumbar fusions (35-84 per 100,000). For patients 60 years and older, utilization also increased for cervical (30-67 per 100,000), thoracolumbar (4-9 per 100,000), and lumbar (42-108 per 100,000). Spinal fusion rose from the 41st most common inpatient procedure in 1997 to the 19th in 2003. CONCLUSION Cervical, thoracolumbar, and lumbar spinal fusion have experienced a rapid increase in utilization in isolation and compared with other surgical procedures in contemporary practice. These changes are most pronounced for patients over 40 years of age, and degenerative disc disease seems to account for much of this increase.

Bone Morphogenetic Proteins and Cancer: Review of the Literature

OBJECTIVEIn addition to their well-known osteogenic properties, bone morphogenetic proteins (BMPs) have developmental and regenerative roles that may impact tumorigenesis and promote tumor spread. Given that the most common site of tumor metastases to bone is the spine, determining whether BMPs can be linked to cancer is of particular relevance to surgeons treating primary or metastatic spinal disease. This article reviews the basic scientific and clinical background of BMPs and their potential role in promoting cancer. METHODSA literature review to identify studies relating to BMP and tumorigenesis was conducted. Databases evaluated included MEDLINE and EMBASE as well as the Cochrane Controlled Trials Register through 2008. RESULTSBone morphogenetic proteins are a diverse class of molecules belonging to the transforming growth factor-β superfamily that serve a variety of biologic functions. Bone morphogenetic proteins have critical roles in stem and progenitor cell biology as regulators of cellular expansion and differentiation. Transforming growth factor-β and related cell signaling pathways as well as stem and progenitor cell signaling have been linked to cancer. Multiple in vitro and in vivo studies suggest a significant role of BMPs in promoting tumorigenesis and metastasis. However, there are also comparable studies that imply that BMPs may have a negative effect on cancer. CONCLUSIONThere is no definitive association between BMPs and the promotion of tumorigenesis or metastasis. However, given the relatively large number of studies reporting a positive effect of BMPs on tumorigenesis or metastasis, the use of BMPs in patients with primary or metastatic spinal tumors should be carefully considered.

Prospective identification of tumorigenic osteosarcoma cancer stem cells in OS99-1 cells based on high aldehyde dehydrogenase activity

High aldehyde dehydrogenase (ALDH) activity has recently been used to identify tumorigenic cell fractions in many cancer types. Herein we hypothesized that a subpopulation of cells with cancer stem cells (CSCs) properties could be identified in established human osteosarcoma cell lines based on high ALDH activity. We previously showed that a subpopulation of cells with high ALDH activity were present in 4 selected human osteosarcoma cell lines, of which a significantly higher ALDH activity was present in the OS99‐1 cell line that was originally derived from a highly aggressive primary human osteosarcoma. Using a xenograft model in which OS99‐1 cells were grown in NOD/SCID mice, we identified a highly tumorigenic subpopulation of osteosarcoma cells based on their high ALDH activity. Cells with high ALDH activity (ALDHbr cells) from the OS99‐1 xenografts were much less frequent, averaging 3% of the entire tumor population, compared to those isolated directly from the OS99‐1 cell line. ALDHbr cells from the xenograft were enriched with greater tumorigenicity compared to their counterparts with low ALDH activity (ALDHlo cells), generating new tumors with as few as 100 cells in vivo. The highly tumorigenic ALDHbr cells illustrated the stem cell characteristics of self‐renewal, the ability to produce differentiated progeny and increased expression of stem cell marker genes OCT3/4A, Nanog and Sox‐2. The isolation of osteosarcoma CSCs by their high ALDH activity may provide new insight into the study of osteosarcoma‐initiating cells and may potentially have therapeutic implications for human osteosarcoma.

Impact of anesthesia on transcranial electric motor evoked potential monitoring during spine surgery: a review of the literature

OBJECT Transcranial motor evoked potential (TcMEP) monitoring is frequently used in complex spinal surgeries to prevent neurological injury. Anesthesia, however, can significantly affect the reliability of TcMEP monitoring. Understanding the impact of various anesthetic agents on neurophysiological monitoring is therefore essential. METHODS A literature search of the National Library of Medicine database was conducted to identify articles pertaining to anesthesia and TcMEP monitoring during spine surgery. Twenty studies were selected and reviewed. RESULTS Inhalational anesthetics and neuromuscular blockade have been shown to limit the ability of TcMEP monitoring to detect significant changes. Hypothermia can also negatively affect monitoring. Opioids, however, have little influence on TcMEPs. Total intravenous anesthesia regimens can minimize the need for inhalational anesthetics. CONCLUSIONS In general, selecting the appropriate anesthetic regimen with maintenance of a stable concentration of inhalational or intravenous anesthetics optimizes TcMEP monitoring.

