Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer.

While mutations affecting protein-coding regions have been examined across many cancers, structural variants at the genome-wide level are still poorly defined. Through integrative deep whole-genome and -transcriptome analysis of 101 castration-resistant prostate cancer metastases (109X tumor/38X normal coverage), we identified structural variants altering critical regulators of tumorigenesis and progression not detectable by exome approaches. Notably, we observed amplification of an intergenic enhancer region 624 kb upstream of the androgen receptor (AR) in 81% of patients, correlating with increased AR expression. Tandem duplication hotspots also occur near MYC, in lncRNAs associated with post-translational MYC regulation. Classes of structural variations were linked to distinct DNA repair deficiencies, suggesting their etiology, including associations of CDK12 mutation with tandem duplications, TP53 inactivation with inverted rearrangements and chromothripsis, and BRCA2 inactivation with deletions. Together, these observations provide a comprehensive view of how structural variations affect critical regulators in metastatic prostate cancer.

Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.

We have observed overexpression of PACS-1, a cytosolic sorting protein in primary cervical tumors. Absence of exonic mutations and overexpression at the RNA level suggested a transcriptional and/or posttranscriptional regulation. University of California Santa Cruz genome browser analysis of PACS-1 micro RNAs (miR), revealed two 8-base target sequences at the 3' terminus for hsa-miR-34a and hsa-miR-449a. Quantitative RT-PCR and Northern blotting studies showed reduced or loss of expression of the two microRNAs in cervical cancer cell lines and primary tumors, indicating dysregulation of these two microRNAs in cervical cancer. Loss of PACS-1 with siRNA or exogenous expression of hsa-miR-34a or hsa-miR-449a in HeLa and SiHa cervical cancer cell lines resulted in DNA damage response, S-phase cell cycle arrest, and reduction in cell growth. Furthermore, the siRNA studies showed that loss of PACS-1 expression was accompanied by increased nuclear γH2AX expression, Lys382-p53 acetylation, and genomic instability. PACS-1 re-expression through LNA-hsa-anti-miR-34a or -449a or through PACS-1 cDNA transfection led to the reversal of DNA damage response and restoration of cell growth. Release of cells post 24-h serum starvation showed PACS-1 nuclear localization at G1-S phase of the cell cycle. Our results therefore indicate that the loss of hsa-miR-34a and hsa-miR-449a expression in cervical cancer leads to overexpression of PACS-1 and suppression of DNA damage response, resulting in the development of chemo-resistant tumors.

PatientExploreR: an extensible application for dynamic visualization of patient clinical history from electronic health records in the OMOP common data model.

MOTIVATION: Electronic health records (EHRs) are quickly becoming omnipresent in healthcare, but interoperability issues and technical demands limit their use for biomedical and clinical research. Interactive and flexible software that interfaces directly with EHR data structured around a common data model (CDM) could accelerate more EHR-based research by making the data more accessible to researchers who lack computational expertise and/or domain knowledge. RESULTS: We present PatientExploreR, an extensible application built on the R/Shiny framework that interfaces with a relational database of EHR data in the Observational Medical Outcomes Partnership CDM format. PatientExploreR produces patient-level interactive and dynamic reports and facilitates visualization of clinical data without any programming required. It allows researchers to easily construct and export patient cohorts from the EHR for analysis with other software. This application could enable easier exploration of patient-level data for physicians and researchers. PatientExploreR can incorporate EHR data from any institution that employs the CDM for users with approved access. The software code is free and open source under the MIT license, enabling institutions to install and users to expand and modify the application for their own purposes. AVAILABILITY AND IMPLEMENTATION: PatientExploreR can be freely obtained from GitHub: https://github.com/BenGlicksberg/PatientExploreR. We provide instructions for how researchers with approved access to their institutional EHR can use this package. We also release an open sandbox server of synthesized patient data for users without EHR access to explore: http://patientexplorer.ucsf.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Blockchain-Authenticated Sharing of Genomic and Clinical Outcomes Data of Patients With Cancer: A Prospective Cohort Study.

