Paul Park

Adjacent segment disease after lumbar or lumbosacral fusion: review of the literature.

Study Design. Review of the literature. Objectives. Review the definition, etiology, incidence, and risk factors associated with as well as potential treatment options. Summary of Background Data. The development of pathology at the mobile segment next to a lumbar or lumbosacral spinal fusion has been termed adjacent segment disease. Initially reported to occur rarely, it is now considered a potential late complication of spinal fusion that can necessitate further surgical intervention and adversely affect outcomes. Methods. MEDLINE literature search. Results. The most common abnormal finding at the adjacent segment is disc degeneration. Biomechanical changes consisting of increased intradiscal pressure, increased facet loading, and increased mobility occur after fusion and have been implicated in causing adjacent segment disease. Progressive spinal degeneration with age is also thought to be a major contributor. From a radiographic standpoint, reported incidence during average postoperative follow-up observation ranging from 36 to 369 months varies substantially from 5.2 to 100%. Incidence of symptomatic adjacent segment disease is lower, however, ranging from 5.2 to 18.5% during 44.8 to 164 months of follow-up observation. The rate of symptomatic adjacent segment disease is higher in patients with transpedicular instrumentation (12.2–18.5%) compared with patients fused with other forms of instrumentation or with no instrumentation (5.2–5.6%). Potential risk factors include instrumentation, fusion length, sagittal malalignment, facet injury, age, and pre-existing degenerative changes. Conclusion. Biomechanical alterations likely play a primary role in causing adjacent segment disease. Radiographically apparent, asymptomatic adjacent segment disease is common but does not correlate with functional outcomes. Potentially modifiable risk factors for the development of adjacent segment disease include fusion without instrumentation, protecting the facet joint of the adjacent segment during placement of pedicle screws,fusion length, and sagittal balance. Surgical management, when indicated, consists of decompression of neural elements and extension of fusion. Outcomes after surgery, however, are modest.

Recombinant activated factor VII for the rapid correction of coagulopathy in nonhemophilic neurosurgical patients.

OBJECTIVECoagulopathy is a significant contraindication for neurosurgery. Unfortunately, many coagulopathic patients require urgent neurosurgical intervention. Standard use of blood products, including fresh-frozen plasma or prothrombin complexes, to correct the coagulopathy often leads to significant delays in treatment. Recombinant activated factor VII (rFVIIa) is a medication originally designed to treat bleeding in hemophiliacs but also seems to correct a wide variety of coagulopathies rapidly and safely in nonhemophilic patients. METHODSThe medical records of nine patients with coagulopathy requiring urgent neurosurgical intervention were reviewed retrospectively. Each patient was given a dose ranging from 40 to 90 &mgr;g/kg of rFVIIa before undergoing surgery. Pre-rFVIIa coagulation and post-rFVIIa coagulation parameters were obtained. Once correction of the coagulopathy was verified, each patient underwent the appropriate neurosurgical procedure. RESULTSThe average age of the patients was 40.9 years; six were women. The causes of the coagulopathy included anticoagulant medication, liver dysfunction, and dilutional coagulopathy after traumatic hemorrhage. Neurosurgical indications included intraparenchymal/intraventricular hemorrhage, hydrocephalus, diffuse cerebral edema, and epidural hematoma. Post-rFVIIa coagulation parameters obtained as early as 20 minutes after infusion of the medication showed normalization of values. There were no procedural or operative complications and no postoperative hemorrhagic complications. No associated thromboembolic or other complications with the use of rFVIIa were observed. CONCLUSIONThe use of rFVIIa for the urgent surgical treatment of coagulopathic patients is quite promising. Further studies, including randomized, prospective trials using rFVIIa to address issues such as optimal dosing, efficacy, surgical indications, cost-effectiveness, morbidity, and mortality are needed.

The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas.

