Anthony C. Wang

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.

Detection of human brain tumor infiltration with quantitative stimulated Raman scattering microscopy

Quantitative SRS microscopy can detect human brain tumor infiltration with high sensitivity and specificity, even in tissues appearing grossly normal. Image-based classifier calls out cancer cells Ji and colleagues used a microscopy technique called stimulated Raman scattering, or SRS, to image cancer cells in human brain tissue. SRS produces different signals for proteins and lipids, which can then be assigned a color (blue and green, respectively), allowing the authors to differentiate brain cortex from tumor from white matter. Biopsies from adult and pediatric patients with glioblastoma revealed not only distinctive features with SRS microscopy but also the presence of infiltrating cells in tissues that appeared otherwise normal with traditional staining. Such infiltrating cells are important to catch early because leaving them behind after surgery nearly always leads to cancer recurrence. To make this SRS microscopy approach amenable to routine use in neuropathology, the authors also created an objective classifier that integrated different image characteristics, such as the protein/lipid ratio, axonal density, and degree of cellularity, into one output, on a scale of 0 to 1, that would alert the pathologist to tumor infiltration. The classifier was built using more than 1400 images from patients with glioblastoma and epilepsy, and could distinguish between tumor-infiltrated and nontumor regions with >99% accuracy, regardless of tumor grade or histologic subtype. This label-free imaging technology could therefore be used to complement existing neurosurgical workflows, allowing for rapid and objective characterization of brain tissues and, in turn, clinical decision-making. Differentiating tumor from normal brain is a major barrier to achieving optimal outcome in brain tumor surgery. New imaging techniques for visualizing tumor margins during surgery are needed to improve surgical results. We recently demonstrated the ability of stimulated Raman scattering (SRS) microscopy, a nondestructive, label-free optical method, to reveal glioma infiltration in animal models. We show that SRS reveals human brain tumor infiltration in fresh, unprocessed surgical specimens from 22 neurosurgical patients. SRS detects tumor infiltration in near-perfect agreement with standard hematoxylin and eosin light microscopy (κ = 0.86). The unique chemical contrast specific to SRS microscopy enables tumor detection by revealing quantifiable alterations in tissue cellularity, axonal density, and protein/lipid ratio in tumor-infiltrated tissues. To ensure that SRS microscopic data can be easily used in brain tumor surgery, without the need for expert interpretation, we created a classifier based on cellularity, axonal density, and protein/lipid ratio in SRS images capable of detecting tumor infiltration with 97.5% sensitivity and 98.5% specificity. Quantitative SRS microscopy detects the spread of tumor cells, even in brain tissue surrounding a tumor that appears grossly normal. By accurately revealing tumor infiltration, quantitative SRS microscopy holds potential for improving the accuracy of brain tumor surgery.

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.

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.

Tarlov cysts: a controversial lesion of the sacral spine

The primary aim of our study was to provide a comprehensive review of the clinical, imaging, and histopathological features of Tarlov cysts (TCs) and to report operative and nonoperative management strategies in patients with sacral TCs. A literature review was performed to identify articles that reported surgical and nonsurgical management of TCs over the last 10 years. Tarlov cysts are often incidental lesions found in the spine and do not require surgical intervention in the great majority of cases. When TCs are symptomatic, the typical clinical presentation includes back pain, coccyx pain, low radicular pain, bowel/bladder dysfunction, leg weakness, and sexual dysfunction. Tarlov cysts may be revealed by MR and CT imaging of the lumbosacral spine and must be meticulously differentiated from other overlapping spinal pathological entities. They are typically benign, asymptomatic lesions that can simply be monitored. To date, no consensus exists about the best surgical strategy to use when indicated. The authors report and discuss various surgical strategies including posterior decompression, cyst wall resection, CT-guided needle aspiration with intralesional fibrin injection, and shunting. In operative patients, the rates of short-term and long-term improvement in clinical symptoms are not clear. Although neurological deficit frequently improves after surgical treatment of TC, pain is less likely to do so.

Complication avoidance and management in anterior lumbar interbody fusion.