BACKGROUND: Efficiently sharing health data produced during standard care could dramatically accelerate progress in cancer treatments, but various barriers make this difficult. Not sharing these data to ensure patient privacy is at the cost of little to no learning from real-world data produced during cancer care. Furthermore, recent research has demonstrated a willingness of patients with cancer to share their treatment experiences to fuel research, despite potential risks to privacy. OBJECTIVE: The objective of this study was to design, pilot, and release a decentralized, scalable, efficient, economical, and secure strategy for the dissemination of deidentified clinical and genomic data with a focus on late-stage cancer. METHODS: We created and piloted a blockchain-authenticated system to enable secure sharing of deidentified patient data derived from standard of care imaging, genomic testing, and electronic health records (EHRs), called the Cancer Gene Trust (CGT). We prospectively consented and collected data for a pilot cohort (N=18), which we uploaded to the CGT. EHR data were extracted from both a hospital cancer registry and a common data model (CDM) format to identify optimal data extraction and dissemination practices. Specifically, we scored and compared the level of completeness between two EHR data extraction formats against the gold standard source documentation for patients with available data (n=17). RESULTS: Although the total completeness scores were greater for the registry reports than those for the CDM, this difference was not statistically significant. We did find that some specific data fields, such as histology site, were better captured using the registry reports, which can be used to improve the continually adapting CDM. In terms of the overall pilot study, we found that CGT enables rapid integration of real-world data of patients with cancer in a more clinically useful time frame. We also developed an open-source Web application to allow users to seamlessly search, browse, explore, and download CGT data. CONCLUSIONS: Our pilot demonstrates the willingness of patients with cancer to participate in data sharing and how blockchain-enabled structures can maintain relationships between individual data elements while preserving patient privacy, empowering findings by third-party researchers and clinicians. We demonstrate the feasibility of CGT as a framework to share health data trapped in silos to further cancer research. Further studies to optimize data representation, stream, and integrity are required.

Whole-genome analysis informs breast cancer response to aromatase inhibition.

To correlate the variable clinical features of oestrogen-receptor-positive breast cancer with somatic alterations, we studied pretreatment tumour biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy by massively parallel sequencing and analysis. Eighteen significantly mutated genes were identified, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) previously linked to haematopoietic disorders. Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment. Pathway analysis demonstrated that mutations in MAP2K4, a MAP3K1 substrate, produced similar perturbations as MAP3K1 loss. Distinct phenotypes in oestrogen-receptor-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumour biology, but most recurrent mutations are relatively infrequent. Prospective clinical trials based on these findings will require comprehensive genome sequencing.

Subtype and pathway specific responses to anticancer compounds in breast cancer.

Breast cancers are comprised of molecularly distinct subtypes that may respond differently to pathway-targeted therapies now under development. Collections of breast cancer cell lines mirror many of the molecular subtypes and pathways found in tumors, suggesting that treatment of cell lines with candidate therapeutic compounds can guide identification of associations between molecular subtypes, pathways, and drug response. In a test of 77 therapeutic compounds, nearly all drugs showed differential responses across these cell lines, and approximately one third showed subtype-, pathway-, and/or genomic aberration-specific responses. These observations suggest mechanisms of response and resistance and may inform efforts to develop molecular assays that predict clinical response.

Applications of SPECT/CT in the Evaluation of Spinal Pathology: A Review.

BACKGROUND: Accurate identification of pain generators in the context of low back and spine-related pain is crucial for effective treatment. This review aims to evaluate the potential usefulness of single photon emission computed tomography with computed tomography (SPECT/CT) as an imaging modality in guiding clinical decision-making. METHODS: A broad scoping literature review was conducted to identify relevant studies evaluating the use of SPECT/CT in patients with spine-related pain. Studies were reviewed for their methodology and results. RESULTS: SPECT/CT appears to have advantages over traditional modalities, such as magnetic resonance imaging and CT, in certain clinical scenarios. It may offer additional information to clinicians and improve the specificity of diagnosis. However, further studies are needed to fully assess its diagnostic accuracy and clinical utility. CONCLUSIONS: SPECT/CT is a promising imaging modality in the evaluation of low back pain, particularly in cases where magnetic resonance imaging and CT are inconclusive or equivocal. However, the current level of evidence is limited, and additional research is needed to determine its overall clinical relevance. CLINICAL RELEVANCE: SPECT/CT may have a significant impact on clinical decision-making, particularly in cases in which traditional imaging modalities fail to provide a clear diagnosis. Its ability to improve specificity could lead to more targeted and effective treatment for patients with spinal pathology.