Surgical management of symptomatic cervical or cervicothoracic kyphosis due to ankylosing spondylitis.

Study Design. Literature review. Objective. To evaluate surgical management and outcomes in the treatment of severe chin-on-chest deformities due to ankylosing spondylitis (AS). Summary of Background Data. AS is a chronic inflammatory disease that can lead to severe flexion deformities involving the cervicothoracic spine. The resulting chin-on-chest deformity can be extremely debilitating. Methods. Literature search using PubMed database. Results. Six retrospective clinical studies were identified. No randomized or prospective studies were found. The indication for surgery was primarily loss of horizontal gaze. The most common surgical technique was based on the original Simmons osteotomy at C7–T1. Analysis of radiographic studies and the chin-brow to vertical angles demonstrated significant improvement in the flexion deformity in all cases after surgery. The complication rate was high, ranging from 26.9% to 87.5%, with a mortality rate of 2.6%. However, most complications were minor, and the permanent neurologic complication rate was 4.3%. All patients had improvement in horizontal gaze, and patient satisfaction after surgery appeared high. Conclusion. Based on these studies, it seems that for the severely impaired patient with loss of horizontal gaze, surgical correction is a reasonable option with a high likelihood of success.

Complications in adult spinal deformity surgery: an analysis of minimally invasive, hybrid, and open surgical techniques.

OBJECT It is hypothesized that minimally invasive surgical techniques lead to fewer complications than open surgery for adult spinal deformity (ASD). The goal of this study was to analyze matched patient cohorts in an attempt to isolate the impact of approach on adverse events. METHODS Two multicenter databases queried for patients with ASD treated via surgery and at least 1 year of follow-up revealed 280 patients who had undergone minimally invasive surgery (MIS) or a hybrid procedure (HYB; n = 85) or open surgery (OPEN; n = 195). These patients were divided into 3 separate groups based on the approach performed and were propensity matched for age, preoperative sagittal vertebral axis (SVA), number of levels fused posteriorly, and lumbar coronal Cobb angle (CCA) in an attempt to neutralize these patient variables and to make conclusions based on approach only. Inclusion criteria for both databases were similar, and inclusion criteria specific to this study consisted of an age > 45 years, CCA > 20°, 3 or more levels of fusion, and minimum of 1 year of follow-up. Patients in the OPEN group with a thoracic CCA > 75° were excluded to further ensure a more homogeneous patient population. RESULTS In all, 60 matched patients were available for analysis (MIS = 20, HYB = 20, OPEN = 20). Blood loss was less in the MIS group than in the HYB and OPEN groups, but a significant difference was only found between the MIS and the OPEN group (669 vs 2322 ml, p = 0.001). The MIS and HYB groups had more fused interbody levels (4.5 and 4.1, respectively) than the OPEN group (1.6, p < 0.001). The OPEN group had less operative time than either the MIS or HYB group, but it was only statistically different from the HYB group (367 vs 665 minutes, p < 0.001). There was no significant difference in the duration of hospital stay among the groups. In patients with complete data, the overall complication rate was 45.5% (25 of 55). There was no significant difference in the total complication rate among the MIS, HYB, and OPEN groups (30%, 47%, and 63%, respectively; p = 0.147). No intraoperative complications were reported for the MIS group, 5.3% for the HYB group, and 25% for the OPEN group (p < 0.03). At least one postoperative complication occurred in 30%, 47%, and 50% (p = 0.40) of the MIS, HYB, and OPEN groups, respectively. One major complication occurred in 30%, 47%, and 63% (p = 0.147) of the MIS, HYB, and OPEN groups, respectively. All patients had significant improvement in both the Oswestry Disability Index (ODI) and visual analog scale scores after surgery (p < 0.001), although the MIS group did not have significant improvement in leg pain. The occurrence of complications had no impact on the ODI. CONCLUSIONS Results in this study suggest that the surgical approach may impact complications. The MIS group had significantly fewer intraoperative complications than did either the HYB or OPEN groups. If the goals of ASD surgery can be achieved, consideration should be given to less invasive techniques.