The goal of this study was to review the literature to compare strategies for avoiding and treating complications from anterior lumbar interbody fusion (ALIF), and thus provide a comprehensive aid for spine surgeons. A thorough review of databases from the US National Library of Medicine and the National Institutes of Health was conducted. The complications of ALIF addressed in this paper include pseudarthrosis and subsidence, vascular injury, retrograde ejaculation, ileus, and lymphocele (chyloretroperitoneum). Strategies identified for improving fusion rates included the use of frozen rather than freeze-dried allograft, cage instrumentation, and bone morphogenetic protein. Lower cage heights appear to reduce the risk of subsidence. The most common vascular injury is venous laceration, which occurs less frequently when using nonthreaded interbody grafts such as iliac crest autograft or femoral ring allograft. Left iliac artery thrombosis is the most common arterial injury, and its occurrence can be minimized by intermittent release of retraction intraoperatively. The risk of retrograde ejaculation is significantly higher with laparoscopic approaches, and thus should be avoided in male patients. Despite precautionary measures, complications from ALIF may occur, but treatment options do exist. Bowel obstruction can be treated conservatively with neostigmine or with decompression. In cases of postoperative lymphocele, resolution can be attained by creating a peritoneal window. By recognizing ways to minimize complications, the spine surgeon can safely use ALIF procedures.

Postoperative Management of Incidental Durotomy in Minimally Invasive Lumbar Spinal Surgery

Unintended durotomy is a relatively common complication in spine surgery, with a reported incidence up to 14%. Traditional management has been mandatory bed rest for at least 48 h following repair, with or without placement of a drain. With the muscle-splitting approach and decreased potential (dead) space created during minimally invasive spinal surgery (MISS), there is less potential likelihood of symptoms such as spinal headaches or cerebrospinal fluid fistulas. We reviewed the cases of 5 patients undergoing lumbar MISS complicated by an incidental dural tear. Surgical treatment consisted of primary repair and/or use of DuraGen followed by application of either DuraSeal or Tisseel. Although the duration of bed rest varied, postoperative management involved early mobilization less than 48 h after surgery without the use of a drain. One patient was mobilized early on the second postoperative day, 2 patients were mobilized the morning after surgery, and 2 patients were mobilized immediately upon recovery from anesthesia. None of the patients developed symptoms related to durotomy. Although this represents a small series, early postoperative mobilization appears to be a reasonable option and results in shorter hospitalization.

Radiation Safety and Spine Surgery: Systematic Review of Exposure Limits and Methods to Minimize Radiation Exposure

BACKGROUND Ionizing radiation is typically used during spine surgery for localization and guidance in instrumentation placement. Minimally invasive (MI) surgical procedures are increasingly popular and often require significantly more fluoroscopy, placing surgeons at risk for increased radiation exposure and radiation-induced complications. This study provides recommendations for minimizing risk of radiation-induced injury to spine surgeons and summarizes studies addressing radiation exposure in spine procedures. METHODS The PubMed database was queried for relevant articles pertaining to radiation exposure in spine surgery. RESULTS Discectomy, percutaneous pedicle screw placement, MI transforaminal lumbar interbody fusion, MI lateral lumbar interbody fusion, and vertebroplasty/kyphoplasty procedures were assessed. The highest radiation doses were seen with MI pedicle screw placement, MI transforaminal lumbar interbody fusion, vertebroplasty and kyphoplasty, and percutaneous endoscopic lumbar discectomy. Use of lead aprons and thyroid shields reduces effective dose by several orders of magnitude. Proper operator positioning also minimizes radiation exposure. Lead gloves decrease dose to the surgeons hand from scatter if the hand is out of the x-ray beam most of the time. If prolonged exposure of the hand cannot be avoided, the technician should collimate the surgeons hand out of the beam or use instruments to position the hand farther from the beam. In addition to using less fluoroscopy, pulsed fluoroscopy can decrease overall dose in a procedure. CONCLUSIONS Spine surgeons should reduce their exposure to radiation to minimize risk of potential long-term complications. Strategies include minimizing fluoroscopy use and dose, proper use of protective gear, and appropriate manipulation of fluoroscopic equipment.

Schmorl's nodes.

IntroductionFirst described in 1927, a Schmorl’s node (SN) is the herniation of nucleus pulposus (NP) through the cartilaginous and bony end plate into the body of the adjacent vertebra. SNs are common findings on imaging, and although most SNs are asymptomatic, some have been shown to become painful lesions. In this manuscript, we review the literature regarding the epidemiology, clinical presentation, pathogenesis, imaging, and management of SNs.Materials and methods Using databases from the US National Library of Medicine and the National Institutes of Health, relevant articles were identified.Results While several theories regarding the pathogenesis of SNs have been proposed, an axial load model appears to have the greatest supporting evidence. Symptomatic SNs are thought to be due to the inflammatory response solicited by the herniation of NP into the well-vascularized vertebral body. Management options for symptomatic SNs vary, ranging from medical management to surgical fusion.ConclusionSNs are common lesions that are often asymptomatic. In certain cases, SNs can cause back pain. No consensus on pathogenesis exists. There is no established treatment modality for symptomatic SNs.