PARADIGM-SHIFT predicts the function of mutations in multiple cancers using pathway impact analysis.

MOTIVATION: A current challenge in understanding cancer processes is to pinpoint which mutations influence the onset and progression of disease. Toward this goal, we describe a method called PARADIGM-SHIFT that can predict whether a mutational event is neutral, gain-or loss-of-function in a tumor sample. The method uses a belief-propagation algorithm to infer gene activity from gene expression and copy number data in the context of a set of pathway interactions. RESULTS: The method was found to be both sensitive and specific on a set of positive and negative controls for multiple cancers for which pathway information was available. Application to the Cancer Genome Atlas glioblastoma, ovarian and lung squamous cancer datasets revealed several novel mutations with predicted high impact including several genes mutated at low frequency suggesting the approach will be complementary to current approaches that rely on the prevalence of events to reach statistical significance. AVAILABILITY: All source code is available at the github repository http:github.org/paradigmshift. CONTACT: jstuart@soe.ucsc.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MAgEC: Using Non-Homogeneous Ensemble Consensus for Predicting Drivers in Unexpected Mechanical Ventilation.

We conduct exploratory analysis of a novel algorithm called Model Agnostic Effect Coefficients (MAgEC) for extracting clinical features of importance when assessing an individual patient's healthcare risks, alongside predicting the risk itself. Our approach uses a non-homogeneous consensus-based algorithm to assign importance to features, which differs from similar approaches, which are homogeneous (typically purely based on random forests). Using the MIMIC-III dataset, we apply our method on predicting drivers/causers of unexpected mechanical ventilation in a large cohort patient population. We validate the MAgEC method using two primary metrics: its accuracy in predicting mechanical ventilation and the similarity of the proposed feature importances to a competing algorithm (SHAP). We also more closely discuss MAgEC itself by examining the stability of our proposed feature importances under different perturbations and whether the non-homogeneity of the approach actually leads to feature importance diversity. The code to implement MAgEC is open-sourced on GitHub (https://github.com/gstef80/MAgEC).

Protected Health Information filter (Philter): accurately and securely de-identifying free-text clinical notes.

There is a great and growing need to ascertain what exactly is the state of a patient, in terms of disease progression, actual care practices, pathology, adverse events, and much more, beyond the paucity of data available in structured medical record data. Ascertaining these harder-to-reach data elements is now critical for the accurate phenotyping of complex traits, detection of adverse outcomes, efficacy of off-label drug use, and longitudinal patient surveillance. Clinical notes often contain the most detailed and relevant digital information about individual patients, the nuances of their diseases, the treatment strategies selected by physicians, and the resulting outcomes. However, notes remain largely unused for research because they contain Protected Health Information (PHI), which is synonymous with individually identifying data. Previous clinical note de-identification approaches have been rigid and still too inaccurate to see any substantial real-world use, primarily because they have been trained with too small medical text corpora. To build a new de-identification tool, we created the largest manually annotated clinical note corpus for PHI and develop a customizable open-source de-identification software called Philter ("Protected Health Information filter"). Here we describe the design and evaluation of Philter, and show how it offers substantial real-world improvements over prior methods.

MEK-ERK signaling is a therapeutic target in metastatic castration resistant prostate cancer.