Developing consistently reproducible intervertebral disc degeneration at rat caudal spine by using needle puncture: Laboratory investigation

OBJECT The goal in this study was to develop a convenient, less-invasive animal model to monitor progression of intervertebral disc (IVD) degeneration for future testing of new treatments for disc degeneration. METHODS Level 5/6 and 7/8 IVDs of rat caudal spine were stabbed laterally with 18- or 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. In vivo MR imaging studies were performed at 4, 8, and 12 weeks postsurgery to monitor progression of IVD degeneration. Histological analysis including H & E and safranin O staining, and immunohistochemical studies of collagen type II and bone morphogenetic protein receptor type II (BMPRII) were assessed at 12 weeks postsurgery. RESULTS The 18- and 21-gauge needle-stabbed discs illustrated decreases in both the T2 density and MR imaging index starting at 4 weeks, with no evidence of spontaneous recovery by 12 weeks. Histological staining demonstrated a decreased nucleus pulposus (NP) area, and the NP-anulus fibrosus border became unclear during the progression of disc degeneration. Similar patterns of degenerative signs were also shown in both safranin O- and collagen type II-stained sections. The BMPRII immunohistochemical analysis of stabbed discs demonstrated an increase in BMPRII expression in the remaining NP cells and became stronger in anulus fibrosus with the severity of disc degeneration. CONCLUSIONS After introducing an 18- or 21-gauge needle into the NP area of discs in the rat tail, the stabbed disc showed signs of degeneration in terms of MR imaging and histological outcome measurements. Changes in BMPRII expression in this animal model provide an insight for the effectiveness of delivering BMPs into the region responsible for chondrogenesis for disc repair. This convenient, less-invasive, reproducible, and cost-effective model may be a useful choice for testing novel treatments for disc degeneration.

BMP-2 inhibits the tumorigenicity of cancer stem cells in human osteosarcoma OS99-1 cell line

Previously, based on high ALDH activity, we showed that cancer stem cells (CSCs) could be identified as ALDHbr cells from an aggressive human osteosarcoma OS99-1 cell line. In this study, we evaluate the impact of BMP-2 on CSCs.Three types of BMP receptors were expressed in freshly sorted ALDHbr cells. In vitro, growth of the sorted ALDHbr cells was inhibited by BMP-2. Using RT-PCR analysis, BMP-2 was found to down-regulate the expression of embryonic stem cell markers Oct3/4, Nanog, and Sox-2, and up-regulate the transcription of osteogenic markers Runx-2 and Collagen Type I. In vivo, all animals receiving ALDHbr cells treated with BMP-2 did not form significant tumors, while untreated ALDHbr cells developed large tumor masses in NOD/SCID mice. Immunostaining confirmed few Ki-67 positive cells were present in the sections of tumor containing ALDHbr cells treated with BMP-2. These results suggest that BMP-2 suppresses tumor growth by reducing the gene expression of tumorigenic factors and inducing the differentiation of CSCs in osteosarcoma. BMP-2 or BMP-2-mimetic drugs, if properly delivered to tumor and combined with traditional therapies, may therefore provide a new therapeutic option for treatment of osteosarcoma.

Outcomes after surgery for cervical spine deformity: review of the literature.

