James D. Lin

Urine Exosomes for Non-Invasive Assessment of Gene Expression and Mutations of Prostate Cancer.

Purpose The analysis of exosome/microvesicle (extracellular vesicles (EVs)) and the RNA packaged within them (exoRNA) has the potential to provide a non-invasive platform to detect and monitor disease related gene expression potentially in lieu of more invasive procedures such as biopsy. However, few studies have tested the diagnostic potential of EV analysis in humans. Experimental Design The ability of EV analysis to accurately reflect prostate tissue mRNA expression was examined by comparing urinary EV TMPRSS2:ERG exoRNA from pre-radical prostatectomy (RP) patients versus corresponding RP tissue in 21 patients. To examine the differential expression of TMPRSS2:ERG across patient groups a random urine sample was taken without prostate massage from a cohort of 207 men including prostate biopsy negative (Bx Neg, n = 39), prostate biopsy positive (Bx Pos, n = 47), post-radical prostatectomy (post-RP, n = 37), un-biopsied healthy age-matched men (No Bx, n = 44), and young male controls (Cont, n = 40). The use of EVs was also examined as a potential platform to non-invasively differentiate Bx Pos versus Bx Neg patients via the detection of known prostate cancer genes TMPRSS2:ERG, BIRC5, ERG, PCA3 and TMPRSS2. Results In this technical pilot study urinary EVs had a sensitivity: 81% (13/16), specificity: 80% (4/5) and an overall accuracy: 81% (17/21) for non-invasive detection of TMPRSS2:ERG versus RP tissue. The rate of TMPRSS2:ERG exoRNA detection was found to increase with age and the expression level correlated with Bx Pos status. Receiver operator characteristic analyses demonstrated that various cancer-related genes could differentiate Bx Pos from Bx Neg patients using exoRNA isolated from urinary EVs: BIRC5 (AUC 0.674 (CI:0.560–0.788), ERG (AUC 0.785 (CI:0.680–0.890), PCA3 (AUC 0.681 (CI:0.567–0.795), TMPRSS2:ERG (AUC 0.744 (CI:0.600–0.888), and TMPRSS2 (AUC 0.637 (CI:0.519–0.754). Conclusion This pilot study suggests that urinary EVs have the potential to be used as a platform to non-invasively differentiate patients with prostate cancer with very good accuracy. Larger studies are needed to confirm the potential for clinical utility.

Trapeziometacarpal Joint Stability: The Evolving Importance of the Dorsal Ligaments

BackgroundTrapeziometacarpal (TMC) arthritis of the thumb is a common source of hand pain and disability. TMC ligamentous instability may play a role in TMC degeneration. However, the relative importance of the TMC ligaments in the etiology of degeneration and the use of surgery to treat instability in early-stage arthritis are unclear.Questions/purposesIn this review, we addressed several questions: (1) What are the primary ligamentous stabilizers of the thumb TMC joint? (2) What is the evidence for ligament reconstruction or ligament imbrication in the treatment of thumb TMC joint osteoarthritis? And (3) what is the evidence for thumb metacarpal osteotomy in the treatment of thumb TMC joint osteoarthritis?MethodsWe performed a systematic review of the literature using PubMed (MEDLINE®) and Scopus® (EMBASE®) for peer-reviewed articles published until November 2012. Fifty-two studies fit the inclusion criteria. Twenty-four studies were anatomic, biomechanical, or histopathologic studies on TMC joint ligamentous anatomy, 16 studies were clinical studies concerning ligament reconstruction, and 12 studies were clinical studies on thumb metacarpal osteotomy.ResultsOver the past two decades, increasing evidence suggests the dorsoradial ligament is the most important stabilizer of the TMC joint. Other ligaments consistently identified are the superficial anterior oblique, deep anterior oblique, intermetacarpal, ulnar collateral, and posterior oblique ligaments. Ligament reconstruction and metacarpal osteotomy relieve pain and improve grip strength based on Level IV studies.ConclusionsThe dorsal ligaments are the primary stabilizers of the TMC joint. Ligament reconstruction and metacarpal osteotomy ameliorate ligamentous laxity and relieve pain based on Level IV studies.

Closed Soft Tissue Extensor Mechanism Injuries (Mallet, Boutonniere, and Sagittal Band)

The extensor mechanism of the hand is complex and can be disrupted at several different points, from hand trauma. This article summarizes current concepts relating to the presentation and treatment of closed soft tissue injuries of the extensor mechanism in zones I, III, and V, commonly known as mallet finger and boutonniere deformities and sagittal band injuries.

Dorsoradial ligament imbrication for thumb carpometacarpal joint instability.

Dorsoradial ligament imbrication is a direct and effective alternative to ligament reconstruction or metacarpal osteotomy in patients with symptomatic thumb carpometacarpal (CMC) joint instability. This procedure is performed by imbricating either the trapezial or the metacarpal attachment of the dorsoradial ligament with the use of a suture anchor. The procedure is indicated in the setting of chronic hyperlaxity or instability of the thumb CMC joint. Significant arthritic changes in the thumb CMC joint are a contraindication for this procedure. We present our technique along with an anatomic dissection to demonstrate the ligament and surgical procedure on an anatomic specimen. We also present results from 3 patients who underwent this technique with images and clinical results for 3 patients with long-term follow-up. Level of Evidence: Level IV—Therapeutic.