OBJECTIVE:Radiotherapy after aggressive surgical resection of nonfunctional macroadenoma (NFA) of the pituitary remains controversial. Historically, immediate postoperative radiotherapy has been recommended to decrease risk of recurrence. With the availability of high-resolution imaging, most neurosurgeons now withhold radiation until recurrence. There is relatively little evidence to support this practice, however. This study reviews postoperative results in a large number of patients with NFA, the majority of whom did not undergo prophylactic radiation. METHODS:Of the 258 patients who underwent surgery from 1979 to 1999 for NFA, medical records were available for 176. Forty-four patients were treated with immediate postoperative radiotherapy after tumor resection, and the remaining 132 patients were followed up with serial imaging studies and treated with radiotherapy only when a recurrence was documented by follow-up imaging. RESULTS:Patients in the group that received immediate postoperative radiotherapy at time of initial diagnosis and surgery did not differ significantly with respect to age or sex from those in the group that was observed. Five- and 10-year recurrence rates were 2.3 and 2.3%, respectively, for patients who received immediate postoperative radiotherapy, as compared with 15.2 and 50.5%, respectively, for patients who were followed up and did not receive radiotherapy unless there was evidence of recurrence or progression. No patient had symptomatic recurrence in the group that was observed if consistent follow-up was performed. Of the 26 patients who received radiotherapy at time of tumor recurrence or progression, 18 had adequate follow-up, and in all cases, the tumors either remained stable or regressed. CONCLUSION:Withholding radiotherapy after a high-percentage resection of NFA leads to a higher recurrence rate, but it avoids exposing all patients to the risks of radiation. Deferring radiotherapy for patients with complete or near-complete resection seems to be a safe and prudent approach, as our data suggest that recurrences may be detected early with high-resolution imaging and treated effectively with radiation at time of recurrence. Therefore, immediate postoperative radiotherapy may be eliminated for patients with complete or near complete resection of NFA and who agree to undergo close follow-up for a long period.

Minimally invasive transforaminal lumbar interbody fusion with reduction of spondylolisthesis: technique and outcomes after a minimum of 2 years' follow-up

Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is a relatively new surgical procedure that appears to minimize iatrogenic soft tissue and muscle injury. The authors describe a technique for MI-TLIF that permits the surgeon to reduce spondylolisthesis percutaneously. The results in 40 consecutive patients who underwent MI-TLIF for symptomatic spondylolisthesis utilizing this approach are reviewed. Thirty cases involved a degenerative spondylolisthesis while the remaining 10 were isthmic. The minimum follow-up was 24 months with a mean of 35 months. The mean preoperative Oswestry Disability Index score was 55, decreasing to a mean of 16 postoperatively. The mean leg and back pain visual analog scale scores were 65 and 52, respectively, improving to means of 8 and 15. Reduction of the spondylolisthesis was achieved in all cases, with a mean decrease in forward translation of 76%. The authors conclude that MI-TLIF for symptomatic spondylolisthesis appears to be an effective surgical option with results that compare favorably to open procedures.

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.

Risk of infection with prolonged ventricular catheterization.

OBJECTIVE:The relationship between extended ventricular catheterization and infection remains controversial. Although studies have substantiated an increasing infection rate with prolonged catheterization, there has been less agreement on whether this trend continues beyond 10 days. Our study reviews the daily infection rate of 595 patients, 213 of whom underwent more than 10 days of catheterization. METHODS:All patients who underwent ventricular monitoring in the neurological intensive care unit from 1995 to 2003 at the University of Michigan Health System were reviewed retrospectively. Infection was defined as a positive cerebrospinal fluid culture. Life-table analysis was used to calculate daily hazard (infection) rates. Patient age, sex, diagnosis, catheter exchanges, location of patient during catheter insertion, and cerebrospinal fluid leak were evaluated as risk factors for infection. RESULTS:The average patient age was 51.3 years, and 51.3% were male. Duration of catheterization averaged 8.6 days. The overall infection rate was 8.6%. Daily infection rates increased from the onset of catheter insertion but reached a plateau after Day 4, with subsequent rates ranging predominantly between 1 and 2%, even with extended catheterization beyond 10 days. Only ventricular catheters that had been placed at other institutions significantly affected the infection rate. CONCLUSION:A relationship between duration of catheterization and infection seems to be present. However, this relationship is not linear. There is an extremely low daily infection rate that rises over the initial 4 days but then remains relatively constant even with prolonged catheter use. Clinical decisions to continue ventricular catheterization should reflect this low daily risk of infection, which does not seem to increase with extended catheter use.