BACKGROUND: Metastatic castration resistant prostate cancer (mCRPC) is incurable and progression after drugs that target the androgen receptor-signaling axis is inevitable. Thus, there is an urgent need to develop more effective treatments beyond hormonal manipulation. We sought to identify activated kinases in mCRPC as therapeutic targets for existing, approved agents, with the goal of identifying candidate drugs for rapid translation into proof of concept Phase II trials in mCRPC. METHODS: To identify evidence of activation of druggable kinases in these patients, we compared mRNA expression from metastatic biopsies of patients with mCRPC (n = 101) to mRNA expression in localized prostate from TCGA and used this analysis to infer differential kinase activity. In addition, we assessed the differential phosphorylation levels for key MAPK pathway kinases between mCRPC and localized prostate cancers. RESULTS: Transcriptomic profiling of 101 patients with mCRPC as compared to patients with localized prostate cancer identified evidence of hyperactive ERK1, and whole genome sequencing revealed frequent amplifications of members of the MAPK pathway in 32% of this cohort. Next, we confirmed elevated levels of phosphorylated ERK1/2 in castration resistant prostate cancer as compared to untreated primary prostate cancer. We observed that the presence of detectable phosphorylated ERK1/2 in the primary tumor is associated with biochemical failure after radical prostatectomy independent of clinicopathologic features. ERK1 is the immediate downstream target of MEK1/2, which is druggable with trametinib, an approved therapeutic for melanoma. Trametinib elicited a profound biochemical and clinical response in a patient who had failed multiple prior treatments for mCRPC. CONCLUSIONS: We conclude that pharmacologic targeting of the MEK/ERK pathway may be a viable treatment strategy for patients with refractory metastatic prostate cancer. An ongoing Phase II trial tests this hypothesis.

Comparative Tumor RNA Sequencing Analysis for Difficult-to-Treat Pediatric and Young Adult Patients With Cancer.

Importance: Pediatric cancers are epigenetic diseases; therefore, considering tumor gene expression information is necessary for a complete understanding of the tumorigenic processes. Objective: To evaluate the feasibility and utility of incorporating comparative gene expression information into the precision medicine framework for difficult-to-treat pediatric and young adult patients with cancer. Design, Setting, and Participants: This cohort study was conducted as a consortium between the University of California, Santa Cruz (UCSC) Treehouse Childhood Cancer Initiative and clinical genomic trials. RNA sequencing (RNA-Seq) data were obtained from the following 4 clinical sites and analyzed at UCSC: British Columbia Children's Hospital (n = 31), Lucile Packard Children's Hospital at Stanford University (n = 80), CHOC Children's Hospital and Hyundai Cancer Institute (n = 46), and the Pacific Pediatric Neuro-Oncology Consortium (n = 24). The study dates were January 1, 2016, to March 22, 2017. Exposures: Participants underwent tumor RNA-Seq profiling as part of 4 separate clinical trials at partner hospitals. The UCSC either downloaded RNA-Seq data from a partner institution for analysis in the cloud or provided a Docker pipeline that performed the same analysis at a partner institution. The UCSC then compared each participant's tumor RNA-Seq profile with more than 11 000 uniformly analyzed tumor profiles from pediatric and young adult patients with cancer, downloaded from public data repositories. These comparisons were used to identify genes and pathways that are significantly overexpressed in each patient's tumor. Results of the UCSC analysis were presented to clinical partners. Main Outcomes and Measures: Feasibility of a third-party institution (UCSC Treehouse Childhood Cancer Initiative) to obtain tumor RNA-Seq data from patients, conduct comparative analysis, and present analysis results to clinicians; and proportion of patients for whom comparative tumor gene expression analysis provided useful clinical and biological information. Results: Among 144 samples from children and young adults (median age at diagnosis, 9 years; range, 0-26 years; 72 of 118 [61.0%] male [26 patients sex unknown]) with a relapsed, refractory, or rare cancer treated on precision medicine protocols, RNA-Seq-derived gene expression was potentially useful for 99 of 144 samples (68.8%) compared with DNA mutation information that was potentially useful for only 34 of 74 samples (45.9%). Conclusions and Relevance: This study's findings suggest that tumor RNA-Seq comparisons may be feasible and highlight the potential clinical utility of incorporating such comparisons into the clinical genomic interpretation framework for difficult-to-treat pediatric and young adult patients with cancer. The study also highlights for the first time to date the potential clinical utility of harmonized publicly available genomic data sets.

Minimally invasive multilevel percutaneous correction and fusion for adult lumbar degenerative scoliosis: a technique and feasibility study.