The effect of c-arm tilt on accuracy of intraoperative fluoroscopy in assessing acetabular component position during direct anterior approach for hip arthroplasty

Intraoperative fluoroscopy can improve the precision of acetabular component positioning during direct anterior hip arthroplasty. However, changes in pelvic tilt with c-arm positioning may compromise accuracy. A geometric model of an acetabular components projection onto fluoroscopy images was created and manipulated to simulate c-arm tilt. An apparently ideally-placed cup will have its effective anteversion changed by 7.5° with just 10° of caudal/cephalad tilt of the c-arm. This effect is greater in cups that are more horizontally placed or less anteverted. Accurate c-arm positioning is crucial, as small errors in tilt can have considerable effects on final cup position.

The posterior superior iliac spine and sacral laminar slope: key anatomical landmarks for freehand S2-alar-iliac screw placement

OBJECTIVE The S2-alar-iliac (S2AI) screw is an increasingly popular method for spinopelvic fixation. The technique of freehand S2AI screw placement has been recently described. The purpose of this study was to demonstrate, through a CT imaging study of patients with spinal deformity, that screw trajectories based on the posterior superior iliac spine (PSIS) and sacral laminar slope result in reliable freehand S2AI trajectories that traverse safely above the sciatic notch. METHODS Fifty consecutive patients (age ≥ 18 years) who underwent primary spinal deformity surgery were included in the study. Simulated S2AI screw trajectories were analyzed with 3D visualization software. The cephalocaudal coordinate for the starting point was 15 mm cephalad to the PSIS. The mediolateral coordinate for the starting point was in line with the lateral border of the dorsal foramina. The cephalocaudal screw trajectory was perpendicular to the sacral laminar slope. Screw trajectories, lengths, and distance above the sciatic notch were measured. RESULTS The mean sagittal screw angle (cephalocaudal angulation) was 44.0° ± 8.4° and the mean transverse angle (mediolateral angulation) was 37.3° ± 4.3°. The mean starting point was 5.9 ± 5.8 mm distal to the caudal border of the S1 foramen. The mean screw length was 99.9 ± 18.6 mm. Screw trajectories were on average 8.5 ± 4.3 mm above the sciatic notch. A total of 97 of 100 screws were placed above the sciatic notch. In patients with transitional lumbosacral anatomy, the starting point on the lumbarized/sacralized side was 3.4 mm higher than on the contralateral unaffected side. CONCLUSIONS The PSIS and sacral laminar slope are two important anatomical landmarks for freehand S2AI screw placement.

Obstructed spinopelvic fixation in the setting of a triangular titanium sacroiliac fusion implant: a case description

Achieving lumbosacral fusion through spinopelvic fixation is an important and challenging aspect of spinal deformity surgery. Numerous instrumentation techniques are available, with iliac screws and S2-alar-iliac (SRAI) screws being most commonly used today. However, the increasing popularity of minimally invasive sacroiliac (SI) fusion as a common procedure performed for SI joint pain presents a distinct challenge in complex adult deformity cases requiring iliac screw fixation. We report a case of a 71-year-old female with a longstanding history of spinal deformity status-post T11-L5 fusion and a subsequent right-sided SI joint fusion who presented with sagittal imbalance. The SI joint fusion implant obstructed the pathway for spinopelvic fixation. Spinopelvic fixation was achieved by burring a pathway through the SI joint implant. The increasing popularity of minimally invasive SI fusion as a common procedure performed for SI joint pain presents a distinct challenge in complex adult deformity cases requiring iliac screw fixation. This is the first report in the literature describing a technique for spinopelvic fixation in the setting of screw obstruction due to an instrumented SI joint.

The hemisoleus rotational flap provides a novel superior autograft reconstructive option for the treatment of chronic extensor mechanism disruption

Chronic disruption of the extensor mechanism is a devastating problem after total knee arthroplasty. Quadriceps tendon ruptures occur at an estimated 0.1% prevalence in the setting of total knee arthroplasty. Complete tears of the quadriceps tendon generally have poor results and high rates of rerupture. We present a case of a quadriceps tendon rupture after total knee arthroplasty which reruptured after initial direct repair. The patient presented to us with a chronically retracted rerupture and was subsequently reconstructed successfully with a novel extended medial gastrocnemius-soleus-calcaneus local rotational pedicle flap.

Abstract C133: The use of exosomal mRNA for noninvasive transcriptional analysis of the prostate.

Background: Prostate cancer studies have used urine as a non-invasive source of nucleic acids for biomarker analysis. These studies have been limited by the need for a digital rectal exam (DRE) or prostate massage prior to urine collection to enable enough cellular material for RNA analysis. Such manipulations can potentially lead to variability in assay performance depending on DRE intensity and may also reduce compliance. Here we investigate the novel use of RNA in urinary exosomes, small lipid bilayer vesicles released from cells into bodily fluids, to analyze previously identified prostate cancer mRNA biomarkers without a prostate massage. Methods: Random urine samples (>20ml) were collected from 207 consecutive patients under a Columbia University IRB approved prospective protocol. Patients were stratified into 5 groups: TRUS biopsy negative (Bx Neg, n=39), TRUS biopsy positive (Bx Pos, n=47), post-radical prostatectomy (RP, n=37), no TRUS biopsy (No Bx, n=44) and control (healthy males Results: All groups were age matched except for control males ( Conclusion: This study confirms that urinary exosomes are a novel source of high quality RNA to examine prostate gene expression. We demonstrate that expression levels of ERG, PCA3, TMPRSS2:ERG, TMPRSS2 and survivin are significantly higher in cases of confirmed prostate cancer, consistent with previous studies using prostate biopsies and/or urinary cells collected after DRE/prostate massage. The unique stability and yield of urinary exoRNA collected without the need for a prostatic massage will hopefully simplify sample handing, obviate sample variability and patient discomfort inherent to prostate massage, and broaden the role of exosomes in future diagnostic testing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C133.