Object Symptomatic cervical kyphosis can result from a variety of causes. Symptoms can include pain, neurological deficits, and functional limitation due to loss of horizontal gaze. Methods The authors review the long-term functional and radiographic outcomes following surgery for symptomatic cervical kyphosis by performing a PubMed database literature search. Results Fourteen retrospective studies involving a total of 399 patients were identified. Surgical intervention included ventral, dorsal, or circumferential approaches. Analysis of the degree of deformity correction and functional parameters demonstrated significant postsurgical improvement. Overall, patient satisfaction appeared high. Five studies reported mortality with rates ranging from 3.1 to 6.7%. Major medical complications after surgery were reported in 5 studies with rates ranging from 3.1 to 44.4%. The overall neurological complication rate was 13.5%. Conclusions Although complications are not insignificant, surgery appears to be an effect...OBJECT The goal of this study was to assess the operative outcomes of adult patients with scoliosis who were treated surgically with minimally invasive correction and fusion. METHODS This was a retrospective study of 28 consecutive patients who underwent minimally invasive correction and fusion over 3 or more levels for adult scoliosis. Hospital and office charts were reviewed for clinical data. Functional outcome data were collected at each visit and at the last follow-up through self-administered questionnaires. All radiological measurements were obtained using standardized computer measuring tools. RESULTS The mean age of the patients in the study was 67.7 years (range 22-81 years), with a mean follow-up time of 22 months (range 13-37 months). Estimated blood loss for anterior procedures (transpsoas discectomy and interbody fusions) was 241 ml (range 20-2000 ml). Estimated blood loss for posterior procedures, including L5-S1 transsacral interbody fusion (and in some cases L4-5 and L5-S1 transsacral interbody fusion) and percutaneous screw fixation, was 231 ml (range 50-400 ml). The mean operating time, which was recorded from incision time to closure, was 232 minutes (range 104-448 minutes) for the anterior procedures, and for posterior procedures it was 248 minutes (range 141-370 minutes). The mean length of hospital stay was 10 days (range 3-20 days). The preoperative Cobb angle was 22 degrees (range 15-62 degrees ), which corrected to 7 degrees (range 0-22 degrees ). All patients maintained correction of their deformity and were noted to have solid arthrodesis on plain radiographs. This was further confirmed on CT scans in 21 patients. The mean preoperative visual analog scale and treatment intensity scale scores were 7.05 and 53.5; postoperatively these were 3.03 and 25.88, respectively. The mean preoperative 36-Item Short Form Health Survey and Oswestry Disability Index scores were 55.73 and 39.13; postoperatively they were 61.50 and 7, respectively. In terms of major complications, 2 patients had quadriceps palsies from which they recovered within 6 months, 1 sustained a retrocapsular renal hematoma, and 1 patient had an unrelated cerebellar hemorrhage. CONCLUSIONS Minimally invasive surgical correction of adult scoliosis results in mid- to long-term outcomes similar to traditional surgical approaches. Whereas operating times are comparable to those achieved with open approaches, blood loss and morbidity appear to be significantly lower in patients undergoing minimally invasive deformity correction. This approach may be particularly useful in the elderly.

Stress Analysis of the Interface Between Cervical Vertebrae End Plates and the Bryan, Prestige LP, and ProDisc-C Cervical Disc Prostheses : An In Vivo Image-Based Finite Element Study

Study Design. Segmental motion and bone-implant interface stresses were analyzed at C5–C6 levels with Bryan, Prestige LP, and ProDisc-C cervical disc prostheses using an image-based finite element modeling technique. Objective. To predict stress patterns at the interface between prosthesis and lower vertebral end plate to better understand the underlying mechanisms of subsidence and how the load transfer pattern of each disc design affects segmental motion. Summary of Background Data. Subsidence is one of the most commonly reported device-related complications in intervertebral disc arthroplasty. Although clinical outcomes have been reported regarding many types of cervical prostheses, few reports have analyzed the effects of stress from cervical artificial discs to the vertebral end plate. Methods. Three-dimensional voxel finite elements were built for C5–C6 spine unit based on computed tomography images acquired from a patient with indication for cervical disc arthroplasty. Models of facet joints and uncovertebral joints were added and artificial disc designs were placed in the intervertebral disc space. Static analyses were conducted under normal physiologic loads in flexion, extension, and lateral bending with precompression. Results. Bryan disc recovered highest range of motion (4.75°) due to the high elastic nucleus, and therefore imposed the lowest stresses superior to C6. The ProDisc-C and Prestige LP discs caused high stress concentrations around their central fins or teeth, and may initiate bone absorption. Analysis of Prestige LP disc may indicate possible subsidence posteriorly caused by the rear-positioned metal-to-metal joint. Conclusion. Rigidity of the cores (“nuclei”) in Prestige LP and ProDisc-C prostheses guarantee initial maintenance of disc height, but high contact stress takes place at the bone-end plate interface if they are improperly placed or undersized. Anchorage designs add an additional factor that may increase propensity of subsidence, indicated by the high contact stress occurring at the end plate flanges of Prestige LP, and at midline keel fixation on the end plate of ProDisc-C. Although Bryan disc differs in these 2 concerns, it also creates much larger displacement during motion with more variation in disc height that may theoretically increase the load sharing of facet and/or uncovertebral joints compared to more rigid artificial discs.