Faculty Bibliography

BACKGROUND: Spine surgery has been transformed significantly by the growth of minimally invasive surgery (MIS) procedures. Easily marketable to patients as less invasive with smaller incisions, MIS is often perceived as superior to traditional open spine surgery. The highest quality evidence comparing MIS with open spine surgery was examined. METHODS: A systematic review of randomized controlled trials (RCTs) involving MIS versus open spine surgery was performed using the Entrez gateway of the PubMed database for articles published in English up to December 28, 2015. RCTs and systematic reviews of RCTs of MIS versus open spine surgery were evaluated for three particular entities: Cervical disc herniation, lumbar disc herniation, and posterior lumbar fusion. RESULTS: A total of 17 RCTs were identified, along with six systematic reviews. For cervical disc herniation, MIS provided no difference in overall function, arm pain relief, or long-term neck pain. In lumbar disc herniation, MIS was inferior in providing leg/low back pain relief, rehospitalization rates, quality of life improvement, and exposed the surgeon to >10 times more radiation in return for shorter hospital stay and less surgical site infection. In posterior lumbar fusion, MIS transforaminal lumbar interbody fusion (TLIF) had significantly reduced 2-year societal cost, fewer medical complications, reduced time to return to work, and improved short-term Oswestry Disability Index scores at the cost of higher revision rates, higher readmission rates, and more than twice the amount of intraoperative fluoroscopy. CONCLUSION: The highest levels of evidence do not support MIS over open surgery for cervical or lumbar disc herniation. However, MIS TLIF demonstrates advantages along with higher revision/readmission rates. Regardless of patient indication, MIS exposes the surgeon to significantly more radiation; it is unclear how this impacts patients. These results should optimize informed decision-making regarding MIS versus open spine surgery, particularly in the current advertising climate greatly favoring MIS.

PURPOSE:: The FDA approved C-11 choline PET/computed tomography (CT) for imaging patients with recurrent prostate cancer in 2012. Subsequently, the 2014 NCCN guidelines have introduced labeled choline PET/CT in the imaging algorithm of patients with suspected recurrent disease. However, there is only scarce data on the impact of labeled choline PET/CT findings on disease management. We hypothesized that labeled-choline PET/CT studies showing local or regional recurrence or distant metastases will have a direct role in selection of appropriate patient management and improve radiation planning in patients with disease that can be controlled using this mode of therapy. METHODS:: This retrospective study was approved by the Tel Aviv Sourasky and Sheba Medical Center's Helsinki ethical review committees. Patient characteristics including age, PSA, stage, prior treatments, and pre-PET choline treatment recommendations based on NCCN guidelines were recorded. Patients with biochemical failure and without evidence of recurrence on physical examination or standard imaging were offered the option of additional imaging with labeled choline PET/CT. Treatment recommendations post-PET/CT were compared with pre-PET/CT ones. Pathologic confirmation was obtained before prostate retreatment. A nonparametric chi test was used to compare the initial and final treatment recommendations following choline PET/CT. RESULTS:: Between June 2010 and January 2014, 34 labeled-choline PET/CT studies were performed on 33 patients with biochemical failure following radical prostatectomy (RP) (n=6), radiation therapy (RT) (n=6), brachytherapy (n=2), RP+salvage prostate fossa RT (n=14), and RP+salvage prostate fossa/lymph node RT (n=6). Median PSA level before imaging was 2 ng/mL (range, 0.16 to 79). Labeled choline PET/CT showed prostate, prostate fossa, or pelvic lymph node increased uptake in 17 studies, remote metastatic disease in 9 studies, and failed to identify the cause for biochemical failure in 7 scans.PET/CT altered treatment approach in 18 of 33 (55%) patients (P=0.05). Sixteen of 27 patients (59%) treated previously with radiation were retreated with RT and delayed or eliminated androgen deprivation therapy: 1 received salvage brachytherapy, 10 received salvage pelvic lymph node or prostate fossa irradiation, 2 brachytherapy failures received salvage prostate and lymph nodes IMRT, and 3 with solitary bone metastasis were treated with radiosurgery. Eleven of 16 patients retreated responded to salvage therapy with a significant PSA response (<0.2 ng/mL), 2 patients had partial biochemical responses, and 3 patients failed. The median duration of response was 500+/-447 days. Two of 6 patients with no prior RT were referred for salvage prostatic fossa RT: 1 received dose escalation for disease identified in the prostate fossa and another had inclusion of "hot" pelvic lymph nodes in the treatment volume. CONCLUSIONS:: These early results suggest that labeled choline PET/CT imaging performed according to current NCCN guidelines may change management and improve care in prostate cancer patients with biochemical failure by identifying patients for referral for salvage radiation therapy, improving radiation planning, and delaying or avoiding use of androgen deprivation therapy.