The impact of minimally invasive spine surgery on perioperative complications in overweight or obese patients.

OBJECTIVEOpen lumbar spinal surgery in overweight or obese patients has been associated with increased risk of perioperative complications. The impact of minimally invasive spinal (MIS) surgery on the incidence of perioperative adverse events in overweight or obese patients, however, has not been well evaluated. METHODSA retrospective review of consecutive patients undergoing lumbar MIS surgery from January 2006 to April 2007 was performed. Of the 77 patients identified, 56 had a body mass index (BMI) of 25.0 kg/m2 or greater. RESULTSOf the 56 patients with a BMI of 25 kg/m2 or greater, 32 (57.1%) were men; the mean age was 54.1 years. The mean BMI was 31.0 kg/m2 (range, 25.1–43.8 kg/m2). Using a broad definition of an adverse event, eight (14.3%) complications were identified. In the discectomy/laminotomy subgroup (31 patients), two (6.5%) adverse events were noted. In the fusion subgroup (25 patients), six (24%) adverse events were noted, most of which were minor. Of the 21 patients with a BMI less than 25 kg/m2, eight (38.1%) were men, and the mean age was 43.7 years. The mean BMI was 22.5 kg/m2 (range, 16.8–24.6 kg/m2). Three (14.3%) complications were noted overall. In the discectomy/laminotomy subgroup (17 patients), two (11.8%) adverse events occurred. One (25%) complication developed in the four patients making up the fusion subgroup. There was no statistically significant difference in complication rates between groups. Logistic regression also found no statistically significant relationship between BMI and perioperative complications. CONCLUSIONThere does not appear to be an increased risk of developing perioperative complications in overweight or obese patients undergoing MIS surgery, which may reflect a potential benefit of the MIS approach.

Characterization of stem cell attributes in human osteosarcoma cell lines

Osteosarcoma is an aggressive primary bone cancer affecting primarily children and young adolescents. Development of valuable diagnostic indicators and therapeutic agents will be enhanced by the identification and characterization of genes that contribute to its aggressive behavior. Emerging evidence suggests a subpopulation of cancer stem cells within tumors that have been implicated in the pathogenesis of heterogeneous malignant tumors. The purpose of our study was to characterize the stem-like cell population in human osteosarcoma. Four human osteosacoma cell lines were cultured using a previously developed sarcosphere formation assay. The results showed that all human osteosarcoma cell lines possessed an ability to form sarcospheres. More spherical and frequent sarcospheres were observed in OS99-1 and MG63 cells than in Hu09 and Saos-2 cells. Moreover, stem cell markers Oct3/4 and Nanog were examined in osteosarcoma cell lines using RT-PCR and immunological techniques. For the first time, we showed that 2 Oct3/4 isoforms, Oct3/4 A and Oct3/4 B, were expressed in all 4 cell lines although they illustrated different expression patterns. Oct3/4 A was expressed in the nuclei while Oct3/4 B was located in the cytoplasm of a subpopulation of cells found within all four cell lines. Furthermore, elevated expression of Oct3/4 A was seen in the OS99-1, Hu09, and MG63 cells compared to Saos-2 cells while significantly higher expression of Oct3/4 B was detected in Hu09 compared with the other cell lines. In addition, Nanog was detected in a subpopulation of all cell lines, where OS99-1 cells expressed significantly higher levels than Hu09, Saos-2 and MG63 cells. Thus, our data support the cancer stem cell hypothesis, which may have important implications for clinic diagnosis and treatment of 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.