STUDY DESIGN: Prospective evaluation of 12 patients undergoing surgery for lumbar degenerative scoliosis. OBJECTIVE: To assess the feasibility of minimally invasive spine surgery (MIS) techniques in the correction of lumbar degenerative deformity. SUMMARY OF BACKGROUND DATA: Patient age, comorbidities, and blood loss may be limiting factors when considering surgical correction of lumbar degenerative scoliosis. MIS may allow for significantly less blood loss and tissue disruption than open surgery. METHODS: Twelve patients underwent circumferential fusion. The age range of these patients was 50 to 85 years (mean of 72.8 y). Of the 12 patients, 7 were men and 5 were women. All patients underwent direct lateral transpsoas approach for discectomy and fusion with polyetheretherketone cage and rh-BMP2. All fusions to the sacrum included L5-S1 fusion with the Trans1 Axial Lumbar Interbody Fusion technique. Posteriorly, multilevel percutaneous screws were inserted using the CD Horizon Longitude system. Radiographs, visual analog scores (VAS), and treatment intensity scores (TIS) were assessed preoperatively and at last postoperative visit. Operative times and estimated blood loss were recorded. RESULTS: Mean number of segments operated on was 3.64 (range: 2 to 8 segments). Mean blood loss for anterior procedures (transpsoas discectomy/fusion and in some cases L5-S1 interbody fusion) was 163.89 mL (SD 105.41) and for posterior percutaneous pedicle screw fixation (and in some cases L5-S1 interbody fusion) was 93.33 mL (SD 101.43). Mean surgical time for anterior procedures was 4.01 hours (SD 1.88) and for posterior procedures was 3.99 hours (SD 1.19). Mean Cobb angle preoperatively was 18.93 degrees (SD 10.48) and postoperatively was 6.19 degrees (SD 7.20). Mean preoperative VAS score was 7.1; mean preoperative TIS score was 56.0. At mean follow-up of 75.5 days, mean VAS was 4.8; TIS was 28.0. CONCLUSIONS: A combination of 3 MIS techniques allows for correction of lumbar degenerative scoliosis. Multisegment correction can be performed with less blood loss and morbidity than for open correction.

TumorMap: Exploring the Molecular Similarities of Cancer Samples in an Interactive Portal.

Vast amounts of molecular data are being collected on tumor samples, which provide unique opportunities for discovering trends within and between cancer subtypes. Such cross-cancer analyses require computational methods that enable intuitive and interactive browsing of thousands of samples based on their molecular similarity. We created a portal called TumorMap to assist in exploration and statistical interrogation of high-dimensional complex "omics" data in an interactive and easily interpretable way. In the TumorMap, samples are arranged on a hexagonal grid based on their similarity to one another in the original genomic space and are rendered with Google's Map technology. While the important feature of this public portal is the ability for the users to build maps from their own data, we pre-built genomic maps from several previously published projects. We demonstrate the utility of this portal by presenting results obtained from The Cancer Genome Atlas project data. Cancer Res; 77(21); e111-4. ©2017 AACR.

PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models.

Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. Cancer Res; 77(21); e62-66. ©2017 AACR.

Molecular pathways: extracting medical knowledge from high-throughput genomic data.

High-throughput genomic data that measures RNA expression, DNA copy number, mutation status, and protein levels provide us with insights into the molecular pathway structure of cancer. Genomic lesions (amplifications, deletions, mutations) and epigenetic modifications disrupt biochemical cellular pathways. Although the number of possible lesions is vast, different genomic alterations may result in concordant expression and pathway activities, producing common tumor subtypes that share similar phenotypic outcomes. How can these data be translated into medical knowledge that provides prognostic and predictive information? First-generation mRNA expression signatures such as Genomic Health's Oncotype DX already provide prognostic information, but do not provide therapeutic guidance beyond the current standard of care, which is often inadequate in high-risk patients. Rather than building molecular signatures based on gene expression levels, evidence is growing that signatures based on higher-level quantities such as from genetic pathways may provide important prognostic and diagnostic cues. We provide examples of how activities for molecular entities can be predicted from pathway analysis and how the composite of all such activities, referred to here as the "activitome," helps connect genomic events to clinical factors to predict the drivers of poor outcome.

Cantilever TLIF with structural allograft and RhBMP2 for correction and maintenance of segmental sagittal lordosis: long-term clinical, radiographic, and functional outcome.