BACKGROUND CONTEXT: Spine surgery has been transformed significantly over the past decade by the growth of minimally invasive surgery (MIS) procedures. Easily marketable to patients as less invasive with smaller incisions, it can be easy to perceive MIS as superior to traditional open spine surgery. However, this perception has yet to be addressed via a systematic review of the highest quality of evidence comparing MIS with open spine surgery. PURPOSE: To review the highest quality of evidence comparing MIS with open spine surgery. STUDY DESIGN/SETTING: Evaluation of MIS vs. open spine surgery for cervical disc herniation, lumbar disc herniation, and posterior lumbar fusion using Class I and Class II evidence. PATIENT SAMPLE: Patients included in published Class I and Class II evidence comparing MIS with open spine surgery. OUTCOME MEASURES: Quality of life, axial pain relief, extremity pain relief, hospital stay duration, infection, nerve root injury, durotomy, readmission rate, reoperation rate, blood loss, medical complications, societal cost, time to return to work, fusion rate, clinical outcome, radiographic outcome and radiation exposure. METHODS: A comprehensive search for randomized controlled trials involving MIS vs. open spine surgery was made using the Entrez gateway of the Pubmed database for articles published in English up to 12/28/15. Randomized controlled trials (RCTs) and systematic reviews of RCTs of MIS vs. open spine surgery were evaluated for three particular entities: cervical disc herniation, lumbar disc herniation, and posterior lumbar fusion. Additional Class II studies were included for clinical aspects not addressed in the RCTs. RESULTS: A total of 17 RCTs were identified, along with six systematic reviews. For cervical disc herniation, MIS was no different with regard to overall function, arm pain relief, or long-term neck pain. In lumbar disc herniation, MIS was inferior in providing leg or low back pain relief, more likely to require rehospitalization, inferior in improving quality-of-life, and exposed the surgeon to at least 10 times more radiation in return for shorter hospital stay and lower risk of surgical site infection. In disc herniation of either the cervical or lumbar spine, MIS trended towards higher rates of nerve root injury, durotomy, and reoperation, but none were statistically significant. In posterior lumbar fusion, MIS transforaminal lumbar interbody fusion (TLIF) had significantly reduced 2-year societal cost, fewer medical complications, reduced time to return to work, and improved short-term Oswestry Disability Index scores at the cost of higher revision rates, higher readmission rates, and more than twice the amount of intraoperative fluoroscopy; there was no difference in fusion rate, clinical outcome or radiographic outcome. CONCLUSIONS: The highest levels of evidence do not support MIS over open surgery for either cervical or lumbar disc herniation. However, for fusion cases, MIS TLIF demonstrates advantages, most prominently in reduced hospitalization, societal cost, and time to return to work at the cost of higher revision and readmission rates. Regardless of patient indication, MIS results in significantly more radiation exposure to the surgeon; it is unclear whether this exposure impacts patients as well. These results should be made clear to patients in order to give them the best chance to make an informed decision when choosing MIS vs. open spine surgery, particularly given the current medical advertising climate which greatly favors the choice of MIS

OBJECTIVES: The purpose of this study was to determine the cost/quality-adjusted life-year (QALY) of the operative treatment of lumbar spondylolisthesis and identify factors associated with cost-effectiveness at 2 years. METHODS: We evaluated patients who underwent surgery for spondylolisthesis. The QALY was determined from the EQ5D. Outcomes were also assessed using the Oswestry Disability Index (ODI). Surgical, neuromonitoring, and anesthesia Current Procedural Terminology (CPT) codes as well as hospital Diagnosis-Related Group codes were used to determine the Medicare direct care costs of surgery. Indirect costs were modeled based on existing literature. A discounting rate of 3% was applied. Analysis was performed to determine which factors were associated with a cost/QALY less than $100,000. RESULTS: There were 44 patients who underwent surgery for either degenerative (30) or isthmic spondylolisthesis (14). There were 27 women and 17 men, with an average age at surgery of 59.7 years (standard deviation [SD] = 14.69) and an average follow-up of 2 years (SD = 0.82). The average postoperative improvement in ODI was 24.77 (SD = 23.9), and change in QALY was 0.43 (SD = 0.30). The average cost/QALY at 2 years for direct care costs was $89,065. The average cost/QALY at 2 years for direct plus indirect costs was $112,588. Higher preoperative leg pain and greater leg pain change was associated with a cost/QALY <$100,000 (p < .005, p < .028). The cost-effective group had a higher proportion of patients with disease extent of two or more levels (p = .021). When comparing surgical techniques of anterior-posterior and posterior only, there was no difference in cost-effectiveness. CONCLUSIONS: Spondylolisthesis surgery is cost-effective at 2 years, with a QALY change of 0.43 and a direct cost/QALY of $89,065. Higher preoperative leg pain and larger extent of disease was associated with cost-effectiveness. LEVEL OF EVIDENCE: IV.

INTRODUCTION: Wound infections following spinal surgery place a high toll on both the patient and the healthcare system. Although several large series studies have examined the incidence and distribution of spinal wound infection, the applicability of these studies varies greatly since nearly every study is either retrospective and/or lacks standard inclusion criteria for defining surgical site infection. To address this void, we present results from prospectively gathered thoracolumbar spine surgery data for which the Centers for Disease Control (CDC) criteria were stringently applied to define a surgical site infection (SSI). METHODS: A prospective randomized trial of 314 patients who underwent multilevel thoracolumbar spinal surgery with instrumentation followed by postoperative drain placement was completed (Takemoto et al., 2015). The trial consisted of two antibiotic arms: one for 24-hours, and the other for the duration of the drain; no differences were found between the arms. All infections meeting CDC criteria for SSI were included. RESULTS: A total of 40 infections met CDC criteria for SSI, for an overall incidence of 12.7%. Of these, 20 (50%) were culture-positive. The most common organism was Staphylococcus aureus (4 total: methicillin-sensitive=2; methicillin-resistant=2), followed by coagulase-negative Staphylococcus (3 cases), Propionibacterium acnes and Escherichia coli (2 cases each). Six infections grew multiple organisms, most commonly involving coagulase-negative staphylococcus and enterococcus. CONCLUSIONS: Our findings indicate that thoracolumbar SSI occurs at the higher end of the range cited in the literature (2-13%), which is largely based on retrospective data not subjected to the inclusivity of SSI as defined by the CDC. The three most common organisms in our analysis (S. aureus, P. acnes, E. coli) are consistent with previous reports. Staphylococcus aureus continues to be the most common causative organism and continued vigilance and searching for preventive measures need to be a high priority. This study provides Level I evidence.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.