STUDY DESIGN/SETTING: Prospective cohort study in a tertiary care spine center. OBJECTIVE: The effectiveness of the cantilever transforaminal lumbar interbody fusion (C-TLIF) technique in creating and maintaining lordosis, avoiding nerve problems, and obtaining fusion was studied. SUMMARY OF BACKGROUND DATA: C-TLIF is a microscope-assisted transforaminal lumbar interbody fusion technique, emphasizing no dural retraction with placement of structural allograft and RhBMP2 anteriorly under the cortical apophyseal ring, followed by middle column cancellous autograft placed under compression with posterior pedicle spinal instrumentation. METHODS: A total of 100 consecutive patients studied with an average of 30 months of follow-up. A total of 48 had prior surgery at the index level; 16 had the procedure done at an adjacent level to a previous fusion; 32 at L5-S1 with 42 at L4-L5 and 26 at L3-L4. There were 76 single-level and 24 two-level fusions. One patient was a smoker with one other patient a compensation case. Outcome was prospectively documented with self-administered Visual Analog Pain Scale, Oswestry Disability Questionnaire, Treatment Intensity Questionnaire, and SF-36 Health Survey. Patients rated the surgery as excellent, good, fair, or poor and whether they would recommend the surgery. Student t test was used for statistical analysis with significance set at P = 0.05. RESULTS: Blood loss and hospital stay averaged 300 mL and 2.2 days, respectively. There was significant reduction (P < 0.05) in pain scores from 9 to 3, Oswestry Disability Index scores from 35 to 12, and Treatment Intensity Score from 21/25 to 2/25 at final follow-up. The SF-36 PCS and MCS scores showed an increasing trend to improvement. A total of 69 rated the surgery as excellent, 23 good, 7 fair, and 1 poor. A total of 97% were satisfied and would recommend the surgery. All had improvement in radicular pain with no dural tears, neural injury, or neuropathic pain. There was significant improvement (P < 0.05) in segmental sagittal lordosis from 2 degrees to 9 degrees, anterior disc height from 6 to 14 mm, and posterior disc height from 4 to 8 mm. There was no subsidence, misplaced screws, or instrumentation failure. Solid fusion was obtained in 99 of 100 patients. CONCLUSIONS: The C-TLIF allows for creation and maintenance of sagittal lordosis while avoiding subsidence and neurologic problems with a 99% fusion rate and 97% patient satisfaction.

Endoscopic lateral transpsoas approach to the lumbar spine.

STUDY DESIGN: A description of a novel surgical approach to the lumbar spine and a prospective evaluation of the early surgical outcomes. OBJECTIVES: Describe the early postoperative results and the operative technique of a new, minimally invasive transpsoas approach for anterior fusion of the lumbar spine that minimizes the risk to large vessels and other critical structures. SUMMARY OF BACKGROUND DATA: Standard anterior endoscopic approaches to the lumbar spine require mobilization of the great vessels and sympathetic plexus. Vascular injury and retrograde ejaculation are complications clearly associated with this approach. A retroperitoneal, transpsoas approach to the lumbar spine may reduce these risks. METHODS: From 1996 to 2002, 21 patients (13 females, 8 males; mean age 50.0 years) underwent an endoscopic, retroperitoneal transpsoas approach for exposure of the lumbar spine. Surgical indications included discogenic pain in 14 patients, spinal instability at a level adjacent to a previous fusion in 3 patients, and progressive degenerative scoliosis in 4 patients. Data were reviewed to document the early postoperative results for this procedure. Illustrations were created to clearly describe this approach. RESULTS: Average operative time for the single level cases was 149 minutes (range 120-170 minutes); blood loss was 150 cc (range 50-650); postoperative hospital stay was 4.1 days. At long-term follow-up, visual analogue scale scores had decreased an average of 5.9. Mean follow-up was 3.1 years (range 2 months-6.0 years). Six patients (30%) experienced paresthesias in the groin/thigh region. Five of these same patients also complained of groin/thigh pain (27%). Two patients had symptoms that lasted longer than 1 month. One patient was converted to a mini-open lateral approach. There were no vascular injuries. CONCLUSIONS: Early results show the endoscopic lateral transpsoas approach to the lumbar spine to be a safe, minimally invasive method for anterior fusion of the first through the fourth lumbar vertebrae. Although there is a risk of groin/thigh numbness or pain, and these symptoms are mostly transient. This approach allows for exposure of the lumbar spine without mobilization of the great vessels or sympathetic plexus.